Community signal

ATR-FTIR spectroscopy coupled with multivariate analysis for monitoring degradation and secondary structure transitions in therapeutic peptide formulations.

Mentions Semaglutide

Discovery of a novel and potent KRAS(G12V)-targeting peptide with antiproliferative activity against colorectal cancer cells.

1. J Enzyme Inhib Med Chem. 2026 Dec;41(1):2684700. doi: 10.1080/14756366.2026.2684700. Epub 2026 Jun 11. Discovery of a novel and potent KRAS(G12V)-targeting peptide with antiproliferative activity against colorectal cancer cells. Zhang H(1), Yang S(2), Wang Y(2), Niu MM(2), She J(3). Author information: (1)Department of Hepatobiliary Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China. (2)Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, Jiangsu, China. (3)Department of Gastrointestinal Surgery, Jintan Affiliated Hospital of Jiangsu University, Changzhou, Jiangsu, China. Despite the clinical relevance of KRASG12V in colorectal cancer, KRASG12V-specific inhibitors remain limited. Through structure-based virtual screening of a 59,319-member peptide library, we identified four KRASG12V-targeting peptides, among which Peptide-1 showed the most favourable docking profile. MST assays confirmed Peptide-1 had the highest affinity among Peptides 1-4, with stronger binding to KRASG12V than to other KRAS mutants. Structural analysis, molecular dynamics simulations, and free-energy calculations indicated that Peptide-1 formed a stable and energetically favourable complex with KRASG12V through extensive hydrogen bonding and hydrophobic interactions. Peptide-1 showed favourable human serum stability and cellular NanoBRET-supported engagement with KRASG12V. Functionally, Peptide-1 displayed potent antiproliferative activity in colorectal cancer cell lines, weaker effects on normal cells and reduced efficacy after KRASG12V knockdown. In SW480 cells, Peptide-1 was associated with reduced ERK1/2 phosphorylation, p21 upregulation, and G0/G1 accumulation. Overall, these findings support further investigation of Peptide-1 as a KRASG12V-targeting peptide for colorectal cancer drug discovery. DOI: 10.1080/14756366.2026.2684700 PMCID: PMC13262105 PMID: 42274165 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the authors.

Mentions P21

Comparison of lifestyle, surgery, and semaglutide for weight management in endometrial cancer: a prospective observational study.

Mentions Semaglutide

Recombinant human collagen XVII protects epidermal stem cells from blue light-induced photoaging by downregulating the Notch pathway.

1. Ann Med. 2026 Dec;58(1):2694876. doi: 10.1080/07853890.2026.2694876. Epub 2026 Jul 16. Recombinant human collagen XVII protects epidermal stem cells from blue light-induced photoaging by downregulating the Notch pathway. Wang X(1)(2)(3), Li Q(4), Yang X(1), Bai Y(1), Sui S(1), Ge G(1), Li H(1), Yang R(1). Author information: (1)Department of Dermatology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China. (2)Department of Dermatology, Medical School of Chinese PLA, Beijing, China. (3)Department of Dermatology, Southern Medical District of Chinese PLA General Hospital, Beijing, China. (4)Medical Health Care Department, Air Force Medical Center PLA, Beijing, China. BACKGROUND: Epidermal stem cell (ESC) degeneration is closely associated with skin aging and functional deterioration. Type XVII collagen (COL17A1) critically regulates ESC polarity and epidermal homeostasis. This study investigated the protective effects of recombinant human COLXVII (rhCol17) against blue light-induced photoaging, particularly on ESC. METHODS: Blue light-induced photoaging models were established using in vitro ESCs and in vivo Sprague-Dawley rats. Transcriptomic profiling was conducted to systematically elucidate the underlying mechanisms. RESULTS: In photoaging ESCs, rhCol17 enhanced ESC viability and migratory capacity, decreased senescence cells, while suppressing ROS production and the secretion of pro-inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Furthermore, rhCol17 upregulated stem cell markers COL17A1, ITGB1, ITGA6 and P63. In photoaging rat models, rhCol17 alleviated skin dryness, reduced epidermal thickness, delayed aging, and increased the levels of COL17A1 and ITGB1. Importantly, rhCol17 treatment does not affect organ histology or biochemical parameters in rats. Mechanistically, rhCol17 could inhibit the levels of Notch1 and HES1, and senescence markers P16, P21, and P53 in photoaging ESCs and rat skin. Additionally, the ADAM10 inhibitor GI254023X slightly reduced or did not significantly alter the proportion of senescent cells or the expression levels of P16, P21, and P53 in rhCol17-treated BL-induced ESCs, whereas the Notch activator VPA significantly reversed these protective effects of rhCol17. CONCLUSION: This study demonstrates that rhCol17 counteracts blue light-induced ESC dysfunction and epidermal photoaging, suggesting therapeutic potential for photoaging intervention. DOI: 10.1080/07853890.2026.2694876 PMID: 42464532 [Indexed for MEDLINE]

Mentions P21

AMD1-mediated polyamine metabolism governs tubular repair fate by restraining senescence after kidney injury.

1. Ren Fail. 2026 Dec;48(1):2680375. doi: 10.1080/0886022X.2026.2680375. Epub 2026 Jun 14. AMD1-mediated polyamine metabolism governs tubular repair fate by restraining senescence after kidney injury. Mao B(1)(2)(3), Zheng Z(1)(2)(3), Fu W(1)(2)(3), Cheng G(1)(2)(3), Wang L(1)(2), Bao J(1)(2), Liu X(4)(5), Zhan H(4)(5), Pan M(4)(5), Liu J(1)(2)(3). Author information: (1)Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. (2)Laboratory of Nephropathy, Translational Medicine Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. (3)Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. (4)Department of Nephrology, Ningde Municipal Hospital of Ningde Normal University, Ningde, China. (5)Department of Nephrology, Shanghai First People's Hospital Ningde Hospital, Ningde, China. Failure of adaptive repair after acute kidney injury (AKI) drives the transition to chronic kidney disease (CKD), yet the metabolic checkpoints governing tubular fate remain incompletely defined. Here, we investigated whether the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase 1 (AMD1) regulates tubular senescence and repair outcomes after AKI and elucidated the underlying mechanism. AMD1 dynamics were examined in an ischemia-reperfusion injury model using male C57BL/6J mice by immunofluorescence. AAV-mediated Ksp promoter-driven tubule-specific Amd1 conditional knockdown male mice (Amd1 cKD) were used to assess renal injury, cell-cycle status, senescence, and remodeling, and exogenous spermidine was administered for rescue. DNA damage signaling and p53/p21 activation were evaluated by immunostaining, Western blotting, and EdU incorporation assays. AMD1 was predominantly expressed in the tubular epithelium, with prominent dynamic induction in proximal tubules early after IRI, but declined to baseline levels during the late phase, representing a relative metabolic insufficiency that correlated inversely with fibrosis. Compared with wild-type controls, Amd1 cKD mice exhibited aggravated tubular injury, an over two-fold increase in SA-β-gal-positive areas, elevated p21, and reduced Ki67+ proliferation. Conversely, spermidine supplementation improved renal function, reduced fibrosis by 75.3%, and decreased senescent regions by 74%. Mechanistically, AMD1 deficiency increased γH2AX-marked DNA damage and activated the p53/p21 checkpoint, whereas spermidine attenuated this response and restored DNA synthesis capacity. Collectively, tubular AMD1 acts as a metabolic checkpoint that preserves polyamine homeostasis to restrain p53/p21-dependent senescence, promote adaptive repair after AKI, and spermidine supplementation represents a potential strategy to mitigate maladaptive AKI-to-CKD progression. DOI: 10.1080/0886022X.2026.2680375 PMCID: PMC13267046 PMID: 42289383 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions P21

Effect of oral calcium carbonate on uterine contractility: a pilot randomised controlled trial.

1. J Obstet Gynaecol. 2026 Dec;46(1):2697258. doi: 10.1080/01443615.2026.2697258. Epub 2026 Jul 21. Effect of oral calcium carbonate on uterine contractility: a pilot randomised controlled trial. Bui TM(1), Nelson M(1), Rehman R(1), Stowe Ii RJ(1), Roloff KA(1), Valenzuela GJ(1). Author information: (1)Department of Women's Health, Arrowhead Regional Medical Center, Colton, California, USA. BACKGROUND: Ineffective uterine contractions contribute to labour dystocia and are a leading indication for primary caesarean delivery. Although oxytocin is the standard therapy for augmentation, prolonged exposure may result in receptor desensitisation and reduced effectiveness. Calcium is essential for myometrial contraction; however, systemic calcium homeostasis is tightly regulated, and it is unclear whether oral calcium supplementation can meaningfully influence uterine activity. This study aimed to evaluate the effect of oral calcium carbonate on uterine contractility. METHODS: We conducted a single-centre randomised controlled pilot trial at a tertiary care teaching hospital (ClinicalTrials.gov: NCT07056062). Term patients with singleton foetus in cephalic presentation and an intrauterine pressure catheter in place were randomised 1:1 to receive a single 2,000 mg oral dose of calcium carbonate or no intervention. Uterine activity was measured using Montevideo units (MVUs) at baseline and at 30-minute intervals for two hours. Secondary outcomes included contraction frequency, peak contraction pressure, labour duration, mode of delivery, oxytocin dose, and postpartum haemorrhage. Oxytocin infusion rates were held constant during the observation period. RESULTS: Eighty-nine patients were analysed (45 control; 44 intervention) with similar baseline characteristics. No statistically significant difference in baseline MVUs was observed between groups (p = 0.1825). Although absolute MVUs were higher in the intervention group at 30 minutes (p = 0.0500), this difference was not sustained at subsequent time points and was absent in change-from-baseline analyses, suggesting no clinically meaningful treatment effect. No statistically significant differences were identified in secondary outcomes. CONCLUSIONS: Oral calcium carbonate did not result in a statistically significant improvement in uterine contractility or clinical outcomes. These findings likely reflect the limited physiologic effect of oral calcium on serum calcium levels. Oral calcium carbonate appears unlikely to be an effective intervention for labour augmentation; future research should focus on strategies with more controllable mechanisms. Plain Language Summary: During labour, the uterus contracts to help the baby move through the birth canal. If contractions are too weak or poorly coordinated, labour may progress slowly, increasing the likelihood of caesarean delivery. Oxytocin is commonly used to strengthen contractions, but prolonged exposure may make the uterus less responsive over time. Calcium is an important mineral that helps muscle cells contract, including the muscles of the uterus. Because of this, we conducted a randomised clinical trial to determine whether providing calcium during labour could improve contractions. We found no meaningful differences in contraction strength or labour outcomes between patients who received calcium and those who did not. Although a difference in contraction strength was observed at one early time point, this was not sustained and did not translate into clinical benefit. These findings suggest that a single dose of oral calcium carbonate does not improve uterine contractions during labour. DOI: 10.1080/01443615.2026.2697258 PMID: 42480078 [Indexed for MEDLINE]

Mentions Oxytocin

Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial.

1. J Med Econ. 2026 Dec;29(1):1258-1278. doi: 10.1080/13696998.2026.2646078. Epub 2026 Apr 21. Cost-effectiveness of tirzepatide versus semaglutide for patients with obesity or overweight in the US: evidence from the SURMOUNT-5 head-to-head phase-3 trial. Johansson E(1), Wilding JPH(2)(3), Upadhyay N(1), van Hest N(4), Kirk M(5), Spaepen E(6), Zimner-Rapuch S(1), Annemans L(7), Bays H(8). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. (2)Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. (3)Clinical Sciences Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. (4)Costello Medical, Bristol, UK. (5)Costello Medical, Manchester, UK. (6)HaaPACS GmbH, Schriesheim, Germany. (7)Interuniversity Center of Health Economic Research (ICHER), Department of Public Health and Primary Care, Ghent University, Ghent, Belgium. (8)Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky, USA. PURPOSE: This study evaluated the cost-effectiveness (from the United States [US] societal perspective) of tirzepatide at its maximum-tolerated-dose (MTD) compared to semaglutide (MTD), both administered adjunct to a reduced-calorie diet and increased physical activity. The analysis focused on individuals with obesity (body mass index [BMI] ≥ 30 kg/m2), or overweight (BMI ≥27 to <30 kg/m2 + ≥1 obesity-related complication), using data from the head-to-head Phase-3 SURMOUNT-5 trial (patients without type 2 diabetes [T2D]). PATIENTS AND METHODS: This patient-level simulation modeling study assessed the cost and long-term clinical outcomes of tirzepatide (MTD) versus semaglutide (MTD), using data from the SURMOUNT-5 trial population. The modeled population were at risk of developing obesity-related complications including cardiovascular disease (CVD) and obstructive sleep apnea (OSA), amongst others. These outcomes were modeled using cardiometabolic parameters including weight, systolic blood pressure, high-density lipoprotein, glycated hemoglobin (HbA1c) and total cholesterol, by assessing their impact on healthcare and wider societal costs, quality of life, and mortality. Incremental cost-effectiveness ratios (ICERs; cost/quality-adjusted life year [QALY]) and incremental net health benefit (iNHBs) were calculated, and uncertainty was assessed through sensitivity and scenario analyses. RESULTS: Tirzepatide (MTD) was estimated to be less costly and more efficacious compared to semaglutide (MTD) with per patient cost savings of $41,688, 0.506 QALYs gained and positive iNHB of 0.784, indicating a net health benefit for tirzepatide. The model predicted that per 1,000 patients, 70 fewer patients will develop T2D, 10 fewer will develop CVD with tirzepatide (MTD) and patients spend 3.07 more years living with moderate/severe OSA when treated with semaglutide (MTD). CONCLUSION: Based on this simulation model, using head-to-head SURMOUNT-5 trial data, tirzepatide (MTD) had lower total costs and higher QALYs compared to semaglutide (MTD). This supports that tirzepatide (MTD) is a cost-effective treatment option for individuals with obesity or overweight compared to semaglutide (MTD). Plain Language Summary: This study focused on evaluating the cost-effectiveness of two weight management drugs, tirzepatide and semaglutide, for adults in the US who are overweight or have obesity. Using data from the SURMOUNT-5 trial, the analysis showed that tirzepatide was more effective and less costly, providing better weight loss and health benefits compared to semaglutide.The findings revealed that for every 1,000 individuals treated with tirzepatide, there were 70 fewer cases of type 2 diabetes and 10 fewer cases of heart disease compared to those treated with semaglutide. Additionally, patients on semaglutide experienced a longer duration living with moderate or severe sleep

Mentions Semaglutide

Role of myometrial relaxants (acute tocolytics) in intrauterine fetal resuscitation at term: why, when, what, How, and why-not?

1. J Matern Fetal Neonatal Med. 2026 Dec;39(1):2698356. doi: 10.1080/14767058.2026.2698356. Epub 2026 Jul 9. Role of myometrial relaxants (acute tocolytics) in intrauterine fetal resuscitation at term: why, when, what, How, and why-not? Mappa I(1), Bolten M(2), Fieni S(3), Tahir N(4), Chandraharan E(5). Author information: (1)Department of Maternal and Child Health and Urological Sciences, Sapienza, Università di Roma, Rome, Italy. (2)Klinikum Leverkusen, Academic Teaching Hospital of Cologne University, Leverkusen, Germany. (3)Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy. (4)Department of Obstetrics & Gynaecology, Bolton NHS Foundation Trust, UK. (5)Global Academy of Medical Education & Training, London, UK. Uterine contractions cause hypoxic stress to human fetuses by repeatedly occluding maternal spiral arterioles which feed the placental bed and/or compressing the loops of the umbilical cord, interrupting blood flow through the umbilical vessels. For some fetuses, even such transient and repeated interruptions of oxygenation due to ongoing uterine contractions may increase the risk of decompensation in the "high priority" central organs (i.e. heart and the brain). The onset of anaerobic metabolism and resultant production of lactate in the central organs may lead to increased likelihood of fetal neurological injury and/or perinatal death. Therefore, an immediate relaxation of the myometrium by abolishing ongoing uterine contractions may help to rapidly restore oxygenation to fetal central organs. Such timely administration of acute tocolytics would help maintain aerobic metabolism in the high-priority fetal central organs, avoiding the onset of neurological injury and/or perinatal death. Commonly used acute tocolytics include beta-sympathomimetics, nitric oxide donors, oxytocin antagonists, which have different mechanisms of actions, and maternal side-effect profile. The indications include elimination of uterotonic-induced excessive uterine contractions to facilitate normalization of the fetal heart rate so as to allow continuation of labor in anticipation of vaginal birth and for rapidly improving the fetal condition immediately prior to an emergency cesarean section. The latter includes umbilical cord prolapse or chronic hypoxia when a delay in birth is anticipated. This review addresses the indications for acute tocolytics (why), the recommended timing of administration (when), ideal tocolytic (what), route of administration (how), side effects and contraindications (why-not). Based on current evidence, and pharmacokinetics, 250 mcg of subcutaneous terbutaline (or another beta-sympathomimetic such as intravenous fenoterol) is the recommended first line tocolytic, unless there are specific maternal contraindications. In the absence of maternal hypotension, 100 mg of intravenous glyceryl trinitrate (GTN) may be administered as an alternative. Acute tocolytics are not recommended to treat myometrial irritability observed in chorioamnionitis or in acute feto-maternal hemorrhage. DOI: 10.1080/14767058.2026.2698356 PMID: 42425549 [Indexed for MEDLINE]

Mentions Oxytocin

Enhancing economic modelling in obesity: integrating novel type 2 diabetes progression & obstructive sleep apnea remission - a UK case study.

1. J Med Econ. 2026 Dec;29(1):1111-1129. doi: 10.1080/13696998.2026.2646079. Epub 2026 Apr 22. Enhancing economic modelling in obesity: integrating novel type 2 diabetes progression & obstructive sleep apnea remission - a UK case study. Annemans L(1), Johansson E(2), Spaepen E(3), van Hest N(4), Grist J(5), Zimner-Rapuch S(2), Wilding JPH(6)(7). Author information: (1)Interuniversity Center of Health Economic Research (ICHER), Department of Public Health and Primary Care, Ghent University, Ghent, Belgium. (2)Eli Lilly and Company, Indianapolis, IN, USA. (3)HaaPACS GmbH, Schriesheim, Germany. (4)Costello Medical, Bristol, UK. (5)Costello Medical, London, UK. (6)Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. (7)Clinical Sciences Centre, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. PURPOSE: This study presents an updated health economic model for evaluating the long-term cost-effectiveness of interventions in overweight and obesity, integrating new clinical evidence from the SURMOUNT clinical trial programme and methodological advancements in type-2 diabetes and obstructive sleep apnea (OSA) modelling. PATIENTS AND METHODS: An updated individual patient simulation model evaluated the costs and long-term clinical outcomes of tirzepatide (5, 10, 15.0 mg) versus diet and exercise (D&E) alone in patients with a body mass index (BMI) ≥30 kg/m2 (obesity), or BMI ≥27 to <30 kg/m2 (overweight) + ≥1 obesity-related complication with a UK healthcare perspective. Key improvements over a previously published model were introduced, including modelling remission and progression of OSA, capturing realistic patterns of D&E discontinuation, incorporating HbA1c as a continuous cardiometabolic endpoint and transition to R-based implementation over VBA. Primary results include incremental cost-effectiveness ratios (ICERs; cost/QALY), costs, life years gained and quality-adjusted life years (QALYs). Secondary outcomes including clinical outcomes, random seed and cohort convergence, deterministic sensitivity results and run time were also calculated. RESULTS: The refined model predicted that all tirzepatide doses were cost-effective compared to D&E at a £20,000/QALY gained WTP (willingness-to-pay) threshold (ICERs: £8,327-£10,157). Refined estimation of long-term D&E discontinuation and OSA remission likely contributed to lower incremental costs, higher QALYs, and reduced ICERs compared with the previous model, aligning outcomes more closely with expected benefits from weight management treatment. Transitioning to R-based implementation reduced run time (e.g. by 4.52 h for deterministic sensitivity analyses) and enhanced model stability in all analyses conducted. CONCLUSION: This enhanced economic model represents a significant advancement in the evaluation of obesity pharmacotherapy, designed to enhance clinical relevance, technical robustness, and increase usability. It supports evidence-based decision-making for chronic weight management treatment in the UK, and beyond, while offering a scalable platform for future therapeutic evaluations. Plain Language Summary: In this study, researchers improved a computer model that estimates how weight-loss treatments affect people’s health and healthcare costs over their lifetime. The model focuses on adults in the UK who are overweight or have obesity and at least one related health condition. It compares treatment with tirzepatide plus diet and exercise to diet and exercise alone. It builds on an earlier model but includes several important updates based on new clinical evidence and feedback from experts.The updated model more accurately reflects real-world health changes by tracking how weight loss affects conditions such as obstructive sleep apnea (a condition where breathing repeatedly stops and starts during sleep) and type 2 diabetes over t

Mentions Tirzepatide

Sauchinone attenuates UVB-induced photoaging by suppressing oxidative stress and ferroptosis through activation of the Keap1-Nrf2 pathway in dermal fibroblasts.

1. Pharm Biol. 2026 Dec;64(1):764-782. doi: 10.1080/13880209.2026.2668138. Epub 2026 May 21. Sauchinone attenuates UVB-induced photoaging by suppressing oxidative stress and ferroptosis through activation of the Keap1-Nrf2 pathway in dermal fibroblasts. Zhang X(1)(2), Wang J(1)(2), Zhou Y(1)(2), Shen C(1)(2), Yuan M(1)(2), Li Q(1)(2), Li W(3). Author information: (1)Shanghai Qiran Biotechnology Co., Ltd, Shanghai, PR China. (2)Shanghai Jinjia Technology Co., Ltd, Shanghai, PR China. (3)Department of Dermatology, Shanghai Institute of Dermatology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. CONTEXT: Skin photoaging induced by chronic ultraviolet B (UVB) exposure is primarily driven by oxidative stress. Emerging evidence suggests that ferroptosis contributes to UVB-induced skin damage. Sauchinone, a phenolic lignan derived from Saururus chinensis, possesses potent antioxidant and anti-inflammatory properties; however, its protective effects and underlying mechanisms against UVB-induced skin damage remain unclear. OBJECTIVE: This study aimed to investigate the potential photoprotective effects and underlying mechanisms of sauchinone against UVB-induced skin damage in dermal fibroblasts. MATERIALS AND METHODS: UVB-induced HFFs were used as an in vitro model of photoaging. Cellular senescence, extracellular matrix (ECM) degradation, oxidative stress, and ferroptosis were evaluated using fluorescence staining, flow cytometry, qPCR, ELISA, and western blot analysis. RESULTS: Sauchinone significantly attenuated cellular senescence and ECM degradation in UVB-induced HFFs, as evidenced by reduced SA-β-gal activity and decreased expression of p16 and p21, increased COL1A1 levels, and decreased MMP1 levels. Sauchinone also alleviated oxidative stress by reducing intracellular ROS and MDA levels while restoring GSH content and antioxidant enzyme activity. In addition, sauchinone attenuated ferroptosis-related features, including reduced lipid ROS and Fe2+ accumulation, and normalized ACSL4, GPX4, FTH1, and SLC7A11 expression. Mechanistically, sauchinone was associated with activation of the Keap1-Nrf2 pathway, as evidenced by decreased Keap1 levels, enhanced nuclear translocation of Nrf2, and upregulation of downstream antioxidant genes. Importantly, pharmacological inhibition of Nrf2 using ML385 partially reversed the protective effects of sauchinone on oxidative stress, ferroptosis, cellular senescence, and ECM degradation. DISCUSSION AND CONCLUSIONS: Our findings revealed that sauchinone protected fibroblasts against UVB-induced photoaging by inhibiting oxidative stress and ferroptosis, potentially through activation of the Keap1-Nrf2 pathway. DOI: 10.1080/13880209.2026.2668138 PMCID: PMC13195707 PMID: 42165632 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest. The funders had no role in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the paper.

Mentions P21

Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway.

1. Ann Med. 2026 Dec;58(1):2663263. doi: 10.1080/07853890.2026.2663263. Epub 2026 Apr 30. Tranexamic acid protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. Lin Y(1)(2)(3), Wang Y(1)(2), Wang W(1)(2)(3), Deng Z(1)(2)(3), Zhang Y(1)(2), Peng Y(1)(2), Tang J(1)(2)(3), Li J(1)(2)(3), Huang C(1)(2)(3)(4), Jian D(1)(2)(3). Author information: (1)Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China. (2)National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. (3)Hunan Key Laboratory of ageing Biology, Xiangya Hospital, Central South University, Changsha, China. (4)Department of Dermatology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. BACKGROUND: Tranexamic acid (TXA) is widely used for pigmentary disorders, but its anti-ageing potential remains unclear. This study aimed to evaluate whether topical 3% TXA improves early periorbital wrinkles in women with facial melasma and to investigate whether TXA protects human dermal fibroblasts from D-galactose-induced senescence via the GPR30/MAPK pathway. METHODS: Fifty women with melasma were randomized to 3% TXA serum plus moisturizer or moisturizer alone for 8 weeks, with follow-up to week 12. Periorbital wrinkles were graded using a modified Fitzpatrick Wrinkle Scale (MFWS). Separately, D-gal-induced senescence in HDFs was assessed via viability, SA-β-gal activity, senescence markers, ROS, antioxidant enzymes, SASP/ECM gene expression, and MAPK activation. GPR30 involvement was examined using antagonist G15, shRNA knockdown, and molecular docking. RESULTS: Topical TXA produced significantly greater MFWS reductions versus moisturizer alone at weeks 4, 8, and 12, with benefit persisting post-treatment. In HDFs, TXA preserved viability, reduced SA-β-gal positivity, attenuated p21/p16, restored Lamin B1, decreased ROS, and rescued antioxidant activities. TXA downregulated IL-6, IL-8, MMP1, and MMP3, and suppressed D-gal-induced ERK, JNK, and p38 phosphorylation. These effects were weakened by G15 or GPR30 knockdown; docking supported a stable TXA-GPR30 interaction. CONCLUSIONS: TXA showed clinical anti-wrinkle activity in melasma patients and protected HDFs from D-gal-induced senescence, partly via GPR30-dependent modulation of oxidative stress, SASP/ECM expression, and MAPK signalling. TXA is a promising candidate for skin ageing intervention. DOI: 10.1080/07853890.2026.2663263 PMCID: PMC13134749 PMID: 42059427 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions P21

Lung microbiota dysbiosis mediates PM(2.5)-induced pulmonary inflammation through antibiotic-reversible mechanisms.

1. J Immunotoxicol. 2026 Dec;23(1):2660647. doi: 10.1080/1547691X.2026.2660647. Epub 2026 Apr 23. Lung microbiota dysbiosis mediates PM(2.5)-induced pulmonary inflammation through antibiotic-reversible mechanisms. Zheng Y(1), Zhang L(2)(3)(4), Tian J(2)(3)(4), Li N(2)(3)(4), Li Q(2)(3)(4), Li F(5), Meng J(5), Zhang Z(2)(6), Yun X(5), Duan S(1). Author information: (1)School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. (2)Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China. (3)Shandong Provincial Key Medical and Health Laboratory of Women's Occupational Exposure and Fertility Preservation, Jinan, China. (4)Jinan (Preparatory) Key Laboratory of Women's Diseases and Fertility Preservation, Jinan, China. (5)School of Public Health, North China University of Science and technology, Tangshan, China. (6)School of Public Health, Qingdao University, Qingdao, China. Fine particulate matter (PM2.5) exposure contributes to over 4 million premature deaths annually, yet the mechanistic role of lung microbiota in PM2.5-induced pulmonary inflammation remains poorly understood. In collaboration of 16S rRNA and single-cell RNA multi-omics analysis and in vivo/in vitro experimental validation with antibiotic intervention strategies, the study here examined PM2.5-microbiota interactions in murine PM2.5 exposure models and cellular systems. It was found that PM2.5 exposure induced lung microbiota dysbiosis characterized by Gram-negative bacterial expansion, particularly Proteobacteria dominance, accompanied by reduced microbial diversity. scRNA analysis revealed coordinated activation of TLR4/MyD88/NLRP3 inflammatory signaling pathways and p53/p21/p16-mediated cell cycle arrest. Moreover, PM2.5 exposure activated NLRP3 inflammosome-dependent macrophage pyroptosis as evidenced by increased interleukin (IL)-1β, IL-18, caspase-1, and GSDMD expression. In vitro studies demonstrated that the inflammatory changes induced by PM2.5 exposure were statistically indistinguishable from those of LPS-positive controls, confirming endotoxin-like mechanisms. Critically, antibiotic pretreatment effectively attenuated PM2.5-induced inflammatory responses, cell cycle arrest, and tissue pathology, which established causality between microbiota disruption and pulmonary dysfunction. In conclusion, this study revealed lung microbiota dysbiosis as a critical mediator of PM2.5-induced pulmonary inflammation through Gram-negative bacterial expansion and subsequent endotoxin-like activation of inflammatory cascades, thereby providing novel mechanistic insights and potential microbiome-targeted therapeutic strategies for air pollution-associated respiratory diseases. DOI: 10.1080/1547691X.2026.2660647 PMID: 42024669 [Indexed for MEDLINE]

Mentions P21

The epigenetic archaeology of human-dog companionship.

1. Epigenetics. 2026 Dec;21(1):2676911. doi: 10.1080/15592294.2026.2676911. Epub 2026 May 24. The epigenetic archaeology of human-dog companionship. Faraji J(1), Metz GAS(1)(2). Author information: (1)Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada. (2)Southern Alberta Genome Sciences Centre, University of Lethbridge, Lethbridge, AB, Canada. Humans have coexisted with dogs for at least 20,000 years, yet the biological consequences of long-term human-dog co-residence remain poorly understood. We propose that sustained exposure to dogs may have contributed to context-dependent variation in human stress regulation, immune function, and socio-emotional neurobiology through environmentally responsive epigenetic mechanisms. Here, we define an epigenetic imprint as detectable differences in gene-regulatory marks, including DNA methylation at environmentally sensitive loci, consistent with developmental plasticity and early-life environmental calibration rather than germline inheritance. In this Commentary, we integrate evidence from genomics, neuroscience, microbiome research, evolutionary anthropology, and palaeoepigenetics to examine whether multispecies living environments may represent an under-recognised biological exposure shaping human regulatory biology. We further outline a framework to test whether archaeologically inferred dog co-residence is associated with epigenetic and regulatory signatures in ancient human populations while accounting for major ecological and demographic confounds. Overall, we argue that human-dog cohabitation provides a plausible and testable model for investigating how long-term social and ecological relationships may influence stress and immune regulation across populations. DOI: 10.1080/15592294.2026.2676911 PMCID: PMC13203029 PMID: 42177806 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions Oxytocin

Vaginal trial outcomes and emergency cesarean section factors among women with different classifications of hypertensive disorders of pregnancy.

1. J Matern Fetal Neonatal Med. 2026 Dec;39(1):2648161. doi: 10.1080/14767058.2026.2648161. Epub 2026 May 5. Vaginal trial outcomes and emergency cesarean section factors among women with different classifications of hypertensive disorders of pregnancy. Zhang Y(1), Sun J(1), Shen J(1). Author information: (1)Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, Shenyang, China. BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a prevalent complication and a leading cause of maternal and perinatal mortality. While vaginal delivery is generally possible for most women with HDP, there is no standardized framework detailing variations in vaginal delivery outcomes across different HDP classifications or identifying the factors influencing emergency cesarean section (EmCS). OBJECTIVE: To explore the vaginal trial outcomes and risk factors associated with emergency cesarean section among women with different classifications of HDP. METHODS: This was a single-center retrospective cohort study of 894 pregnant women with HDP who underwent a vaginal trial. Of these, 584 were diagnosed with gestational hypertension, 216 with pre-eclampsia, and 94 with chronic hypertension. The study collected and compared detailed maternal and perinatal outcomes. RESULTS: (1) The success rate of vaginal delivery ranged from 85.1% to 90.8% across various classifications of HDP without significant differences. (2) Chronic hypertension was four times more likely to lead to intrapartum poorly controlled blood pressure than gestational hypertension. (3) Factors influencing EmCS in HDP included parity, antepartum BMI, labor induction, intrapartum fever, intrapartum antihypertensive use, and oxytocin during stages of labor. Parity served as an independent protective factor across all HDP classifications. Stratified analysis revealed that for gestational hypertension, risk factors included antepartum BMI ≥ 30 kg/m2, labor induction, and intrapartum antihypertensive use. For pre-eclampsia, oxytocin and intrapartum fever were risk factors. In chronic hypertension, antepartum BMI ≥ 30 kg/m2 and intrapartum fever were identified as risk factors, although the former was not significant. CONCLUSION: The success rate of vaginal trials across various classifications of HDP is high. Vaginal trial can impact intrapartum blood pressure, particularly for women with chronic hypertension. Tailored management strategies should include encouraging vaginal trial for multiparous women, control of antepartum BMI, judicious use of labor induction, and vigilant monitoring of hypertension and fever, with individualized evaluation and treatment based on HDP classification. DOI: 10.1080/14767058.2026.2648161 PMID: 42086488 [Indexed for MEDLINE]

Mentions Oxytocin

Retraction statement: carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery.

1. J Matern Fetal Neonatal Med. 2026 Dec;39(1):2667973. doi: 10.1080/14767058.2026.2667973. Epub 2026 May 12. Retraction statement: carbetocin versus oxytocin for prevention of postpartum hemorrhage in obese nulliparous women undergoing emergency cesarean delivery. [No authors listed] Retraction of J Matern Fetal Neonatal Med. 2016;29(8):1257-60. doi: 10.3109/14767058.2015.1043882. DOI: 10.1080/14767058.2026.2667973 PMID: 42120321

Mentions Oxytocin

GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers.

1. Ann Med. 2026 Dec;58(1):2660386. doi: 10.1080/07853890.2026.2660386. Epub 2026 Apr 18. GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers. Chikatimalla R(1), Shah A(2), Shah T(3), Perry G(4), Banker H(5), Aggarwal K(6), Jain R(7). Author information: (1)Kamineni Institute of Medical Sciences, Narketpally, India. (2)GMERS Medical College, Gotri, Vadodara, India. (3)GMERS Medical College, Valsad, India. (4)Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. (5)Maulana Azad Medical College, New Delhi, India. (6)Dayanand Medical College and Hospital, Ludhiana, Punjab, India. (7)Division of Hospital Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. OBJECTIVES: To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention. METHODS: A narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy. RESULTS: GLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities. CONCLUSION: GLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management. Plain Language Summary: GLP-1 receptor agonist (GLP-1RA) therapy should be incorporated into a broad approach for risk reduction for stroke in patients with type 2 DM, especially in situations where prevention of ischaemic stroke is of high importance.Long-acting GLP-1 receptor agonists (e.g., semaglutide and dulaglutide) are preferred over shorter-acting preparations for their cerebrovascular protective effects, properties of which are more consistent and beneficial for the risk of ischaemia.GLP-1RA therapy could provide a special advantage to patients with multiple risk factors for cardiometabolic diseases such as obesity, hypertension, dyslipidemia and documented atherosclerotic cardiovascular disease.On the other hand, the neuroprotective properties of GLP-1RAs, which occur through anti-inflammatory, antioxidant, endothelial-stabilising or mitochondrial-protective actions, provide rationale for the use.Treatment should be individualised for renal function, tolerance, potential for compliance, cost and accessibility. This allows for maximal long-term cerebrovascular benefits. DOI: 10.1080/07853890.2026.2660386 PMCID: PMC13094292 PMID: 41999297 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the authors.

Mentions Semaglutide

A qualitative study exploring experiences about using semaglutide for weight loss in a rural setting in Denmark - 'she is probably on the meds'.

1. Scand J Prim Health Care. 2026 Dec;44(1):2636584. doi: 10.1080/02813432.2026.2636584. Epub 2026 Mar 16. A qualitative study exploring experiences about using semaglutide for weight loss in a rural setting in Denmark - 'she is probably on the meds'. Guldhammer A(1), Drivsholm T(1), Tomova-Olsen SA(1), Tranberg Jensen K(1). Author information: (1)The Section of General Practice and the Research Unit for General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. INTRODUCTION: Semaglutide has gained attention for its efficacy in weight loss. However, little is known about patients' experiences. This study explores patient experiences with using Semaglutide for weight loss (SEMA-WL) in a rural Danish context. METHODS: We conducted semi-structured interviews with nine participants from a rural Danish municipality, recruited from a local clinic. The sample included six women and three men, aged 33-65, who had been prescribed SEMA-WL for at least two months. Data was analysed using systematic text condensation. FINDINGS: We identified four themes. First, we highlight different experiences of negative perceptions from the local community for using SEMA-WL, often perceived as 'cheating' or as 'an easy way out'. Furthermore, we describe how SEMA-WL is experienced to provide more energy in the participants everyday lives but also viewed as a short-term intervention rather than a permanent solution, assisted by concerns of weight regain. Finally, we show how the participants continuously outweigh the risks of using new medication fearing potential long-term side effects versus living with obesity. CONCLUSION: The study highlights the complex social dynamics and personal experiences of using SEMA-WL. While medication offers benefits, it also presents challenges such as social stigma, concerns about long-term effectiveness and side effects, and financial costs. Future research should focus on investigating the experiences of using SEMA-WL in other and more diverse settings as well as the contact and information exchange between patients and healthcare providers. DOI: 10.1080/02813432.2026.2636584 PMCID: PMC12997375 PMID: 41838446 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Mentions Semaglutide

Design, synthesis, and stability evaluation of semaglutide-derived lactam-stapled peptide scaffolds for GLP-1R targeting.

1. J Enzyme Inhib Med Chem. 2026 Dec;41(1):2714331. doi: 10.1080/14756366.2026.2714331. Epub 2026 Aug 11. Design, synthesis, and stability evaluation of semaglutide-derived lactam-stapled peptide scaffolds for GLP-1R targeting. Liu T(1), Ren X(1), Li Y(1), Wang J(1), Chen J(1), Lin R(1), Zhang J(1). Author information: (1)School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Glucagon-like peptide-1 receptor (GLP-1R) ligands including semaglutide play an important role in drug discovery. Herein, a short semaglutide-derived GLP-1R-engaging segment was used as the basis for scaffold construction, and conformational restabilisation was introduced through lactam stapling and bulky aromatic non-natural amino acid substitution. A total of 108 stapled peptide candidates were designed by structure-guided modelling and virtual screening. Among them, 35 peptides were synthesised and characterised. Most stapled analogues showed improved serum and proteolytic stability relative to semaglutide, and 11CP-17B, 11CP-17N, and 11CP-19N showed the most favourable stability profiles. Molecular dynamics simulations and MM-GBSA analysis were consistent with receptor-compatible poses and favourable predicted interaction patterns for these representative analogues. Collectively, these results define a practical strategy for constructing stabilised semaglutide-derived peptide scaffolds and provide a basis for subsequent functional optimisation of GLP-1R-targeting peptides. DOI: 10.1080/14756366.2026.2714331 PMID: 42578506 [Indexed for MEDLINE]

Mentions Semaglutide

Meox1 promotes hepatocellular carcinoma progression potentially via regulation of cell cycle and p21 expression.

1. Cell Adh Migr. 2026 Dec;20(1):2658289. doi: 10.1080/19336918.2026.2658289. Epub 2026 Apr 19. Meox1 promotes hepatocellular carcinoma progression potentially via regulation of cell cycle and p21 expression. Ruan J(1), Xie Y(2), Zhang C(3), Sun D(3). Author information: (1)Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shan'xi, People's Republic of China. (2)Hebei Key Laboratory of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, People's Republic of China. (3)The Liver Disease Center of PLA, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, People's Republic of China. Meox1 is aberrantly expressed in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the effects of Meox1 on HCC cells and explore the underlying molecular mechanisms. Cell proliferation, colony formation, migration, invasion, and cell cycle distribution were assessed by CCK-8, clonogenic, Transwell, and flow cytometry assays, respectively. Protein expression was examined by Western blotting. Meox1 silencing significantly inhibited proliferation, clonogenic capacity, migration and invasion of HCC cells. Cell cycle analysis showed a reduction in G1-phase cells with a marked accumulation in the G2 phase following Meox1 knockdown. Western blot analysis revealed that suppression of Meox1 reduced p21CIP1/WAF1 expression. Meox1 contributest to HCC progression and may represent a potential therapeutic target. DOI: 10.1080/19336918.2026.2658289 PMCID: PMC13097779 PMID: 42002886 [Indexed for MEDLINE] Conflict of interest statement: The authors have no relevant financial or non-financial interests to disclose.

Mentions P21

Nucleus accumbens oxytocin modulates avoidance-related behaviors following social isolation in prairie voles.

1. Neuropharmacology. 2026 Nov 15;299:111113. doi: 10.1016/j.neuropharm.2026.111113. Epub 2026 Jul 24. Nucleus accumbens oxytocin modulates avoidance-related behaviors following social isolation in prairie voles. Liu Y(1), Duclot F(2), Jia X(1), Wang Z(3), Kabbaj M(4). Author information: (1)Department of Psychology, Florida State University, Tallahassee, FL, USA; Program in Neuroscience, Florida State University, Tallahassee, FL, USA. (2)Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA; Program in Neuroscience, Florida State University, Tallahassee, FL, USA. (3)Department of Psychology, Florida State University, Tallahassee, FL, USA; Program in Neuroscience, Florida State University, Tallahassee, FL, USA. Electronic address: zwang@psy.fsu.edu. (4)Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA; Program in Neuroscience, Florida State University, Tallahassee, FL, USA. Electronic address: mohamed.kabbaj@med.fsu.edu. Chronic social isolation and loneliness are associated with several neuropsychiatric disorders including depression and anxiety. Given its ability to modulate a wide range of processes linked to social interactions, the therapeutic potential of the neuropeptide oxytocin has gathered interest. However, its effects are highly context-dependent, highlighting the need for preclinical models that better capture the breadth of human social interactions and the consequences of their loss. The socially monogamous prairie vole carries a high translational value due to its ability to form enduring social attachments. Here, we aimed at characterizing the role of the oxytocin neurotransmission in the nucleus accumbens (NAc) in the negative consequences of social isolation in prairie voles. Following six weeks of isolation, females exhibited an avoidance of the open arms of an elevated plus maze EPM), lower NAc oxytocin receptor (OXTR) expression, and reduced activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVN) that project to the NAc. Using a combination of site- and projection-specific pharmacological and chemogenetic approaches, we show that the activation of oxytocin neurotransmission in the NAc originating from the PVN reverses the avoidance-related behaviors in the EPM induced by isolation in an OXTR-dependent manner, whereas its blockade promotes avoidance-related behaviors in group-housed control females. Altogether, our findings delineate a model in which the promotion of avoidance-related behaviors following social isolation in female prairie voles is mediated by a dampened response of PVN-to-NAc oxytocin projections, providing additional insights into the negative consequences of social isolation associated with anxiety disorders. Copyright © 2026. Published by Elsevier Ltd. DOI: 10.1016/j.neuropharm.2026.111113 PMID: 42498141 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no competing financial interests that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

Hydrogen reshapes the senescent microenvironment of callus to enhance the healing of anti-osteoporotic-drug-induced atypical femoral fracture.

1. Biomaterials. 2026 Nov;334:124287. doi: 10.1016/j.biomaterials.2026.124287. Epub 2026 May 7. Hydrogen reshapes the senescent microenvironment of callus to enhance the healing of anti-osteoporotic-drug-induced atypical femoral fracture. An Y(1), Zhang H(2), Zhang Y(3), Zhang S(3), Zheng L(4), Shao H(3), Du W(5), Cheng L(6), Sun W(7), Ma J(6), Ruan Y(5), Xu J(8), Qin L(9). Author information: (1)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; The Sir Yue-Kong Pao Cancer Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany. (2)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; The Sir Yue-Kong Pao Cancer Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. (3)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. (4)Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Chinese Academy of Sciences Limited, Hong Kong Special Administrative Region of China. (5)Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region of China. (6)Department of Orthopedics & Joint Surgery, National Center of Integrated Chinese and Western Medicine, Center for Osteonecrosis and Hip Dysplasia Preservation, China-Japan Friendship Hospital, Beijing, PR China. (7)Chengdu Hip and Femoral Head Hospital, Chengdu, PR China. (8)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: jiankunxu@cuhk.edu.hk. (9)Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China. Electronic address: lingqin@cuhk.edu.hk. Long-term bisphosphonates (BPs) are widely used to treat osteoporosis, however, they are paradoxically associated with the development of atypical femoral fractures (AFFs), which often characterized by impaired healing. In this study, we induced an AFF model using zoledronate (ZOL) administration in ovariectomized (OVX) osteoporotic rats, following a unilateral femoral fracture. Here we identified that a local pro-senescent microenvironment causes persistent inflammation and impairs effective regeneration in rat AFFs. Molecular hydrogen has demonstrated anti-senescence and anti-inflammatory properties, yet its effects on AFF healing remain unexplored. Therefore, we treated the AFF rats with hydrogen rich water (HRW). The outcomes were assessed by radiographs, histology, micro-CT, and biomechanical tests. The fr

Mentions P21

Yi-Qi-Jian-Pi formula alleviates hepatic fibrosis in acute-on-chronic liver failure by regulating ferritinophagy-mediated hepatic stellate cell senescence.

1. J Ethnopharmacol. 2026 Oct 28;369:121865. doi: 10.1016/j.jep.2026.121865. Epub 2026 May 15. Yi-Qi-Jian-Pi formula alleviates hepatic fibrosis in acute-on-chronic liver failure by regulating ferritinophagy-mediated hepatic stellate cell senescence. Chen J(1), Tang X(1), Fang M(1), Hu S(1), Wang J(1), Chen X(2), Xiao Q(2), Wang X(1), Xie F(3), Tan S(4). Author information: (1)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Clinical Research Center, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. (2)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. (3)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China; Department of Liver Disease, Jinling Hospital affiliated to Medical College of Nanjing University, Nanjing, Jiangsu Province, 210001, China. Electronic address: rosemary1223@126.com. (4)Department of Integrated TCM and Western Medicine, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China. Electronic address: fsyy01455@njucm.edu.cn. ETHNOPHARMACOLOGICAL RELEVANCE: Acute-on-chronic liver failure (ACLF) represents a severe clinical syndrome characterized by rapid exacerbation of chronic hepatic disease. Liver fibrosis (LF) significantly contributes to the advancement of ACLF pathology. The traditional Chinese medicine (TCM) preparation Yi-Qi-Jian-Pi formula (YQJPF) exhibits promising therapeutic effects on ACLF and LF; however, the underlying pharmacological mechanisms and active components remain incompletely understood. AIM OF THE STUDY: This study seeks to elucidate the pharmacodynamic properties, active constituents, and underlying mechanisms of YQJPF in treating liver fibrosis within an ACLF rat model, focusing specifically on ferritinophagy activation and the induction of hepatic stellate cell (HSC) senescence. MATERIALS AND METHODS: A rat model of ACLF was induced via combined administration of CCl4 and LPS/D-GalN, and an in vitro model was established using human hepatic stellate cells (LX2). Liver-targeted active components were characterized using UHPLC-Q-Orbitrap-MS/MS analysis, with network pharmacology utilized to predict critical molecular targets. NCOA4 siRNA and ferrostatin-1 were used to validate mechanism specificity. The therapeutic effects and associated mechanisms were systematically evaluated through biochemical assays, histopathological examinations, and molecular and cellular analyses. RESULTS: YQJPF improved liver histopathology and attenuated fibrosis and ACLF in rats. It inhibited viability and proliferation of LX2 cells, decreased TGF-β1 secretion, and downregulated α-SMA and Collagen I expression. UHPLC-Q-Orbitrap-MS/MS identified 82 liver-tropic components (including 50 prototypes and 32 metabolites) in rat liver tissues. Network pharmacology revealed 257 potential targets, with 135 overlapping with hepatic fibrosis-related targets (core targets included TP53, NCOA4, and CDKN2A). YQJPF induced HSC senescence (upregulated p16, p21, and HMGA1; downregulated TERT; triggered cell cycle arrest) and activated ferritinophagy (upregulated NCOA4, Beclin1, LC3BII/I; downregulated FTH1 and p62; increased ROS/iron accumulation). NCOA4 knockdown or Fer-1 treatment reduced YQJPF-induced HSC senescence and antifibrotic effects. CONCLUSION: YQJPF reduces ACLF-related LF by NCOA4-mediated ferritinophagy, which promotes HSC senescence. The 82 liver-tropic components and 135 overlapping targets highlight its multi-component, multi-target effects, providing a scientific foundation for its clinical application. Copyri

Mentions P21

From evidence to practice: Identifying candidates for semaglutide in chronic atherosclerotic disease.

1. Int J Cardiol. 2026 Oct 15;461:134646. doi: 10.1016/j.ijcard.2026.134646. Epub 2026 Jun 26. From evidence to practice: Identifying candidates for semaglutide in chronic atherosclerotic disease. Maggioni AP(1), Orso F(2), Lucci D(2), De Luca L(3), Colivicchi F(4). Author information: (1)ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. Electronic address: maggioni@heartcarefoundation.it. (2)ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. (3)Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. (4)Clinical and Rehabilitation Cardiology Department, San Filippo Neri Hospital, ASL Roma 1, Roma, Italy. BACKGROUND AND AIM: Randomised clinical trials (SELECT and SOUL) demonstrated that semaglutide, a GLP-1 receptor agonist, reduces the combined outcome measure of atherothrombotic events or cardiovascular mortality in patients with coronary artery disease, both with and without diabetes. Because real-world populations may differ from trial cohorts, we assessed the proportion of patients potentially eligible for semaglutide using the criteria set out by the regulatory authorities based on the SELECT and SOUL results. METHODS AND RESULTS: Patients whose clinical characteristics were comparable to those of patients enrolled in the SELECT and SOUL trials were identified within the START and BRING-UP prevention registries. Among 12,430 patients, 623 were excluded because of severe renal impairment or ongoing GLP-1 receptor agonist therapy. The final population included 11,807 patients: 8682 without diabetes and 3125 with diabetes. Among non-diabetic patients, 3689 (42.5%) were SELECT-like, defined as overweight or obese individuals with established coronary disease. Among diabetic patients, 3059 (97.9%) were SOUL-like, defined as individuals aged ≥50 years with cardiovascular disease. Overall, 6748 of 12,430 patients (54.3%) theoretically fulfilled eligibility criteria for semaglutide treatment in real-world cardiology practice. CONCLUSIONS: According to the criteria set out by the regulatory authorities based on the SELECT and SOUL trial results, a large proportion of patients with coronary artery disease managed by cardiologists may be potentially eligible for semaglutide therapy. Identifying the target population for this therapeutic strategy may help clinicians and healthcare authorities estimate unmet clinical needs and evaluate the sustainability of innovative approaches for secondary cardiovascular prevention. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.ijcard.2026.134646 PMID: 42361988 [Indexed for MEDLINE]

Mentions Semaglutide

Apabetalone mediates HIV-1 transcriptional activation and clearance of latently infected cells via LncRNA OSER1-AS1.

1. Gene. 2026 Oct 10;1006:150248. doi: 10.1016/j.gene.2026.150248. Epub 2026 Jun 1. Apabetalone mediates HIV-1 transcriptional activation and clearance of latently infected cells via LncRNA OSER1-AS1. Song B(1), Lin X(1), Cao L(1), Zhang L(1), Liu S(1), Wang X(1), Fan G(1), Chen X(1), Zhu L(2). Author information: (1)Harbin Medical University Affiliated Fourth Hospital, No. 23 Yiyuan Street, Nangang District, Harbin 150001, Heilongjiang Province, China. (2)Harbin Medical University Affiliated Fourth Hospital, No. 23 Yiyuan Street, Nangang District, Harbin 150001, Heilongjiang Province, China. Electronic address: zlyhydsy@126.com. PURPOSE: To explore the effect of Apabetalone on activating HIV-1 virus transcription and its molecular mechanism. METHODS: Peripheral blood mononuclear cells(PBMCs) latently infected with HIV-1 and J-Lat 10.6 cells were divided into two groups: a blank control group and an Apabetalone-treated group. After 48 h of culture with Apabetalone, bioinformatics and qRT-PCR were performed. Recombinant lentiviral vectors containing OSER1-AS1 and CDK9, along with empty vectors, were transfected into the cells for subsequent green fluorescent protein(GFP) fluorescence detection, cell cycle analysis, and apoptosis assays. RESULTS: Apabetalone efficiently activated HIV-1 viral transcription in J-Lat 10.6 and PBMC cells, increased the G0/G1 ratio of cells, and induced apoptosis. Apabetalone also downregulated the expression levels of MYC and p-Rb, and upregulated the expression levels of Tat and P21. Silencing OSER1-AS1 reduced apabetalone activation of HIV-1 transcription and inhibited apoptosis. CONCLUSION: Apabetalone enhances HIV-1 transcription by upregulating OSER1-AS1 expression, thereby promoting Tat-CDK9 binding. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.gene.2026.150248 PMID: 42229576 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions P21

Central administration of oxytocin increases social interaction and shoaling behaviour in guppies.

1. Behav Brain Res. 2026 Oct 2;514:116363. doi: 10.1016/j.bbr.2026.116363. Epub 2026 Jul 7. Central administration of oxytocin increases social interaction and shoaling behaviour in guppies. Cabrera-Álvarez MJ(1), Swaney WT(2), Reader SM(3). Author information: (1)Department of Biology, McGill University, Montreal, Quebec, Canada; FishEthoGroup Association, Faro, Portugal; Centre of Marine Sciences (CCMAR/CIMAR LA), Campus de Gambelas, Universidade do Algarve, Faro, Portugal. (2)Department of Biology, McGill University, Montreal, Quebec, Canada; School of Biological and Environmental Sciences, Liverpool John Moores University, Liverpool, UK. Electronic address: w.t.swaney@ljmu.ac.uk. (3)Department of Biology, McGill University, Montreal, Quebec, Canada. The nonapeptides vasotocin, oxytocin and their homologues regulate a wide range of social behaviours such as mating, aggression, social recognition and parental care across vertebrates. These varied influences across diverse taxa suggest a highly-conserved, ancestral role for nonapeptides in animal social behaviour. Here, we address the role of nonapeptides in a foundational social behaviour, the tendency of individuals to group with conspecifics. We investigated the effects of administration of nonapeptides on shoaling behaviour in the guppy (Poecilia reticulata), a small freshwater fish that is a model system for studying the evolution of social behaviour in the wild. We conducted two experiments using intracerebroventricular administration in wild-origin guppies to investigate the effects of nonapeptides and their antagonists on grouping behaviour, focusing first on oxytocin, and then on vasotocin. We monitored shoaling behaviour for 2.5 h after each administration and found that after 90 min, oxytocin significantly increased social interaction, with a similar effect on shoaling behaviour. Vasotocin did not produce significant changes in social interaction or shoaling preferences, and putative receptor antagonists for oxytocin and vasotocin did not have clear behavioural effects. These findings show that central administration of oxytocin increases shoaling tendencies in guppies, suggesting it influences this fundamental social behaviour. We also found that effects were time-dependent, highlighting the importance of studying the temporal dynamics of nonapeptide actions on behaviour. Our work also demonstrates the feasibility of intracerebroventricular injections for central pharmacological manipulations in small fish, opening new potential avenues for behavioural neuroscience in non-model species. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.bbr.2026.116363 PMID: 42413702 [Indexed for MEDLINE]

Mentions Oxytocin

Age-dependent effects of cannabidiol on cortical hyperexcitability in an experimental model of malformation of cortical development.

1. Exp Neurol. 2026 Oct;404:115879. doi: 10.1016/j.expneurol.2026.115879. Epub 2026 Jun 22. Age-dependent effects of cannabidiol on cortical hyperexcitability in an experimental model of malformation of cortical development. Martins de Lima T(1), Dos Santos FM(2), Schmidt Michel B(2), Schonhofen P(3), Schroder N(4), Klamt F(5), Calcagnotto ME(6). Author information: (1)Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. (2)Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. (3)Laboratory of Cellular Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. (4)Laboratory of Memory Dysfunctions, Department of Physiology, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. (5)Graduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Laboratory of Cellular Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. (6)Neurophysiology and Neurochemistry of Neuronal Excitability and Synaptic Plasticity Laboratory (NNNESP Lab), Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Graduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: elisa.calcagnotto@ufrgs.br. Malformations of cortical development (MCD) are major causes of refractory epilepsies, particularly in children. Cannabidiol (CBD) has demonstrated efficacy in treatment of refractory pediatric epilepsy syndromes. However, preclinical studies addressing its developmental stage-dependent effects, particularly in experimental models of MCD, remain limited. We evaluated the effects of CBD on induced hyperexcitability in cortical brain slices from Wistar rats with and without MCD at distinct developmental stages and examined whether alterations in endocannabinoid system (ECS) components are associated with CBD responsiveness. MCD was induced by bilateral cortical freeze lesion at postnatal day (P0-1) to generate microgyria in the somatosensory cortex. Local field potentials were recorded from cortical slices of juvenile (P21-30) and adolescent (P35-60) Sham and MCD rats. CBD was applied under three different timing paradigms to assess its effects on epileptiform activity induced by modified artificial cerebrospinal fluid containing 4-aminopiridine (4-AP) and 0 Mg2+ (mACSF). Gene expression of ECS components was quantified in cortical tissue by RT-qPCR at both developmental stages. CBD co-applied with mACSF reduced short (>2-10 s) ictal events in slices from Sham and decreased prolonged (>100 s) ictal events in slices mainly from MCD animals at both ages. CBD did not attenuate pre-established hyperexcitability. However, pre-exposure to CBD delayed ictal onset, reduced overall ictal events frequency, particularly in juvenile Sham animals, and abolished long-lasting ictal events in slices from adolescent animals. Cortical samples from juvenile MCD animals exhibited increased gene expression of NAPE-PLD, MGLL, CB1R and CB2R, whereas DAGL was reduced in adolescence. CBD exerted age- and context-dependent modulatory effects on cortical hyperexcitability, with stronger preventive than therapeutic actions. Developmental stage, cortical organization and alterations in ECS components may influence CBD responsiveness. These findings highlight the importance of maturational, cortical network and molecular context when evaluating can

Mentions P21

Changes in salivary biomarkers before farrowing in sows.

1. Theriogenology. 2026 Oct 1;263:117992. doi: 10.1016/j.theriogenology.2026.117992. Epub 2026 May 15. Changes in salivary biomarkers before farrowing in sows. Ortín-Bustillo A(1), Botía M(1), Ornelas MAS(2), Ortiz Sanjuán JM(3), Oudada A(1), Llamas-Amor E(1), Martínez-Subiela S(1), Tvarijonaviciute A(1), Muñoz-Prieto A(1), Arense J(4), Cerón JJ(5), Manzanilla EG(2), Tecles F(1). Author information: (1)Salilab-UMU, Interdisciplinary Laboratory of Clinical Analysis, Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo, 30100, Murcia, Spain. (2)Pig and Poultry Research and Knowledge Transfer Department, Animal and Grassland Research Centre, Teagasc, Irish Agriculture and Food Development Authority, Fermoy, P61 C996, Cork, Ireland; School of Veterinary Medicine, University College Dublin, D04 W6F6, Dublin, Ireland. (3)Pig and Poultry Research and Knowledge Transfer Department, Animal and Grassland Research Centre, Teagasc, Irish Agriculture and Food Development Authority, Fermoy, P61 C996, Cork, Ireland. (4)Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120, Murcia, Spain. (5)Salilab-UMU, Interdisciplinary Laboratory of Clinical Analysis, Veterinary School, Regional Campus of International Excellence 'Campus Mare Nostrum', University of Murcia, Campus de Espinardo, 30100, Murcia, Spain. Electronic address: jjceron@um.es. In this report, a comprehensive panel of analytes, including biomarkers of stress, reproduction-related hormones, biomarkers of inflammation and immunity, oxidative stress biomarkers, minerals, and enzymes, was monitored daily from 3 days before farrowing until the day of farrowing in the saliva of 23 healthy sows. All the analytes with the exception of testosterone, serum amyloid-A, uric acid, calcium, and phosphorous showed an increase on the day of farrowing. Cortisol, cortisone, oxytocin, estradiol, haptoglobin, the cupric reducing antioxidant capacity, and zinc also showed increases on the day just before farrowing compared to the previous days. These results indicated that stress, inflammation, and oxidative stress could occur just the day prior to parturition in sows, as well as changes in some reproductive-related hormones. The results can contribute to improve the understanding of physiological changes preceding parturition in pigs. Whether these changes could be used as farrowing predictors should be further studied in a larger population. Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.theriogenology.2026.117992 PMID: 42172962 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

The kisspeptin analog C6 elicits greater tachyphylaxis and transcriptional activation than kisspeptin-10 and -54.

Mentions Kisspeptin

Acute sublethal ammonia exposure suppresses neurotransmitter expression and impairs behaviors in the early development stages of zebrafish.

1. Comp Biochem Physiol C Toxicol Pharmacol. 2026 Oct;308:110607. doi: 10.1016/j.cbpc.2026.110607. Epub 2026 Jul 1. Acute sublethal ammonia exposure suppresses neurotransmitter expression and impairs behaviors in the early development stages of zebrafish. Liu ST(1), Lin LY(2), Shiao MS(3), Chou MY(4). Author information: (1)Department of Life Science, National Taiwan University, Taipei, 10617, Taiwan. (2)Department of Life Science, School of Life Science, National Taiwan Normal University, Taipei, 11677, Taiwan. (3)Research Laboratory Section, Offices of Health Science Research, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand. (4)Department of Life Science, National Taiwan University, Taipei, 10617, Taiwan. Electronic address: mingyichou@ntu.edu.tw. Ammonia is a pervasive environmental pollutant and a potent neurotoxicant in aquatic ecosystems. Teleosts rely on behavioral plasticity to mitigate environmental stressors; however, embryos, with incomplete organogenesis and developing blood-brain barriers, may lack the acclimation strategies available to adults. Despite this vulnerability, the behavioral responses of early-stage embryos to ammonia exposure remain poorly understood compared with those of adult teleosts. In this study, zebrafish embryos were exposed to sublethal concentrations of NH₄Cl for 96 h, which led to reduced spontaneous locomotion, disrupted light-dark preference, diminished touch-evoked escape responses, and impaired feeding behavior. RT-qPCR revealed marked decreases in oxytocin, vasopressin, tyrosine hydroxylase, choline acetyltransferase, and glutamate decarboxylase transcripts. These data indicate that even nonlethal ammonia levels can induce coordinated neurobehavioral and neurotransmitter deficits during critical windows of vertebrate development. By elucidating the sensitivity of early-life stages to ammonia stress, our findings underscore the necessity of accounting for embryonic sensitivity when evaluating ecological risks and establishing water-quality standards. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.cbpc.2026.110607 PMID: 42385925 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No financial support or compensation has been received from any individuals or organizations that might have an interest in the submitted work. The authors have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter or materials discussed in this manuscript. All authors have disclosed any potential sources of conflict of interest, and none were identified.

Mentions Oxytocin

Association between salivary oxytocin concentration and social loneliness in older adults: Findings from an uncontrolled pre-post multimodal intervention study.

1. Psychoneuroendocrinology. 2026 Oct;192:107968. doi: 10.1016/j.psyneuen.2026.107968. Epub 2026 Jul 20. Association between salivary oxytocin concentration and social loneliness in older adults: Findings from an uncontrolled pre-post multimodal intervention study. Zaharia G(1), Valle VI(2), Corchón S(3), Cauli O(3). Author information: (1)Department of Nursing, Faculty of Nursing and Podiatry, University of Valencia, c/de Méndez y Pelayo, 19, Valencia 46010, Spain. (2)Department of Nursing, Faculty of Nursing and Podiatry, University of Valencia, c/de Méndez y Pelayo, 19, Valencia 46010, Spain; Frailty Research Organized Group (FROG), University of Valencia, Valencia 46010, Spain; Chair of Healthy, Active and Participative Ageing, University of Valencia, Valencia 46010, Spain. Electronic address: maria.v.ibanez@uv.es. (3)Department of Nursing, Faculty of Nursing and Podiatry, University of Valencia, c/de Méndez y Pelayo, 19, Valencia 46010, Spain; Frailty Research Organized Group (FROG), University of Valencia, Valencia 46010, Spain; Chair of Healthy, Active and Participative Ageing, University of Valencia, Valencia 46010, Spain. BACKGROUND: loneliness, whether social or emotional, is a significant public health issue due to its substantial impact on physical and mental health. Building on studies showing that oxytocin levels rise during social interactions, we hypothesised that oxytocin concentration associates with loneliness, and that an intervention aimed at alleviating loneliness could be accompanied by changes in peripheral oxytocin concentration. METHODS: An intervention based on a 13-week multimodal programme (Clinicaltrials.gov identifier: NCT06382181) was conducted with 62 participants (79% women) aged 60 or over, recruited from municipal activity centres in Valencia, Spain. The study was carried out between March and June 2023. The assessment used sociodemographic questionnaires and the De Jong-Gierveld Loneliness Scale, as well as saliva samples collected before and after the multimodal programme aimed at alleviating loneliness in older individuals. Bivariate analyses were used to examine the association between sociodemographic factors, oxytocin and loneliness, and oxytocin concentrations before and after the intervention were compared using the Wilcoxon signed-rank test. A linear regression analysis was performed to determine which variable predicts changes in oxytocin concentration. RESULTS: An increase in salivary oxytocin concentration was observed following the intervention across the entire sample. In the sub-sample of individuals who reported loneliness at baseline, oxytocin concentration in saliva correlated significantly with baseline loneliness (social loneliness, p = 0.003; total loneliness, p = 0.025). Thus, the more intense the perception of loneliness, the lower the baseline levels of oxytocin. Correlations were found between baseline oxytocin and age (p = 0.011, inverse correlation) and level of education (p = 0.019, direct correlation). A direct and significant correlation was observed between loneliness (emotional, social and total) and the number of children (p = 0.04, p = 0.01, p = 0.02, respectively), as well as between social loneliness and caring for grandchildren (p = 0.04). Multivariate analysis revealed that caring for grandchildren had a significant effect (p = 0.008) on changes in oxytocin levels following the intervention. CONCLUSION: The results suggest that salivary oxytocin may be associated with loneliness in older adults; however, further validation is required before salivary oxytocin can be considered a reliable biomarker of loneliness. Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.psyneuen.2026.107968 PMID: 42475809 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or per

Mentions Oxytocin

Lead-guided prodrug development of small molecules as GLP-1R agonists.

1. Bioorg Chem. 2026 Sep 15;180:110210. doi: 10.1016/j.bioorg.2026.110210. Epub 2026 Jul 4. Lead-guided prodrug development of small molecules as GLP-1R agonists. Lentschat H(1), Aboelfotouh HG(2), Nabil P(2), Abdallah M(2), Khalifa H(2), Stichel J(1), Abdel-Halim M(2), Abadi AH(3), Beck-Sickinger AG(4). Author information: (1)Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Bruederstr. 34, 04103 Leipzig, Germany. (2)Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835 Cairo, Egypt. (3)Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835 Cairo, Egypt. Electronic address: ashraf.abadi@guc.edu.eg. (4)Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Bruederstr. 34, 04103 Leipzig, Germany. Electronic address: abeck-sickinger@uni-leipzig.de. The glucagon-like peptide-1 receptor (GLP-1R) is a well-established target for treating obesity and T2DM. To date almost all approved therapies targeting this receptor are peptide-based. The small-molecule GLP-1R agonist danuglipron, developed by Pfizer, demonstrated strong GLP-1 agonistic properties, reductions in body weight and improved glycemic control. Yet, its short duration of action, gastrointestinal side effects, and a potential case of drug-induced liver disease led to discontinuation in clinical trials. In this study, we designed and synthesized a series of acid and ester analogs of danuglipron, incorporating diverse substitution patterns and deliberate modifications, including variable substitutions and key moiety replacements. The corresponding acid forms retained activity comparable to the lead compound and the peptide drug tirzepatide. Notably, the ester compound 4 exhibited a controlled and sustained conversion to its active metabolite 4a in human plasma, as confirmed by mass spectrometry and in vitro GLP-1R activity assays. These findings suggest that the ester derivatives might represent a potential approach for modulating the pharmacokinetic properties of these compounds, and the resulting prodrugs could potentially provide more sustained systemic exposure and possibly offer safety-related advantages; however, these hypotheses require further validation through appropriate in vivo pharmacokinetic and toxicological studies. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.bioorg.2026.110210 PMID: 42424921 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Annette Beck-Sickinger reports financial support was provided by German Research Foundation. All authors, except Peter Nabil and Jan Stichel, have patent pending to no. 26172275.5. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Tirzepatide

Brain kappa opioid receptor availability across stress and social buffering conditions: A positron emission tomography study in coppery titi monkeys.

1. Neuroscience. 2026 Sep 11;611:155-169. doi: 10.1016/j.neuroscience.2026.06.028. Epub 2026 Jun 21. Brain kappa opioid receptor availability across stress and social buffering conditions: A positron emission tomography study in coppery titi monkeys. Manca C(1), Paulus JP(2), Almeida AJ(3), Caceres A(4), Sosnowski MJ(5), Hobson BA(6), Ferrer E(7), Chaudhari AJ(8), Bales KL(9). Author information: (1)Department of Psychology, University of California-Davis, College of Letters and Science, Davis, CA 95616, USA; California National Primate Research Center, Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: cmanca@ucdavis.edu. (2)California National Primate Research Center, Davis, One Shields Avenue, Davis, CA 95616, USA; Neuroscience Graduate Group, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: jppaulus@ucdavis.edu. (3)Department of Biomedical Engineering, University of California-Davis, College of Engineering, Davis, CA 95616, USA; Department of Radiology, University of California-Davis, School of Medicine, Sacramento, CA 95817, USA. Electronic address: ajdalmeida@ucdavis.edu. (4)Department of Biomedical Engineering, University of California-Davis, College of Engineering, Davis, CA 95616, USA. Electronic address: ajcaceres02@gmail.com. (5)Department of Psychology, University of California-Davis, College of Letters and Science, Davis, CA 95616, USA; California National Primate Research Center, Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: meg.sosnowski@gmail.com. (6)Center for Molecular and Genomic Imaging, Department of Biomedical Engineering, University of California-Davis College of Engineering, Davis, CA 95616, USA. Electronic address: bahobson@ucdavis.edu. (7)Department of Psychology, University of California-Davis, College of Letters and Science, Davis, CA 95616, USA. Electronic address: eferrer@ucdavis.edu. (8)California National Primate Research Center, Davis, One Shields Avenue, Davis, CA 95616, USA; Center for Molecular and Genomic Imaging, Department of Biomedical Engineering, University of California-Davis College of Engineering, Davis, CA 95616, USA; Department of Radiology, University of California-Davis, School of Medicine, Sacramento, CA 95817, USA. Electronic address: ajchaudhari@ucdavis.edu. (9)Department of Psychology, University of California-Davis, College of Letters and Science, Davis, CA 95616, USA; California National Primate Research Center, Davis, One Shields Avenue, Davis, CA 95616, USA; Neuroscience Graduate Group, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: klbales@ucdavis.edu. Update of bioRxiv. 2026 Feb 18:2026.02.17.706461. doi: 10.64898/2026.02.17.706461. Social connectedness strongly influences health and longevity, and adult pair bonds provide psychological benefits distinct from other social relationships. Oxytocin (OT), corticotropin-releasing hormone (CRH), and opioids play an important role in pair bond formation and maintenance. OT modulates the stress response via the hypothalamic-pituitary-adrenal (HPA) axis, while the kappa (κ) opioid system may modulate OT signaling in contexts of stress and separation. Here, 20 male and female coppery titi monkeys (Plecturocebus cupreus), a unique non-human primate model for the study of pair bonding and social buffering, were exposed to a physical stressor under three social conditions: baseline (no stressor, partner present), stress (stressor, no partner) and buffering (stressor, partner present). We predicted stress would engage the dynorphin/κ-opioid receptor system, reflected in reduced κ-opioid receptor (KOR) availability measured via [11C]GR103545 Positron Emission Tomography (PET) and lower cerebrospinal fluid (CSF) OT, whereas partner presence would attenuate this response. The social buffering effect was successfully replicated: cortisol was significantly

Mentions Oxytocin

GLP-1 receptor agonists in ADPKD: from metabolic rationale to phenotype-enriched translational testing.

1. Transl Res. 2026 Sep;295:148-154. doi: 10.1016/j.trsl.2026.07.001. Epub 2026 Jul 12. GLP-1 receptor agonists in ADPKD: from metabolic rationale to phenotype-enriched translational testing. Corrêa LMA(1), Brandão LKV(2), Delmiro Silva YR(3), Ferreira GD(4), Mazur GR(5), Arruda SLP(6). Author information: (1)Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Address: Avenida Brigadeiro Faria Lima, 5544, Vila São Pedro, CEP 15090-000, Brazil. Electronic address: lucasmacielll@icloud.com. (2)Centro Universitário Uninorte (UNINORTE), Rio Branco, Acre, Address: BR 364, Km 02, Alameda Hungria, 200, Jardim Europa II, CEP 69915-497, Brazil. (3)Universidade Federal de Alagoas (UFAL), Campus Arapiraca, Arapiraca, Alagoas, Address: Avenida Manoel Severino Barbosa, s/n, Bom Sucesso, CEP 57309-005, Brazil. (4)Faculdade de Ciências Médicas de Minas Gerais (CMMG), Belo Horizonte, Minas Gerais, Address: Alameda Ezequiel Dias, 275, CEP 30130-110, Brazil. (5)Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Address: Rua Imaculada Conceição, 1155, Prado Velho, CEP 80215-901, Brazil. (6)Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Address: Avenida Brigadeiro Faria Lima, 5544, Vila São Pedro, CEP 15090-000, Brazil. Autosomal dominant polycystic kidney disease (ADPKD) remains therapeutically anchored to vasopressin V2-receptor antagonism, yet progression heterogeneity and persistent unmet need increasingly suggest residual disease biology beyond cAMP-centered control. Converging experimental and observational human phenotype data suggest that metabolic reprogramming, mitochondrial dysfunction, impaired fatty-acid oxidation, obesity, and visceral adiposity may modify cyst growth, kidney-volume expansion, eGFR decline, or treatment-response heterogeneity, although causal and therapeutic evidence remains incomplete. In this review, we synthesize mechanistic, human, and trial-design evidence-from studies of cystic bioenergetics and human phenotype modifiers of progression to metabolism-oriented interventions, recent direct semaglutide data in Pkd1 models, and the design logic of ongoing early-phase clinical evaluation-to examine whether GLP-1 receptor agonists deserve consideration as orthogonal metabolic candidates for translational disease modification in ADPKD. Across these lines of evidence, GLP-1 receptor agonists should be viewed not as mechanistic surrogates for tolvaptan, but as plausible candidates to engage adiposity-related and metabolic stress pathways that may contribute to progression heterogeneity. At the same time, the field remains at an early translational stage, with important uncertainties regarding patient selection, trial enrichment, endpoint selection, co-administration with tolvaptan, and safety monitoring. GLP-1-based therapy should not currently be regarded as a treatment for ADPKD; rather, the available evidence supports a phenotype-aware translational program in which metabolic burden, visceral adiposity, and residual risk beyond tolvaptan guide early clinical testing and endpoint selection. Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.trsl.2026.07.001 PMID: 42398811 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors have declared that no conflict of interest exists.

Mentions Semaglutide

Adolescent cannabinoid type 1 receptor (CB1R) blockade mitigates the effects of adolescent social instability stress (SS) on socially directed behaviour in female rats.

1. Psychoneuroendocrinology. 2026 Sep;191:107937. doi: 10.1016/j.psyneuen.2026.107937. Epub 2026 Jun 8. Adolescent cannabinoid type 1 receptor (CB1R) blockade mitigates the effects of adolescent social instability stress (SS) on socially directed behaviour in female rats. Leonetti AM(1), White B(2), Burke FF(2), Sheehan AC(2), Murray SH(2), Fletcher BCJ(2), McCormick CM(3). Author information: (1)Biological Sciences Department, Brock University, St. Catharines, ON, Canada. (2)Psychology Department, Brock University, St. Catharines, ON, Canada. (3)Biological Sciences Department, Brock University, St. Catharines, ON, Canada; Psychology Department, Brock University, St. Catharines, ON, Canada. Electronic address: cmccormick@brock.ca. The endocannabinoid system undergoes maturation during adolescence and is involved in the development of social behaviour. In separate studies, we found: (1) that repeated cannabinoid type 1 receptor (CB1R) blockade during adolescence increased social interaction and neuronal activity in the medial prefrontal cortex and nucleus accumbens of female rats, and (2) that adolescent social instability stress (SS; daily 1-h isolation and pairing with a new cage partner from postnatal day (P) 30-45) reduced social interaction and social reward motivation in female rats. Here, we tested the possibility that adolescent CB1R blockade would mitigate the effects of SS on social behavioural deficits in female rats. The CB1R antagonist AM251 (or vehicle) was administered from P30-45 to SS or to non-stressed controls (CTL). AM251 increased social interaction and increased social reward motivation (as measured by a progressive ratio test in a social operant conditioning task) in SS female rats, with no effect in CTLs. To investigate potential molecular correlates of the increased social reward motivation in SS rats treated with AM251, we measured the abundance of signaling proteins within the endocannabinoid, dopamine, and oxytocin systems in the medial prefrontal cortex, nucleus accumbens, and medial amygdala of adult female rats. Neither SS nor AM251 treatment affected protein levels in these regions. Nevertheless, the behavioural results implicate adolescent endocannabinoid signaling as a mechanism through which adolescent social stressors shape social behaviour in female rats. Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.psyneuen.2026.107937 PMID: 42263537 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system.

1. Int J Cardiol. 2026 Sep 1;458:134560. doi: 10.1016/j.ijcard.2026.134560. Epub 2026 May 19. Cost-effectiveness and budget-impact analysis of tirzepatide in heart failure with preserved ejection fraction and obesity in the German health-care system. Estler B(1), Fröhlich H(1), Täger T(1), Heins J(1), Frey N(1), Frankenstein L(2). Author information: (1)Department of Cardiology, Angiology and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. (2)Department of Cardiology, Angiology and Pulmology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: Lutz.Frankenstein@med.uni-heidelberg.de. BACKGROUND: Heart failure with preserved ejection fraction is common, obesity-related, and associated with high symptom burden and healthcare use. Tirzepatide, a dual GIP/GLP-1 receptor agonist, improved symptoms and outcomes in SUMMIT, but its acquisition cost raises concerns about value and affordability. METHODS: We developed a Markov model comparing tirzepatide versus placebo, both added to standard care, in the SUMMIT population from the German statutory health insurance perspective. The model used monthly cycles over 5 years with four Kansas City Cardiomyopathy Questionnaire clinical summary score-defined health states (Q1-Q4) plus death. Arm-specific transitions and rates of all-cause death and worsening heart failure were derived from SUMMIT. Deterministic and probabilistic sensitivity analyses, including tirzepatide price-reduction scenarios, were conducted to explore parameter uncertainty and price thresholds simultaneously. A prevalence-based budget impact analysis extrapolated results to the German HFpEF-obesity population under alternative eligibility (SUMMIT-like vs broad) and uptake (30%, 50%, 100%) scenarios. RESULTS: Discounted per-patient costs were €5827 (placebo) and €31,052 (tirzepatide), with quality-adjusted life years of 3.539 and 3.638. Tirzepatide generated 0.100 additional quality-adjusted life years at an incremental cost of €25,225, yielding an incremental cost-effectiveness ratio of 252,611€/quality-adjusted life year, with low probability of cost-effectiveness at €100,000/QALY. Five-year incremental spending was ∼€1.9-6.2 billion with SUMMIT-like and ∼ €3.8-12.6 billion with broad eligibility, depending on uptake. CONCLUSIONS: Tirzepatide provides modest quality-adjusted life year gains at substantially higher costs and, at current price, appears neither cost-effective nor affordable at scale in German care. Substantial price reductions would be required to improve economic attractiveness and budgetary impact. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.ijcard.2026.134560 PMID: 42155673 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest NF declares “Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events” from Novo Nordisk. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijcard.2026.134560.

Mentions Tirzepatide

Atrazine alters kisspeptin signaling and downstream neuroendocrine regulation following embryonic exposure in zebrafish.

1. Toxicology. 2026 Sep;525:154503. doi: 10.1016/j.tox.2026.154503. Epub 2026 May 15. Atrazine alters kisspeptin signaling and downstream neuroendocrine regulation following embryonic exposure in zebrafish. Stradtman SC(1), Sathisaran U(1), Dierolf BK(1), Sumner G(1), Tamagno WA(1), Freeman JL(2). Author information: (1)School of Health Sciences, Purdue University, West Lafayette, IN, USA. (2)School of Health Sciences, Purdue University, West Lafayette, IN, USA. Electronic address: jfreema@purdue.edu. Atrazine is an herbicide used to control broadleaf and grassy weeds but is also a known endocrine disrupting chemical classified by the US EPA for its effect on the luteinizing hormone (LH) surge. The US EPA's maximum contaminant level (MCL) for atrazine in drinking water is 3 parts per billion (ppb; µg/L), though concentrations may exceed this during peak crop seasons. Because drinking water is the primary exposure route, studying environmentally relevant concentrations near the MCL is critical for understanding public health impacts. Atrazine has been shown in epidemiological and toxicological studies to disrupt neuroendocrine and reproductive functions, including suppression of gonadotropin-releasing hormone (GnRH) neuron activity, leading to decreased LH and follicle-stimulating hormone (FSH) surges. Given the breadth of observed effects, this study hypothesized that atrazine targets an upstream neuroendocrine regulator-the kisspeptin signaling pathway-due to its dual role in reproductive and dopaminergic regulation. Kisspeptin expression was characterized in developing zebrafish, showing increases every 24 h from 1 to 120 h post fertilization (hpf). Zebrafish were exposed during embryogenesis (1-72 hpf) to atrazine at 0, 0.3, 3, or 30 ppb. Immunofluorescence at 120 hpf showed reduced kisspeptin expression in the habenula at 3 ppb and near-complete loss of kiss1/kiss2 expression with brain disorganization at 30 ppb. Kisspeptin, LH, and FSH levels were measured at 168 hpf and 6 months post fertilization (mpf). Age- and sex-dependent alterations were observed. Behavioral tests revealed anxiety-like phenotypes in larvae and adults. These findings indicate atrazine disrupts neuroendocrine and behavioral function through kisspeptin pathway dysfunction. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.tox.2026.154503 PMID: 42142733 Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Kisspeptin

GLP-1 receptor agonists and post-endovascular thrombectomy outcomes in acute ischemic stroke: a multicenter propensity score matched analysis.

1. J Clin Neurosci. 2026 Sep;151:112089. doi: 10.1016/j.jocn.2026.112089. Epub 2026 May 30. GLP-1 receptor agonists and post-endovascular thrombectomy outcomes in acute ischemic stroke: a multicenter propensity score matched analysis. Rai P(1), Bathla G(2), Praveen N(3), Kakadiya J(4), Dhaduk V(5), Chen HA(6), Salim HA(7), Azzam AY(8), Essibayi MA(9), Altschul DJ(10), Dmytriw AA(11), Yedavalli VS(12), Aggarwal E(13), Latifi S(14), Malhotra A(15), Colasurdo M(16), Gandhi D(17), Lakhani DA(18). Author information: (1)Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: rai.pranjal@mayo.edu. (2)Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: bathla.girish@mayo.edu. (3)Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: niharika.praveen@outlook.com. (4)Department of Radiology and Radiological Sciences, Johns Hopkins Medical Center, Baltimore, MD, USA. Electronic address: jaykakadiya07@gmail.com. (5)Shantabaa Medical College and General Hospital, Amreli, India. Electronic address: vidhidhaduk1@gmail.com. (6)Department of Neurosurgery, University of Maryland Medical Center, Baltimore, MD, USA. Electronic address: alvin.huanwen.chen@gmail.com. (7)Department of Neuroradiology, MD Anderson Medical Center, Houston, TX, USA. Electronic address: hamza.sleeem@gmail.com. (8)Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA. Electronic address: ahmedyazzam@gmail.com. (9)Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: m.amir.essibayi@gmail.com. (10)Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: daltschu@montefiore.org. (11)Neuroendovascular Program, Massachusetts General Hospital, Harvard University, Boston, MA, USA; Neurovascular Centre, Departments of Medical Imaging and Neurosurgery, St Michael's Hospital, Toronto, ON, Canada. Electronic address: adam.dmytriw@gmail.com. (12)Department of Radiology and Radiological Sciences, Johns Hopkins Medical Center, Baltimore, MD, USA. Electronic address: vyedava1@jhmi.edu. (13)Department of Endocrinology, Mayo Clinic, Rochester, MN, USA. Electronic address: Aggarwal.eishvauk@mayo.edu. (14)Department of Neurosciences, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA. Electronic address: shahrzad.latifikhereshky@hsc.wvu.edu. (15)Department of Radiology, Yale New Haven Hospital, New Haven, CT, USA. Electronic address: ajay.malhotra@yale.edu. (16)Department of Interventional Radiology, Portland, OR, USA. Electronic address: mcolasurdo@gmail.com. (17)Department of Neurosurgery, University of Maryland Medical Center, Baltimore, MD, USA. Electronic address: dheeraj.gandhi@som.umaryland.edu. (18)Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA. Electronic address: dhairyalakhani@gmail.com. BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1As) have demonstrated cardiovascular and cerebrovascular benefits in high-risk populations, but their impact in patients with acute ischemic stroke (AIS) requiring endovascular thrombectomy (EVT) remains uncertain. METHODS: We performed a retrospective cohort analysis using the TriNetX Network, identifying adults (≥18 years) with AIS treated with EVT from January 1, 2016 through December 31, 2025. Patients with GLP-1A exposure within three months prior to EVT constituted the exposure cohort; those without served as comparators. This pre-index window was specified to eliminate immortal time bias, with follow-up beginning on the EVT date for both cohorts. Three-year outcomes included all-cause mortality and inpat

Mentions Semaglutide

Salivary oxytocin research clings strongly to early theories, despite new frameworks attributing versatile roles to the neuropeptide.

1. Psychoneuroendocrinology. 2026 Sep;191:107950. doi: 10.1016/j.psyneuen.2026.107950. Epub 2026 Jul 1. Salivary oxytocin research clings strongly to early theories, despite new frameworks attributing versatile roles to the neuropeptide. Winters C(1), Gorssen W(2), Ulbrich SE(3), Goumon S(4). Author information: (1)ETH Zurich, Animal Physiology, Institute of Agricultural Sciences, Zurich, Switzerland. Electronic address: carmenwinters@hotmail.com. (2)ETH Zurich, Animal Genomics, Institute of Agricultural Sciences, Zurich, Switzerland. (3)ETH Zurich, Animal Physiology, Institute of Agricultural Sciences, Zurich, Switzerland. (4)ETH Zurich, Animal Physiology, Institute of Agricultural Sciences, Zurich, Switzerland. Electronic address: sebastien.goumon@usys.ethz.ch. Salivary oxytocin is a widely used peripheral measure for investigating neuroendocrine correlates of social, stress-related, and adaptive physiological processes. While theoretical interpretations of oxytocin have evolved substantially beyond early prosocial accounts and recognized context dependency, individual variability, and regulatory functions, more recent studies introducing oxytocin measures in non-human species often rely exclusively on early prosocial interpretations. This striking limitation to just one of several conceptualizations prompted us to examine how theoretical perspectives are represented in the literature on salivary oxytocin. To address this, we conducted a bibliometric and semantic analysis of 445 publications on salivary oxytocin (2005-2026) to identify historical trends, citation patterns, thematic concentrations, and alignment with current theoretical frameworks. A citation analyses revealed the dominance of early canonical studies, with a small number of papers accounting for a disproportionate share of citations. Keyword and semantic cluster analyses identified seven thematic domains, including stress research, parental care, and clinical studies, while integration across species was limited. Explicit citation of selected landmark publications representing major conceptual frameworks of oxytocin function was uncommon (16.6% of studies), with human studies primarily referencing the publication representing social salience theory and animal studies primarily referencing the publication representing the prosocial framework. Thus, despite its evolutionary conservation and translational potential, salivary oxytocin research showed limited explicit theoretical engagement, while citation and semantic patterns remained disproportionately centered on early socially oriented literature. Together, these findings suggest that the rapid expansion of the field has not been accompanied by comparable structural diversification. This highlights the need for future research to apply models, integrate findings, and contextualize applications to produce informed insights into oxytocin's physiological, behavioral, and adaptive functions. Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.psyneuen.2026.107950 PMID: 42402227 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

Intranasal oxytocin for alcohol use disorder: A systematic review and multilevel, bayesian, and variance meta-analyses of randomized clinical trial data.

1. Psychoneuroendocrinology. 2026 Sep;191:107915. doi: 10.1016/j.psyneuen.2026.107915. Epub 2026 Jun 11. Intranasal oxytocin for alcohol use disorder: A systematic review and multilevel, bayesian, and variance meta-analyses of randomized clinical trial data. Santos VH(1), Paloyelis Y(2), Morgado M(3), Rodrigues JR(4), Tjeng R(5), Fraga M(6), Carriço P(6), Fernandes L(7), Martins D(8). Author information: (1)Department of Psychiatry and Mental Health, Cova da Beira Local Health Unit, Covilhã, Portugal; RISE-Health, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Electronic address: vitor.santos@ubi.pt. (2)Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom. (3)Pharmaceutical Services, Cova da Beira Local Health Unit, Covilhã, Portugal. (4)RISE-Health, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal; Rheumatology Department, Cova da Beira Local Health Unit, Covilhã, Portugal. (5)RISE-Health, Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal; Intensive Care Unit, Cova da Beira Local Health Unit, Covilhã, Portugal. (6)Equipa de Tratamento Especializada, Instituto para os Comportamentos Aditivos e as Dependências, Administração Regional de Saúde do Centro, I.P, Coimbra, Portugal. (7)RISE-Health, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Portugal; Psychiatry Service, São João University Hospital, Porto, Portugal. (8)Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; RISE-Health, Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Portugal. BACKGROUND: Intranasal oxytocin (OT) has been proposed as a promising adjunctive treatment for Alcohol Use Disorder (AUD), yet randomized controlled trials (RCTs) have yielded mixed and inconclusive findings. To clarify its therapeutic potential, we conducted a comprehensive meta-analysis using frequentist, Bayesian, and variability-based approaches. METHODS: We performed a multilevel random-effects meta-analysis of six eligible RCTs comparing intranasal OT with placebo for alcohol-related outcomes. Hedges' g values were calculated and winsorised at |g| = 3 to limit leverage from extreme small-sample effects. Moderator analyses assessed outcome domain, OT dose, treatment duration, year of publication, administration frequency, and clinical setting. Publication bias was evaluated using multilevel PET-PEESE with cluster-robust correction, Egger's test, trim-and-fill, and limit meta-analysis. Bayesian multilevel models examined average treatment effects and outcome variability. RESULTS: The overall pooled effect was not statistically significant (Hedges' g = 0.34, 95% CI -0.48-1.17, p = 0.47), with substantial between-study heterogeneity (Q(48) = 504.40, p < .001). Cook's distance identified Pedersen et al. (2013) as statistically influential; moderator and publication bias analyses were conducted on the remaining five studies. No significant moderation was observed by outcome domain, dose, duration, frequency, or setting. Year of publication showed a nominally significant positive association with effect size in the restricted sample (β = 0.184, p = .042). Multiple publication bias diagnostics converged on the absence of a systematic adjusted effect. Bayesian multilevel analysis confirmed the absence of a credible treatment effect (posterior mean μ = -0.005, 95% CrI -0.53-0.52). Robust Bayesian meta-analysis provided moderate support for the null hypothesis (BF₀₁ = 4.74). Variability analyses found no evidence that OT increased outcome dispersion relative to placebo (lnVR = -0.146, p = .153 after robust correction), providing no support for latent responder subgroups. CONCLUSIONS: Contrary to early expectations, intranasal OT does not

Mentions Oxytocin

Semaglutide, at a dose that produces modest weight loss, induces mild suppression of bone remodeling in healthy control rats and those with chronic kidney disease.

1. Bone. 2026 Sep;210:117933. doi: 10.1016/j.bone.2026.117933. Epub 2026 May 12. Semaglutide, at a dose that produces modest weight loss, induces mild suppression of bone remodeling in healthy control rats and those with chronic kidney disease. Allen MR(1), Metzger CE(2), Chen NX(3), Tinsley IC(4), DiMarchi RD(4), O'Neill K(3), Matter EK(2), Moe SM(5). Author information: (1)Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Roudebush VA, Indianapolis, IN, United States of America. Electronic address: matallen@iu.edu. (2)Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America. (3)Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States of America. (4)Department of Chemistry, Indiana University, Bloomington, IN, United States of America. (5)Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN, United States of America; Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States of America. The effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment on bone are unclear. The goal of this study was to investigate the effects of semaglutide, a GLP-1RA, on bone structure, remodeling, and mechanical properties in healthy control animals and those with chronic kidney disease (CKD). Male Cy/+IU rats with progressive CKD and littermate controls were treated with escalating doses of semaglutide for 28 days. Endpoint measures included bone structure, assessed by micro-CT, bone remodeling, assessed by histomorphometry, and bone mechanical properties, assessed by 3-point bending tests. Semaglutide treatment led to reduced food intake and weight loss, with CKD rats receiving semaglutide having 15% lower body weight at the end of the study compared to untreated CKD rats, while control rats did not have a statistical difference in weight (-5%) at the end of the study. Muscle mass was also lower in semaglutide-treated animals compared to untreated groups. CKD led to higher blood urea nitrogen with no effect of semaglutide. Serum PTH was lower in control rats treated with semaglutide, but this effect was not seen in the CKD cohorts. There were also main effects of semaglutide on serum calcium and phosphorus levels. CKD resulted in lower trabecular bone volume and higher cortical porosity with no effect of semaglutide. Mineralizing surfaces from dynamic histomorphometry were lower in control rats treated with semaglutide compared to untreated control and bone formation rate also trended lower in semaglutide-treated animals (∼20%). CKD animals had lower mechanical properties; semaglutide effects were only noted in toughness. At doses causing mild weight loss, semaglutide modestly lowered trabecular bone remodeling with little interaction with CKD disease status. Published by Elsevier Inc. DOI: 10.1016/j.bone.2026.117933 PMID: 42128321 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew R. Allen reports financial support was provided by U.S. Department of Veterans Affairs. Matt Allen, Ian Tinsley, Richard DiMarchi reports a relationship with MBX Bioscience that includes: consulting or advisory and funding grants. Matt Allen, Richard DiMarchi reports a relationship with BWB Bioscience that includes: consulting or advisory and funding grants. Sharon Moe reports a relationship with Eli Lilly and Company that includes: equity or stocks. If there ar

Mentions Semaglutide

Integrated in silico transdermal prediction, serum pharmacochemistry, and experimental validation reveal the active constituents and therapeutic mechanism of Aifu Nuangong plaster against primary dysm

1. J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Sep 1;1281:125204. doi: 10.1016/j.jchromb.2026.125204. Epub 2026 Jul 3. Integrated in silico transdermal prediction, serum pharmacochemistry, and experimental validation reveal the active constituents and therapeutic mechanism of Aifu Nuangong plaster against primary dysmenorrhea. Ren W(1), Zhang L(2), Mahemuti A(3), Li X(2), Han C(4). Author information: (1)School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China. (2)Jinan Zhangqiu District Hospital of Traditional Chinese Medicine, Jinan 250200, PR China. (3)Shache County Uyghur Medical Hospital, Kashgar 844700, PR China. (4)School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China. Electronic address: chunchaoh@126.com. BACKGROUND: Primary dysmenorrhea (PD) is a prevalent gynecological disease that significantly impairs women's quality of life. Although Aifu Nuangong Wan (AFNGW) has demonstrated therapeutic efficacy on PD, its conventional oral administration is hindered by the first-pass effect and gastrointestinal adverse reactions. This study developed a novel traditional Chinese medicine transdermal plaster, Aifu Nuangong Plaster (AFNGP), based on Aifu Nuangong Wan (AFNGW). Nevertheless, the molecular mechanisms by which AFNGP alleviates PD have not yet been fully clarified. AIM OF THE STUDY: To reveal the bioactive constituents and potential mechanisms of AFNGP in treating PD. METHODS: UPLC-Q-Exactive Orbitrap-MS was employed to identify the chemical components in AFNGP extract and drug-containing serum, while the Deep-PK model was utilized to predict the transdermal properties of components in AFNGP extract. Network pharmacology and molecular docking were performed based on the analysis of blood-absorbed prototype components. A PD rat model was established using estradiol benzoate and oxytocin to evaluate the therapeutic effects of AFNGP. Furthermore, the functional mechanism of AFNGP on PD was predicted using network pharmacology and transcriptomics, followed by further validation using Western blotting. RESULTS: Pharmacodynamic assessment demonstrated that AFNGP improved symptoms in PD rats, as demonstrated by reduced writhing responses, alleviated uterine histopathological damage, and decreased levels of PGF₂α and IL-6 in serum and uterine tissues in a dose-dependent manner. A total of 82 compounds in AFNGP extract and 19 prototype components in serum. Integrated network pharmacology and RNA-seq analysis indicated that AFNGP exerted therapeutic effects on PD through the PI3K-AKT signaling pathway. Moreover, Western blotting revealed that AFNGP inhibited the expression of key proteins in the PI3K-AKT signaling pathway. CONCLUSION: AFNGP protected against PD by targeting the PI3K-AKT signaling pathway, thereby providing novel evidence for its potential application in PD. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.jchromb.2026.125204 PMID: 42413359 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

Corrigendum to "Associations of intrapartum synthetic oxytocin administration with reduced neonatal salivary oxytocin levels and altered sucking patterns" [Early Hum. Dev. 218 (2026) 106539].

1. Early Hum Dev. 2026 Sep;220:106584. doi: 10.1016/j.earlhumdev.2026.106584. Epub 2026 May 15. Corrigendum to "Associations of intrapartum synthetic oxytocin administration with reduced neonatal salivary oxytocin levels and altered sucking patterns" [Early Hum. Dev. 218 (2026) 106539]. Omaru M(1), Fujita F(2), Kajiwara S(2), Wakamatsu E(2), Kuroishi S(3), Ochiai Y(3), Morokuma S(4). Author information: (1)Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address: omaru.machiko.348@m.kyushu-u.ac.jp. (2)Department of Nursing, Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, 812-8582, Japan. (3)Research & Development Division, Pigeon Corporation, Tokyo, 103-8480, Japan. (4)Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address: morokuma.seiichi.845@m.kyushu-u.ac.jp. Erratum for Early Hum Dev. 2026 Jul;218:106539. doi: 10.1016/j.earlhumdev.2026.106539. DOI: 10.1016/j.earlhumdev.2026.106584 PMID: 42140803

Mentions Oxytocin

Oxytocin modulates glucose metabolism to protect against cardiac remodeling via the STAT3/eNOS Axis.

1. Cell Signal. 2026 Sep;145:112605. doi: 10.1016/j.cellsig.2026.112605. Epub 2026 May 15. Oxytocin modulates glucose metabolism to protect against cardiac remodeling via the STAT3/eNOS Axis. Zhao Y(1), Qian X(1), Wang Q(1), Wang Z(1), Fu N(1), Wang L(1), Feng R(1), Yang W(1), Bai X(2), Qian J(3), Yang Y(4). Author information: (1)Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. (2)Department of Cardiac Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. (3)Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. Electronic address: qianjinqiao@ydyy.cn. (4)Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. Electronic address: yangyuqiao@ydyy.cn. Oxytocin (OT), an endogenous cardiovascular homeostatic hormone, is currently attracting considerable attention because it can improve energy metabolism and cardiac function. This study investigated whether OT mitigates cardiac remodeling in association with alterations in glucose metabolism. In vivo, cardiac hypertrophy and fibrosis were induced in C57BL/6 J mice via angiotensin II (Ang II), while in vitro H9c2 cardiomyoblasts and neonatal rat cardiac fibroblasts (NRCFs) were treated with Ang II or TGF-β1, respectively, with or without OT. We found that OT suppressed cardiac hypertrophy and fibrosis, increased ATP and glucose levels, reduced lactate accumulation, suppressed glycolysis, and enhanced glucose oxidation in cardiomyocytes. Mechanistically, OT upregulated its receptor and inhibited pyruvate kinase M2 (PKM2) in TGF-β1-stimulated NRCFs. In hypertrophic cardiomyocytes induced by Ang II, transcription factor STAT3 was activated and eNOS was downregulated, while OT suppressed STAT3 activation and nuclear translocation of p-STAT3, and enhanced the expression of eNOS. Either Stat3 overexpression or Nos3 downregulation attenuated OT's beneficial and metabolic effects. Additionally, we demonstrated that the transcription factor STAT3 is enriched at and interacts with the Nos3 promoter region. Overexpression of eNOS partially restored OT-associated protective effects that were attenuated by Stat3 overexpression. Collectively, these findings suggest that OT attenuates cardiac remodeling, at least in part, in association with modulation of glucose metabolism and the STAT3/eNOS pathway, providing mechanistic insight into its cardioprotective effects. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.cellsig.2026.112605 PMID: 42142820 Conflict of interest statement: Declaration of competing interest The authors declare that they have no competing interests.

Mentions Oxytocin

Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study.

1. J Affect Disord. 2026 Aug 15;407:121802. doi: 10.1016/j.jad.2026.121802. Epub 2026 Apr 17. Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study. Aboukaoud M(1), Hoch B(2), Weiser M(3), Amiaz R(3). Author information: (1)Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il. (2)Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. (3)Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. INTRODUCTION: Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability. METHODS: We conducted a disproportionality analysis of the WHO VigiBase (2010-2024), including T2DM patients. Reports of depressed mood and suicidal thoughts associated with GLP-1RAs were compared with other glucose-lowering medications. Analyses incorporated age, sex, time-to-onset, dose, comorbid depression, and concomitant antidepressant use. Adjusted reporting odds ratios (RORs) and a Weibull time-to-event model were applied. Causality was explored using Bradford Hill criteria. RESULTS: A total of 1,183,817 adverse events related to GLP-1RA were identified. Depressed mood and suicidality signals were observed with semaglutide, liraglutide, and tirzepatide (adjusted ROR0.25: 2.13, 1.52, 1.07) and (adjusted ROR0.25: 6.76, 2.43, 3.39), respectively. No signal was identified for suicide attempts or completed suicide. Absolute reporting frequencies were low. Concomitant antidepressant use was 2.3-5 times more frequent, and comorbid depression 25%-120% higher, compared with other glucose-lowering medications. Median time-to-onset was 96 days. Survival analysis demonstrated an early increase in reporting followed by stabilization over time. Adjustment for antidepressant use modestly attenuated associations. CONCLUSION: GLP-1RAs were associated with increased reporting of depressed mood and suicidal thoughts, particularly in patients receiving concomitant antidepressants. These findings support a patient-centered model in which underlying affective vulnerability or reporting factors drive reported mood symptoms rather than a uniform drug-specific effect. GLP-1RAs remain clinically valuable, but psychiatric monitoring during early treatment in vulnerable patients is warranted. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.jad.2026.121802 PMID: 42002107 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors, Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser, and Revital Amiaz, have no conflicts of interest to declare and no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Simplified definition and imaging-based stratification of at-risk MASH using magnetic resonance elastography.

1. Hepatol Commun. 2026 Aug 11;10(9):e1024. doi: 10.1097/HC9.0000000000001024. eCollection 2026 Sep 1. Simplified definition and imaging-based stratification of at-risk MASH using magnetic resonance elastography. Li J(1), Wu H(1), Glaser KJ(1), Ou FS(2), Manduca A(1), Venkatesh SK(1), Sirlin C(3), Loomba R(4), Shah VH(5), Ehman RL(1), Allen AM(5), Yin M(1). Author information: (1)Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA. (2)Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA. (3)Department of Radiology, University of California at San Diego, La Jolla, California, USA. (4)Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, La Jolla, California, USA. (5)Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA. BACKGROUND: Accurate identification of patients with metabolic dysfunction-associated steatohepatitis (MASH) at risk of disease progression (at-risk MASH) is critical for guiding resmetirom and semaglutide therapy. Inconsistent definitions of at-risk MASH complicate clinical risk classification and comparisons across studies. This study aimed to standardize the definition of at-risk MASH and propose optimized MRE-based liver stiffness (LS-MRE) cutoffs to improve noninvasive risk stratification and better guide pharmacotherapy. METHODS: In this prospective study, 413 patients with suspected or diagnosed MASLD from two medical centers underwent liver biopsy and MRE. RESULTS: A simplified definition of at-risk MASH (MASH with fibrosis stage≥2) identified a broader group of patients requiring clinical attention than a stricter definition requiring NAFLD Activity Score≥4 with ≥1 point in steatosis, inflammation, and ballooning (n=122 vs. 77). LS-MRE alone showed the highest diagnostic accuracy for identifying at-risk MASH using the simplified definition (AUC 0.91 [0.87, 0.95]) and cirrhosis (AUC 0.93 [0.88, 0.99]), compared with FIB-4 and individual laboratory parameters (AST, ALT, and platelet count) (p<0.01 for all, paired DeLong tests). Optimized LS-MRE cutoffs (2.8-6.4 kPa) captured 25 additional biopsy-proven pharmacotherapy candidates (28% of all eligible patients) compared to AASLD guidelines-recommended cutoffs (3.1-4.4 kPa), improving sensitivity (80% vs. 50%) with acceptable specificity (73% vs. 88%). CONCLUSIONS: A simplified definition of at-risk MASH enables broader identification of treatment candidates. LS-MRE demonstrates excellent diagnostic performance and improves noninvasive risk stratification when paired with optimized cutoffs. These findings support the use of MRE to guide resmetirom and semaglutide eligibility and improve access to emerging therapies. Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, LLC. on behalf of the American Association for the Study of Liver Diseases. DOI: 10.1097/HC9.0000000000001024 PMID: 42579768 [Indexed for MEDLINE]

Mentions Semaglutide

Peptide Supplements and Their Therapeutic Applications in Sports Medicine.

1. Am J Sports Med. 2026 Aug 11:3635465261464420. doi: 10.1177/03635465261464420. Online ahead of print. Peptide Supplements and Their Therapeutic Applications in Sports Medicine. Tewari K(1), Liu TP(1), Im C(1), Hamad C(1), Petrigliano F(1), Cheung EC(1), Kremen TJ Jr(1). Author information: (1)Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. BACKGROUND: The peptide supplement market has experienced rapid growth due to marketing claims of enhanced performance and accelerated recovery from musculoskeletal injury. These peptides are increasingly popular with patients and athletes and are often perceived as low risk, despite the absence of efficacy or safety data for many emerging peptides. PURPOSE: To summarize existing peer-reviewed data on 6 emerging peptides (BPC-157, thymosin beta-4 or TB-500, CJC-1295, MK-677, ipamorelin, and GHK-Cu [copper peptide]) for musculoskeletal recovery and enhancement in animal and human models. STUDY DESIGN: Scoping review. METHODS: Three independent reviewers searched the PubMed database using permutations of peptide search terms (BPC-157, TB-500, CJC-1295, MK-677 [ibutamoren], ipamorelin, and GHK-Cu) combined with musculoskeletal tissue search terms (bone, fracture, muscle, tendon, ligament, meniscus, and cartilage) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Papers were independently screened by 2 reviewers, with a third serving as a tiebreaker. Papers examining these peptides for musculoskeletal treatment, tissue recovery, or performance in animal or human models were included. RESULTS: Overall, 67% of identified publications utilized preclinical animal models. In animal models, most commonly rats, each compound demonstrated unique mechanisms with promising but variable effects on tendon, muscle, bone, and ligament healing. Human clinical studies were limited to a handful of investigations, most lacking robust controls or rigorous study designs. Human data were heterogeneous and revealed modest improvements at best for metabolic bone health and degenerative knee pain. Some peptides such as MK-677 were associated with significant risks including congestive heart failure, and significant heterogeneity existed in dosing and route of administration. CONCLUSION: Despite promising findings in animal studies, the claimed benefits of emerging peptide supplements for musculoskeletal recovery and performance remain unsubstantiated by current human trials. Documented risks include cardiovascular complications and metabolic dysfunction such as insulin resistance. Because of the lack of robust efficacy and safety data, peptide supplements should not currently be recommended as a replacement or adjunct for existing orthopaedic standard of care. DOI: 10.1177/03635465261464420 PMID: 42578445

Mentions CJC-1295 / Ipamorelin

KPV attenuates adipogenesis and lipid metabolism through modulation of ROS-mediated AKT/mTORC1/PPARγ signaling.

1. Tissue Cell. 2026 Aug 9;104(Pt 1):103837. doi: 10.1016/j.tice.2026.103837. Online ahead of print. KPV attenuates adipogenesis and lipid metabolism through modulation of ROS-mediated AKT/mTORC1/PPARγ signaling. An SH(1), Park JY(1), Lee SJ(2). Author information: (1)Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea. (2)Major of Human Bio-convergence, Division of Smart Healthcare, Pukyong National University, Busan 48513, Republic of Korea. Electronic address: seijung1@pknu.ac.kr. Lysine-Proline-Valine (KPV), an endogenous tripeptide derived from α-melanocyte-stimulating hormone, has been recognized for its anti-inflammatory and antioxidant activities. However, its role in adipocyte differentiation has not been investigated. In this study, we investigated the regulatory effects of KPV on MDI-induced adipocyte differentiation in 3T3-L1 preadipocytes. KPV treatment dose-dependently suppressed adipocyte differentiation. Specifically, treatment with 100 μg/mL KPV reduced Oil Red O staining intensity by approximately 55% and intracellular triglyceride content by approximately 38% compared with the MDI-treated group. In addition, KPV decreased the expression of key adipogenic markers, including peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FAS). Mechanistically, KPV attenuated reactive oxygen species (ROS) production and was associated with reduced AKT-dependent mTOR signaling and altered PPARγ phosphorylation during adipocyte differentiation. This regulatory effect was accompanied by suppression of FAS expression. In addition, in a high-fat diet-induced obesity mouse model, oral administration of KPV alleviated body weight gain, white adipose tissue expansion, liver mass increase, and obesity-associated dyslipidemia, including elevated plasma total cholesterol levels. Collectively, these findings suggest that KPV suppresses adipocyte differentiation, at least in part, in association with the modulation of ROS-related AKT/mTOR/PPARγ signaling in vitro, while its in vivo administration mitigates diet-induced obesity-related metabolic alterations. These results highlight the potential of KPV as an endogenous peptide-based candidate for the prevention and management of obesity. Copyright © 2026 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.tice.2026.103837 PMID: 42585803

Mentions KPV

Seminal Plasma Kisspeptin-1 and Kisspeptin-54 Levels Are Associated With Semen Parameters and Oxidative Stress in Male Infertility.

1. Clin Endocrinol (Oxf). 2026 Aug 7. doi: 10.1111/cen.70199. Online ahead of print. Seminal Plasma Kisspeptin-1 and Kisspeptin-54 Levels Are Associated With Semen Parameters and Oxidative Stress in Male Infertility. Korkmaz O(1), Karabulut S(2), Macit P(3). Author information: (1)Department of Histology and Embryology, Faculty of Medicine, Malatya Turgut Özal University, Malatya, Türkiye. (2)Department of Histology and Embryology, International Faculty of Medicine, Istanbul Medipol University, Istanbul, Türkiye. (3)In Vitro Fertilization Center, Istanbul Okan University Hospital, Istanbul, Türkiye. OBJECTIVE: Kisspeptin-1 and Kisspeptin-54 are key regulators of the hypothalamic-pituitary-gonadal axis and may play a role in male reproductive function. This study aimed to evaluate the association between seminal plasma kisspeptin levels and male infertility, and to examine their relationships with semen parameters and oxidative stress markers. DESIGN: Retrospective cross-sectional study. METHODS: Fifty men attending an in vitro fertilization centre were classified into normozoospermia (n = 20), oligoasthenoteratozoospermia (OAT) (n = 18) and azoospermia (n = 12) groups according to WHO 2021 criteria. Seminal plasma Kisspeptin-1 and Kisspeptin-54 levels were measured using ELISA. Oxidative stress parameters, including total antioxidant capacity (TAC), total oxidant capacity (TOC) and oxidative stress index (OSI), were assessed using spectrophotometric methods. Correlation and regression analyses were performed to evaluate associations between variables. RESULTS: Kisspeptin-1 and Kisspeptin-54 levels showed a progressive decrease with increasing infertility severity (normozoospermia→OAT→azoospermia; p < 0.05). Both kisspeptins were positively associated with sperm concentration and progressive motility, and negatively associated with TOC and OSI (p < 0.01). TAC levels were higher in normozoospermic men, whereas oxidative load was increased in azoospermic individuals. Regression analyses indicated that seminal kisspeptin levels were significantly associated with sperm concentration and progressive motility. Parallel alterations in kisspeptin levels and oxidative stress markers suggest a relationship between these peptides and the seminal microenvironment. CONCLUSIONS: Seminal plasma kisspeptin levels are associated with semen quality and oxidative stress parameters in male infertility. These findings suggest that kisspeptin may represent a potential biomarker candidate for the evaluation of male infertility, although further validation is required. © 2026 John Wiley & Sons Ltd. DOI: 10.1111/cen.70199 PMID: 42566672

Mentions Kisspeptin

Stigmasterol alleviates central precocious puberty by targeting the IGF-1/PI3K/Akt/mTOR signaling pathway and modulating the Kisspeptin/GnRH axis.

1. Biochim Biophys Acta Mol Basis Dis. 2026 Aug 6:168398. doi: 10.1016/j.bbadis.2026.168398. Online ahead of print. Stigmasterol alleviates central precocious puberty by targeting the IGF-1/PI3K/Akt/mTOR signaling pathway and modulating the Kisspeptin/GnRH axis. Dong L(1), Xing Y(1), Li X(2), Xu B(3), Chen H(4). Author information: (1)Department of endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Sciences and Technology of China, Hefei City, 230001, Anhui Province, China. (2)College of Animal Science and Technology, Henan University of Science and Technology, No. 263, Kaiyuan Avenue, Luolong District, Luoyang City, 471023, Henan Province, China. (3)Department of Anesthesiology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai City, 200040, China. Electronic address: xubomazui@163.com. (4)Department of Child Health Care, First Affiliated Hospital of Gannan Medical University, 128 Jinling West Road, Ganzhou Economic and Technological Development Zone, Ganzhou City, 341000, Jiangxi Province, China. Electronic address: drhengweichen@163.com. BACKGROUND: Central precocious puberty (CPP) results from premature activation of the hypothalamic-pituitary-gonadal axis, causing early sexual development and related health risks. Stigmasterol (ST), a natural phytosterol with diverse pharmacological activities, has not been fully evaluated for CPP. METHODS: This study integrated network pharmacology, molecular docking, and molecular dynamics simulations to identify ST targets in CPP. Experimental validation used an N-Methyl aspartic acid-induced CPP rat model and high-glucose high-fat-stimulated GT1-7 hypothalamic neurons. Techniques included histology, ELISA, qPCR, western blot, and flow cytometry. RESULTS: In silico analyses demonstrated favorable binding of ST to core proteins within the IGF-1/PI3K/Akt/mTOR signaling pathway. In vivo, ST treatment significantly delayed vaginal opening, reduced serum levels of estradiol and testosterone, and ameliorated pathological abnormalities in uterine and ovarian tissues. At the molecular level, ST suppressed the hypothalamic overactivation of the IGF-1/PI3K/Akt/mTOR pathway and attenuated neuronal damage and apoptosis. In vitro, ST inhibited HGHF-induced proliferation, inflammatory cytokine release, and apoptosis in GT1-7 cells, while concurrently modulating the expression of key puberty-related genes and proteins, including those within the Kisspeptin/GnRH axis. Conversely, pharmacological reactivation of PI3K signaling with the agonist 740YP attenuated selected protective effects the protective effects of ST, supporting the functional involvement the PI3K/Akt/mTOR pathway in mediating these benefits. CONCLUSIONS: Stigmasterol exhibits significant therapeutic effects against CPP by concurrently targeting the IGF-1/PI3K/Akt/mTOR and Kisspeptin/GnRH signaling pathways. These findings provide robust preclinical evidence supporting ST as a promising multi-targeted natural candidate for CPP management. Copyright © 2026. Published by Elsevier B.V. DOI: 10.1016/j.bbadis.2026.168398 PMID: 42562054 Conflict of interest statement: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Mentions Kisspeptin

Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent models of polycystic ovary syndrome and its implications for mental health disorders: A systematic review.

1. Behav Brain Res. 2026 Aug 5;511:116262. doi: 10.1016/j.bbr.2026.116262. Epub 2026 May 14. Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent models of polycystic ovary syndrome and its implications for mental health disorders: A systematic review. Dutra JB(1), Gregorio T(1), Lorenzon F(1), Peixe CMS(2), Bernuci MP(3), Lima FB(4). Author information: (1)Departamento de Ciências Fisiológicas, Campus Trindade, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, Florianópolis, SC, Brazil. (2)Programa de Pós-Graduação em Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, Florianópolis, SC, Brazil. (3)Departamento de Fisiologia, ACF Centro Politécnico, Universidade Federal do Paraná, Curitiba, PR, Brazil. Electronic address: marcelo.bernuci@ufpr.br. (4)Departamento de Ciências Fisiológicas, Campus Trindade, Florianópolis, SC, Brazil; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina - UFSC, Campus Trindade, Florianópolis, SC, Brazil. Electronic address: fernanda.lima@ufsc.br. BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disease associated with hyperandrogenism, which causes infertility and often leads to mental health disorders. Although gonadotropin-releasing hormone (GnRH) neuronal dysfunction may contribute to PCOS, the pathophysiology of mood disorders associated with the syndrome remains unclear. OBJECTIVE: We raise the question of whether imbalanced neurotransmitters controlling the mood state, such as GABA and monoamines, impact the reproductive neural circuit and may facilitate the emergence of mental health disorders in PCOS. METHODS: We systematically reviewed gene and protein expressions, and neurotransmitter contents related to GnRH signaling in studies of rats and mice models of PCOS. Searches were conducted through PubMed and Web of Science and 52 research articles were included. RESULTS: Our findings showed that the kisspeptinergic and noradrenergic signaling stimulates GnRH neurons in non-PCOS-like rodents. In contrast, serotonergic and GABAergic pathways exert receptor-dependent bidirectional effects, with distinct receptor subtypes mediating either inhibitory or excitatory influences. PCOS-like rodents present dysfunctional signaling to GnRH neurons, which is dependent on the PCOS model applied: i) postnatal androgenization leads to decreased kisspeptinergic, monoaminergic, and GABAergic signaling to GnRH neurons; ii) prenatal androgenization does not change kisspeptinergic signaling but monoaminergic and GABAergic alterations need further investigation in this model; iii) postnatal estrogenization results in reduced kisspeptinergic and GABAergic signaling, but the monoaminergic neurotransmission is increased in this model. CONCLUSION: The reduction in kisspeptinergic, monoaminergic, and GABAergic neurotransmission in postnatally androgenized rats and mice suggests that pathways regulating reproduction and mood may share underlying neurobiological mechanisms under an androgenic milieu. Whether this signaling is similarly altered in PCOS patients with mental health disorders remains to be determined. Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.bbr.2026.116262 PMID: 42140496 [Indexed for MEDLINE]

Mentions Kisspeptin

Rates of, Reasons for, and Reactions to Discontinuation of GLP-1 Receptor Agonists: A Narrative Review.

1. Diabetes Obes Metab. 2026 Aug;28(8):6533-6549. doi: 10.1111/dom.70913. Epub 2026 Jun 5. Rates of, Reasons for, and Reactions to Discontinuation of GLP-1 Receptor Agonists: A Narrative Review. Heisey HD(1)(2)(3), Gregg LP(1)(4), Verrico CD(1)(3), Villareal DT(5)(6), Fletcher TL(1)(2)(3). Author information: (1)Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. (2)South Central Mental Illness Research, Education and Clinical Center, Houston, Texas, USA. (3)Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. (4)Selzman Institute for Kidney Health, Section of Nephrology, Baylor College of Medicine, Houston, Texas, USA. (5)Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston, Texas, USA. (6)Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, Texas, USA. GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual framework. Patient-related factors, especially related to patient behaviors, are understudied in relation to GLP-1RA discontinuation. Patients treated for type 2 diabetes mellitus or weight management with GLP-1RAs often discontinue the medication, but this is often nonpermanent. Improving adherence to and persistence on GLP-1RAs will require nuanced attention to care trajectories as well as an integrated understanding of GLP-1RA tolerability, expectations, and the understudied role of patient behaviors and the healthcare system. To clarify relevant mechanisms and guide targeted intervention for highest-risk individuals, further study should standardize definitions of persistence and discontinuation and implement patient-centered qualitative work, especially related to health behaviors. Published 2026. This article is a U.S. Government work and is in the public domain in the USA. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.70913 PMCID: PMC13341420 PMID: 42244474 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Orforglipron

Missense mutations in MKRN3 and central precocious puberty: a mutational approach to understanding protein function.

1. Curr Opin Pediatr. 2026 Aug 1;38(4):424-433. doi: 10.1097/MOP.0000000000001588. Epub 2026 Jun 8. Missense mutations in MKRN3 and central precocious puberty: a mutational approach to understanding protein function. Franssen D(1), Kaiser UB. Author information: (1)Division of Endocrinology, Diabetes, and Metabolism, Mass General Brigham, Harvard Medical School, Boston, Massachusetts, USA. PURPOSE OF REVIEW: Loss-of-function mutations in MKRN3 are the most common monogenic cause of central precocious puberty (CPP), yet the functional consequences of missense variants, which account for the majority of such cases, remain incompletely understood. A growing body of genetic, biochemical, computational, and in vivo studies now allows a domain-by-domain dissection of how missense mutations impair MKRN3 function, offering mechanistic insight into pubertal regulation that extends beyond individual variant reporting. RECENT FINDINGS: Missense mutations in the C3HC4 RING finger domain consistently reduce ubiquitin ligase activity and impair MKRN3-mediated repression of neurokinin B, kisspeptin, and GnRH, while mutations in C3H zinc finger domains paradoxically enhance auto-ubiquitination or disrupt RNA binding, revealing distinct pathogenic mechanisms. Computational stability analysis shows that destabilizing and stabilizing variants can both be pathogenic, underscoring the limitations of in silico tools alone. Phenotypic variability is shaped by the classes of mutations, sexually dimorphic neuroendocrine sensitivity, epigenetic regulation of MKRN3 promoter activity, and polygenic modifiers of pubertal timing. SUMMARY: Understanding the domain-specific effects of MKRN3 missense mutations refines genotype-phenotype correlations and improves variant interpretation in clinical practice. Integration of functional assays with polygenic risk assessment is essential for accurate genetic counseling in families with CPP. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MOP.0000000000001588 PMID: 42290210 [Indexed for MEDLINE]

Mentions Kisspeptin

Tirzepatide ameliorates cisplatin-induced acute kidney injury by restoring NAMPT/NAD + homeostasis and enhancing Pink1-Parkin-mediated mitophagy.

1. Biochem Pharmacol. 2026 Aug;250(Pt 2):118040. doi: 10.1016/j.bcp.2026.118040. Epub 2026 May 9. Tirzepatide ameliorates cisplatin-induced acute kidney injury by restoring NAMPT/NAD + homeostasis and enhancing Pink1-Parkin-mediated mitophagy. Han C(1), Tan Z(2), Wang Y(3), Jing X(4), Cui X(5), Zhang Y(2), Yan P(2), Cheng Y(2), Yue H(2), Wang B(6), Guo H(7). Author information: (1)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Nephrology, Heping Branch, Shanxi Provincial People's Hospital , Taiyuan, 030027, China; Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China. (2)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Nephrology, Heping Branch, Shanxi Provincial People's Hospital , Taiyuan, 030027, China. (3)Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China. (4)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Laboratory of Shanxi Provincial People's Hospital, Taiyuan, 030012, China. (5)Department of Reproductive Medicine Center, Children's Hospital of Shanxi, The Affiliated Children's Hospital of Shanxi Medical University, Shanxi Maternal and Child Health Hospital, Taiyuan 030001, China. (6)The Fifth Clinical Medical College of Shanxi Medical University (Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University), Taiyuan, 030012, China; Department of Nephrology, Heping Branch, Shanxi Provincial People's Hospital , Taiyuan, 030027, China. Electronic address: docwangbaodong@sxmu.edu.cn. (7)Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China; Department of Nephrology, Shenzhen Bao'an Shiyan People's Hospital, Shenzhen 518100, China. Electronic address: guohui8688@126.com. Mitochondrial dysfunction and insufficient mitophagy are central to cisplatin-induced acute kidney injury (AKI). Tirzepatide, a dual GLP‑1/GIP receptor agonist, exhibits reno-protective effects, but its mechanism related to mitochondrial homeostasis remains unclear. Here, we used metabolomics, in vivo mouse AKI model, and in vitro cisplatin-injured HK‑2 cells to explore the protective effects and underlying mechanisms. Tirzepatide pretreatment significantly alleviated renal dysfunction, tubular injury, and mitochondrial damage caused by cisplatin. Metabolomic analysis revealed that tirzepatide strongly regulated energy metabolism and autophagy , particularly NAD + homeostasis. Mechanistically, tirzepatide boosted NAD+ levels by nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme for NAD + synthesis , which in turn activating the Pink1-Parkin mitophagy pathway. Inhibition of autophagy or NAMPT abolished the mitochondrial and reno-protective effects of tirzepatide. Taken together, our findings demonstrate that tirzepatide protects against cisplatin‑induced AKI by enhancing NAMPT‑dependent NAD + restoration and promoting mitophagy, highlighting a promising therapeutic strategy for chemotherapy‑related nephrotoxicity. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.bcp.2026.118040 PMID: 42114682 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Tirzepatide

Cosmetic potential of Ganoderma lucidum (Reishi) extract in a topical cream formulation.

1. Int J Cosmet Sci. 2026 Aug;48(4):828-840. doi: 10.1111/ics.70079. Epub 2026 Feb 9. Cosmetic potential of Ganoderma lucidum (Reishi) extract in a topical cream formulation. Dikmen Kucuk S(1), Jabet P(2), Groso A(2), Collet G(2), Daniellou R(2), Karadeniz B(1). Author information: (1)Coordination Office of Specialization in Environment and Health Technologies, University of Düzce, Düzce, Turkey. (2)Chaire de Cosmétologie, Institute of AgroParisTech, Orleans, France. OBJECTIVE: The primary objective of this study was to investigate the biological activities of freeze-dried Ganoderma lucidum (Reishi) extract obtained from hazelnut pruning waste and to compare its antioxidant, tyrosinase inhibitory and cytotoxic properties with two widely used cosmetic actives-argireline peptide and α-arbutin. Additionally, the study aimed to develop a topical cream formulation containing Reishi extract and to assess its microbiological safety, preservative efficacy and physicochemical stability under controlled environmental conditions. By integrating bioactivity evaluation with formulation performance, the research sought to determine the potential applicability of Reishi extract as a natural and multifunctional cosmetic ingredient suitable for anti-aging and skin-brightening applications. METHODS: The antioxidant capacity of Reishi extract, argireline peptide and α-arbutin was determined using a copper(II)-based total antioxidant capacity assay. Tyrosinase inhibitory activity was measured with human tyrosinase sourced from MNT-1 melanoma cells, while cytotoxicity and safe dose limits were determined in HaCaT human keratinocyte cells via the AlamarBlue® method. A topical cream formulation was prepared using a multi-phase emulsification technique and characterized physicochemically. Microbiological safety was assessed according to Turkish Cosmetic Regulations, and preservative efficacy was determined through challenge testing. Stability assessments included temperature cycling, long-term storage at different temperatures and centrifugation tests, monitoring visual, physicochemical and microbiological parameters over a three-month period. RESULTS: Reishi extract demonstrated 861 μmol TE/g antioxidant activity, 30% tyrosinase inhibition and a broader safety margin compared with argireline peptide and α-arbutin, which exhibited cytotoxicity at lower concentrations. The formulated cream retained a skin-compatible pH and stable viscosity, while showing no signs of phase separation, colour change or integrity loss under all storage conditions. Microbiological analysis confirmed microbial counts below regulatory limits, and challenge testing revealed rapid log reductions in all tested microorganisms, satisfying the acceptance criteria for preservative efficacy. Stability studies supported the physical robustness and microbiological safety of the final product throughout the evaluation period. CONCLUSION: Overall, the findings highlight Reishi extract as a bioactive-rich, safe and stable natural ingredient with strong potential for incorporation into cosmetic formulations. Its antioxidant performance, moderate tyrosinase inhibition and compatibility within the cream matrix support its use in multifunctional anti-aging and skin-brightening products. Publisher: OBJECTIF: L'objectif principal de cette étude était d'étudier les activités biologiques de l'extrait de Ganoderma lucidum lyophilisé (Reishi) obtenu à partir des déchets d'élagage des noisettes et de comparer ses propriétés antioxydantes, inhibitrices de la tyrosinase et cytotoxiques avec deux actifs cosmétiques largement utilisés : un peptide d'argireline et d'α‐arbutine. Par ailleurs, l'étude visait à développer une formulation de crème topique contenant de l'extrait de Reishi et à évaluer sa sécurité microbiologique, son efficacité de conservation et sa stabilité physicochimique dans des conditions environnementales contrôlées. En intégrant l'é

Mentions Argireline

GLP-1 receptor agonists in pediatric obesity and diabetes: a systematic review of efficacy, metabolic effects, and safety.

1. Diabetes Res Clin Pract. 2026 Aug;238:113400. doi: 10.1016/j.diabres.2026.113400. Epub 2026 Jun 28. GLP-1 receptor agonists in pediatric obesity and diabetes: a systematic review of efficacy, metabolic effects, and safety. Soliman AT(1), Alyafei F(2), Khalil A(3), Kardousha AT(3), Ahmed S(2), Alaaraj N(2), Hamed N(2). Author information: (1)Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. Electronic address: atsoliman56@gmail.com. (2)Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. (3)Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. Childhood obesity and youth-onset type 2 diabetes mellitus (T2DM) are increasing, highlighting the need for effective treatments beyond lifestyle intervention and metformin. This review systematically evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or T2DM. PubMed-indexed studies published from 2000 to 2025 were reviewed, including seven pivotal randomized controlled trials and six meta-analyses involving 901 participants aged 6 to < 18 years. Semaglutide 2.4 mg/week produced the greatest BMI reduction in adolescents with obesity, followed by liraglutide 3.0 mg/day, which also improved BMI SDS in adolescents and younger children. In youth-onset T2DM, liraglutide 1.8 mg/day and dulaglutide significantly improved HbA1c compared with placebo. Weight-reducing agents also improved insulin resistance and modestly reduced triglycerides, while LDL-cholesterol changes were minimal. Gastrointestinal adverse events, mainly nausea and vomiting, were the most frequent and were generally transient and dose dependent. No significant adverse effects on linear growth or pubertal progression were reported. GLP-1 RAs are effective adjuncts for pediatric obesity and T2DM, but longer-term studies are needed to assess cardiovascular safety, bone health, and growth outcomes. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.diabres.2026.113400 PMID: 42365860 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison.

1. Diabetes Obes Metab. 2026 Aug;28(8):7247-7256. doi: 10.1111/dom.70919. Epub 2026 Jun 1. Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. Michalak W(1), Bøg M(2), Bendixen T(2), Chowdhury R(3), Cowley P(3), Laugesen C(2), Rathor N(2), Kushner RF(4). Author information: (1)Novo Nordisk Inc., Plainsboro, New Jersey, USA. (2)Novo Nordisk A/S, Søborg, Denmark. (3)Petauri Evidence, Bicester, UK. (4)Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. AIMS: This study aimed to indirectly compare the effects of oral semaglutide 25 mg versus orforglipron 36 mg on body weight loss, other cardiometabolic biomarkers, and tolerability in adults with overweight (body mass index [BMI] ≥ 27 kg/m2 and at least one obesity-related complication) or obesity (BMI ≥ 30 kg/m2), without diabetes, using data from OASIS 4 and ATTAIN-1. MATERIALS AND METHODS: Individual patient data from OASIS 4 and aggregate data from ATTAIN-1 informed anchored indirect treatment comparisons (ITCs). Baseline differences in sex, body weight and normoglycaemic status were adjusted for using population-adjustment methods. Efficacy (percentage body weight change, categorical body weight loss thresholds, other cardiometabolic biomarkers) and tolerability outcomes (treatment discontinuation due to any adverse event [AE] and due to gastrointestinal [GI] AEs) were analysed. RESULTS: Population-adjusted analyses showed a significantly greater percentage change from baseline in body weight with oral semaglutide 25 mg than with orforglipron 36 mg, with mean differences (MDs) of -3.2%-points (95% confidence intervals [CIs]: -5.9, -0.4; treatment-regimen estimand) and -3.0%-points (95% CI: -5.8, -0.3; efficacy estimand). Discontinuation was higher with orforglipron (due to any AE: odds ratio [OR]: 4.1 [95% CI: 1.3, 13.0] and due to GI AEs: OR: 13.9 [95% CI: 2.0, 96.0]). CONCLUSIONS: In this ITC, oral semaglutide 25 mg was associated with greater body weight loss and fewer discontinuations due to any AEs and due to GI AEs compared with orforglipron 36 mg. These findings provide insight into the comparative effectiveness and tolerability in the absence of head-to-head clinical trials. © 2026 Novo Nordisk Inc. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.70919 PMCID: PMC13341387 PMID: 42225305 [Indexed for MEDLINE] Conflict of interest statement: Wojciech Michalak, Martin Bøg, Theiss Bendixen, Christian Laugesen, and Naveen Rathor are employees and shareholders of Novo Nordisk. Rohan Chowdhury and Phoebe Cowley are employees of Petauri Evidence, who were paid by Novo Nordisk to support with this study. Robert F. Kushner serves as a consultant to AbbVie, Antag Therapeutics, AstraZeneca, Boehringer Ingelheim, Currax Pharmaceuticals, Eli Lilly, Structure Therapeutics, Novo Nordisk, Weight Watchers and Viking Therapeutics.

Mentions Orforglipron

Molecular targets of oleoylethanolamide in the pathogenesis of alcohol use disorder: Mechanisms of central and peripheral action.

1. Alcohol. 2026 Aug;134:9-23. doi: 10.1016/j.alcohol.2026.04.004. Epub 2026 Apr 18. Molecular targets of oleoylethanolamide in the pathogenesis of alcohol use disorder: Mechanisms of central and peripheral action. Ivashkevich D(1), Manzhulo I(2). Author information: (1)A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041, Vladivostok, Russia. (2)A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 690041, Vladivostok, Russia. Electronic address: i-manzhulo@bk.ru. Alcohol use disorder (AUD) is a complex disease whose pathogenesis involves profound neurobiological disturbances in reward, stress, and cognitive control systems, as well as systemic peripheral pathological processes, including inflammation and organ damage. Oleoylethanolamide (OEA) - an endogenous lipid mediator synthesized from oleic acid, with the nuclear receptor PPAR-α as its primary target. Accumulated evidence indicates the multi-level therapeutic potential of OEA in correcting key aspects of AUD. Its central action importantly involves the ability to modulate dopaminergic transmission in the reward system and influence the balance of orexin and oxytocin signaling pathways, contributing to a reduction in motivation to consume alcohol. A significant aspect of its activity is its antidepressant and anxiolytic properties, associated with the normalization of monoaminergic neurotransmitter activity and the hypothalamic-pituitary-adrenal (HPA) axis during withdrawal. A substantial contribution to OEA's therapeutic profile is its pronounced anti-inflammatory and neuroprotective action, including strengthening of the intestinal barrier, suppression of neuroinflammatory cascades, and stimulation of neurotrophic support. Furthermore, OEA demonstrates hepatoprotective potential aimed at reducing steatosis, oxidative stress, and inflammation in the liver. Thus, the multi-organ mechanism of action of OEA corresponds to the multifactorial nature of AUD, justifying its consideration as a promising basis for developing comprehensive therapeutic strategies. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.alcohol.2026.04.004 PMID: 42009176 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Oxytocin

Beyond weight loss: multisystem benefits of obesity medications.

1. Lancet Diabetes Endocrinol. 2026 Aug;14(8):678-692. doi: 10.1016/S2213-8587(26)00100-2. Epub 2026 May 28. Beyond weight loss: multisystem benefits of obesity medications. Savas M(1), Kuckuck S(2), Boon MR(3), van Rossum EFC(3). Author information: (1)Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.savas@erasmusmc.nl. (2)Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. (3)Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Obesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical conditions. This Review synthesises evidence from randomised controlled trials and high-quality meta-analyses on approved and late-stage investigational obesity medications, including phentermine-topiramate, naltrexone-bupropion, glucagon-like peptide-1 (GLP-1) receptor agonists (eg, liraglutide, semaglutide, subcutaneously and orally), and newer GLP-1 receptor agonist-based agents (eg, tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). We evaluated the effects of obesity medications across major obesity-related conditions, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnoea syndrome, polycystic ovary syndrome (recently named polyendocrine metabolic ovarian syndrome), osteoarthritis, muscle mass, depression, quality of life, and food cravings, along with binge-eating disorders, substance use disorders, and neurodegenerative diseases. Overall, GLP-1-based and multiagonist therapies show beneficial effects across these comorbid conditions. While many benefits of obesity medications are mediated by weight loss, accumulating evidence indicates important weight loss-independent effects, particularly with GLP-1 receptor agonist-based therapies. A broader understanding of these pleiotropic effects is essential to inform personalised obesity management and optimise long-term clinical outcomes. Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. DOI: 10.1016/S2213-8587(26)00100-2 PMID: 42208956 [Indexed for MEDLINE] Conflict of interest statement: Declaration of interests MS received honoraria for lectures and educational events from Obesitas Platform–MedOnline, SCEM, Health Investment, Public Eyes Healthcare Communications, BSL, Medische Scholing, and MedClass–Boehringer Ingelheim; and support for attending a meeting from Rhythm Pharmaceuticals. MRB received honoraria for lectures and educational events from Obesitas Platform–MedOnline, SCEM, Health Investment, Public Eyes Healthcare Communications, Goodlife, and Eli Lilly; support for attending a meeting from Rhythm Pharmaceuticals; and receives royalties from Ambo Anthos for a book for lay and professional audiences: FAT, the secret organ (Dutch: VET Belangrijk, 2019; VET Belangrijk 2.0, 2026). EFCvR reports

Mentions Retatrutide

Exogenous Kisspeptin-10 inhibits ovarian cancer progression through targeting the SP1-hTERT-ZEB1 regulatory axis.

Mentions Kisspeptin

Transforming a protease inhibitor into a peptide Guardian: BBI-armed hydrogel beads for Oral delivery of active peptides.

1. Food Res Int. 2026 Jul 31;236:119229. doi: 10.1016/j.foodres.2026.119229. Epub 2026 Apr 20. Transforming a protease inhibitor into a peptide Guardian: BBI-armed hydrogel beads for Oral delivery of active peptides. Xu Q(1), Li W(1), An J(2), Li J(1), Liu X(2), Li H(3). Author information: (1)Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China. (2)Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China; Key Laboratory of Plant Protein Innovation and Resource Development, China National Light Industry, Beijing Technology and Business University, Beijing 100048, China. (3)Key Laboratory of Geriatric Nutrition and Health (Beijing Technology and Business University), Ministry of Education, Beijing 100048, China. Electronic address: lihe@btbu.edu.cn. This study repurposes the Bowman-Birk inhibitor (BBI), traditionally viewed as an antinutritional factor for its protease inhibition, as a protective agent for peptide therapeutics. We co-encapsulated BBI with semaglutide in hydrogel beads to orchestrate their release, thereby leveraging protease inhibition to enhance peptide stability. In vitro studies with ionically crosslinked beads showed that BBI release effectively inhibited trypsin. Crucially, this extended semaglutide's intestinal residence time from 2.5 to 4 h (1.6-fold increase over control, p < 0.05), showcasing a direct protective benefit. Release kinetics revealed a temporal synergy: early-phase BBI release (60% within 2 h) established a low-protease environment enabling sustained semaglutide release. Our findings not only offer a novel strategy for oral peptide delivery but also redefine antinutritional factors as valuable functional excipients in drug formulation. Copyright © 2024. Published by Elsevier Ltd. DOI: 10.1016/j.foodres.2026.119229 PMID: 42116484 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Research-Evidence-Practice Gaps in Post-stroke Neuro-recovery Pharmacological Therapies in Asia.

Mentions Cerebrolysin

Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.

1. Diabetes Obes Metab. 2026 Jul 26. doi: 10.1111/dom.71134. Online ahead of print. Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1. Busetto L(1), Contreras CO(2), Christensen MH(2), Garvey TW(3), Horn DB(4), McGowan B(5), Miller CP(2), Schnecke V(2), le Roux CW(6)(7). Author information: (1)Department of Medicine, University of Padova, Padova, Italy. (2)Novo Nordisk A/S, Søborg, Denmark. (3)University of Alabama at Birmingham, Birmingham, Alabama, USA. (4)Center for Obesity Medicine and Metabolic Performance, University of Texas McGovern Medical School, Houston, Texas, USA. (5)Guy's and St. Thomas' NHS Foundation Trust, London, UK. (6)Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland. (7)Diabetes Research Centre, Ulster University, Coleraine, UK. AIMS: To assess the added value of absolute anthropometric targets alongside percentage weight loss in the clinical management of obesity. MATERIALS AND METHODS: The phase 3a, 68-week REDEFINE 1 trial randomised adults without diabetes with BMI ≥ 30 kg/m2, or ≥ 27 kg/m2 with ≥ 1 obesity-related complication, to once-weekly CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, plus lifestyle intervention. This secondary, post hoc analysis assessed the proportions of participants achieving BMI < 27 kg/m2 and/or WHtR < 0.53 targets, and percentage weight loss by anthropometric target. The association between the proportion of participants maintaining or achieving normalisation of four cardiometabolic outcomes: normoglycemia (glycated haemoglobin < 5.7% and fasting plasma glucose < 5.6 mmol/L); blood pressure (< 130/80 mmHg); triglycerides (< 1.7 mmol/L); lipids (high-density lipoprotein cholesterol ≥ 1.3 mmol/L [female] or ≥ 1.0 mmol/L [male]) and reaching anthropometric targets or change in body weight (%) was also assessed. RESULTS: The proportion of participants achieving both BMI < 27 kg/m2 and WHtR < 0.53 targets at week 68 was 30.3%, 19.1%, 9.0%, and 3.3% in participants who received CagriSema, semaglutide, cagrilintide, or placebo respectively. Both BMI and WHtR performed similarly as indicators for all four cardiometabolic outcomes. At more stringent cut-off values, anthropometric targets were better measures than percentage weight loss. CONCLUSIONS: The proportion of participants achieving anthropometric targets was greater with CagriSema Versus other treatments. These findings support further validation of BMI and WHtR anthropometric treatment targets and indicate a potential for indicating amelioration of clinical outcomes in obesity and a greater emphasis on target-based treatment strategies. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.71134 PMID: 42503495

Mentions CagriSema

Incretin analogues as cardiovascular agents: a state-of-the-art review.

1. Front Endocrinol (Lausanne). 2026 Jul 24;17:1898812. doi: 10.3389/fendo.2026.1898812. eCollection 2026. Incretin analogues as cardiovascular agents: a state-of-the-art review. Araiza-Garaygordobil D(1)(2), Rico-Fontalvo J(3)(4), Hernández-Balbuena B(1), Vinay-Coro M(1), González-Arias M(5). Author information: (1)Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Ciudad de México, Mexico. (2)División de Estudios de Posgrado, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, Mexico. (3)Comité de Riñón, diabetes y metabolismo, Asociación Colombiana de Nefrología e HTA, Bogotá, Colombia. (4)Department of Nephrology, Nephromedicall Health Services Provider Institution (IPS), Medellín, Colombia. (5)Department of Endocrinology, Hospital Center, New York, NY, United States. Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide have evolved over the past decade from glucose-lowering antidiabetic agents into a cardiovascular drug class with proven outcome benefit across multiple clinical scenarios. This state-of-the-art review synthesizes the cardiovascular evidence base for incretin analogues, organized by clinical scenario, and addresses the structural challenges that constrain their deployment in low- and middle-income countries (LMICs). We review the pharmacology and proposed cardiovascular mechanisms, including direct effects on the vascular endothelium, macrophage inflammation, and epicardial adipose tissue, alongside indirect benefits mediated by weight loss, glycemic control, and blood pressure reduction. We summarize the evidence in five clinical scenarios: type 2 diabetes with established atherosclerotic cardiovascular disease or high cardiovascular risk; overweight or obesity with established cardiovascular disease but without diabetes; obesity-related heart failure with preserved ejection fraction; chronic kidney disease; and symptomatic peripheral artery disease. Pipeline agents (retatrutide, CagriSema, survodutide, orforglipron, zenagamtide, and MariTide) are reviewed alongside their ongoing cardiovascular outcome trials. A dedicated section examines the global access perspective, including the disproportionately high burden of cardiometabolic disease in LMICs, the limited representation of regional populations in pivotal trials, and the structural barriers of cost and reimbursement that constrain access. We close with a practical algorithm for the clinician, an honest assessment of evidence gaps, and a calibrated outlook on the next generation of incretin-based cardiovascular therapy. Copyright © 2026 Araiza-Garaygordobil, Rico-Fontalvo, Hernández-Balbuena, Vinay-Coro and González-Arias. DOI: 10.3389/fendo.2026.1898812 PMCID: PMC13447287 PMID: 42568490 [Indexed for MEDLINE] Conflict of interest statement: DA-G has received speaking fees from Novo Nordisk, AstraZeneca, Novartis, Bayer, Adium, Boehringer-Ingelheim, Servier, and Silanes, and declares active research grants with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, and Bayer. JR-F has received speaking fees from Novo Nordisk, AstraZeneca, Eli Lilly, Bayer, Sanofi, Boehringer-Ingelheim, Merck, and MSD. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Mentions CagriSema

Naringenin protects against renal ischemia-reperfusion injury following unilateral nephrectomy via modulation of oxidative stress and kisspeptin expression.

Mentions Kisspeptin

Orforglipron: First Approval.

1. Drugs. 2026 Jul 21. doi: 10.1007/s40265-026-02363-5. Online ahead of print. Orforglipron: First Approval. Shirley M(1). Author information: (1)Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. dru@adis.com. Orforglipron (Foundayo™) is an orally administered, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist being developed by Eli Lilly and Co. for use in long-term weight management and for the treatment of type 2 diabetes (T2D) among other indications. In April 2026, orforglipron received its first approval, in the USA, for use in combination with a reduced-calorie diet and increased physical activity for long-term weight management in adults with obesity or adults with overweight in the presence of one or more weight-related comorbid condition. Orforglipron has also been submitted for regulatory review in the EU for long-term weight management and T2D, in Japan for long-term weight management, and in Canada for T2D. In addition to long-term weight management and T2D treatment, orforglipron is currently under phase III clinical evaluation for use in the treatment of obstructive sleep apnoea, hypertension, stress urinary incontinence in females, osteoarthritis pain and peripheral arterial disease. This article summarises the milestones in the development of orforglipron leading to this first approval for long-term weight management in adults with obesity or overweight. © 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. DOI: 10.1007/s40265-026-02363-5 PMID: 42479349 Conflict of interest statement: Declarations. Authorship and Conflict of interest: During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Matt Shirley is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to this article and are responsible for its content. Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability: Not applicable.

Mentions Orforglipron

Involvement of cocaine- and amphetamine-regulated transcript neurons in glucoprivic suppression of pulsatile luteinizing hormone secretion in female rats.

1. J Reprod Dev. 2026 Jul 17. doi: 10.1262/jrd.2026-059. Online ahead of print. Involvement of cocaine- and amphetamine-regulated transcript neurons in glucoprivic suppression of pulsatile luteinizing hormone secretion in female rats. Matsuzaki S(1), Hazim S(1), Toyohama Y(1), Yamada K(1), Seki S(1), Inamura K(1), Otsuka Y(1), Takizawa M(1), Noda C(1), Inoue N(1), Tsukamura H(1), Uenoyama Y(1). Author information: (1)Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. Malnutrition often suppresses reproductive function by inhibiting the pulsatile secretion of gonadotropin-releasing hormone (GnRH)/gonadotropins in mammals. This study aimed to determine whether cocaine- and amphetamine-regulated transcript (CART) neurons mediate the suppression of GnRH/gonadotropin pulses under malnutrition, since CART neurons have been reported to project to kisspeptin/neurokinin B/dynorphin A neurons (also known as the GnRH pulse generator) and GnRH neurons in rats. Wistar-Imamichi female rats were ovariectomized (OVX), and some of these rats were immediately implanted with subcutaneous Silastic tubing containing estradiol-17β (OVX + low E2) to maintain a diestrous level of estrogen. Free-moving conscious OVX and OVX + low E2 rats were subjected to 1-h frequent blood sampling followed by brain sampling to examine whether acute glucoprivation by peripheral administration of 2-deoxy-D-glucose (2DG), a glucose utilization inhibitor, suppressed the secretion of luteinizing hormone (LH) and activated hypothalamic CART neurons. The other cohort of animals was subjected to 3-h frequent blood sampling to examine whether central CART administration suppresses pulsatile LH secretion. Peripheral 2DG administration suppressed LH secretion and activated CART neurons in the hypothalamic supraoptic nucleus (SON) and parvocellular paraventricular nucleus (PVN), but not in the magnocellular PVN-zona incerta-dorsomedial nucleus continuum and arcuate nucleus, in OVX and OVX + low E2 rats. In addition, central CART administration suppressed pulsatile LH secretion in OVX and OVX + low E2 rats. These results suggest the possible involvement of CART neurons in the SON and parvocellular PVN in malnutrition-induced suppression of pulsatile LH secretion in female rats. DOI: 10.1262/jrd.2026-059 PMID: 42476751

Mentions Kisspeptin

Comparison of the effects of atypical antipsychotics on decreased libido in zebrafish and their mechanisms.

1. Behav Brain Res. 2026 Jul 16:116384. doi: 10.1016/j.bbr.2026.116384. Online ahead of print. Comparison of the effects of atypical antipsychotics on decreased libido in zebrafish and their mechanisms. Shinokawa K(1), Hattori S(2), Miyauchi M(3), Noguchi N(3), Eto Y(3), Suda A(3), Kishida I(4), Hishimoto A(5), Asami T(3). Author information: (1)Department of Psychiatry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. Electronic address: t256046a@yokohama-cu.ac.jp. (2)Department of Psychiatry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. Electronic address: saki1122@yokohama-cu.ac.jp. (3)Department of Psychiatry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. (4)Department of Psychiatry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan; Fujisawa Hospital, 383 Kotsuka, Fujisawa, Kanagawa 251-0013, Japan. (5)Department of Psychiatry, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. Antipsychotic-induced decreased libido is a common clinical concern, yet drug-specific differences and their underlying neurobiological mechanisms remain poorly understood. We chronically exposed adult male zebrafish to risperidone (RIS), olanzapine (OLZ), quetiapine (QTP), or aripiprazole (ARP) to evaluate their effects on courtship behavior. Brain and testicular transcripts related to the hypothalamic-pituitary-gonadal (HPG) axis, kisspeptin, and monoamine receptors, along with systemic 11-ketotestosterone (11-KT) concentrations, were subsequently analyzed. RIS significantly decreased courtship duration, followed by a downward trend in the OLZ group, whereas QTP and ARP showed no detrimental effects. At the molecular level, RIS significantly reduced brain kiss2 and upregulated prl1 transcript levels. Conversely, the ARP group demonstrated a local transcriptional upregulation of neurosteroidogenic enzymes (cyp11c1 and hsd11b2) and downregulation of the inhibitory gnihr1 pathway in the brain, which may help preserve reproductive drive. Furthermore, RIS and OLZ groups showed significant transcriptional upregulation of central dopamine and serotonin receptors, reflecting marked monoaminergic alterations. These findings suggest that QTP and ARP have minimal impacts on libido, while RIS and OLZ carry a higher risk. This differential susceptibility is likely mediated by a complex interplay of kiss2 downregulation, prolactin elevation, altered local neurosteroidogenesis, and monoamine receptor transcript adjustments, rather than a uniform suppression of the peripheral HPG axis. Copyright © 2026. Published by Elsevier B.V. DOI: 10.1016/j.bbr.2026.116384 PMID: 42463028 Conflict of interest statement: Declaration of Competing Interest The authors declare no conflict of interest.

Mentions Kisspeptin

Medical Treatments for Obesity: What Does the Future Have in Store?

1. J Clin Endocrinol Metab. 2026 Jul 14:dgag274. doi: 10.1210/clinem/dgag274. Online ahead of print. Medical Treatments for Obesity: What Does the Future Have in Store? Bassatne A(1), Rizo I(1). Author information: (1)Section of Endocrinology Diabetes and Nutrition, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts. CONTEXT: Obesity is a chronic relapsing disease associated with substantial morbidity, mortality, and health care costs. Contemporary obesity pharmacotherapies extend beyond weight reduction, with evidence for improvements across multiple obesity-related complications, supporting a shift toward phenotype-guided, complication-centric care. EVIDENCE ACQUISITION: A systematic literature search of the Medline database using MeSH terms and keywords related to new-generation obesity pharmacotherapy was conducted to identify articles published between 2021 and 2026. Reference lists of relevant reviews were screened to identify additional eligible studies. Phase 2 and 3 clinical trials evaluating emerging obesity pharmacotherapies in adults and reporting outcomes, including weight loss and obesity-related complications, were included. EVIDENCE SYNTHESIS: Entero-pancreatic hormone-based therapies targeting GLP-1, GIP, amylin, and glucagon pathways demonstrate substantial efficacy beyond weight reduction. These hormones act through complementary mechanisms regulating appetite, energy balance, and metabolic homeostasis. GLP-1 based agents achieve approximately 10-15% weight loss, whereas agents targeting multiple pathways demonstrate greater efficacy. Tirzepatide, CagriSema, and amycretin achieved weight reductions exceeding 20% and the triple agonist retatrutide produced reductions exceeding 25%. Beyond weight loss, these agents improve glycemia, support diabetes prevention, and produce organ-specific benefits, including reduced cardiovascular events, improved heart failure symptoms, decreased obstructive sleep apnea severity, improvement of metabolic dysfunction-associated steatohepatitis, slowing chronic kidney disease progression, and reduced osteoarthritis-related pain. CONCLUSIONS: Next-generation obesity pharmacotherapies represent a major advance in obesity management and support a treat-to-target approach prioritizing improvement in obesity-related complications and metabolic health. Effective implementation will require individualized therapy and attention to long-term safety, access, and equitable delivery of care. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. DOI: 10.1210/clinem/dgag274 PMID: 42444567

Mentions Retatrutide

Resolution of anhedonia-like symptoms in patients treated for obesity with tirzepatide: A three-case series.

1. Obes Pillars. 2026 Jul 14;19:100302. doi: 10.1016/j.obpill.2026.100302. eCollection 2026 Sep. Resolution of anhedonia-like symptoms in patients treated for obesity with tirzepatide: A three-case series. Nadolsky S(1), Kessel S(1), Krumm ZA(2)(3), Tinsley GM(1)(4). Author information: (1)Vineyard Health, Holland, MI, USA. (2)Department of Neuroscience, University of Florida, Gainesville, FL, USA. (3)McKnight Brain Institute, University of Florida, Gainesville, FL, USA. (4)Department of Kinesiology & Sport Management, Texas Tech University, Lubbock, TX, USA. INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP1RAs) have demonstrated substantial efficacy for obesity and metabolic disease treatment, with emerging evidence suggesting effects on reward-processing pathways and motivated behaviors. Although reductions in food craving and addictive behaviors may be beneficial, some patients anecdotally report diminished motivation and anhedonia-like symptoms during high-dose therapy. This case series highlights a potentially underrecognized neurobehavioral effect associated with high-dose tirzepatide and explores clinical management strategies. CASE PRESENTATION: Three female patients with obesity treated with high-dose tirzepatide (15 mg·week-1) reported reduced motivation, emotional "flatness," or loss of interest in exercise and previously enjoyable activities despite successful weight loss. Two patients had no prior history of mood disorders, while one patient had a history of depression and anxiety. Symptoms were described as distinct from depressive episodes and emerged after prolonged treatment at or near maximal dosing. One patient independently noted symptom improvement after temporary discontinuation and dose reduction surrounding a medical procedure. INTERVENTIONS AND OUTCOMES: All patients underwent tirzepatide dose reduction to 10 mg·week-1 or lower. Two patients experienced marked improvement in motivation and enjoyment of daily activities after dose reduction alone. One patient required adjunctive bupropion therapy, which produced additional symptomatic improvement. Re-escalation of the tirzepatide dose in one patient resulted in recurrence of symptoms without additional weight loss benefit, whereas subsequent dose reduction restored motivation while maintaining weight-loss outcomes. Across all cases, symptom improvement occurred alongside continued weight maintenance or further weight reduction. CONCLUSION: This case series suggests that anhedonia-like symptoms may occur in a subset of patients receiving high-dose tirzepatide, potentially related to GLP1RA-mediated modulation of mesolimbic dopaminergic pathways. Clinicians should consider monitoring for changes in motivation and reward perception during treatment, particularly at higher doses. Dose reduction, with or without adjunctive dopaminergic therapy such as bupropion, may alleviate symptoms while preserving therapeutic benefits. © 2026 The Authors. DOI: 10.1016/j.obpill.2026.100302 PMCID: PMC13382402 PMID: 42518361

Mentions Tirzepatide

Amylin-based obesity therapy: a meta-analysis of Cagrilintide and CagriSema versus placebo.

1. Ann Med Surg (Lond). 2026 Jul 13;88(8):5317-5326. doi: 10.1097/MS9.0000000000005353. eCollection 2026 Aug. Amylin-based obesity therapy: a meta-analysis of Cagrilintide and CagriSema versus placebo. Yaseen M(1), Ameer A(2), Ali Z(3), Jamali JA(2), Kumar A(3), Basit Ali Siddiqui M(4), Kumari P(1), Hassaan M(4), Nanwani P(5), Abdul Basit M(4), Lohana N(1), Qureshi R(4), Tesfaye M(6). Author information: (1)Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan. (2)University Hospital Limerick, Limerick, Ireland. (3)Chandka Medical College, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Pakistan. (4)Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. (5)University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. (6)Addis Ababa University, Addis Ababa, Ethiopia. BACKGROUND: Obesity remains a major global health challenge, driving demand for effective pharmacotherapies. Cagrilintide, a once-weekly amylin receptor agonist, and its fixed-dose combination with semaglutide (CagriSema) represent novel therapeutic approaches. This systematic review and meta-analysis evaluated their efficacy and safety in adults with overweight or obesity. METHODS: Four databases were searched from inception to March 2026. Eligible randomized controlled trials (RCTs) assessed Cagrilintide monotherapy or CagriSema versus placebo. Outcomes included percentage and absolute body weight change, waist circumference, blood pressure, HbA1c, and adverse events. Data were pooled using random-effects models in RevMan, with results expressed as mean differences (MD) or risk ratios (RR) with 95% confidence intervals. RESULTS: Four RCTs encompassing 5425 participants were included. Cagrilintide monotherapy produced significant reductions in body weight (MD: -6.08%; MD: -5.89 kg) and blood pressure, without meaningful HbA1c improvement. CagriSema significantly reduced body weight (MD: -5.98%; MD: -4.68 kg), waist circumference (MD: -10.91 cm), systolic blood pressure, and HbA1c. Both treatments showed modest but statistically significant increases in adverse events. Substantial heterogeneity was observed across most outcomes. CONCLUSION: Cagrilintide-based therapies produce clinically meaningful weight loss and cardiometabolic improvements. CagriSema demonstrates additional glycemic benefits over monotherapy. Larger, longer-duration trials are needed to confirm long-term efficacy and safety. Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/MS9.0000000000005353 PMCID: PMC13461105 PMID: 42583410 Conflict of interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions CagriSema

Predictors of Psychoactive and Nootropic Substance Use Among Romanian University Healthcare Students: The Interplay Between Academic Anxiety and Educational Advancement.

1. Healthcare (Basel). 2026 Jul 11;14(14):2079. doi: 10.3390/healthcare14142079. Predictors of Psychoactive and Nootropic Substance Use Among Romanian University Healthcare Students: The Interplay Between Academic Anxiety and Educational Advancement. Caba IC(1), Iorga M(2)(3), Mihăianu IG(2), Agoroaei L(1), Jităreanu A(1), Iurcov ROC(4). Author information: (1)Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania. (2)Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania. (3)Faculty of Psychology and Educational Sciences, "Alexandru Ioan Cuza" University, 700554 Iasi, Romania. (4)Faculty of Medicine, University of Oradea, 410087 Oradea, Romania. Background: The use of cognitive enhancers (CEs) is becoming increasingly widespread among students, especially in health fields, with significant implications for both academic performance and student well-being. The aim of the study was to investigate the use of CEs among healthcare university students in relationship with stimulant intake, academic progression, and academic anxiety. Material and Methods: The cross-sectional study included 402 students enrolled in medical studies (general medicine, pharmacy, dentistry, and physiotherapy). Socio-demographic characteristics, health-related and academic data, lifestyle behaviors, and the consumption of different CEs were collected. The Academic Anxiety Scale was used to evaluate university students' perceived stressors that contribute to academic anxiety. Data processing analysis was performed using IBM Statistical Package for Social Sciences. Results: The frequency of cognitive compound intake exhibits a positive correlation with the consumption of group B vitamins (r = 0.170, p = 0.001), tea (r = 0.158, p = 0.003), and coffee (r = 0.113, p = 0.031). Lecithin and Ginkgo biloba were significant independent predictors (p < 0.05) of enhanced alertness, memory, and academic performance. The only significant independent predictor of cardiovascular events (palpitations, tachycardia) is caffeine consumption, which increases the risk by nearly three times (OR = 2.96; p = 0.001). In terms of addictive risk, drinking caffeine raises the likelihood of being addicted by 4.78 times (p = 0.014). It has been demonstrated that the probability of using synthetic nootropics (piracetam/cerebrolysin) increases by 1.86 times (OR = 1.86, p = 0.021) as university education progresses (nN= 335). Academic anxiety had a mean score of 23.27 ± 7.38. Unemployed students exhibit markedly elevated anxiety levels compared to employed students. Respondents who justify the use of stimulants by feeling stressed or overwhelmed present the highest levels of academic distress, in contrast to those who use them to combat fatigue or out of curiosity. A large majority (95.0%) do not consider use of CEs as a form of cheating on examinations, and 88.9% are against its prohibition. Conclusions: The findings of this study highlight that many university students in the healthcare field use cognitive stimulants during periods of intellectual overload, with more than 40% of participants utilizing CEs daily or weekly in periods of academic stress. Overload schedule, academic stress, the knowledge about their positive effects, and psychosocial contexts influence consumption. DOI: 10.3390/healthcare14142079 PMCID: PMC13410115 PMID: 42512595 Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Cerebrolysin

Real-world treatment satisfaction and experience with once-weekly tirzepatide: Insights from prescribing physicians and people with obesity or overweight.

1. Obes Pillars. 2026 Jul 10;19:100300. doi: 10.1016/j.obpill.2026.100300. eCollection 2026 Sep. Real-world treatment satisfaction and experience with once-weekly tirzepatide: Insights from prescribing physicians and people with obesity or overweight. Gibble TH(1), Leith A(2), Harrison L(2), Gerber C(1), Raikar SK(1), Seth E(1), Artime E(1). Author information: (1)Eli Lilly and Company, Indianapolis, IN, USA. (2)Adelphi Real World, Bollington, UK. BACKGROUND: Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated its efficacy in clinical trials; however, real-world evidence on treatment satisfaction and experiences among people with obesity or overweight (PwO) and their prescribing physicians remains limited. This study aimed to assess the real-world clinical characteristics, treatment patterns, and satisfaction with tirzepatide among PwO without type 2 diabetes (T2D) and their prescribing physicians in the United States. METHODS: This secondary analysis utilized data from a cross-sectional survey of physicians and PwO from October 2023 to April 2024, and from October 2024 to January 2025. Physicians provided data for PwO meeting selection criteria, at data capture/previous body mass index (BMI) ≥30 or ≥27 and < 30 kg/m2 with at least one obesity-related complication (ORC), without T2D, enrolled in a weight management program, and were receiving tirzepatide at the time of data collection. Sociodemographic and clinical characteristics, treatment history, and satisfaction measures were analyzed. RESULTS: Data from 151 physicians and 199 PwO without T2D using tirzepatide were included. Most PwO (84.4%) had ≥1 ORC, with hypertension and dyslipidemia being the most prevalent. Over 90% (n = 45/48) of PwO reported likelihood to recommend tirzepatide reflecting high satisfaction and willingness to recommend tirzepatide to others. Physicians reported long-term safety, ease of dosing, and reduced appetite as key reasons for prescribing tirzepatide. Physicians reported that tirzepatide treatment was successful in the majority of people (78.5%) being treated for obesity. CONCLUSIONS: The data in these surveys reflected that PwO without T2D prescribed tirzepatide had high motivation, adherence, and satisfaction. These findings provide real-world insights into treatment and satisfaction with tirzepatide. © 2026 The Authors. DOI: 10.1016/j.obpill.2026.100300 PMCID: PMC13377426 PMID: 42491427 Conflict of interest statement: Theresa Hunter Gibble, Claire Gerber, Sonya Kokil Raikar, Era Seth, and Esther Artime are employees and stockholders of Eli Lilly and Company, Indianapolis, United States. Andrea Leith, Lewis Harrison are employees of Adelphi Real World, Bollington, UK.

Mentions Tirzepatide

Employee perceptions and experiences with tirzepatide treatment for obesity or overweight in the US: Insights from the PERCEPTIONS Survey.

1. Obes Pillars. 2026 Jul 9;19:100298. doi: 10.1016/j.obpill.2026.100298. eCollection 2026 Sep. Employee perceptions and experiences with tirzepatide treatment for obesity or overweight in the US: Insights from the PERCEPTIONS Survey. Gibble TH(1), Al-Zubeidi T(2), Gerber C(1), Collins E(2), Vardavoulia A(2), Lin A(1), He X(1), Shepherd M(1), Fitch A(3), Bays H(4). Author information: (1)Eli Lilly and Company, Indianapolis, IN, USA. (2)Clarivate, London, UK. (3)Knownwell, Needham, MA, USA. (4)Monroe Biomedical Research, Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. OBJECTIVE: To characterize real-world experiences, perceptions, and workplace-related outcomes among full-time employed adults in the United States with obesity or overweight initiating tirzepatide for obesity management, and to assess perceptions of employer-provided insurance coverage for obesity medications (OMs). METHODS: This analysis reports baseline findings from the PERCEPTIONS survey, an observational, longitudinal, real-world study conducted in the United States. Full-time employed adults (≥18 years) with obesity (body mass index [BMI] ≥30 kg/m2) or overweight (BMI ≥27 kg/m2 with ≥1 obesity related complication [ORC]) initiating tirzepatide for obesity management were recruited via clinical sites and specialist recruitment agencies and completed a self-administered electronic survey (June to November 2025). Demographic, clinical, and employment characteristics; engagement in employer-sponsored wellness programs; perceptions of employer-provided insurance coverage for OMs; and patient-reported outcomes, including work productivity and activity impairment (WPAI) assessed using the WPAI questionnaire were reported. RESULTS: Among the 518 full-time employees included, mean (SD) age was 46.0 (11.6) years, BMI was 38.4 (8.4) kg/m2, and mean employment duration was 89.8 months (∼7.5 years). Most participants had employer-provided health insurance (80.9%), among these, 55.9% reported coverage for OMs. Majority (96.5%) believed employer-provided insurance should include OM coverage, citing improved health, productivity, and management of obesity-related complications. 81.7% reported that OM coverage may increase job satisfaction and 52.3% reported that they would consider changing jobs in order to receive OM coverage. WPAI results indicated substantial impairment, with mean activity impairment of 43.0% and overall work impairment of 32.4%, driven primarily by presenteeism. CONCLUSION: Among full-time employees initiating tirzepatide, obesity was associated with considerable work and activity impairment, and strong support was expressed for employer-provided OM coverage. These findings highlight the potential clinical and functional value of obesity pharmacotherapy and may inform employer and insurer policies aimed at reducing barriers to care and supporting long-term obesity management. © 2026 The Authors. DOI: 10.1016/j.obpill.2026.100298 PMCID: PMC13382417 PMID: 42518363 Conflict of interest statement: THG, CG, EC, XH, MS are employees and shareholders of Eli Lilly and Company. TZ, EC, AV are employees and TZ is a stockholder of Clarivate. HB: research site institution has received research grants from 89Bio, Abbvie, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, AstraZeneca, Bioage, Biohaven, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Corbus, Eli Lilly, Esperion, Evidera, ERX, Fractyl, Gasherbrum, Genentec, GlaxoSmithKline, Graviton, HighTide, Hoffman LaRoche, Home Access, Horizon, Ionis, Kailera, Kallyope, LG-Chem, Marea, Madrigal, Marea, Merck, Metsera, Mineralys, New Amsterdam, Novartis, NovoNordisk, Pfizer, Regeneron, Roche, Satsuma, Selecta, Shionogi, Skye/Birdrock, Terns, TIMI, Veru, Viking, Vivus, Zomagen. Dr. Harold Bays has served as a advisor (e.g., executive/national committee member and/or protocol/drug development advisor) for 89Bi

Mentions Tirzepatide

Retatrutide fact check: Has a man died after taking the unapproved weight loss jab?

1. BMJ. 2026 Jul 9;394:e100245. doi: 10.1136/bmj-2026-100245. Retatrutide fact check: Has a man died after taking the unapproved weight loss jab? Mahase E(1). Author information: (1)The BMJ. DOI: 10.1136/bmj-2026-100245 PMID: 42425580

Mentions Retatrutide

Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.

Mentions CagriSema

Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH): a clinical trial protocol.

1. BMJ Open. 2026 Jul 8;16(7):e120740. doi: 10.1136/bmjopen-2026-120740. Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH): a clinical trial protocol. Erlandson KM(1), Gustafson L(2), Johnson JE(3), Kulik GL(2), Khuu V(2), Chahal N(3), Walpert AR(3), Galdamez ME(4)(5), Zorgno I(4)(5), Foldyna B(4), Jarraya M(6)(7), Reusch JE(2), Lee H(8), Grinspoon SK(3), Jankowski CM(9), Fourman LT(3). Author information: (1)Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA Kristine.Erlandson@cuanschutz.edu. (2)Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. (3)Metabolism Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. (4)Cardiovascular Imaging Research Center (CIRC), Massachusetts General Hospital, Boston, Massachusetts, USA. (5)Harvard Medical School, Boston, Massachusetts, USA. (6)Department of Radiology, Harvard Medical School, Boston, Massachusetts, USA. (7)Massachusetts General Hospital, Boston, Massachusetts, USA. (8)Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA. (9)College of Nursing, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. BACKGROUND: The Tesamorelin as an Adjunct to Exercise for Improving Physical Function in HIV (TRIUMPH) study is a randomised controlled trial with the overall goal of examining the combined effect of exercise and the growth hormone-releasing hormone analogue tesamorelin on physical function. METHODS: TRIUMPH is a two-site, double-blind, randomised trial of 100 sedentary older adults (aged 50-80 years) living with HIV who are frail or at risk for frailty and have excess abdominal adiposity. Enrolled participants will be randomised to receive tesamorelin or placebo as an adjunct to a home-based semisupervised exercise programme for 24 weeks, followed by a 24-week extension phase of independent exercise. We will determine short-term and sustained effects of tesamorelin plus exercise on clinical endpoints, including physical function, muscle content and quality, quality of life, and exercise adherence at Weeks 24 and 48. We also will elucidate effects of tesamorelin plus exercise on biological endpoints, including muscle fat and mitochondrial function at Week 24. ETHICS AND DISSEMINATION: Ethical approval for the TRIUMPH study was obtained from the Institutional Review Boards at participating sites. All participants provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and scientific conferences and may inform future interventions to improve physical function among older adults living with HIV. TRIAL REGISTRATION NUMBER: NCT06554717. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. DOI: 10.1136/bmjopen-2026-120740 PMCID: PMC13347827 PMID: 42419889 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: KME has served on advisory board for Merck, Gilead and ViiV (with payments to her employer). SKG has received grants from the National Institutes of Health, Kowa Pharmaceuticals, Gilead Sciences and ViiV Healthcare, outside the submitted work and has received personal consulting fees from TheraTechnologies and ViiV Healthcare. He has served on scientific advisory boards for Marathon Asset Management and Exavir Therapeutics, outside of the submitted work. BF has been awarded grants from the National Institutes of Health, MedImmune, AstraZeneca, Cleerly and MedTrace beyond the scope of the submitted work. Additionally, he has served on the scientific advisory board and received personal consulting fees from Cleerly, outside of the submitted work. MJ received consultancy fees from Boston Imaging Core Lab (BICL). LTF serves as a consultant to Theratechnologies, Chiesi Farmaceutici and R

Mentions Tesamorelin

Neuroendocrine mechanisms of stress-induced KNDy-GnRH pulse generator suppression: Linking HPA-axis activation to female reproductive dysfunction.

1. Front Neuroendocrinol. 2026 Jul 4:101270. doi: 10.1016/j.yfrne.2026.101270. Online ahead of print. Neuroendocrine mechanisms of stress-induced KNDy-GnRH pulse generator suppression: Linking HPA-axis activation to female reproductive dysfunction. Bo W(1), Li Y(1), Wang R(1), Qiao X(1), Zhong Y(1), Liu T(1), Liang J(1), Lai H(1), Huang W(2). Author information: (1)Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China; NHC Key Laboratory of Chronobiology, West China School of Basic Medical Sciences & Forensic Medicine, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China. (2)Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China; NHC Key Laboratory of Chronobiology, West China School of Basic Medical Sciences & Forensic Medicine, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: weihuang64@163.com. Chronic stress disrupts female reproductive function, but the central mechanisms linking stress exposure to altered gonadotropin-releasing hormone (GnRH) pulsatility remain incompletely defined. The arcuate kisspeptin/neurokinin B/dynorphin (KNDy) network is a core component of the GnRH pulse generator, yet it functions within an expanded regulatory system involving fast amino-acid neurotransmission, steroid feedback, nitric oxide signaling, glial communication, metabolic cues, and stress-responsive neuropeptides. This review synthesizes evidence showing how hypothalamic-pituitary-adrenal (HPA)-axis activation may suppress KNDy-GnRH output. Corticotropin-releasing hormone, glucocorticoids, gonadotropin-inhibitory hormone/RFamide-related peptide-3, glial inflammatory mediators, serotonergic input, and energy-sensitive neuropeptides may converge to impair GnRH pulse-generator function. We further discuss the relevance of these mechanisms to functional hypothalamic amenorrhea, stress-sensitive polycystic ovary syndrome (PCOS) phenotypes, and developmental versus adult stress exposure. Overall, stress-induced reproductive dysfunction is best understood as disrupted network-level neuroendocrine rhythm regulation. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.yfrne.2026.101270 PMID: 42401315 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Kisspeptin

Anterior cervical osteophyte-related dysphagia in a long-term growth hormone user: a case report.

Mentions Sermorelin

Clinical Characterization of Enzyme and Transporter Precipitants to Evaluate Drug-Drug Interactions for Orforglipron, a Small Molecule Glucagon-Like Peptide-1 Receptor Agonist.

1. Clin Pharmacol Ther. 2026 Jul 3. doi: 10.1002/cpt.70377. Online ahead of print. Clinical Characterization of Enzyme and Transporter Precipitants to Evaluate Drug-Drug Interactions for Orforglipron, a Small Molecule Glucagon-Like Peptide-1 Receptor Agonist. Morse BL(1), Coutant DE(1), Ma X(1), Raha S(1), Aithal K(1), Nicoll C(1), Rougée LRA(1), Bhattachar S(1). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. Orforglipron is an orally administered, small-molecule glucagon-like peptide-1 receptor agonist in clinical development for the treatment of type 2 diabetes and obesity. Orforglipron is a substrate of CYP3A4, organic anion transporting polypeptides (OATPs) 1B/1B3, and P-glycoprotein (P-gp); however, precipitants commonly used to define these mechanisms have not been fully characterized. The enzyme- and transporter-mediated DDI profile of orforglipron and that of CYP3A4/OATP1B/P-gp precipitants were characterized in six phase 1 clinical studies in healthy participants. Orforglipron pharmacokinetics were assessed with clarithromycin, carbamazepine, cyclosporine, and quinidine. Precipitant effects on CYP3A and OATP1B activity were measured using midazolam and coproporphyrin-I (CP-I). Orforglipron effects on CYP3A, P-gp, BCRP, and OATP1B were evaluated using midazolam, digoxin, rosuvastatin, simvastatin, atorvastatin, and CP-I. Mechanistic interrogation of the simvastatin interaction was also conducted. Clarithromycin, carbamazepine, and quinidine had minimal effect on CP-I pharmacokinetics, while the cyclosporine effect was substantial. Cyclosporine and quinidine weakly increased midazolam exposure. Orforglipron exposure increased in the presence of clarithromycin and cyclosporine and decreased with carbamazepine, demonstrating orforglipron exposure is affected by precipitants of CYP3A4 and OATP1B. Quinidine did not meaningfully change orforglipron exposure. Orforglipron had no clinically meaningful effect on the exposure of midazolam, digoxin, or atorvastatin. A weak increase in rosuvastatin exposure was consistent with BCRP inhibition, as CP-I data confirmed orforglipron does not affect OATP1B. Increase in simvastatin acid exposure was attributed to the unique disposition of simvastatin rather than enzyme or transporter inhibition. These findings address mechanistic precipitant knowledge gaps and provide a framework for managing potential orforglipron DDIs in clinical practice. © 2026 Eli Lilly and Company. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. DOI: 10.1002/cpt.70377 PMID: 42399716

Mentions Orforglipron

Direct effects of glucagon-like Peptide-1 receptor agonists on mitochondrial function in human-derived in vitro models: A systematic review and meta-analysis.

1. Metabol Open. 2026 Jul 2;31:100484. doi: 10.1016/j.metop.2026.100484. eCollection 2026 Sep. Direct effects of glucagon-like Peptide-1 receptor agonists on mitochondrial function in human-derived in vitro models: A systematic review and meta-analysis. Greenblatt ZL(1), Tork A(1), Cruz I(1), Fausak ED(2), Tran HA(1), Krovidy M(1), Giulivi C(1)(3). Author information: (1)Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA. (2)University Library, University of California, Davis, CA, 95616, USA. (3)MIND Institute, University of California at Davis Medical Center, Sacramento, CA, USA. GLP-1 receptor agonists (e.g., semaglutide; GLP-1 RAs) treat Type 2 Diabetes and obesity, mainly by improving glycemic control, suppressing appetite, delaying gastric emptying, and inducing weight loss. Emerging evidence suggests they also directly affect mitochondrial function independently of systemic metabolism. To our knowledge, this is the first systematic review and meta-analysis examining direct mitochondrial effects of GLP-1 RAs in human-derived in vitro models. Of 1547 records identified (1203 screened after deduplication), 17 studies met the criteria, and only 11 contributed to the quantitative synthesis of mitochondrial outcomes. Outcomes included mitochondrial membrane potential (MMP), bioenergetics (ATP-linked oxygen consumption, respiration, ATP production), and mitochondrial reactive oxygen species (MitoROS). Meta-analysis demonstrated significantly improved bioenergetics (SMD = 1.109, 95% CI: 0.556-1.662, P < 0.001) and reduced MitoROS (SMD = -3.489, 95% CI: -6.690 to -0.288, P = 0.034) following GLP-1RA treatment. No significant effect on MMP was observed in the primary analysis (SMD = 0.997, 95% CI: -1.678 to 3.672, P = 0.459), although an exploratory sensitivity analysis excluding statistically identified outlying effect sizes suggested a potential improvement in MMP (SMD = 3.145, 95% CI: 2.147-4.144, P < 0.01); however, this finding should be interpreted cautiously. Overall certainty of the evidence was very low for the primary outcomes due to methodological limitations, substantial heterogeneity, imprecision, and publication bias in some outcomes. Only the MMP sensitivity analysis achieved low-certainty evidence. These findings suggest that GLP-1 RAs may directly promote mitochondrial health, but more rigorous, standardized, and independent studies are needed to confirm their relevance to whole-body physiology. © 2026 The Authors. Published by Elsevier Inc. DOI: 10.1016/j.metop.2026.100484 PMCID: PMC13351396 PMID: 42434480 Conflict of interest statement: All authors have disclosed any financial or other interests related to the submitted work that could impact the authors' objectivity or influence the article's content. No financial or non-financial competing interests were identified that could compromise the objectivity, integrity, or value of this publication by influencing the authors' judgment and actions in data presentation, analysis, and interpretation. C.G. serves as an Editorial Board Member of Scientific Reports. She has received compensation as a Field Chief Editor for Frontiers in Molecular Biosciences and honoraria for participating in NIH peer review meetings.

Mentions Semaglutide

Acylglycerol Kinase Sensitizes Glioblastoma to Temozolomide via Limiting Mitochondrial Damage Related Cellular Senescence.

Mentions FOXO4-DRI

Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight.

1. Diabetes Obes Metab. 2026 Jul;28(7):5803-5809. doi: 10.1111/dom.70783. Epub 2026 Apr 17. Pharmacokinetic Bioequivalence of Orforglipron Tablets and Capsules in Healthy Participants With Obesity or Overweight. Ma X(1), Li YG(1), Raha S(1), Sperry DC(1), Coutant DE(1), Bhattachar S(1). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. AIMS: To evaluate the bioequivalence of orally administered orforglipron tablets and capsules in participants with obesity or overweight who were otherwise healthy. MATERIALS AND METHODS: This phase 1, multicenter, open-label, multiple-dose, dose-escalation study was conducted in 429 healthy adults. Study participants received each orforglipron capsule and tablet dose strength once daily for 7 days in the fasted state at capsule doses of 1, 3, 6, 12, 24, or 36 mg and corresponding tablet doses of 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg. The primary endpoint was steady-state area under the concentration-time curve from 0 to 24 h (AUC0-24,ss) and steady-state maximum observed drug concentration (C max,ss). A prespecified mixed scaling approach was applied to evaluate bioequivalence. Safety and tolerability of the tablets and capsules were also assessed. RESULTS: Bioequivalence was demonstrated between capsules and dose-adjusted tablets across all six doses. The 90% confidence interval of the ratios of the geometric least-squares means of AUC0-24,ss and C max,ss between each capsule dose and corresponding tablet dose met the predefined criteria for bioequivalence. The safety profiles were similar between tablets and capsules, with no apparent differences or trends in the incidence of treatment-emergent adverse events by presentation or with increasing dose. CONCLUSIONS: Once-daily orforglipron capsules and dose-adjusted tablets demonstrated pharmacokinetic bioequivalence at all tested doses and showed similar safety and tolerability profiles, with mostly mild treatment-emergent adverse events consistent with previous orforglipron clinical trials. ClinicalTrials .gov Identifier: NCT06440980. © 2026 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.70783 PMCID: PMC13243956 PMID: 41994902 [Indexed for MEDLINE] Conflict of interest statement: Xiaosu Ma, Ying Grace Li, David C. Sperry, David E. Coutant and Shobha Bhattachar are employees of Eli Lilly and Company and may be shareholders. Sohini Raha was an employee of Eli Lilly and Company at the time the described work was conducted and is now an employee of Novartis.

Mentions Orforglipron

Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.

1. Diabetes Obes Metab. 2026 Jul;28(7):5761-5766. doi: 10.1111/dom.70742. Epub 2026 Apr 16. Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis. Lu Y(1), Chen J(1), Guo Y(1), Ding H(1), Liu YL(2), Van Name MA(3), Sharifi M(4), Lu Y(5)(6), Chen Y(7). Author information: (1)Ividence Inc, Newark, Delaware, USA. (2)UT Southwestern Medical Center, Peter O'Donnell Jr. School of Public Health, Dallas, Texas, USA. (3)Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. (4)Section of General Pediatrics, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. (5)Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. (6)Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA. (7)The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AIMS: To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA). MATERIALS AND METHODS: PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity. The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure. Secondary outcomes included treatment effects for each individual CEI component. RESULTS: Nineteen RCTs (N = 13 117) were analysed. Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%. CEI rankings were generally consistent across T2D and non-T2D subgroups. Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63). CONCLUSIONS: Higher-dose GLP-1 receptor mono-agonists, particularly semaglutide 7.2 mg and orforglipron 36 mg (Foundayo 17.2 mg tablet), demonstrated the most consistent multidimensional cardiometabolic improvements, although domain-specific differences were observed across agents. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.70742 PMCID: PMC13243969 PMID: 41992023 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Orforglipron

Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials.

1. Endocrinol Diabetes Metab. 2026 Jul;9(4):e70248. doi: 10.1002/edm2.70248. Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials. Hamarsheh S(1), Jaber AR(2), Abu-Khazneh O(1), Andonie CR(3), Majadleh S(1), Zahran A(1), Ayesh H(4)(5). Author information: (1)Department of Medicine, An-Najah National University, Nablus, Palestine. (2)School of Medicine, University of Jordan, Amman, Jordan. (3)Al-Quds University, Jerusalem, Palestine. (4)Deaconess Health System, Evansville, Indiana, USA. (5)Adjunct Clinical Assistant Professor of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. BACKGROUND: Obesity is a chronic, progressive disease affecting over 1 billion adults worldwide, linked to serious comorbidities, including diabetes, hypertension, and cardiovascular disease and associated with increased mortality. Achieving clinically meaningful weight loss is critical to reducing cardiometabolic risk. Tirzepatide, semaglutide, cagrilintide and their combination (CagriSema) have demonstrated efficacy in clinical trials; however, no direct head-to-head studies have compared all advanced anti-obesity medications. This network meta-analysis examines their comparative efficacy and safety. METHODS: We systematically searched PubMed, Scopus and Cochrane Central for randomized controlled trials comparing these medications with placebo in adults with overweight or obesity. Outcomes included changes in percent body weight, absolute weight, waist circumference, BMI, patients achieving ≥ 5% to ≥ 20% weight loss, HDL-C and safety outcomes (AEs, serious AEs, gastrointestinal AEs and treatment discontinuation). Random-effects model and network meta-analysis methods were employed. RESULTS: Twenty-five trials involving 12 interventions met the inclusion criteria. Tirzepatide 15 mg resulted in the greatest percent weight reduction (MD -17.97%), followed by CagriSema (MD -17.84%) and semaglutide 7.2 mg (MD -14.66%). At the ≥ 20% weight-loss threshold, CagriSema demonstrated marked superiority (RR 27.82), followed by tirzepatide 15 mg (RR 23.70). Gastrointestinal adverse events increased with all treatments (RR 1.33-1.91), and treatment discontinuation was highest with semaglutide 7.2 mg (RR 3.09). Serious adverse events remained comparable to placebo across all regimens. CONCLUSION: Tirzepatide 15 mg and CagriSema achieve the greatest weight reduction, including ≥ 20% body weight loss. Gastrointestinal adverse events rise with treatment intensity, while serious adverse events remain comparable to placebo. These findings support dual-pathway and combination incretin therapies as preferred options for patients requiring substantial weight loss. Treatment selection should be individualized based on comorbidity burden, tolerability and weight loss goals, recognizing that ≥ 5% weight loss improves metabolic parameters while ≥ 10% is needed for meaningful comorbidity reduction. Future head-to-head trials are needed. © 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. DOI: 10.1002/edm2.70248 PMCID: PMC13239642 PMID: 42207966 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions CagriSema

LAT1-mediated delivery of engineered R13A-MOTS-c attenuates radiation-induced lung injury via Nrf2 activation and mitochondrial protection.

Mentions MOTS-c

Development of an electrochemiluminescence immunoassay for quantitative determination of semaglutide in human serum.

1. Anal Biochem. 2026 Jul;714:116115. doi: 10.1016/j.ab.2026.116115. Epub 2026 Mar 21. Development of an electrochemiluminescence immunoassay for quantitative determination of semaglutide in human serum. Luo Y(1), Zhang J(1), Chen W(1), Zhang H(2), Zou L(3). Author information: (1)Wenzhou Medical University, Wenzhou City, 325024, Zhejiang province, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou City, 325038, Zhejiang province, China. (2)Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou City, 325038, Zhejiang province, China. Electronic address: hefengzhang@ucas.ac.cn. (3)Wenzhou Medical University, Wenzhou City, 325024, Zhejiang province, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou City, 325038, Zhejiang province, China; Wenzhou KanryBio Biotech Co., Ltd, Wenzhou City, 325038, Zhejiang province, China. Electronic address: Michael_zou@ucas.ac.cn. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), is widely used in the treatment of patients with type 2 diabetes mellitus and obesity. A sensitive and reliable quantification method is essential for bioanalysis of semaglutide in clinical studies. To develop a sensitive and specific immunoassay, we have prepared a pair of highly specific anti-semaglutide monoclonal antibodies and subsequently employed them as critical reagents in the development of an electrochemiluminescence immunoassay (ECLIA) for the quantification of semaglutide levels in human serum. The assay validation data presented here demonstrate that the performance of the ECLIA method meets prespecified criteria for all validation parameters within the quantitative range of 0.5 ng/mL to 200.0 ng/mL. The intra- and inter-assay precision (%CV) are both ≤14.4%, and accuracy (%RE) ranges from -12.5% to 15.3%. No interference is found with recombinant human GLP-1 as the endogenous counterpart, confirming the assay specificity. Additional assay performance parameters, including selectivity, dilutional linearity, hook effect, and sample stability, all meet the acceptance criteria preset in accordance with international guidelines for bioanalytical method validation. The method is suitable for bioanalysis of semaglutide in human serum. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.ab.2026.116115 PMID: 41871707 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Semaglutide

Effects of retatrutide on learning and memory in streptozotocin-induced male diabetic rats.

1. Behav Brain Res. 2026 Jul 1;514:116343. doi: 10.1016/j.bbr.2026.116343. Online ahead of print. Effects of retatrutide on learning and memory in streptozotocin-induced male diabetic rats. Keskin U(1), Altın E(2), Kara MK(3), Tekin B(2), Çakırçoban KN(2), Özatik FY(1), Arı NS(4), Sezgin AK(5), Güngor E(6). Author information: (1)Kütahya Health Sciences University, School of Medicine, Department of Medical Pharmacology, Türkiye. (2)Kütahya Health Sciences University, School of Medicine, Türkiye. (3)Kütahya Health Sciences University, School of Medicine, Türkiye. Electronic address: melkankkara@hotmail.com. (4)Kütahya Health Sciences University, School of Medicine, Department of Histology and Embryology, Türkiye. (5)Kütahya Health Sciences University, School of Medicine, Department of Biochemistry, Türkiye. (6)Kütahya Health Sciences University, Faculty of Engineering and Natural Sciences, Computer Engineering, Türkiye. Diabetes mellitus is associated with cognitive impairment and neurodegenerative changes, partly through hyperglycaemia-driven neuroinflammation and disrupted neuronal signalling. Retatrutide, a triple GIP/GLP-1/glucagon receptor agonist, has shown strong metabolic efficacy, but its effects on diabetes-associated cognitive dysfunction remain unclear. The present study investigated whether Retatrutide attenuates learning- and memory-related impairments in a streptozotocin-induced, insulin-deficient diabetic rat model. Male Sprague-Dawley rats were allocated to four groups: control (C), streptozotocin-induced diabetic (STZ), streptozotocin-induced diabetic treated with Retatrutide (STZR), and Retatrutide alone (R). Diabetes was induced with streptozotocin, and spatial learning and memory were assessed using the Morris Water Maze and Passive Avoidance tests. Metabolic parameters were monitored, while hippocampal cytokine levels (IL-1β, TNF-α), BDNF, CREB, and AKT mRNA expression, Tau protein levels, and cortical and hippocampal histopathology were evaluated using biochemical, molecular, and histological methods. Streptozotocin-induced diabetes produced persistent hyperglycaemia, marked body weight loss, and impaired behavioural performance, particularly prolonged escape latencies in the Morris Water Maze and a selective short-term Passive Avoidance deficit. Retatrutide reduced blood glucose levels but did not prevent diabetes-associated weight loss. In behavioural testing, Retatrutide-treated diabetic rats showed preserved overall Morris Water Maze performance relative to untreated diabetic rats and a limited, task-dependent attenuation of short-term avoidance deficits rather than complete normalisation across all memory measures. These effects were accompanied by a significant reduction in hippocampal TNF-α, a non-significant trend toward lower IL-1β, and partial preservation of cortical and hippocampal cytoarchitecture. Retatrutide alone did not improve behavioural performance beyond control levels, although BDNF and CREB mRNA expression were increased in the non-diabetic Retatrutide group. These findings indicate that Retatrutide is associated with a partial attenuation of streptozotocin-induced behavioural and neuroinflammatory alterations in male rats. The observed effects are consistent with actions extending beyond glycaemic control alone, although direct central exposure of Retatrutide was not established in the present study. Further studies in insulin-resistant and type 2 diabetes-like models are needed to clarify the underlying mechanisms and translational relevance. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.bbr.2026.116343 PMID: 42385950 Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Retatrutide

Mitochondrial-derived peptide MOTS-c targets SLC7A11 to preserve spermatogenesis by suppressing ferroptosis.

1. Free Radic Biol Med. 2026 Jul;250:284-297. doi: 10.1016/j.freeradbiomed.2026.03.074. Epub 2026 Mar 31. Mitochondrial-derived peptide MOTS-c targets SLC7A11 to preserve spermatogenesis by suppressing ferroptosis. Liu S(1), Ru K(2), Shen YJ(1), Yan Y(1), Zhu C(2), Wang H(1), Xu Y(1), Wang X(2), Yang H(2), Zhao S(1), Gong Y(1), Tian Y(3), Qian A(4), Yang H(5), Chen Z(6). Author information: (1)Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. (2)Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China. (3)Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China. Electronic address: tianye@nwpu.edu.cn. (4)Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China. Electronic address: qianair@nwpu.edu.cn. (5)Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: yanghong@fmmu.edu.cn. (6)Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, Research Center for Special Medicine and Health Systems Engineering, School of Life Science and Technology, Northwestern Polytechnical University, Xi'an, Shaanxi, 710072, China; Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. Electronic address: chenzhihao@nwpu.edu.cn. Mitochondrial function is critical for spermatogenesis and male fertility. MOTS-c, a mitochondrially encoded regulatory peptide, has recently been reported to effectively protect testicular spermatogenesis in mice, but its specific role and mechanism remain unclear. This study first demonstrated that MOTS-c levels were significantly reduced in the serum of patients with oligoasthenozoospermia, and these levels correlated with semen quality parameters. Spermatogenic dysfunction, including decreased sperm concentration, disrupted seminiferous tubule architecture, and a reduction in spermatogonia, was induced by mechanical stress through microgravity model. Notably, exogenous MOTS-c ameliorated spermatogenic impairment by suppressing oxidative stress and ferroptosis induced by mechanical stress. Solute Carrier Family 7 Member 11 (SLC7A11), a key molecule in ferroptosis, was identified as a target of MOTS-c. Moreover, loss- and gain-of-function studies showed that SLC7A11 inhibited ferroptosis and oxidative stress and promoted spermatogonia proliferation. Furthermore, MOTS-c enhanced the protection against spermatogenic impairment by increasing SLC7A11 levels under mechanical stress. Collectively, this study elucidates the crucial role of MOTS-c in protecting spermatogenesis by antagonizing ferroptosis, providing a theoretical foundation for its potential therapeutic use in male infertility associated with spermatogenic defects. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.freeradbiomed.2026.03.074 PMID: 41933740 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare no competing interests.

Mentions MOTS-c

Changes in food cravings, dietary quality, body composition, and dietary intake during GLP-1 receptor agonist therapy: The CRAVE study.

1. Obes Pillars. 2026 Jun 29;19:100292. doi: 10.1016/j.obpill.2026.100292. eCollection 2026 Sep. Changes in food cravings, dietary quality, body composition, and dietary intake during GLP-1 receptor agonist therapy: The CRAVE study. Babazadeh D(1)(2), Therrien S(3), Fitch AK(3), Steinberg FM(1)(2). Author information: (1)Graduate Group in Nutritional Biology, University of California, Davis, Davis, CA, USA. (2)Department of Nutrition, University of California, Davis, Davis, CA, USA. (3)Knownwell Clinic, Needham, MA, USA. OBJECTIVE: To evaluate changes in diet quality, food cravings, dietary intake, and body composition during 24 weeks of GLP-1 RA OMM therapy in a real-world clinical setting. METHODS: In this prospective observational study, adults with obesity initiating semaglutide or tirzepatide were followed for 24 weeks (analytic n = 28). Participants did not receive structured nutrition intervention. Dietary intake was assessed using food records, and diet quality was evaluated using the Healthy Eating Index (HEI-2020). Food cravings were measured using the Food Cravings Inventory-III questionnaire. Body composition was assessed via bioelectrical impedance analysis. RESULTS: GLP-1 RA OMM therapy was associated with significant reductions in body weight, adiposity, and BIA-estimated skeletal muscle mass (all P < 0.001); with approximately one-quarter of weight loss attributable to estimated skeletal muscle mass. Total energy intake decreased significantly, with parallel reductions in macronutrient intake. Higher absolute protein intake was associated with greater preservation of estimated skeletal muscle mass (r = 0.41, P = 0.0498). Diet quality did not significantly improve in our sample and food cravings were unchanged overall, although higher baseline cravings were associated with greater reductions over time (r = -0.69, P < 0.001). Significant declines in intake were observed across multiple micronutrients. CONCLUSIONS: In this small prospective cohort, GLP-1 RA OMM therapy in a real-world setting without structured nutrition support, was associated with substantial weight and fat loss accompanied by reductions in estimated skeletal muscle mass, energy intake, and micronutrient consumption, without improvement in diet quality or food cravings. Given the modest sample size and participant attrition, these findings should be considered exploratory and hypothesis-generating. The observed changes in dietary intake and body composition may highlight a critical gap in obesity management that warrants further investigation in larger, adequately powered studies to evaluate the role of nutrition-focused care, particularly strategies targeting protein adequacy and nutrient density during pharmacologic weight loss. CLINICAL TRIALS REGISTRATION: NCT06467604. © 2026 The Authors. DOI: 10.1016/j.obpill.2026.100292 PMCID: PMC13334816 PMID: 42440974 Conflict of interest statement: A.K.F. reports work on advisory boards for Currax Pharmaceuticals LLC, Eli Lilly, Ms.Medicine, Novo Nordisk, Rhythm Pharmaceuticals, SideKick Health, Seca, and VIVUS.

Mentions Semaglutide

Ease of Use, Ease of Learning, and Convenience of the CagriSema Dual-Chamber Pen: Results From a Usability Study in Adults With Overweight, Obesity, or Type 2 Diabetes.

1. J Diabetes Sci Technol. 2026 Jun 28:19322968261461530. doi: 10.1177/19322968261461530. Online ahead of print. Ease of Use, Ease of Learning, and Convenience of the CagriSema Dual-Chamber Pen: Results From a Usability Study in Adults With Overweight, Obesity, or Type 2 Diabetes. Gulisano W(1), Ter-Borch G(2), Brown P(1), Feinberg JB(1), Gonczi M(3), Hildebrand E(3), Legere-DeJohn G(4), Sustarsic R(1), Sparre T(1). Author information: (1)Novo Nordisk A/S, Søborg, Denmark. (2)Novo Nordisk A/S, Hillerød, Denmark. (3)Research Collective LLC, Tempe, AZ, USA. (4)Novo Nordisk Inc., Plainsboro, NJ, USA. This study evaluated the usability of the CagriSema dual-chamber pen, a single-dose, single-use, pre-filled autoinjector for once-weekly subcutaneous administration of a fixed-dose combination of cagrilintide and semaglutide. Adults with overweight/obesity (n = 85) or type 2 diabetes (n = 65) performed simulated injections after standardized training. Endpoints included injection completeness, task durations, and user feedback via the Injection Device Experience and Acceptability-Ease of Use and Convenience Questionnaire (IDEA-ECQ; content validity supported by cognitive interviews, n = 50). All but one participant completed the injection successfully. Median training time was 3 minutes, and time to prepare and inject was 15 seconds. Participants rated the device easy/very easy to use (100%), easy/very easy to learn (98.7%), and an injection with the pen convenient (99.3%). Results were consistent across populations and unaffected by prior device experience. DOI: 10.1177/19322968261461530 PMCID: PMC13314649 PMID: 42366647 Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Walter Gulisano, Paul Brown, Joshua Buron Feinberg, Gina Legere-DeJohn, Gitte Ter-Borch, Riia Sustarsic, and Thomas Sparre are employees of Novo Nordisk. Walter Gulisano, Gina Legere-DeJohn, Gitte Ter-Borch, and Thomas Sparre are also shareholders of Novo Nordisk. Emily Hildebrandt and Maya Gonczi are employees of Research Collective, which has received funding from Novo Nordisk for research carried out in this work.

Mentions CagriSema

Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche.

1. Clin Chim Acta. 2026 Jun 27:121207. doi: 10.1016/j.cca.2026.121207. Online ahead of print. Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche. Banerjee AA(1), Bhanarkar SR(1), Kashikar S(1), Keshwani R(2), Walia S(2), Kavya DR(2), Bombe S(1), Pande S(1), Modi DN(1), Pathak BR(1), Joshi B(1), Tandon D(1), Patil A(1), Begum S(1), Mahale SD(1), Rao S(3), Surve SV(4). Author information: (1)ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400 012, India. (2)Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai 400 012, India. (3)Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai 400 012, India. Electronic address: c_sudha@hotmail.com. (4)ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400 012, India. Electronic address: surves@nirrch.res.in. BACKGROUND: Distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10 (Kp-10), Neurokinin B (NKB), and Neuropeptide Y (NPY) are key regulators of GnRH secretion and may serve as surrogate biomarkers. We evaluated whether these neuropeptides, alone or in combination with basal gonadotropins, could provide clinically useful discrimination of ICPP and PT. METHODS: In this prospective study, Indian girls aged 6-9 years were enrolled as controls (n = 40), ICPP (n = 33), and PT (n = 23). Anthropometry, basal LH, FSH, estradiol, pelvic ultrasonography, and plasma Kp-10, NKB, and NPY levels were assessed. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Logistic regression models assessed incremental predictive value: Model 1 included the Kp-10/basal LH ratio; Model 2 added bone age advancement (BA-CA); and Model 3 further included basal estradiol. Clinical utility was examined using decision curve analysis (DCA). RESULTS: Anthropometric parameters did not differ between ICPP and PT. Kp-10 and NKB levels were higher in both early-puberty groups than controls, but neither marker alone discriminated ICPP from PT. The composite Kp-10/basal LH ratio showed superior performance, with an ROC-derived cut-off <4.07 ng/mIU (sensitivity 72.7%, specificity 87.0%, accuracy 78%). All three models showed similar discrimination (AUC 0.78-0.79), with no meaningful improvement after adding BA-CA or estradiol. DCA demonstrated a higher net benefit for the Kp-10/basal LH ratio compared with treat-all or treat-none strategies across clinically relevant thresholds. CONCLUSION: The Kp-10/basal LH ratio provides robust discrimination and meaningful clinical utility in differentiating ICPP from PT and may reduce reliance on GnRH stimulation testing. Copyright © 2026. Published by Elsevier B.V. DOI: 10.1016/j.cca.2026.121207 PMID: 42364891 Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions Kisspeptin

Kisspeptin-2 stimulates testicular function in adult pejerrey (Odontesthes bonariensis): Does it act directly on the testes?

Mentions Kisspeptin

Efficacy and safety of orforglipron in obesity with type 2 diabetes mellitus: a GRADE-assessed meta-analysis of randomized controlled trials.

1. Diabetol Metab Syndr. 2026 Jun 26. doi: 10.1186/s13098-026-02218-9. Online ahead of print. Efficacy and safety of orforglipron in obesity with type 2 diabetes mellitus: a GRADE-assessed meta-analysis of randomized controlled trials. Emara A(1), Emara M(1), Mansour A(1), Elkholy MH(2), Abbas OF(1), Abdul-Hafez HA(3), Azzawi MADA(4), Shubietah A(5). Author information: (1)Faculty of Medicine, Al-Azhar University, Cairo, Egypt. (2)Faculty of Medicine, Alexandria National University, Alexandria, Egypt. (3)Department of Medicine, An-Najah National University, Nablus, West Bank, Palestine. hamzaakrm12@gmail.com. (4)Faculty of Medicine, The National Ribat University, Khartoum, Sudan. (5)Department of Medicine, Advocate Illinois Masonic Medical Center, Chicago, IL, USA. BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) frequently coexist and markedly increase cardiometabolic risk. Orforglipron is a novel oral glucagon-like peptide-1 receptor agonist developed to improve adherence compared with injectable therapies. We performed a systematic review and meta-analysis to evaluate its efficacy and safety. METHODS: PubMed, Scopus, Cochrane CENTRAL, and Web of Science were searched through January 2026 for randomized controlled trials (RCTs) comparing orforglipron with placebo in adults with obesity and T2DM. Random-effects models were used to pool mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Three RCTs, including 2,505 participants, were analyzed. Dose-subgroup analyses demonstrated a consistent dose-response pattern across all efficacy outcomes. For body weight, reductions versus placebo ranged from MD - 2.43% at 3 mg to MD - 7.80% at 24 mg. BMI reductions ranged from MD - 0.88 kg/m² at 3 mg to MD - 2.70 kg/m² at 45 mg. Waist circumference reductions were significant at doses ≥ 6 mg, reaching MD - 5.90 cm at 24 mg. HbA1c reductions ranged from MD - 0.80% at 3 mg to MD - 1.67% at 45 mg, and fasting serum glucose reductions ranged from MD - 20.62 mg/dL at 3 mg to MD - 44.80 mg/dL at 45 mg. Treatment discontinuation due to adverse events was higher with orforglipron across doses, while serious adverse events were not significantly different from placebo at any dose. CONCLUSIONS: Orforglipron may improve weight and glycemic outcomes in obese patients with T2DM; however, these findings are based on only three randomized controlled trials, and several key efficacy outcomes were rated as low certainty, so the results should be interpreted cautiously pending larger confirmatory studies. © 2026. The Author(s). DOI: 10.1186/s13098-026-02218-9 PMID: 42363271 Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not applicable. AI use: The authors confirm that no artificial intelligence was used. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Mentions Orforglipron

Copper peptide activated cascade catalysis for glucose regulation and hypoxia reversing in infected diabetic wound healing.

1. Mater Today Bio. 2026 Jun 26;39:103396. doi: 10.1016/j.mtbio.2026.103396. eCollection 2026 Aug. Copper peptide activated cascade catalysis for glucose regulation and hypoxia reversing in infected diabetic wound healing. Huang ZJ(1), Huang RF(2), Jiao PP(1), Zheng S(1), Wang M(1), Teng FW(1), Chen T(1), Zhou ZS(1)(3), Wang GH(4), Jiao GL(1). Author information: (1)Dongguan Key Laboratory of Central Nervous System Injury and Repair/Dongguan Institute of Spine and Spinal Cord Injury, The Sixth Affiliated Hospital of Jinan University (Dongguan), Dongguan, 523573, China. (2)The Ninth People's Hospital of Dongguan, Dongguan, 523888, China. (3)Zhou Zhi Sen Inheritance Studio of Renowned Traditional Chinese Medicine Experts of Dongguan, Dongguan, 523573, China. (4)School of Pharmacy, The Second School of Clinical Medicine, Guangdong Medical University, Dongguan, 523808, China. Starvation therapy has emerged as a promising strategy in diabetic wounds treating by regulating glucose level to deplete microbial nutrients without inducing antimicrobial resistance. However, this process consumes large amounts of oxygen, exacerbating wound hypoxia and compromising therapeutic efficacy. In this study, we designed a GOX-loaded hydrogel incorporated with copper peptide (GHK-Cu) to construct a copper peptide-activated cascade catalysis system for concurrent glucose regulation and hypoxia reversing. GOX initiates the cascade by catalyzing glucose oxidation, which reduces local hyperglycemia levels and generates hydrogen peroxide (H2O2). Subsequently, copper ions in GHK-Cu activate the subsequent step by mediating the decomposition of H2O2 through a catalase(CAT)-like reaction, releasing local oxygen to effectively alleviate the hypoxic state of the wound, and its own biological activity can further promote skin repair. The research results show that the Gel@GHK-Cu/GOX hydrogel can efficiently facilitates the decomposition of glucose into oxygen via the cascade reaction. Moreover, this hydrogel has been confirmed to have multiple therapeutic effects, including antibacterial activity, tissue repair promotion, antioxidant capacity, and angiogenesis stimulation. In conclusion, the Gel@GHK-Cu/GOX hydrogel provides an effective approach for chronic diabetic wound therapy. Its multifunctional synergistic mechanism offers novel insights for addressing clinical challenges in refractory diabetic wound healing. © 2026 The Authors. Published by Elsevier Ltd. DOI: 10.1016/j.mtbio.2026.103396 PMCID: PMC13330688 PMID: 42404628 Conflict of interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Mentions GHK-Cu

Circulating mitochondrial-derived microproteins at rest and in response to an acute bout of endurance exercise in individuals with cerebral palsy.

1. Exp Physiol. 2026 Jun 25. doi: 10.1113/EP093298. Online ahead of print. Circulating mitochondrial-derived microproteins at rest and in response to an acute bout of endurance exercise in individuals with cerebral palsy. Horwath O(1)(2), Corell L(1), Wan J(3), Hjalmarsson E(1)(4), Starck J(1), Reitzner SM(5)(6), Norrbom J(5), Fernandez-Gonzalo R(7)(8), Kvist O(1)(9), Cohen P(3), von Walden F(1), Edman S(1)(2)(10). Author information: (1)Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. (2)Department of Physiology, Nutrition and Biomechanics, The Swedish School of Sport and Health Sciences, Stockholm, Sweden. (3)The Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA. (4)Medical Unit Allied Health Professionals, Women's Health and Allied Health Professionals Theme, Karolinska University Hospital, Stockholm, Sweden. (5)Molecular Exercise Physiology Group, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. (6)Division of Clinical Pediatrics, Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden. (7)Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. (8)Unit of Clinical Physiology, Karolinska University Hospital, Huddinge, Sweden. (9)Department of Radiology, Columbia University Irvine Medical Center, New York, New York, USA. (10)Molecular Muscle Physiology & Pathophysiology Group, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. Regular exercise using assistive movement devices, such as running frames, has emerged as a promising strategy to improve cardiorespiratory fitness in individuals with cerebral palsy (CP). However, the molecular pathways underlying these adaptations remain poorly understood. Here, we examined a novel class of signalling molecules, mitochondrial-derived microproteins (MDPs), and assessed whether individuals with CP exhibit altered circulating levels compared with typically developing (TD) individuals at rest and following an acute bout of endurance exercise. Three groups were included: TD adults (31 ± 6 years), TD adolescents (16 ± 1 years) and adults with CP (25 ± 6 years). Individuals with CP were classified as Gross Motor Function Classification System (GMFCS) levels II-IV and had at least 3 months of frame running experience. Habitual physical activity, ultrasound-derived muscle thickness, and peak oxygen uptake were assessed. The exercise session consisted of 45 min of frame running for individuals with CP and conventional running for TD participants. Blood samples were obtained before and 1 h after exercise, and plasma MDP concentrations were measured using in-house enzyme-linked immunosorbent assay. Adults with CP had reduced muscle mass and maximal oxygen uptake compared to TD individuals. Despite this, they exhibited basal circulating levels of MDPs, including humanin, MOTS-c and SHMOOSE, comparable to TD adults and adolescents, with no associations with CP subtype or motor impairment severity. Following exercise, circulating MDPs showed no or only modest changes across groups, with no differences between CP and TD individuals. Overall, these findings suggest preserved mitochondrial-derived signalling via MDPs in individuals with CP. © 2026 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. DOI: 10.1113/EP093298 PMID: 42349896

Mentions MOTS-c

Impact of tirzepatide on systemic arterial stiffness assessed by cardio-ankle vascular index in individuals with obesity complicated by type 2 diabetes: A retrospective cohort study in Japan.

1. Obes Pillars. 2026 Jun 24;19:100291. doi: 10.1016/j.obpill.2026.100291. eCollection 2026 Sep. Impact of tirzepatide on systemic arterial stiffness assessed by cardio-ankle vascular index in individuals with obesity complicated by type 2 diabetes: A retrospective cohort study in Japan. Nagayama D(1)(2), Wakamatsu M(2), Watanabe Y(2), Ikeda M(2), Koshikawa Y(2), Horikawa O(2), Tsuji S(2), Shirai K(3), Saiki A(2). Author information: (1)Department of Internal Medicine, Nagayama Clinic, Oyama-City, Tochigi, 323-0032, Japan. (2)Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, Sakura-City, Chiba, 285-0841, Japan. (3)Department of Internal Medicine, Mihama Hospital, Chiba-City, Chiba, 261-0013, Japan. BACKGROUND: Tirzepatide, a multi-agonist incretin agent that targets body weight and metabolic parameters, has stronger weight reduction and glycemic control effects than existing agents. This study aimed to elucidate the effects of tirzepatide on vascular function in individuals with obesity complicated by type 2 diabetes (T2D). METHODS: This retrospective observational cohort study evaluated the effects of weekly tirzepatide (5-15 mg, median treatment duration 12.7 months) on vascular function and body composition in 24 individuals [45.8% male, median 48.6 years, body mass index (BMI) 32.3 kg/m2] with obesity and T2D. Sixteen individuals (66.7%) were switched from glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Vascular function was assessed using the cardio-ankle vascular index (CAVI), and body composition was evaluated using skeletal muscle index (SMI) and body fat index (BFI) measured by InBody720. RESULTS: Tirzepatide treatment significantly decreased CAVI (post-treatment to baseline: median 8.5 to 7.8) accompanied by significant reductions in BMI (mean 33.8 to 31.8 kg/m2), SMI (median 11.4 to 10.7 kg/m2), BFI (median 12.8 to 11.3 kg/m2) and glycemic parameters (including HbA1c: median 6.6 to 5.6%). The urinary albumin/creatinine ratio (UACR) tended to decrease with tirzepatide (median 11.9 to 7.2 mg/gCr, p = 0.067), and change in (Δ)UACR showed a trend of positive correlation with ΔCAVI (r s  = 0.403, p = 0.057). BMI reduction was greater (p = 0.040) and CAVI reduction tended to be greater (p = 0.089) at higher tirzepatide doses (10 and 15 mg) than at lower doses (5 and 7.5 mg). Prior GLP-1 RA use did not affect tirzepatide efficacy. Baseline SMI, but not BFI, correlated significantly and negatively with ΔCAVI (r s  = -0.424). CONCLUSION: Tirzepatide may dose-dependently reduce body weight and CAVI, contributed by decreased UACR and relatively high baseline SMI. Although tirzepatide is expected to improve kidney and vascular dysfunction in individuals with obesity complicated by T2D, careful attention to body composition is warranted. © 2026 The Authors. Published by Elsevier Inc. on behalf of Obesity Medicine Association. DOI: 10.1016/j.obpill.2026.100291 PMCID: PMC13320546 PMID: 42388688 Conflict of interest statement: Atsuhito Saiki has received lecture fees from Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Tanabe Pharma Corporation, Kowa Company, Ltd., and Nippon Boehringer Ingelheim Co., Ltd. The other authors declare no conflicts of interest.

Mentions Tirzepatide

Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells.

1. Inflamm Regen. 2026 Jun 22. doi: 10.1186/s41232-026-00431-7. Online ahead of print. Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells. Xing L(1)(2), Lu B(1)(3), Zhu X(1), Al Saeedi M(1), Lerman A(4), Eirin A(1), Cohen P(5), Lerman LO(6). Author information: (1)Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. (2)Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China. (3)Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. (4)Department of Cardiology, Mayo Clinic, Rochester, MN, USA. (5)USC Leonard Davis School of Gerontology, Los Angeles, CA, USA. (6)Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA. lerman.lilach@mayo.edu. BACKGROUND: Mesenchymal stromal cells (MSCs) possess therapeutic potential largely reliant on intact mitochondrial function to maintain reparative function. However, obesity compromises MSC metabolism and reparative capacity. MOTS-c, a mitochondria-derived peptide, is known to regulate cellular metabolism, but its role in human MSC biology remains unclear. We hypothesized that restoring MOTS-c signaling rescues the impaired functionality of adipose-derived MSCs from individuals with obesity. METHODS: MSCs isolated from abdominal fat of patients with obesity (BMI ≥ 30 kg/m2) and lean donors (BMI < 30 kg/m2) (n = 6/group) were assessed in vitro for changes in proliferation, senescence (p16, p21) TNF-α, and antioxidant gene expression following MOTS-c co-incubation. In vivo, the effects of MOTS-c pre-treatment on the reparative capacity of obese MSC were tested in stenotic mouse kidneys. RESULTS: Basal MOTS-c expression was lower in obese vs. lean MSCs. Nevertheless, although exogenous MOTS-c restored intracellular levels and activated AMPK signaling in obese MSCs, it reduced proliferation, increased expression of senescence-associated genes (p16, p21), and upregulated TNF-α. In vivo, in a murine model of renal artery stenosis, MOTS-c-pretreated MSCs failed to improve renal perfusion, fibrosis, or tubular injury, while pretreatment also blunted the reparative efficacy of lean MSCs. These findings reveal that restoration of mitochondrial metabolic signaling is insufficient to reverse obesity-induced MSC dysfunction and may paradoxically exacerbate senescence and inflammation. CONCLUSION: These results suggest a dissociation between metabolic activation and functional stemness, underscoring context-dependent effects of mitochondrial-derived peptides in MSC biology. © 2026. The Author(s). DOI: 10.1186/s41232-026-00431-7 PMID: 42324588 Conflict of interest statement: Declarations. Ethics approval and consent to participate: Title of the approved human study: “Obesity-induced mesenchymal stem cell senescence”. Name of the approving ethics committee: Mayo Clinic Institutional Review Board. Ethics approval reference number: 18-005076. Date approved: August 17, 2018. Consent for publication: Not applicable. Competing interests: Dr. Lerman is an advisor to CureSpec, LiveKidney.bio, and Cellergy. The authors declare no conflict.

Mentions MOTS-c

Rapid and harmonized analytical workflow for the determination of peptidic and non-peptidic doping agents in dried and liquid blood matrices.

1. Analyst. 2026 Jun 22. doi: 10.1039/d6an00455e. Online ahead of print. Rapid and harmonized analytical workflow for the determination of peptidic and non-peptidic doping agents in dried and liquid blood matrices. Mazzarino M(1), Colpaert T(1), Deventer K(1), Van Eenoo P(1). Author information: (1)Doping Control Laboratory, Department of Diagnostic Sciences, Ghent University, Block B, Ottergemsesteenweg 460, BE-9000, Ghent, Belgium. monica.mazzarino@ugent.be. Recently, methods for detecting small peptides in dried blood spots have been published. These procedures typically involve multiple sample preparation steps, resulting in labor-intensive and costly workflows. In the present study, we report a fast, streamlined, and harmonized analytical workflow to detect 54 prohibited peptidic and non-peptidic compounds in dried blood spots, serum, and plasma. Sample preparation is based on a single microextraction step using 500 µL of a methanol/water (8 : 2, v/v) mixture. Detection was performed using liquid chromatography coupled with high-resolution mass spectrometry. The validation results showed satisfactory performance with respect to selectivity (no interferences were detected at the retention times of the analytes), detection limits (0.05-1.25 ng mL-1), carry-over (no signals in the negative sample injected after the positive sample), matrix effect (5-33%), extraction yield (15-80%), and extract stability (the target analytes were stable for at least 72 h in the autosampler at 10 °C). The method was successfully applied to samples containing sub-ng levels of ibutamoren, confirming that the analytical procedure presented in this study is fit for purpose within the doping-control framework. Stability studies showed that all compounds were stable (variation lower than 15%) for at least two months at -20 °C in all the blood matrices considered. At 4 and 22 °C, alexamorelin, AOD9604, buserelin, hGH 176-191, kisspeptin-10 and LHRH were extensively degraded after one week in serum and plasma, whereas BPC-157, TB500, vasopressin, lypressin, and terlipressin showed complete degradation only in serum. In contrast, in dried matrices all compounds remained detectable throughout the entire duration of the study, indicating that samples can be transported and stored under non-refrigerated conditions, thereby reducing costs. DOI: 10.1039/d6an00455e PMID: 42328738

Mentions Kisspeptin

A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation.

1. Nat Commun. 2026 Jun 20. doi: 10.1038/s41467-026-74598-5. Online ahead of print. A synaptoid connectome differentiates tanycytic subpopulations and underlies neuroglial communication and neuroendocrine regulation. Neve V(#)(1), Fernandois D(#)(2), Rai S(1), Özorhan Ü(1), Nampoothiri S(2), Ternier G(2), Sideromenos S(3), Gallet S(2), Allet C(2), Stahr M(1), Klaus N(1), Martinez-Corral I(2), Coêlho CFF(2), Chandrasekar A(1), Constantinescu A(1), Rivagorda M(1), Dührkop S(1), Cases Bazarra J(1), Binder S(1), Giacobini P(2), Rasika S(2), Nogueiras R(4), Harkany T(3)(5), Schwarz MK(6), Müller-Fielitz H(1), Prevot V(7), Schwaninger M(8). Author information: (1)Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck, Germany. (2)University Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France. (3)Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Vienna, Austria. (4)Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain. (5)Department of Neuroscience, Karolinska Institutet, Solna, Sweden. (6)Institute for Experimental Epileptology and Cognition Research, University of Bonn Medical Center, Bonn, Germany. (7)University Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, DISTALZ, EGID, Lille, France. vincent.prevot@inserm.fr. (8)Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck, Germany. markus.schwaninger@uni-luebeck.de. (#)Contributed equally Tanycytes are radial-glia-like cells that play important roles in regulating the neuroendocrine system and metabolism. Synapse-like (synaptoid) connections have previously been described between neurons and tanycytes, but their structure and function are unclear. Here, we report that neuron-tanycyte synaptoids are abundant and resemble typical neuronal synapses in shape and composition. Tanycytic subtypes receive specific inputs from a variety of hypothalamic as well as extrahypothalamic neuronal populations and respond to several neurotransmitters and neuromodulators. As proof-of-principle of their functional relevance, we demonstrate in mice, that two distinct populations of kisspeptin neurons, which stimulate the gonadotropic axis, innervate different tanycytic subsets of the mediobasal hypothalamus to control basal levels of the gonadotropin luteinizing hormone (LH) and its pulsatile release pattern, in a sex‑ and region‑specific manner. Neuron-tanycyte synaptoid connections are thus widespread, diverse and functionally specific elements of hypothalamic neural circuits that play a key role in finetuning hormonal axes. © 2026. The Author(s). DOI: 10.1038/s41467-026-74598-5 PMID: 42323316 Conflict of interest statement: Competing interests: The authors declare no competing interests.

Mentions Kisspeptin