Community signal

Hunger pain and its reduction; qualitative insight from people with schizophrenia on semaglutide.

1. Int J Qual Stud Health Well-being. 2026 Dec 31;21(1):2717809. doi: 10.1080/17482631.2026.2717809. Epub 2026 Aug 18. Hunger pain and its reduction; qualitative insight from people with schizophrenia on semaglutide. Rasmussen BS(1), Simonÿ C(1)(2)(3), Poulsen ML(1), Uhrenholt NG(1)(4), Lundberg B(1)(5), Rønne ST(6), Uhrenholt PG(1)(7), Gæde PH(1)(3)(8), Arnfred SM(1)(7). Author information: (1)Department of Research, Central and Western Zealand Hospital, Copenhagen University Hospital, Slagelse, Denmark. (2)The Research and Implementation Unit PROgrez, Central and West Zealand Hospital, Slagelse, Denmark. (3)Institute of the Regional Health, University of Southern Denmark, Odense, Denmark. (4)Department of Clinical Research, Faculty of Health Science, University of Southern Denmark, Odense, Denmark. (5)Central and Western Zealand Hospital, Psychiatry South, Vordingborg, Denmark. (6)Department of Research & Psychiatry Westh, Central and Western Zealand Hospital, Copenhagen University Hospital, Slagelse, Denmark. (7)Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. (8)Department of Internal Medicine, Central and Western Zealand Hospital, Geriatrics and Neurology, Slagelse, Denmark. PURPOSE: It is often reported that people with schizophrenia experience weight gain and disordered eating, partly due to antipsychotics. As part of the RCT "Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes, HISTORI", the present study investigates experiences of hunger and eating habits in people using antipsychotics during semaglutide treatment. METHODS: Eleven semi-structured interviews were conducted 4 months to 1,5 years after treatment completion. Six women and 5 men were interviewed. The interviews were analysed using Braun & Clarke's reflexive thematic analysis. RESULTS: Three themes were identified; "Hunger pain induced by antipsychotic medicine", "Positive and negative experiences of reduced hunger", and "Eating habits and what influences them". The term "Hunger pain" was applied. It defines an excruciating combination of feeling extremely hungry, never achieving satiety, and relentless preoccupation with thoughts about food. The analysis suggested a focus on the patients' coping styles. CONCLUSION: The hunger pain, probably induced by antipsychotics, seemed to reinforce maladaptive coping styles. The relief from hunger pain due to semaglutide was in most cases a liberation. Yet, it is important also to pay attention to the negative effects of reduced hunger. It is relevant to assess patients' eating problems prior to semaglutide treatment. DOI: 10.1080/17482631.2026.2717809 PMCID: PMC13487855 PMID: 42610532 [Indexed for MEDLINE] Conflict of interest statement: The HISTORI RCT: Financial, material, and other support for the study was obtained from private foundations, including the Novo Nordisk Foundation; the Steno Diabetes Centre Sjaelland; the Steno Diabetes Centre Odense, Denmark; Slagelse Research Grants; and Region Zealand Health Research Foundation. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Mentions Semaglutide

Rethinking dog stress behaviours: contextual and physiological insights from the attachment framework.

Mentions Oxytocin

Limosilactobacillus reuteri normalizes gut microbiota dysfunction and social deficits of rat offspring associated with prenatal exposure to stress.

Mentions Oxytocin

Exploring spin-phonon coupling, barocaloric, and polar phonon features in the multiferroic [(CH(3))(2)NH(2)][Mn(N(3))(3)] hybrid perovskite.

Mentions P21

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

Mentions Semaglutide

Associations between human oxytocin receptor gene promoter DNA methylation and brain structural connectome in panic disorder in Korea.

1. J Affect Disord. 2026 Dec 15;415:122425. doi: 10.1016/j.jad.2026.122425. Epub 2026 Aug 26. Associations between human oxytocin receptor gene promoter DNA methylation and brain structural connectome in panic disorder in Korea. Kim HJ(1), Pae C(2), Bang M(1), Kim IB(3), Lee SH(4). Author information: (1)Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea. (2)Brain Imaging Center, Seoul National University, Seoul, Republic of Korea. (3)Department of Psychiatry, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Republic of Korea. Electronic address: ilbin49@chamc.co.kr. (4)Department of Psychiatry, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea. Electronic address: drshlee@cha.ac.kr. AIMS: Epigenetic regulation of the oxytocin receptor gene (OXTR), particularly DNA methylation (DNAm), has been linked to insecure attachment, anxiety-related phenotypes, and suicidality. However, its role in panic disorder (PD) and brain network dysfunction remains unclear. This study examined whether peripheral OXTR DNAm and OXTR DNAm-associated structural connectivity are related to clinical symptoms of PD. METHODS: We investigated OXTR DNAm and its structural connectivity in 563 patients with PD and 210 healthy controls (HCs). Peripheral blood OXTR promoter (-934) DNAm was quantified by pyrosequencing. In a neuroimaging subset, diffusion MRI tractography reconstructed the structural connectome. Network-based statistics tested the diagnosis-by-OXTR DNAm and diagnosis-by-clinical symptomatology effects using separation-related life events (SLEs), Anxiety Sensitivity Index-Revised (ASI-R), and the Scale for Suicidal Ideation (SSI). A preliminary bagging ensemble regression model was used to evaluate treatment response prediction. RESULTS: Patients with PD exhibited significantly lower OXTR DNAm levels than HCs, adjusting for age, sex, education, smoking status, and body mass index. Within PD, reduced OXTR DNAm was significantly negatively correlated with elevated SLEs, ASI-R, and SSI scores. Diagnosis-by-OXTR DNAm interactions revealed reduced connectivity across the hippocampus, amygdala, orbitofrontal, and precentral regions converging on the extended fear network. Importantly, OXTR DNAm-associated connectivity in the orbitofrontal and lateral occipital cortices showed a cross-validated association with the 8-week treatment outcomes. CONCLUSION: Lower peripheral OXTR DNAm was associated with higher PD-related symptomatology and altered extended fear network connectivity. These findings suggest that peripheral OXTR DNAm may index aspects of clinical and neural heterogeneity in PD. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.jad.2026.122425 PMID: 42648552 [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

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

Clinical practice patterns and unmet needs in the use of GLP-1 receptor agonists in sleep medicine: A pan-European survey performed in the European sleep apnoea database network.

Mentions Tirzepatide

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

Structure-based screening and identification of a novel Aurora-A-targeting peptide with antiproliferative activity against prostate cancer cells.

1. J Enzyme Inhib Med Chem. 2026 Dec;41(1):2700842. doi: 10.1080/14756366.2026.2700842. Epub 2026 Aug 11. Structure-based screening and identification of a novel Aurora-A-targeting peptide with antiproliferative activity against prostate cancer cells. Huang BB(1), Jiang H(1), Hu Y(2), Ge JJ(1), Liu X(2). Author information: (1)Drug Clinical Trial Facility Office, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. (2)Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China. Aurora-A is a potential therapeutic target in prostate cancer. In this study, virtual screening identified four Aurora-A-targeting peptides, among which Peptide-1 showed the most favourable profile. Molecular docking and MST assays demonstrated that Peptide-1 had the lowest predicted binding free energy and the strongest binding affinity towards Aurora-A (Kd = 0.72 ± 0.04 μM). MD simulation, MM/PBSA, and free-energy landscape analyses indicated that the Aurora-A-Peptide-1 complex was conformationally stable and mainly driven by electrostatic interactions. MTT assays showed that Peptide-1 inhibited the proliferation of PC3, DU145, and NCI-H660 cells, with weaker activity in RWPE-1 cells. Aurora-A knockdown reduced cellular sensitivity to Peptide-1, supporting its target-dependent activity. qRT-PCR further showed increased p53 and p21 mRNA expression after Peptide-1 treatment in PC3/p53WT cells. These findings suggest that Peptide-1 may act as an Aurora-A-targeting peptide with antiproliferative activity in prostate cancer cells. DOI: 10.1080/14756366.2026.2700842 PMCID: PMC13463526 PMID: 42578512 [Indexed for MEDLINE] Conflict of interest statement: 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 P21

Pathological α-synuclein propagation via the gut-liver axis induces liver injury in gut-origin Parkinson's disease mouse models.

1. Exp Neurol. 2026 Dec;406:115965. doi: 10.1016/j.expneurol.2026.115965. Epub 2026 Aug 17. Pathological α-synuclein propagation via the gut-liver axis induces liver injury in gut-origin Parkinson's disease mouse models. Hu R(1), Wu J(1), Song YZ(1), Tao Y(1), Tan LL(1), Ma XY(1), Xia YM(1), Nie X(1), Li T(1), Li MA(1), Yao L(1), Huang SB(1), Jia XB(1), Qiao CM(1), Zhao WJ(1), Cui C(2), Shen YQ(3). Author information: (1)Lab of Neurodegeneration and Injury, Wuxi School of Medicine, Jiangnan University, No. 1800, Lihu Avenue, Binhu District, Wuxi 214122, China; MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China. (2)Lab of Neurodegeneration and Injury, Wuxi School of Medicine, Jiangnan University, No. 1800, Lihu Avenue, Binhu District, Wuxi 214122, China; MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address: cuichun@jiangnan.edu.cn. (3)Lab of Neurodegeneration and Injury, Wuxi School of Medicine, Jiangnan University, No. 1800, Lihu Avenue, Binhu District, Wuxi 214122, China; MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China; Wuxi Central Rehabilitation Hospital, The Affiliated Mental Health Center of Jiangnan University, Wuxi, Jiangsu 214151, China. Electronic address: shenyanqin@jiangnan.edu.cn. Parkinson's disease (PD) pathogenesis involves α-synuclein (α-syn) aggregation in substantia nigra. The "gut-origin hypothesis" proposes α-syn propagates from gut to brain, but its peripheral effects remain unclear. Using a gut-origin PD mouse model by intestinal wall injecting α-syn preformed fibrils (α-syn PFFs), we tracked hepatic pathology for 8 months. Hepatic α-syn pathology appeared at 6 months post-injection, hepatic senescence and inflammation were induced, with increased p16, p21, and senescence-associated secretory phenotype factors, alongside decreased LaminB1. By 8 months, proliferation markers PCNA, Ki67, SOX2 declined; fibrosis markers α-SMA, MAO-A/B, Col1α1/2, Col3α1 and hepatic hydroxyproline (HYP) rose; and serum aspartate aminotransferase (AST) and AST/ALT ratio increased, indicating liver fibrosis and dysfunction. We also detected serological indicators of liver function and fibrosis in PD patients, the serum ALT levels were significantly elevated compared to healthy controls, while AST showed a similar trend; meanwhile, hyaluronic acid (HA) and procollagen III N-terminal peptide (PIIINP) were significantly elevated compared to healthy controls, suggesting subclinical hepatic injury and fibrotic activity. We further found that hepatic TLR4/NF-κB pathway was upregulated from 6 months. In vitro, the TLR4 inhibitor mitigated α-syn PFFs-induced activation of the TLR4/NF-κB pathway, thereby alleviating hepatocyte senescence and hepatic stellate cell activation. This study provides the first evidence that gut-origin α-syn may spread to the liver, associated with senescence, inflammation, and fibrosis via triggering TLR4/NF-κB, highlighting gut-liver-brain axis in PD progression. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.expneurol.2026.115965 PMID: 42607920 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors Rui Hu, Jian Wu, Yi-Zhi Song, Yue Tao, Lu-Lu Tan, Xiao-Yu Ma, Yi-Meng Xia, Xin Nie, Ting Li, Ming-an Li, Li Yao, Shu-Bing Huang, Xue-Bing Jia, Chen-Meng Qiao, Wei-Jiang Zhao, Chun Cui and Yan-Qin Shen have no relevant financial or non-financial interests to disclose.

Mentions P21

Role of the tail of the ventral tegmental area in the regulation of maternal behaviour: a pharmacological study in postpartum rats.

1. Neuropharmacology. 2026 Dec 1;300:111147. doi: 10.1016/j.neuropharm.2026.111147. Epub 2026 Aug 16. Role of the tail of the ventral tegmental area in the regulation of maternal behaviour: a pharmacological study in postpartum rats. Pérez-Gozalbo C(1), Sanahuja-Irene S(1), Martínez-García F(1), Sánchez Catalán MJ(2). Author information: (1)Research Unit on Functional Neuroanatomy (NeuroFun) - Predepartamental Unit of Medicine, Faculty of Health Sciences. Universitat Jaume I de Castellón (UJI), Campus Riu Sec. Av. Vicente Sos Baynat s/n, de la Plana, Castellón, 12071, Spain. (2)Research Unit on Functional Neuroanatomy (NeuroFun) - Predepartamental Unit of Medicine, Faculty of Health Sciences. Universitat Jaume I de Castellón (UJI), Campus Riu Sec. Av. Vicente Sos Baynat s/n, de la Plana, Castellón, 12071, Spain. Electronic address: macatala@uji.es. Maternal behaviour is characterized by increased motivation for pups, which facilitates the expression of behaviours promoting offspring survival and development. Motivated behaviours are critically dependent on brain dopamine systems, thus, understanding its functioning is necessary to elucidate maternal reward brain processing. The activity of dopamine systems is controlled by the inhibitory GABA cells of the tail of the ventral tegmental area or rostromedial tegmental nucleus (tVTA/RMTg). This brain region is involved in reward and avoidance behaviour, among other functions, however, its role in maternal behaviour remains poorly understood. In the present study, we assess the effect of pharmacological manipulation of the tVTA/RMTg on maternal behaviour in postpartum female rats. To this end, pregnant Sprague-Dawley female rats underwent stereotaxic implantation of a guide cannula in the tVTA/RMTg. During the first week after delivery, female rats received intra-tVTA/RMTg microinjections of vehicle and/or several pharmacological agents (glutamate, DAMGO, muscimol, oxytocin or atosiban) in a cross-design. Our results reveal that pharmacological activation and inhibition of the tVTA/RMTg can increase or decrease maternal behaviour, respectively, by altering some specific behaviours, such as pup retrieval, pup exploration or time spent in nest. Otherwise, modulation of the oxytocinergic transmission at the tVTA/RMTg reveals mild effects on maternal behaviour and the observed effect depend on the oxytocin dose. Overall, our results reveal an involvement of the tVTA/RMTg in maternal reward processing, since its activation or inhibition can critically modulate maternal behaviour. Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.neuropharm.2026.111147 PMID: 42604662 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interests 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

Predicting Category II and III foetal heart rate patterns during epidural analgesia: a retrospective cohort study.

Mentions Oxytocin

Perfusion response to treatment outcome: CEUS links oxytocin to HIFU efficacy prediction for uterine fibroids.

1. Int J Hyperthermia. 2026 Dec;43(1):2706038. doi: 10.1080/02656736.2026.2706038. Epub 2026 Sep 22. Perfusion response to treatment outcome: CEUS links oxytocin to HIFU efficacy prediction for uterine fibroids. Zhang DL(1), Wu S(2), Ding G(2), Chen XW(1), Chen M(2), Chen S(1). Author information: (1)Department of Ultrasonography, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. (2)Department of Ultrasonography, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China. OBJECTIVES: To evaluate oxytocin-induced perfusion changes in uterine fibroids using contrast-enhanced ultrasound(CEUS) and determine their predictive value for high-intensity focused ultrasound (HIFU) ablation efficacy. METHODS: Fifty-five patients (mean age 42.15 ± 5.34 years). with 78 uterine fibroids underwent oxytocin-enhanced HIFU therapy. CEUS was performed before and after intravenous oxytocin infusion (0.10 U/ml over 10 min). Perfusion changes were assessed using two parameters:(1) Arterial-phase Perfusion Delay Time difference (APDTΔt), defined as the time difference in enhancement onset of fibroids before and after oxytocin exposure; (2) Visual Perfusion Grading (VPG), based on relative contrast perfuse reduction of fibroids at the end of the arterial phase(Grade1:≤30%;Grade2:30-70%;Grade3:≥70%). Post-treatment contrast-enhanced pelvic MRI was used to calculate fibroid volume and non-perfused volume(NPV),from which ablation ratio was derived. Fibroids were dichotomized by ablation efficacy (≥70%vs < 70%), and correlation analyses and ROC curves were used to evaluate predictive performance. RESULTS: Fibroids in the <70% ablation group showed a mean APDT(Δt) of 8.32 ± 5.61s and 52.2%(12/23) VPG as Grade1. In the ≥70% group, APDT(Δt) was significantly longer (16.76 ± 12.12 s), and 54.5%(30/55) VPG were Grade3. Both APDT(Δt) and VPG differed significantly between groups (p < 0.05), Showing strong correlations with ablation ratio (r = 0.577 and r = 0.585; both p < 0.001). Thresholds of APDT(Δt) >3.5 s and VPG >1.5 yielded sensitivities of 83.6% and 87.3%, specificity of 65.2% and 52.3%, with AUCs of 0.791 and 0.725, respectively. CONCLUSION: CEUS can effectively detect oxytocin-mediated perfusion changes in uterine fibroids. These changes are strongly associated with HIFU ablation outcomes, and in particular, Arterial-phase Perfusion Delay Time demonstrates robust predictive value for treatment efficacy. DOI: 10.1080/02656736.2026.2706038 PMID: 42773797 [Indexed for MEDLINE]

Mentions Oxytocin

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

Targeting p21-activated kinase 4: Recent advances in the discovery of PAK4 inhibitors and strategies for isoform selectivity.

1. Eur J Med Chem. 2026 Nov 15;318:119187. doi: 10.1016/j.ejmech.2026.119187. Epub 2026 Jul 31. Targeting p21-activated kinase 4: Recent advances in the discovery of PAK4 inhibitors and strategies for isoform selectivity. Shi R(1), Feng X(1), Wang Z(2), Xing Y(1), Yan X(1), Xing R(3), Zhang G(4). Author information: (1)Hebei University of Science & Technology, Shijiazhuang, 050018, People's Republic of China. (2)Department of Medicinal Chemistry, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, People's Republic of China. (3)Department of Medicinal Chemistry, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, People's Republic of China. Electronic address: xingruijuan@hebmu.edu.cn. (4)Hebei University of Science & Technology, Shijiazhuang, 050018, People's Republic of China. Electronic address: zggg1980@hotmail.com. p21-activated kinase 4 (PAK4), a Group II PAK family member, is a therapeutically relevant candidate target in cancer, metabolic disease, and tissue injury. However, translation of PAK4 biology into drug candidates has been constrained by the conserved ATP-binding architecture of PAK isoforms, unfavorable pharmacokinetic profiles, and suboptimal clinical efficacy. We summarize the evolution of ATP-competitive Type I inhibitors, Type I½ back-pocket inhibitors, allosteric modulators, and PROTAC degraders, and compare representative compounds using potency, isoform selectivity, cellular activity, oral bioavailability, and development status. Particular emphasis is placed on structural determinants of selectivity, including the αC-helix-dependent hydrophobic back pocket, the inward Asp444/Asp458 floor pocket arrangement, and peripheral microenvironment differences that distinguish PAK4 from Group I PAKs. We also summarize the potential ADMET liabilities-such as pronounced efflux, metabolic instability, and poor oral bioavailability-that may arise from structural modifications aimed at enhancing PAK4 selectivity, and discuss rational optimization strategies to navigate these inherent barriers. Finally, we discuss clinical lessons from PF-3758309 and KPT-9274/padnarsertib and highlight how allosteric inhibitors and PROTAC degraders may help address limitations of conventional ATP-site inhibitors. Copyright © 2026 Elsevier Masson SAS. All rights reserved. DOI: 10.1016/j.ejmech.2026.119187 PMID: 42546589 [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

Discovery of a quinoline-based senomorphic agent for the treatment of chronic kidney disease.

1. Eur J Med Chem. 2026 Nov 15;318:119164. doi: 10.1016/j.ejmech.2026.119164. Epub 2026 Jul 17. Discovery of a quinoline-based senomorphic agent for the treatment of chronic kidney disease. Chen Y(1), Qiao S(2), Chen X(3), Li L(1), Wu J(1), Shi C(1), Li J(4), Guo Y(5), Huang Y(6), Liu W(7). Author information: (1)Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Hainan Province Key Laboratory of One Health, Hainan International One Health Institute, Haikou, 570228, China. (2)Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. (3)State Key Laboratory of Bioactive Molecules and Assessment, College of Pharmacy, Jinan University, Guangzhou, 510632, China. (4)Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Hainan Province Key Laboratory of One Health, Hainan International One Health Institute, Haikou, 570228, China; State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Material Biology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China. (5)Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing of the Ministry of Education, School of Chemical Engineering, Northwest University, Xi'an, 710127, China. (6)Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, 430079, China. (7)Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Hainan Province Key Laboratory of One Health, Hainan International One Health Institute, Haikou, 570228, China. Electronic address: wenwenliu@hainanu.edu.cn. Senescence is a risk factor for chronic diseases, making anti-aging interventions a promising strategy for geriatric conditions. While a non-antibacterial derivative C1 of enrofloxacin has been proposed to extend lifespan in Caenorhabditis elegans (C. elegans), its unresolved cytotoxicity in healthy mammalian cells limits its combinatory potential and safety as an anti-aging agent. With the aim of preserving anti-aging activity while enhancing safety, we here performed structural optimization of C1 and created 37 derivatives. Among them, C36, which derived from introducing an isopropoxy group at the R7 position, exhibited the most potent lifespan extending effect (11.49%) in C. elegans with low cytotoxicity (IC50 > 100 μM) in two commonly used aging relevant mammalian cell lines. In a mouse model with doxorubicin induced senescence, C36 treatment attenuated the senescence associated secretory phenotype (SASP), mitigated cell cycle arrest, and significantly lowered aging markers in kidney tissue. Given the central role of cellular senescence and SASP in the progression of chronic kidney disease (CKD), we evaluated C36 in mice with kidney failure. The results showed that C36 effectively reduced the level of SASP and thus alleviated senescence of the diseased kidney through a senomorphic approach. In comparison to the model group, C36 significantly improved renal function, reduced renal fibrosis by approximately 50%, and decreased the renal expression of the senescence-associated markers p21, p16, and p53. These findings imply that C36 could have a role in modulating organismal s

Mentions P21

Reprogramming NAD(+) homeostasis and FOXO3a-Nrf2 signaling mitigates bleomycin-driven pulmonary fibrosis.

1. Toxicol Appl Pharmacol. 2026 Nov;516:118045. doi: 10.1016/j.taap.2026.118045. Epub 2026 Sep 19. Reprogramming NAD(+) homeostasis and FOXO3a-Nrf2 signaling mitigates bleomycin-driven pulmonary fibrosis. Mo'men M(1), Saber S(2), Amer AE(3), El-Kashef HA(4). Author information: (1)Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. (2)Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: sameh.saber@deltauniv.edu.eg. (3)Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: ahmed.amer@deltauniv.edu.eg. (4)Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Pulmonary fibrosis arises from intertwined oxidative, inflammatory, and profibrotic processes, whereas current therapies target only parts of this network. Here, we evaluated an adjunctive strategy in which nicotinic acid (NA), a NAD+-supporting supplement/adjuvant, was added to semaglutide (SEMA), a GLP-1 receptor agonist. The prespecified objective was to determine whether adding NA to SEMA provides greater protection than SEMA alone in bleomycin (BLM)-induced pulmonary fibrosis. Rats were challenged with BLM and treated with SEMA, NA, or SEMA+NA for 21 days. Biochemical, molecular, histological, and western blot endpoints were assessed, and the fixed-dose Highest Single Agent (HSA) and Bliss independence models were used as exploratory interaction metrics. BLM induced oxidative stress, inflammatory cytokine elevation, NAD+ and SIRT1 depletion, FOXO3a suppression, TGF-β/SMAD activation, and collagen deposition. Compared with SEMA alone, SEMA+NA produced broader protection, restoring NAD+/SIRT1-FOXO3a-Nrf2 pathway-associated readouts and suppressing NF-κB/TGF-β-linked inflammatory and fibrotic markers. Exploratory HSA and Bliss analyses suggested enhanced fixed-dose effects across several endpoints but were interpreted descriptively, not as definitive pharmacological synergy. These findings indicate that NA-driven NAD+ metabolic support can amplify the protective profile of SEMA in experimental pulmonary fibrosis. Dose-response matrices, pathway-inhibition studies, temporal profiling, and lung-function testing remain required to establish definitive synergy, mechanism, and translational relevance. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.taap.2026.118045 PMID: 42763059 [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

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

Orforglipron alleviates aortic aneurysm and dissection via inhibiting WNT5A noncanonical signaling.

1. Biochem Pharmacol. 2026 Nov;253(Pt 1):118294. doi: 10.1016/j.bcp.2026.118294. Epub 2026 Jul 27. Orforglipron alleviates aortic aneurysm and dissection via inhibiting WNT5A noncanonical signaling. Deng Y(1), Guo Z(2), Yu L(2), Zhang J(3), Qian J(1), Wang J(3), Chen X(1), Xu Z(2), Wang D(4), Kong C(5). Author information: (1)Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. (2)The Affiliated Huai an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China. (3)Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China. (4)Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: glwdj@nju.edu.cn. (5)Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: chuiyukong@njglyy.com. Aortic aneurysm and dissection (AAD) are life-threatening vascular diseases for which effective pharmacological therapies remain limited. Smooth muscle cell phenotypic switching plays a central role in AAD development and progression. Orforglipron, a novel orally active non-peptide glucagon-like peptide-1 receptor agonist, has shown potential cardiovascular benefits; however, its role in AAD remains unclear. In this study, male B6 humanized GLP-1R mice were treated with orforglipron by oral gavage for 28 consecutive days and subjected to beta-aminopropionitrile combined with angiotensin II infusion to induce AAD. Orforglipron treatment protected mice from smooth muscle cell phenotypic switching, medial degeneration, and AAD formation. RNA sequencing of human aortic smooth muscle cells identified Wnt5a as a key downstream target regulated by orforglipron. Mechanistically, orforglipron inhibited ERK phosphorylation, reduced EGR1 expression, and thereby suppressed EGR1-mediated Wnt5a transcription. Conditional deletion of Wnt5a in smooth muscle cells significantly attenuated AAD progression, whereas activation of JNK signaling aggravated vascular remodeling and AAD development. These findings demonstrate that orforglipron attenuates smooth muscle cell phenotypic switching and AAD progression by modulating the ERK/EGR1/Wnt5a/JNK signaling axis, supporting orforglipron as a promising therapeutic candidate for aortic diseases. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.bcp.2026.118294 PMID: 42508653 [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: Chuiyu Kong reports financial support was provided by National Natural Science Foundation of China. 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 Orforglipron

Progesterone regulates the secretion of GnRH in bovine endometrial cells via the Erk1/2-ARRB1 pathway.

Mentions Oxytocin

Positive actions of fibroblast growth factor 21 on female zebrafish reproductive axis.

1. Theriogenology. 2026 Nov;265:118106. doi: 10.1016/j.theriogenology.2026.118106. Epub 2026 Jul 30. Positive actions of fibroblast growth factor 21 on female zebrafish reproductive axis. Uju CN(1), Unniappan S(2). Author information: (1)Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7V 1H2, Canada. Electronic address: chinelo.uju@usask.ca. (2)Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7V 1H2, Canada. Electronic address: suraj.unniappan@usask.ca. Fibroblast growth factor 21 (Fgf21) is a member of the endocrine subfamily of fibroblast growth factors. In mammals, FGF21 regulates glucose and lipid metabolism, and energy balance. Fgf21 was recently demonstrated to stimulate feed intake and regulate energy balance in zebrafish. The physiological mechanisms that regulate energy balance are tightly interlinked with reproduction. As a first step to extend our original findings on Fgf21 and energy balance, this research aimed to determine whether Fgf21 regulates the reproductive axis in zebrafish. Using quantitative PCR, we demonstrate the expression of fgf21, its receptor fgfr1c, and co-receptor β-klotho; and FGF21-like immunoreactivity (immunohistochemistry) in the zebrafish ovary and liver cells. These results suggest local production of FGF21 and possible actions within the ovary. Single intraperitoneal (IP) injection of 1, 10, or 100 ng/g bodyweight FGF21 significantly (ANOVA, P < 0.05) upregulated reproductive hormone genes in the brain; gonadotropin-releasing hormone isoforms (sgnrh/cgnrh-III) and kisspeptin (kiss1), and gonads; aromatase (cyp19a1a) and gonadotropin receptors (fshr, lhr) that are critical for reproductive success. FGF21 significantly (ANOVA, P < 0.05) upregulated vitellogenin transcript levels and total vitellogenin concentration (ELISA) in zebrafish liver cells at 1 h and 24 h post-incubation, respectively. Lastly, at 100 ng/mL, FGF21 induced (ANOVA P < 0.05) oocyte maturation in vitro (determined by germinal vesicle breakdown quantification). These results support a very strong positive role for Fgf21 in the reproductive endocrine axis of zebrafish. Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.theriogenology.2026.118106 PMID: 42541973 [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:Suraj Unniappan reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. 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 Kisspeptin

Exposure to polystyrene nanoplastics provokes vascular endothelial senescence through eliciting nucleolar stress.

1. Toxicology. 2026 Nov;526:154548. doi: 10.1016/j.tox.2026.154548. Epub 2026 Jul 23. Exposure to polystyrene nanoplastics provokes vascular endothelial senescence through eliciting nucleolar stress. Wang L(1), Wan Y(2), Wu L(3), Cao H(4), Xiong X(1), Zhai X(5), Wang B(6), Cai B(6), Zhang D(7), Kuang X(8). Author information: (1)Pathology Center of the First Affiliated Hospital of Nanchang University/Jiangxi Provincial Key Laboratory of Precision Pathology and Intelligent Diagnosis, Nanchang University, Nanchang 330006, China; Pathology Teaching and Research Office, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. (2)Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. (3)Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, School of Public Health, Nanchang University, Nanchang 330019, China. (4)Department of Cardiology, Shi bei Hospital, Shanghai 200443, China. (5)Pathology Teaching and Research Office, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. (6)The Second Clinical Medical College of Nanchang University, Nanchang 330031, China. (7)Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, School of Public Health, Nanchang University, Nanchang 330019, China. Electronic address: zhangdalei@ncu.edu.cn. (8)Pathology Center of the First Affiliated Hospital of Nanchang University/Jiangxi Provincial Key Laboratory of Precision Pathology and Intelligent Diagnosis, Nanchang University, Nanchang 330006, China; Pathology Teaching and Research Office, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330006, China. Electronic address: happy_kuang@ncu.edu.cn. Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants with unclear cardiovascular impacts. This study evaluated PS-NPs-induced endothelial senescence using murine models and HUVECs. PS-NPs caused aortic wall thickening and structural disruption in mice, and induced DNA damage, apoptosis, cell cycle arrest, and impaired migration/vasculogenesis in vitro. Both models showed excessive ROS production and nucleolar stress (NPM1 relocalization), leading to premature senescence via p53/p21 upregulation. These effects were reversed by NPM1 inhibitor NSC348884 or ROS scavenger N-acetylcysteine. Collectively, PS-NPs promote vascular endothelial senescence through ROS-dependent nucleolar stress, highlighting their vasotoxic potential and cardiovascular risks. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.tox.2026.154548 PMID: 42492616 [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

Analytical methods for the determination of semaglutide in pharmaceutical formulations and biological matrices: A comprehensive review.

1. J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Nov 1;1283:125267. doi: 10.1016/j.jchromb.2026.125267. Epub 2026 Aug 26. Analytical methods for the determination of semaglutide in pharmaceutical formulations and biological matrices: A comprehensive review. Kavibharathi V(1), Thirusha KM(2), Vijayadevan G(2), Vijayakumar R(2), Nalini CN(2). Author information: (1)Department of Pharmaceutical Analysis, C.L Baid Metha College of Pharmacy, Chennai, India. Electronic address: kavib8720@gmail.com. (2)Department of Pharmaceutical Analysis, C.L Baid Metha College of Pharmacy, Chennai, India. Semaglutide is a potent long-acting glucagon-like peptide-1 receptor agonist with outstanding therapeutic efficacy for type 2 diabetes and obesity. Because of its widespread clinical use, there is an increasing demand for analytical techniques to identify semaglutide in pharmaceutical formulations and biological matrices. The current study provides an overview of analytical methodologies for determining semaglutide across various disciplines. The material may be analysed using the following techniques: chromatography, spectroscopy, electrophoresis, and mass spectrometry. Some of these approaches include reversed-phase high-performance liquid chromatography, liquid chromatography/tandem mass spectrometry, ultraviolet-visible spectrophotometry, Fourier-transform infrared spectroscopy, Raman spectroscopy and others. The reported methodological characteristics, including validation parameters are discussed. In addition, a comparison and discussion of analytical performance, approaches, advantages, and disadvantages are presented. Chromatographic techniques are presented as the most effective, sensitive, and reliable analytical methods for semaglutide determination, but alternative approaches are also described. The current study may provide a comprehensive and informative guide for further investigations into semaglutide analysis and related research. Copyright © 2026 Elsevier B.V. All rights reserved. DOI: 10.1016/j.jchromb.2026.125267 PMID: 42664897 [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

[Expression of Concern] Ganoderma lucidum polysaccharide inhibits prostate cancer cell migration via the protein arginine methyltransferase 6 signaling pathway.

1. Mol Med Rep. 2026 Nov;34(5):299. doi: 10.3892/mmr.2026.14010. Epub 2026 Sep 11. [Expression of Concern] Ganoderma lucidum polysaccharide inhibits prostate cancer cell migration via the protein arginine methyltransferase 6 signaling pathway. Zhao X(1), Zhou D(2), Liu Y(3), Li C(4), Zhao X(1), Li Y(1), Li W(1). Author information: (1)Oncology Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China. (2)Virology Laboratory, Microbiology Department, The Center of Jinzhou Disease Control and Prevention, Jinzhou, Liaoning 121000, P.R. China. (3)Laboratory of Rescue Center of Severe Wound and Trauma PLA, Emergency Medicine Department, General Hospital of Shenyang Military Command, Shenyang, Liaoning 110016, P.R. China. (4)College of Mathematics and Physics, Bohai University, Jinzhou, Liaoning 121000, P.R. China. Expression of concern for Mol Med Rep. 2018 Jan;17(1):147-157. doi: 10.3892/mmr.2017.7904. Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the histological images shown in Fig. 1B on p. 149, the "Ctrl" and "GLPs 5μg/ml" data panels contained an overlapping section of data, suggesting that these data panels were derived from the same original source where different experimental conditions were reported. In addition, a concern was raised regarding the antibody that had been used to probe for p21 in the western blot experiments in Fig. 5 (cat. no. sc‑136020, purchased from Santa Cruz Biotechnology, Inc.), since apparently this antibody is specific for a different protein, sometimes referred to as p21‑ARC, which is related to the actin cytoskeleton. The authors have been contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in their paper, and we are awaiting their response. Due to the fact that we have been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Molecular Medicine Reports 17: 147‑157, 2018; DOI: 10.3892/mmr.2017.7904]. DOI: 10.3892/mmr.2026.14010 PMCID: PMC13587023 PMID: 42725400 [Indexed for MEDLINE]

Mentions P21

Impaired mitochondrial quality control and stress signalling machinery modulate senescence induction by genotoxic challenge.

1. Cell Signal. 2026 Nov;147:112763. doi: 10.1016/j.cellsig.2026.112763. Epub 2026 Jul 24. Impaired mitochondrial quality control and stress signalling machinery modulate senescence induction by genotoxic challenge. Simons-Weston M(1), Dominguez-Prieto M(1), Moisoi N(2). Author information: (1)Leicester School of Pharmacy, Leicester Institute for Pharmaceutical and Health Innovations, Faculty of Health Sciences, De Montfort University, The Gateway, Hawthorn Building, Leicester LE1 9BH, UK. (2)Leicester School of Pharmacy, Leicester Institute for Pharmaceutical and Health Innovations, Faculty of Health Sciences, De Montfort University, The Gateway, Hawthorn Building, Leicester LE1 9BH, UK. Electronic address: nicoleta.moisoi@dmu.ac.uk. Cellular senescence is a hallmark of ageing and age-related disease and is closely associated with mitochondrial dysfunction and the accumulation of DNA damage. However, the contribution of mitochondria-nucleus communication, mitochondrial quality control (mtQC) and stress signalling to senescence remains incompletely understood. Here, we investigated the interplay between mtQC pathways and cellular stress responses in DNA damage-induced senescence using mouse embryonic fibroblasts (MEFs). MEFs deficient in the mitochondrial protease HtrA2 (proteostasis), the transcription factor Chop (integrated stress response; ISR) or the mitophagy regulator Pink1 were exposed to three mechanistically distinct DNA-damaging agents: bleomycin, etoposide and doxorubicin. Senescence was characterised using multiple complementary markers, including the proportion of high senescence-associated β-galactosidase-positive cells, nuclear size, total and nuclear p21 abundance, and transcriptional analysis of p16, p21 and genes associated with cell-cycle regulation and stress signalling. Mitochondrial dysfunction through mtQC impairment enhanced sensitivity to senescence with HtrA2 and Pink1 loss promoting increased senescence under DNA damage. Although DNA damage response (DDR) was activated as seen by changes in p21 homeostasis, this did not always correlate with senescence levels, which indicates that DDR alone cannot account for all senescence characteristics. The ISR played a modulatory role in the senescence induction, with Chop loss of function reducing senescence induction following DNA damage despite DDR activation. The different DNA damaging drugs produced different senescence outcomes, thus highlighting the importance of the stressor context in addition to the cellular homeostasis mechanisms in the overall senescence profile. This approach allowed, for the first time, to identify senescence subtypes dependent of mtQC and ISR integrity in the context of genotoxic stress. Crown Copyright © 2026. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.cellsig.2026.112763 PMID: 42498093 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no conflict of interest.

Mentions P21

Lipid-lowering and hepatoprotective effects of Ocimum sanctum L. (Thai holy basil) flower against MASLD and liver inflammation in rats.

1. Food Res Int. 2026 Oct 31;242(Pt 3):119968. doi: 10.1016/j.foodres.2026.119968. Epub 2026 Jul 10. Lipid-lowering and hepatoprotective effects of Ocimum sanctum L. (Thai holy basil) flower against MASLD and liver inflammation in rats. Inchai J(1), Phatsara M(2), Yoonakorn R(3), Holasut P(4), Saithong T(5), Tunkaew K(6), Ontawong A(7), Yasanga T(8), Nuengchamnong N(9), Lailerd N(10), Amornlerdpison D(11), Vaddhanaphuti CS(12). Author information: (1)Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: jakkapong.inc@gmail.com. (2)Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: msethadavit@gmail.com. (3)Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: ratchadaporn_yo@cmu.ac.th. (4)Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: ompnth@gmail.com. (5)Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: icethuntakarn@gmail.com. (6)Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: kornwalai_tu@cmu.ac.th. (7)Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand. Electronic address: atcharaporn.on@up.ac.th. (8)Medical Science Research Equipment Center, Faculty of Medicine, Chiangmai University, Chiang Mai 50200, Thailand. Electronic address: thippawan.y@cmu.ac.th. (9)Science Laboratory Centre, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand. Electronic address: nitran@nu.ac.th. (10)Nutrition Research Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: narissara.lailerd@cmu.ac.th. (11)Center of Excellence in Agricultural Innovation for Graduate Entrepreneur, Maejo University, Chiang Mai 50290, Thailand. Electronic address: doungpornfishtech@gmail.com. (12)Innovative Research Unit of Epithelial Transport and Regulation (iETR), Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address: chutima.srimaroeng@cmu.ac.th. Metabolic dysfunction-associated steatotic liver disease (MASLD) has been defined as the fatty liver disease associated with systemic metabolic dysregulation, lipid dysregulation, and inflammation. Although the U.S. FDA has approved semaglutide and resmetirom as the options for treatment of non-alcoholic steatohepatitis or metabolic dysfunction-associated steatohepatitis, warnings on hepatotoxicity and drug interactions remain. Therefore, alternative candidates exhibiting lipid-lowering activity against MASLD are still required. Aqueous extract from Ocimum sanctum L. flowers (OSLE) has recently been reported to interfere with choline metabolism in high-fat diet (HFD)-induced MASLD rats. However, the hepatoprotective mechanisms of OSLE against MASLD remain inconclusive. This study aims to clarify the mechanisms of OSLE in HFD-induced MASLD rats. Normal and MASLD rats were supplemented for 12 weeks with OSLE (1000 mg/kg BW), atorvastatin (10 mg/kg BW), or their combination. The molecular mechanisms underlying the effects of OSLE were identified using histological analyses, qPCR, and western blotting. The results demonstrated that OSLE improved lipid profiles and reduced hepatic lipid accumulation by increasing cholesterol excretion. Additionally, OSLE activated AMPK and promoted hepatic lipophagy, as evidenced by inc

Mentions Semaglutide

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

From FLOW to translational positioning in chronic kidney disease: mechanistic complementarity of SGLT2 inhibitors and GLP-1 receptor agonists.

1. Transl Res. 2026 Oct;296:86-96. doi: 10.1016/j.trsl.2026.07.008. Epub 2026 Jul 21. From FLOW to translational positioning in chronic kidney disease: mechanistic complementarity of SGLT2 inhibitors and GLP-1 receptor agonists. Tian X(1), Ma X(2), Song E(3), Li X(4), Fu W(5), He H(6), Gao Z(7), Gao B(8). Author information: (1)Department of Nutrition, Cangzhou Central Hospital, No. 16 Xinhua W Rd, Yunhe District, Cangzhou 061001, Cangzhou, Hebei, 061012, China. Electronic address: da.xuefenfen@163.com. (2)Department of Nutrition, Cangzhou Central Hospital, No. 16 Xinhua W Rd, Yunhe District, Cangzhou 061001, Cangzhou, Hebei, 061012, China. Electronic address: 916733108@qq.com. (3)Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Rd, Eco-Tech Zone, Hefei, 230601, Anhui, China. Electronic address: nx_s10@126.com. (4)Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, No. 128 Shenyang Rd, Yangpu District, Shanghai, 200090, China. Electronic address: xilianli@aliyun.com. (5)Department of Obstetrics and Gynecology, The Third People's Hospital of Hubei Province, No. 26 Zhongshan Avenue, Qiaokou District, Wuhan, 430033, China. Electronic address: fwlan@126.com. (6)Department of Urology, Changhai Hospital, Naval Medical University, No. 168 Changhai Rd, Shanghai, 200433, China. Electronic address: hehaiwei0117@126.com. (7)Yueyang Integrated Traditional Chinese and Western Medicine Hospital, Shanghai University of TCM, No. 110 Ganhe Rd, Shanghai, 200437, China. Electronic address: gaozhiyuan20@126.com. (8)Teaching and Research Support Center, Naval Medical University, No. 800 Xiangyin Rd, Shanghai, 200433, China. Electronic address: gbdata@163.com. Chronic kidney disease is a central node of the cardio-kidney-metabolic continuum and carries substantial residual cardiovascular and kidney risk. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have reproducibly reduced kidney disease progression and heart failure risk in CKD outcomes trials, whereas GLP-1RAs have established cardiovascular benefit across cardiometabolic populations. The FLOW trial (Evaluate Renal Function With Semaglutide Once Weekly) established hard kidney-outcome evidence for semaglutide in type 2 diabetes with CKD, although whether this renal benefit represents a broader GLP-1RA class effect remains unresolved. This review synthesizes current evidence through a translational framework centered on mechanistic complementarity rather than simple add-on therapy. SGLT2 inhibitors predominantly provide proximal tubular and hemodynamic offloading, coupled with fasting-mimetic metabolic reprogramming that may improve oxygen-stress balance and cellular housekeeping. GLP-1RAs predominantly support an immune-vascular repair program by dampening sterile inflammation, preserving endothelial integrity, and limiting fibrotic amplification. These pathways appear to converge at mitochondrial homeostasis, autophagy, and barrier stability. We argue that the most useful clinical implication at present is not a fixed prescribing algorithm, but a phenotype-aware way to frame residual risk, sequence future studies, and define mechanistic endpoints for combination strategies across chronic kidney disease phenotypes. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.trsl.2026.07.008 PMID: 42480913 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest All authors have read the journal's policy on disclosure of potential conflicts of interest. The authors declare no competing interests.

Mentions Semaglutide

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

Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents.

1. Nutr Clin Pract. 2026 Oct;41(5):1318-1333. doi: 10.1002/ncp.70180. Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents. Singhani V(1), Ehsan M(2), Valencia S(1), Nadeem A(1), Moazzam E(3), Butsch WS(4)(5)(6), Garg S(1)(7). Author information: (1)Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. (2)Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. (3)Department of Internal Medicine, King Edward Medical University, Lahore, Pakistan. (4)Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. (5)Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. (6)Novo Nordisk, Copenhagen, Denmark. (7)Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation. METHODS: This narrative expert review synthesizes evidence from randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance data to characterize the incidence, mechanisms, and clinical implications of GI adverse effects across approved agents and late-stage pipeline therapies. RESULTS: Nausea, vomiting, diarrhea, and constipation are established class effects, occurring in approximately 30%-50% of patients, typically during initiation and dose escalation. These events are generally mild to moderate and manageable with dose titration and dietary modification. Mechanisms include delayed gastric emptying, central activation of emetic pathways, altered intestinal motility, and physiologic effects of rapid weight loss itself. Randomized trial data are reassuring for acute pancreatitis, with no class-level excess risk demonstrated; pharmacovigilance signals are most plausibly explained by diagnostic misclassification rather than true causal risk. Cholelithiasis shows a probable class-level association, substantially mediated by weight loss rather than direct receptor signaling. Peri-procedural data show increased residual gastric volume without confirmed aspiration events. Preliminary data on late-stage pipeline agents (retatrutide, survodutide, and cagrilintide-semaglutide) suggest a similar GI adverse event profile to approved agents, though evidence remains largely limited. CONCLUSION: GI adverse events with GLP-1-based therapies are predictable and manageable. A proactive, patient-centered approach is essential to optimize adherence, safety, and clinical outcomes as newer agents expand the therapeutic landscape. © 2026 The Author(s). Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition. DOI: 10.1002/ncp.70180 PMCID: PMC13622393 PMID: 42808923 [Indexed for MEDLINE] Conflict of interest statement: Samita Garg reports receiving an Investigator Initiated grant from Abbott, research grants with Enterra and Atmo Biosciences, and serving as a speaker/consultant for Novo Nordisk and Ardelyx. W. Scott Butsch is an employee of Novo Nordisk. All other authors have no disclosures to declare.

Mentions Retatrutide

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 endogenous ghrelin antagonist, LEAP2, accelerates puberty onset in conditions of early obesity.

1. Metabolism. 2026 Oct;183:156695. doi: 10.1016/j.metabol.2026.156695. Epub 2026 Jul 10. The endogenous ghrelin antagonist, LEAP2, accelerates puberty onset in conditions of early obesity. Torres-Granados C(1), Morris PG(2), Ruiz-Cruz M(1), Pomares O(3), Guerrero-Ruiz Y(1), Uceda-Rodríguez E(1), Rodríguez-Vázquez E(1), Aranda-Torrecillas Á(1), Garcés C(3), Gaytan F(1), Soriano-Guillén L(4), Herbison AE(2), Tena-Sempere M(5), Roa J(6). Author information: (1)Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofia, Córdoba, Spain. (2)Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. (3)Lipid Research Laboratory, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain. (4)Department of Pediatrics, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain. (5)Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofia, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 14004, Córdoba, Spain. Electronic address: fi1tesem@uco.es. (6)Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain; Hospital Universitario Reina Sofia, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 14004, Córdoba, Spain. Electronic address: b62rorij@uco.es. BACKGROUND: Puberty is a key maturational process, highly dependent on energy resources. Ghrelin, a key orexigenic hormone that is increased during conditions of energy insufficiency, has been shown to partially inhibit puberty, acting via the growth hormone secretagogue receptor (GHSR). The hepatic peptide, LEAP2, has recently emerged as a potential GHSR antagonist involved in energy homeostasis, but its eventual function in pubertal regulation remains unexplored. AIM: To investigate the role of LEAP2 in the control of pubertal maturation using an integral translational approach combining clinical data and preclinical models. METHODS: Circulating levels of LEAP2 were measured in prepubertal girls with obesity and in a preclinical model of overweight associated with advanced puberty. The impact of central acute and chronic administration of LEAP2 on various pubertal parameters was explored in female rats under distinct metabolic and hormonal conditions. The effects of LEAP2 on hypothalamic Kiss1 expression and Kiss1 neurons calcium activity were studied in rodent models. RESULTS: Circulating LEAP2 levels were elevated in prepubertal girls with obesity and in a preclinical model of overweight associated with advanced puberty. Central injection of LEAP2 increased luteinizing hormone (LH) secretion in a dose-dependent manner in peripubertal female rats, either fed ad libitum or after 24-hour fasting, a condition known to elevate circulating ghrelin. Chronic central administration of LEAP2 in prepubertal female rats significantly advanced puberty onset; a phenomenon also observed in immature females subjected to 20% food restriction. The stimulatory effect of central LEAP2 on LH secretion was associated with increased hypothalamic Kiss1 expression. Analyses in brain slices from Kiss1-GCaMP mice showed that LEAP2 could attenuate ghrelin effects on calcium activity in RP3V and ARC Kiss1 neurons, which express Ghsr, supporting a modulatory effect at the level of the Kiss1 circuitry which drives GnRH release. CONCLUSIONS: Our data provide the first evidence of the role of LEAP2 in the metabolic control of pubertal maturation, acting potentially via Kiss1 neurons. Copyrigh

Mentions Kisspeptin

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

Mentions Kisspeptin

A tea exosome-integrated self‑oxygenating cascade chitosan/oxidized alginate hydrogel for remodeling the hyperglycemic and hypoxic microenvironment in diabetic wound healing.

Mentions GHK-Cu

The neuroendocrine-appetite-mental health triangle in PMOS: Implications for GLP-1 receptor agonist therapy.

1. Neurosci Biobehav Rev. 2026 Oct;189:106846. doi: 10.1016/j.neubiorev.2026.106846. Epub 2026 Jul 8. The neuroendocrine-appetite-mental health triangle in PMOS: Implications for GLP-1 receptor agonist therapy. Xu W(1), Lu C(2), Xu J(3), Wang L(4). Author information: (1)Department of Reproduction, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, China. (2)Department of Gynecology, Changshu TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, China. (3)Department of General Medicine, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, China. Electronic address: love_jessie@126.com. (4)Department of Reproduction, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, China. Electronic address: zjgzywlh@njucm.edu.cn. Polyendocrine metabolic ovarian syndrome (PMOS) is the most prevalent endocrine disorder in women of reproductive age, yet its management remains fragmented across metabolic, reproductive, and psychological domains. This review uses a descriptive clinical framework-the "neuroendocrine-appetite-mental health triangle"-to organize existing evidence on three interacting pathogenic domains in PMOS: hypothalamic neuroendocrine dysfunction (aberrant GnRH pulsatility, central leptin resistance, and hypothalamic inflammation), appetite dysregulation and disordered eating (binge eating disorder, food addiction, and reward pathway dysfunction), and psychological comorbidities (depression, anxiety, and HPA axis hyperactivity). Within this framework, we evaluate the therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs), whose central and peripheral mechanisms may address multiple aspects of this pathology. We synthesize current evidence on their metabolic, reproductive, and emerging psychotropic effects, while providing a balanced and objective assessment of their safety profile, with particular emphasis on the unresolved questions surrounding reproductive safety, the necessity for preconception washout periods, and conflicting signals regarding psychiatric adverse events. We conclude that while GLP-1RAs show therapeutic potential for PMOS, their clinical application requires further evidence, particularly regarding reproductive safety and psychiatric effects, and should be embedded within a multidisciplinary care model that integrates metabolic, psychological, and reproductive management. Copyright © 2026 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.neubiorev.2026.106846 PMID: 42419462 [Indexed for MEDLINE]

Mentions Semaglutide

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

Real-World Effectiveness and Treatment Patterns of Tirzepatide in a Large UK Digital Health Cohort.

1. Diabetes Obes Metab. 2026 Oct;28(10):9621-9632. doi: 10.1111/dom.71067. Epub 2026 Aug 6. Real-World Effectiveness and Treatment Patterns of Tirzepatide in a Large UK Digital Health Cohort. Rosenior-Patten O(1), Lees Z(1), Rowe R(1), Hussain S(1), Ahmad E(1)(2), Brooke E(1), Dix S(1), Maybury C(1). Author information: (1)HeliosX Group, Leamington Spa, Warwickshire, UK. (2)University Hospitals of Leicester NHS Trust, Leicester, UK. BACKGROUND: Tirzepatide has demonstrated substantial weight-loss efficacy in clinical trials, but real-world evidence from routine digital prescribing remains limited. METHODS: We conducted a retrospective cohort study of adults initiating tirzepatide for obesity via a UK digital prescribing service between March 2024 and July 2025. Linked order-level prescribing data and self-reported weights were analysed to estimate percentage weight change at 3, 6, 9, and 12 months. Adherence was assessed using mean days between medication orders. A 6-month survey captured patient-reported outcomes including lifestyle changes and side effects. The primary endpoint was percentage weight change at 6 months. RESULTS: Following analysis of 630 545 eligible patients (80.3% female, mean BMI 36.1 kg/m2 [SD 5.8]), mean weight loss in those with recorded weights was -13.5% (95% CI: -13.56 to -13.51) at 6 months (n = 270 309) and -17.4% (95% CI: -17.5 to -17.3) at 12 months (n = 58 434). At 6 months, 89.9% achieved ≥ 5% weight loss and 72.1% achieved ≥ 10%. More regular ordering cadence was associated with greater weight loss, and clinically meaningful outcomes were frequently achieved without escalation beyond intermediate doses. Treatment persistence was higher among patients from less deprived areas, with 26.1% more prescription orders than those from the most deprived areas. Patients reported improvements in mobility (46.7%) and mood (45.9%), and reduced alcohol consumption (26.7%). CONCLUSIONS: Tirzepatide was associated with substantial weight loss and significant patient-reported benefits including mood and mobility improvement. Treatment continuity was a correlate of effectiveness, and maximal dose escalation was often unnecessary. These findings support the effective delivery of GLP-1 medication for the treatment of obesity via digital prescribing pathways. © 2026 HeliosX Holdings Limited. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.71067 PMID: 42560020 [Indexed for MEDLINE]

Mentions Tirzepatide

Maternal-Neonatal Metabolic Continuity and Early Postnatal HPG Axis Activity in Healthy Term Neonates.

1. Clin Endocrinol (Oxf). 2026 Oct;105(4):432-441. doi: 10.1111/cen.70193. Epub 2026 Jul 30. Maternal-Neonatal Metabolic Continuity and Early Postnatal HPG Axis Activity in Healthy Term Neonates. Koca M(1), Karaoglan M(1), Tepe NB(2), Isbilen E(3), Sahan MH(4), Disibuyuk U(4). Author information: (1)Department of Pediatric Endocrinology, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye. (2)Department of Obstetrics and Gynecology, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye. (3)Department of Medical Biochemistry, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye. (4)Department of Radiology, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye. BACKGROUND: Leptin integrates metabolic and reproductive signaling later in life; however, whether maternal metabolic cues influence early neonatal hypothalamic-pituitary-gonadal (HPG) axis activity remains unclear. OBJECTIVE: To evaluate associations between maternal metabolic markers and early neonatal reproductive hormone activity. METHODS: Forty healthy term neonates (20 males) were prospectively evaluated. Maternal venous blood samples were collected at delivery, and neonatal blood samples were obtained within the first 24 h after birth. Maternal and neonatal adipokines and reproductive hormones were analyzed using correlation and simplified multivariable regression analyses. False discovery rate (FDR) correction using the Benjamini-Hochberg procedure was applied for multiple testing. RESULTS: Maternal leptin was positively associated with neonatal leptin concentrations (r = 0.52, p = 0.001; adjusted β = 0.47, p = 0.001), supporting maternal-neonatal metabolic continuity. However, maternal leptin was not significantly associated with neonatal LH concentrations (β = 0.00009, p = 0.347). Sex remained the strongest independent predictor of neonatal LH levels (β = 1.21, p = 0.011). Neonatal leptin was positively associated with triceps skinfold thickness (β = 1503.14, p = 0.034). Most exploratory associations did not remain statistically significant after FDR correction. CONCLUSIONS: Maternal metabolic markers were associated with neonatal metabolic parameters but were not strongly associated with early neonatal gonadotropin levels in this cohort. Larger longitudinal studies are required to clarify potential interactions between metabolic and reproductive pathways during later phases of mini-puberty. © 2026 John Wiley & Sons Ltd. DOI: 10.1111/cen.70193 PMCID: PMC13532110 PMID: 42529951 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Mentions Kisspeptin

GLP-1 Receptor Agonist Therapy for Obesity Under Japan's Optimal Use Guideline: A Prospective Real-World Study of Lifestyle Pre-Treatment, Time-Limited Treatment Cap, and Post-Cessation Regain.

1. Diabetes Obes Metab. 2026 Oct;28(10):9595-9606. doi: 10.1111/dom.71190. Epub 2026 Aug 4. GLP-1 Receptor Agonist Therapy for Obesity Under Japan's Optimal Use Guideline: A Prospective Real-World Study of Lifestyle Pre-Treatment, Time-Limited Treatment Cap, and Post-Cessation Regain. Inamine S(1), Uesato Y(1). Author information: (1)Center for Metabolic and Bariatric Surgery, Ohama Daiichi Hospital, Naha, Okinawa, Japan. AIMS: Japan's optimal use guideline restricts insurance-reimbursed GLP-1 receptor agonist (GLP-1 RA) therapy for obesity to patients completing a mandatory 6-month lifestyle intervention, caps treatment at 68 weeks (semaglutide 2.4 mg) or 72 weeks (tirzepatide), and mandates subsequent washout. We evaluated the clinical implications of this regulated program in a real-world cohort of patients with obesity treated with semaglutide or tirzepatide, with particular attention to pre-treatment weight change during the mandated lifestyle phase, on-treatment response, and post-cessation weight regain. MATERIALS AND METHODS: We prospectively followed 104 patients with obesity without type 2 diabetes (45 primary, 59 post-metabolic/bariatric-surgery rescue) treated with semaglutide (n = 43) or tirzepatide (n = 61) under Japan's optimal use guideline. Both cohorts qualified for GLP-1 RA under the same insurance eligibility criteria (BMI ≥ 27 kg/m2 with obesity-related comorbidities). Body weight was recorded bimonthly from 6 months before drug initiation through the post-cessation washout phase. Outcomes included percent body weight change from baseline and rates of weight loss and regain across phases. RESULTS: During the mandated lifestyle phase, the rescue cohort gained weight (+2.28 ± 4.16 kg; 69% gained weight), while the primary cohort remained essentially stable (-0.65 ± 5.51 kg; p = 0.004). Once GLP-1 RA was initiated, % body weight change trajectories were comparable between cohorts from month 4 onward (month 6: -11.8% vs. -10.8%, p = 0.57). Aggregate % body weight change reached a partial plateau by months 10-14 (-16.3%, -16.1%, -15.5%) and was -16.0% at the treatment endpoint (month 16, n = 30, all semaglutide-treated). After mandated cessation, 95% (21/22) of patients regained weight by 2 months, and 83% (10/12) by 6 months. Indexed to month -6, mean change reverted from -14.4% at month 16 to -7.0% at month 22, indicating substantial loss of achieved treatment benefit. CONCLUSIONS: Under Japan's current regulatory framework, GLP-1 RAs produced comparable weight loss in primary and rescue cohorts sharing the same eligibility criteria. Phase-specific observations-pre-treatment weight gain in the rescue cohort and achieved treatment effect that reverted rapidly after mandated cessation-provide a real-world basis for examining whether mandated treatment cessation is compatible with the chronic nature of obesity. © 2026 John Wiley & Sons Ltd. DOI: 10.1111/dom.71190 PMID: 42552238 [Indexed for MEDLINE]

Mentions Tirzepatide

SURPASS-CVOT and the Emerging Biology of Cardiometabolic Benefit.

1. Diabetes Obes Metab. 2026 Oct;28(10):8753-8756. doi: 10.1111/dom.71175. Epub 2026 Jul 30. SURPASS-CVOT and the Emerging Biology of Cardiometabolic Benefit. Corrao S(1)(2), Cosentino F(3), Federici M(4). Author information: (1)Department of Clinical Medicine, Unit of Internal Medicine, National Relevance and High Specialization Hospital Trust ARNAS Civico Di Cristina Benfratelli, Palermo, Italy. (2)Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy. (3)Department of Medicine, Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. (4)Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. DOI: 10.1111/dom.71175 PMID: 42530340

Mentions Tirzepatide

Monosynaptic GABAergic projections from a subset of suprachiasmatic nucleus neuromedin S neurons suppress preoptic area kisspeptin neuron firing in female mice.

1. J Neurosci. 2026 Sep 29:e2277252026. doi: 10.1523/JNEUROSCI.2277-25.2026. Online ahead of print. Monosynaptic GABAergic projections from a subset of suprachiasmatic nucleus neuromedin S neurons suppress preoptic area kisspeptin neuron firing in female mice. Abdulmajeed WI(1), Neuman PN(1), Jamieson BB(2), Thomas SX(2), Rim Y(2), Novak AG(1), Lehman MN(1), Campbell RE(2), Piet R(3). Author information: (1)Brain Health Research Institute and Department of Biological Sciences, Kent State University, Kent, OH 44242, United States. (2)Centre for Neuroendocrinology and Department of Physiology, University of Otago, Dunedin 9054, New Zealand. (3)Brain Health Research Institute and Department of Biological Sciences, Kent State University, Kent, OH 44242, United States; rpiet@kent.edu. Neural control of ovulation is critical for reproductive success. In spontaneous ovulators, this is achieved through hypothalamic neural circuits relaying ovarian follicle maturity cues to gonadotropin-releasing hormone (GnRH)-secreting neurons to drive the preovulatory luteinizing hormone (LH) surge. Within these circuits, kisspeptin-expressing neurons in the rostral periventricular region of the third ventricle (RP3VKISS1 neurons) are thought to stimulate GnRH neurons for the LH surge. In female rodents, the central circadian clock in the suprachiasmatic nucleus (SCN) regulates the timing of RP3VKISS1 and GnRH neuron activation, coordinating neuroendocrine control of ovulation and behavior. However, the mechanisms thereof are not fully understood. Here, we examined the potential regulation of RP3VKISS1 neuron activity by neuromedin S (NMS)-expressing SCN neurons - a neuronal population essential for circadian rhythms - using anatomical tract-tracing, optogenetics and electrophysiology in female mice. Our observations indicate that a subset of SCNNMS neurons, likely distinct from the canonical arginine vasopressin and vasoactive intestinal peptide SCN populations, projects to RP3VKISS1 neurons. Optogenetic activation of these projections evokes monosynaptic release of GABA onto ≈ 75% of RP3VKISS1 neurons. Whereas exogenous NMS only moderately affected RP3VKISS1 neuron activity, with no effect on firing and altered intracellular calcium concentration in subsets of cells, GABA release from SCNNMS fibers in the RP3V potently suppressed KISS1 neuron action potential firing, through activation of GABAA receptors. Together, these findings reveal additional complexity in the regulation of the GnRH neuronal network by the central circadian clock. Potential implications of these observations for the timing of the LH surge are discussed.Significance statement In females of multiple species, neuroendocrine circuits in the hypothalamus, which include preoptic area kisspeptin neurons and converge on the gonadotropin-releasing hormone (GnRH) neurons, integrate information about gonadal state with circadian cues to triggers ovulation. The mechanisms though which the central circadian clock in the suprachiasmatic nucleus (SCN) relays timing cues to the GnRH neuronal network are, however, incompletely understood. Using anatomical and functional approaches, we found that a previously unsuspected subpopulation of SCN neurons projects to preoptic area kisspeptin neurons and, unexpectedly, suppresses these cells' activity through the release of the inhibitory neurotransmitter GABA. Our observations suggest that control of activity within the GnRH neuronal network for ovulation might extend beyond modulation by canonical SCN neuropeptides. Copyright © 2026 the authors. DOI: 10.1523/JNEUROSCI.2277-25.2026 PMID: 42810967

Mentions Kisspeptin

Physiopathology of PMOS from a Neuroendocrine Perspective.

1. Physiology (Bethesda). 2026 Sep 29. doi: 10.1152/physiol.00034.2026. Online ahead of print. Physiopathology of PMOS from a Neuroendocrine Perspective. Cotellessa L(1), Bongiovanni S(1), Giacobini P(1). Author information: (1)Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, UMR-S 1172, Lille, France. Polyendocrine metabolic ovarian syndrome (PMOS) is the most common reproductive and cardiometabolic disorder in women of reproductive age. Once viewed as primarily an ovarian disease, it is now recognized as a neuroendocrine-metabolic disorder driven by dysregulation of the hypothalamic-pituitary-gonadal axis. A central feature of the syndrome is increased gonadotropin releasing hormone (GnRH) pulsatility, which drives excess luteinizing hormone (LH) secretion, disrupts the LH/follicle stimulating hormone (FSH) balance, and promotes ovarian androgen excess and anovulation. Hypothalamic Kisspeptin neurons, the principal regulators of GnRH pulse generation, show altered activity and impaired steroid feedback sensitivity. Anti-Müllerian hormone (AMH) has emerged as an ovary-to-brain signal that directly stimulates GnRH neurons and remodels the neuroendocrine interface, amplifying LH secretion and perpetuating reproductive dysfunction. Developmental programming, through interactions among genetic, environmental, and epigenetic factors, may durably alter the organization and function of hypothalamic circuits, predisposing to neuroendocrine dysfunction later in life. In parallel, metabolic dysfunction, including insulin resistance and adipose tissue dysfunction, can interact bidirectionally with reproductive and neuroendocrine pathways, reinforcing hyperandrogenism and perturbing both reproductive and energy homeostasis. This review summarizes current knowledge of the neuroendocrine mechanisms underlying PMOS and discusses emerging targeted therapies that may offer disease-modifying approaches for this prevalent and heterogeneous disorder. DOI: 10.1152/physiol.00034.2026 PMID: 42809619

Mentions Kisspeptin

Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.

1. N Engl J Med. 2026 Sep 29. doi: 10.1056/NEJMoa2604169. Online ahead of print. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. Jastreboff AM(1)(2)(3), Kaplan LM(4), Davies MJ(5)(6), Wilding JPH(7), Ahmad NN(8), Murray M(8), Du Y(8), Makarova N(8), Giblin K(8), Schloot NC(8), Wang Y(8); TRIUMPH-1 Investigators. Author information: (1)Department of Medicine (Endocrinology and Metabolism), Yale University School of Medicine, New Haven, CT. (2)Department of Pediatrics (Pediatric Endocrinology), Yale University School of Medicine, New Haven, CT. (3)Yale Obesity Research Center (Y-Weight), Yale University School of Medicine, New Haven, CT. (4)Obesity and Metabolism Institute, Boston. (5)Diabetes Research Centre, University of Leicester, Leicester, United Kingdom. (6)NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom. (7)Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom. (8)Eli Lilly, Indianapolis. BACKGROUND: Retatrutide is a triple-receptor agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors. METHODS: In this phase 3, randomized, double-blind trial, we assigned adults with obesity without diabetes to receive a once-weekly subcutaneous injection of retatrutide (at a dose of 4 mg, 9 mg, or 12 mg) or placebo for 80 weeks. Primary outcomes (evaluated in the 9-mg and 12-mg groups each vs. placebo) were the percent change in body weight and the change in the WOMAC pain score (ranging from 1 to 10, with higher scores indicating worse pain) in the subgroup of 574 participants with knee osteoarthritis and the change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea. For weight-related end points, intercurrent events were handled by a treatment-regimen estimand (intention-to-treat [ITT]). For end points in participants with knee osteoarthritis or obstructive sleep apnea, a hybrid-treatment estimand was applied, with a hypothetical strategy for intercurrent events suggesting treatment failure; ITT results are also reported. RESULTS: A total of 2339 participants underwent randomization. The mean percent change in body weight in the retatrutide groups was -17.6% (4-mg dose), -23.7% (9-mg dose), and -25.0% (12-mg dose) versus -3.9% in the placebo group (differences, -19.8 and -21.0 percentage points, respectively; P<0.001 for both comparisons). Among the participants with knee osteoarthritis, the corresponding changes in the pain score in the retatrutide groups for the hybrid estimand were -3.2, -3.5, and -3.6 versus -1.9 with placebo (differences, -1.6 and -1.8 points; both P<0.001); the corresponding changes for the ITT estimand were -3.4, -3.9, and -4.1 versus -2.5 with placebo (differences, -1.4 and -1.6 points; both P<0.001). Among the participants with obstructive sleep apnea, the corresponding changes in events per hour in the retatrutide groups for the hybrid-treatment estimand were -22.9, -34.3, and 31.7 versus -9.9 (differences, -24.4 and -21.9; both P<0.001); the corresponding changes for the ITT estimand were -22.8, -34.3, and -32.1 versus -9.6 (differences, -24.7 and -22.5; both P<0.001). The most common adverse events were gastrointestinal. CONCLUSIONS: In adults with obesity, retatrutide resulted in significant weight reduction, reduced pain in participants with knee osteoarthritis, and reduced apnea-hypopnea events in participants with obstructive sleep apnea. (Funded by Eli Lilly; TRIUMPH-1 ClinicalTrials.gov number, NCT05929066.). Copyright © 2026 Massachusetts Medical Society. DOI: 10.1056/NEJMoa2604169 PMID: 42814954

Mentions Retatrutide

Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis.

1. Diabetes Obes Metab. 2026 Sep 29. doi: 10.1111/dom.71400. Online ahead of print. Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis. Amjad MM(1), Khan MM(1), Sarwar F(2), Ali A(3), Ali M(4), Bakhash F(3), Abid H(2), Ibrahim F(5), Mustafa K(5), Ali DE(6), Fayyaz MMN(1), Hassan H(7), Mian SM(1), Yaseen M(8), Qamar I(9), Khan AH(10), Ullah S(11), Khan BW(1). Author information: (1)Khyber Medical College, Peshawar, Pakistan. (2)Watim Medical and Dental College, Rawat, Pakistan. (3)Federal Medical College, Islamabad, Pakistan. (4)Rawalpindi Medical University, Punjab, Pakistan. (5)Isra University, Hyderabad, Pakistan. (6)Shahida Islam Medical and Dental College, Lodhran, Pakistan. (7)Khyber Girls Medical College, Peshawar, Pakistan. (8)Khyber Teaching Hospital, Peshawar, Pakistan. (9)Faculty of Medicine, Spinghar University, Kabul, Afghanistan. (10)Shifa College of Medicine, Islamabad, Pakistan. (11)Saidu Medical College, Swat, Pakistan. BACKGROUND: Dual glucagon-like peptide-1/glucagon receptor (GLP-1/GCGR) agonists represent a novel obesity treatment class, but existing meta-analyses often conflate them with GIP-containing agents (tirzepatide, retatrutide) or restrict analysis to one or two drugs, leaving class-specific efficacy and safety incompletely characterized. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Scopus and ClinicalTrials.gov through 20 July 2026 for randomized controlled trials of mazdutide, survodutide, cotadutide, and efinopegdutide in adults with overweight/obesity (PROSPERO CRD420261456447). Random-effects meta-analysis pooled mean differences (MDs) and risk ratios (RRs) with 95% CIs; heterogeneity, subgroup, sensitivity, GRADE and publication bias analyses were performed. RESULTS: Nineteen RCTs were included. Dual agonists significantly reduced absolute body weight (MD: -6.65 kg, moderate certainty), relative weight (MD: -7.15%), and increased likelihood of ≥ 5% weight loss (RR: 4.75, low certainty), with mazdutide and survodutide showing the largest effects. Significant improvements occurred in HbA1c, BMI, waist circumference, systolic blood pressure and triglycerides. Any adverse events were more frequent with dual agonists (RR: 1.16), while serious adverse events did not differ from controls (RR: 0.90, high certainty). CONCLUSION: Dual GLP-1/GCGR agonists produce meaningful weight loss and metabolic improvements with acceptable short-term safety, though longer head-to-head trials are needed to confirm durability and cardiovascular safety. © 2026 John Wiley & Sons Ltd. DOI: 10.1111/dom.71400 PMID: 42811393

Mentions Retatrutide

Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.

1. Lancet. 2026 Sep 29:S0140-6736(26)01861-1. doi: 10.1016/S0140-6736(26)01861-1. Online ahead of print. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Bellido V(1), le Roux CW(2), Ekinci EI(3), Bjornstad P(4), Frias JP(5), Giblin K(6), Eyde S(6), Park SY(6), Ferro J(6), Johnson C(6), Taylor A(6). Author information: (1)Department of Endocrinology and Nutrition, Virgen del Rocío University Hospital, Seville, Spain. Electronic address: virginiabellido@gmail.com. (2)School of Medicine, University College Dublin, Dublin, Ireland; Diabetes Research Centre, Ulster University, Coleraine, UK. (3)Australian Centre for Accelerating Diabetes Innovations and Department of Medicine, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia; Centre for Research and Education in Diabetes and Obesity and Department of Endocrinology Austin Health, Melbourne, VIC, Australia. (4)University of Washington School of Medicine, Seattle, WA, USA. (5)Los Angeles Institute for Metabolic Research, Los Angeles, CA, USA. (6)Eli Lilly and Company, Indianapolis, IN, USA. BACKGROUND: Retatrutide is an agonist of GIP, GLP-1, and glucagon receptors, and is currently under investigation for the treatment of obesity, type 2 diabetes, and other comorbidities, including knee osteoarthritis and obstructive sleep apnoea. We aimed to assess the efficacy and safety of retatrutide in adults with obesity and type 2 diabetes. METHODS: TRIUMPH-2 was a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial conducted at 92 medical and research centres and hospitals across eight countries. We enrolled adults (aged ≥18 years) with a BMI of 27 kg/m2 or higher and type 2 diabetes (glycated haemoglobin [HbA1c] 6·5-10·5%) on stable treatment for type 2 diabetes for at least 90 days before screening (diet or exercise alone, or up to three oral glucose-lowering medications), and a history of at least one self-reported unsuccessful dietary effort to reduce bodyweight. Participants were randomly assigned (1:1:1:1), using an interactive web-response system, to receive once-weekly subcutaneous injections (self-administered) of placebo or retatrutide 4 mg, 9 mg, or 12 mg. The primary endpoint was the percentage change from baseline to week 80 in bodyweight for the retatrutide 9 mg and 12 mg doses versus placebo, with 4 mg versus placebo a key secondary endpoint. Efficacy analyses included all randomly assigned participants, with missing data imputed with a primary multiple imputation strategy for the treatment regimen estimand. Safety analyses included all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05929079 (completed). FINDINGS: Between July 11, 2023, and Nov 1, 2024, 2047 participants were screened, and 1152 (mean age 55·1 years [SD 10·8], 554 [48%] females and 598 [52%] males, and 672 [58%] of White ethnicity) were randomly assigned to retatrutide 4 mg (n=292), 9 mg (n=284), or 12 mg (n=287), or placebo (n=289). At baseline, the mean BMI was 38·2 kg/m2 (SD 7·4), mean HbA1c was 7·71% (1·07), median duration of obesity was 21 years (IQR 11-31), and median duration of diabetes was 5·6 years (2·6-10·4). At baseline, 1055 (92%) of 1152 participants were on any oral glucose-lowering medication, including biguanides, SGLT2 inhibitors, sulfonylureas, and other oral glucose-lowering medications. Of 1152 participants, 965 (84%) completed the study drug. For the treatment regimen estimand, the mean percentage change from baseline in bodyweight at week 80 was -11·9% (SE 0·6) with retatrutide 4 mg, -16·8% (0·7) with retatrutide 9 mg, -18·8% (0·7) with retatrutide 12 mg, and -5·1% (0·7) with placebo. Estimated treatment differences compared with placebo for percentage change in bodyweight were -6·9% (95% CI -8·7 to -5·1) with

Mentions Retatrutide

Kisspeptin-10 Alleviates Obesity-induced Testicular Oxidative Stress and Mitochondrial Dysfunction via Modulation of Mitophagy and Autophagy Signaling.

1. Reprod Sci. 2026 Sep 28. doi: 10.1007/s43032-026-02211-7. Online ahead of print. Kisspeptin-10 Alleviates Obesity-induced Testicular Oxidative Stress and Mitochondrial Dysfunction via Modulation of Mitophagy and Autophagy Signaling. Arkalı G(1), Çay M(2), Güler Ekmen E(2), Acısu TC(3), Fi̇ri̇k M(4), Toz A(4), Yüce A(2), Aksakal M(2). Author information: (1)Department of Physiology, Faculty of Veterinary Medicine, Fırat University, Elazığ, Türkiye. garkali@firat.edu.tr. (2)Department of Physiology, Faculty of Veterinary Medicine, Fırat University, Elazığ, Türkiye. (3)Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Fırat University, Elazığ, Türkiye. (4)Institute of Health Sciences, Veterinary Physiology Doctorate Program, Fırat University, Elazığ, Türkiye. Obesity impairs male reproductive function via oxidative stress and mitochondrial dysfunction. Kisspeptin-10 may regulate redox balance and mitochondrial homeostasis, but its role in obesity-related testicular dysfunction remains unclear. This study aimed to investigate whether Kisspeptin-10 ameliorates obesity-induced testicular oxidative stress and sperm dysfunction, with particular emphasis on mitophagy, autophagy, and apoptosis-related pathways. Forty male Sprague Dawley rats were divided into four groups: Control, Obesity, Kisspeptin-10, and Obesity+Kisspeptin-10. Obesity was induced by feeding rats a high-fat diet (60% kcal from fat) for 12 weeks. At the end of week 12, rats with a Lee index ≥ 300 were considered obese. During the subsequent 4-week treatment period, the Obesity and Obesity+Kisspeptin-10 groups continued to receive the high-fat diet, whereas the Control and Kisspeptin-10 groups continued to receive the standard diet. Kisspeptin-10 (50 nmol/kg, i.p.) was administered to both the Kisspeptin-10 and Obesity+Kisspeptin-10 groups from week 13 to week 16. Oxidative stress markers in the testes, sperm parameters, sperm mitochondrial membrane potential (MMP), and sperm deoxyribonucleic acid (DNA) integrity were assessed; in addition, protein expression levels of markers for mitophagy, autophagy, and apoptosis were evaluated. Obesity impaired antioxidant capacity, sperm quality, mitochondrial function, and reproductive organ weight, while increasing lipid peroxidation and sperm abnormalities. Kisspeptin-10 reduced oxidative stress by lowering malondialdehyde (MDA) and increasing glutathione (GSH) levels, improved sperm motility and concentration, reduced tail abnormal sperm ratio, showed a non-significant tendency toward partial restoration of mitochondrial function, decreased DNA damage, and increased prostate weight. It was also associated with increased expression of the mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and Prohibitin 2 (PHB2), and increased Beclin-1 expression, with no significant effects on Parkin, Microtubule-associated protein 1 light chain 3-II (LC3-II), or apoptosis-related proteins. Kisspeptin-10 may alleviate obesity-induced testicular dysfunction, potentially through modulation of redox balance and mitochondrial quality-control mechanisms, including changes in mitophagy- and autophagy-related protein expression. Although these findings suggest that Kisspeptin-10 is a promising candidate for the treatment of obesity-related male infertility, its effects on downstream autophagy-related signaling and apoptosis appear to be limited. © 2026. The Author(s), under exclusive licence to Society for Reproductive Investigation. DOI: 10.1007/s43032-026-02211-7 PMID: 42806235 Conflict of interest statement: Declarations. Ethics Statement: The study was approved by the Fırat University Animal Ethics Committee (Protocol No: 2022/13; Dated 03.08.2022). Consent for Publication: Not applicable. Consent to Participate: Not applicable. Conflicts of interest: The authors declare that there are no conflicts of interest.

Mentions Kisspeptin

New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus.

1. Diabetes Ther. 2026 Sep 28. doi: 10.1007/s13300-026-01921-0. Online ahead of print. New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus. Panou T(1), Gouveri E(1), Popovic DS(2)(3), Papanas N(4). Author information: (1)Second Department of Internal Medicine, Diabetes Centre, Democritus University of Thrace, Alexandroupolis, Greece. (2)Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Novi Sad, Serbia. (3)Medical Faculty, University of Novi Sad, Novi Sad, Serbia. (4)Second Department of Internal Medicine, Diabetes Centre, Democritus University of Thrace, Alexandroupolis, Greece. papanasnikos@yahoo.gr. INTRODUCTION: Type 2 diabetes mellitus (T2DM) and obesity represent two major global health challenges. Amylin-based agonists offer a promising perspective. Three frontrunner agents of this class are increasingly being investigated: zenagamtide, eloralintide and cagrilintide-semaglutide (CagriSema). METHODS: A search in PubMed/MEDLINE, Scopus and Google Scholar was conducted with the use of appropriate keywords until June 2026 for this narrative review. RESULTS: Zenagamtide (formerly known as amycretin), a unimolecular long-lasting amylin and glucagon-like peptide-1 receptor (GLP-1R) co-agonist, achieved weight loss up to 13.1% (phase 1 study, 85 days) in obesity trials as an oral formulation and up to 24.3% (phase 1b/2a study, 36 weeks) as a subcutaneous formulation. Moreover, eloralintide, a long-acting mostly amylin type 1 receptor (AMY1R) agonist, achieved weight loss up to 20.1% (phase 2 study, 48 weeks), and CagriSema resulted in weight loss up to 22.7% (phase 3a study, 68 weeks). All these agents reduced body mass index (BMI) and waist circumference (WC). In T2DM, CagriSema reduced glycated haemoglobin (HbA1c) by up to 2.0% (trial product estimand, phase 3a study, 68 weeks) and is currently the most well-studied agent in T2DM. In treatment-naïve people with T2DM, this agent has been successfully used, leading even to T2DM remission in approximately one out of two CagriSema users (phase 3a, 40 weeks). In individuals with T2DM receiving basal insulin, it reduced insulin dose by 20 units compared with the control arm (phase 3a, 40 weeks). The safety profile of amycretin and CagriSema is overall consistent with that of glucagon-like peptide 1 receptor agonists (GLP-1RAs). Preliminary evidence suggests that eloralintide, as an AMY1R monoagonist, was associated with a distinct adverse events profile, including fatigue, headache and appetite loss. CONCLUSIONS: These agents hold therapeutic potential in the management of both T2DM and obesity, as shown by preliminary clinical trial outcomes. Further trials are now needed to validate them in clinical practice. © 2026. The Author(s). DOI: 10.1007/s13300-026-01921-0 PMID: 42803913 Conflict of interest statement: Declarations. Conflict of Interest: Theodoros Panou has nothing to disclose. Evanthia Gouveri has attended conferences sponsored by Berlin-Chemie, Sanofi, AstraZeneca, Novo Nordisk, Lilly and Boehringer Ingelheim; received speaker honoraria by Boehringer Ingelheim, Sanofi and Menarini. Djordje S. Popovic declares associations with Abbott, Alkaloid, Amicus, AstraZeneca, Boehringer Ingelheim, Berlin-Chemie, Eli Lilly, Galenika, Krka, Merck, Novo Nordisk, PharmaSwiss, Sanofi-Aventis, Servier, Viatris, and Wörwag Pharma. Nikolaos Papanas has been an advisory board member of AstraZeneca, Bayer, Boehringer Ingelheim, Menarini, MSD, Novo Nordisk, Pfizer, Takeda and TrigoCare International; has participated in sponsored studies by AstraZeneca, Eli Lilly, GSK, MSD, Novo Nordisk, Novartis and Sanofi-Aventis; has received honoraria as a speaker for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elpen, KRKA, Menarini, MSD, Mylan, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis and Vianex; and has attended conferences sponsored by TrigoCare International, Eli Lilly,

Mentions CagriSema

Current perspectives on the pharmacologic treatment of boys and adolescents with congenital hypogonadotropic hypogonadism.

1. Expert Opin Pharmacother. 2026 Sep 27. doi: 10.1080/14656566.2026.2741490. Online ahead of print. Current perspectives on the pharmacologic treatment of boys and adolescents with congenital hypogonadotropic hypogonadism. Rey RA(1), Grinspon RP(1). Author information: (1)Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET - FEI - División de Endocrinología, Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina. INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) in boys and adolescents requires age- and developmentally appropriate treatment to address androgen deficiency, testicular maturation, pubertal development, and ultimately fertility. The dynamic physiology of the hypothalamic-pituitary-testicular axis necessitates therapeutic strategies that differ substantially between infancy and adolescence. AREAS COVERED: This review examines current pharmacological approaches to CHH across childhood and adolescence, focusing on testosterone, dihydrotestosterone, gonadotropins, pulsatile gonadotropin-releasing hormone (GnRH), and emerging kisspeptin-based therapies. Literature search was made in Pubmed for the period 1990-2026. EXPERT OPINION: Testosterone remains the standard approach for for inducing secondary sexual characteristics and effectively promotes virilization, growth, bone accrual, and psychosocial well-being, but does not induce testicular maturation or spermatogenesis. Gonadotropin therapy, particularly sequential follicle-stimulating hormone followed by luteinizing hormone or human chorionic gonadotropin, more directly promotes Sertoli-cell maturation, testicular growth, and spermatogenesis. Early gonadotropin treatment in infancy can reproduce several features of physiological mini-puberty, although its long-term reproductive benefits remain uncertain. Pulsatile GnRH is physiologically attractive but limited by availability and treatment complexity, whereas kisspeptin remains investigational. Treatment should be individualized according to developmental stage, testicular phenotype, therapeutic goals, anticipated fertility, treatment burden, and patient preferences. Major unmet needs include pediatric-specific formulations, optimized regimens, comparative trials, biomarkers of treatment response, and long-term reproductive outcomes. DOI: 10.1080/14656566.2026.2741490 PMID: 42802581

Mentions Kisspeptin

Implications of neuropeptide Y in the regulation of testicular functions in wall lizard, Hemidactylus flaviviridis.

1. Comp Biochem Physiol A Mol Integr Physiol. 2026 Sep 26:112079. doi: 10.1016/j.cbpa.2026.112079. Online ahead of print. Implications of neuropeptide Y in the regulation of testicular functions in wall lizard, Hemidactylus flaviviridis. Chauhan V(1), Rai U(2), Tripathy M(3), Kumar S(4). Author information: (1)Department of Zoology, University of Delhi, Delhi 110007, India; Zakir Husain Delhi College, University of Delhi, Delhi 110002, India. (2)University of Jammu, Jammu and Kashmir 180006, India. (3)Department of Zoology, University of Delhi, Delhi 110007, India. Electronic address: mtripathy@zoology.du.ac.in. (4)Zakir Husain Delhi College, University of Delhi, Delhi 110002, India. Electronic address: skumar.zoology@zh.du.ac.in. The testicular functions of neuropeptide Y are largely unexplored in non-mammalian vertebrates as the few reports available remain restricted to fishes. Current research work reveals the testicular presence of npy and npyr in Hemidactylus flaviviridis and its variation in expression depending upon reproductive phases, marking the first documentation of such findings in reptilian species. Expression analysis of npy/npyr across different reproductive phases showed peak levels of both ligand and receptor during the recrudescent period, while the lowest expression occurred in regression. The investigation also examined the influence of NPY on markers of testicular spermatogenesis and steroidogenesis in H. flaviviridis. The in vitro exposure of wall lizard testes to NPY during recrudescent phase stimulated bcl 2, while simultaneously reduced caspase 3. NPY treatment also stimulated testicular expression of scf, c-kit, pcna, bmp-15 and gdf-9, along with gonadotropin receptor (fshr), and sex-steroid receptors (er-α, er-β, and ar). Further, NPY elevated star expression and promoted testosterone synthesis in wall lizard. Regarding the regulation of testicular npy and its receptor, npyr the expression of both ligand and its receptor was upregulated by the neuropeptide, kisspeptin, adipokines like leptin and nesfatin-1, and sex steroids such as DHT, and E2, while they were suppressed by the gonadotropin, FSH and the neuropeptide, substance P. Overall, this investigation provides a detailed documentation of the presence, phase-specific pattern of expression, role, and hormonal regulation of NPY and its receptor in wall lizard testes. Copyright © 2026. Published by Elsevier Inc. DOI: 10.1016/j.cbpa.2026.112079 PMID: 42800552 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

Permeation behaviour of cosmetic actives into the human stratum corneum.

Mentions Matrixyl 3000

BPC 157 in Rodent Ischemia-Reperfusion Injury: A Critical Review of Preclinical Evidence.

Mentions BPC-157

Orforglipron: An Oral GLP-1 Receptor Agonist for Obesity Treatment.

1. Ann Pharmacother. 2026 Sep 18:10600280261486055. doi: 10.1177/10600280261486055. Online ahead of print. Orforglipron: An Oral GLP-1 Receptor Agonist for Obesity Treatment. Wietholter JP(1), Terpening CM(2). Author information: (1)Department of Clinical Pharmacy, West Virginia University School of Pharmacy, Morgantown, USA. (2)Department of Clinical Pharmacy, West Virginia University School of Pharmacy, Charleston, USA. OBJECTIVE: To describe the properties of a newly approved oral glucagon-like peptide-1 receptor agonist for the treatment of obesity. DATA SOURCES: A literature search of MEDLINE and SCOPUS was performed without date range exclusions using the search terms orforglipron and obesity. Additional articles were identified from review of clinical trial bibliographies and product monograph. STUDY SELECTION AND DATA EXTRACTION: Two phase 1 studies in healthy individuals and in patients with type 2 diabetes mellitus and 4 phase 2/3 clinical trials specifically evaluating orforglipron use for obesity were identified for analysis, using no date exclusion criteria. DATA SYNTHESIS: Orforglipron was evaluated in 4 phase 2/3 trials regarding its efficacy for weight loss. These trials showed a mean 7.1% to 10.6% placebo-adjusted weight reduction with orforglipron. Adverse events seen with its use were primarily gastrointestinal.Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs:Orforglipron provides an oral weight management option that is potentially more effective than liraglutide, similarly effective compared with semaglutide, and less effective than tirzepatide. As a non-injectable option that does not require strict oral administration parameters, orforglipron has advantages in certain patient populations. CONCLUSIONS: Orforglipron is a potentially useful addition for the treatment of obesity, but it still requires additional data on efficacy in treatment of obesity-related comorbidities for full comparison. DOI: 10.1177/10600280261486055 PMID: 42760621

Mentions Orforglipron

Predicting the Long-Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial.

1. Diabetes Obes Metab. 2026 Sep 17. doi: 10.1111/dom.71322. Online ahead of print. Predicting the Long-Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN-1 Trial. Shinde S(1), Kahles F(2), Vasileva-Metodiev S(1), Griffin R(1), Liu-Seifert H(1), Lebrec J(3), Xavier NA(1), Li R(1), Klise SR(1), Singh A(1), Aberle J(4). Author information: (1)Eli Lilly and Company, Indianapolis, Indiana, USA. (2)Department of Cardiology, Angiology and Intensive Care Medicine, University Hospital RWTH Aachen, Aachen, Germany. (3)HaaPACS GmbH, Schriesheim, Germany. (4)University Medical Center Hamburg-Eppendorf, Hamburg, Germany. OBJECTIVE: To assess change in long-term predicted 10-year cardiometabolic risk (Type 2 diabetes [T2D] and cardiovascular disease [CVD]) in adults with overweight or obesity without T2D. METHODS: This post hoc analysis used data from ATTAIN-1, a Phase 3 trial in adults (≥ 18 years) with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2 with ≥ 1 obesity-related complication) without T2D. Participants received orforglipron 5.5 mg, 9 mg, or 17.2 mg, or placebo for 72 weeks. Changes in predicted risk from baseline to 72 weeks were assessed using three validated risk prediction engines: Cardiometabolic Disease Staging (T2D risk), Framingham (total CVD risk), and PREVENT (total CVD, ASCVD, and HF risk). Mixed models for repeated measures compared change from baseline risk scores between groups. RESULTS: At week 72, mean relative reduction from baseline (median baseline scores: 16.0%-17.3%) in T2D risk score was significantly greater with orforglipron than placebo (-48.6% to -59.4% vs. -10.5%; p < 0.0001; HR-range 0.43-0.55). Using Framingham, at week 72, orforglipron was associated with a significant decrease in mean absolute change in total CVD risk vs placebo (-0.6% to -1.00% vs. +0.6%; p < 0.0001; HR range: 0.82-0.87). Similarly, at week 72, orforglipron was associated with reduced predicted ASCVD, HF, and total CVD risks compared to placebo, assessed using PREVENT (p < 0.0001). CONCLUSIONS: In this post hoc analysis, once-daily oral orforglipron was associated with statistically significant improvements in predicted 10-year risk of incident T2D and CVD compared with placebo over 72 weeks using three validated risk prediction models. TRIAL REGISTRATION: ATTAIN-1: NCT05869903. © 2026 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.71322 PMID: 42750540

Mentions Orforglipron

Preferences for Obesity Medications Among People With Overweight or Obesity in the United States: A Discrete-Choice Experiment (OPTIC).

1. Diabetes Obes Metab. 2026 Sep 17. doi: 10.1111/dom.71318. Online ahead of print. Preferences for Obesity Medications Among People With Overweight or Obesity in the United States: A Discrete-Choice Experiment (OPTIC). Almandoz JP(1), Tchang BG(2), Myers K(3), Traina A(4), Bhavsar J(4), Divino V(4), Kent C(3), Bell ST(4). Author information: (1)Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. (2)Department of Clinical Medicine, Weill Cornell Medicine, New York, New York, USA. (3)RTI Health Solutions, Durham, North Carolina, USA. (4)Novo Nordisk Inc, Plainsboro, New Jersey, USA. AIMS: To evaluate the relative importance of attributes driving obesity medication (OM) choice and preferences among individuals with overweight or obesity. MATERIALS AND METHODS: US adults with obesity or overweight and ≥ 1 obesity-related complication completed an online survey including a discrete-choice experiment (DCE) in October-November 2025. In the DCE, participants chose between 2 hypothetical, experimentally designed OM profiles with attributes/levels related to efficacy, cardiovascular (CV) risk reduction, side effects, administration (route/frequency), and dosing instruction requirements. In a fixed-choice comparison, participants chose between 2 predefined oral OM profiles. Relative preference weights for the DCE attribute levels were estimated using a random-parameters logit model to estimate attribute importance, tradeoffs, and predicted treatment choice. RESULTS: Among 800 participants (400 OM-naïve/400 OM-experienced, 400 injection-naïve/400 injection-experienced), the most important attributes were route of administration, average weight-loss percentage, CV risk reduction, and the proportion of people achieving ≥ 20% weight loss. Dosing instructions had the lowest relative importance. There was a preference for 1 OM profile (Treatment A-a hypothetical oral semaglutide-like profile) over the alternative OM profile (Treatment B-a hypothetical orforglipron-like profile), according to the responses from the DCE (84.2% vs. 15.8%) and the fixed-choice question (90.0% vs. 10.0%). Only 23.4% indicated that taking an OM treatment on an empty stomach and waiting 30 min to eat would be disruptive to their lives. Most (73.3%) OM-naïve participants were open to taking an oral OM. CONCLUSIONS: Individuals with overweight or obesity prioritise weight-loss efficacy, CV risk reduction, and oral administration in OM treatment decisions; dosing instruction requirements were of low importance. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. DOI: 10.1111/dom.71318 PMID: 42755136

Mentions Orforglipron

Enzymatic Stability and Comparative Effects of Kisspeptin-14, Kisspeptin-13 and Kisspeptin-10 on Beta-Cell Function, Glucose Homeostasis and Appetite Regulation.

1. Metabolites. 2026 Sep 17;16(9):686. doi: 10.3390/metabo16090686. Enzymatic Stability and Comparative Effects of Kisspeptin-14, Kisspeptin-13 and Kisspeptin-10 on Beta-Cell Function, Glucose Homeostasis and Appetite Regulation. Spratt JA(1), Tanday N(1), McGinn DM(1), Chukwu CD(1), Gault VA(1), Irwin N(1). Author information: (1)Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. Background/Objective: Kisspeptin peptides are being increasingly recognised as regulators of metabolism, but whether these actions differ depending on peptide isoform remains unclear. Methods: The current study compared the enzymatic stability and biological effects of kisspeptin-14 (KP-14), kisspeptin-13 (KP-13) and kisspeptin-10 (KP-10) on beta-cell health and function, glucose homeostasis and appetite. Peptide stability was assessed in murine plasma and, following confirmation of KISS1R expression in BRIN-BD11 beta-cells, actions on insulin secretion, beta-cell proliferation and apoptosis were investigated, with additional secretory studies in isolated murine islets. Metabolic effects of KP-14, KP-13 and KP-10 were subsequently evaluated in healthy male and female mice. Results: KP-14 was resistant to plasma degradation, whereas KP-13 and KP-10 underwent N-terminal proteolysis, with KP-13 degradation generating KP-10 amongst other fragment peptides. The kisspeptin peptides exerted modest direct effects on insulin secretion from BRIN-BD11 cells, with KP-13 being the most efficacious, a bioactivity profile that was confirmed in islets. In addition, KP-13 significantly enhanced beta-cell proliferation and protected against cytokine-induced apoptosis, producing superior beta-cell proliferative effects compared to exenatide. Acute administration of all kisspeptin peptides elevated circulating glucose concentrations, and while KP-14 and KP-10 impaired glucose tolerance, KP-13 did not. Interestingly, KP-14 enhanced glucose-stimulated insulin secretion, with KP-13 and KP-10 being devoid of such actions. All kisspeptin isoforms suppressed food intake, although only KP-13, and especially KP-10 administration, led to an inhibition of feeding. Conclusions: Taken together, these data identify KP-13 as possessing the most favourable overall metabolic actions, based on a combination of beneficial actions on beta-cell health and function together with inhibition of feeding and lack of prominent glucose-elevating actions, suggesting possible therapeutic application for type 2 diabetes. DOI: 10.3390/metabo16090686 PMID: 42783811

Mentions Kisspeptin

Sustained weight loss exceeding 100 kg with sequential incretin-based therapy in Prader-Willi syndrome.

1. JCEM Case Rep. 2026 Sep 16;4(10):luag260. doi: 10.1210/jcemcr/luag260. eCollection 2026 Oct. Sustained weight loss exceeding 100 kg with sequential incretin-based therapy in Prader-Willi syndrome. Yovera-Aldana M(1), Manrique-Hurtado H(2), Umpierrez GE(3). Author information: (1)Grupo de Investigación de Neurociencias, Metabolismo, Efectividad Clínica y Sanitaria, Universidad Científica del Sur, Lima 15816, Perú. (2)Deparment of Endocrinology, Clínica Delgado-AUNA, Lima 15074, Perú. (3)Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by hyperphagia, severe obesity, and early-onset metabolic complications, in which durable weight loss is rarely achieved. We report a 29-year-old man with genetically confirmed maternal uniparental disomy PWS who presented with severe obesity (185 kg; body mass index [BMI] 59.7 kg/m2) and newly diagnosed type 2 diabetes (glycated hemoglobin [HbA1c], 8.3% [SI: 67 mmol/mol] [reference range, <5.7% (SI: <39 mmol/mol)]). He received sequential incretin-based therapy, initiated with retatrutide (1-12 mg weekly) within a clinical trial, followed by oral semaglutide and then dulaglutide after retatrutide became unavailable, together with a structured hypocaloric diet and supervised exercise. At 18 months, total weight loss reached 58.8% (-108.7 kg), with HbA1c of 4.9% (SI: 30 mmol/mol), consistent with diabetes remission after discontinuation of all glucose-lowering medications. Mild transient gastrointestinal symptoms occurred during dose escalation, with no serious adverse events. Follow-up bioimpedance showed a skeletal muscle mass of 38.5 kg after a 58.8% reduction in total body weight. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. DOI: 10.1210/jcemcr/luag260 PMCID: PMC13579046 PMID: 42751099

Mentions Retatrutide

Efficacy and safety of orforglipron 12 mg versus orforglipron 36 mg maintenance dose among patients with obesity with or without diabetes: a systematic review and comprehensive meta-analysis.

1. BMC Endocr Disord. 2026 Sep 15;26(1):273. doi: 10.1186/s12902-026-02538-x. Efficacy and safety of orforglipron 12 mg versus orforglipron 36 mg maintenance dose among patients with obesity with or without diabetes: a systematic review and comprehensive meta-analysis. Hegaz MG(1), Aboud MYA(2), Kamel AII(3), Naveed MA(4), Elsayed OG(5), Sorathia AZ(6). Author information: (1)Faculty of Medicine, Tanta University, Tanta, Egypt. (2)Faculty of Medicine, Latakia University, Latakia, Syria. (3)Faculty of Pharmacy, Minia University, Minya, Egypt. abanoub.ibrahim.kamel@gmail.com. (4)Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. abdullahnaveed120703@gmail.com. (5)Faculty of Medicine, Kafr El-Sheikh University, Kafr El-Sheikh, Egypt. (6)St Joseph's University Medical Center, Paterson, NJ, USA. BACKGROUND: Obesity is projected to affect about one billion adults by 2030 and is associated with cardiometabolic morbidity. Orforglipron is an oral, non-peptide glucagon-like peptide-1 receptor agonist developed to provide weight and metabolic benefits. Prior meta-analyses have supported its efficacy and safety but were limited by shorter follow-up and a predominance of non-diabetic populations. This meta-analysis aims to provide the most comprehensive head-to-head comparison between the two most commonly studied maintenance doses (12 mg vs. 36 mg), assessing weight, glycemic, cardiometabolic, and safety outcomes. METHODS: We searched PubMed, Web of Science, Cochrane, and Scopus until March 1, 2026, for randomized controlled trials (RCTs) comparing orforglipron 12 mg and 36 mg in obese adults. Outcomes of interest included percentage and absolute body weight change, BMI, HbA1c, waist circumference, lipid parameters, blood pressure, and adverse events. Results were pooled using a fixed-effects model, and prespecified subgroup analyses examined differences by diabetes status and treatment duration. RESULTS: Six RCTs (3459 participants) were included. Compared with the 12 mg dose, the 36 mg dose was associated with greater reductions in percentage body weight change (p < 0.00001), absolute body weight change (p < 0.00001), body mass index (p < 0.00001), HbA1c (p < 0.00001), waist circumference (P < 0.00001), percent change in triglycerides (P = 0.002), and systolic blood pressure (P = 0.002). Adverse events were comparable between doses. No significant differences were observed in gastrointestinal events or pancreatic functions. A small difference in pulse rate was noted but was not considered clinically significant. CONCLUSION: In obese adults, orforglipron 36 mg improved weight and metabolic outcomes compared with 12 mg. No statistically significant differences between doses were detected for the prespecified safety outcomes, although small increases in ALT and AST were observed with the 36 mg dose and the trials included were not powered to detect rare or long-term adverse events. These findings support consideration of the higher maintenance dose when clinically appropriate. Longer-term studies are needed to confirm the benefit and cardiovascular outcomes. CLINICAL TRIAL NUMBER: Not applicable. © 2026. The Author(s). DOI: 10.1186/s12902-026-02538-x PMID: 42750018 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethical approval: No humans participate in this study, and informed consent is not required. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Mentions Orforglipron

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

Efficacy and Safety of CagriSema for Metabolic Outcomes: Systematic Review and Pairwise Meta-Analysis of Randomized Controlled Trials.

1. Diabetes Metab Syndr Obes. 2026 Sep 15;19:616418. doi: 10.2147/DMSO.S616418. eCollection 2026. Efficacy and Safety of CagriSema for Metabolic Outcomes: Systematic Review and Pairwise Meta-Analysis of Randomized Controlled Trials. Shao C(1), Lin H(1), Yu J(1), Chen H(1), Ren Y(1), Ren J(1), Zeng Y(1), Wu Y(1), Bai H(1), Zhang Q(1), Xiao X(1). Author information: (1)NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Diabetes Research Center of Chinese Academy of Medical Sciences, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People's Republic of China. BACKGROUND: Overweight status, obesity, and diabetes represent significant socioeconomic burdens that require long-term management. METHODS: To evaluate the efficacy and safety of dual-agonist CagriSema vs semaglutide monotherapy, cagrilintide monotherapy, and placebo in adults with overweight/obese status and type 2 diabetes, we searched Embase, MEDLINE, PubMed, and the Cochrane Library up to 14 June 2026 for randomized controlled trials (RCTs). Separate pairwise meta-analyses were conducted using random effects models. RESULTS: Eight RCTs comprising 6898 participants were included. CagriSema was associated with significantly greater percentage body weight reduction compared to semaglutide [MD -6.60%; 95%CI: -8.51 to -4.68; P<0.0001; I2 =82%], cagrilintide [MD -8.15%; 95%CI: -11.40 to -4.89; P<0.0001; I2 =95%], and placebo [MD -14.30%; 95%CI: -17.41 to -11.19; P<0.0001; I2 =99%]. A greater decrease in the percentage of glycated hemoglobin was also observed for CagriSema than for semaglutide [MD -0.09%; 95%CI: -0.14 to -0.04; P=0.0004; I2 =39%], cagrilintide [MD -0.87%; 95% CI -1.48 to -0.26; p = 0.005; I2 = 97%], and placebo [MD -1.55%; 95% CI -2.14 to -0.97; p < 0.0001; I2 = 99%]. Furthermore, CagriSema achieved significantly greater reductions in absolute body weight, waist circumference and body mass index across all comparators (all p < 0.0001). CagriSema demonstrated better blood pressure control compared with cagrilintide and placebo, with effects comparable to those of semaglutide. Moreover, CagriSema significantly decreased C-reactive protein and improved lipid profiles compared with cagrilintide and placebo. CagriSema increased any adverse events and gastrointestinal adverse events compared with all comparators. Substantial statistical heterogeneity was observed in several continuous outcomes, driven by diverse baseline clinical characteristics and background therapies. CONCLUSION: Compared with current standard monotherapies and placebos, CagriSema demonstrates superior weight loss, glucose, and lipid control. Key limitations include the relatively small number of eligible trials and the current lack of long-term cardiovascular endpoints. © 2026 Shao et al. DOI: 10.2147/DMSO.S616418 PMCID: PMC13589532 PMID: 42763732 Conflict of interest statement: The authors report no conflicts of interest in this work.

Mentions CagriSema

The Periprocedural Safety of Continued GLP-1 Receptor Agonist Prior to Cardiac Catheterization.

1. Am J Cardiol. 2026 Sep 15;275:1-3. doi: 10.1016/j.amjcard.2026.06.029. Epub 2026 Jul 11. The Periprocedural Safety of Continued GLP-1 Receptor Agonist Prior to Cardiac Catheterization. Chi KY(1), Adhikari S(1), Chang Y(2), Mangalesh S(1), Lee PL(1), Damluji AA(3), Hu JR(4), Nanna MG(5). Author information: (1)Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York. (2)Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan. (3)The Cardiovascular Center on Aging, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio. (4)Department of Cardiology, Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California. (5)Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut. Electronic address: michael.nanna@yale.edu. DOI: 10.1016/j.amjcard.2026.06.029 PMID: 42435980 Conflict of interest statement: Declaration of competing interest Dr. Nanna reports serving as a consultant for Novo Nordisk, Merck, Novartis, and HeartFlow, Inc. All other authors report no disclosures relevant to the present work.

Mentions Tirzepatide

Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.

Mentions MOTS-c

Obesity, Oxidative Stress, and Inflammation in Precocious Puberty: Do All Roads Lead to the Hypothalamus?

1. Int J Mol Sci. 2026 Sep 13;27(18):8159. doi: 10.3390/ijms27188159. Obesity, Oxidative Stress, and Inflammation in Precocious Puberty: Do All Roads Lead to the Hypothalamus? Bizerea-Moga TO(1)(2), Chișavu F(3)(4), Chișavu L(3)(5), Pitulice L(6)(7), Moga TV(8)(9), Bugi MA(2)(10), Foghiș CF(1)(2)(11), Isac R(4)(12), Mărginean O(1)(2), Balica NC(13)(14). Author information: (1)Department XI of Pediatrics, First Pediatric University Clinic, Center for Research on Growth and Developmental Disorders in Children, 'Victor Babeș' University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No. 2, 300041 Timișoara, Romania. (2)1st Pediatric Clinic, 'Louis Țurcanu' Children's Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timișoara, Romania. (3)Nephrology University Clinic, Centre for Molecular Research in Nephrology and Vascular Disease, 'Victor Babeș' University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No. 2, 300041 Timișoara, Romania. (4)4th Pediatric Clinic, 'Louis Țurcanu' Children's Clinical and Emergency Hospital, Iosif Nemoianu 2, 300011 Timișoara, Romania. (5)Nephrology Clinic, 'Pius Brînzeu' County Emergency Clinical Hospital, Liviu Rebreanu 156, 300723 Timișoara, Romania. (6)Department of Chemistry, West University of Timişoara, Pestallozi 16, 300115 Timişoara, Romania. (7)Institute of Advanced Environmental Research, Oituz 4c, 300086 Timişoara, Romania. (8)Department VII of Internal Medicine, Gastroenterology University Clinic, Advanced Regional Research Center in Gastroenterology and Hepatology, 'Victor Babeș' University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No. 2, 300041 Timișoara, Romania. (9)Gastroenterology and Hepatology Clinic, 'Pius Brînzeu' County Emergency Clinical Hospital, Liviu Rebreanu 156, 300723 Timișoara, Romania. (10)Department of Pharmacy, University of Medicine and Pharmacy 'Vasile Goldis', 310025 Arad, Romania. (11)Ph.D. School Department, 'Victor Babeș' University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No. 2, 300041 Timișoara, Romania. (12)Department XI of Pediatrics, Third Pediatric University Clinic, 'Victor Babeș' University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq No. 2, 300041 Timișoara, Romania. (13)Department IX, Otolaryngology University Clinic, OftalmoSensory-Tumor Research Center-ORL (EYE-ENT), 'Victor Babeș' University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania. (14)Otorhinolaryngology Clinic, Emergency City Hospital, 300054 Timisoara, Romania. Childhood obesity is consistently associated with earlier pubertal timing, particularly in girls, whereas its relationship with true central precocious puberty (CPP), defined by premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, is less clearly established. An increased frequency of CPP diagnoses and referrals was reported during the COVID-19 pandemic, alongside changes in body weight, lifestyle, sleep, and psychosocial exposures. Human studies link excess adiposity to hyperleptinemia, insulin resistance, reduced adiponectin, altered sex-steroid bioavailability, and systemic low-grade inflammation, and associate these features with earlier pubertal development-consistently in girls, less so in boys. However, such associations do not establish that obesity directly induces premature hypothalamic activation. Mechanistic understanding of how these peripheral signals may influence pubertal timing derives predominantly from experimental models. The arcuate nucleus kisspeptin/neurokinin B/dynorphin (KNDy) network, a key component of the gonadotropin-releasing hormone (GnRH) pulse generator, interacts with hypothalamic metabolic circuits. In animal models of obesity and overnutrition, altered leptin and insulin signaling, mitochondrial reactive oxygen species generation, and activation of microglia and astrocytes remodel the mediobasal hypothalamus through inflammatory and stress-respo

Mentions Kisspeptin

Effect of Zinc Status on Pubertal and Cognitive Functions in Male Offspring of Rats with Induced Zinc Deficiency During Gestation and Lactation.

Mentions Kisspeptin

Effects of high frequency administration of GnRH or kisspeptin on LH pulse and surge profiles in ovariectomized Bos taurus and Bos indicus heifers†.

1. Biol Reprod. 2026 Sep 11:ioag198. doi: 10.1093/biolre/ioag198. Online ahead of print. Effects of high frequency administration of GnRH or kisspeptin on LH pulse and surge profiles in ovariectomized Bos taurus and Bos indicus heifers†. eSilva LO(1)(2)(3), West S(2), Garza V(2), Sustaita-Monroe J(2), King L(1), Sellers H(2), Weynand M(2), Feist H(2), Perry G(4), Sartori R(3), Cardoso RC(2). Author information: (1)Department of Animal Reproduction, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, SP, 13635-900, Brazil. (2)Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA. (3)Department of Animal Science, Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, SP, 13418-900, Brazil. (4)Texas A&M AgriLife Research and Extension Center, Overton, TX, 75684, USA. We hypothesized that high-frequency stimulation with kisspeptin or GnRH, mimicking increased GnRH pulsatility, would amplify the GnRH-induced LH surge in heifers. Additionally, LH pulse and surge parameters were compared between Bos taurus and Bos indicus heifers. Ovariectomized estradiol-replaced Hereford (n=6) and Brahman (n=8) heifers received two intravaginal progesterone devices on d -5. On d -0.5, jugular catheters were placed and on d 0 blood samples were collected every 15 min for 12 h. In a crossover design, each heifer received all three treatments in separate replicates, administered hourly during the first 8 h: Control = saline; Kisspeptin = 0.4 μg/kg of kisspeptin; or GnRH = 0.005 μg/kg of gonadorelin acetate. At 8 h, 100 μg of gonadorelin acetate was administered to induce an LH surge. Both kisspeptin and GnRH treatments effectively induced high-frequency LH pulses. Regardless of the genetic group, 75% of kisspeptin and 87.5% of GnRH injections resulted in detectable LH pulses. LH pulsatility was greater (P<0.01) in kisspeptin- and GnRH-treated heifers compared to controls (6.1±0.6, 7.0±0.4, 2.3±0.5 pulses/8 h; respectively). Nevertheless, neither endogenous nor treatment-induced LH pulse parameters differed between breeds. The GnRH-induced LH surge was not enhanced by the high-frequency stimulation, however, it was markedly reduced in Brahman compared to Hereford heifers (P<0.01). In conclusion, the high-frequency GnRH stimulation did not enhance LH surge response to a GnRH challenge. Although LH pulsatile secretion was similar, differential pituitary responsiveness to a GnRH ovulatory stimulus may contribute to differences in reproductive function between Bos taurus and Bos indicus heifers. © The Author(s) 2026. Published by Oxford University Press on behalf of the Society for the Study of Reproduction. DOI: 10.1093/biolre/ioag198 PMID: 42725801

Mentions Kisspeptin

Maternal Kisspeptin-10 Treatment Partially Rescues Fetal and Postnatal Cardiac Programming Disrupted by Maternal Hypothyroidism.

1. Cardiovasc Toxicol. 2026 Sep 11;26(10):104. doi: 10.1007/s12012-026-10185-w. Maternal Kisspeptin-10 Treatment Partially Rescues Fetal and Postnatal Cardiac Programming Disrupted by Maternal Hypothyroidism. Barbosa EM(1), Rodrigues NP(1), Santos BR(1), Dos Anjos Cordeiro JM(1), da Silva TQM(1), Oliveira CL(1), Santos LC(1), Cunha MCDSG(1), Serakides R(2), Silva JF(3). Author information: (1)Centro de Microscopia Eletrônica, Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Campus Soane Nazaré de Andrade, Ilhéus, 45662-900, Brasil. (2)Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, 31270-901, Minas Gerais, Brasil. (3)Centro de Microscopia Eletrônica, Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Campus Soane Nazaré de Andrade, Ilhéus, 45662-900, Brasil. jfsilva@uesc.br. Cardiovascular diseases are the leading cause of global mortality and have been associated with alterations in fetal programming. Maternal hypothyroidism (MH) impairs placental function and induces intrauterine growth restriction (IUGR), both of which are risk factors for cardiovascular disease. Kisspeptin-10 (Kp10) has been shown to improve feto-placental development in hypothyroid rats, but its effects on intrauterine cardiac development remain unknown. MH was induced in Wistar rats using propylthiouracil (PTU), and Kp10 administration began on gestational day 8. Offspring hearts were analyzed at fetal day 18 and postnatal days 3 and 21. MH reduced fetal and postnatal body and heart mass, impaired cardiomyocyte proliferation, and dysregulated apoptotic and angiogenic markers. Maternal Kp10 administration enhanced postnatal weight gain, restored cardiomyocyte proliferation and nuclear density, and positively modulated apoptotic (Bax/Bcl2) and angiogenic (Vegf, Ang2, Flk1) pathways. However, it increased redox (8-OHdG) and endoplasmic reticulum (ER) stress (Grp78, Chop) mediators in fetal hearts, while reduced postnatal Chop expression in both sexes. Collectively, these findings demonstrate that maternal hypothyroidism disrupts cardiac development and postnatal cardiac programming, whereas maternal Kp10 administration partially mitigates these effects, highlighting novel mechanisms through which kisspeptin may positively regulate cardiac development. © 2026. The Author(s). DOI: 10.1007/s12012-026-10185-w PMCID: PMC13569559 PMID: 42726152 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of Interest: The authors declare no conflict of interest.

Mentions Kisspeptin

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

Current and forthcoming pharmacotherapies for adolescent obesity: Evidence-based review.

1. World J Clin Pediatr. 2026 Sep 9;15(3):118730. doi: 10.5409/wjcp.118730. eCollection 2026 Sep 9. Current and forthcoming pharmacotherapies for adolescent obesity: Evidence-based review. Fuentes-Mendoza JM(1), Concepción-Zavaleta MJ(2), Dongo-Dueñas LG(3), Jara-Pianto JMJ(3), Sierra-Martel JA(3), Medina-Angulo CA(4), Virú-Flores HM(3), Mendoza-Godoy JJ(5), Zavaleta-Gutiérrez FE(6), Paz-Ibarra J(7)(8). Author information: (1)Grupo de Investigación en Neurociencias, Metabolismo, Efectividad Clínica y Sanitaria, Universidad Científica del Sur, Lima 15067, Peru. (2)Grupo de Investigación en Neurociencias, Metabolismo, Efectividad Clínica y Sanitaria, Universidad Científica del Sur, Lima 15067, Peru. mconcepcion@cientifica.edu.pe. (3)School of Medicine, Universidad Cientifica Del Sur, Lima 15054, Peru. (4)School of Medicine, Universidad Nacional San Luis Gonzaga, Lima 15054, Peru. (5)School of Medicine, Universidad Privada de Huancayo Franklin Roosevelt, Huancayo 12001, Peru. (6)Department of Pediatrician and Neonatologist, Hospital Belen de Trujillo, Trujillo 12590, Peru. (7)School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru. (8)Department of Endocrinology, Edgardo Rebagliati Martins National Hospital, Lima 15087, Peru. The prevalence of adolescent obesity has increased substantially in recent decades. This disease affects more than 20% of young people. Obesity is associated with metabolic disorders and heart disease. Conservative treatments are not effective in severe obesity. Therefore, this minireview aims to compare and clarify the effectiveness of treatments. It also seeks to identify areas requiring attention to guide clinical practice and future research. A literature search was conducted in databases including PubMed and Scopus. The study focused on randomised trials and meta-analyses in patients aged 12 to 18 years and lasting more than 12 weeks. The results show an improvement induced by glucagon-like peptide 1 receptor agonists, such as semaglutide. Semaglutide reduces body mass index by 16.1%. It is more effective than liraglutide in improving insulin sensitivity. The use of these drugs faces challenges, such as cost. There are also social inequalities that affect health equity. Although no short-term safety issues have been reported, there is still little information available on Tirzepatide and CagriSema in adolescents, compared to their known effect on adults. Therefore, we conclude that semaglutide is the current gold standard, but that there is an urgent need for longer-term studies, comparative evaluations, and safety trials that include paediatric cohorts in order to ensure safe access to pharmacological innovations. ©Author(s) 2026. DOI: 10.5409/wjcp.118730 PMCID: PMC13491103 PMID: 42625929 Conflict of interest statement: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Mentions CagriSema

Correction: Reduced serum and skeletal muscle MOTS c levels in women with polycystic ovary syndrome are associated with mitochondrial dysfunction.

1. Sci Rep. 2026 Sep 9;16(1):28209. doi: 10.1038/s41598-026-70401-z. Correction: Reduced serum and skeletal muscle MOTS c levels in women with polycystic ovary syndrome are associated with mitochondrial dysfunction. Kutuk IS(1), Akin S(2), Demirel H(3), Mumusoglu S(4), Ciftci T(5), Yildiz BO(6)(7)(8). Author information: (1)Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey. (2)Division of Exercise and Sport Physiology, Faculty of Sport Sciences, Hacettepe University, Ankara, Turkey. (3)Center for Sport Sciences, Near East University, Nicosia, Cyprus. (4)Department of Obstetrics and Gynecology, Hacettepe University School of Medicine, Ankara, Turkey. (5)Department of Radiology, Hacettepe University School of Medicine, Ankara, Turkey. (6)Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey. yildizbo@yahoo.com. (7)Division of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey. yildizbo@yahoo.com. (8)Division of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University School of Medicine, Hacettepe, Ankara, 06100, Turkey. yildizbo@yahoo.com. Erratum for Sci Rep. 2026 Feb 12;16(1):8593. doi: 10.1038/s41598-026-39687-x. DOI: 10.1038/s41598-026-70401-z PMCID: PMC13558634 PMID: 42716952

Mentions MOTS-c

From insulin resistance to incretin receptor agonism in the prevention of type 2 diabetes mellitus in obese individuals.

1. Curr Med Res Opin. 2026 Sep 3:1-15. doi: 10.1080/03007995.2026.2727202. Online ahead of print. From insulin resistance to incretin receptor agonism in the prevention of type 2 diabetes mellitus in obese individuals. Teofilović B(1), Trkulja J(1), Grujić-Letić N(1), Gligorić E(1), Baletic D(1)(2), Tomić L(2), Mesarović A(2), Rašković A(1). Author information: (1)Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia. (2)Faculty of Pharmacy, Bijeljina University, Bijeljina, Bosnia and Herzegovina. Type 2 diabetes mellitus (T2DM) represents one of the most significant metabolic challenges of the modern era, with more than 828 million people worldwide living with diabetes. Obesity and insulin resistance are major modifiable contributors to T2DM risk and progression, although the disease is heterogeneous and arises from complex interactions among β-cell dysfunction, hepatic glucose dysregulation, adipose-tissue dysfunction, altered incretin biology, chronic low-grade inflammation, and genetic susceptibility. In individuals with obesity and insulin resistance, progression through prediabetes to overt hyperglycaemia represents an important, although not universal, disease trajectory and provides a clinically relevant window for preventive intervention. This review examines pharmacological strategies relevant to T2DM prevention in individuals without established diabetes who have prediabetes and/or obesity associated with a high risk of progression to T2DM, with particular emphasis on incretin-based obesity pharmacotherapy. Metformin remains the glucose-lowering agent with the most established long-term evidence for diabetes prevention in selected high-risk individuals with prediabetes, acting through multiple hepatic and intestinal mechanisms involving both AMPK-dependent and AMPK-independent pathways. Other established antihyperglycaemic drug classes are discussed primarily to distinguish therapies with evidence for delaying progression to diabetes from agents whose principal role remains the treatment of established T2DM. SGLT2 inhibitors provide substantial cardiovascular and renal protection, although current evidence is insufficient to support their routine use solely for T2DM prevention. GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide have substantially advanced obesity pharmacotherapy, producing clinically meaningful weight loss and broader cardiometabolic benefits that may reduce progression to T2DM in high-risk individuals.Next-generation incretin-based therapies, including triple receptor agonists, may further expand therapeutic options but remain an evolving area of investigation. Lifestyle intervention and sustained weight management remain the foundation of T2DM prevention, with pharmacological strategies selected according to individual metabolic risk, obesity-related treatment indications, comorbidities, and the strength of evidence supporting diabetes prevention. DOI: 10.1080/03007995.2026.2727202 PMID: 42690722

Mentions Retatrutide

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

Signal thresholds and causal inference in pharmacovigilance studies of glucagon-like Peptide-1 receptor agonists.

1. Clin Nutr. 2026 Sep;64:106731. doi: 10.1016/j.clnu.2026.106731. Epub 2026 Jul 21. Signal thresholds and causal inference in pharmacovigilance studies of glucagon-like Peptide-1 receptor agonists. Li L(1). Author information: (1)Department of Laboratory Medicine, The Fourth Affiliated Hospital of Southwest Medical University, No. 168, Huantianfu New Area Expressway, Meishan Tianfu New Area, Meishan Sichuan, 620564, PR China. Electronic address: Lilan_0321@163.com. DOI: 10.1016/j.clnu.2026.106731 PMID: 42520369 Conflict of interest statement: Conflict of interest The author declares that there is no conflict of interest.

Mentions Tirzepatide

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

Kisspeptin System: A Modulator of Neuroinflammation and Behaviour in Temporal Lobe Epileptic Rats.

1. Mol Neurobiol. 2026 Sep 1;63(1):874. doi: 10.1007/s12035-026-06171-6. Kisspeptin System: A Modulator of Neuroinflammation and Behaviour in Temporal Lobe Epileptic Rats. Jaldhi(1), Kumar S(2), Shanker OR(2), Banerjee J(3), Dixit AB(4), Maurya SK(5), Bakshi A(6)(7). Author information: (1)Biochemistry and Molecular Biology Laboratory, Faculty of Science, Department of Zoology, University of Delhi, Delhi, 110007, India. (2)Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India. (3)Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India. (4)Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India. aparnabanerjeedixit@gmail.com. (5)Biochemistry and Molecular Biology Laboratory, Faculty of Science, Department of Zoology, University of Delhi, Delhi, 110007, India. smaurya1@zoology.du.ac.in. (6)Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi, 110007, India. amrita25du@gmail.com. (7)Neuroendocrine Physiology Laboratory, Department of Zoology, Ramjas College, University of Delhi, Delhi, 110007, India. amrita25du@gmail.com. Temporal lobe epilepsy (TLE) is the most prevalent form of drug-resistant epilepsy and is driven by persistent neuroinflammatory cascades wherein interactions between inflammatory mediators and hormones play a crucial role. Kisspeptin (Kiss1), a neuropeptide known to modulate synaptic transmission in the hippocampus, has an unclear role in pathophysiology of epilepsy. To investigate this, a lithium-pilocarpine TLE rat model was established. Expression profiles of Kiss1, Kiss1r, and key neuroinflammatory molecules were assessed in the hippocampus, anterior temporal lobe (ATL), and neocortex at the transcript and protein levels. Neuroinflammatory markers were correlated with the expression of Kiss1 and its receptor under epileptic conditions. The cellular localization of Kiss1r with microglia (Iba1), astrocytic (Gfap), and neuronal (NeuN) markers was examined in TLE. Additionally, kisspeptin-10 (Kp-10) was administered to TLE rats, and its effects on cytoarchitecture, neuroinflammation, and long-term memory were evaluated. The results demonstrated significant downregulation of Kiss1 and Kiss1r mRNA across brain regions (P < 0.05). At the protein level, Kiss1 was significantly downregulated in the hippocampus and ATL but remained unchanged in the neocortex. Kiss1r levels increased in the hippocampus, decreased in the ATL, and remained unchanged in the neocortex. Kp-10 administration led to restoration of cellular alterations in the hippocampus of TLE rats. Kp-10 treatment upregulated the levels of anti-inflammatory cytokine Il-10 in the hippocampus and ATL. A downregulation in the levels of pro-inflammatory cytokine Il-1β in the hippocampus, but no alteration in ATL was seen upon Kp-10 treatment. Novel object recognition test indicated improved memory discrimination in Kp-10-treated TLE rats. These findings suggest that chronic neuroinflammation in TLE disrupts the kisspeptin signalling system, further aggravating disease pathology. Conversely, exogenous Kp-10 administration attenuated neuroinflammation, enhanced cognitive function and survival rate, highlighting a potential neuroprotective role of kisspeptin in TLE pathogenesis. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. DOI: 10.1007/s12035-026-06171-6 PMID: 42680947 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Competing interests: The authors declare no competing interests.

Mentions Kisspeptin