What the peptide community is saying — and living

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

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.

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).

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

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

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.

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).

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]

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).

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]

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

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.

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).

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.

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

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

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.

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.

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

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

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

Corrigendum to "Associations of intrapartum synthetic oxytocin administration with reduced neonatal salivary oxytocin levels and altered sucking patterns" [Early Hum. Dev. 218 (202

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Good morning, Just wrapped my first 2 nights on Epitalon and my Oura is already showing +16 minutes of REM sleep. I’m

Good morning, Just wrapped my first 2 nights on Epitalon and my Oura is already showing +16 minutes of REM sleep. I’m waking up feeling sharper, more restored; telomere support hitting different. Anyone else using Epitalon?