Community signal

Mounjaro dose side effects

Mounjaro dose side effects

Mentions Tirzepatide

Does a 30 mL Hospira bac water vial actually contain 30 mL? I measured it on camera, covered why bac water quality matte

Does a 30 mL Hospira bac water vial actually contain 30 mL? I measured it on camera, covered why bac water quality matters. 🛒 https://t.co/RDX4VhlGWn 💬 https://t.co/4nsbCKMwyc https://t.co/Hqevp4Dtpp

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

Mounjaro Miracles (and the Peloton😊)

Mounjaro Miracles (and the Peloton😊)

Mentions Tirzepatide

@Nick2k25 Oh yeah. So you can get 50/10/10/10 KLOW and add 20mg more each of BPC-157, TB4 and 5mg more of KPV and transf

@Nick2k25 Oh yeah. So you can get 50/10/10/10 KLOW and add 20mg more each of BPC-157, TB4 and 5mg more of KPV and transfer it to a bigger vial. The standard issue ChiCom KLOW is decent, but I’m really big into bigger doses of the BPC-157 and TB4 (and a bit bigger KPV) these days for max effectiveness

Mentions BPC-157

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

Mentions Oxytocin

Retatrutide - dieting on ez mode

Retatrutide - dieting on ez mode

Mentions Retatrutide

@Nick2k25 I've heard a lot of similar stories like this. Really glad to hear this. Did you use oral or injected KPV?

@Nick2k25 I've heard a lot of similar stories like this. Really glad to hear this. Did you use oral or injected KPV?

Mentions KPV

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

Mentions Oxytocin

Help! EXTREME Ongoing Reaction to CJC/Ipramorelin

Help! EXTREME Ongoing Reaction to CJC/Ipramorelin

Mentions CJC-1295 / Ipamorelin

What other people say about BPC-157: https://t.co/7QGuUroPsn

What other people say about BPC-157: https://t.co/7QGuUroPsn

Mentions BPC-157

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

Sept 2019 vs June 2026

Sept 2019 vs June 2026

Mentions Tirzepatide

the BPC-157 I take — Barrier Health, enteric-coated tablets, 500mcg. the coating is the whole thing. plain capsules get

the BPC-157 I take — Barrier Health, enteric-coated tablets, 500mcg. the coating is the whole thing. plain capsules get destroyed by stomach acid, which is why most people feel nothing after six weeks and write it off. ALFRED = 15% off https://t.co/bbQQkcxcjy

Mentions BPC-157

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

Mentions Semaglutide

Selank

Selank

Mentions Selank

BPC-157 healed almost every injury they tested it on. ➤ tendon cut off bone — reattached in 21 days ➤ nerve sliced in h

BPC-157 healed almost every injury they tested it on. ➤ tendon cut off bone — reattached in 21 days
➤ nerve sliced in half — reconnected
➤ spinal cord crushed — walking again
➤ hole through an eye — sealed in 24h
➤ bone sawed out — matched a graft
➤ muscle torn off bone — reattached
➤ gut perforated by ibuprofen — closed every one of these are built to be permanent. every control group stayed broken. injury that's been there for years? one you've stopped mentioning? I take the oral version every morning. everything's in the replies ↓

Mentions BPC-157

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

Benzodiazepines and Mounjaro ?

Benzodiazepines and Mounjaro ?

Mentions Tirzepatide

“Signaling molecules shouldn’t be macro dosed” sounds good until you look at the actual MOTS-c literature. AMPK activat

“Signaling molecules shouldn’t be macro dosed” sounds good until you look at the actual MOTS-c literature. AMPK activation isn’t the only endpoint. Researchers have reported dose-dependent effects on endurance, glucose metabolism, mitochondrial adaptation, and cellular stress responses. Nobody is claiming 5x the dose gives 5x the AMPK signal. The question is whether greater exposure produces greater downstream biological effects. For MOTS-c, the evidence suggests it often does.

Mentions MOTS-c

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

Is it possible to start mounjaro when you already have gallstones?

Is it possible to start mounjaro when you already have gallstones?

Mentions Tirzepatide

Or buy your MOTS-c from https://t.co/dzeRFW4NqQ that already comes in a 6ml vial. And we have a guarantee. If your vial

Or buy your MOTS-c from https://t.co/dzeRFW4NqQ that already comes in a 6ml vial. And we have a guarantee. If your vial gels or doesn’t perform like you want it, we will replace it for free. Every time. We also do include sterile empty 10ml vials with another 30mg product. WELCOME15 for 15% off your first order.

Mentions MOTS-c

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

Mentions Semaglutide

Just wanted to share my success story

Just wanted to share my success story

Mentions Tirzepatide

my bicep tendon had refused to heal for months on BPC-157 ... took normal standard subq dose, guess i should of added tb

my bicep tendon had refused to heal for months on BPC-157 ... took normal standard subq dose, guess i should of added tb500? feels dissapointing? where that magic at

Mentions BPC-157

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

is it really necessary to inject ghk-cu at night?

is it really necessary to inject ghk-cu at night?

Mentions GHK-Cu

Learn how to optimize for strength, vitality, and longevity inside my Living Leaner. Longer. Stronger. Masterclass. htt

Learn how to optimize for strength, vitality, and longevity inside my Living Leaner. Longer. Stronger. Masterclass.  https://t.co/0fNHTEDgCu https://t.co/QquYcaYAU6

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

What app do you guys use with mounjaro ?

What app do you guys use with mounjaro ?

Mentions Tirzepatide

what I noticed on oral BPC-157. the bloating went first, inside a week. I hadn't realised how normal that tight feeling

what I noticed on oral BPC-157. the bloating went first, inside a week. I hadn't realised how normal that tight feeling after eating had become until it wasn't there. the head cleared after that. less of the fog I'd been blaming on sleep. the back took eight weeks. twelve years of nerve damage, two doctors, both said permanent. one person, no control group, and I wanted it to work. I know what that does to what you notice. but that's the order it happened in.

Mentions BPC-157

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

Monaural and HRT

Monaural and HRT

Mentions Tirzepatide

same peptide, other tissues: ➤ tendon cut off bone — reattached in 21 days ➤ spinal cord crushed — recovered ➤ nerve se

same peptide, other tissues: ➤ tendon cut off bone — reattached in 21 days
➤ spinal cord crushed — recovered
➤ nerve severed — reconnected
➤ hole through an eye — sealed in 24h
➤ bone sawed out — matched a graft thirty years. no dose has ever killed anything. https://t.co/87tj9RDwVP

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

Mounjaro isn't helping me lose weight

Mounjaro isn't helping me lose weight

Mentions Tirzepatide

it's BPC-157. a 15-amino-acid fragment of something already in your gastric juice. the oral version I take — Barrier He

it's BPC-157. a 15-amino-acid fragment of something already in your gastric juice. the oral version I take — Barrier Health, enteric-coated tablets, 500mcg. plain capsules get destroyed by stomach acid, which is why most people feel nothing and write it off. ALFRED = 15% off https://t.co/5HSNWbgD8V

Mentions BPC-157

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

Mounjaro after Bariatric Surgery

Mounjaro after Bariatric Surgery

Mentions Tirzepatide

I used to roll my eyes when people suddenly lost loads of weight and credited keto or “just eating less.” I suspected GL

I used to roll my eyes when people suddenly lost loads of weight and credited keto or “just eating less.” I suspected GLP-1s and thought they should admit it. Then I started Zepbound. Promised myself I’d be open about it. A year later, thirty pounds down, almost nobody knows. When people ask, I lie.

Mentions Tirzepatide

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

Gaining weight on Monjauro

Gaining weight on Monjauro

Mentions Tirzepatide

@Max_hubz KPV

@Max_hubz KPV

Mentions KPV

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

HW: 270; SW: 220; GW: 170-175; CW: 159-155; BD: 2.5; CD: 5.0

HW: 270; SW: 220; GW: 170-175; CW: 159-155; BD: 2.5; CD: 5.0

Mentions Tirzepatide

I avoided SSRIs because the side effects scared me. Always wanted to do things https://t.co/hRRXLj8MSk I inject Selank..

I avoided SSRIs because the side effects scared me. Always wanted to do things https://t.co/hRRXLj8MSk I inject Selank... honestly? I feel better!! Social anxiety had reached the point where even being around longtime friends felt uncomfortable. On Selank, conversations became easier and I stopped analysing myself so much.

Mentions Selank

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

I took a selfie every month on this journey

I took a selfie every month on this journey

Mentions Tirzepatide

@SSavson https://t.co/rNNujLF2qy https://t.co/GsNR9f3gbg https://t.co/Gey0XkHBRq https://t.co/dv927j0sim This is going

@SSavson https://t.co/rNNujLF2qy https://t.co/GsNR9f3gbg https://t.co/Gey0XkHBRq https://t.co/dv927j0sim This is going to be big. You can see all the investors salivating over it. And just like GLP1 drugs, I already solved this problem. 🤣

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

3 Months Completed 28 Lbs Lost(315-287)

3 Months Completed 28 Lbs Lost(315-287)

Mentions Tirzepatide

@AtomP2P I don’t think so. The copper is bound to the GHK.

@AtomP2P I don’t think so. The copper is bound to the GHK.

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

DMV and mounjaro

DMV and mounjaro

Mentions Tirzepatide

You’re searching for a GLP-1 but don’t know what the costs are for each of the pharmacies if you have to have a membersh

You’re searching for a GLP-1 but don’t know what the costs are for each of the pharmacies if you have to have a membership, etc. Check this out ⬇️ https://t.co/6w1UmwEjhQ

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

First 5mg dose + new symptoms, should I be concerned or am I being a drama queen?

First 5mg dose + new symptoms, should I be concerned or am I being a drama queen?

Mentions Tirzepatide

Living Leaner Longer Stronger is my blueprint for optimal health and longevity... Built from 25+ years of research, exp

Living Leaner Longer Stronger is my blueprint for optimal health and longevity... Built from 25+ years of research, experimentation, and real-world application. Get your copy on Amazon or read 2 chapters! https://t.co/XhdmGdW0gC https://t.co/cC3Im7vk03

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

Using golden dose to titrate up slowly?

Using golden dose to titrate up slowly?

Mentions Tirzepatide

I love being tan year-round on Melanotan II. What bothers me is how quickly I get used to the colour and start wanting

I love being tan year-round on Melanotan II. What bothers me is how quickly I get used to the colour and start wanting to be darker again.

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

Mounjaro as an active person?

Mounjaro as an active person?

Mentions Tirzepatide

circadion = epitalon btw https://t.co/IMer5CJIbQ

circadion = epitalon btw https://t.co/IMer5CJIbQ

Mentions Epitalon

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

Not sure i did my first injection right

Not sure i did my first injection right

Mentions Tirzepatide

bryan once did 5 days of epitalon and never mentioned it again. i wonder why. https://t.co/8VICsGo5RN

bryan once did 5 days of epitalon and never mentioned it again. i wonder why. https://t.co/8VICsGo5RN

Mentions Epitalon

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

Single use pen taking forever to inject?

Single use pen taking forever to inject?

Mentions Tirzepatide

Do you have an injury that never came back right? BPC-157 HEALED every version of that they could build in a lab. ➤ sp

Do you have an injury that never came back right? BPC-157 HEALED every version of that they could build in a lab. 
➤ spinal cord crushed — recovered
➤ nerve severed — reconnected
➤ hole through an eye — sealed in 24h
➤ bone sawed out — matched a graft
➤ muscle torn off bone — reattached every one built to be permanent. every control group stayed broken. (PMID: 16583442 · 31266512 · 10071911) the one you train around. the one you've stopped mentioning. the one they told you to live with. everything's in the replies ↓

Mentions BPC-157

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

Tips needed to lose weight

Tips needed to lose weight

Mentions Tirzepatide

@GilaMonstrum @JCanNuSH @ObsvRetardation It's very weird to compare tiny Phase 1 data versus large phase 3 trials. Cagri

@GilaMonstrum @JCanNuSH @ObsvRetardation It's very weird to compare tiny Phase 1 data versus large phase 3 trials. Cagrisema phase 3 diabetes had serious AE events from ~8-13% if we're doing that. Otherwise this study did what it was supposed to. That's the whole point of phase 1. Ph2 diabetes has one outlier

Mentions CagriSema

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

GHK-Cu isn’t as flashy as some of the other peptides but it’s actually a real banger. https://t.co/7n4xBP4CPi

GHK-Cu isn’t as flashy as some of the other peptides but it’s actually a real banger. https://t.co/7n4xBP4CPi

Mentions GHK-Cu

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

Chinese pharma grade Cerebrolysin (allegedly)? Came in a box with instructions. Let’s see how it goes. Starting day 2

Chinese pharma grade Cerebrolysin (allegedly)? Came in a box with instructions. Let’s see how it goes. Starting day 2 of 10 now. https://t.co/Jo75RBC82w

Mentions Cerebrolysin

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

Mentions Oxytocin

@NovaForgeLab @RegenRandy Since starting TRT, I haven't gotten a single pimple. Not sure if KPV helped, but no acne. It

@NovaForgeLab @RegenRandy Since starting TRT, I haven't gotten a single pimple. Not sure if KPV helped, but no acne. It also seemed to help 9th Life, so worth a shot!

Mentions KPV

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.

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