Community signal

Walking + GLP-1 = the ultimate fat-burning combo that doesn't wreck your body. Gentle movement meets smart science for r

Walking + GLP-1 = the ultimate fat-burning combo that doesn't wreck your body. Gentle movement meets smart science for results that actually last. Who's trying this? Want a slightly softer one instead? The secret sauce to fat loss without the burnout: daily walks paired with GLP-1. Sustainable, effective, and kind to your system. Save this for your next walk!

Mk-677

Mk-677

Mentions MK-677 (Ibutamoren)

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

Mentions Semaglutide

Reducing protein intake could increase human longevity, researchers recently suggested. That's a bad idea, for several r

Reducing protein intake could increase human longevity, researchers recently suggested. That's a bad idea, for several reasons, experts say. https://t.co/dl22JztLgj

Diabetes - 2nd update on semaglutide

Diabetes - 2nd update on semaglutide

Mentions Semaglutide

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

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

Mentions P21

Took Peptide Critic’s Advice and Did Some Research Yesterday I posted about Ion asking a customer for additional govern

Took Peptide Critic’s Advice and Did Some Research Yesterday I posted about Ion asking a customer for additional government ID before processing an order. Peptide Critic responded with several negative comments, accused me of failing to understand the transaction and suggested that I was engagement farming. So I took the advice and did some research, on Peptide Critic. Ion is labelled a Premium Partner on Peptide Critic’s own site. The platform advertises that tier at $499 per month. Ion also has a Peptide Critic discount code and affiliate-tracked links through which the platform states it may earn commission. A commercial relationship exists, and it wasn’t disclosed while Peptide Critic publicly defended Ion and attacked my reporting. No one else complained about the post. Could this financial relationship explain why Peptide Critic was so upset by it? Perhaps the person accusing others of insufficient research should have led with that? FYI My original post about Ion remains valid. A customer was asked to provide additional ID, and questioning why a grey-market peptide vendor wanted that personal information was entirely reasonable. Peptide Critic didn't show that anything I posted was false or provide missing context that disproved it. He attacked my research and motives instead. Whatever explanation Ion may have for requesting the ID doesn't change the fact that the request was made.

Question about injection technique / possible dose loss

Question about injection technique / possible dose loss

Mentions Semaglutide

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

Mentions Semaglutide

neuroplasticity is always on your side with dihexa. everybody says neuroplasticity drops to 0 when you become 25 which

neuroplasticity is always on your side with dihexa. everybody says neuroplasticity drops to 0 when you become 25 which is not true, but even then nootropics exist. you will learn faster, remember more, think quicker, recover smoothly and never burn out if you know how to use nootropics correctly. ps: dont randomly start taking nootropics thinking you are "biohacking". everything needs the correct timing, dosing, stack and potential ancillaries. be responsible about this and DYOR, your brain is on the line.

Mentions Dihexa

Starting to think I'm a non-responder

Starting to think I'm a non-responder

Mentions Semaglutide

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

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

Mentions P21

Based off your experience with researching peptides, give me one piece of advice you would pass on to someone just start

Based off your experience with researching peptides, give me one piece of advice you would pass on to someone just starting to do their research. It can be about any peptide, any lesson… anything that may be helpful to someone considering them. Go 👇🏼

Storing reconstituted peptide in freezer for later user/ Peptides for field sports recovery

Storing reconstituted peptide in freezer for later user/ Peptides for field sports recovery

Mentions CJC-1295 / Ipamorelin

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

My wife and I brought a peptide on our anniversary trip because we thought it might make the weekend more interesting.I

My wife and I brought a peptide on our anniversary trip because we thought it might make the weekend more interesting.I gave her a tiny test amount before we left, thirty minutes later, she was vomiting. was fun sitting on the bathroom floor beside near my wife while realizing the “fun peptide” has officially cancelled the night i paid, planned, and counted on to reignite us.

Has anyone had to go through PA approval with Caremark?

Has anyone had to go through PA approval with Caremark?

Mentions Tirzepatide

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

Tik Tok's Step-by-Step Guide to Building an “Unkillable” Peptide Business Step 1: Announce that 90% of peptide compani

Tik Tok's Step-by-Step Guide to Building an “Unkillable” Peptide Business Step 1: Announce that 90% of peptide companies will disappear within 12 months. Nothing sells mentorship quite like opening with the apocalypse. Step 2: Use cheaper payment processors instead of expensive high-risk ones. Better margins today; potential payment chaos apparently reserved for another video. Step 3: Don’t build one brand. Build an entire internet ecosystem of blogs, social accounts and recommendation pages around it. Step 4: If the lab receives a cease-and-desist, shut it down, launch a replacement and change every recommendation link. The brand is disposable; the traffic isn’t. Step 5: Update every external page so it recommends the newly reincarnated lab. Same funnel, different lab coat. Step 6: Create a peptide-tracking app offering schedules, reminders and research, plus a helpful signpost to whichever lab survived this week. Step 7: Keep the audience, SEO and app separate from the disposable storefront, allowing the marketing machine to live forever. Step 8: Call it “building for the long haul.” It’s less of a conventional business plan and more of a peptide Hydra: cut off one website and three landing pages grow back.

Quick recap of my journey so far (Jan 2026 - Aug 2026)

Quick recap of my journey so far (Jan 2026 - Aug 2026)

Mentions Semaglutide

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

This is one of the many heavy-hitting peptides you can get prescribed by a US clinician and filled from a US compounding

This is one of the many heavy-hitting peptides you can get prescribed by a US clinician and filled from a US compounding pharmacy at https://t.co/1sx28z3Tll. Get this along with Tesamoreln, Ipamorelin, GLOW, Wolverine, BPC-157, Tirzepatide, KLOW, Epitalon and more. For human use. Not for research.

Mentions Tirzepatide

Stomach ache after eating sweets

Stomach ache after eating sweets

Mentions Semaglutide

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

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

Mentions Oxytocin

Good thing I haven’t started Ipamorelin. I was waiting on these results. What I am going to do is a washout period so

Good thing I haven’t started Ipamorelin. I was waiting on these results. What I am going to do is a washout period so stop CJC completely, go back to maintenance calories, stop fasting, and then re-test again. Try to isolate if the issue is with calorie restriction or something else.

Mentions CJC-1295 / Ipamorelin

Mounjaro

Mounjaro

Mentions Tirzepatide

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

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

Mentions Tirzepatide

When the “Responsible” Age Gate Becomes Evidence Most RUO vendors probably assume that a 21+ age gate is the responsibl

When the “Responsible” Age Gate Becomes Evidence Most RUO vendors probably assume that a 21+ age gate is the responsible thing to add. Keep minors away, restrict access and provide another layer between an RUO website and the general public. Some attorneys have also recommended age gates and account creation for precisely that reason. Eli Lilly has now cited 21+ age gates in three of its four lawsuits against “research use only” peptide sellers. In its complaint against Lone Star Peptide Co., Lilly specifically lists the age-verification gate among the practices it says demonstrate that retatrutide was being marketed and sold for human consumption. The other evidence, weight-loss advertising, dosing information and reconstitution guidance, is hardly surprising. Everyone already knows that openly telling customers what a product does and how to use it undermines an RUO disclaimer. The age gate is the interesting part because it was presumably added to do the opposite. Lilly doesn't explain why it considers the age gate relevant. It simply includes it among the practices that, taken together, it says show the products were intended for human consumption. That makes its inclusion particularly notable: a restriction vendors may regard as a responsible safeguard is being used in the opposite direction, without Lilly explaining what the gate itself proves. An age gate may still be a responsible precaution, but vendors should not assume it provides legal protection. Lilly has taken the very safeguard that was supposed to help them and placed it inside the paragraph alleging human consumption.

Mentions Retatrutide

Side effect??

Side effect??

Mentions Tirzepatide

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

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

Mentions P21

Well apparently a few of you liked the prices of our Tesamorelin. (2) 10 packs and (1) 5 pack sold in the last hour. L

Well apparently a few of you liked the prices of our Tesamorelin. (2) 10 packs and (1) 5 pack sold in the last hour. Lead time should be closer to 1-2 weeks on COA. Again, if COA comes back failing any of the tests or below 99% purity a refund will be sent back. We have strict standards. Also, I have come to realize that we significantly under priced this compared to the rest of the market and I'm 100% ok with it. Huge thank you to those of you supporting the efforts!

Mentions Tesamorelin

I’m starting Mounjaro 5mg

I’m starting Mounjaro 5mg

Mentions Tirzepatide

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

Something odd just popped up on my bloodwork… My IGF-1 came back at 51 ng/mL with a -2.4 Z-score lol Which is especial

Something odd just popped up on my bloodwork… My IGF-1 came back at 51 ng/mL with a -2.4 Z-score lol Which is especially weird considering I’ve been taking CJC-1295 https://t.co/UqjBlRyCR4

Tirzepatide 10 mg Vial

Tirzepatide 10 mg Vial

Mentions Tirzepatide

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

injecting purified pig brains is the number 1 best thing you can do for your brain, whether you are young or old. cereb

injecting purified pig brains is the number 1 best thing you can do for your brain, whether you are young or old. cerebrolysin repairs the brain like no other. - antioxidant enzymes are enhanced - mitochondria are enhanced - cognition is enhanced - recovery is enhanced - plasticity is enhanced everything just levels the fuck up and everything that doesnt need to be in your brain and is causing dysfunctions, malfunctions and issues gets removed. the number one nootropic. nothing comes close. perfection.

Mentions Cerebrolysin

Splitting 10mg Mounjaro Vials?

Splitting 10mg Mounjaro Vials?

Mentions Tirzepatide

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

IT’S OFFICIALLY HERE. My new book, Living Leaner Longer Stronger, is OUT NOW on Amazon & Kindle. https://t.co/JqhQURQ

IT’S OFFICIALLY HERE. My new book, Living Leaner Longer Stronger, is OUT NOW on Amazon & Kindle.  https://t.co/JqhQURQOd5 I took 25+ years of studying, testing, refining, and LIVING human optimization and put it into one blueprint for becoming leaner, stronger, healthier, and harder to kill as you age. This isn’t another book telling you to accept decline as “normal aging"... It’s about understanding your biology, taking ownership of it, and becoming the engineer of your own health. 21 chapters. 7 parts. One operating system for optimal health and longevity. Leave an Amazon review, send a screenshot to contact@jaycampbell.com, and get access to an EXCLUSIVE private webinar with me and @MindsetFreek next week.

Splitting 10mg Mounjaro Vials?

Splitting 10mg Mounjaro Vials?

Mentions Tirzepatide

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

Sorry. But while we’re at it, If you wanna go out and not drink alcohol… -selank -alpha gpc -modaf(wakefulness) -caf

Sorry. But while we’re at it, If you wanna go out and not drink alcohol… -selank -alpha gpc -modaf(wakefulness) -caffeine -L-theanine PLEASE DO NOT USE phenibut, benzos, pregabalin/gabapentin, and kratom.

Mentions Selank

First Injection

First Injection

Mentions Tirzepatide

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

Gating Taken to the Extreme? Ion Peptide already had the customer’s full name, shipping address and bank-approved paym

Gating Taken to the Extreme? Ion Peptide already had the customer’s full name, shipping address and bank-approved payment. Apparently that only gets you into the waiting room. To have the order processed, they also wanted government-issued photo ID. But don’t worry about privacy, you can redact everything except your name, address and face. The customer cancelled before the fingerprinting and retina scan. The peptides are “research use only.” The buyers apparently require full human verification.

Mounjaro doses help

Mounjaro doses help

Mentions Tirzepatide

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

Everyone talked about BPC-157, TB-500 and SS-31 like they were the ultimate recovery stack. My body treated all three l

Everyone talked about BPC-157, TB-500 and SS-31 like they were the ultimate recovery stack. My body treated all three like poison.

Mentions BPC-157

Am I cooked?.

Am I cooked?.

Mentions MOTS-c

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

Berberine has been on my radar for glucose control for years, and this new study caught my attention. People who took a

Berberine has been on my radar for glucose control for years, and this new study caught my attention. People who took a biooptimized form of berberine at just 200 mg/day for 2 weeks saw reductions in fasting glucose, improved glucose tolerance, and a 22-29% increase in fasting and post-meal GLP-1 levels. The GLP-1 finding is particularly interesting because it suggests berberine may influence some of the same incretin biology that has become such a major focus in metabolic health. Berberine isn’t part of my regular supplement routine anymore (I've shifted more toward alpha-lipoic acid), although I still think the evidence for glucose and lipid control is interesting. These results make me interested in seeing larger, independent, longer-term trials of lower-dose, more bioavailable formulations.

Explain a semaglutide like I'm 5.. because I have a question..

Explain a semaglutide like I'm 5.. because I have a question..

Mentions Semaglutide

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

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

Mentions Semaglutide

The biggest truth about peptides that is completely overlooked most times is that a vast majority of them have very limi

The biggest truth about peptides that is completely overlooked most times is that a vast majority of them have very limited data. Does it mean that they don't work as intended? No. However, as you navigate the space and as you research you need to do a significant amount of due diligence with whatever peptide you're looking at. Don't just trust the guys & gals talking about how well it worked for them. Trust the science and data. If you're bold enough to go down the rabbit hole and research it... make sure you log everything as an independent researcher should be doing.

Selank x Semax Stack at 22?

Selank x Semax Stack at 22?

Mentions Selank

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

Ask and you shall receive. We just launched 23mg BPC-157 vials at a 35% lower cost/mg than our 10mg vials. https://t.co/

Ask and you shall receive. We just launched 23mg BPC-157 vials at a 35% lower cost/mg than our 10mg vials. https://t.co/mYy96dGGlJ (For research use only. Not for human consumption)

Mentions BPC-157

Week 11 no pounds

Week 11 no pounds

Mentions Semaglutide

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.

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Peptide math class: figuring out how many milligrams last a month. https://t.co/zp6ameyEdA

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Maintenance Weight

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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

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Don’t miss it tonight live on X 7pm EST ! and if you do, no worries, it’ll be recorded. Stick around until the end for

Don’t miss it tonight live on X 7pm EST ! and if you do, no worries, it’ll be recorded. Stick around until the end for Q&amp;A with some of the most experienced people in the peptide space.

Canadians without a family doctor: how can I get Ozempic prescribed?

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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

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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]

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I took Epitalon hoping it would fix my sleep and It did the opposite.thought it was maybe part of the process and it get

I took Epitalon hoping it would fix my sleep and It did the opposite.thought it was maybe part of the process and it gets bad before doing its job . I started waking up three hours earlier every morning. I stopped taking it and assumed my sleep would eventually reset. Six months later and my life is in shambles, still can't sleep and it's worse than before.

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Has Mounjaro triggered your period?

Has Mounjaro triggered your period?

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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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Found out yesterday that the ability to cook/psycho ratio apparently doesn’t pertain to my wife. She’s on the “MT2 main

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Mentions Semaglutide

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

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

Mentions Oxytocin

Thinking of trying Selank, should I add Semax?

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

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

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Miracle Drug(for me)

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Mentions Semaglutide

Changes in salivary biomarkers before farrowing in sows.

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

Mentions Oxytocin

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

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Stopping starting or any advice please?

Stopping starting or any advice please?

Mentions Tirzepatide

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

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

Mentions Oxytocin

How to cope with poor quality sleep, bad and strange dreams while on Mounjaro?

How to cope with poor quality sleep, bad and strange dreams while on Mounjaro?

Mentions Tirzepatide

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

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

Mentions Oxytocin

Rybelsus

Rybelsus

Mentions Semaglutide

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

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

Mentions Tirzepatide

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

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

Mentions Oxytocin

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

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

Mentions Semaglutide

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

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

Mentions Oxytocin

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

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

Mentions Tirzepatide

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

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

Mentions Kisspeptin

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

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

Mentions Semaglutide

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

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

Mentions Oxytocin

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

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

Mentions Oxytocin

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

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

Mentions Semaglutide

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

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

Mentions Oxytocin

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

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

Mentions Oxytocin

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

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

Mentions Oxytocin