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

Mentions Oxytocin

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

Mentions Semaglutide

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

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

Mentions P21

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

Mentions Semaglutide

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

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

Mentions P21

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

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

Mentions P21

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

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

Mentions Oxytocin

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

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

Mentions Semaglutide