Peptides最新文献

{"title":"MPN-12-NH2 shows potent antinociception effects by targeting opioid, cannabinoid, and neuropeptide FF receptors","authors":"Lanxia Zhou ,&nbsp;Jing Zhang ,&nbsp;Chenxi Mei ,&nbsp;Zhanyu Niu ,&nbsp;Huiming Bao ,&nbsp;Yaofeng Zhao ,&nbsp;Zhonghua Zhang ,&nbsp;Dingnian Gou ,&nbsp;Shouliang Dong","doi":"10.1016/j.peptides.2025.171453","DOIUrl":"10.1016/j.peptides.2025.171453","url":null,"abstract":"<div><div>The neuropeptide FF (NPFF) system plays an important role in regulating the analgesic effects of opioids and cannabis. Incorporating NPFF pharmacophores at the C-terminus of opioid or cannabinoid peptides has emerged as a strategy to enhance analgesic potency while mitigating adverse effects. However, the development of such multi-target compounds has been limited to two systems, with no successful commercialization to date. Hence, we developed the chimeric peptide MPN-12-NH₂ by incorporating the opioid peptide morphiceptin, the core sequence of pepcans NFKL, and the NPFF analog PFR(Tic)-NH₂. In the mouse tail flick test, intracerebroventricular (i.c.v.) injection of MPN-12-NH₂ demonstrated dose-dependent analgesic effects (ED₅₀ = 0.71 nmol/mouse). Furthermore, molecular docking and molecular dynamics (MD) simulations were employed to elucidate the binding patterns of MPN-12-NH₂ with opioid receptors, cannabinoid receptors, and neuropeptide receptors. <em>In vitro</em> studies revealed that MPN-12-NH₂ is a multifunctional agonist of mu opioid receptors (MOR), delta opioid receptors, cannabinoid 1 receptors (CB1), CB2, and NPFF2 receptors. Subsequently, receptor antagonism studies suggested that the central analgesic effects of MPN-12-NH₂ were primarily mediated by MOR, CB1, and NPFF receptors. Furthermore, we found that i.c.v. injection of MPN-12-NH₂ dose-dependently alleviated pathological pain responses in the SNI, carrageenan, and acetic acid writhing models. However, MPN-12-NH₂ (3 nmol/mouse, i.c.v.) did not result in addiction, analgesic tolerance, or microglial cell alterations in the PAG region. Additionally, MPN-12-NH₂ effectively differentiated its analgesic effects on acute pain from its inhibitory effects on gastrointestinal motility, with an ED₅₀ ratio of 14.21-fold. In summary, the multi-target compound MPN-12-NH₂ exhibited potent analgesic activity mediated by MOR, CB1, and NPFF receptors in mice, along with a favorable side-effect profile. These findings pave a new way for the development of opioid/cannabinoid/NPFF agonists.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171453"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relaxin-2 counteracts TNF-α-induced senescence in human primary chondrocytes by enhancing telomerase activity and modulating SIRT1/p53 signaling","authors":"Jinfeng Pei,&nbsp;Guohui Wang,&nbsp;Minwei Yang,&nbsp;Liwei Liu","doi":"10.1016/j.peptides.2025.171445","DOIUrl":"10.1016/j.peptides.2025.171445","url":null,"abstract":"<div><div>The pro-inflammatory cytokine TNF-α plays a crucial role in promoting cellular senescence in chondrocytes, contributing to the pathological progression of osteoarthritis (OA). Relaxin-2, a biologically active peptide hormone with diverse effects, has been investigated for its potential protective role against TNF-α-induced cellular senescence in human primary chondrocytes. In this study, human primary chondrocytes were exposed to TNF-α (10 ng/mL) with and without the presence of recombinant human relaxin-2 (rh relaxin-2). SA-β-gal staining indicated that rh relaxin-2 effectively mitigated TNF-α-induced cellular senescence in these cells. Furthermore, rh relaxin-2 enhanced telomerase activity and prevented cell cycle arrest at the G0/G1 phase induced by TNF-α. Additionally, rh relaxin-2 reduced the expression levels of plasminogen activator Inhibitor-1 (PAI-1) and p21, key regulators of cellular senescence. Interestingly, TNF-α increased K382 acetylation of p53 but decreased SIRT1 expression. Notably, knocking down SIRT1 negated the protective effects of rh relaxin-2 on cellular senescence, suggesting that SIRT1 is involved in mediating the protective effects of rh relaxin-2. These findings provide new insights into the potential therapeutic use of rh relaxin-2 for OA treatment through a novel mechanism.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171445"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Greetings page","authors":"","doi":"10.1016/S0196-9781(25)00120-2","DOIUrl":"10.1016/S0196-9781(25)00120-2","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171459"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythropoietin attenuates lead-induced spatial memory deficits and anxiety-like behavior by suppressing hippocampal oxidative stress, cell death inhibition, and inflammation reduction","authors":"Sina Vahedi ,&nbsp;Mehdi Khaksari ,&nbsp;Shahram Sharafi ,&nbsp;Vida Hojati ,&nbsp;Nahid Masoudian","doi":"10.1016/j.peptides.2025.171449","DOIUrl":"10.1016/j.peptides.2025.171449","url":null,"abstract":"<div><div>Lead, a neurotoxic metal, impairs hippocampal structure by inducing cell death, promoting neuroinflammation, and disrupting the oxidant–antioxidant balance. Additionally, lead-exposed animals display anxiety-like behaviors and deficits in hippocampal-dependent learning and memory. Erythropoietin (EPO), a glycoprotein hormone, stands out as a promising candidate, given its potential to enhance neuronal survival, reduce inflammation, and restore the antioxidant, offering hope for mitigating lead-induced neurodegeneration. This study examined EPO's neuroprotective effect against lead-induced hippocampal damage in male Wistar rats. Rats were divided into four groups (n = 16): control, lead acetate, and lead acetate with EPO (1000 or 2500 IU/kg). Lead (25 mg/kg) was given i.p. for 3 days; EPO was administered i.p. for 7 days after. Controls received distilled water. Spatial memory and anxiety were evaluated using the Morris water maze and elevated plus maze, respectively. Concentrations of antioxidant enzymes and TNF-α were measured using an ELISA assay. Nissl staining assessed necrotic cell death. GFAP and caspase-3 expression were evaluated by immunohistochemistry. The results indicate that EPO administration significantly ameliorated spatial memory deficits and anxiety-like behavior induced by lead exposure. EPO significantly elevates superoxide dismutase, glutathione and catalase levels (P &lt; 0.001). It results in a notable reduction in malondialdehyde (P &lt; 0.001) and TNF-α (P &lt; 0.05) levels relative to the lead group. The EPO group showed reduced necrotic cell death (P &lt; 0.01), and lower caspase-3 and GFAP-positive cell levels (P &lt; 0.001). The research indicates that EPO provides significant neuroprotection against lead via antioxidant activity, inflammation reduction, and apoptosis suppression.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171449"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon acutely stimulates hepatic gluconeogenesis","authors":"Caroline Hansen ,&nbsp;Josephine Fisker-Andersen ,&nbsp;Christine Rasmussen ,&nbsp;Frederik R. Ceutz ,&nbsp;Jens J. Holst ,&nbsp;Marie Winther-Sørensen ,&nbsp;Nicolai J. Wewer Albrechtsen","doi":"10.1016/j.peptides.2025.171448","DOIUrl":"10.1016/j.peptides.2025.171448","url":null,"abstract":"<div><div>Glucagon increases hepatic glucose production by activating both glycogenolysis and gluconeogenesis. Its effect on gluconeogenesis is traditionally attributed to increased expression of gluconeogenic enzyme genes. However, whether glucagon’s transcription-independent actions are sufficient to acutely stimulate hepatic glucose output remains uncertain. To investigate this, we examined the acute effects of glucagon on hepatic gluconeogenesis using an <em>in situ</em> perfused mouse liver model. Livers from male, freely fed C57BL/6JRj mice (11–16 weeks) were perfused via the portal vein with oxygenated Krebs–Henseleit bicarbonate buffer. Hepatic glucose output was measured every three minutes. Glucagon (10 nM) added to the perfusate rapidly increased hepatic glucose production, with a 3.6-fold rise observed within minutes. This effect was absent in overnight-fasted mice. When gluconeogenic substrates (6 mM lactate, pyruvate, or both) were added to the perfusate, acute glucose production was stimulated. Co-administration of glucagon (10 nM) further enhanced glucose output by 36–43 % (p ≤ 0.044). Repeated stimulation experiments confirmed the reproducibility and reversibility of the response. These findings demonstrate that glucagon acutely and reversibly enhances hepatic gluconeogenesis, independent of transcriptional regulation and in the absence of hepatic glycogen. Our data redefine glucagon as a rapid metabolic modulator capable of minute-to-minute control of hepatic glucose output in the fasted state. This has important implications for our understanding of glucose homeostasis during fasting, stress, and disease, and challenges conventional textbook views of glucagon’s role as solely a transcriptional regulator of gluconeogenic genes.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171448"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyridostigmine attenuates placental-ischemia-upregulated placental angiotensin II type 1 receptor in rats","authors":"Abdoulaye Issotina Zibrila ,&nbsp;Asma A. Alkuhali ,&nbsp;Meng Yuan ,&nbsp;Zhaoshu Zeng ,&nbsp;Md. Ahasan Ali ,&nbsp;Ming Zeng ,&nbsp;Amr Mostafa Elenany ,&nbsp;Manza Manzoor ,&nbsp;Xiaomin Wang ,&nbsp;Ming Zhao ,&nbsp;Lianhai Jin ,&nbsp;Jinjun Liu","doi":"10.1016/j.peptides.2025.171450","DOIUrl":"10.1016/j.peptides.2025.171450","url":null,"abstract":"<div><div>Preeclampsia (PE) is associated with increased activation and sensitivity of the Angiotensin II type 1 receptor (AT1R) and inflammation. In this work, we assessed the effect of Pyridostigmine (PYR), with reported anti-inflammatory properties, on placental AT1R in a rat model of PE with placental ischemia. AT1R expression in the placenta from pregnant women (with and without PE) was assessed. Pregnant rats underwent sham or reduced uterine perfusion pressure (RUPP) operation on gestational day 14 (GD14). Dams were treated with either losartan (20 mg/kg/day) or PYR (20 mg/kg/day) or water for five days. Blood pressure and feto-maternal data were collected and placental samples were harvested and processed for molecular analysis. The human trophoblast (HTR-8/SVneo) cell lines were stimulated with Angiotensin II to activate AT1R and treated with Acetylcholine (ACh) to simulate the effects of PYR-increased ACh on trophoblasts. RUPP upregulated the placental AT1R expression. We confirmed that losartan lowers the mean arterial pressure (MAP) in RUPP rats and showed that losartan inhibited RUPP-upregulated placental AT1R, NOX4, TNF-α, IL-1β, and NF-κBp65. On the other hand, PYR lowered the elevated MAP in RUPP and inhibited the placental expression of AT1R, NOX4, TNF-α, IL-1β and NF-κBp65 and reduced the circulating and placental AChE activities. At the cellular level, ACh reduced the angiotensin II-increased NOX4 and NF-κBp65 expressions in the HTR-8/SVneo cell line. This study has confirmed the anti-hypertensive effects of losartan and that of PYR and revealed the anti-inflammatory effect of AT1R antagonism with losartan and the ability of PYR to mitigate the expression and the signaling of placental AT1R.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171450"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewer Acknowledgement page","authors":"","doi":"10.1016/S0196-9781(25)00121-4","DOIUrl":"10.1016/S0196-9781(25)00121-4","url":null,"abstract":"","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171460"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FSTL1 silencing protects against lipopolysaccharide-induced ferroptosis in renal tubular cells by regulating the PI3K/Akt pathway","authors":"Minyu Shi ,&nbsp;Yuting Luan ,&nbsp;Ziqing Zhang,&nbsp;Xixiang Xi,&nbsp;Wufeng Li","doi":"10.1016/j.peptides.2025.171454","DOIUrl":"10.1016/j.peptides.2025.171454","url":null,"abstract":"<div><div>Sepsis-associated acute kidney injury (AKI) is a major cause of morbidity and mortality, and lipopolysaccharide (LPS)-induced ferroptosis is a critical mechanism of renal tubular cell injury. Follistatin-like 1 (FSTL1) is a matricellular protein implicated in inflammation and oxidative stress; however, its role in LPS-induced ferroptosis in renal tubular cells remains unknown. Human renal proximal tubular epithelial (HK-2) cells were exposed to increasing concentrations of LPS to evaluate FSTL1 expression levels. FSTL1 silencing was achieved by siRNA transfection, and its effects on PI3K/Akt signaling, apoptosis, oxidative stress, and ferroptosis were assessed using western blotting, RT-qPCR, flow cytometry, and fluorescent probes. The PI3K/Akt inhibitor LY294002 was used to validate the involvement of this pathway. FSTL1 expression was significantly upregulated by LPS in a dose-dependent manner at both the mRNA and protein levels. Silencing FSTL1 markedly increased the phosphorylation of PI3K and Akt and significantly attenuated LPS-induced apoptosis, as evidenced by increased cell viability and decreased number of Annexin V-positive cells. FSTL1 silencing also decreased reactive oxygen species and malondialdehyde levels, while enhancing superoxide dismutase activity and glutathione content. Moreover, FSTL1 silencing reduced mitochondrial ferrous iron accumulation and restored Nrf2, SLC7A11, GPX4, and FTH1, alongside decreased ACSL4 expression. These protective effects were reversed by LY294002, indicating a dependence on PI3K/Akt signaling. FSTL1 mediates LPS-induced apoptosis, oxidative stress, and ferroptosis in renal tubular cells via the PI3K/Akt pathway. Targeting FSTL1-PI3K/Akt signaling may represent a novel approach to mitigate ferroptotic injury in endotoxin-stimulated renal tubular cells, providing mechanistic insights relevant to LPS-induced tubular injury model.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"194 ","pages":"Article 171454"},"PeriodicalIF":2.9,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive peptides in cosmetic formulations: Review of current in vitro and ex vivo evidence","authors":"Nathalie van Walraven ,&nbsp;Richard J. FitzGerald ,&nbsp;Hans-Jürgen Danneel ,&nbsp;Miryam Amigo-Benavent","doi":"10.1016/j.peptides.2025.171440","DOIUrl":"10.1016/j.peptides.2025.171440","url":null,"abstract":"<div><div>Bioactive peptides are increasingly employed in cosmetic products and these are generically known as cosmetic peptides. This review aims to provide an update on current information related to commercially available cosmetic peptides, and the <em>in vitro</em> and <em>ex vivo</em> evidence for their potential biological effects. A total of 102 commercially available cosmetic peptides were identified. The majority of these peptides are inspired by molecules already found in the human body, including sequences from extracellular matrix molecules, also known as matrikines. Cosmetic peptides are produced either through chemical synthesis or via biotechnological processes. Their claimed biological activities include signaling to increase collagen and hyaluronic acid production, modulation of pigmentation, maintenance of a healthy skin microbiome, antioxidant activity and cellular defense, immunomodulation, neurotransmitter inhibition, enzyme activity inhibition and trace mineral carriers. The primary structure and current scientific evidence for the bioactivities of these peptides are presented and discussed. The review highlights the diverse methodological approaches used and the outcomes measured in the assessment of cosmetic peptide efficacy. Overall, a large range of cosmetic peptides are commercially available whose efficacy is supported by divergent levels of <em>in vitro</em> and <em>ex vivo</em> data.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"193 ","pages":"Article 171440"},"PeriodicalIF":2.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive peptide HX-12C enhances fibroblast function through TGF-β/Smad signaling pathway and promotes wound healing in vitro and in vivo","authors":"Yujing Wang ,&nbsp;Baisheng Wang ,&nbsp;Yiyang Li ,&nbsp;Zhenmin Cao ,&nbsp;Zuodong Qin ,&nbsp;Xiaofang Luo ,&nbsp;Kun Li","doi":"10.1016/j.peptides.2025.171446","DOIUrl":"10.1016/j.peptides.2025.171446","url":null,"abstract":"<div><div>Closure of skin wounds is essential for resistance to pathogens. Collagen synthesis dominated by fibroblasts, re-epithelialization driven by keratinocytes, and angiogenesis governed by vascular endothelial cell lumen formation all play crucial roles in wound healing. Our previous study revealed that the small peptide HX-12C modified from the antimicrobial peptide Temporin had favorable antimicrobial activity and that a hydrogel complex containing HX-12C accelerates the healing of infected wounds. Here, we demonstrated that HX-12C promoted the proliferation, migration and collagen synthesis of fibroblasts, the proliferation of keratinocytes and the proliferation and migration of vascular endothelial cells <em>in vitro</em>, and accelerated the healing of mice skin wounds <em>in vivo</em>. Moreover, we found that HX-12C activated collagen synthesis in fibroblasts early by activating the TGF-β/Smad signaling axis. Thus, we suggested that HX-12C is a promising candidate for clinical application with therapeutic potential to promote wound healing.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"193 ","pages":"Article 171446"},"PeriodicalIF":2.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}