IF 2.9 4区医学

Peptides Pub Date : 2026-05-01 Epub Date: 2026-05-05 DOI: 10.1016/j.peptides.2026.171491

Mengjing Wu , Yixi Wu , Xiaoli Feng , Yusheng Huang , Lijun Chen , Ge Li , Da-Qi Zhang , Wenjie Zhao , Yongmin Chen

{"title":"STING-dependent microglial inhibition by irisin ameliorates neuroinflammation in experimental autoimmune encephalomyelitis","authors":"Mengjing Wu , Yixi Wu , Xiaoli Feng , Yusheng Huang , Lijun Chen , Ge Li , Da-Qi Zhang , Wenjie Zhao , Yongmin Chen","doi":"10.1016/j.peptides.2026.171491","DOIUrl":"10.1016/j.peptides.2026.171491","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system (CNS), characterized by microglial activation and polarization as key drivers of disease pathogenesis. Irisin, an exercise-induced myokine, has been reported to exhibit neuroprotective effects, including anti-inflammatory activity and cognitive improvement. To investigate the therapeutic potential of irisin in the experimental autoimmune encephalomyelitis (EAE) mouse model and its effects on microglial behavior along with the underlying molecular mechanisms, we conducted the present study. Results demonstrated that irisin treatment significantly alleviated EAE severity, evidenced by reduced disease incidence, attenuated weight loss, and improved neurological scores. Histopathological analysis revealed that irisin suppressed inflammatory cell infiltration and reduced demyelination in spinal cord tissues. Furthermore, irisin inhibited microglial overactivation and promoted a phenotypic shift from the pro-inflammatory M1 to the anti-inflammatory M2 microglia. Mechanistically, immunofluorescence co-localization and Western blot analyses confirmed that these beneficial effects were mediated via suppression of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, as indicated by downregulation of STING and phosphorylated interferon regulatory factor 3 (p-IRF3) expression. Collectively, these findings indicate that irisin alleviates neuroinflammation and exerts neuroprotective effects in EAE by modulating microglial activity through inhibition of the cGAS-STING pathway, underscoring its potential as a novel therapeutic candidate for MS.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"197 ","pages":"Article 171491"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841205","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}

引用次数: 0

Comparative characterization of two scorpion toxins, BlTx1 and BlTx2, identifies BlTx2 as a Kv4.1-selective peptide 对两种蝎子毒素BlTx1和BlTx2的比较分析表明，BlTx2是kv4.1选择性肽。

IF 2.9 4区医学

Peptides Pub Date : 2026-05-01 Epub Date: 2026-04-26 DOI: 10.1016/j.peptides.2026.171490

Yuval Levy , Ayalon Reis , Galit Blecher , Oksana Daron , Sara Dadon , Noam Zilberberg

{"title":"Comparative characterization of two scorpion toxins, BlTx1 and BlTx2, identifies BlTx2 as a Kv4.1-selective peptide","authors":"Yuval Levy , Ayalon Reis , Galit Blecher , Oksana Daron , Sara Dadon , Noam Zilberberg","doi":"10.1016/j.peptides.2026.171490","DOIUrl":"10.1016/j.peptides.2026.171490","url":null,"abstract":"<div><div>Voltage-gated potassium channels of the Kv4 subfamily (Kv4.1, Kv4.2, and Kv4.3) mediate transient A-type potassium currents that regulate neuronal excitability, dendritic integration, and cardiac repolarization. Despite their importance, no pharmacological tool has been available to selectively dissect the role of Kv4.1, as existing peptide toxins from the α-KTx15 family display broad activity across Kv4 isoforms. Here, we report the discovery and characterization of two novel scorpion toxins, BlTx1 and BlTx2, isolated from the venom gland transcriptome of <em>Buthacus leptochelys</em>. Both toxins were heterologously expressed in yeast and purified to homogeneity. Electrophysiological recordings from <em>Xenopus laevis</em> oocytes revealed that BlTx1 and BlTx2 potently inhibited Kv4.1 currents, while sparing Kv4.2 and Kv4.3. Among a panel of 20 tested potassium channels, BlTx2 exhibited clear functional selectivity for Kv4.1, with an IC₅₀ of 28 nM, whereas BlTx1 also inhibited Kv1.2. Sequence comparison with related nonselective toxins suggests that a small number of substitutions in the N-terminal half of the peptides underlie BlTx2's unique selectivity profile. This unique isoform selectivity establishes BlTx2 as, to our knowledge, the first toxin showing clear functional selectivity for Kv4.1 within the tested panel, providing a molecular probe for delineating the physiological and pathological contributions of Kv4.1. Such a tool may facilitate clarification of Kv4.1's role in neuronal firing patterns, circadian regulation, and tumor cell proliferation, while avoiding the off-target effects associated with nonselective Kv4 inhibitors. Our findings highlight scorpion venoms as a valuable source of isoform-selective ion channel ligands and open new avenues for basic research and therapeutic development.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"197 ","pages":"Article 171490"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777993","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}

引用次数: 0

Genetic deletion of neuromedin U and neuromedin S confers transient reno-protection in adenine-induced chronic kidney disease 神经medin U和神经medin S基因缺失在腺嘌呤诱导的慢性肾脏疾病中具有短暂的肾保护作用。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-18 DOI: 10.1016/j.peptides.2026.171474

Hiroshi Yoshida , Hitoshi Teranishi , Kenshiro Shikano , Haruka Kato , Magdeline E. Carrasco Apolinario , Toshikatsu Hanada , Takatoshi Hikida , Reiko Hanada

{"title":"Genetic deletion of neuromedin U and neuromedin S confers transient reno-protection in adenine-induced chronic kidney disease","authors":"Hiroshi Yoshida , Hitoshi Teranishi , Kenshiro Shikano , Haruka Kato , Magdeline E. Carrasco Apolinario , Toshikatsu Hanada , Takatoshi Hikida , Reiko Hanada","doi":"10.1016/j.peptides.2026.171474","DOIUrl":"10.1016/j.peptides.2026.171474","url":null,"abstract":"<div><div>Neuromedin U (NMU) and neuromedin S (NMS) are neuropeptides that regulate metabolic, inflammatory, and fibrotic responses through shared receptors. Although dysregulated NMU/NMS signaling has been implicated in metabolic and inflammatory disorders, its involvement in chronic kidney disease (CKD) is unknown. In this study, using an adenine-induced CKD model, we demonstrated that renal mRNA expression of NMU and its receptor NMUR1 was significantly upregulated in parallel with disease progression, suggesting a potential role for this signaling system in CKD pathophysiology. Based on this observation, we examined the impact of genetic deletion of NMU and NMS on adenine-induced renal injury, and demonstrate for the first time that loss of NMU/NMS signaling confers transient reno-protection in experimental CKD.　NMU/NMS double-knockout (dKO) and wild-type mice were fed a 0.2 % adenine diet for 2, 4, or 6 weeks. Renal atrophy and elevations in blood urea nitrogen progressed similarly in both groups; however, serum creatinine levels were significantly lower in dKO mice at 4 weeks, indicating partial preservation of renal function. Gene expression analyses revealed attenuated early inflammatory–fibrotic responses in dKO kidneys, including reduced Tgfb1 mRNA expression at 2 weeks and decreased F4/80 and Col1a1 expression at 4 weeks. Importantly, renal TGF-β1 protein levels were also significantly reduced in dKO mice at 2 weeks. Histological analysis demonstrated a marked reduction in interstitial fibrosis in dKO mice at 4 weeks, whereas no differences were observed at 6 weeks. Together, these findings identify NMU/NMS signaling as a previously unrecognized regulator of early injury responses in experimental CKD.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171474"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258787","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}

引用次数: 0

Apelin-36 attenuates diabetic glomerular endothelial hyperpermeability via the KLF2/Occludin pathway Apelin-36通过KLF2/Occludin通路减轻糖尿病肾小球内皮高通透性

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.peptides.2026.171472

Jinxiao Jiang , Liu Yang , Yuhao Cheng , Meiqin Xiong , Xiaoqin Zhou

{"title":"Apelin-36 attenuates diabetic glomerular endothelial hyperpermeability via the KLF2/Occludin pathway","authors":"Jinxiao Jiang , Liu Yang , Yuhao Cheng , Meiqin Xiong , Xiaoqin Zhou","doi":"10.1016/j.peptides.2026.171472","DOIUrl":"10.1016/j.peptides.2026.171472","url":null,"abstract":"<div><div>An increase in glomerular endothelial cell (GEC) permeability is an early trigger for diabetic nephropathy (DN). This study investigated the protective role of the Apelin-36/APJ axis under diabetic conditions. <em>In vitro</em>, high glucose (HG) downregulated APJ expression and secretion of Apelin-36 in human renal glomerular endothelial cells (HRGECs) in a time-dependent manner and induced endothelial hyperpermeability. Apelin-36 treatment dose-dependently mitigated this hyperpermeability, restored the expression of Occludin and Krüppel-like factor 2 (KLF2) suppressed by HG, and activated the Apelin/APJ system. KLF2 knockdown or pharmacological APJ inhibition abolished the protective effects of Apelin-36. <em>In vivo</em>, Apelin-36 treatment ameliorated albuminuria, restored glomerular Occludin expression, and partially rescued the disrupted Apelin/APJ axis in db/db mice. These findings demonstrate that the Apelin-36/APJ axis protects against glomerular endothelial dysfunction in DN via the KLF2/Occludin pathway, highlighting its potential as a therapeutic target for diabetic renal injury, particularly in the glomerular endothelium.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171472"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197910","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}

引用次数: 0

Human β-defensin-3 as a transcriptional convergence point linking innate immunity, endocrine signals, and tissue repair 人β-防御素-3作为先天免疫、内分泌信号和组织修复的转录趋同点。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-16 DOI: 10.1016/j.peptides.2026.171476

Yolanda M. Jacobo-Delgado , Jaime Eduardo Huerta-Elías , Valeria Cabral-Venegas, Mariana García-Hernández, Bruno Rivas-Santiago

{"title":"Human β-defensin-3 as a transcriptional convergence point linking innate immunity, endocrine signals, and tissue repair","authors":"Yolanda M. Jacobo-Delgado , Jaime Eduardo Huerta-Elías , Valeria Cabral-Venegas, Mariana García-Hernández, Bruno Rivas-Santiago","doi":"10.1016/j.peptides.2026.171476","DOIUrl":"10.1016/j.peptides.2026.171476","url":null,"abstract":"<div><div>Human β-defensin 3 (hBD-3) is a multifunctional host defense peptide with exceptional antimicrobial, immunomodulatory, and tissue-repair properties. Beyond its potent activity against gram-positive and gram-negative bacteria, fungi, and selected viruses, hBD-3 plays a central role in epithelial barrier integrity, chemotactic signaling, and wound healing. Its expression is tightly regulated by an intricate network of pattern-recognition receptors, inflammatory cytokines, growth factors, vitamins, and endocrine mediators. Emerging evidence indicates that hBD-3 functions as a transcriptional convergence point, integrating signals from NF-κB, AP-1, STATs, and nuclear receptors to coordinate antimicrobial and immune responses. Notably, glucocorticoids selectively modulate hBD-3 in ways that differ from other defensins, suggesting unique regulatory mechanisms within immune-endocrine environments. hBD-3 also contributes to angiogenesis, fibroblast activation, and keratinocyte migration, supporting its role in tissue repair and chronic wound management, including in diabetic microenvironments. Recent promoter analyses further reveal potential non-classical regulatory elements that expand current understanding of hBD-3 transcriptional control. Despite these advances, therapeutic manipulation of hBD-3 remains controversial due to its context dependent immunologic effects, potential oncogenic implications, and delivery challenges. This review synthesizes current knowledge on hBD-3 biology, regulation, and function, and discusses the opportunities and limitations for its therapeutic application in infectious and inflammatory diseases.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171476"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220752","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}

引用次数: 0

The roles of nesfatin-1 in the lateral parabrachial nucleus on feeding and glucose metabolism in type 1 diabetic rats 臂旁外侧核内脂素-1在1型糖尿病大鼠摄食和糖代谢中的作用。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-04 DOI: 10.1016/j.peptides.2026.171468

Caishun Zhang , Qing Zhang , Liuxin Wang , Haidan Wang , Qian Lin , Yuxuan Wang , Jiaqing Yu , Kun Zhu , Yunqiu Xia , Jing Dong

{"title":"The roles of nesfatin-1 in the lateral parabrachial nucleus on feeding and glucose metabolism in type 1 diabetic rats","authors":"Caishun Zhang , Qing Zhang , Liuxin Wang , Haidan Wang , Qian Lin , Yuxuan Wang , Jiaqing Yu , Kun Zhu , Yunqiu Xia , Jing Dong","doi":"10.1016/j.peptides.2026.171468","DOIUrl":"10.1016/j.peptides.2026.171468","url":null,"abstract":"<div><div>Nesfatin-1 assumes a crucial role in the regulation of appetite and glucose metabolism. The present study aimed to determine the effect of LPBN nesfatin-1 on food intake and blood glucose in type 1 diabetes (T1DM) rats and underlying mechanisms. Catheter implantation and nucleus microinjection were employed to investigate the effect of LPBN nesfain-1 on the regulation of food intake and blood glucose in Rats with T1DM. <em>In vivo</em> electrophysiological technique was used to record LPBN glucose-sensitive (GS) neurons to explore central underlying mechanisms. ELISA kits were utilized to assess the plasma levels of nesfatin-1, norepinephrine (NE), and epinephrine (E). We found LPBN nesfatin-1 inhibited nocturnal feeding in Rats with T1DM. The glucose regulation of LPBN nesfatin-1 is closely associated with insulin. LPBN nesfatin-1 increased the firing rate of glucose-excited neurons in Rats with T1DM and the firing rate of glucose-inhibited neurons in Wistar Rats. LPBN nesfatin-1 increased plasma NE levels in Wistar Rats under hypoglycemia and decreased plasma E levels in Rats with T1DM with hyperglycemia. These findings suggested that LPBN nesfatin-1 was involved in food intake and blood glucose regulation in Rats with T1DM, which may be achieved by influencing GS neurons and subsequent putative modulation of sympathetic nervous system activity, a pathway that requires further mechanistic validation.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171468"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132551","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}

引用次数: 0

EPI-X4 is a peptide antagonist of CXCR4 with therapeutic prospects for cancer and inflammatory disorders EPI-X4是CXCR4的肽拮抗剂，具有治疗癌症和炎性疾病的前景。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-21 DOI: 10.1016/j.peptides.2026.171479

Micah N. Sagini , Martin R. Berger , Jürgen Muthmann , Eckhard Alt , Wolf-Georg Forssmann

引用次数: 0

Vasopressin and oxytocin: From basic to clinic 抗利尿激素和催产素：从基础到临床。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-17 DOI: 10.1016/j.peptides.2026.171477

Yoichi Ueta, Tatsushi Onaka

引用次数: 0

A pioneer at the interface: Annette Beck-Sickinger – The 2026 Victor Mutt Award Awardee 界面上的先锋：安妮特·贝克-西金格- 2026年维克多·穆特奖得主。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-10 DOI: 10.1016/j.peptides.2026.171473

Herbert H. Herzog, William F. Colmers

引用次数: 0

The protective role of Nesfatin-1 against TNF-α-induced ferroptosis in chondrocytes: Implications for osteoarthritis therapy Nesfatin-1对TNF-α-诱导的软骨细胞铁下垂的保护作用：对骨关节炎治疗的意义。

IF 2.9 4区医学

Peptides Pub Date : 2026-03-01 Epub Date: 2026-02-15 DOI: 10.1016/j.peptides.2026.171475

Yue Wang, Kaili Hu, Fenglin Jiang, Ting Han, Zhangdi Liao, Zixin Gao, Jinhua Yan

{"title":"The protective role of Nesfatin-1 against TNF-α-induced ferroptosis in chondrocytes: Implications for osteoarthritis therapy","authors":"Yue Wang, Kaili Hu, Fenglin Jiang, Ting Han, Zhangdi Liao, Zixin Gao, Jinhua Yan","doi":"10.1016/j.peptides.2026.171475","DOIUrl":"10.1016/j.peptides.2026.171475","url":null,"abstract":"<div><div>Osteoarthritis (OA) progression is significantly driven by chondrocyte ferroptosis, a form of iron-dependent cell death triggered by oxidative stress and lipid peroxidation. This study investigated the protective effect of Nesfatin-1 against TNF-α-induced ferroptosis in mouse primary chondrocytes and explored the underlying mechanism. A ferroptosis model was established using TNF-α (10 ng/mL). Cell viability, cytotoxicity, and key ferroptosis markers were assessed. We found that endogenous NUCB2/nesfatin-1 is expressed in chondrocytes and downregulated by TNF-α. Nesfatin-1 treatment significantly mitigated TNF-α-induced cytotoxicity and improved cell viability. It effectively attenuated lipid peroxidation, as evidenced by reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels, and restored glutathione peroxidase (GPx) activity. Nesfatin-1 also reduced 4-hydroxynonenal (4-HNE) protein adducts, preserved SLC7A11 expression, and restored total glutathione (GSH) content. Furthermore, Nesfatin-1 reduced intracellular Fe<sup>2 +</sup> accumulation by downregulating transferrin receptor 1 (TFR1) and upregulating ferritin heavy chain (FTH). It also suppressed the ferroptosis driver ACSL4 and upregulated the key inhibitor GPx4. Crucially, Nesfatin-1 preserved the expression of extracellular matrix components, collagen II, and aggrecan, similar to the ferroptosis inhibitor Ferrostatin-1. Mechanistically, Nesfatin-1 activated the Nrf2/HO-1 signaling pathway, and its protective effects were abolished by the Nrf2 inhibitor ML385. In conclusion, Nesfatin-1 alleviates TNF-α-induced chondrocyte ferroptosis by activating the Nrf2/HO-1 pathway, suggesting its potential as a therapeutic agent for OA.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"196 ","pages":"Article 171475"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146213738","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}

引用次数: 0

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