Peptides最新文献

{"title":"Protective effects of PACAP against high glucose-induced inflammation on air-liquid interface corneal epithelium barrier","authors":"Grazia Maugeri ,&nbsp;Agata Grazia D’Amico ,&nbsp;Nicoletta Palmeri ,&nbsp;Elisabetta Pricoco ,&nbsp;Desiree Brancato ,&nbsp;Concetta Federico ,&nbsp;Velia D’Agata","doi":"10.1016/j.peptides.2025.171432","DOIUrl":"10.1016/j.peptides.2025.171432","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is a chronic metabolic disease considered the “epidemic” of the new millennium, with devastating impacts on quality of life and global prevalence. One of the most common ocular complications is diabetic keratopathy (DK), often overlooked compared to other diabetes-related diseases. This disease causes significant corneal damage and is characterized by an overactive inflammatory condition, alteration of the corneal epithelial barrier, and delayed wound healing. Current therapies do not always ensure effective restoration of corneal function. In our previous study, we found that changes in the endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) expression can concur for delayed epithelial wound healing in diabetic cornea. Moreover, the peptide showed cytoprotective effects on the corneal epithelium, promoting cell viability and wound healing under high glucose conditions, suggesting its potential effect in this diabetes-related disease. Therefore, this study aims to investigate the effect of PACAP against hyperglycemia-induced inflammation. To better resemble the natural conditions of corneal epithelium in vivo, an air-liquid interface (ALI) culture of the corneal epithelial cells was performed. The ALI corneal epithelium was cultured under high-glucose conditions to generate a model of DK. Our model reproduced well-established molecular and cellular characteristics of this pathology, including barrier thickness decrease and inflammation, with increased expression of IL-1β, TNF-α, and p-NF-kB. Our results indicated that PACAP significantly reduced the levels of proinflammatory cytokines IL-1β and TNF-α and inhibited the activation of NF-kB, an important mediator of inflammation. Moreover, PACAP improved epithelial morphology and corneal barrier thickness, suggesting its therapeutic potential in the treatment of DK.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"192 ","pages":"Article 171432"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656020","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":"Synthesis of the plant cyclotide cyO14 via the hydrazide strategy and investigation of its antibacterial and insecticidal activities","authors":"Fawei He ,&nbsp;Yunfei Cui ,&nbsp;Xue Tang ,&nbsp;Dongting Zhangsun ,&nbsp;Sulan Luo ,&nbsp;Yong Wu","doi":"10.1016/j.peptides.2025.171423","DOIUrl":"10.1016/j.peptides.2025.171423","url":null,"abstract":"<div><div>The plant cyclotide <strong>cyO14</strong>, a member of the Möbius subfamily, was synthesized using an hydrazide-based strategy, and its antibacterial, insecticidal, and hemolytic activities were investigated. The linear precursor of cyO14 was prepared via solid-phase peptide synthesis (SPPS) on an hydrazide resin, followed by head-to-tail cyclization through an hydrazide-mediated ligation and disulfide bond formation via spontaneous oxidation. The synthesized cyclotide exhibited a structure identical to that of the naturally occurring counterpart. Biological evaluation demonstrated that <strong>cyO14</strong> possessed significant antibacterial activity against <em>Cryptococcus neoformans</em> and <em>Bacillus subtilis</em>, with a minimum inhibitory concentration (MIC) of 1 μM. Mechanistic studies revealed that <strong>cyO14</strong> exerted its antibacterial effects by disrupting bacterial membranes. Moreover, <strong>cyO14</strong> exhibited negligible hemolytic activity (HD₅₀ &gt; 1000 μM), suggesting excellent biocompatibility. In insecticidal assays, <strong>cyO14</strong> effectively inhibited the growth and development of <em>Helicoverpa armigera</em>. These findings indicate that the hydrazide-mediated cyclization strategy is an efficient method for the synthesis of Möbius subfamily cyclotides, and that <strong>cyO14</strong> possesses promising pharmaceutical and agricultural potential due to its potent antibacterial and insecticidal activities coupled with high biological safety.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171423"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340341","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":"Characterization of thyrotropin-releasing hormone (TRH) and its receptors (TRHRs) in Nile tilapia: Molecular identification, ligand-receptor interaction and expression profile","authors":"Guixian Bu ,&nbsp;Tao Yong ,&nbsp;Yuqing Tang ,&nbsp;Jingyan Luo ,&nbsp;Yu Ji ,&nbsp;Li Guo ,&nbsp;Shasha Guo ,&nbsp;Shuai Yang ,&nbsp;Linyan Huang ,&nbsp;Xianyin Zeng ,&nbsp;Caiyun Sun ,&nbsp;Fengyan Meng","doi":"10.1016/j.peptides.2025.171426","DOIUrl":"10.1016/j.peptides.2025.171426","url":null,"abstract":"<div><div>Thyrotropin-releasing hormone (TRH) is a highly conserved tripeptide across vertebrates and regulates various biological processes, including energy metabolism, appetite, and reproduction. The functions of TRH are mediated by TRH receptors (TRHRs). In vertebrates, three <em>TRHR</em> subtypes have been identified, namely <em>TRHR1</em>, <em>TRHR2</em>, and <em>TRHR3</em>. However, <em>TRHR2</em> and <em>TRHR3</em> are often lost in some vertebrate lineages, highlighting the evolutionary divergence of the TRH-TRHR system. Although extensive research has been conducted in mammals, studies concerning the biological roles of TRH-TRHR system remain limited in fish. Therefore, using Nile tilapia (ti-) as a teleost model, we cloned the full-length cDNA of <em>TRH</em> and its receptors. Based on sequence alignment, synteny analysis and phylogenetic tree construction, we observed that <em>TRHR2</em> has been lost in Nile tilapia. The cloned <em>tiTRHRs</em> were designated as <em>tiTRHR1a</em>, <em>tiTRHR1b</em>, and <em>tiTRHR3</em>. Using luciferase reporter assays, signal pathway inhibitors and western blot analysis, we demonstrated that tiTRH could effectively activate tiTRHR1a, tiTRHR1b, and tiTRHR3, leading to the stimulation of intracellular calcium mobilization, MAPK/ERK, and cAMP/PKA signaling cascades. However, the efficiencies in activating signaling pathways differed between tiTRHR subtypes upon tiTRH treatment. Quantitative real-time PCR revealed that <em>tiTRH</em> and <em>tiTRHRs</em> were mainly expressed in the central nervous system (CNS) including the hypothalamus. Moreover, hypothalamic mRNA levels of <em>tiTRH</em> and <em>tiTRHR1b</em> were significantly downregulated in response to short-term fasting and acute cold exposure, while <em>tiTRHR1a</em> expression was only responsive to acute cold stress. Collectively, our data will facilitate a better understanding of the components and functions of the TRH-TRHR system in teleost.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171426"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549721","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":"PACAP inhibits sepsis-associated acute lung injury by inhibiting the Sp1/AQP1 pathway","authors":"Zhuangzhi Xiong ,&nbsp;Xiaoqin Zhou ,&nbsp;Yufeng Li ,&nbsp;Liu Yang","doi":"10.1016/j.peptides.2025.171411","DOIUrl":"10.1016/j.peptides.2025.171411","url":null,"abstract":"<div><div>Sepsis-induced acute lung injury (ALI) represents a severe pathological state marked by uncontrolled inflammation, redox imbalance, and alveolar-capillary barrier breakdown. Here, we evaluated the therapeutic potential of pituitary adenylate cyclase-activating polypeptide (PACAP) in a murine sepsis-ALI model. PACAP treatment notably ameliorated histological damage, reduced oxidative stress biomarkers, and mitigated inflammatory processes, including neutrophil accumulation and pro-inflammatory cytokine release. Molecular analysis revealed PACAP-mediated downregulation of Aquaporin-1 (AQP1) and specificity protein 1 (Sp1), key regulators of alveolar fluid homeostasis and inflammatory signaling. Genetic Sp1 overexpression abrogated PACAP-induced AQP1 suppression, validating the Sp1/AQP1 signaling pathway as a critical mediator of PACAP’s protective effects. Additionally, in vitro MTT assays on RAW 264.7 macrophages demonstrated that PACAP has low toxicity at biologically relevant levels. These findings demonstrate PACAP’s therapeutic promise for sepsis-ALI through modulation of the Sp1/AQP1 axis.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171411"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132597","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":"Recombinant production of isotope-labeled human α-defensin 5 via calmodulin fusion and insights into its expression enhancement","authors":"Shaonan Yan ,&nbsp;Hao Gu ,&nbsp;Mitsuki Shibagaki ,&nbsp;Jeremia Oktavian Chrisnanto ,&nbsp;Fumi Hirai ,&nbsp;Hiroyuki Kumeta ,&nbsp;Yasuhiro Kumaki ,&nbsp;Yuki Yokoi ,&nbsp;Kiminori Nakamura ,&nbsp;Takashi Kikukawa ,&nbsp;Tokiyoshi Ayabe ,&nbsp;Tatsuya Arai ,&nbsp;Tomoyasu Aizawa","doi":"10.1016/j.peptides.2025.171425","DOIUrl":"10.1016/j.peptides.2025.171425","url":null,"abstract":"<div><div>Human α-defensin 5 (HD5), a cysteine-rich antimicrobial peptide critical for intestinal innate immunity, has been extensively studied for its structural and functional properties. Both the reduced form (HD5red) and the oxidized form (HD5oxi) exist <em>in vivo</em> and exhibit distinct antimicrobial activity spectra. In this study, we developed an efficient method to overexpress recombinant HD5 in <em>Escherichia coli</em> (<em>E. coli</em>) BL21 (DE3) strain by using calmodulin (CaM), which also interacts with antimicrobial peptides, as a fusion partner. Fusion expression suppressed the degradation of HD5 and reduced its toxicity to host cells. Following purification of the fusion protein and enzymatic cleavage to release the HD5 region, we successfully obtained sufficient amounts (yielding 1.5–1.7 mg/L culture) of active recombinant HD5oxi and HD5red for various applications, including stable isotope-labeled peptides for NMR analysis. Furthermore, we investigated the protective effect of CaM fusion and the mechanism of disulfide bond formation using CD and NMR spectroscopy, structural prediction, and molecular dynamics simulations. Our results suggest that the appropriate interaction strength between CaM and the HD5 region in the fusion state is a key factor for stable production.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171425"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529211","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":"Impact of galanin receptors 2 and 3 double-knockout on neuroinflammation and functional recovery following traumatic brain injury","authors":"Susanne M. Brunner ,&nbsp;Stefanie Gaisbauer ,&nbsp;Patrick N. Pallier ,&nbsp;Ping K. Yip ,&nbsp;Andrea Ramspacher ,&nbsp;Julia Leitner ,&nbsp;Felix Sternberg ,&nbsp;Christina Erhardt-Kreutzer ,&nbsp;Theresa Haslauer ,&nbsp;Sara Huber ,&nbsp;Lara Bieler ,&nbsp;Sebastien Couillard-Despres ,&nbsp;Barbara Kofler","doi":"10.1016/j.peptides.2025.171415","DOIUrl":"10.1016/j.peptides.2025.171415","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is one of the world’s leading causes of death and disability in young individuals and the mechanism underlying TBI-associated neuroinflammation is poorly understood. The regulatory neuropeptide galanin (GAL) and its three receptors (GAL_1–3R) are assumed to modulate the neuroinflammatory response following TBI, especially by signalling via GAL₂R and GAL₃R. Therefore, the role of GALRs in acute neuroinflammation and functional recovery following moderate Controlled Cortical Impact TBI was studied using GAL_2/3R-double-KO (GAL_2/3R-KO) mice. Brains and cerebrospinal fluid (CSF) were collected at day 1 and 30 days post TBI. Functional recovery post TBI was assessed by the modified Neurological Severity Score (mNSS), Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test. Post TBI (day 1–28 post injury), neurological dysfunction was more severe in GAL_2/3R-KO mice than in WT mice. At 1 day post TBI, inflammatory markers and several nerve growth factors significantly increased in the ipsilateral hemisphere, compared to the contralateral hemisphere in both GAL_2/3R-KO and WT mice. At 4 days post surgery, TBI mice entered significantly more frequent the open-arms in the EPM compared to Sham-operated mice, suggestive of increased exploratory behaviour in TBI mice. At 30 days post TBI, immunostaining of brain sections revealed significant differences in vascularisation and glial scarring in the cortex when comparing TBI and Sham-operated mice, but genotypes were similar. In summary, the results indicate that GAL₂R and/or GAL₃R have a neuroprotective role following moderate TBI, as the severity was significantly lower in their presence than in their absence.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171415"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143283","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":"Endogenous opiates and behavior: 2024","authors":"Richard J. Bodnar","doi":"10.1016/j.peptides.2025.171422","DOIUrl":"10.1016/j.peptides.2025.171422","url":null,"abstract":"<div><div>This paper is the forty-seventh consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2024 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18).</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171422"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314462","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":"Mechanical stretch improves high glucose-induced leptin resistance thus promoting glucose uptake of C2C12 myoblasts","authors":"Shaoting Fu ,&nbsp;Jin Peng ,&nbsp;Xiaohui Wang","doi":"10.1016/j.peptides.2025.171424","DOIUrl":"10.1016/j.peptides.2025.171424","url":null,"abstract":"<div><div>Exercise has been shown to alleviate central leptin resistance (LR), while the effects of exercise on peripheral especially skeletal muscle LR and its mechanisms remain poorly understood. In this study, we explored the effect and mechanisms of mechanical stretch (mimic exercise in vitro) on high glucose-induced LR of C2C12 myoblasts. We found (1) 65 mM glucose-induced LR of C2C12 cells was improved by 15 % stretch lasting for 3 or 6 h (represented as decrease of leptin and increases of leptin receptor (LepR) and glucose uptake), with more glucose uptake in 6h-stretch than 3h-stretch; (2) 15 % stretch changed the levels of important regulators of LR, including increasing signal transducer and activator of transcription 3 (STAT3), decreasing protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling-3 (SOCS3), with higher alterations of STAT3 and SOCS3 in 6h-stretch than 3h-stretch; (3) 15 % stretch activated the classical pathway regulating glucose metabolism, including increasing the levels of insulin-like growth factor (IGF-1), IGF-1 receptor (IGF-1R), insulin receptor substrate 1 (IRS-1), protein kinase B (Akt) and glucose transporter 4 (GLUT4), enhancing activities of phosphoinositide 3-kinase (PI3K) and Akt, with more increases of IGF-1R and IRS1 in 6h-stretch than 3h-stretch and enhanced GLUT4 only in 6h-stretch. Altogether, 15 % stretch alleviated high glucose-induced LR of C2C12 myoblasts through increasing STAT3 and decreasing PTP1B and SOCS3, then enhancing glucose uptake via IGF-1/IGF-1R-PI3K/Akt-GLUT4 pathway, which would deepen our understanding how exercise improved skeletal muscle LR and subsequent glucose uptake.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171424"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522375","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":"Effect of central UAG on metabolic associated fatty liver disease: A possible mechanism involving in GLP-1 neural pathway","authors":"Wenxiu Xu ,&nbsp;Zixin Du ,&nbsp;Jing Wang ,&nbsp;Yating Gong ,&nbsp;Jiantong Yu ,&nbsp;Xueyuying Wang ,&nbsp;Xiangrong Sun ,&nbsp;Yanling Gong","doi":"10.1016/j.peptides.2025.171427","DOIUrl":"10.1016/j.peptides.2025.171427","url":null,"abstract":"<div><h3>Objective</h3><div>The study aimed to investigate the possible effect of central unacylated ghrelin (UAG) on metabolic associated fatty liver disease (MAFLD) and its underlying mechanism.</div></div><div><h3>Methods</h3><div>A high fat diet (HFD) was fed to rat to construct MAFLD model. UAG was administered via intra-cerebroventricular injection (ICV) and its effect on MAFLD was observed. Glucagon-like peptide-1 (GLP-1) neural pathway was observed via FluoroGold (FG) retrograde tracking combined with immunofluorescence. To assess the involvement of the GLP-1 pathway, GLP-1 receptor (GLP-1R) inhibitor Exendin (9−39) was injected prior to ICV of UAG.</div></div><div><h3>Results</h3><div>ICV administration of UAG significantly reduced lipid accumulation in liver and liver injury in MAFLD rats which was partially attenuated by Exendin(9−39). Central UAG upregulated and activated GLP-1 neurons in nucleus tractus solitarii (NTS), and increased GLP-1 projections from NTS to paraventricular hypothalamic nucleus (PVN) and ventral tegmental area (VTA), respectively. Consequently, GLP-1R in PVN and VTA was activated, resulting in decreased food intake and reward behavior, as well as increased hepatic insulin sensitivity via activation of IRS-1/PI3K/Akt signaling pathway. These changes downregulated key lipogenic enzymes, including fatty acid synthase (FAS), acetyl-CoA Carboxylase (ACC) and stearoyl-CoAdesaturase-1 (SCD-1), thereby alleviating MAFLD.</div></div><div><h3>Conclusion</h3><div>These findings suggest that central UAG might alleviate MAFLD by modulating GLP-1 neuronal pathway from NTS to PVN and VTA. Further studies are needed to identify the specific receptor for UAG and its potential interaction with GLP-1 or GLP-1R, which could provide direct evidence for the role of central UAG in regulating food intake and lipid metabolism in MAFLD.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171427"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567720","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":"Neurokinin B is a potential target for treating disruption of intestinal mucosal barrier in acute mechanical intestinal obstruction","authors":"Feifan Wang ,&nbsp;Xia Jiang ,&nbsp;Zifeng Zhao ,&nbsp;Yuanyuan Wang ,&nbsp;Haibo Jiang ,&nbsp;Yingchao Gao ,&nbsp;Haobo Wang ,&nbsp;Zhongxin Li","doi":"10.1016/j.peptides.2025.171419","DOIUrl":"10.1016/j.peptides.2025.171419","url":null,"abstract":"<div><h3>Background</h3><div>The neurokinin-B (NKB)/neurokinin-3-receptor (NK3R) pathway is involved in the inflammatory response. However, its role in the disruption of intestine mucosal barrier during mechanical intestinal obstruction (IO) remains unknown.</div></div><div><h3>Methods</h3><div>We collected serum samples from 30 mechanical IO patients and 30 healthy volunteers and measured the serum levels of NKB, lipopolysaccharide (LPS), diamine oxidase (DAO), and D‑lactate (D‑LA) by using ELISA. We subsequently used a mechanical IO mice model and intraperitoneally injected the mice with NKB (Senktide) and NK3R antagonist (NK3Ra). We used the ELISA to measure the tumor necrosis factor (TNF)-α, interleukin (IL)-6, LPS, DAO, and D-LA serum concentrations in the mice. Hematoxylin-eosin (H&amp;E) staining and transmission electron microscopy (TEM) were used to observe structural changes in the intestinal mucosa. Immunohistochemistry was used to detect the expression of claudin-1, occludin and ZO-1 in intestinal tissues.</div></div><div><h3>Results</h3><div>Serum NKB (75.36 ± 28.67 pg/mL <em>vs.</em> 44.95 ± 16.92 pg/mL) and LPS (7.38 ± 3.63 μg/mL <em>vs.</em> 4.50 ± 2.94 μg/mL) levels were higher in mechanical IO patients than in control people (<em>P</em> &lt; 0.05). We found a positive correlation between serum NKB and LPS levels in mechanical IO patients. The serum LPS concentration in the IO+NKB mice was greater than that in the IO mice (<em>P</em> = 0.001). After the use of NK3Ra, the serum LPS, DAO and D-LA levels decreased (<em>P</em> &lt; 0.05). H&amp;E staining indicated that the intestinal mucosal epithelial structure was severely damaged, including lamina propria hemorrhage, atrophied villi, and inflammatory cell infiltration in IO+NKB mice. TEM revealed that the junctional complexes between epithelial cells were disrupted and absent in the IO+NKB mice. Compared with those in the IO mice, the expression levels of claudin-1 and occludin in intestinal tissues were lower in the IO+NKB mice. However, the intraperitoneal injection of NK3Ra attenuated the damage to tight junction proteins and the intestinal mucosal structure caused by NKB. Additionally, we observed that the serum IL-6 and TNF-α levels in the IO+NK3Ra mice were lower than those in the IO mice (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>NKB might increase the levels of serum IL-6 and TNF-α by acting on the NK3 receptor, promoting intestinal inflammation, and subsequently destroying the intestinal mucosal barrier during mechanical IO.</div></div>","PeriodicalId":19765,"journal":{"name":"Peptides","volume":"191 ","pages":"Article 171419"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205435","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}