Gastroenterology Report最新文献

{"title":"USP38 protects intestinal epithelial cells from ischemia/reperfusion injury by stabilizing BIRC5.","authors":"Mandong Pan, Xianwei Huang, Xiaodong Huang, Xiong Liu, Jiyan Lin","doi":"10.1093/gastro/goaf024","DOIUrl":"10.1093/gastro/goaf024","url":null,"abstract":"<p><strong>Background: </strong>Intestinal ischemia/reperfusion (II/R) is a severe condition with high mortality and limited treatment options. Extracellular vesicles that are derived from bone marrow mesenchymal stem cells (BM-MSC-EVs) exhibit therapeutic potential in alleviating II/R injury. However, the mechanism by which BM-MSC-EVs fulfill this function requires further characterization. The ubiquitin-proteasome system plays an essential role in II/R, but the functions of individual ubiquitination regulators such as ubiquitin-specific proteases (USPs) in this process remain incompletely understood.</p><p><strong>Methods: </strong>An II/R cellular model was established by using IEC-6 intestinal epithelial cells with oxygen-glucose deprivation/reperfusion (OGD/R) treatment. The expression of USPs was evaluated by using quantitative polymerase chain reaction and Western blot. The role of USP38 on the viability, apoptosis, migration, and reactive oxygen species (ROS) levels in OGD/R-treated IEC-6 cells were measured by using CCK-8, Annexin V/PI staining, transwell assay, and 2',7'-dichlorofluorescin diacetate (DCFDA) staining, respectively. The interaction between USP38 and BIRC5 was explored by using co-immunoprecipitation (Co-IP) and the ubiquitination level and stability of BIRC5 were examined by using Western blot. USP38-overexpressing BM-MSC-EVs were produced to treat OGD/R-treated IEC-6 cells.</p><p><strong>Results: </strong>USP38 expression was significantly downregulated in OGD/R-treated IEC-6 cells. Incubation of these cells with BM-MSC-EVs substantially elevated the USP38 expression, resulting in improved viability, reduced apoptosis, enhanced migration, and decreased ROS levels. Furthermore, overexpression of USP38 in BM-MSC-EVs further enhanced their protective effect on OGD/R-treated IEC-6 cells. At the molecular level, USP38 interacts with and stabilizes BIRC5 by decreasing its ubiquitination. Knock-down of BIRC5 abolished the protective effect of excessive USP38 on OGD/R-treated IEC-6 cells.</p><p><strong>Conclusion: </strong>USP38 protects intestinal epithelial cells from I/R injury by enhancing the stability of BIRC5.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf024"},"PeriodicalIF":3.8,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gasdermin E-mediated intestinal epithelial pyroptosis promotes chemically induced colitis in mice.","authors":"Yi-Zhong Wu, Yao Xie, Lin Chen, Lei Ning, Xiao-Qi Hu, Xiao-Ping Xu","doi":"10.1093/gastro/goaf021","DOIUrl":"10.1093/gastro/goaf021","url":null,"abstract":"<p><strong>Background: </strong>Gasdermin E (GSDME) is a newly identified pyroptosis executioner and is upregulated in the intestinal epithelial cell (IEC) of ulcerative colitis (UC) patients. However, the effects of epithelial GSDME on UC remain unknown.</p><p><strong>Methods: </strong>Bone marrow chimera experiments were performed to investigate the role of GSDME in nonhematopoietic cells, mainly including IECs. An FITC-dextran assay was used to assess the integrity of the intestinal epithelial barrier.</p><p><strong>Results: </strong><i>Gsdme^-/-</i> chimeras that were reconstituted with wild-type bone marrow cells exhibited lower weight loss, disease activity index, colon shortening, and histology scores than wild-type chimeras after treatment with dextran sulfate sodium (DSS). However, <i>Gsdme</i> ^+/+ chimeras that were reconstituted with <i>Gsdme</i>-deficient bone marrow cells were not protected from DSS-induced colitis compared with wild-type chimeras. Importantly, DSS treatment activated Caspase-3 and cleaved GSDME to generate GSDME-N terminal fragments that are responsible for the induction of pyroptosis in IECs, but not in the intestinal lamina propria cell. Additionally, GSDME deficiency inhibited DSS-induced disruption of the intestinal epithelial barrier. Mechanistically, GSDME-mediated IEC pyroptosis is dependent on Caspase-3 activation, which is supported by the observation that the Caspase-3 inhibitor Z-DEVD-FMK inhibited DSS-induced GSDME cleavage in IECs.</p><p><strong>Conclusions: </strong>We show that GSDME-mediated epithelial pyroptosis contributes to the development of DSS-induced colitis by promoting intestinal inflammation and disrupting the intestinal epithelial barrier.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf021"},"PeriodicalIF":3.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gastric antrum submucosal tumor caused by inverted gastric diverticulum: a case report.","authors":"Jun-Jie Hou, Xiao-Fei Yao, Liang Ding, Tao Yang, Yan-Fei Yang, Yue-Ping Jin, Xiao-Li Wang, Yue-Hua Qin, Wei-Wei Li","doi":"10.1093/gastro/goaf025","DOIUrl":"10.1093/gastro/goaf025","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf025"},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparan sulfate chains in hepatocellular carcinoma.","authors":"Erwan Guyot","doi":"10.1093/gastro/goaf023","DOIUrl":"https://doi.org/10.1093/gastro/goaf023","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) corresponds to the vast majority of liver cancer cases, with one of the highest mortality rates. Major advances have been made in this field both in the characterization of the molecular pathogenesis and in the development of systemic therapies. Despite these achievements, biomarkers and more efficient treatments are still needed to improve its management. Heparan sulfate (HS) chains are polysaccharides that are present at the cell surface or in the extracellular matrix that are able to bind various types of molecules, such as soluble factors, affecting their availability and thus their effects, or to contribute to interactions that position cells in their environments. Enzymes can modify HS chains after their synthesis, thus changing their properties. Numerous studies have shown HS-related proteins to be key actors that are associated with cellular effects, such as tumor growth, invasion, and metastasis, including in the context of liver carcinogenesis. The aim of this review is to provide a comprehensive overview of the biology of HS chains and their potential importance in HCC, from biological considerations to clinical development, and the identification of biomarkers, as well as therapeutic perspectives.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf023"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of major liver-related events in the population using prognostic models.","authors":"Fredrik Åberg, Ville Männistö","doi":"10.1093/gastro/goaf028","DOIUrl":"https://doi.org/10.1093/gastro/goaf028","url":null,"abstract":"<p><p>Liver disease poses a significant global health burden, with steatotic liver disease related to metabolic dysfunction and/or alcohol use being the most prevalent type. Current risk stratification strategies emphasize detecting advanced fibrosis as a surrogate marker for liver-related events (LREs), such as hospitalization, liver cancer, or death. However, fibrosis alone does not adequately predict imminent outcomes, particularly in fast-progressing individuals without advanced fibrosis at evaluation. This underscores the need for models designed specifically to predict LREs, enabling timely interventions. The Chronic Liver Disease (CLivD) risk score, the dynamic aspartate aminotransferase-to-alanine aminotransferase ratio (dAAR), and the Cirrhosis Outcome Risk Estimator (CORE) were explicitly developed to predict LRE risk rather than detect fibrosis. Derived from general population cohorts, these models incorporate either standard liver enzymes (dAAR and CORE) or risk factors (CLivD), enabling broad application in primary care and population-based settings. They directly estimate the risk of future LREs, improving on traditional fibrosis-focused approaches. Conversely, widely used models like the Fibrosis-4 index and newer ones, such as the LiverRisk and LiverPRO scores, were initially developed to detect significant/advanced fibrosis or liver stiffness. While not designed for LRE prediction, they have later been analyzed for this purpose. Integrating fibrosis screening with LRE-focused models like CLivD, dAAR, and CORE can help healthcare systems adopt proactive, preventive care. This approach emphasizes identifying individuals at imminent risk of severe outcomes, potentially ensuring better resource allocation and personalized interventions.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf028"},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Los Angeles-B esophagitis is a conclusive diagnostic evidence for gastroesophageal reflux disease: the validation of Lyon Consensus 2.0.","authors":"Jing Chen, Peiwen Dong, Songfeng Chen, Qianjun Zhuang, Mengyu Zhang, Kaidi Sun, Feng Tang, Qiong Wang, Yinglian Xiao","doi":"10.1093/gastro/goaf004","DOIUrl":"10.1093/gastro/goaf004","url":null,"abstract":"<p><strong>Background and aims: </strong>Recently, Lyon Consensus 2.0 recommended Los Angeles (LA)-B esophagitis as conclusive evidence and LA-A esophagitis as borderline evidence for gastroesophageal reflux disease (GERD). This study aimed to investigate the diagnostic value of LA-B and LA-A esophagitis.</p><p><strong>Methods: </strong>Patients with typical reflux symptoms who underwent endoscopy examination and received acid-suppressive therapy from two tertiary hospitals [the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, P. R. China) and the Third People's Hospital of Chengdu (Chengdu, P. R. China)] were retrospectively included. Acid-suppression response rates, endoscopy results, motility, and reflux parameters were compared between patients with different grades of esophagitis.</p><p><strong>Results: </strong>In total, 401 patients were enrolled, among whom 254 were without reflux esophagitis (RE), 51 had LA-A esophagitis, 44 had LA-B esophagitis, and 52 had LA-C/D esophagitis. Patients with LA-B esophagitis and LA-C/D esophagitis had significantly higher acid-suppressive response rates than non-RE patients (<i>P </i><<i> </i>0.05), whereas no significant difference was found between patients with LA-A esophagitis and non-RE patients (non-RE vs LA-A vs LA-B vs LA-C/D: 52.4% vs 70.6% vs 75.0% vs 82.7%). Among patients with LA-A esophagitis, those with a number of reflux episodes that exceeded 80 per day (90.0% vs 52.4%, <i>P </i>=<i> </i>0.044) or hypotensive esophagogastric junction (72.4% vs 52.4%, <i>P </i>=<i> </i>0.040) had significantly higher acid-suppressive response rates than non-RE patients.</p><p><strong>Conclusions: </strong>LA-B esophagitis can be regarded as conclusive evidence for GERD and initiate acid-suppressive therapy. LA-A esophagitis did not establish a definite GERD diagnosis alone. When combined with adjunctive or supportive evidence, the acid-suppressive therapy response rate of LA-A esophagitis improved.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf004"},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nedd4L signaling contributes to carbon tetrachloride-induced liver fibrosis in female mice and is associated with enteric dysbacteriosis.","authors":"Cheng Chen, Yanghui Bi, Bangtao Chen, Song He","doi":"10.1093/gastro/goaf022","DOIUrl":"10.1093/gastro/goaf022","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis is characterized by hepatic stellate cell (HSC) activation and collagen overproduction, but its pathogenesis remains largely unknown. This study aimed to uncover the role of neural precursor cell expressed developmentally downregulated 4-like (Nedd4L) signaling in liver fibrosis and its relationship with gut microbiota.</p><p><strong>Methods: </strong>Intraperitoneal injection of carbon tetrachloride (CCl₄) was used to induce liver fibrosis in 8-week-old female C57BL/6J mice with <i>Nedd4L</i> knockout or administration of the Nedd4L protein phosphorylation inhibitor EMD638683. HSCs isolated from mice were activated with transforming growth factor-beta 1 (TGFβ1) with or without EMD638683.</p><p><strong>Results: </strong>An approximately 3-fold elevation in <i>Nedd4L</i> mRNA was observed in hepatocytes and liver tissues, and significantly higher hepatic Nedd4L phosphorylation was observed in fibrotic mice than in non-fibrotic mice. <i>Nedd4L</i> mRNA level in HSCs isolated from fibrotic livers and Nedd4L protein level in TGFβ1-stimulated HSCs from wild-type livers remained unchanged. In isolated HSCs, TGFβ1-induced Nedd4L phosphorylation and cell activation were suppressed with EMD638683. In CCl₄-treated mice, EMD638683 alleviated liver fibrosis and induced a relative increase in fecal <i>Bacteroides</i>, <i>Parabacteroides</i>, <i>Erysipelatoclostridium</i>, <i>Blautia</i>, and <i>Klebsiella</i>, whereas Nedd4L deficiency predisposed mice to liver injury and liver fibrosis with a remarkable reduction in fecal <i>Lactobacillus</i>, <i>Enterorhabdus</i>, and <i>Bacteroides</i>.</p><p><strong>Conclusion: </strong>Hepatic Nedd4L signaling contributes to CCl₄-induced liver fibrosis in female mice, which is associated with alterations in the gut microbiota, and Nedd4L phosphorylation is involved in TGFβ1-mediated HSC activation.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf022"},"PeriodicalIF":3.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etiologies of exocrine pancreatic insufficiency.","authors":"Chengji Tang, Jia Zhou, Yinghui Song, Sulai Liu","doi":"10.1093/gastro/goaf019","DOIUrl":"10.1093/gastro/goaf019","url":null,"abstract":"<p><p>Exocrine pancreatic insufficiency (EPI) is a major cause of maldigestion and malnutrition, resulting from primary pancreatic diseases or other conditions. As the prevalence of EPI continues to rise, accurate identification of its etiology has become critical for the diagnosis and treatment of pancreatic secretory insufficiency. EPI can result from both pancreatic and non-pancreatic disorders. Pancreatic disorders include acute and chronic pancreatitis, pancreatic tumors, cystic fibrosis, procedures that involve pancreatic resection, and other rare causes. Non-pancreatic disorders of EPI include diabetes mellitus, celiac disease, inflammatory bowel disease, gastrointestinal and esophagectomy surgery, as well as advanced patient age. This review aims to provide a comprehensive analysis of the literature on EPI etiology, with a thorough overview to support its consideration as a potential diagnosis.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf019"},"PeriodicalIF":3.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential function of hepatic Niemann-Pick C1-like 1: cholesterol homeostasis regulation of the canalicular lipid bilayer membrane.","authors":"Hongtan Chen, Pingfan Mo, Guoqiang Xu","doi":"10.1093/gastro/goaf010","DOIUrl":"10.1093/gastro/goaf010","url":null,"abstract":"<p><p>Niemann-Pick C1-like 1 (NPC1L1) is distributed in the human liver and intestine but only slightly expressed in the mouse liver. While it is well established that intestinal NPC1L1 is crucial for the absorption of exogenous cholesterol, the physiological and pathological roles of canalicular membrane-localized NPC1L1 in human hepatic cholesterol transport remain unclear. In this review, we discussed the potential function of human hepatic NPC1L1 and proposed that the disparity in NPC1L1 abundance between humans and mice in the liver may be attributable to their distinct bile hydrophobicity. Human hepatic NPC1L1 might interact with other proteins in the canalicular membrane, regulate membrane cholesterol homeostasis, and contribute to the stability of the canalicular lipid bilayer membrane in response to the greater detergent properties of human bile salts. We hoped to provide novel perspectives on hepatic NPC1L1 for future investigations.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf010"},"PeriodicalIF":3.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing the role of nitric oxide in the pathogenesis of sphincter of Oddi dysfunction.","authors":"Haonan Lin, Yixuan Liang, Wangqiang Zhao, Junwei Cao, Tianqi Wang, Changmiao Wang","doi":"10.1093/gastro/goaf001","DOIUrl":"10.1093/gastro/goaf001","url":null,"abstract":"<p><p>The pathogenic mechanisms underlying sphincter of Oddi dysfunction (SOD) remain incompletely understood, and it often leads to severe symptoms encompassing nausea, vomiting, and abdominal pain. New evidence now suggests correlations between nitric oxide (NO) and SOD. In this review, we summarized the factors influencing SOD pathogenesis via NO and its derivative, the peroxynitrite anion. NO appears to enhance SOD progression by modulating sphincter of Oddi (SO) contractions via NO-sGC-cGMP signaling or inducing the apoptosis of enteric neurons, interstitial cells of Cajal, smooth muscle cells, and other cellular components via peroxynitrite anion-mediated organelle damage. Thus, a comprehensive understanding of SOD will provide a foundation for the identification of potential drugs and treatment approaches.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf001"},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}