Gastroenterology最新文献

{"title":"Fidaxomicin reduces collagen expression in intestinal fibroblasts via platelet-derived growth factor receptor beta and glycogen synthase kinase-3 beta inhibition.","authors":"Sophie Irwin, Mieke van Daelen, Isabella Almaraz, Rebecca Park, Becca Nelson, Swapna Mahurkar-Joshi, Florian Rieder, David Q. Shih, Wendy Ho, Berkeley Limketkai, Hon Wai Koon","doi":"10.1053/j.gastro.2025.04.028","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.04.028","url":null,"abstract":"<h3>Introduction</h3>About 30-50% of patients with Crohn’s disease (CD) eventually develop intestinal strictures, with intestinal fibrosis being a major component of them. There is currently no approved medication to treat fibrotic strictures.<h3>Methods</h3>10X Genomics Visium spatial RNA sequencing and high-throughput screening (HTS) were used to discover the molecular targets of intestinal fibrosis. Stricturing CD (CDS) patient-derived primary intestinal fibroblasts (CD-HIFs), CDS patient-derived serum exosomes (CDSE), fresh surgically resected whole-thickness ileal tissues, and mouse models of intestinal fibrosis were used.<h3>Results</h3>Spatial RNA sequencing found overexpression of platelet-derived growth factor receptor beta (PDGFRB) in the fibrotic ileal tissues of CDS patients. PDGFRB siRNA inhibited collagen expression in the CDSE-treated CD-HIFs. HTS identified PDGFRB inhibitors that suppressed collagen promoter activity in CDSE-treated CD-HIFs. A machine learning algorithm and molecular docking predicted PDGFR as a target for fidaxomicin. Fidaxomicin, an FDA-approved drug for <em>C. difficile</em> infection, inhibited collagen and PDGFRB mRNA expression in CDSE-treated CD-HIFs and CDS patient-derived ileal tissues. CDSE-treated CD-HIFs had increased PDGFRβ and glycogen synthase kinase-3 alpha/beta (GSK3α/β) phosphorylation. Fidaxomicin inhibited PDGFRβ phosphorylation, PDGFRB mRNA expression, and GSK3β phosphorylation in CDSE-treated CD-HIFs. The anti-fibrogenic effect of fidaxomicin was attenuated by platelet-derived growth factor-BB (PDGF-BB) and insulin-like growth factor 1 (IGF-1), which are a PDGFRβ ligand and a GSK3α/β phosphorylation activator, respectively. In the SAMP1/YitFc mice, oral fidaxomicin treatment inhibited ileal fibrosis and ileal PDGFRB mRNA expression and PDGFRβ and GSK3β phosphorylation, which were abolished by Pdgfrb and Gsk3b overexpression.<h3>Conclusions</h3>Fidaxomicin inhibits intestinal fibrosis by reducing PDGFRβ phosphorylation and expression, GSK3β phosphorylation, and collagen expression in intestinal fibroblasts.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"18 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEVELOPMENT OF ACUTE KIDNEY INJURY IN A PATIENT WITH ALCOHOL-RELATED CIRRHOSIS: THE IMPORTANCE OF DIAGNOSING THE CAUSE OF AKI","authors":"Adrià Juanola, Ann T. Ma, Giuseppe Cullaro, Mariam P. Alexander, Andrew S. Allegretti, Pere Ginès","doi":"10.1053/j.gastro.2025.03.056","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.03.056","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"30 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Effect of an Endoscopy Screening on Upper Gastrointestinal Cancer Mortality: A Community-Based Multicenter Cluster Randomized Clinical Trial”","authors":"Lei Liu, Chunying Jiang, Hongyu Zhao","doi":"10.1053/j.gastro.2025.03.055","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.03.055","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"21 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mis-lead by obstruction","authors":"Ashok Jhajharia, Devank Shah, Prachis Ashdhir","doi":"10.1053/j.gastro.2025.03.054","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.03.054","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"4 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergies between Clinicians, Academia and Industry in the Age of AI","authors":"Michael F. Byrne, Jens Rittscher, James E. East","doi":"10.1053/j.gastro.2025.05.007","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.05.007","url":null,"abstract":"In the rapidly evolving landscape of GI healthcare, the integration of artificial intelligence (AI) presents unprecedented opportunities for enhancing patient outcomes, improving efficiency, and driving innovation. Effective collaboration among clinicians, academia, and industry is crucial to harness the full potential of AI technologies.Clinicians offer invaluable insights from real-world practice, ensuring that AI solutions address genuine clinical needs and improve patient care. Academia plays a pivotal role in advancing research, developing new methodologies, and training the next generation of professionals who will navigate this transformative field. Industry drives the commercialization of AI tools, providing the resources and infrastructure necessary for widespread adoption.Achieving these synergies is challenging. Issues including data privacy, regulatory hurdles, and interdisciplinary communication must be addressed to foster effective partnerships. By embracing collaborative models, including public-private partnerships, clinical trials, and innovation hubs, stakeholders can work together to overcome barriers and promote responsible AI integration in gastroenterology.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"29 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary fiber modulates the window of susceptibility to Clostridioides difficile infection","authors":"Katharine K. Hewlett, Amanda PeBenito, Aaron L. Hecht, Connor Tiffany, Ceylan Tanes, Rochelle C. Glover, Jibraan A. Fawad, Elliot S. Friedman, James C. Reynolds, Kyle Bittinger, James D. Lewis, Gary D. Wu, Nitin K. Ahuja, Joseph P. Zackular","doi":"10.1053/j.gastro.2025.04.027","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.04.027","url":null,"abstract":"<h3>Background &amp; Aims</h3><em>Clostridioides difficile</em> epidemiology is rapidly evolving, and understanding the factors that contribute to one’s risk of <em>C. difficile</em> infection (CDI) is urgently needed. Based on our observations in a dietary intervention study, we hypothesized that fiber modulates susceptibility to <em>C. difficile</em> post-antibiotic exposure and investigated this using human specimens and murine models.<h3>Methods</h3>To determine whether fiber impacts factors known to mediate colonization resistance against <em>C. difficile,</em> we investigated bile acid and microbiota composition in human subjects on a low-fiber diet. To directly test the impact of a fiber-free diet on CDI susceptibility, we treated mice with fiber-rich or fiber-free diets and quantified CDI susceptibility after antibiotic use, as well as characterized alterations in both bile acid and microbiota composition.<h3>Results</h3>A low-fiber diet leads to increased fecal primary conjugated bile acids in humans, including bile acids known to promote <em>C. difficile</em> colonization such as taurocholic acid (TCA). Using a novel mouse model of CDI, we show that a fiber-free diet leads to prolonged and increased susceptibility to CDI that is associated with alterations in bile acids. We further report long-lasting perturbation to the microbiota, highlighted by depletion of commensals known to promote colonization resistance against <em>C. difficile</em>.<h3>Conclusions</h3>Consumption of a low-fiber diet after antibiotic use contributes to a prolonged susceptibility to CDI that corresponds to a perturbation in both microbiota and bile acid composition. These results suggest that in the context of antibiotic treatment, diet is a critical, modifiable risk factor for CDI susceptibility.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"16 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of regular surveillance versus endoscopy at need for patients with Barrett’s esophagus: economic evaluation alongside the BOSS randomized controlled trial","authors":"Manuela Deidda, Oliver Old, Janusz Jankowski, Stephen Attwood, Clive Stokes, Catherine Kendall, Cathryn Rasdell, Alex Zimmermann, Sofia Massa, Sharon Love, Scott Sanders, Julie Hapeshi, Chris Foy, Andrew Briggs, Hugh Barr, Paul Moayyedi","doi":"10.1053/j.gastro.2025.04.026","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.04.026","url":null,"abstract":"<h3>Introduction</h3>The Barrett’s esophagus surveillance study (BOSS) was the first randomized study of surveillance. This study reports the costs and quality of life outcomes from the BOSS trial and models the outcomes and cost-effectiveness of surveillance beyond the follow up period of the BOSS study. This trial showed similar stages and rates of esophageal cancer in both arms, but the regular surveillance arm did identify more high-grade dysplasia after a median of 12.8 years follow up.<h3>Methods</h3>We used a decision tree model based on results from BOSS to conduct a cost-effectiveness analysis of costs and quality adjusted life years (QALYs). A Markov model was used to extrapolate costs and outcomes over a further 10 years after the trial had ended representing a 22.8 year time horizon. The proportion with high grade dysplasia and QALYs were derived from the randomized trial.<h3>Results</h3>The total costs associated with two yearly surveillance was $5,309 vs. $3,182 in the at need arm. Total QALY in the two-yearly endoscopy arm were 8.647 as compared to 8.629 in the at need arm. Compared with at need endoscopy, two-yearly surveillance costs $115,563/QALY gained. In the sensitivity analyses around assumptions on the proportion of high-grade dysplasia that is undetected in the at need endoscopy arm, surveillance had an incremental cost effectiveness ratio of $94,513/QALY for the best-case and $146,272/QALY for the worst-case scenario.<h3>Conclusion</h3>BE surveillance every 2-3 years is unlikely to be a cost-effective strategy. Guidelines should take this into account when deciding surveillance intervals","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"35 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Analytical Framework for Complex Biological Data: Beyond Principal Component Analysis in Cancer Research","authors":"Yoshiyasu Takefuji","doi":"10.1053/j.gastro.2025.03.053","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.03.053","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights and Perspectives on AVL9-Mediated Chemoresistance in Pancreatic Ductal Adenocarcinoma","authors":"Xinyi Tang, Jiaruo Xu, Qingzhi Ran, Yongkang Zhang","doi":"10.1053/j.gastro.2025.03.052","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.03.052","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comments on “Hypoxic and acidic tumor microenvironment-driven AVL9 promotes chemoresistance of pancreatic ductal adenocarcinoma via the AVL9-IκBα-SKP1 complex”","authors":"Saisai Jing, Jiazhao Song","doi":"10.1053/j.gastro.2024.12.042","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.042","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"4 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}