Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"Microbiota-Gut-Brain Axis in Neurodegenerative diseases: The Role of Bacterial Amyloids.","authors":"Moustapha Cissé, Valentine Moullé, Rodrigue Brossaud, Thibauld Oullier, Michel Neunlist","doi":"10.1016/j.jcmgh.2026.101802","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101802","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101802"},"PeriodicalIF":7.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857755","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":"Beyond the Alpha and Omega: Redefining the PPARa Gut-Liver Axis in intestinal failure-associated liver disease (IFALD).","authors":"Chaowapong Jarasvaraparn, Brian J DeBosch, Abigail E Russi","doi":"10.1016/j.jcmgh.2026.101801","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101801","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101801"},"PeriodicalIF":7.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846556","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":"PROTEASES AND ABDOMINAL PAIN - OLD DOG, NEW (MICROBIAL) TRICKS.","authors":"Yasaman B Habibyan, Keith A Sharkey, Yasmin Nasser","doi":"10.1016/j.jcmgh.2026.101803","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101803","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101803"},"PeriodicalIF":7.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846623","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":"From Kimchi to PSC: Leuconostoc citreum LB-P8 as a microbiome-based therapeutic approach.","authors":"Sarah Peisl, Espen Melum","doi":"10.1016/j.jcmgh.2026.101800","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101800","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101800"},"PeriodicalIF":7.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846574","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":"VPS35 controls hepatocellular proliferation through SRC signalling and promotes diethyl nitrosamine-induced tumor initiation.","authors":"Markus G Barbosa, Dyonne Y Vos, Cristy R C Verzijl, Andries H Heida, Marco Bakker, Niels J Kloosterhuis, Mirjam H Koster, Marieke Smit, Alba Fajardo, Dicky Struik, Peter Olinga, Johan W Jonker, Rachel Thomas, Albert Pol, Vincent de Meijer, Anna Moles, Umesh Tharehalli, Jan Albert Kuivenhoven, Bart van de Sluis","doi":"10.1016/j.jcmgh.2026.101788","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101788","url":null,"abstract":"<p><strong>Background & aims: </strong>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Therapeutic options for HCC remain limited, and the mechanisms underlying HCC are not fully understood. Therefore, gaining a comprehensive understanding of the pathways that drive HCC is essential for improving treatments. Recent studies have identified VPS35, a component of the endosomal cargo sorting machinery called retromer, as a novel oncogene in various types of cancer, including HCC. However, its role in the initiation and progression of HCC is still unclear.</p><p><strong>Methods: </strong>To study the role of VPS35 in hepatocellular proliferation and the development of HCC, we generated a liver-specific Vps35 knockout mouse model using the Cre-LoxP system (Vps35^HepKO). Hepatocellular proliferation was studied in young and middle-aged mice, as well as during liver regeneration after two-thirds partial hepatectomy (PH). Diethyl nitrosamine (DEN) was used to induce HCC. Livers were analyzed at histological, transcriptional, and proteomic levels.</p><p><strong>Results: </strong>Hepatic loss of VPS35 enhanced hepatocellular proliferation in post-natal livers via SRC and its downstream target STAT3. Pharmacologic inhibition of SRC with Saracatinib normalized hepatocellular proliferation in Vps35^HepKO mice. In contrast, hepatic VPS35 deficiency did not alter hepatocellular proliferation after PH in adult mice. Although VPS35-deficient postnatal livers exhibited an increased proliferative phenotype, hepatic loss of VPS35 reduced the number of DEN-induced liver lesions without affecting tumor size.</p><p><strong>Conclusions: </strong>Our in vivo data identify murine VPS35 as a critical regulator of hepatocellular proliferation in postnatal livers, but not after PH. Although VPS35 deficiency mitigates DEN-induced liver lesion formation, it does not affect tumor progression, arguing against a role for VPS35 as a canonical oncogene.</p>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101788"},"PeriodicalIF":7.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846579","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":"Portal Fibroblasts: A Hidden Driver of Cholestasis-associated Liver Cancer.","authors":"Sadam H Bhat, Ekihiro Seki","doi":"10.1016/j.jcmgh.2026.101798","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101798","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101798"},"PeriodicalIF":7.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823917","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":"Commentary Interleukin-6 (IL-6): The unexpected opponent to pancreatic cancer.","authors":"Gregory B Lesinski","doi":"10.1016/j.jcmgh.2026.101799","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101799","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101799"},"PeriodicalIF":7.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824011","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":"Restoring Balance in Autoimmune Hepatitis.","authors":"Urs Christen","doi":"10.1016/j.jcmgh.2026.101797","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101797","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101797"},"PeriodicalIF":7.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823986","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":"Early gut-vascular barrier breakdown precedes colitis onset in murine models.","authors":"Mariam Mohamed Abdou, Lucas Kreiß, Benjamin Schmid, Oana-Maria Thoma, René Krüger, Alan Bénard, Tanja M Müller, Annkathrin Knauss, Michael Gabel, Miguel González-Acera, Yanmin Lyu, Katja Petter, Aylin Lindemann, Mina Saad Aziz Saad, Philip Eichhorn, Christoph Becker, Elisabeth Naschberger, Sebastian Zundler, Benno Weigmann, Timo Rath, Raja Atreya, Anja A Kühl, Zlatko Trajanoski, Oliver Friedrich, Maximilian J Waldner, Markus F Neurath, Martin Herrmann, Sebastian Schürmann, Nathalie Britzen-Laurent, Michael Stürzl","doi":"10.1016/j.jcmgh.2026.101795","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101795","url":null,"abstract":"<p><strong>Background & aims: </strong>The gut-vascular barrier (GVB) plays a pivotal role in inflammatory bowel disease (IBD) pathogenesis. We introduce a novel three-dimensional (3D) multiphoton endomicroscopy (MPEM) approach for real-time and sensitive detection of vascular permeability (VP) in the colon to identify colitis-associated vascular changes in the early stages.</p><p><strong>Methods: </strong>Using fluorescence-based MPEM, we visualized dynamic changes in VP in vivo during longitudinal observations in different experimental colitis models (DSS- and T cell transfer-induced colitis). VP changes were systematically compared with conventional inflammatory markers, including weight loss, endoscopic scoring, colon length, histopathology, and immune cell infiltration. To assess molecular regulation of barrier functions, the expression of key molecules of vascular (PV1, VE-cadherin) and epithelial (E-cadherin) barriers was investigated during development of colitis at the single-cell level.</p><p><strong>Results: </strong>MPEM provided unprecedented 3D visualization of VP dynamics and showed that vascular dysfunction occurs prior to epithelial barrier breakdown and the detection of traditional inflammatory markers across all colitis models. Distinct spatial VP patterns strongly correlated with mucosal damage severity, further supporting that early GVB disruption precedes mucosal barrier breakdown. Additionally, this sequence was confirmed at the molecular level, with the vascular upregulation of the trans-endothelial permeability channel PV1 occurring before downregulation of the epithelial barrier molecule E-cadherin.</p><p><strong>Conclusions: </strong>MPEM with 3D imaging demonstrated GVB dysfunction in the very early stages of experimental colitis. Further development of MPEM-based VP analysis for use in routine clinical monitoring of patients may provide new perspectives to improve diagnosis and clinical decision-making in IBD.</p>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101795"},"PeriodicalIF":7.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823951","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":"Mucosal-associated invariant T cells drive bile duct inflammation.","authors":"Kathrine S Nordhus, Fei Zheng, Natalie L Berntsen, Oda Helgesen Ramberg, Laura Valestrand, Jonas Øgaard, Brian K Chung, Xiaojun Jiang, Espen Melum","doi":"10.1016/j.jcmgh.2026.101794","DOIUrl":"https://doi.org/10.1016/j.jcmgh.2026.101794","url":null,"abstract":"<p><strong>Background & aims: </strong>Mucosal-associated invariant T (MAIT) cells recognize microbial-derived vitamin B metabolites presented by MR1. Since bile from patients with chronic biliary inflammation contain MAIT antigens, we investigated whether intrabiliary MAIT antigen exposure activates MAIT cells and induce pathogenic biliary inflammation.</p><p><strong>Methods: </strong>E.coli, PBS or the known MAIT ligand 5-OP-RU were injected into bile ducts of mice with increased MAIT cell frequencies (Mr1⁺ B6- MAIT^CAST and iVα19 Cα^-/- Tg). Mice were monitored clinically and liver tissue analyzed after 1-14 days. Portal inflammation was assessed histologically. The immunophenotype of lymphocytes was determined by flow cytometry, and serum liver enzymes were measured. Hepatic MAIT cell transcriptional profiles were analyzed by single-nucleus RNA sequencing (snRNA-seq) RESULTS: Intrabiliary injection of E.coli in iVα19 Cα^-/- Tg mice caused cholangitis at day 2, elevated ALT, increased histologic grade of cholangitis and portal accumulation of T-lymphocytes and macrophages. This coincided with marked hepatic MAIT cells activation. Similar signs of experimental cholangitis were observed in mice containing 2% MAIT cells (Mr1⁺ B6- MAIT^CAST). Selective activation with 5-OP-RU in iVα19 Cα^-/- Tg mice confirmed the MAIT specificity of the inflammatory response. In Mr1⁺ B6-MAIT^CAST mice, the MAIT cell frequency was too low to induce biliary inflammation. snRNA-seq of MAIT cells from 5-OP-RU injected iVα19 Cα^-/- Tg mice demonstrated antigen-driven transcriptional reprogramming toward a MAIT17-skewed phenotype with enrichment of TCR signaling pathways.</p><p><strong>Conclusions: </strong>MAIT cells can drive pathogenic bile duct inflammation in vivo when locally exposed to antigens. These findings suggest that modulation of MAIT driven immune pathways may represent a therapeutic approach in inflammatory cholangiopathies.</p>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101794"},"PeriodicalIF":7.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823984","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}