Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"Metabolic Signatures of Acinetobacter baumannii and Klebsiella pneumoniae Infections in Acute-on-chronic Liver Failure","authors":"Camilla Cadoli ,&nbsp;Sania Arif ,&nbsp;Wibke Ballhorn ,&nbsp;Angela Brieger ,&nbsp;Maximilian Joseph Brol ,&nbsp;Florence Castelli ,&nbsp;Hans-Peter Erasmus ,&nbsp;Julia Fischer ,&nbsp;Robert Gurke ,&nbsp;Lisa Hahnefeld ,&nbsp;Christophe Junot ,&nbsp;Nico Kraus ,&nbsp;Cristina Ortiz ,&nbsp;Robert Schierwagen ,&nbsp;Sara Garcia Torres ,&nbsp;Frank Erhard Uschner ,&nbsp;Volker Müller ,&nbsp;Jonel Trebicka ,&nbsp;Christoph Welsch ,&nbsp;Volkhard A.J. Kempf","doi":"10.1016/j.jcmgh.2025.101707","DOIUrl":"10.1016/j.jcmgh.2025.101707","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome of acute hepatic decompensation (AD) that leads to multiorgan failure and high mortality. Bacterial infections are often implicated in ACLF pathogenesis; however, their underlying molecular mechanisms remain poorly understood. This study employed a combined in vitro-ex vivo metabolomics approach to investigate infection-associated metabolic alterations relevant to ACLF.</div></div><div><h3>Methods</h3><div>Gut (Caco-2) cells were infected with <em>Acinetobacter baumannii</em> and <em>Klebsiella pneumoniae</em> strains. Metabolite profiling was conducted on cell culture supernatants, and selected metabolites were tested for hepatotoxicity in vitro using liver (HepG2) cells. Metabolomic analysis of sera from 2 independent patient cohorts (AD and ACLF) was conducted to validate in vitro findings and to assess their clinical relevance.</div></div><div><h3>Results</h3><div>Distinct metabolic signatures were identified in <em>A</em> <em>baumannii</em> (19 metabolites) and <em>K</em> <em>pneumoniae</em> (15 metabolites)-infected Caco-2 cells. Four key metabolites from each bacterial species were prioritized for further experiments: α-ketoglutarate, indoleacetic acid, p-coumaric acid, uridine (<em>A</em> <em>baumannii</em>), desthiobiotin, N8-acetylspermidine, N-acetylglutamine, and β-pinene (<em>K</em> <em>pneumoniae</em>). Hepatotoxicity was demonstrated in liver (HepG2) cells exposed to Caco-2 infected cell-derived supernatants, infection-associated metabolites, and metabolite mixtures (in all conditions, <em>P</em> &lt; .0001). Increased levels of α-ketoglutarate (<em>P</em> = .0002), N-acetylglutamine (<em>P</em> = .0153), indoleacetic acid (<em>P</em> &lt; .05), and N8-acetylspermidine (<em>P</em> &lt; .01) have been confirmed in the sera of patients with AD and ACLF.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that metabolites associated with bacterial infections and hepatotoxic potential are significantly elevated in patients with AD and ACLF. These compounds may contribute to disease-related metabolic disturbances, representing promising candidates as early diagnostic biomarkers and targeted therapeutic strategies for ACLF.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 4","pages":"Article 101707"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752469","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":"Loss of NKCC1 Activates the NLRP3 Inflammasome in Intestinal Epithelia","authors":"Rainelli B. Koumangoye,&nbsp;Mohammed Z. Ferdaus,&nbsp;Xenia Davis,&nbsp;Julia K. Bohannon,&nbsp;Eric Delpire","doi":"10.1016/j.jcmgh.2025.101681","DOIUrl":"10.1016/j.jcmgh.2025.101681","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Potassium and chloride efflux have been reported to regulate nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Aberrant activation of NLRP3 inflammasome causes autoimmune and chronic inflammatory diseases. The Na⁺-K⁺-2Cl^- cotransporter (NKCC1) maintains the intracellular concentrations of sodium, potassium, and chloride. Here we ask whether NKCC1 modulates NLRP3 inflammasome activation.</div></div><div><h3>Methods</h3><div>Mice with intestinal epithelial-specific deletion of NKCC1, CRISPR-Cas9 NKCC1-deleted Caco-2 and HT-29 cells, and human fibroblasts expressing mutant NKCC1 were used to evaluate NLRP3 inflammasome activation.</div></div><div><h3>Results</h3><div>We found that deletion of NKCC1 in established intestinal epithelial cells (IECs) in culture causes increased pyroptosis and interleukin (IL)-1β and IL-18 secretion upon NLRP3 inflammasome activation. Similarly, organoids derived from mice with conditional NKCC1 <em>knockout</em> in IECs also exhibit increased IL-1β secretion when stimulated with adenosine triphosphate (ATP). Moreover, fibroblasts from a patient with NKCC1 mutant also showed increased pyroptosis and IL-1β and IL-18 secretion. Loss of NKCC1 sensitizes IECs to changes in intracellular concentration of K⁺ and decreases the threshold required for NLRP3 inflammasome activation. Finally, we showed that NKCC1^ΔIEC mice have increased infiltration of innate immune cells in the colon mucosa and peritoneal cavity.</div></div><div><h3>Conclusions</h3><div>NKCC1 functions as a negative regulator of NLRP3 inflammasome activation and this may explain why patients of loss-of-function mutations in NKCC1 are susceptible to inflammatory diseases.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 3","pages":"Article 101681"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558291","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":"Inhibition of Adipocyte Lipolysis Reduces Liver Injury in a Mouse Model of Ischemia Reperfusion Injury","authors":"Kim H.H. Liss ,&nbsp;Samantha Goldman ,&nbsp;Mai He ,&nbsp;Trevor M. Shew ,&nbsp;Daniel Ferguson ,&nbsp;Brian N. Finck","doi":"10.1016/j.jcmgh.2025.101679","DOIUrl":"10.1016/j.jcmgh.2025.101679","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hepatic ischemia reperfusion injury (IRI) is unavoidable in most liver operations and is associated with poor patient and graft outcomes in the setting of liver transplantation. However, there are no pharmacological interventions available for treatment of IRI. Prior work has demonstrated that liver IRI leads to hepatic lipid accumulation, suggesting that increased adipocyte lipolytic rates may contribute to hepatic steatosis. Inhibition of adipose triglyceride lipase (ATGL), the rate-limiting enzyme involved in triglyceride hydrolysis, may be beneficial in cardiac injury and alcoholic liver disease, but its role in liver IRI has not been investigated. Our objective was to assess the effects of inhibition of adipose tissue lipolysis in the setting of liver IRI.</div></div><div><h3>Methods</h3><div>Wild-type mice were treated with Atglistatin, a small molecule inhibitor of ATGL, prior to IRI. Mice with hepatocyte- or adipocyte-specific deletion of <em>Pnpla2</em>, the gene encoding ATGL, were generated and subjected to a mouse model of IRI. Mouse hepatocytes were cultured with fatty acids in an in vitro model of IRI.</div></div><div><h3>Results</h3><div>We demonstrated that experimental IRI was associated with increased adipocyte lipolysis. Pharmacological and genetic inhibition of adipocyte lipolysis reduced plasma and hepatic free fatty acids and decreased circulating transaminases and liver inflammation following hepatic IRI. Furthermore, exogenous fatty acids were sufficient to increase cell death and the expression of inflammatory cytokines in in vitro IRI.</div></div><div><h3>Conclusions</h3><div>These data suggest that targeting adipocyte lipolysis may represent a novel therapeutic approach in the prevention of hepatic IRI, which could improve patient and graft outcomes following liver transplantation.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 3","pages":"Article 101679"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566188","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":"A New Model of Gastric Pre-neoplasia Induced by Aberrant ADAR1-mediated Double-stranded RNA Signaling","authors":"Angela M. Halstead ,&nbsp;Chinye Nwokolo ,&nbsp;Stella Hoft ,&nbsp;Jinsheng Yu ,&nbsp;Lifei Zhu ,&nbsp;Brendan Tuley ,&nbsp;Nancy Vargas ,&nbsp;RuiRui Liu ,&nbsp;Francisco Ramirez Victorino ,&nbsp;Simrin Phatak ,&nbsp;Wandy Beatty ,&nbsp;Chun-Kan Chen ,&nbsp;Richard DiPaolo ,&nbsp;Paul Cliften ,&nbsp;Tarin M. Bigley ,&nbsp;José B. Sáenz","doi":"10.1016/j.jcmgh.2025.101673","DOIUrl":"10.1016/j.jcmgh.2025.101673","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Recent evidence suggests that endogenously derived double-stranded RNA (dsRNA) impacts multiple cellular processes, although its role in epithelial injury remains understudied. We previously identified the response to dsRNA as the most upregulated pathway across 2 distinct murine models of spasmolytic polypeptide-expressing metaplasia (SPEM), a critical pre-neoplastic transition in the progression to gastric cancer. The aim of this study was to define how dysregulation of the dsRNA response within gastric epithelium impacts gastric pre-neoplasia.</div></div><div><h3>Methods</h3><div>We specifically deleted ADAR1, a central regulator of dsRNA signaling, from gastric parietal cells (<em>Adar1</em>^{<em>ΔPC</em>}). <em>Adar1</em>^{<em>ΔPC</em>} and age-matched controls stomachs were histologically, transcriptionally, and immunologically profiled. The source of dsRNA in <em>Adar1</em>^{<em>ΔPC</em>} gastric epithelium was assessed by dsRNA immunoprecipitation and immuno-electron microscopy. Finally, to define the contributions of interferon (IFN) signaling, <em>Adar1</em>^{<em>ΔPC</em>}<em>;Ifnar1</em>^<em>-/-</em> <em>and Adar1</em>^{<em>ΔPC</em>}<em>;Ifnlr1</em>^<em>-/-</em> mice, defective in type I and type III IFN signaling, respectively, were characterized.</div></div><div><h3>Results</h3><div><em>Adar1</em>^{<em>ΔPC</em>} mice spontaneously developed SPEM and gastric dysplasia, in the absence of exogenous injury. Our phenotype depended on <em>Mavs</em>, a key dsRNA signaling hub, implying that our model of gastric pre-neoplasia was specific to dsRNA signaling. Further characterization of this pre-neoplastic environment by single-cell RNA sequencing and flow cytometry noted a chronic and sustained transcriptional upregulation of the dsRNA response throughout gastric epithelium that was independent of adaptive immunity and that depended on both type I and type III IFN signaling. Finally, we identified an enrichment of mitochondrial dsRNA within the gastric epithelium of <em>Adar1</em>^{<em>ΔPC</em>} stomachs.</div></div><div><h3>Conclusions</h3><div>Our new genetic model implicates ADAR1-mediated dsRNA signaling in gastric pre-neoplasia.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 3","pages":"Article 101673"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460738","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":"The Glutamine Metabolic Switch Influences the Response of Neonatal Intestinal Macrophages to Breast Milk","authors":"Xu Han ,&nbsp;Yutong Hou ,&nbsp;Taoying Chen ,&nbsp;Zhenyu Jia ,&nbsp;Fuqiang Yuan ,&nbsp;Mingxin Wang ,&nbsp;Yinling Su ,&nbsp;Ru Yan ,&nbsp;Xiaolei Wang ,&nbsp;Weilai Jin ,&nbsp;Yahui Zhou ,&nbsp;Yun Li ,&nbsp;Le Zhang","doi":"10.1016/j.jcmgh.2025.101683","DOIUrl":"10.1016/j.jcmgh.2025.101683","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Breast milk contains abundant glutamine and glutamate, yet their roles in neonatal gut health remain controversial. We aimed to investigate how these amino acids influence neonatal enteritis and the underlying mechanisms.</div></div><div><h3>Methods</h3><div>We used a neonatal rat necrotizing enterocolitis (NEC) model to test the effects of glutamine and glutamate given either before disease onset or during NEC progression. Previously published human neonatal NEC single-cell RNA psequencing (scRNA-seq) data were reanalyzed to assess immune cell composition and pathway activity. Bone marrow-derived macrophages (BMDMs) were used to examine inflammatory responses in vitro. Flow cytometry and transcriptomics were applied to analyze metabolic reprogramming of ileal macrophages.</div></div><div><h3>Results</h3><div>Glutamine and glutamate prevented NEC when administered prophylactically but worsened disease when given during NEC progression. scRNA-seq revealed enrichment of macrophages with activated inflammatory pathways in NEC ileum. In vitro, pretreatment with glutamine or glutamate reduced lipopolysaccharide-induced cytokine expression in BMDMs, whereas administration after stimulation had no benefit. In vivo, glutamine pretreatment decreased CD45⁺F4/80⁺CD11b/c⁺TNFα⁺ macrophages, whereas treatment during NEC increased this subset. Integrated analyses showed NEC upregulated glutaminase (GLS) and downregulated glutamate dehydrogenase (GLUD1) in ileal macrophages. Pretreatment with glutamine or glutamate restored GLUD1 expression, favoring α-ketoglutarate (α-KG) rather than succinate metabolism. Supplementation with α-KG reversed glutamine-induced macrophage activation during NEC, whereas succinate abolished the protective effect of glutamine pretreatment.</div></div><div><h3>Conclusions</h3><div>Glutamine and glutamate exert dual, context-dependent effects in neonatal enteritis by modulating macrophage glutamine metabolism. These findings provide mechanistic insight and suggest a basis for personalized glutamine supplementation strategies in neonatal gut disorders.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 3","pages":"Article 101683"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650222","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":"Anesthetic Agents as Modulators of Antitumor Immunity: Repurposing Etomidate for Hepatocellular Carcinoma Therapy","authors":"Hanchao Lin,&nbsp;Qiongzhu Dong","doi":"10.1016/j.jcmgh.2025.101650","DOIUrl":"10.1016/j.jcmgh.2025.101650","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 2","pages":"Article 101650"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208129","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":"When Liver Slices Meet Single-cell Technology","authors":"Mi Jeong Heo,&nbsp;Kang Ho Kim","doi":"10.1016/j.jcmgh.2025.101661","DOIUrl":"10.1016/j.jcmgh.2025.101661","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 2","pages":"Article 101661"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338266","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":"In Vivo Determinants of Hepatitis C Virus Adaptation and Escape From Neutralizing Antibody AR5A","authors":"Rodrigo Velázquez-Moctezuma ,&nbsp;Rani Burm ,&nbsp;Lieven Verhoye ,&nbsp;Laura Collignon ,&nbsp;Kenn Holmbeck ,&nbsp;Erick Giang ,&nbsp;Mansun Law ,&nbsp;Jens Bukh ,&nbsp;Philip Meuleman ,&nbsp;Jannick Prentoe","doi":"10.1016/j.jcmgh.2025.101684","DOIUrl":"10.1016/j.jcmgh.2025.101684","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Mechanisms of hepatitis C virus (HCV) adaptation and escape from broadly neutralizing antibodies (bNAbs) have been primarily studied in vitro. Here, we used a previously developed in vivo adapted J6/JFH1_A876P virus and the highly bNAb sensitive hypervariable region 1 (HVR1) deleted variant, J6/JFH1_A876P,ΔHVR1, to study adaptation and bNAb AR5A escape in the HCV-permissive human-liver chimeric mouse model.</div></div><div><h3>Methods</h3><div>In vitro identified AR5A escape substitution, L665S, was introduced into J6/JFH1_A876P with or without HVR1. The infection of human liver chimeric mice with these recombinants revealed adaptive mutations, and the potential mechanism of adaptation was extensively characterized in vitro. Finally, we tested the barrier to resistance of AR5A in vivo by challenging passively immunized animals with HVR1-deleted viruses, either with or without the AR5A escape substitution, L665S.</div></div><div><h3>Results</h3><div>L665S was found to be an escape substitution in vivo. Furthermore, sequence analysis showed that the escape substitution L665S arose as early as 2 weeks post infection. At week 8, we also identified antibody escape substitutions as well as several potential in vivo adaptive substitutions in E2. For J6/JFH1_A876P, S449P and M702L increased cell-free particle infection and broadly affected antibody sensitivity for virus with HVR1. For J6/JFH1_A876P,ΔHVR1, N430D and M702L substitutions increased both cell-free particle mediated infection and cell-to-cell spread, whereas N430D also increased thermal stability at 37°C.</div></div><div><h3>Conclusions</h3><div>We show that L665S is an AR5A escape mutation in vivo, supporting the use of cost-effective vaccine escape studies in vitro. We also identify novel in vivo adaptive mutations and characterize their mechanism of action, thus facilitating interpretation of future HCV in vivo studies.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"20 4","pages":"Article 101684"},"PeriodicalIF":7.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558307","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":"The P2X7 Receptor Promotes Intestinal Fibrosis by Modulating the Gut Microbiota and the Inflammasome.","authors":"Beatriz Elias Ribeiro, Isadora Schmukler de Lima, Karen Cristina da Silva E Souza, Siane Lopes Bittencourt Rosas, Patrícia Teixeira Santana, Gilda Amaral, João Carlos Machado, Rodrigo Pereira de Oliveira, Camille Leal, Cristiane Thompson, Fabiano Thompson, Morgana Teixeira Lima Castelo-Branco, Robson Coutinho-Silva, Heitor Siffert Pereira de Souza","doi":"10.1016/j.jcmgh.2025.101718","DOIUrl":"10.1016/j.jcmgh.2025.101718","url":null,"abstract":"<p><strong>Background & aims: </strong>Considering the role of the P2X7 receptor in intestinal inflammation, we examined its potential involvement in fibrosis development.</p><p><strong>Methods: </strong>Colonic biopsies from patients with inflammatory bowel disease (IBD) were analyzed via double immunofluorescence under confocal microscopy. Colon fibroblasts were used to analyze P2X7 receptor modulation and chemotaxis. Experimental chronic colitis was induced with 3 cycles of oral dextran sodium sulfate (DSS) treatment in P2X7^+/+ and P2X7^-/- mice. The mice were evaluated via follow-up video endoscopy with an endoluminal ultrasound biomicroscopic (eUBM) system, histological scoring, immunohistochemistry, cytokine measurement in colon explants, gene expression analysis of P2X7 signaling targets via quantitative real-time polymerase chain reaction (qRT-PCR), and microbiome composition analysis.</p><p><strong>Results: </strong>Colocalization studies revealed a greater density of P2X7⁺/alpha smooth muscle actin (α-SMA)⁺ cells in colon sections from patients than in those from controls, especially in patients with Crohn's disease (P < .05). Activation of the adenosine triphosphate (ATP)-P2X7 pathway in human fibroblasts increased cell migration, calcium influx, and collagen production. Video colonoscopy with the eUBM system revealed significantly more inflammation, with greater wall thickness and stiffness, in P2X7^+/+ mice than in P2X7^-/- and P2X7^+/+ mice treated with A740003 (a P2X7-selective inhibitor). P2X7^+/+ mice exhibited increased caspase-1 and NLRP3 expression, as well as nuclear factor κB (NF-κB) and extracellular signal-regulated kinase (ERK) activation, accompanied by decreased peroxisome proliferator-activated receptor gamma (PPARγ) expression. In the supernatants of colon explants, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-10, and collagen production were increased in P2X7^+/+ mice. Various microbial changes were observed in P2X7^-/- and P2X7^+/+ mice.</p><p><strong>Conclusions: </strong>Regulatory mechanisms downstream of P2X7, combined with signals from a dysbiotic microbiota, activate intracellular signaling pathways and the inflammasome, leading to intestinal inflammation and promoting fibrogenesis.</p>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101718"},"PeriodicalIF":7.1,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890609","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":"ΔNP63 Defines an Exocrine-committed Subset of Murine Pancreatic Progenitor Cells.","authors":"Katarina Coolens, Melissa Van Der Vliet, Jente Van Campenhout, Natalia Del Pozo, Alejo Torres-Cano, Catharina Olson, Jianming Xu, Heiko Lickert, Meritxell Rovira, Isabelle Houbracken, Jonathan Baldan, Francisco X Real, Francesca M Spagnoli, Ilse Rooman","doi":"10.1016/j.jcmgh.2025.101715","DOIUrl":"10.1016/j.jcmgh.2025.101715","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":" ","pages":"101715"},"PeriodicalIF":7.1,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844307","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}