Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"Myeloid Deletion of Cdc42 Protects Liver From Hepatic Ischemia-Reperfusion Injury via Inhibiting Macrophage-Mediated Inflammation in Mice","authors":"Jing He ,&nbsp;Meng-Yu Tang ,&nbsp;Li-Xin Liu ,&nbsp;Chen-Xian Kong ,&nbsp;Wen Chen ,&nbsp;Lu Wang ,&nbsp;Shao-Bin Zhi ,&nbsp;Hong-Wei Sun ,&nbsp;Yu-Chun Huang ,&nbsp;Guo-Yu Chen ,&nbsp;Hong-Bo Xin ,&nbsp;Ke-Yu Deng","doi":"10.1016/j.jcmgh.2024.01.023","DOIUrl":"10.1016/j.jcmgh.2024.01.023","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Hepatic ischemia-reperfusion injury (HIRI) often occurs in liver surgery, such as partial hepatectomy and liver transplantation, in which myeloid macrophage-mediated inflammation plays a critical role. Cell division cycle 42 (Cdc42) regulates cell migration, cytoskeleton rearrangement, and cell polarity. In this study, we explore the role of myeloid Cdc42 in HIRI.</p></div><div><h3>Methods</h3><p>Mouse HIRI models were established with 1-hour ischemia followed by 12-hour reperfusion in myeloid Cdc42 knockout (Cdc42^mye) and Cdc42^flox mice. Myeloid-derived macrophages were traced with Rosa^mTmG fluorescent reporter under LyzCre-mediated excision. The experiments for serum or hepatic enzymic activities, histologic and immunologic analysis, gene expressions, flow cytometry analysis, and cytokine antibody array were performed.</p></div><div><h3>Results</h3><p>Myeloid deletion of Cdc42 significantly alleviated hepatic damages with the reduction of hepatic necrosis and inflammation, and reserved hepatic functions following HIRI in mice. Myeloid Cdc42 deficiency suppressed the infiltration of myeloid macrophages, reduced the secretion of proinflammatory cytokines, restrained M1 polarization, and promoted M2 polarization of myeloid macrophages in livers. In addition, inactivation of Cdc42 promoted M2 polarization via suppressing the phosphorylation of STAT1 and promoting phosphorylation of STAT3 and STAT6 in myeloid macrophages. Furthermore, pretreatment with Cdc42 inhibitor, ML141, also protected mice from hepatic ischemia-reperfusion injury.</p></div><div><h3>Conclusions</h3><p>Inhibition or deletion of myeloid Cdc42 protects liver from HIRI via restraining the infiltration of myeloid macrophages, suppressing proinflammatory response, and promoting M2 polarization in macrophages.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000262/pdfft?md5=aa01dbc5afa72ad4cc3376c2f7d3039f&pid=1-s2.0-S2352345X24000262-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telocytes in the Luminal GI Tract","authors":"Michal Shoshkes-Carmel","doi":"10.1016/j.jcmgh.2024.02.002","DOIUrl":"10.1016/j.jcmgh.2024.02.002","url":null,"abstract":"<div><p>Telocytes are unique mesenchymal cells characterized by multiple remarkably long cytoplasmic extensions that extend hundreds of micron away from the cell body. Through these extensions, telocytes establish a 3-dimensional network by connecting with other telocytes and various cell types within the tissue. In the intestine, telocytes have emerged as an essential component of the stem cell niche, providing Wnt proteins that are critical for the proliferation of stem and progenitor cells. However, the analysis of single-cell RNA sequencing has revealed other stromal populations and mechanisms for niche organization, raising questions about the role of telocytes as a component of the stem cell niche. This review explores the current state-of-the-art, existing controversies, and potential future directions related to telocytes in the luminal gastrointestinal tract.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000304/pdfft?md5=7bf8e35c578d5aba21d10e490c9f4326&pid=1-s2.0-S2352345X24000304-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Interactions and Crosstalk Facilitating Biliary Fibrosis in Cholestasis","authors":"Ludovica Ceci ,&nbsp;Eugenio Gaudio ,&nbsp;Lindsey Kennedy","doi":"10.1016/j.jcmgh.2024.01.005","DOIUrl":"10.1016/j.jcmgh.2024.01.005","url":null,"abstract":"<div><p>Biliary fibrosis is seen in cholangiopathies, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). In PBC and PSC, biliary fibrosis is associated with worse outcomes and histologic scores. Within the liver, both hepatic stellate cells (HSCs) and portal fibroblasts (PFs) contribute to biliary fibrosis, but their roles can differ. PFs reside near the bile ducts and may be the first responders to biliary damage, whereas HSCs may be recruited later and initiate bridging fibrosis. Indeed, different models of biliary fibrosis can activate PFs and HSCs to varying degrees. The portal niche can be composed of cholangiocytes, HSCs, PFs, endothelial cells, and various immune cells, and interactions between these cell types drive biliary fibrosis. In this review, we discuss the mechanisms of biliary fibrosis and the roles of PFs and HSCs in this process. We will also evaluate cellular interactions and mechanisms that contribute to biliary fibrosis in different models and highlight future perspectives and potential therapeutics.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000067/pdfft?md5=69124d11679325fa2b26f3fba0f9eabb&pid=1-s2.0-S2352345X24000067-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139433156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover - F-Actin and Rab11 Super-Resolution Imaging in Intestinal Organoids","authors":"","doi":"10.1016/S2352-345X(24)00103-6","DOIUrl":"https://doi.org/10.1016/S2352-345X(24)00103-6","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001036/pdfft?md5=eee78113db978c4e454185969eca960a&pid=1-s2.0-S2352345X24001036-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140952400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of V-ATPase V0 Sector Induces Microvillus Atrophy Independently of Apical Trafficking in the Mammalian Intestine","authors":"Aurélien Bidaud-Meynard,&nbsp;Anne Bourdais,&nbsp;Ophélie Nicolle,&nbsp;Maela Duclos,&nbsp;Jad Saleh,&nbsp;Frank M. Ruemmele,&nbsp;Henner F. Farin,&nbsp;Delphine Delacour,&nbsp;Despina Moshous,&nbsp;Grégoire Michaux","doi":"10.1016/j.jcmgh.2024.02.011","DOIUrl":"10.1016/j.jcmgh.2024.02.011","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000390/pdfft?md5=599b16d87cbdee3b161037a3c262ebde&pid=1-s2.0-S2352345X24000390-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Brain–Gut–Microbiome Interactions: A Comprehensive Update on Signaling Mechanisms, Disorders, and Therapeutic Implications","authors":"Tien S. Dong ,&nbsp;Emeran Mayer","doi":"10.1016/j.jcmgh.2024.01.024","DOIUrl":"10.1016/j.jcmgh.2024.01.024","url":null,"abstract":"<div><p>The complex, bidirectional interactions between the brain, the gut, and the gut microbes are best referred to as the <em>brain gut microbiome system</em>. Animal and clinical studies have identified specific signaling mechanisms within this system, with gut microbes communicating to the brain through neuronal, endocrine, and immune pathways. The brain, in turn, modulates the composition and function of the gut microbiota through the autonomic nervous system, regulating gut motility, secretion, permeability, and the release of hormones impacting microbial gene expression. Perturbations at any level of these interactions can disrupt the intricate balance, potentially contributing to the pathogenesis of intestinal, metabolic, neurologic, and psychiatric disorders. Understanding these interactions and their underlying mechanisms holds promise for identifying biomarkers, as well as novel therapeutic targets, and for developing more effective treatment strategies for these complex disorders. Continued research will advance our knowledge of this system, with the potential for improved understanding and management of a wide range of disorders. This review provides an update on the current state of knowledge regarding this system, with a focus on recent advancements and emerging research areas.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000274/pdfft?md5=d4669a02dd3b453d86ad04ae4f48c667&pid=1-s2.0-S2352345X24000274-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy Contributes to Homeostasis in Esophageal Epithelium Where High Autophagic Vesicle Level Marks Basal Cells With Limited Proliferation and Enhanced Self-Renewal Potential","authors":"Alena Klochkova ,&nbsp;Adam L. Karami ,&nbsp;Annie D. Fuller ,&nbsp;Louis R. Parham ,&nbsp;Surali R. Panchani ,&nbsp;Shruthi Natarajan ,&nbsp;Jazmyne L. Jackson ,&nbsp;Anbin Mu ,&nbsp;Yinfei Tan ,&nbsp;Kathy Q. Cai ,&nbsp;Andres J. Klein-Szanto ,&nbsp;Amanda B. Muir ,&nbsp;Marie-Pier Tétreault ,&nbsp;Xavier Graña ,&nbsp;Kathryn E. Hamilton ,&nbsp;Kelly A. Whelan","doi":"10.1016/j.jcmgh.2024.02.018","DOIUrl":"10.1016/j.jcmgh.2024.02.018","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Autophagy plays roles in esophageal pathologies both benign and malignant. Here, we aim to define the role of autophagy in esophageal epithelial homeostasis.</p></div><div><h3>Methods</h3><p>We generated tamoxifen-inducible, squamous epithelial-specific <em>Atg7</em> (autophagy related 7) conditional knockout mice to evaluate effects on esophageal homeostasis and response to the carcinogen 4-nitroquinoline 1-oxide (4NQO) using histologic and biochemical analyses. We fluorescence-activated cell sorted esophageal basal cells based on fluorescence of the autophagic vesicle (AV)-identifying dye Cyto-ID and then subjected these cells to transmission electron microscopy, image flow cytometry, three-dimensional organoid assays, RNA sequencing, and cell cycle analysis. Three-dimensional organoids were subjected to passaging, single-cell RNA sequencing, cell cycle analysis, and immunostaining.</p></div><div><h3>Results</h3><p>Genetic autophagy inhibition in squamous epithelium resulted in increased proliferation of esophageal basal cells under homeostatic conditions and also was associated with significant weight loss in mice treated with 4NQO that further displayed perturbed epithelial tissue architecture. Esophageal basal cells with high AV level (Cyto-ID^High) displayed limited organoid formation capability on initial plating but passaged more efficiently than their counterparts with low AV level (Cyto-ID^Low). RNA sequencing suggested increased autophagy in Cyto-ID^High esophageal basal cells along with decreased cell cycle progression, the latter of which was confirmed by cell cycle analysis. Single-cell RNA sequencing of three-dimensional organoids generated by Cyto-ID^Low and Cyto-ID^High cells identified expansion of 3 cell populations and enrichment of G2/M-associated genes in the Cyto-ID^High group. Ki67 expression was also increased in organoids generated by Cyto-ID^High cells, including in basal cells localized beyond the outermost cell layer.</p></div><div><h3>Conclusions</h3><p>Autophagy contributes to maintenance of the esophageal proliferation-differentiation gradient. Esophageal basal cells with high AV level exhibit limited proliferation and generate three-dimensional organoids with enhanced self-renewal capacity.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000523/pdfft?md5=e2d18b5bd1b82ad91790c506ab4361dd&pid=1-s2.0-S2352345X24000523-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOC","authors":"","doi":"10.1016/S2352-345X(24)00064-X","DOIUrl":"https://doi.org/10.1016/S2352-345X(24)00064-X","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X2400064X/pdfft?md5=e3158678ed27588eb60a4808f9e53833&pid=1-s2.0-S2352345X2400064X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antagonism Between Gut Ruminococcus gnavus and Akkermansia muciniphila Modulates the Progression of Chronic Hepatitis B","authors":"Huey-Huey Chua ,&nbsp;Ya-Hui Chen ,&nbsp;Li-Ling Wu ,&nbsp;Hung-Chih Yang ,&nbsp;Chia-Ray Lin ,&nbsp;Huey-Ling Chen ,&nbsp;Jia-Feng Wu ,&nbsp;Mei-Hwei Chang ,&nbsp;Pei-Jer Chen ,&nbsp;Yen-Hsuan Ni","doi":"10.1016/j.jcmgh.2023.12.003","DOIUrl":"10.1016/j.jcmgh.2023.12.003","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB.</p></div><div><h3>Methods</h3><p>To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed.</p></div><div><h3>Results</h3><p><em>Ruminococcus gnavus</em> was the most abundant species in CHB patients in the IT phase, whereas <em>Akkermansia muciniphila</em> was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because <em>R gnavus</em> encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. <em>A muciniphila</em> counteracted this activity through the direct removal of cholesterol. The secretome metabolites of <em>A muciniphila</em>, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of <em>R gnavus</em> to allow HBV elimination.</p></div><div><h3>Conclusions</h3><p><em>R gnavus</em> and <em>A muciniphila</em> play opposite roles in HBV infection. <em>A muciniphila</em> metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X23002163/pdfft?md5=252a4af93854ce66d91bf84bb81b972b&pid=1-s2.0-S2352345X23002163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138575130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Microbiota Conducts the Vasoactive Intestinal Polypeptide Orchestra in the Small Intestine","authors":"Jacques Gonzales,&nbsp;Brian D. Gulbransen","doi":"10.1016/j.jcmgh.2023.11.013","DOIUrl":"10.1016/j.jcmgh.2023.11.013","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X23002126/pdfft?md5=aa392c5ac5107706f5ec250554cfffaa&pid=1-s2.0-S2352345X23002126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138688875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}