Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"Altered B-Cell Expansion and Maturation in Draining Mesenteric Lymph Nodes of Inflamed Gut in Crohn’s Disease","authors":"Sonja Kappel-Latif , Prasanti Kotagiri , Lukas Schlager, Gabor Schuld, Natalie Walterskirchen, Vanessa Schimek, Gavin Sewell, Carina Binder, Johanna Jobst, Supriya Murthy, Barbara Messner, Stefanie Dabsch, Arthur Kaser, Paul A. Lyons, Michael Bergmann, Anton Stift, Rudolf Oehler, Lukas W. Unger","doi":"10.1016/j.jcmgh.2023.12.006","DOIUrl":"10.1016/j.jcmgh.2023.12.006","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/S2352345X23002199/pdfft?md5=b050b2f9497dd146dabefe65a195421b&pid=1-s2.0-S2352345X23002199-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027716","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":"Scattered Crypt Intestinal Epithelial Cell Apoptosis Induces Necrotizing Enterocolitis Via Intricate Mechanisms","authors":"Saravanan Subramanian ,&nbsp;Heng-Fu Bu ,&nbsp;Pauline M. Chou ,&nbsp;Xiao Wang ,&nbsp;Hua Geng ,&nbsp;Suhail Akhtar ,&nbsp;Chao Du ,&nbsp;Stephanie C. Tan ,&nbsp;Justin Eze Ideozu ,&nbsp;Aasrita Tulluri ,&nbsp;Yuxiang Sun ,&nbsp;Wen-Xing Ding ,&nbsp;Isabelle G. De Plaen ,&nbsp;Xiao-Di Tan","doi":"10.1016/j.jcmgh.2024.05.012","DOIUrl":"10.1016/j.jcmgh.2024.05.012","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Necrotizing enterocolitis (NEC) is a life-threatening disease affecting mostly the ileum of preemies. Intestinal epithelial cell (IEC) apoptosis contributes to NEC pathogenesis. However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear.</p></div><div><h3>Methods</h3><p>A novel triple-transgenic mouse model, namely, 3xTg-iAP^cIEC (inducible apoptosis phenotype in crypt-IEC), was developed to induce IEC-specific overexpression of <em>Fasl</em> transgene using doxycycline (Dox)-inducible tetO-rtTA system and villin-cre technology. The 3-days-old neonatal 3xTg-iAP^cIEC mice and their littermate controls were subcutaneously (s.c.) challenged with a single dose of Dox. Intestinal tissues were processed at different time points to examine scattered crypt IEC apoptosis-mediated NEC development. Gene knockout technology, antibody-mediated cell depletion, and antibiotic-facilitated Gram-positive bacteria depletion were used to study mechanisms.</p></div><div><h3>Results</h3><p>Treatment of 3xTg-iAP^cIEC mouse pups with Dox induces scattered crypt IEC apoptosis followed by crypt inflammation and excessive villous necrosis resembling NEC. This progression correlated with elevated <em>Ifng</em>, <em>Rip3</em>, CD8⁺ T cells, and Gram-positive bacteria in the ileum. Mechanistically, IFN-γ and RIP3-activated signals mediate the effect of scattered crypt IEC apoptosis on the induction of intestinal crypt inflammation and villous necrosis. Meanwhile, pathophysiological events of CD8⁺ T cell infiltration and dysbiosis with Gram-positive bacteria primarily contribute to excessive villous inflammation and necrosis. Notably, blocking any of these events protects against NEC development in 3xTg-iAP^cIEC mouse pups, underlining their central roles in NEC pathogenesis.</p></div><div><h3>Conclusions</h3><p>Scattered crypt IEC apoptosis induces NEC in mouse pups via IFN-γ, RIP3, CD8⁺ T cells, and Gram-positive bacteria-mediated comprehensive pathophysiological events. Our findings may advance knowledge in the prevention and treatment of NEC.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001188/pdfft?md5=314170d104b613a125b2a2202708d984&pid=1-s2.0-S2352345X24001188-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094749","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":"Enteric Glial Cells at the Crossroads Between Intestinal Inflammation and Amyloids Diseases","authors":"","doi":"10.1016/j.jcmgh.2024.05.007","DOIUrl":"10.1016/j.jcmgh.2024.05.007","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001139/pdfft?md5=0824419f0a830e9b5ccc5e54b3618e14&pid=1-s2.0-S2352345X24001139-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186923","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":"Tolerogenic pDCs Turn the Inflammatory Tide and Protect Against Acute Liver Failure","authors":"","doi":"10.1016/j.jcmgh.2024.101370","DOIUrl":"10.1016/j.jcmgh.2024.101370","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001255/pdfft?md5=62294a2f6607114fbe2c85c1cc957a87&pid=1-s2.0-S2352345X24001255-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592239","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","authors":"","doi":"10.1016/S2352-345X(24)00151-6","DOIUrl":"10.1016/S2352-345X(24)00151-6","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001516/pdfft?md5=f69a8da5f1bd8fbfe178866795f93d73&pid=1-s2.0-S2352345X24001516-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239831","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":"Ablation of Intestinal Epithelial Sialylation Predisposes to Acute and Chronic Intestinal Inflammation in Mice","authors":"","doi":"10.1016/j.jcmgh.2024.101378","DOIUrl":"10.1016/j.jcmgh.2024.101378","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis.</div></div><div><h3>Methods</h3><div>Mice with constitutive deletion of intestinal epithelial sialylation (IEC <em>Slc35a1</em>^{<em>–/–</em>} mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC <em>Slc35a1</em>^{<em>–/–</em>} mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and mutiomics studies.</div></div><div><h3>Results</h3><div>IEC <em>Slc35a1</em>^{<em>–/–</em>} mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC <em>Slc35a1</em>^{<em>–/–</em>} mice had spontaneous tumors in the rectum greater than the age of 12 months. TM-IEC <em>Slc35a1</em>^{<em>–/–</em>} mice were highly susceptible to acute inflammation induced by 1% dextran sulfate sodium versus control animals. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC <em>Slc35a1</em>^{<em>–/–</em>} mice showed altered microbiota with an increase in <em>Clostridium disporicum</em>, which is associated a global reduction in the abundance of at least 10 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil led to more severe small intestine mucositis in the IEC <em>Slc35a1</em>^{<em>–/–</em>} mice versus wild-type littermates, which was associated with reduced Lgr5⁺ cell representation in small intestinal crypts in IEC <em>Slc35a1</em>^{<em>-/-</em>;<em>Lgr5-GFP</em>} mice.</div></div><div><h3>Conclusions</h3><div>Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.</div></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592238","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":"BRD4 Regulates Glycolysis-Dependent Nos2 Expression in Macrophages Upon H pylori Infection","authors":"Nikita Modi ,&nbsp;Yanheng Chen ,&nbsp;Xingchen Dong ,&nbsp;Xiangming Hu ,&nbsp;Gee W. Lau ,&nbsp;Keith T. Wilson ,&nbsp;Richard M. Peek Jr. ,&nbsp;Lin-Feng Chen","doi":"10.1016/j.jcmgh.2023.10.001","DOIUrl":"10.1016/j.jcmgh.2023.10.001","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Metabolic reprogramming is essential for the activation and functions of macrophages, including bacterial killing and cytokine production. Bromodomain-containing protein 4 (BRD4) has emerged as a critical regulator of innate immune response. However, the potential role of BRD4 in the metabolic reprogramming of macrophage activation upon <em>Helicobacter pylori</em> infection remains unclear.</p></div><div><h3>Methods</h3><p>Bone marrow–derived macrophages (BMDMs) from wild-type (WT) and <em>Brd4-</em>myeloid deletion conditional knockout (<em>Brd4</em>-CKO) mice were infected with <em>H pylori</em>. RNA sequencing was performed to evaluate the differential gene expression between WT and <em>Brd4</em>-deficient BMDMs upon infection. An in vivo model of <em>H pylori</em> infection using WT and <em>Brd4</em>-CKO mice was used to confirm the role of BRD4 in innate immune response to infection.</p></div><div><h3>Results</h3><p>Depletion of <em>Brd4</em> in BMDMs showed impaired <em>H pylori</em>–induced glycolysis. In addition, <em>H pylori</em>–induced expression of glycolytic genes, including <em>Slc2a1</em> and <em>Hk2</em>, was decreased in <em>Brd4</em>-deficient BMDMs. BRD4 was recruited to the promoters of <em>Slc2a1</em> and <em>Hk2</em> via hypoxia-inducible factor-1α, facilitating their expression. BRD4-mediated glycolysis stabilized <em>H pylori</em>–induced nitric oxide synthase (<em>Nos2</em>) messenger RNA to produce nitric oxide. The NO-mediated killing of <em>H pylori</em> decreased in <em>Brd4</em>-deficient BMDMs, which was rescued by pyruvate. Furthermore, <em>Brd4</em>-CKO mice infected with <em>H pylori</em> showed reduced gastric inflammation and increased <em>H pylori</em> colonization with reduced inducible NO synthase expression in gastric macrophages.</p></div><div><h3>Conclusions</h3><p>Our study identified BRD4 as a key regulator of hypoxia-inducible factor-1α–dependent glycolysis and macrophage activation. Furthermore, we show a novel regulatory role of BRD4 in innate immunity through glycolysis to stabilize <em>Nos2</em> messenger RNA for NO production to eliminate <em>H pylori</em> infection.</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/S2352345X23001807/pdfft?md5=040896a362f7f6eaf447d7e1b5a53ee0&pid=1-s2.0-S2352345X23001807-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41221049","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":"NF-κB Inducing Kinase Attenuates Colorectal Cancer by Regulating Noncanonical NF-κB Mediated Colonic Epithelial Cell Regeneration","authors":"Holly A. Morrison ,&nbsp;Kristin Eden ,&nbsp;Brie Trusiano ,&nbsp;Daniel E. Rothschild ,&nbsp;Yufeng Qin ,&nbsp;Paul A. Wade ,&nbsp;Audrey J. Rowe ,&nbsp;Christina Mounzer ,&nbsp;Morgan C. Stephens ,&nbsp;Katherine M. Hanson ,&nbsp;Stephan L. Brown ,&nbsp;Eda K. Holl ,&nbsp;Irving C. Allen","doi":"10.1016/j.jcmgh.2024.05.004","DOIUrl":"10.1016/j.jcmgh.2024.05.004","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Dysregulated colonic epithelial cell (CEC) proliferation is a critical feature in the development of colorectal cancer. We show that NF-κB-inducing kinase (NIK) attenuates colorectal cancer through coordinating CEC regeneration/differentiation via noncanonical NF-κB signaling that is unique from canonical NF-kB signaling.</p></div><div><h3>Methods</h3><p>Initial studies evaluated crypt morphology/functionality, organoid generation, transcriptome profiles, and the microbiome. Inflammation and inflammation-induced tumorigenesis were initiated in whole-body NIK knockout mice (<em>Nik</em>^<em>-/-</em>) and conditional-knockout mice following administration of azoxymethane and dextran sulfate sodium.</p></div><div><h3>Results</h3><p>Human transcriptomic data revealed dysregulated noncanonical NF-kB signaling. In vitro studies evaluating <em>Nik</em>^<em>-/-</em> crypts and organoids derived from mature, nondividing CECs, and colonic stem cells exhibited increased accumulation and stunted growth, respectively. Transcriptomic analysis of <em>Nik</em>^<em>-/-</em> cells revealed gene expression signatures associated with altered differentiation-regeneration. When assessed in vivo, <em>Nik</em>^<em>-/</em>- mice exhibited more severe colitis with dextran sulfate sodium administration and an altered microbiome characterized by increased colitogenic microbiota. In the inflammation-induced tumorigenesis model, we observed both increased tumor burdens and inflammation in mice where NIK is knocked out in CECs (<em>Nik</em>^{<em>ΔCEC</em>}). Interestingly, this was not recapitulated when NIK was conditionally knocked out in myeloid cells (<em>Nik</em>^{<em>ΔMYE</em>}<em>)</em>. Surprisingly, conditional knockout of the canonical pathway in myeloid cells (<em>RelA</em>^{<em>ΔMYE</em>}) revealed decreased tumor burden and inflammation and no significant changes when conditionally knocked out in CECs <em>(RelA</em>^ΔCEC).</p></div><div><h3>Conclusions</h3><p>Dysregulated noncanonical NF-κB signaling is associated with the development of colorectal cancer in a tissue-dependent manner and defines a critical role for NIK in regulating gastrointestinal inflammation and regeneration associated with colorectal cancer.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001103/pdfft?md5=6ac6e1f3eb040b81a90657641751df32&pid=1-s2.0-S2352345X24001103-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946680","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":"WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production","authors":"Amy E. O’Connell ,&nbsp;Sathuwarman Raveenthiraraj ,&nbsp;Luiz Fernando Silva Oliveira ,&nbsp;Comfort Adegboye ,&nbsp;Venkata Siva Dasuri ,&nbsp;Wanshu Qi ,&nbsp;Radhika S. Khetani ,&nbsp;Akaljot Singh ,&nbsp;Nambirajam Sundaram ,&nbsp;Jasmine Lin ,&nbsp;Prathima Nandivada ,&nbsp;Lorena Rincón-Cruz ,&nbsp;Jeffrey D. Goldsmith ,&nbsp;Jay R. Thiagarajah ,&nbsp;Diana L. Carlone ,&nbsp;Jerrold R. Turner ,&nbsp;Pankaj B. Agrawal ,&nbsp;Michael Helmrath ,&nbsp;David T. Breault","doi":"10.1016/j.jcmgh.2024.04.006","DOIUrl":"10.1016/j.jcmgh.2024.04.006","url":null,"abstract":"<div><h3>Background &amp; aims</h3><p>Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis.</p></div><div><h3>Methods</h3><p>We investigated the intestinal health of <em>Wnt2b</em> knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue.</p></div><div><h3>Results</h3><p>Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. <em>Wnt2b</em> KO mice showed an enhanced inflammatory signature after DSS treatment. <em>Wnt2b</em> KO colon and human WNT2B-deficient organoids had increased levels of <em>CXCR4</em> and <em>IL6</em>, and biopsy tissue from humans showed increased neutrophils.</p></div><div><h3>Conclusions</h3><p>WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.</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/S2352345X24001000/pdfft?md5=aad7f8851649bbb9688db7c5a88219f4&pid=1-s2.0-S2352345X24001000-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871550","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":"Promises and Limitations of Current Models for Understanding Barrett’s Esophagus and Esophageal Adenocarcinoma","authors":"Omar Martinez-Uribe ,&nbsp;Thomas C. Becker ,&nbsp;Katherine S. Garman","doi":"10.1016/j.jcmgh.2024.01.017","DOIUrl":"10.1016/j.jcmgh.2024.01.017","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>This review was developed to provide a thorough and effective update on models relevant to esophageal metaplasia, dysplasia, and carcinogenesis, focusing on the advantages and limitations of different models of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).</p></div><div><h3>Methods</h3><p>This expert review was written on the basis of a thorough review of the literature combined with expert interpretation of the state of the field. We emphasized advances over the years 2012–2023 and provided detailed information related to the characterization of established human esophageal cell lines.</p></div><div><h3>Results</h3><p>New insights have been gained into the pathogenesis of BE and EAC using patient-derived samples and single-cell approaches. Relevant animal models include genetic as well as surgical mouse models and emphasize the development of lesions at the squamocolumnar junction in the mouse stomach. Rat models are generated using surgical approaches that directly connect the small intestine and esophagus. Large animal models have the advantage of including features in human esophagus such as esophageal submucosal glands. Alternatively, cell culture approaches remain important in the field and allow for personalized approaches, and scientific rigor can be ensured by authentication of cell lines.</p></div><div><h3>Conclusions</h3><p>Research in BE and EAC remains highly relevant given the morbidity and mortality associated with cancers of the tubular esophagus and gastroesophageal junction. Careful selection of models and inclusion of human samples whenever possible will ensure relevance to human health and disease.</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/S2352345X24000201/pdfft?md5=02615a07a567c8760236e308035da1af&pid=1-s2.0-S2352345X24000201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704136","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}