{"title":"Actinomyces odontolyticus: From Carries to Colorectal Cancer","authors":"Keith A. Breau","doi":"10.1016/j.jcmgh.2024.02.009","DOIUrl":"10.1016/j.jcmgh.2024.02.009","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/S2352345X24000377/pdfft?md5=e9b59bca61ebfdcf587c6bec689dab66&pid=1-s2.0-S2352345X24000377-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139948825","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 Progress and Promise of Lineage Reprogramming Strategies for Liver Regeneration","authors":"","doi":"10.1016/j.jcmgh.2024.101395","DOIUrl":"10.1016/j.jcmgh.2024.101395","url":null,"abstract":"<div><div>The liver exhibits remarkable regenerative capacity. However, the limited ability of primary human hepatocytes to proliferate <em>in vitro</em>, combined with a compromised regenerative capacity induced by pathological conditions <em>in vivo</em>, presents significant obstacles to effective liver regeneration following liver injuries and diseases. Developing strategies to compensate for the loss of endogenous hepatocytes is crucial for overcoming these challenges, and this remains an active area of investigation. Lineage reprogramming, the process of directly converting one cell type into another bypassing the intermediate pluripotent state, has emerged as a promising method for generating specific cell types for therapeutic purposes in regenerative medicine. Here, we discuss the recent progress and emergent technologies in lineage reprogramming into hepatic cells, and their potential applications in enhancing liver regeneration or treating liver disease models. We also address controversies and challenges that confront this field.</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":"142115214","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}
Zi Yi Wang , Rui Xiang Chen , Ji Fei Wang, Shuo Chen Liu, Xiao Xu, Tao Zhou, Yan An Lan Chen, Yao Dong Zhang, Xiang Cheng Li, Chang Xian Li
{"title":"Apolipoprotein A-1 Accelerated Liver Regeneration Through Regulating Autophagy Via AMPK-ULK1 Pathway","authors":"Zi Yi Wang , Rui Xiang Chen , Ji Fei Wang, Shuo Chen Liu, Xiao Xu, Tao Zhou, Yan An Lan Chen, Yao Dong Zhang, Xiang Cheng Li, Chang Xian Li","doi":"10.1016/j.jcmgh.2023.12.004","DOIUrl":"10.1016/j.jcmgh.2023.12.004","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration.</p></div><div><h3>Methods</h3><p>Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration.</p></div><div><h3>Results</h3><p>We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy.</p></div><div><h3>Conclusions</h3><p>These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.</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/S2352345X23002175/pdfft?md5=093ec20b1fc8839a746c04f68c8d4394&pid=1-s2.0-S2352345X23002175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715131","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 Empowers Macrophages to Fight Helicobacter pylori","authors":"Stella G. Hoft, Richard J. DiPaolo","doi":"10.1016/j.jcmgh.2023.11.008","DOIUrl":"10.1016/j.jcmgh.2023.11.008","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/S2352345X23002035/pdfft?md5=e4c2ea915cc71ef21f21ade2312ea238&pid=1-s2.0-S2352345X23002035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138453204","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}
Mirco Glitscher, Inga Mareike Spannaus, Fabiane Behr, Robin Oliver Murra, Kathrin Woytinek, Daniela Bender, Eberhard Hildt
{"title":"The Protease Domain in HEV pORF1 Mediates the Replicase’s Localization to Multivesicular Bodies and Its Exosomal Release","authors":"Mirco Glitscher, Inga Mareike Spannaus, Fabiane Behr, Robin Oliver Murra, Kathrin Woytinek, Daniela Bender, Eberhard Hildt","doi":"10.1016/j.jcmgh.2024.01.001","DOIUrl":"10.1016/j.jcmgh.2024.01.001","url":null,"abstract":"<div><h3>Background</h3><p>A peculiar feature of the hepatitis E virus (HEV) is its reliance on the exosomal route for viral release. Genomic replication is mediated via the viral polyprotein pORF1, yet little is known about its subcellular localization.</p></div><div><h3>Methods</h3><p>Subcellular localization of pORF1 and its subdomains, generated and cloned based on a structural prediciton of the viral replicase, was analyzed via confocal laser scanning microscopy. Exosomes released from cells were isolated via ultracentrifugation and analyzed by isopycnic density gradient centrifugation. This was followed by fluorimetry or Western blot analyses or reverse transcriptase–polymerase chain reaction to analyze separated particles in more detail.</p></div><div><h3>Results</h3><p>We found pORF1 to be accumulating within the endosomal system, most dominantly to multivesicular bodies (MVBs). Expression of the polyprotein’s 7 subdomains revealed that the papain-like cysteine-protease (PCP) is the only domain localizing like the full-length protein. A PCP-deficient pORF1 mutant lost its association to MVBs. Strikingly, both pORF1 and PCP can be released via exosomes. Similarly, genomic RNA still is released via exosomes in the absence of pORF2/3.</p></div><div><h3>Conclusions</h3><p>Taken together, we found that pORF1 localizes to MVBs in a PCP-dependent manner, which is followed by exosomal release. This reveals new aspects of HEV life cycle, because replication and release could be coupled at the endosomal interface. In addition, this may mediate capsid-independent spread or may facilitate the spread of viral infection, because genomes entering the cell during de novo infection readily encounter exosomally transferred pORF1.</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/S2352345X24000018/pdfft?md5=7472c1e2654f8f451df01ffc51d5e0ee&pid=1-s2.0-S2352345X24000018-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139374519","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}
Ravi Holani , Paula T. Littlejohn , Karlie Edwards , Charisse Petersen , Kyung-Mee Moon , Richard G. Stacey , Tahereh Bozorgmehr , Zachary J. Gerbec , Antonio Serapio-Palacios , Zakhar Krekhno , Katherine Donald , Leonard J. Foster , Stuart E. Turvey , B. Brett Finlay
{"title":"A Murine Model of Maternal Micronutrient Deficiencies and Gut Inflammatory Host-microbe Interactions in the Offspring","authors":"Ravi Holani , Paula T. Littlejohn , Karlie Edwards , Charisse Petersen , Kyung-Mee Moon , Richard G. Stacey , Tahereh Bozorgmehr , Zachary J. Gerbec , Antonio Serapio-Palacios , Zakhar Krekhno , Katherine Donald , Leonard J. Foster , Stuart E. Turvey , B. Brett Finlay","doi":"10.1016/j.jcmgh.2024.01.018","DOIUrl":"10.1016/j.jcmgh.2024.01.018","url":null,"abstract":"<div><h3>Background & Aims</h3><p>Micronutrient deficiency (MND) (ie, lack of vitamins and minerals) during pregnancy is a major public health concern. Historically, studies have considered micronutrients in isolation; however, MNDs rarely occur alone. The impact of co-occurring MNDs on public health, mainly in shaping mucosal colonization by pathobionts from the <em>Enterobacteriaceae</em> family, remains undetermined due to lack of relevant animal models.</p></div><div><h3>Methods</h3><p>To establish a maternal murine model of multiple MND (MMND), we customized a diet deficient in vitamins (A, B12, and B9) and minerals (iron and zinc) that most commonly affect children and women of reproductive age. Thereafter, mucosal adherence by <em>Enterobacteriaceae</em>, the associated inflammatory markers, and proteomic profile of intestines were determined in the offspring of MMND mothers (hereafter, low micronutrient [LM] pups) via bacterial plating, flow cytometry, and mass spectrometry, respectively. For human validation, <em>Enterobacteriaceae</em> abundance, assessed via 16s sequencing of 3-month-old infant fecal samples (n = 100), was correlated with micronutrient metabolites using Spearman’s correlation in meconium of children from the CHILD birth cohort.</p></div><div><h3>Results</h3><p>We developed an MMND model and reported an increase in colonic abundance of <em>Enterobacteriaceae</em> in LM pups at weaning. Findings from CHILD cohort confirmed a negative correlation between <em>Enterobacteriaceae</em> and micronutrient availability. Furthermore, pro-inflammatory cytokines and increased infiltration of lymphocyte antigen 6 complex high monocytes and M1-like macrophages were evident in the colons of LM pups. Mechanistically, mitochondrial dysfunction marked by reduced expression of nicotinamide adenine dinucleotide (NAD)H dehydrogenase and increased expression of <em>NAD phosphate oxidase</em> (<em>Nox</em>) <em>1</em> contributed to the <em>Enterobacteriaceae</em> bloom.</p></div><div><h3>Conclusion</h3><p>This study establishes an early life MMND link to intestinal pathobiont colonization and mucosal inflammation via damaged mitochondria in the offspring.</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/S2352345X24000213/pdfft?md5=2ac9ea2e4d626e38a8ad7594e501a39f&pid=1-s2.0-S2352345X24000213-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669120","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}
Subinuer Abudukelimu , Noel F.C.C. de Miranda , Lukas J.A.C. Hawinkels
{"title":"Fibroblasts in Orchestrating Colorectal Tumorigenesis and Progression","authors":"Subinuer Abudukelimu , Noel F.C.C. de Miranda , Lukas J.A.C. Hawinkels","doi":"10.1016/j.jcmgh.2024.01.013","DOIUrl":"10.1016/j.jcmgh.2024.01.013","url":null,"abstract":"<div><p>Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have been shown to possess critical functions in tumor progression. Although their roles predominantly have been described as tumor-promoting, more recent findings have identified subsets of CAFs with tumor-restraining functions. Accumulating evidence underscores large heterogeneity in fibroblast subsets in which distinct subsets differentially impact the initiation, progression, and metastasis of colorectal cancer. In this review, we summarize and discuss the evolving role of CAFs in colorectal cancer, highlighting the ongoing controversies regarding their distinct origins and multifaceted functions. In addition, we explore how CAFs can confer resistance to current therapies and the challenges of developing effective CAF-directed therapies. Taken together, we believe that, in this rapidly evolving field, it is crucial first to understand CAF dynamics comprehensively, and to bridge existing knowledge gaps regarding CAF heterogeneity and plasticity before further exploring the clinical targeting of CAFs.</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/S2352345X24000134/pdfft?md5=c5b9bf3bb91618ff2771c0ab88d93c54&pid=1-s2.0-S2352345X24000134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669121","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":"Introducing Article Numbering to Cellular and Molecular Gastroenterology and Hepatology","authors":"","doi":"10.1016/S2352-345X(24)00128-0","DOIUrl":"10.1016/S2352-345X(24)00128-0","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/S2352345X24001280/pdfft?md5=73473c812c56b99a8ef4dbc7c0028904&pid=1-s2.0-S2352345X24001280-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637004","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":"Fibroblast Growth Factor 19 in Alcohol-Associated Liver Disease: Bile Acids and Dysbiosis and Inflammation, Oh My!","authors":"Lindsey Kennedy","doi":"10.1016/j.jcmgh.2024.03.014","DOIUrl":"10.1016/j.jcmgh.2024.03.014","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/S2352345X24000699/pdfft?md5=edd68269c1caa81d05bfc67d73175250&pid=1-s2.0-S2352345X24000699-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797544","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}