eGastroenterology最新文献

{"title":"Mechanistic role of long non-coding RNAs in the pathogenesis of metabolic dysfunction-associated steatotic liver disease and fibrosis.","authors":"Henry Wade, Kaichao Pan, Bingrui Zhang, Wenhua Zheng, Qiaozhu Su","doi":"10.1136/egastro-2024-100115","DOIUrl":"10.1136/egastro-2024-100115","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease, encompasses a broad range of hepatic metabolic disorders primarily characterised by the disruption of hepatic lipid metabolism, hepatic lipid accumulation and steatosis. Severe cases of MASLD might progress to metabolic dysfunction-associated steatohepatitis, characterised by hepatic inflammation, hepatocyte ballooning degeneration, activation of hepatic stellate cells (HSCs) and fibrogenesis. It may further progress to hepatocellular carcinoma. In the liver, long non-coding RNAs (lncRNAs) target multiple metabolic pathways in hepatocytes, HSCs, and Kupffer cells at different stages of MASLD and liver fibrosis. In this study, we overview recent findings on the potential role of lncRNAs in the pathogenesis of MASLD and liver fibrosis via modulation of de novo lipid synthesis, fatty acid β-oxidation, lipotoxicity, oxidative stress, metabolic inflammation, mammalian target of rapamycin signalling, apoptosis, ubiquitination and fibrogenesis. We critically assess the literature reports that investigate the complex interplay between lncRNA, microRNA and key mediators in liver injury, in both human participants and animal models of MASLD and liver fibrosis. We also highlight the therapeutic potential of lncRNAs in chronic liver diseases.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":"e100115"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine pathology in young rabbits with cystic fibrosis.","authors":"Xiubin Liang, Xia Hou, Y Eugene Chen, Jian-Ping Jin, Kezhong Zhang, Jie Xu","doi":"10.1136/egastro-2024-100102","DOIUrl":"10.1136/egastro-2024-100102","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by loss-of-function mutations in the <i>CF</i> transmembrane conductance regulator gene. CF-related pancreatic lesions are known to cause exocrine dysfunctions such as pancreatic insufficiency, and endocrine dysfunctions, including CF related diabetes. In a previous study, we generated CF rabbits using CRISPR/Cas9-mediated gene editing.</p><p><strong>Methods: </strong>CF rabbits were subjected to histological analysis with a focus on CF associated pancreatic lesions. Endocrine function related assays were conducted to evaluate CF related pancreatic endocrine disorders in these animals.</p><p><strong>Results: </strong>We report that CF rabbits develop spontaneous pancreatic lesions at a young age, characterised by pancreatic inflammation and fibrosis, vacuolar degeneration, epithelium mucus-secretory cell metaplasia, and pancreatic duct dilation. The size of the pancreatic islets in the CF rabbits is significantly smaller than that of the wild type animals. Consistent with these pathological findings, young CF rabbits exhibited signs of pancreatic endocrine related disorders such as lower insulin levels and impaired glucose metabolism.</p><p><strong>Conclusions: </strong>Our results suggest that the CF rabbit could serve as a valuable model for translational research on CF related pancreatic endocrine dysfunction.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.","authors":"Meihua Hao, Sara C Sebag, Qingwen Qian, Ling Yang","doi":"10.1136/egastro-2024-100096","DOIUrl":"10.1136/egastro-2024-100096","url":null,"abstract":"<p><p>Endocrine and exocrine functions of the pancreas control nutritional absorption, utilisation and systemic metabolic homeostasis. Under basal conditions, the lysosome is pivotal in regulating intracellular organelles and metabolite turnover. In response to acute or chronic stress, the lysosome senses metabolic flux and inflammatory challenges, thereby initiating the adaptive programme to re-establish cellular homeostasis. A growing body of evidence has demonstrated the pathophysiological relevance of the lysosomal stress response in metabolic diseases in diverse sets of tissues/organs, such as the liver and the heart. In this review, we discuss the pathological relevance of pancreatic lysosome stress in diabetes mellitus. We begin by summarising lysosomal biology, followed by exploring the immune and metabolic functions of lysosomes and finally discussing the interplay between lysosomal stress and the pathogenesis of pancreatic diseases. Ultimately, our review aims to enhance our understanding of lysosomal stress in disease pathogenesis, which could potentially lead to the discovery of innovative treatment methods for these conditions.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New therapeutic target for alcohol-associated hepatitis (AH): AH-associated IL-8⁺ neutrophils.","authors":"Yukun Guan, Dechun Feng, Luca Maccioni, Yang Wang, Bin Gao","doi":"10.1136/egastro-2024-100166","DOIUrl":"10.1136/egastro-2024-100166","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.","authors":"Hui Gao, Yanchao Jiang, Ge Zeng, Nazmul Huda, Themis Thoudam, Zhihong Yang, Suthat Liangpunsakul, Jing Ma","doi":"10.1136/egastro-2024-100104","DOIUrl":"10.1136/egastro-2024-100104","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD. It examines the contributions of both parenchymal cells, like hepatocytes, and non-parenchymal cells, such as hepatic stellate cells, Kupffer cells, neutrophils, and liver sinusoidal endothelial cells, in driving the progression of the disease. Additionally, we explored the involvement of key mediators, including cytokines, chemokines and inflammasomes, which regulate inflammatory responses and promote liver injury and fibrosis. A particular focus has been placed on extracellular vesicles (EVs) as essential mediators of intercellular communication both within and beyond the liver. These vesicles facilitate the transfer of signalling molecules, such as microRNAs and proteins, which modulate immune responses, fibrogenesis and lipid metabolism, thereby influencing disease progression. Moreover, we underscore the importance of organ-to-organ crosstalk, particularly in the gut-liver axis, where dysbiosis and increased intestinal permeability lead to microbial translocation, exacerbating hepatic inflammation. The adipose-liver axis is also highlighted, particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases.","authors":"Fernanda Raya Tonetti, Alvaro Eguileor, Cristina Llorente","doi":"10.1136/egastro-2024-100098","DOIUrl":"https://doi.org/10.1136/egastro-2024-100098","url":null,"abstract":"<p><p>Goblet cells (GCs) are specialised guardians lining the intestine. They play a critical role in gut defence and immune regulation. GCs continuously secrete mucus creating a physical barrier to protect from pathogens while harbouring symbiotic gut bacteria adapted to live within the mucus. GCs also form specialised GC-associated passages in a dynamic and regulated manner to deliver luminal antigens to immune cells, promoting gut tolerance and preventing inflammation. The composition of gut bacteria directly influences GC function, highlighting the intricate interplay between these components of a healthy gut. Indeed, imbalances in the gut microbiome can disrupt GC function, contributing to various gastrointestinal diseases like colorectal cancer, inflammatory bowel disease, cystic fibrosis, pathogen infections and liver diseases. This review explores the interplay between GCs and the immune system. We delve into the underlying mechanisms by which GC dysfunction contributes to the development and progression of gastrointestinal diseases. Finally, we examine current and potential treatments that target GCs and represent promising avenues for further investigation.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics","authors":"Amy Cross, James M. Harris, Edward Arbe-Barnes, Colin Nixon, R. Dhairyawan, Andrew Hall, Alberto Quaglia, Fadi Issa, Patrick T F Kennedy, Jane A. McKeating, U. Gill, Dimitra Peppa","doi":"10.1136/egastro-2024-100067","DOIUrl":"https://doi.org/10.1136/egastro-2024-100067","url":null,"abstract":"The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection.The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions.Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses. Shared features including ‘cytotoxicity’ and ‘B cell receptor signalling’ were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of γδT cells in the HDV/HBV sample, were observed within analysed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression.This proof-of-principle study shows the value of this platform in investigating the complex immune landscape, highlighting relevant host pathways to disease pathogenesis.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"61 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141699020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prebiotic selection influencing inflammatory bowel disease treatment outcomes: a review of the preclinical and clinical evidence","authors":"Amin Ariaee, Sabrina Koentgen, Hannah R. Wardill, Georgina L Hold, C. Prestidge, H. Armstrong, P. Joyce","doi":"10.1136/egastro-2023-100055","DOIUrl":"https://doi.org/10.1136/egastro-2023-100055","url":null,"abstract":"Inflammatory bowel disease (IBD) is characterised by chronic inflammation in the gastrointestinal tract, with unclear aetiology but with known factors contributing to the disease, including genetics, immune responses, environmental factors and dysbiosis of the gut microbiota. Existing pharmacotherapies mainly target the inflammatory symptoms of disease, but recent research has highlighted the capacity for microbial-accessible carbohydrates that confer health benefits (ie, prebiotics) to selectively stimulate the growth of beneficial gut bacteria for improved IBD management. However, since prebiotics vary in source, chemical composition and microbiota effects, there is a clear need to understand the impact of prebiotic selection on IBD treatment outcomes. This review subsequently explores and contrasts the efficacy of prebiotics from various sources (β-fructans, galacto-oligosaccharides, xylo-oligosaccharides, resistant starch, pectin, β-glucans, glucomannans and arabinoxylans) in mitigating IBD symptomatology, when used as either standalone or adjuvant therapies. In preclinical animal colitis models, prebiotics have revealed type-dependent effects in positively modulating gut microbiota composition and subsequent attenuation of disease indicators and proinflammatory responses. While prebiotics have demonstrated therapeutic potential in animal models, clinical evidence for their precise efficacy remains limited, stressing the need for further investigation in human patients with IBD to facilitate their widespread clinical translation as microbiota-targeting IBD therapies.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"104 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140768597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFDN6 contributes to colorectal cancer progression via transcriptional regulation","authors":"Fenghua Xu, Lingyang Kong, Xiao Sun, WenXiang Hui, Lan Jiang, Wenxin Han, ZhiFeng Xiao, Ning Li, DongFeng Chen, Nan Zheng, Jing Han, Lei Liu","doi":"10.1136/egastro-2023-100001","DOIUrl":"https://doi.org/10.1136/egastro-2023-100001","url":null,"abstract":"Colorectal cancer (CRC) is a common cancer worldwide. Although there are several treatments for cancer, the therapeutic effect on CRC remains unsatisfactory, and it is imperative to identify new therapeutic targets.Prefoldin (PFDN) is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers. However, whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated. In this study, molecular biology, cell culture, transcriptome sequencing and other experimental techniques, combined with bioinformatics, were used to verify the regulatory effects of PFDN6 on CRC.PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC. Knockdown of PFDN6 reduced the tumour cell number, promoted apoptosis, and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines. Mechanistically, differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575. These results open new avenues for therapeutic interventions for patients with CRC.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"20 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140791923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile acids regulation of cellular stress responses in liver physiology and diseases.","authors":"Tiangang Li, Mohammad Nazmul Hasan, Lijie Gu","doi":"10.1136/egastro-2024-100074","DOIUrl":"10.1136/egastro-2024-100074","url":null,"abstract":"<p><p>Bile acids are physiological detergents and signalling molecules that are critically implicated in liver health and diseases. Dysregulation of bile acid homeostasis alters cell function and causes cell injury in chronic liver diseases. Therapeutic agents targeting bile acid synthesis, transport and signalling hold great potential for treatment of chronic liver diseases. The broad cellular and physiological impacts of pharmacological manipulations of bile acid metabolism are still incompletely understood. Recent research has discovered new links of bile acid signalling to the regulation of autophagy and lysosome biology, redox homeostasis and endoplasmic reticulum stress. These are well-conserved mechanisms that allow cells to adapt to nutrient and organelle stresses and play critical roles in maintaining cellular integrity and promoting survival. However, dysregulation of these cellular pathways is often observed in chronic liver diseases, which exacerbates cellular dysfunction to contribute to disease pathogenesis. Therefore, identification of these novel links has significantly advanced our knowledge of bile acid biology and physiology, which is needed to understand the contributions of bile acid dysregulation in disease pathogenesis, establish bile acids as diagnostic markers and develop bile acid-based pharmacological interventions. In this review, we will first discuss the roles of bile acid dysregulation in the pathogenesis of chronic liver diseases, and then discuss the recent findings on the crosstalk of bile acid signalling and cellular stress responses. Future investigations are needed to better define the roles of these crosstalks in regulating cellular function and disease processes.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}