eGastroenterology最新文献

{"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":"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}

{"title":"Incorporating biological and clinical insights into variant choice for Mendelian randomisation: examples and principles","authors":"S. Burgess, H. T. Cronjé","doi":"10.1136/egastro-2023-100042","DOIUrl":"https://doi.org/10.1136/egastro-2023-100042","url":null,"abstract":"Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes. However, if performed without critical thought, we may simply have replaced one set of implausible assumptions (no unmeasured confounding or reverse causation) with another set of implausible assumptions (no pleiotropy or other instrument invalidity). The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables. Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy; in general, a biologically motivated strategy is preferred. In this review, we discuss various ways of implementing a biologically motivated selection strategy: using variants in a coding gene region for the exposure or a gene region that encodes a regulator of exposure levels, using a positive control variable and using a biomarker as the exposure rather than its behavioural proxy. In some cases, a genome-wide analysis can provide important complementary evidence, even when its reliability is questionable. In other cases, a biologically-motivated analysis may not be possible. The choice of genetic variants must be informed by biological and functional considerations where possible, requiring collaboration to combine biological and clinical insights with appropriate statistical methodology.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"103 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139638552","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":"Pathogenesis and precision medicine for predicting response in inflammatory bowel disease: advances and future directions","authors":"R. Little, Thisun Jayawardana, Sabrina Koentgen, Fan Zhang, Susan J Connor, Alex Boussioutas, M. Ward, Peter R. Gibson, Miles P Sparrow, Georgina L Hold","doi":"10.1136/egastro-2023-100006","DOIUrl":"https://doi.org/10.1136/egastro-2023-100006","url":null,"abstract":"The pathogenesis of inflammatory bowel disease (IBD) is complex and multifactorial. Undertreated disease has substantial individual and societal consequences. Current patient classification and subsequent positioning of IBD therapy are based on crude, readily accessible clinical data. These broad parameters are unlikely to reflect underlying molecular profiles and may account for the observed heterogeneity in treatment response. Precision medicine offers identification and integration of molecular profiles into clinical decision-making. Despite several promising scientific and technological advances, the pathogenesis and targetable molecular drivers of IBD remain incompletely understood. Precision medicine therefore remains aspirational. This comprehensive narrative review describes our current understanding of IBD pathophysiology, highlights preliminary genetic, immunological and microbial predictors of treatment response and outlines the role of ‘big data’ and machine learning in the path towards precision medicine.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"23 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139631601","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":"Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases","authors":"B. Chang, Hui Tian, Ang Huang, Xingran Zhai, Qiaoling Wang, Lin Han, Xueyuan Jin, Li Gao, Qing-xiang Liang, Baosen Li, Yinying Lu, Huan Xie, Dong Ji, Zhengsheng Zou","doi":"10.1136/egastro-2023-100036","DOIUrl":"https://doi.org/10.1136/egastro-2023-100036","url":null,"abstract":"To explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated liver disease (ALD)-related HCC risk.A database of 136 571 inpatients in the Fifth Medical Center of Chinese PLA General Hospital from 2002 to 2018 with chronic liver disease was established. Data were collected by medical records review. Multivariate logistic regression was used to identify the independent high-risk factors associated with HCC, and then were incorporated into a novel nomogram. Afterward, the new established model was validated using external cohort by receiver operating characteristic curves analysis. For external cohort, 1646 patients with ALD admitted to our hospital from 2019 to 2021 were included. ALD was diagnosed on the basis of a history of sustained heavy alcohol intake greater than 40 g/day for men and 20 g/day for women for >5 years, clinical evidence of liver disease and supporting laboratory abnormalities.Over the last 17 years, trends showed obviously increases in ALD. ALD-related HCC experienced a significant increase from 5.8% to 30.7%, whereas hepatitis B virus (HBV)-related HCC declined from 77.6% to 52.0%. In patients with ALD-related HCC (5119), 3816 (74.54%) cases had HBV infection, 493 (9.63%) cases had hepatitis C virus (HCV) infection, 71 (1.39%) cases were coinfected with both HBV and HCV, and 739 (14.44%) cases had neither HBV nor HCV infection. Drinking years (OR 1.009, 95% CI (1.000 to 1.017)), age (OR 1.060, 95% CI (1.051 to 1.069)), diabetes mellitus (OR 1.314, 95% CI (1.123 to 1.538)), HBV infection (OR 4.905, 95% CI (4.242 to 5.671)), liver cirrhosis (OR 4.922, 95% CI (3.887 to 6.232)) and male sex (OR 17.011, 95%CI (2.296 to 126.013)) were associated with increased risk of HCC in patients with ALD. A nomogram had a concordance index of 0.786 (95% CI 0.773 to 0.799) and had well-fitted calibration curves. These results were successfully validated both in the internal cohort and external cohort.The prevalence of ALD and ALD-related HCC has been increased dramatically. The nomogram model established here with its high accuracy and easy-to-use features achieved an optimal prediction of HCC development in patients with ALD, which can help clinicians to develop an individualised and precise treatment strategy.","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"262 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139636209","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}