eGastroenterology最新文献

{"title":"Multimodal decoding of human liver regeneration uncovers novel ANXA2+ migratory hepatocytes for wound healing.","authors":"Khue Nguyen, Wen-Xing Ding, Hong-Min Ni","doi":"10.1136/egastro-2025-100205","DOIUrl":"10.1136/egastro-2025-100205","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100205"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103256","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":"Epigenetic mechanisms involved in hepatocellular carcinoma development and progression.","authors":"Barbara Bueloni, Maite Garcia Fernandez de Barrena, Matias Antonio Avila, Juan Bayo, Guillermo Mazzolini","doi":"10.1136/egastro-2025-100186","DOIUrl":"https://doi.org/10.1136/egastro-2025-100186","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) typically develops in the context of chronic liver disease, where prolonged hepatocyte exposure to inflammation drives the synergistic accumulation of genetic and epigenetic alterations. Epigenetic regulation encompasses multiple mechanisms that govern the transcription machinery accessibility to DNA. This process is regulated by the addition and removal of covalent marks on chromatin, which can either affect DNA-histone interactions or serve as scaffolds for other proteins, among other mechanisms. Recent research has revealed that epigenetic alterations can disrupt chromatin homeostasis, redirecting transcriptional regulation to favour cancer-promoting states. Consequently, these alterations play a pivotal role in the acquisition of cancer hallmarks and provide insights into several biological processes involved in hepatocarcinogenesis. This review highlights the key epigenetic mechanisms underlying the development, progression and dissemination of HCC, with a particular focus on DNA methylation and histone post-translational modifications. This knowledge is relevant for guiding the development of innovative therapeutic approaches based on epigenetic modulators.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100186"},"PeriodicalIF":0.0,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164206","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":"Burden of digestive system malignancies and its impact on life expectancy in China, 2004-2021.","authors":"Ting Hu, Shiyue Wang, Yingying Wang, Xinlong Wang, Lin Shang, Kaijuan Wang","doi":"10.1136/egastro-2024-100148","DOIUrl":"https://doi.org/10.1136/egastro-2024-100148","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100148"},"PeriodicalIF":0.0,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164162","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":"Pentoxifylline use in alcohol-associated hepatitis with acute kidney injury does not improve survival: a global study.","authors":"Francisco Idalsoaga, Luis Antonio Diaz, Winston Dunn, Heer Mehta, Vicente Caldentey, Jorge Arnold, Gustavo Ayares, Shiv K Sarin, Rakhi Maiwall, Wei Zhang, Steve Qian, Douglas Simonetto, Ashwani K Singal, Mohamed A Elfeki, Mohammad Qasim Khan, Rokhsana Mortuza, Gurpreet Malhi, Alvi Husni Islam, Leonardo Guizzetti, Carolina Ramirez-Cadiz, Joaquín Cabezas, Victor Echavarria, Maria Poca, Berta Cuyas, German Soriano, Meritxell Ventura Cots, María Fátima Higuera-De La Tijera, Juan G Abraldes, Mustafa Al-Karaghouli, Lubomir Skladaný, Daniel Jan Havaj, Diego Rincón, Vijay Shah, Marco Arrese, Patrick S Kamath, Ramon Bataller, Juan Pablo Arab","doi":"10.1136/egastro-2024-100179","DOIUrl":"https://doi.org/10.1136/egastro-2024-100179","url":null,"abstract":"<p><strong>Background: </strong>Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with high mortality, where corticosteroid use is the only treatment that has shown short-term benefits. Pentoxifylline, an anti-tumour necrosis factor-alpha agent, has been proposed for its potential to improve outcomes, especially in patients with acute kidney injury (AKI). We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.</p><p><strong>Methods: </strong>We conducted a retrospective, registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI. Mortality was the primary endpoint, with liver transplantation as a competing risk. Statistical analysis included Cox regression and Kaplan-Meier survival estimates.</p><p><strong>Results: </strong>We included 525 patients from 20 centres across eight countries. The median age was 48 years, with 26.1% females, and 76.9% had a history of cirrhosis. Multivariable Cox regression models showed that pentoxifylline use was not associated with survival (HR 1.20, 95% CI 0.85 to 1.69, p=0.291). Factors associated with mortality included age (HR 1.23, 95% CI 1.10 to 1.36, p<0.001), Model for End-Stage Liver Disease score at admission (HR 1.06, 95% CI 1.04 to 1.08, p<0.001) and renal replacement therapy use (HR 1.39, 95% CI 1.05 to 1.84, p=0.019). The main causes of death were multiple organ failure (42%), infections (10%), oesophageal varices bleeding (7%) and renal failure (6%).</p><p><strong>Conclusion: </strong>Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI. Further studies are needed to refine treatment strategies for this high-risk group.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100179"},"PeriodicalIF":0.0,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051449","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 macrophages in healthy and diseased livers in mice: identification of necrotic lesion-associated macrophages.","authors":"Dechun Feng, Yukun Guan, Yang Wang, Luca Maccioni, Bryan Mackowiak, Bin Gao","doi":"10.1136/egastro-2025-100189","DOIUrl":"10.1136/egastro-2025-100189","url":null,"abstract":"<p><strong>Background: </strong>Healthy livers contain a large number of resident macrophages named Kupffer cells (KCs), which are partially replaced by infiltrating monocyte-derived macrophages (MoMFs) during acute or chronic liver injury. Despite extensive research, understanding macrophage heterogeneity, spatial distribution and interactions with other cells within the liver remains challenging.</p><p><strong>Methods: </strong>This study employs sequential multiplex immunofluorescence staining, advanced image analysis and single-cell RNA sequencing (scRNA-seq) analysis to characterise macrophages in both healthy and diseased livers in mice.</p><p><strong>Results: </strong>Our data revealed that liver KCs made up more than 80% of total immune cells in healthy mouse livers, while massive amounts of MoMFs infiltrated into the livers after acute and chronic liver injury. KCs were more abundant and larger in Zones 1 and 2 compared with Zone 3 in healthy livers. Zone 1 KCs exhibited higher phagocytic activity than Zone 2/3 KCs and MoMFs. We simultaneously evaluated cell proliferation and apoptosis on one slide and found that proliferation and apoptosis of KCs and MoMFs significantly increased in acutely injured livers. We also performed scRNA-seq to investigate liver macrophage gene expression in naïve and concanavalin A (ConA)-treated mice. MoMF clusters expanded following ConA treatment, while KCs remained stable. Macrophages were divided into distinct subtypes, including <i>C1q⁺</i> MoMFs, with differential expression of genes like <i>Trem2, Spp1, Fabp5</i> and <i>Gpnmb</i>. Newly recruited <i>C1q^-</i> MoMFs expressed high levels of <i>Lyz</i> and <i>Ccr2</i>, while <i>Itgax</i> (<i>Cd11c</i>)⁺ MoMFs expressed endothelin converting enzyme 1 (<i>Ece1</i>), a gene encoding ECE1 enzyme that activates endothelin to promote hepatic stellate cell contraction and necrotic lesion resolution. By immunostaining analysis of the proteins encoded by these signature genes, we identified several populations of MoMFs that were mainly located surrounding the necrotic lesion area and expressed various proteins that are involved in dead cell debris clearance.</p><p><strong>Conclusion: </strong>We developed a robust framework for studying liver macrophages <i>in vivo</i>, offering insights into their roles in host defence and liver injury/repair. We identified several populations of MoMFs that surround necrotic lesion areas and express proteins that promote dead cell debris clearance. These necrotic lesion-associated macrophages likely play key roles in promoting necrotic lesion resolution.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 2","pages":"e100189"},"PeriodicalIF":0.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043769","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":"Gasdermin D deletion prevents liver injury and exacerbates extrahepatic damage in a murine model of alcohol-induced ACLF.","authors":"Martí Ortega-Ribera, Yuan Zhuang, Veronika Brezani, Radhika S Joshi, Zsuzsanna Zsengeller, Prashanth Thevkar Nagesh, Aditi Datta, Gyongyi Szabo","doi":"10.1136/egastro-2024-100151","DOIUrl":"10.1136/egastro-2024-100151","url":null,"abstract":"<p><strong>Background: </strong>Gasdermin D (GSDM-D), a key executor of pyroptosis, is increased in various liver diseases and contributes to disease progression. Alcohol induces inflammasome activation and cell death, which are both linked to GSDM-D activation. However, its role in alcohol-induced acute-on-chronic liver failure (ACLF) remains unclear.</p><p><strong>Methods: </strong>ACLF was induced in GSDM-D-deficient or wild-type (WT) mice by 28-day bile duct ligation surgery plus a single 5 g/kg alcohol binge leading to acute decompensation. Nine hours after the alcohol binge, blood, liver, kidney and cerebellum specimens were collected for analysis.</p><p><strong>Results: </strong>Active GSDM-D was significantly increased in humans and mice ACLF livers compared with both healthy controls and cirrhotic livers. GSDM-D-deficient mice with ACLF showed decreased inflammation, neutrophil infiltration and fibrosis in the liver, together with a reduction in pyroptotic, apoptotic and necroptotic death, compared with WT ACLF mice. Notably, GSDM-D-deficient mice also showed decreased liver regeneration and hepatocyte function. This was associated with an increase in senescence and expression of stem-like/cholangiocyte markers in the liver. Interestingly, in the kidney, GSDM-D-deficient mice showed an increase in histopathological damage score, decreased function and increased expression of necroptosis-related genes. In the cerebellum, GSDM-D deficiency increased the expression of neuroinflammation markers, astrocyte activation and apoptosis-related genes.</p><p><strong>Conclusion: </strong>Our data indicate that GSDM-D deficiency has organ-specific effects in ACLF. While it reduces inflammation, neutrophil activation, cell death and fibrosis in the liver, GSDM-D deficiency impairs the synthetic function and increases senescence in hepatocytes. GSDM-D deficiency also increases kidney injury and neuroinflammation in ACLF.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":"e100151"},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712457","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":"Bacterial dysbiosis and decrease in SCFA correlate with intestinal inflammation following alcohol intoxication and burn injury.","authors":"Caroline J Herrnreiter, Mary Grace Murray, Marisa Luck, Chirag Ganesa, Paulius V Kuprys, Xiaoling Li, Mashkoor A Choudhry","doi":"10.1136/egastro-2024-100145","DOIUrl":"10.1136/egastro-2024-100145","url":null,"abstract":"<p><strong>Background: </strong>Patients intoxicated at the time of burn experience increased rates of sepsis and death compared with that observed in similarly sized burns alone. We sought to characterise changes in the intestinal microbiome and short-chain fatty acids (SCFAs) following alcohol intoxication and burn injury and to determine whether these changes are associated with intestinal inflammation.</p><p><strong>Methods: </strong>10-12-week-old C57BL/6 male and female mice were subjected to ethanol intoxication and a 12.5% total body surface area scald burn injury. The following day, mice were euthanised and faecal contents from the caecum and small intestine (SI) were harvested for 16S sequencing for microbial analysis and caecum contents underwent high-performance liquid chromatography mass spectroscopy to assess SCFAs.</p><p><strong>Results: </strong>The intestinal microbiome of ethanol burn (EB) mice exhibited decreased alpha diversity and distinct beta diversity compared with sham vehicle (SV). EB faeces were marked by increased Proteobacteria and many pathobionts. EB caecum faeces exhibited a significant decrease in butyrate and a downward trend in acetate and total SCFAs. SCFA changes correlated with microbial changes particularly in the SI. Treatment of murine duodenal cell clone-K (MODE-K) cells with faecal slurries led to upregulation of interleukin-6 (IL-6) from EB faeces compared with SV faeces which correlated with levels of Enterobacteriaceae. However, supplementation of butyrate reduced faecal slurry-induced MODE-K cells IL-6 release.</p><p><strong>Conclusion: </strong>Together, these findings suggest that alcohol and burn injury induce bacterial dysbiosis and a decrease in SCFAs, which together can promote intestinal inflammation and barrier disruption, predisposing to postinjury pathology.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":"e100145"},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652410","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":"Steatosis is not associated with increased risk of chemotherapy-associated liver injury in metastatic colorectal cancer.","authors":"Rebecca Squires, Cameron Blair, Hedvig Karteszi, Pedram Modarres, Chloe Caws, Syamantak Mookherjee, Timothy Robinson, Kushala W Abeysekera","doi":"10.1136/egastro-2024-100157","DOIUrl":"10.1136/egastro-2024-100157","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":"e100157"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652417","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":"Periodontal disease and cirrhosis: current concepts and future prospects.","authors":"David Hudson, Gustavo Ayares, Zahra Taboun, Gurpreet Malhi, Francisco Idalsoaga, Rokhsana Mortuza, Maite Souyet, Carolina Ramirez-Cadiz, Luis Antonio Díaz, Marco Arrese, Juan Pablo Arab","doi":"10.1136/egastro-2024-100140","DOIUrl":"10.1136/egastro-2024-100140","url":null,"abstract":"<p><p>Periodontal diseases are prevalent among the general population and are associated with several systemic conditions, such as chronic kidney disease and type 2 diabetes mellitus. Chronic liver disease and cirrhosis have also been linked with periodontal disease, an association with complex underlying mechanisms, and with potential prognostic implications. Multiple factors can explain this relevant association, including nutritional factors, alcohol consumption, disruption of the oral-gut-liver axis and associated dysbiosis. Additionally, patients with liver disease have been observed to exhibit poorer oral hygiene practices compared with the general population, potentially predisposing them to the development of periodontal disease. Therefore, it is recommended that all patients with liver disease undergo screening and subsequent treatment for periodontal disease. Treatment of periodontal disease in patients with cirrhosis may help reduce liver-derived inflammatory damage, with recent research indicating a potential benefit in terms of reduced mortality. However, further studies on periodontal disease treatment in patients with liver disease are still warranted to determine optimal management strategies. This narrative review describes current concepts on the association between periodontal disease and chronic liver disease.</p>","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":"e100140"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756308","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":"Attention to the misuse of Mendelian randomisation in medical research.","authors":"Lanlan Chen, Adrien Guillot, Carolin Victoria Schneider","doi":"10.1136/egastro-2025-100187","DOIUrl":"10.1136/egastro-2025-100187","url":null,"abstract":"","PeriodicalId":72879,"journal":{"name":"eGastroenterology","volume":"3 1","pages":"e100187"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756242","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}