Gut最新文献

{"title":"Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B: still needs further discussion.","authors":"Taiyu He, Dazhi Zhang","doi":"10.1136/gutjnl-2023-331443","DOIUrl":"10.1136/gutjnl-2023-331443","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e28"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"eCura and W-eCura: different scores, different populations, same goal.","authors":"Rui Morais, Diogo Libanio, João Santos-Antunes","doi":"10.1136/gutjnl-2024-331924","DOIUrl":"10.1136/gutjnl-2024-331924","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e29"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug targets for haemorrhoidal disease: proteome-wide Mendelian randomisation and colocalisation analyses.","authors":"Shifang Li, Meijiao Gong","doi":"10.1136/gutjnl-2023-330967","DOIUrl":"10.1136/gutjnl-2023-330967","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e31"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis.","authors":"Mrigya Babuta, Caroline Morel, Marcelle de Carvalho Ribeiro, Charles Calenda, Martí Ortega-Ribera, Prashanth Thevkar Nagesh, Christopher Copeland, Yuan Zhuang, Yanbo Wang, Yeonhee Cho, Radhika Joshi, Viliam Brezani, Danielle Hawryluk, Aditi Ashish Datta, Jeeval Mehta, Imad Nasser, Gyongyi Szabo","doi":"10.1136/gutjnl-2023-331447","DOIUrl":"10.1136/gutjnl-2023-331447","url":null,"abstract":"<p><strong>Objective: </strong>Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH.</p><p><strong>Design: </strong>C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) and fibrosis were evaluated.</p><p><strong>Results: </strong>We found that alcohol binges in MASH increase liver injury and fibrosis. Liver transcriptomic profiling revealed differential expression of genes involved in extracellular matrix reorganisation, neutrophil activation and inflammation compared with alcohol or the MASH diet alone. Alcohol binges specifically increased NET formation in MASH livers in mice, and NETs were also increased in human livers with MASH plus alcohol use. We discovered that cell-free NETs are sensed via Nod-like receptor protein 3 (NLRP3). Furthermore, we show that cell-free NETs in vitro induce a profibrotic phenotype in hepatic stellate cells (HSCs) and proinflammatory monocytes. In vivo, neutrophil depletion using anti-Ly6G antibody or NET disruption with deoxyribonuclease treatment abrogated monocyte and HSC activation and ameliorated liver damage and fibrosis. In vivo, inhibition of NLRP3 using MCC950 or NLRP3 deficiency attenuated NET formation, liver injury and fibrosis in MASH plus alcohol diet-fed mice (graphical abstract).</p><p><strong>Conclusion: </strong>Alcohol binges promote liver fibrosis via NET-induced activation of HSCs and monocytes in MASH. Our study highlights the potential of inhibition of NETs and/or NLRP3, as novel therapeutic strategies to combat the profibrotic effects of alcohol in MASH.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1854-1869"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081156","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":"When alcohol and fat meet, neutrophil traps form to promote liver injury.","authors":"Gavin E Arteel, Bin Gao","doi":"10.1136/gutjnl-2024-332514","DOIUrl":"10.1136/gutjnl-2024-332514","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1778-1779"},"PeriodicalIF":23.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537822","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":"Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates.","authors":"Karol M Córdoba, Daniel Jericó, Lei Jiang, María Collantes, Manuel Alegre, Leyre García-Ruiz, Oscar Manzanilla, Ana Sampedro, Jose M Herranz, Iñigo Insausti, Antonio Martinez de la Cuesta, Francesco Urigo, Patricia Alcaide, María Morán, Miguel A Martín, José Luis Lanciego, Thibaud Lefebvre, Laurent Gouya, Gemma Quinconces, Carmen Unzu, Sandra Hervas-Stubbs, Juan M Falcón-Pérez, Estíbaliz Alegre, Azucena Aldaz, María A Fernández-Seara, Iván Peñuelas, Pedro Berraondo, Paolo G V Martini, Matias A Avila, Antonio Fontanellas","doi":"10.1136/gutjnl-2024-332619","DOIUrl":"10.1136/gutjnl-2024-332619","url":null,"abstract":"<p><strong>Objective: </strong>Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors.</p><p><strong>Design: </strong>We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic <i>PBGD</i> gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue.</p><p><strong>Results: </strong>Intrahepatic administration of a recombinant adeno-associated viral vector containing short hairpin RNA against endogenous PBGD mRNA resulted in sustained PBGD activity inhibition in liver tissue for up to 7 months postinjection. The administration of porphyrinogenic drugs to NHPs induced hepatic heme synthesis, elevated urinary porphyrin precursors and reproduced acute attack symptoms in patients with AIP, including pain, motor disturbances and increased brain GABAergic activity. The model also recapitulated functional anomalies associated with AIP, such as reduced brain perfusion and cerebral glucose uptake, disturbances in hepatic TCA cycle, one-carbon metabolism, drug biotransformation, lipidomic profile and abnormal mitochondrial respiratory chain activity. Additionally, repeated systemic administrations of hPBGD mRNA in this AIP NHP model restored hepatic PBGD levels and activity, providing successful protection against acute attacks, metabolic changes in the liver and CNS disturbances. This approach demonstrated better efficacy than the current standards of care for AIP.</p><p><strong>Conclusion: </strong>This novel model significantly expands our understanding of AIP at the molecular, biochemical and clinical levels and confirms the safety and translatability of multiple systemic administration of hPBGD mRNA as a potential aetiological AIP treatment.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<b>Unravelling lipidomic disruptions across multiple tissues in</b> <i><b>Chd8</b></i> -<b>mutant ASD mice through integration of lipidomics and single-cell transcriptomics</b>.","authors":"You Yu, Bing Zhang, Ning Wang, Zhenqiang Zuo, Peifeng Ji, Fangqing Zhao","doi":"10.1136/gutjnl-2024-332972","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332972","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Need for standardised approaches to human microbiome research using the example of colorectal neoplasia research.","authors":"Sarah Manning, Rashmi Sinha, Colin J Rees","doi":"10.1136/gutjnl-2024-333765","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333765","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental and healthcare trade-offs between single-use and reusable gastroscopes.","authors":"Jiashu Han, Dan Shan","doi":"10.1136/gutjnl-2024-333827","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333827","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of enterically transmitted hepatitis virus animal models using lipid nanoparticle-based full-length viral genome RNA delivery system","authors":"Tianxu Liu, Jian Li, Xin Yin, Fengmin Lu, Hui Zhao, Lin Wang, Cheng-Feng Qin","doi":"10.1136/gutjnl-2024-332784","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332784","url":null,"abstract":"Background Enterically transmitted hepatitis viruses, such as hepatitis A virus (HAV) and hepatitis E virus (HEV), remain notable threats to public health. However, stable and reliable animal models of HAV and HEV infection are lacking. Objective This study aimed to establish HAV and HEV infections in multiple small animals by intravenously injecting lipid nanoparticle (LNP)-encapsulated full-length viral RNAs (LNP-vRNA). Design In vitro transcribed and capped full-length HAV RNA was encapsulated into LNP and was intravenously inoculated to Ifnar −/− mice, and HEV RNA to rabbits and gerbils. Virological parameters were determined by RT-qPCR, ELISA and immunohistochemistry. Liver histopathological changes were analysed by H&E staining. Antiviral drug and vaccine efficacy were further evaluated by using the LNP-vRNA-based animal model. Results On intravenous injection of LNP-vRNA, stable viral shedding was detected in the faeces and infectious HAV or HEV was recovered from the livers of the inoculated animals. Liver damage was observed in LNP-vRNA (HAV)-injected mice and LNP-vRNA (HEV)-injected rabbits. Mongolian gerbils were also susceptible to LNP-vRNA (HEV) injections. Finally, the antiviral countermeasures and in vivo function of HEV genome deletions were validated in the LNP-vRNA-based animal model. Conclusion This stable and standardised LNP-vRNA-based animal model provides a powerful platform to investigate the pathogenesis and evaluate countermeasures for enterically transmitted hepatitis viruses and can be further expanded to other viruses that are not easily cultured in vitro or in vivo. All data relevant to the study are included in the article or uploaded as online supplemental information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"28 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}