Gut最新文献

{"title":"FTO/m6A/GPNMB axis: a novel promising target for hepatocellular carcinoma (HCC) treatment?","authors":"Bernd Heinrich, Francisco Javier Cubero","doi":"10.1136/gutjnl-2024-332934","DOIUrl":"10.1136/gutjnl-2024-332934","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"5-6"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874643","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":"Gastrointestinal syndromes in Parkinson's disease: risk factors or comorbidities?","authors":"Jiangwei Sun, Dan Yan, Karin Wirdefeldt, Jialu Yao, Jonas F Ludvigsson","doi":"10.1136/gutjnl-2024-332352","DOIUrl":"10.1136/gutjnl-2024-332352","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e1"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119306","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":"Long-term stability of the faecal microbiome profile in faecal immunochemical test (FIT) samples.","authors":"Suparna Mitra, Christopher J Stewart, Andrew Nelson, James S Hampton, Andrea C Masi, Sarah Manning, Linda Sharp, Mark A Hull, Colin J Rees","doi":"10.1136/gutjnl-2024-332584","DOIUrl":"10.1136/gutjnl-2024-332584","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"e8"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431836","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":"Sclerosing cholangitis and inflammatory bowel disease: a paradoxical relationship?","authors":"Johannes R Hov","doi":"10.1136/gutjnl-2024-332835","DOIUrl":"10.1136/gutjnl-2024-332835","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"1-2"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723367","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":"Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC.","authors":"Jianan Chen, Youhai Jiang, Minghui Hou, Chunliang Liu, Erdong Liu, Yali Zong, Xiang Wang, Zhengyuan Meng, Mingye Gu, Yu Su, Hongyang Wang, Jing Fu","doi":"10.1136/gutjnl-2024-332902","DOIUrl":"10.1136/gutjnl-2024-332902","url":null,"abstract":"<p><strong>Background: </strong>The potency of T cell-mediated responses is a determinant of immunotherapy effectiveness in treating malignancies; however, the clinical efficacy of T-cell therapies has been limited in hepatocellular carcinoma (HCC) owing to the extensive immunosuppressive microenvironment.</p><p><strong>Objective: </strong>Here, we aimed to investigate the key genes contributing to immune escape in HCC and raise a new therapeutic strategy for remoulding the HCC microenvironment.</p><p><strong>Design: </strong>The genome-wide in vivo clustered regularly interspaced short palindromic repeats (CRISPR) screen library was conducted to identify the key genes associated with immune tolerance. Single-cell RNA-seq (scRNA-seq), flow cytometry, HCC mouse models, chromatin immunoprecipitation and coimmunoprecipitation were used to explore the function and mechanism of adenylate cyclase 7 (ADCY7) in HCC immune surveillance.</p><p><strong>Results: </strong>Here, a genome-wide in vivo CRISPR screen identified a novel immune modulator-ADCY7. The transmembrane protein ADCY7 undergoes subcellular translocation via caveolae-mediated endocytosis and then translocates to the nucleus with the help of leucine-rich repeat-containing protein 59 (LRRC59) and karyopherin subunit beta 1 (KPNB1). In the nucleus, it functions as a transcription cofactor of CCAAT/enhancer binding protein alpha (CEBPA) to induce <i>CCL5</i> transcription, thereby increasing CD8⁺ T cell infiltration to restrain HCC progression. Furthermore, ADCY7 can be secreted as exosomes and enter neighbouring tumour cells to promote CCL5 induction. Exosomes with high ADCY7 levels promote intratumoural infiltration of CD8⁺ T cells and suppress HCC tumour growth.</p><p><strong>Conclusion: </strong>We delineate the unconventional function and subcellular location of ADCY7, highlighting its pivotal role in T cell-mediated immunity in HCC and its potential as a promising treatment target.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"128-140"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345115","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":"Understanding tissue injury and remodelling in eosinophilic oesophagitis: development towards personalised medicine.","authors":"Giovanni Santacroce, Carlo Maria Rossi, Marco Vincenzo Lenti, Subrata Ghosh, Marietta Iacucci, Antonio Di Sabatino","doi":"10.1136/gutjnl-2024-333994","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-333994","url":null,"abstract":"<p><p>Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated condition characterised by eosinophilic infiltration of the oesophagus, leading to significant morbidity due to oesophageal dysfunction. The pathogenic course of EoE begins with tissue injury, marked by the intricate interplay of oesophageal barrier dysfunction and T helper 2-mediated inflammation. In response to tissue damage, a subsequent phase of tissue remodelling features a complex interaction between epithelial cells and stromal cells, aimed at tissue repair. The persistence of inflammation drives these mechanisms towards oesophageal fibrostenosis, mainly through the transforming growth factor-dependent, myofibroblast-driven accumulation of the extracellular matrix. Currently, treatment options for EoE are limited, with dietary intervention, proton pump inhibitors and oral steroids serving as first-line therapies. Dupilumab, an antiinterleukin (IL) 4/IL-13 agent, is the only biologic that has been approved by European and American regulatory authorities. However, emerging OMIC technologies significantly advance our understanding of EoE pathogenesis, revealing novel cellular and molecular mechanisms driving the disease. This progress has accelerated the identification of new therapeutic targets and agents, some already under clinical investigation, potentially expanding our therapeutic arsenal and paving the way for more personalised approaches. In this evolving landscape, artificial intelligence (AI) has shown great potential to further elaborate on the complexities of EoE heterogeneity, offering standardised tools for diagnosis, disease phenotyping, and prediction of treatment response. Though still in their early stages, integrating OMICs and AI marks a pivotal step towards precision medicine in EoE.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806864","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":"Sphincterotomy for biliary sphincter of Oddi disorder and idiopathic acute recurrent pancreatitis: the RESPOnD longitudinal cohort.","authors":"Gregory A Coté, Badih Joseph Elmunzer, Haley Nitchie, Richard S Kwon, Field Willingham, Sachin Wani, Vladimir Kushnir, Amitabh Chak, Vikesh Singh, Georgios I Papachristou, Adam Slivka, Martin Freeman, Srinivas Gaddam, Priya Jamidar, Paul Tarnasky, Shyam Varadarajulu, Lydia D Foster, Peter Cotton","doi":"10.1136/gutjnl-2024-332686","DOIUrl":"10.1136/gutjnl-2024-332686","url":null,"abstract":"<p><strong>Objective: </strong>Sphincter of Oddi disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurisation at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.</p><p><strong>Design: </strong>Prospective cohort conducted at 14 US centres with 12 months follow-up. Patients undergoing first-time endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy for suspected SOD were eligible: pancreatobiliary-type pain with or without iAP. The primary outcome was defined as the composite of improvement by Patient Global Impression of Change (PGIC), no new or increased opioids and no repeat intervention. Missing data were addressed by hierarchal, multiple imputation scheme.</p><p><strong>Results: </strong>Of 316 screened, 213 were enrolled with 190 (89.2%) of these having a dilated bile duct, abnormal labs, iAP or some combination. By imputation, an average of 122/213 (57.4% (95% CI 50.4% to 64.4%)) improved; response rate was similar for those with complete follow-up (99/161, 61.5% (54.0% to 69.0%)); of these, 118 (73.3%) improved by PGIC alone. Duct size, elevated labs and patient characteristics were not associated with response. AP occurred in 37/213 (17.4%) at a median of 6 months post ERCP and was more likely in those with a history of AP (30.9% vs 2.9%, p<0.0001).</p><p><strong>Conclusion: </strong>Nearly 60% of patients undergoing ERCP for suspected SOD improve, although the contribution of a placebo response is unknown. Contrary to prevailing belief, duct size and labs are poor response predictors. AP recurrence was common and like observations from prior non-intervention cohorts, suggesting no benefit of sphincterotomy in mitigating future AP episodes.</p>","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"58-66"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145555","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":"Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer","authors":"Ramani Soundararajan, Michelle M Maurin, Jetsen Rodriguez-Silva, Gunjan Upadhyay, Ashley J Alden, Siddabasave Gowda B Gowda, Michael J Schell, Mingli Yang, Noah Jhad Levine, Divyavani Gowda, Punith M Sundaraswamy, Shu-Ping Hui, Lance Pflieger, Heiman Wang, Jorge Marcet, Carolina Martinez, Robert David Bennett, Allen Chudzinski, Andreas Karachristos, Timothy M Nywening, Paul M Cavallaro, Matthew Linley Anderson, Robert J Coffey, Michael V Nebozhyn, Andrey Loboda, Domenico Coppola, Warren Jackson Pledger, Ganesh Halade, Timothy J Yeatman","doi":"10.1136/gutjnl-2024-332535","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-332535","url":null,"abstract":"Background Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced ‘lipid class switching’ producing inflammation-quenching lipoxins (LXA4, LXB4). Objective We explored if lipid dysregulation in colorectal cancers (CRCs) is driven by a failure to resolve inflammation. Design We performed liquid chromatography and tandem mass spectrometry (LC–MS/MS) untargeted analysis of 40 human CRC and normal paired samples and targeted, quantitative analysis of 81 human CRC and normal paired samples. We integrated analysis of lipidomics, quantitative reverse transcription-PCR, large scale gene expression, and spatial transcriptomics with public scRNASEQ data to characterize pattern, expression and cellular localisation of genes that produce and modify lipid mediators. Results Targeted, quantitative LC–MS/MS demonstrated a marked imbalance of pro-inflammatory mediators, with a dearth of resolving lipid mediators. In tumours, we observed prominent over-expression of arachidonic acid derivatives, the genes encoding their synthetic enzymes and receptors, but poor expression of genes producing pro-resolving synthetic enzymes and resultant lipoxins (LXA4, LXB4) and associated receptors. These results indicate that CRC is the product of defective lipid class switching likely related to inadequate or ineffective levels of PGE2/PGD2. Conclusion We show that the lipidomic profile of CRC tumours exhibits a distinct pro-inflammatory bias with a deficiency of endogenous resolving mediators secondary to defective lipid class switching. These observations pave the way for ‘resolution medicine’, a novel therapeutic approach for inducing or providing resolvins to mitigate the chronic inflammation driving cancer growth and progression. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable as data is uploaded as supplementary information.","PeriodicalId":12825,"journal":{"name":"Gut","volume":"19 1","pages":""},"PeriodicalIF":24.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797045","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":"Combining epigenetic modulation: the next step for HCC immunotherapy?","authors":"Chi Ma, Bertram Bengsch","doi":"10.1136/gutjnl-2024-334033","DOIUrl":"https://doi.org/10.1136/gutjnl-2024-334033","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":""},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806852","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":"Unusual cause of rectal bleeding in a patient with schizophrenia.","authors":"Rebecca K Grant, Charu Chopra, Pujit Gandhi, Natarajan Manimaran, Jonathan T Serhan, Kate L Struthers, William M Brindle","doi":"10.1136/gutjnl-2024-332234","DOIUrl":"10.1136/gutjnl-2024-332234","url":null,"abstract":"","PeriodicalId":12825,"journal":{"name":"Gut","volume":" ","pages":"25-88"},"PeriodicalIF":23.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189657","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}