Pub Date : 2025-02-14DOI: 10.1053/j.gastro.2025.02.003
Maria T. Abreu, Suzanne Devkota, Kelly Issokson
No Abstract
{"title":"A Mediterranean diet for Crohn’s disease: Embracing colorful diversity to improve the microbiome","authors":"Maria T. Abreu, Suzanne Devkota, Kelly Issokson","doi":"10.1053/j.gastro.2025.02.003","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.02.003","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"23 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417462","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}
Pub Date : 2025-02-13DOI: 10.1053/j.gastro.2024.11.011
Seamus O’Mahony
No Abstract
{"title":"The Thing Itself: Medicine as Craft","authors":"Seamus O’Mahony","doi":"10.1053/j.gastro.2024.11.011","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.11.011","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"59 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401242","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}
Pub Date : 2025-02-11DOI: 10.1053/j.gastro.2025.02.001
Ariel S. Bar-Mashiah, Kate Mason, Megan Marsiglio, Dana J. Lukin
No Abstract
{"title":"Forecasting IBD Activity Using Wearable Devices","authors":"Ariel S. Bar-Mashiah, Kate Mason, Megan Marsiglio, Dana J. Lukin","doi":"10.1053/j.gastro.2025.02.001","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.02.001","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385122","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}
Pub Date : 2025-02-10DOI: 10.1053/j.gastro.2024.08.046
Brett McGettigan, Maria Hernandez-Tejero, Harmeet Malhi, Vijay Shah
The risk of microbial infections is increased in cirrhosis and other forms of advanced liver disease such as alcohol-associated hepatitis. Such infections may precipitate new or further decompensation and death, especially in patients with clinical features of acute-on-chronic liver failure. The severe immune dysfunction or "immune paralysis" caused by advanced liver disease is associated with high short-term mortality. However, the pathogenic mechanisms underlying immune dysfunction and immunodeficiency are incompletely understood. Evidence to date suggests a complex, dynamic process that perturbs the physiological roles of the liver as a master regulator of systemic immunity and protector against noxious effects of exogenous molecules in the portal vein flowing from the gut. Thus, in cirrhosis and severe alcohol-associated hepatitis, the ability of hepatocytes and intrahepatic immune cells to balance normal context-dependent dichotomous responses of tolerance vs immune activation is lost. Contributing factors include loss of the gut barrier with translocation of microbial products through the portal vein, culminating in development of functional defects in innate and adaptive immune cells, and generation of immune-regulatory myeloid cells that permit microbial colonization and infection. This review addresses key evidence supporting the paradigm of immune dysfunction as a risk for microbial infections and identifies potential therapeutic targets for intervention. The primary focus is on cirrhosis-associated immune dysfunction and alcohol-associated liver disease, because the bulk of available data are from these 2 conditions.
{"title":"Immune Dysfunction and Infection Risk in Advanced Liver Disease.","authors":"Brett McGettigan, Maria Hernandez-Tejero, Harmeet Malhi, Vijay Shah","doi":"10.1053/j.gastro.2024.08.046","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.08.046","url":null,"abstract":"<p><p>The risk of microbial infections is increased in cirrhosis and other forms of advanced liver disease such as alcohol-associated hepatitis. Such infections may precipitate new or further decompensation and death, especially in patients with clinical features of acute-on-chronic liver failure. The severe immune dysfunction or \"immune paralysis\" caused by advanced liver disease is associated with high short-term mortality. However, the pathogenic mechanisms underlying immune dysfunction and immunodeficiency are incompletely understood. Evidence to date suggests a complex, dynamic process that perturbs the physiological roles of the liver as a master regulator of systemic immunity and protector against noxious effects of exogenous molecules in the portal vein flowing from the gut. Thus, in cirrhosis and severe alcohol-associated hepatitis, the ability of hepatocytes and intrahepatic immune cells to balance normal context-dependent dichotomous responses of tolerance vs immune activation is lost. Contributing factors include loss of the gut barrier with translocation of microbial products through the portal vein, culminating in development of functional defects in innate and adaptive immune cells, and generation of immune-regulatory myeloid cells that permit microbial colonization and infection. This review addresses key evidence supporting the paradigm of immune dysfunction as a risk for microbial infections and identifies potential therapeutic targets for intervention. The primary focus is on cirrhosis-associated immune dysfunction and alcohol-associated liver disease, because the bulk of available data are from these 2 conditions.</p>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381303","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}
Pub Date : 2025-02-07DOI: 10.1053/j.gastro.2024.12.001
Gayathri Krishnan, Jennifer O Spicer, Elizabeth Blaney, Darcy Wooten
{"title":"Designing and Delivering Chalk Talks in the Clinical Setting.","authors":"Gayathri Krishnan, Jennifer O Spicer, Elizabeth Blaney, Darcy Wooten","doi":"10.1053/j.gastro.2024.12.001","DOIUrl":"https://doi.org/10.1053/j.gastro.2024.12.001","url":null,"abstract":"","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":" ","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364413","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}
Elevated PD-L1 expression in tumour cells facilitates immune evasion. However, the mechanism via which PD-L1 expression is regulated in pancreatic ductal adenocarcinoma (PDAC) cells remains inadequately elucidated.
Methods
Immunoprecipitation, pull-down assays, and mass spectrometry were used to identify glutamine synthase 2 (GLS2) and yes1 associated transcriptional regulator (YAP1) binding proteins and modification sites. Immunoblotting, immunofluorescence, chromatin immunoprecipitation (ChIP), and luciferase reporter assays were used to analyze YAP1 activation. Protein expression levels were assessed by immunoblotting, immunoprecipitation, immunofluorescence, and immunohistochemistry. RNA expression levels were analyzed using RT-qPCR.
Results
Hypoxia-induced GCN5-mediated acetylation of GLS2 at K151, which enhanced GLS2 interaction with YAP1. Subsequently, tubulin tyrosine ligase-like 1 (TTLL1) mediated YAP1 glutamylation at E100 and promoted its nuclear translocation and the activation-dependent transcriptional upregulation of PD-L1 expression. The expression of GLS2-K151R or YAP1-E100A mutants in PDAC cells blocked hypoxia-induced PD-L1 expression, enhanced CD4+ and CD8+ T cell activation and tumour infiltration, thereby suppressing PDAC tumour growth. Simultaneous administration of MB-3, a GCN5 inhibitor, and an anti-PD-1 antibody abolished tumour immune evasion, boosting the anti-tumour efficacy of immune checkpoint blockade. Furthermore, GLS2-K151 acetylation and YAP1 E100 glutamylation levels correlated positively with PD-L1 expression and poor prognosis in PDAC patients.
Conclusions
The present study revealed a novel mechanism by which hypoxia upregulates PD-L1 expression and highlighted the involvement of GLS2 in non-canonical metabolic pathways involved in tumour immune evasion, with implications for PDAC treatment.
{"title":"The Moonlighting Function of GLS2 Promotes Immune Evasion of Pancreatic Ductal Adenocarcinoma by TTLL1-mediated YAP1 Glutamylation","authors":"Xiao Chen, Haotian Fu, Shimao Zhu, Zheng Xiang, Hong Fu, Zhongquan Sun, Sitong Zhang, Xiaofeng Zheng, Xun Hu, Ming Chao, Zhengwei Mao, Yanli Bi, Weilin Wang, Yuan Ding","doi":"10.1053/j.gastro.2025.01.240","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.01.240","url":null,"abstract":"<h3>Background & Aims</h3>Elevated PD-L1 expression in tumour cells facilitates immune evasion. However, the mechanism via which PD-L1 expression is regulated in pancreatic ductal adenocarcinoma (PDAC) cells remains inadequately elucidated.<h3>Methods</h3>Immunoprecipitation, pull-down assays, and mass spectrometry were used to identify glutamine synthase 2 (GLS2) and yes1 associated transcriptional regulator (YAP1) binding proteins and modification sites. Immunoblotting, immunofluorescence, chromatin immunoprecipitation (ChIP), and luciferase reporter assays were used to analyze YAP1 activation. Protein expression levels were assessed by immunoblotting, immunoprecipitation, immunofluorescence, and immunohistochemistry. RNA expression levels were analyzed using RT-qPCR.<h3>Results</h3>Hypoxia-induced GCN5-mediated acetylation of GLS2 at K151, which enhanced GLS2 interaction with YAP1. Subsequently, tubulin tyrosine ligase-like 1 (TTLL1) mediated YAP1 glutamylation at E100 and promoted its nuclear translocation and the activation-dependent transcriptional upregulation of PD-L1 expression. The expression of GLS2-K151R or YAP1-E100A mutants in PDAC cells blocked hypoxia-induced PD-L1 expression, enhanced CD4<sup>+</sup> and CD8<sup>+</sup> T cell activation and tumour infiltration, thereby suppressing PDAC tumour growth. Simultaneous administration of MB-3, a GCN5 inhibitor, and an anti-PD-1 antibody abolished tumour immune evasion, boosting the anti-tumour efficacy of immune checkpoint blockade. Furthermore, GLS2-K151 acetylation and YAP1 E100 glutamylation levels correlated positively with PD-L1 expression and poor prognosis in PDAC patients.<h3>Conclusions</h3>The present study revealed a novel mechanism by which hypoxia upregulates PD-L1 expression and highlighted the involvement of GLS2 in non-canonical metabolic pathways involved in tumour immune evasion, with implications for PDAC treatment.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"42 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371503","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}
Pub Date : 2025-02-07DOI: 10.1053/j.gastro.2025.01.233
Jaya Agarwal, Himani Chandra, Rashmi Kapoor
No Abstract
{"title":"Unravelling a Case of Fatty Pancreas in a Child","authors":"Jaya Agarwal, Himani Chandra, Rashmi Kapoor","doi":"10.1053/j.gastro.2025.01.233","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.01.233","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"16 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371504","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}
Pub Date : 2025-02-07DOI: 10.1053/j.gastro.2025.01.241
Elin M. Hård af Segerstad, Lazarus K. Mramba, Carin Andrén Aronsson, Ulla Uusitalo, Suvi M. Virtanen, Daniel Agardh
No Abstract
{"title":"Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights from the TEDDY study","authors":"Elin M. Hård af Segerstad, Lazarus K. Mramba, Carin Andrén Aronsson, Ulla Uusitalo, Suvi M. Virtanen, Daniel Agardh","doi":"10.1053/j.gastro.2025.01.241","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.01.241","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"55 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371544","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}
Pub Date : 2025-02-07DOI: 10.1053/j.gastro.2025.01.239
Anna-Klara Wiklund, Giola Santoni, Jane Yan, Cecilia Radkiewicz, Shaohua Xie, Helgi Birgisson, Eivind Ness-Jensen, My von Euler-Chelpin, Joonas H. Kauppila, Jesper Lagergren
Background and aims
Helicobacter pylori infection of the stomach is the main risk factor for gastric non-cardia adenocarcinoma, however less is known on how eradication of Helicobacter pylori influences the risk of this tumor over time, particularly in Western populations. The aim of this study was to delineate how the risk of gastric non-cardia adenocarcinoma develops over time after Helicobacter pylori eradication treatment in a Western population compared with the background population.
Methods
This population-based cohort study included all adults having received Helicobacter pylori eradication treatment between 1995-2019 in any of the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated by comparing the gastric non-cardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country. Time trends in SIR were assessed using Poisson regression.
Results
Among 659,592 participants having received Helicobacter pylori eradication treatment, contributing 5,480,873 person-years at risk, 1311 developed gastric non-cardia adenocarcinoma. During up to 24 years of follow-up, the SIR was initially higher than the background population (SIR=2.27 [95% CI 2.10-2.44] 1-5 years after treatment), and then gradually decreased over time and approached the level of the background population from 11 years after treatment (SIR=1.11 [95% CI 0.98-1.27] 11-24 years after treatment).
Conclusion
This study revealed a decreasing incidence of gastric non-cardia adenocarcinoma after Helicobacter pylori eradication treatment in five Western populations. The risk became virtually similar to the background population from 11 years after treatment.
{"title":"Risk of gastric adenocarcinoma after eradication of Helicobacter pylori","authors":"Anna-Klara Wiklund, Giola Santoni, Jane Yan, Cecilia Radkiewicz, Shaohua Xie, Helgi Birgisson, Eivind Ness-Jensen, My von Euler-Chelpin, Joonas H. Kauppila, Jesper Lagergren","doi":"10.1053/j.gastro.2025.01.239","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.01.239","url":null,"abstract":"<h3>Background and aims</h3><em>Helicobacter pylori</em> infection of the stomach is the main risk factor for gastric non-cardia adenocarcinoma, however less is known on how eradication of <em>Helicobacter pylori</em> influences the risk of this tumor over time, particularly in Western populations. The aim of this study was to delineate how the risk of gastric non-cardia adenocarcinoma develops over time after <em>Helicobacter pylori</em> eradication treatment in a Western population compared with the background population.<h3>Methods</h3>This population-based cohort study included all adults having received <em>Helicobacter pylori</em> eradication treatment between 1995-2019 in any of the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated by comparing the gastric non-cardia adenocarcinoma incidence in the study cohort with the incidence in the background population of the same age, sex, calendar period, and country. Time trends in SIR were assessed using Poisson regression.<h3>Results</h3>Among 659,592 participants having received <em>Helicobacter pylori</em> eradication treatment, contributing 5,480,873 person-years at risk, 1311 developed gastric non-cardia adenocarcinoma. During up to 24 years of follow-up, the SIR was initially higher than the background population (SIR=2.27 [95% CI 2.10-2.44] 1-5 years after treatment), and then gradually decreased over time and approached the level of the background population from 11 years after treatment (SIR=1.11 [95% CI 0.98-1.27] 11-24 years after treatment).<h3>Conclusion</h3>This study revealed a decreasing incidence of gastric non-cardia adenocarcinoma after <em>Helicobacter pylori</em> eradication treatment in five Western populations. The risk became virtually similar to the background population from 11 years after treatment.","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"41 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371587","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}
Pub Date : 2025-02-06DOI: 10.1053/j.gastro.2025.01.006
Trent Walradt, Daniel Szvarca, Christopher C. Thompson
No Abstract
{"title":"Shining a New Light on Gastrointestinal Endoscopy: Evaluating the Effect of Green Light Versus Dim Light on Performance in the Endoscopy Suite","authors":"Trent Walradt, Daniel Szvarca, Christopher C. Thompson","doi":"10.1053/j.gastro.2025.01.006","DOIUrl":"https://doi.org/10.1053/j.gastro.2025.01.006","url":null,"abstract":"No Abstract","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"58 1","pages":""},"PeriodicalIF":29.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258066","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}
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