Gastroenterology ReportPub Date : 2025-10-06eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf088
Queralt Herms, Jordi Gratacós-Ginès, Elisa Pose
{"title":"Alcohol-related liver disease.","authors":"Queralt Herms, Jordi Gratacós-Ginès, Elisa Pose","doi":"10.1093/gastro/goaf088","DOIUrl":"https://doi.org/10.1093/gastro/goaf088","url":null,"abstract":"<p><p>Alcohol-related liver disease (ALD) is a prevalent global health issue, contributing to significant mortality and encompassing a spectrum of liver damage from steatosis to decompensated cirrhosis and hepatocellular carcinoma. This review summarizes the current state of ALD, emphasizing both early and advanced stages, including alcohol-related hepatitis (AH). The epidemiology, diagnostic tools, natural history, and key progression factors of ALD are discussed, highlighting the role of diagnostic tools and pathways in early and advanced stages of ALD. The review also addresses the importance and particularities of the treatment of alcohol use disorder in patients with ALD, covering both psychological and pharmaceutical interventions. Finally, treatments for ALD-related fibrosis and AH are discussed, presenting both the currently available and future treatment options. The conclusions of this review underscore the need for comprehensive strategies to improve diagnosis, prognostic stratification, and treatment strategies at all stages of ALD.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf088"},"PeriodicalIF":4.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-10-03eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf086
Alexandra Endrizzi, Pauline Grunst, Silvia Rudloff, Jan De Laffolie, Klaus-Peter Zimmer, Sebastian Stricker
{"title":"Targeting transglutaminase 2: pathways to celiac disease therapies.","authors":"Alexandra Endrizzi, Pauline Grunst, Silvia Rudloff, Jan De Laffolie, Klaus-Peter Zimmer, Sebastian Stricker","doi":"10.1093/gastro/goaf086","DOIUrl":"10.1093/gastro/goaf086","url":null,"abstract":"<p><strong>Background: </strong>Transglutaminase 2 (TG2)-mediated enzymatic modification of gliadin peptides plays a major role in the pathogenesis of celiac disease (CD). Different inhibitory mechanisms have been reported to reduce TG2 activity but comparative data on the cellular level are lacking. Furthermore, recent evidence suggested that endogenous redox proteins such as endoplasmic reticulum resident protein 57 (ERp57, inhibits TG2) and thioredoxin-1 (TRX, activates TG2) may regulate TG2 activity. In this study, we aimed to compare the effects and applicability of different inhibitors on the activity of recombinant and cellular TG2. Furthermore, we investigated the role of ERp57 and TRX in the context of CD by using siRNA-mediated knockdown in Caco-2 cells.</p><p><strong>Methods: </strong>The effect of TG2 inhibitors on recombinant and extracellular TG2 activity was investigated by using photometric and fluorometric quantitation of the cross-linking of biotinylated gliadin peptide P56-88 or 5-(biotinamido)-pentylamine. After siRNA knockdown, the protein levels of ERp57, TRX, and TG2 as well as TG2 activity were investigated by using Western blotting and fluorometry in Caco-2 cells.</p><p><strong>Results: </strong>The active-site-directed inhibitors ERW1041, KCC009, and cysteamine as well as the allosteric inhibitor LDN27219 revealed the most prominent reduction in recombinant and cellular (35%-50%) TG2 activity. In contrast, PX12, <i>S</i>-Nitroso-<i>N</i>-acetyl-DL-penicillamine, zinc chloride, and ascorbic acid either did not affect TG2 activity or had only moderate effects at high doses close to cytotoxic concentrations. SiRNA knockdown of TG2 resulted in a prominent reduction (63%) in TG2 activity, whereas knockdown of ERp57 did not; knockdown of TRX only slightly (27%) reduced TG2 activity.</p><p><strong>Conclusion: </strong>Active-site-directed inhibitors, LDN27219 and knockdown of TG2 expression significantly reduced extracellular TG2 activity and represent potential alternative treatment targets in the context of CD.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf086"},"PeriodicalIF":4.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12496130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Function of histamine-driven cancer-associated fibroblast and hepatocyte growth factor in the progression of cholangiocarcinoma.","authors":"Xin Wang, Guoli Sheng, Zhangdi Yan, Anda Shi, Zengli Liu, Yongchang Tang, Guangzhen Li, Zongli Zhang","doi":"10.1093/gastro/goaf090","DOIUrl":"10.1093/gastro/goaf090","url":null,"abstract":"<p><strong>Background: </strong>Here, we aimed to identify the impact of the histamine (HA)-histamine receptor H2 (HRH2) signaling pathway on stimulating the secretion of hepatocyte growth factor (HGF) by cancer-associated fibroblasts (CAFs), as well as elucidating the mechanisms through which HGF promotes the progression of cholangiocarcinoma. In addition, our study has identified novel targets and investigated the potential use of Cimetidine and Capmatinib in cholangiocarcinoma.</p><p><strong>Methods: </strong>Single-cell RNA sequencing revealed a noteworthy correlation between the expression of <i>HRH2</i> and <i>HGF</i> in CAFs. HA was able to promote the transcription of HGF through the upregulation of the transcription factor hypoxia inducible factor 1 subunit alpha (HIF-1α), which was revealed by using <i>in vitro</i>/<i>vivo</i> experiments. That HGF promotes the progression of cholangiocarcinoma was identified by using orthotopic models and <i>in vitro</i> experiments.</p><p><strong>Results: </strong>HRH2 and HGF were primarily expressed in CAFs within the tumor microenvironment of cholangiocarcinoma. HA sourced from mast cells could bind to the HRH2 receptor on CAFs, consequently upregulating HIF-1α and subsequently enhancing the transcription and secretion levels of HGF. HGF upregulates the phosphorylation of FOS-like 1 (FOSL1) within cholangiocarcinoma cells, promoting the expression of matrix metallopeptidase 10 (MMP10), and consequently enhancing the invasive and migratory abilities of cholangiocarcinoma cells.</p><p><strong>Conclusions: </strong>The HA-HRH2 signaling pathway mediates the proliferation and secretion of HGF in CAFs. HIF-1α and FOSL1 played crucial roles in driving the proliferation, invasion, and migration of cholangiocarcinoma cells within the tumor microenvironment, orchestrated by CAFs. Furthermore, this study has provided theoretical support for the application of the HA receptor HRH2 inhibitor, Cimetidine, and the HGF receptor cellular mesenchymal-epithelial transition factor (c-MET) inhibitor, Capmatinib, in biliary tract tumors.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf090"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revolutionizing inflammatory bowel disease healthcare communication: a head-to-head comparison of gastroenterologist and ChatGPT responses.","authors":"Zixuan He, Yilong Liu, Zhaoming Wang, Xiaoyu Zhou, Xuanming Fan, Miao He, Chengcheng Wang, Hongyu Fu, Zhijie Wang, Yu Bai","doi":"10.1093/gastro/goaf087","DOIUrl":"10.1093/gastro/goaf087","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence-driven large language models demonstrate immense potential in the medical field. It remains unclear whether ChatGPT has the ability to provide appropriate recommendations for patients with inflammatory bowel disease (IBD) that are comparable to those of gastroenterologists. This study quantitatively assessed the performance of ChatGPT's generated IBD-related recommendations from the distinct perspectives of gastroenterologists and patients.</p><p><strong>Methods: </strong>Healthcare questions regarding IBD were solicited from IBD patients and specialized physicians. Those questions were then presented to GPT-4 Omni and three independent senior gastroenterologists for responses. These responses were subsequently evaluated by a blinded panel of five board-certified gastroenterologists using a five-point Likert scale, assessing accuracy, completeness, and readability. Furthermore, 10 IBD patients as blinded assessors performed assessments of both ChatGPT's and gastroenterologists' responses.</p><p><strong>Results: </strong>Thirty high-frequency questions were selected, encompassing basic knowledge, treatment, and management domains. ChatGPT demonstrated high reproducibility in responding to these questions. Regarding accuracy and readability, ChatGPT's performance was comparable to that of gastroenterologists. For completeness of responses, ChatGPT outperformed gastroenterologists (4.42 ± 0.67 vs 4.19 ± 0.65; <i>P </i>= 0.012). Overall, IBD patients were satisfied with both ChatGPT's and gastroenterologists' responses but, for treatment-related questions, patients rated gastroenterologists higher than ChatGPT (4.54 ± 0.32 vs 4.21 ± 0.38; <i>P </i>= 0.040).</p><p><strong>Conclusions: </strong>ChatGPT has the potential to provide stable, accurate, comprehensive, and comprehensible healthcare-related information for IBD patients. Further validation of the reliability and practicality of large language models in real-world clinical settings is crucial.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf087"},"PeriodicalIF":4.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-09-30eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf091
Leichang Zhang, Pan Shen, Xiao Yuan, Guanghua Chen, Wei Ge, Wu Liao, Xiaonan Zhang, Chen Wang, Lu Li
{"title":"A randomized controlled trial of trans-intersphincteric double seton (TRISDS) for the treatment of perianal abscess.","authors":"Leichang Zhang, Pan Shen, Xiao Yuan, Guanghua Chen, Wei Ge, Wu Liao, Xiaonan Zhang, Chen Wang, Lu Li","doi":"10.1093/gastro/goaf091","DOIUrl":"10.1093/gastro/goaf091","url":null,"abstract":"<p><strong>Background: </strong>Incision and drainage (I&D) for perianal abscesses is associated with high rates of fistula formation. Our study aimed to evaluate the effectiveness of a novel technique, trans-intersphincteric double seton (TRISDS), designed to preserve anal sphincter integrity and improve clinical outcomes compared to I&D.</p><p><strong>Methods: </strong>This prospective, randomized, non-blinded controlled study included adult patients with perianal abscesses located below the levator ani muscle with an internal opening. Patients were randomly assigned to either the TRISDS group (<i>n </i>= 55) or the I&D group (<i>n </i>= 51). The TRISDS technique involved two incisions: intersphincteric and drainage incisions with the placement of two loose setons. One seton was positioned to preserve the internal anal sphincter and facilitate drainage through the intersphincteric space, while the other seton aimed to protect the external anal sphincter to ensure comprehensive drainage. The I&D group underwent conventional I&D without damaging the anal sphincter complex. The primary outcome was the cure rate of perianal abscesses, which was defined as complete epithelialization of wounds without fistula or exudate and no recurrence within 12 months after surgery.</p><p><strong>Results: </strong>The TRISDS group achieved a significantly higher cure rate of 78.2% (43/55) compared to 41.2% (21/51) in the I&D group (<i>P </i>< 0.05). There were no significant differences in anal function at 2 months postoperatively between the groups (median Wexner score, IQR: 1.0 [0.0-1.0] vs 1.0 [0.0-1.0], <i>P </i>> 0.05).</p><p><strong>Conclusions: </strong>The study highlighted the effectiveness of TRISDS in improving cure rate without compromising anal function. The TRISDS technique represents a promising strategy for the treatment of perianal abscesses. Further multicenter studies are recommended to validate these findings and expand the application of TRISDS in diverse patient populations.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf091"},"PeriodicalIF":4.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long non-coding RNAs promote colorectal cancer development through other epigenetic modifications.","authors":"Guojuan Wang, Qingqing Ma, Naicheng Zhu, Yuwei Yan, Chen Zhong, Xinlin Hong, Yujuan Lai, Xiudan Chen, Nanxin Li, Wenyan Yu","doi":"10.1093/gastro/goaf081","DOIUrl":"10.1093/gastro/goaf081","url":null,"abstract":"<p><p>Colorectal cancer is one of the most prevalent malignant tumors worldwide, and it has one of the highest rates of mortality and morbidity. Its emergence and progression are intricately linked to various genetic and epigenetic factors influencing colonic epithelial cells. Long non-coding RNAs function as crucial regulators of the epigenetic landscape, playing significant roles in the development, progression, invasion, metastasis, and drug resistance of various tumors, particularly colorectal cancer. Epigenetic modifications, such as DNA methylation, RNA methylation, and histone modification, facilitate heritable gene expression regulation without changing the underlying DNA sequence. Recent studies have increasingly highlighted the intricate interactions between lncRNAs and these epigenetic modifications in colorectal cancer, illuminating their participation in critical processes, including cell proliferation, apoptosis, invasion, and metastasis. This review concentrates on the relationship between long non-coding RNAs and several significant epigenetic modifications that drive colorectal cancer development, offering fresh insights for future research that aims at devising more effective treatment strategies.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf081"},"PeriodicalIF":4.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A modified sphincter-preserved procedure for high complex anal fistulas: a preliminary study.","authors":"Guozhong Xiao, Huaxian Chen, Heng Zhang, Yihui Zheng, Minyi Luo, Chaoxin Yang, Donglin Ren, Genggang Lin, Hongcheng Lin","doi":"10.1093/gastro/goaf084","DOIUrl":"10.1093/gastro/goaf084","url":null,"abstract":"<p><strong>Background: </strong>The management of high complex anal fistulas has posed a significant challenge for surgeons. In this study, we presented a novel surgical procedure for managing high complex anal fistulas that combines core-out fistulectomy with suture repair of the external anal sphincter defect and endorectal advancement flap.</p><p><strong>Methods: </strong>A cohort of patients with high complex anal fistulas undergoing core-out fistulectomy combined with suture repair of the external anal sphincter defect and endorectal advancement flap between December 2020 and December 2021 was reviewed retrospectively.</p><p><strong>Results: </strong>The median age of the patients was 43 (range: 25-53) years. All patients had high transsphincteric fistulas. Two of the five cases involved recurrent anal fistulas. During the median follow-up period of 23 (range: 23-34) months, no recurrence events were observed in the cohort. Furthermore, it was noted that no patients developed anal incontinence after the operation.</p><p><strong>Conclusion: </strong>Core-out fistulectomy combined with suture repair of the external anal sphincter defect and endorectal advancement flap is an effective procedure for the treatment of high complex anal fistulas.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf084"},"PeriodicalIF":4.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-09-19eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf083
Xiaoxia Qiu, Ziqing Ye, Ying Huang
{"title":"Achalasia and mental retardation in a child with uniparental disomy of <i>GMPPA</i> treated with POEM.","authors":"Xiaoxia Qiu, Ziqing Ye, Ying Huang","doi":"10.1093/gastro/goaf083","DOIUrl":"10.1093/gastro/goaf083","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf083"},"PeriodicalIF":4.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-09-18eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf079
Yuchen He, Duote Cai, Shuhao Zhang, Kun Zhu, Yi Jin, Qingjiang Chen, Zhigang Gao
{"title":"Cyst of right hepatic duct in children.","authors":"Yuchen He, Duote Cai, Shuhao Zhang, Kun Zhu, Yi Jin, Qingjiang Chen, Zhigang Gao","doi":"10.1093/gastro/goaf079","DOIUrl":"10.1093/gastro/goaf079","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf079"},"PeriodicalIF":4.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gastroenterology ReportPub Date : 2025-09-15eCollection Date: 2025-01-01DOI: 10.1093/gastro/goaf066
Xianhong Zhao, Zhifa Zhang, Zhihua Du, Xiaohua Du, Wenbin Wu, Haiyan Zhang
{"title":"Multiple gastric adenocarcinoma of the fundic gland type with various endoscopic features in autoimmune gastritis: a case report and literature review.","authors":"Xianhong Zhao, Zhifa Zhang, Zhihua Du, Xiaohua Du, Wenbin Wu, Haiyan Zhang","doi":"10.1093/gastro/goaf066","DOIUrl":"10.1093/gastro/goaf066","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":"13 ","pages":"goaf066"},"PeriodicalIF":4.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}