Journal of Gastroenterology最新文献

{"title":"Response to letter to the editor regarding: \"Alcohol-associated liver disease increases the risk of muscle reduction and mortality in patients with cirrhosis\".","authors":"Tatsunori Hanai, Kayoko Nishimura, Shinji Unome, Takao Miwa, Yuki Nakahata, Kenji Imai, Atsushi Suetsugu, Koji Takai, Masahito Shimizu","doi":"10.1007/s00535-024-02153-4","DOIUrl":"10.1007/s00535-024-02153-4","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1144-1145"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological dynamics in MASH: from landscape analysis to therapeutic intervention.","authors":"Lawan Rabiu, Pengchao Zhang, Lukman O Afolabi, Muhammad A Saliu, Salisu M Dabai, Rabiatu B Suleiman, Khalid I Gidado, Mark A Ige, Abdulrahman Ibrahim, Guizhong Zhang, Xiaochun Wan","doi":"10.1007/s00535-024-02157-0","DOIUrl":"10.1007/s00535-024-02157-0","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH), previously known as nonalcoholic steatohepatitis (NASH), is a multifaceted liver disease characterized by inflammation and fibrosis that develops from simple steatosis. Immune and inflammatory pathways have a central role in the pathogenesis of MASH, yet, how to target immune pathways to treat MASH remains perplexed. This review emphasizes the intricate role that immune cells play in the etiology and pathophysiology of MASH and highlights their significance as targets for therapeutic approaches. It discusses both current strategies and novel therapies aimed at modulating the immune response in MASH. It also highlights challenges in liver-specific drug delivery, potential off-target effects, and difficulties in targeting diverse immune cell populations within the liver. This review is a comprehensive resource that integrates current knowledge with future perspectives in the evolving field of MASH, with the goal of driving forward progress in medical therapies designed to treat this complex liver disease.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1053-1078"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small extracellular vesicles derived from adipose mesenchymal stem cells alleviate intestinal fibrosis by inhibiting the FAK/Akt signaling pathway via MFGE8.","authors":"Zhizhong Xiong, Xianzhe Li, Minghao Xie, Jianping Guo, Shi Yin, Dayin Huang, Longyang Jin, Caiqin Wang, Fengxiang Zhang, Chaobin Mao, Huaxian Chen, Dandong Luo, Haijie Tang, Xijie Chen, Lei Lian","doi":"10.1007/s00535-024-02152-5","DOIUrl":"10.1007/s00535-024-02152-5","url":null,"abstract":"<p><strong>Background: </strong>Intestinal fibrosis is one of the most frequent and severe complications of Crohn's disease. Accumulating studies have reported that adipose mesenchymal stem cell-derived small extracellular vesicles (AMSC-sEVs) could alleviate renal fibrosis, hepatic fibrosis, etc., while their potential for treating intestinal fibrosis remains uncertain. Therefore, this study aims to determine the therapeutic effects of AMSC-sEVs on intestinal fibrosis and identify the mechanisms underlying these effects.</p><p><strong>Methods: </strong>AMSC-sEVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blot. Whether AMSC-sEVs exert antifibrotic effects was investigated in two different murine models of intestinal fibrosis. Besides, AMSC-sEVs were co-cultured with primary human fibroblasts and CCD18co during transforming growth factor (TGF)-β1 stimulation. Label-free proteomics and rescue experiments were performed to identify candidate molecules in AMSC-sEVs. Transcriptome sequencing revealed changes in mRNA levels among different groups. Lastly, proteins related to relevant signaling pathways were identified by western blotting, and their expression and activation status were assessed.</p><p><strong>Results: </strong>AMSC-sEVs positively expressed CD63 and Alix and presented a classical \"rim of a cup\" and granule shape with approximately 43-100 nm diameter. AMSCs significantly alleviated intestinal fibrosis through secreted sEVs in vitro and in vivo. The milk fat globule-EGF factor 8 (MFGE8) was stably enriched in AMSC-sEVs and was an active compound contributing to the treatment of intestinal fibrosis by AMSCs. Mechanistically, AMSC-sEV-based therapies attenuated intestinal fibrosis by inhibiting the FAK/Akt signaling pathway.</p><p><strong>Conclusions: </strong>MFGE8-containing AMSC-sEVs attenuate intestinal fibrosis, partly through FAK/Akt pathway inhibition.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1092-1106"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of circulating cytokine levels and tissue-infiltrating myeloid cells with achalasia: results from Mendelian randomization and validation through clinical characteristics and single-cell RNA sequencing.","authors":"Xin-Yue Li, An-Yi Xiang, Xin-Yang Liu, Ke-Hao Wang, Yun Wang, Hai-Ting Pan, Ji-Yuan Zhang, Lu Yao, Zu-Qiang Liu, Jia-Qi Xu, Xiao-Qing Li, Zhao-Chao Zhang, Wei-Feng Chen, Ping-Hong Zhou, Quan-Lin Li","doi":"10.1007/s00535-024-02155-2","DOIUrl":"10.1007/s00535-024-02155-2","url":null,"abstract":"<p><strong>Background: </strong>Achalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood.</p><p><strong>Methods: </strong>We utilized Mendelian randomization (MR) to explore the causal effects of cytokine levels on achalasia, with cis-expression/protein quantitative trait loci (cis-eQTLs/pQTLs) for 47 cytokines selected from a genome-wide association study (GWAS) meta-analysis and GWAS data for achalasia obtained from FinnGen. For cytokines significantly linked to achalasia, we analyzed their plasma concentrations and expression differences in the lower esophageal sphincter (LES) using enzyme-linked immunosorbent assay and single-cell RNA sequencing (scRNA-seq) profiling, respectively. We further employed bioinformatics approaches to investigate underlying mechanisms.</p><p><strong>Results: </strong>We revealed positive associations of circulating Eotaxin, macrophage inflammatory protein-1b (MIP1b), soluble E-selectin (SeSelectin) and TNF-related apoptosis-inducing ligand (TRAIL) with achalasia. When combining MR findings with scRNA-seq data, we observed upregulation of TRAIL (OR = 2.70, 95% CI, 1.20-6.07), encoded by TNFSF10, in monocytes and downregulation of interleukin-1 receptor antagonist (IL-1ra) (OR = 0.70, 95% CI 0.59-0.84), encoded by IL1RN, in FOS_macrophages in achalasia. TNFSF10^high monocytes in achalasia displayed activated type I interferon signaling, and IL1RN^low FOS_macrophages exhibited increased intercellular communications with various lymphocytes, together shaping the proinflammatory microenvironment of achalasia.</p><p><strong>Conclusions: </strong>We identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10^high monocytes and IL1RN^low macrophages may play a role in the pathogenesis of achalasia.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1079-1091"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol-associated liver disease increases the risk of muscle loss and mortality in patients with cirrhosis.","authors":"Izadora Luiza Kunzler, Marco Antônio Da Croce, Fernando Fornari","doi":"10.1007/s00535-024-02154-3","DOIUrl":"10.1007/s00535-024-02154-3","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1143"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan.","authors":"Takumi Kawaguchi, Yoshiyuki Fujishima, Daisuke Wakasugi, Fusayo Io, Yuri Sato, Saeko Uchida, Yukiko Kitajima","doi":"10.1007/s00535-024-02158-z","DOIUrl":"10.1007/s00535-024-02158-z","url":null,"abstract":"<p><strong>Background & aim: </strong>SGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan.</p><p><strong>Methods: </strong>We conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6 months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12 months.</p><p><strong>Results: </strong>After 6 months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12 months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01-0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30-0.84, P = 0.009) compared to DPP4i.</p><p><strong>Conclusion: </strong>SGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1120-1132"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between advanced fibrosis and epigenetic age acceleration among individuals with MASLD.","authors":"Haili Wang, Zhenqiu Liu, Hong Fan, Chengnan Guo, Xin Zhang, Yi Li, Suzhen Zhao, Luojia Dai, Ming Zhao, Tiejun Zhang","doi":"10.1007/s00535-024-02181-0","DOIUrl":"https://doi.org/10.1007/s00535-024-02181-0","url":null,"abstract":"<p><strong>Background: </strong>The biological process of aging plays an important role in the progress of liver fibrosis. However, epidemiological evidence about the associations between advanced fibrosis and epigenetic age acceleration (EAA) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) is limited.</p><p><strong>Methods: </strong>We utilized publicly available DNA methylation data (GSE180474) for our analysis. Five EAA measures were calculated in this study, including IEAA, PhenoAA, GrimAA, DunedinPACE, and DNAmTLAA. Separate linear regression models were conducted to explore the associations between different fibrosis grades and each measure of EAA.</p><p><strong>Results: </strong>A total of 325 participants were included in this study, with a mean (± SD) age of 48.56 ± 11.50 years. Of these participants, 64.6% with no fibrosis, 16.9% with bridging fibrosis, 11.1% with incomplete cirrhosis, and 7.4% with cirrhosis. After adjusting for demographics and medication status, MASLD individuals with advanced fibrosis were associated with a 5% increase in the pace of aging (DunedinPACE, β = 0.05, 95% CI: 0.03-0.07) and a 10% decrease in DNAmTLAA (β = -0.10, 95% CI: -0.13 to -0.07) compared those without fibrosis. Similarly, higher stages of fibrosis were associated with an increased pace of aging (DunedinPACE, β = 0.02, 95% CI: 0.01-0.03, P_trend < 0.001) and decreased DNAmTLAA (β = -0.05, 95% CI: -0.07 to -0.04, P_trend < 0.001). However, no significant association was found between advanced fibrosis and IEAA, PhenoAA, and GrimAA.</p><p><strong>Conclusions: </strong>Our findings suggest that advanced fibrosis was associated with an accelerated pace of aging, as measured by the third-generation EA measure DunedinPACE, and shorter telomere length, captured by DNAmTLAA, among individuals with MASLD. This finding has potential prognostic implications and suggests EAA may serve as a surrogate marker of therapeutic efficacy in MASLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP acts as an independent prognostic marker and regulates growth and metastasis of gastrointestinal stromal tumors via FBXW7-YAP pathway.","authors":"Xiyu Wu, Kohei Yamashita, Chihiro Matsumoto, Weiliyun Zhang, Ming Ding, Kazuto Harada, Keisuke Kosumi, Kojiro Eto, Satoshi Ida, Yuji Miyamoto, Masaaki Iwatsuki","doi":"10.1007/s00535-024-02180-1","DOIUrl":"10.1007/s00535-024-02180-1","url":null,"abstract":"<p><strong>Background: </strong>Although imatinib (IM) and subsequent tyrosine kinase inhibitors (TKIs) significantly improve the prognosis of GIST patients by delaying metastasis and recurrence, most patients experience limited efficacy due to toxicity and secondary resistance. We evaluated Yes-associated protein (YAP), a coactivator of the Hippo pathway accounting for IM resistance and aggressive GIST phenotypes, in GISTs. The degradation of YAP is mediated by FBXW7, and FBXW7 predicts recurrence and IM efficacy for GIST patients. Here, we aimed to identify the potential of YAP as a prognostic marker for patients with GISTs, and the molecular mechanism of FBXW7-YAP pathway in GIST cells.</p><p><strong>Methods: </strong>We measured YAP expression in 167 GIST cases using immunohistochemical staining, correlated its expression levels with clinicopathological features, and the molecular mechanism underlying the FBXW7-YAP pathway was further examined in vitro and in vivo.</p><p><strong>Results: </strong>Compared to 80 (47.9%) cases in the low YAP expression group, 87 (52.1%) cases with high YAP expression associated with a poorer prognosis in terms of overall survival (P = 0.004) and recurrence-free survival (P = 0.003). YAP expression was identified as a significant independent factor affecting the 5-year overall survival (P = 0.005) and recurrence-free survival rates (P = 0.007). Moreover, YAP was directly targeted by FBXW7 to affect proliferation, invasion, and migration in GIST cells. High YAP expression correlated with FBXW7 deficiency, as shown in xenograft and metastasis mouse models.</p><p><strong>Conclusions: </strong>YAP expression serves as a predictive marker of recurrence for GIST patients with curative resection, highlighting its potential as a novel therapeutic target that warrants further investigation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study.","authors":"Muneji Yasuda, Masahiro Shiokawa, Takeshi Kuwada, Yoshihiro Nishikawa, Risa Nakanishi, Ikuhisa Takimoto, Koki Chikugo, Masataka Yokode, Yuya Muramoto, Shimpei Matsumoto, Takeharu Nakamura, Sakiko Ota, Tomoaki Matsumori, Keiko Kuroda, Takahisa Hachiya, Hajime Yamazaki, Norimitsu Uza, Yuzo Kodama, Tsutomu Chiba, Toshio Fujisawa, Atsumasa Komori, Masanori Abe, Izumi Yamaguchi, Fumihiko Matsuda, Hiroyuki Isayama, Atsushi Tanaka, Hiroshi Seno","doi":"10.1007/s00535-024-02169-w","DOIUrl":"https://doi.org/10.1007/s00535-024-02169-w","url":null,"abstract":"<p><strong>Background: </strong>Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities.</p><p><strong>Methods: </strong>Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA.</p><p><strong>Results: </strong>Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001).</p><p><strong>Conclusions: </strong>We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer pathways in serrated polyposis syndrome: is conventional more crucial than serrated?","authors":"Munehiro Ikeda, Yuki Nakanishi, Hiroshi Seno","doi":"10.1007/s00535-024-02177-w","DOIUrl":"https://doi.org/10.1007/s00535-024-02177-w","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}