Journal of Gastroenterology最新文献

{"title":"HLA-DQB1*03:01 and HLA-DQA1*05:05 as key genetic determinants of infliximab response and immunogenicity in Japanese patients with inflammatory bowel disease.","authors":"Ryuya Osaka, Takeo Naito, Seik-Soon Khor, Yoichi Kakuta, Yosuke Kawai, Masao Nagasaki, Hiroshi Meguro, Hideya Iwaki, Daisuke Okamoto, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Atsushi Masamune","doi":"10.1007/s00535-026-02354-z","DOIUrl":"10.1007/s00535-026-02354-z","url":null,"abstract":"<p><strong>Background: </strong>Specific human leukocyte antigen (HLA) genotypes, particularly HLA-DQA1*05, have been proposed as predictors for infliximab (IFX) treatment response and immunogenicity in Western populations. However, the evidence regarding the effect of HLA-DQA1*05 remains limited in East Asian populations, including in Japan. Moreover, HLA-DQA1*05 frequency differs substantially from those in Western populations. Comprehensive analyses of the association between HLA alleles and IFX treatment outcomes may contribute to the identification of novel prognostic markers for IFX therapies.</p><p><strong>Methods: </strong>We retrospectively analyzed 301 biologic-naïve Japanese patients with inflammatory bowel disease (IBD). IFX persistence was assessed at both 2-digit and 4-digit HLA allele resolutions, and associations with anti-drug antibody levels at 1 year after the initiation of IFX therapy were evaluated.</p><p><strong>Results: </strong>At the 2-digit resolution analysis, HLA-DQB1*03 (hazard ratio [HR] = 2.39, p = 1.89E-06) and HLA-DQA1*05 (HR = 1.99, p = 3.91E-04) were significantly associated with early IFX discontinuation. At the 4-digit resolution analysis, HLA-DQB1*03:01 (HR = 2.03, p = 9.42E-05) and HLA-DQA1*05:05 (HR = 2.18, p = 4.42E-05) showed similar associations. All HLA-DQA1*05:05 alleles formed haplotypes with HLA-DQB1*03:01. Importantly, HLA-DQB1*03:01 was also associated with early discontinuation of IFX even when it formed haplotypes with alleles other than HLA-DQA1*05:05. Both HLA-DQB1*03:01 and HLA-DQA1*05:05 were significantly associated with elevated anti-drug antibody levels (p = 3.23E-03 and 3.54E-03, respectively).</p><p><strong>Conclusions: </strong>HLA-DQB1*03:01 encompasses the information of HLA-DQA1*05:05 and serves as a strong genetic predictor of IFX treatment persistence and immunogenicity in Japanese patients with IBD, offering a potential biomarker for personalized therapy.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"547-558"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132166","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":"Letter to the editor to ''Serum zinc levels as predictors of covert hepatic encephalopathy in patients with liver cirrhosis''.","authors":"Jingsong Liu, Tianyu Jia","doi":"10.1007/s00535-026-02375-8","DOIUrl":"10.1007/s00535-026-02375-8","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"685-686"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284081","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":"Correction: Optimising carotegrast methyl use in ulcerative colitis: patient profiling, predictive biomarkers, and timing of efficacy evaluation (ASPECT study).","authors":"Katsuyoshi Matsuoka, Fumihito Hirai, Kenji Watanabe, Ryota Hokari, Taku Kobayashi, Masayuki Saruta, Hiroshi Nakase, Takahiro Suzuki, Gakuto Yamazaki, Toshifumi Hibi, Mamoru Watanabe, Tadakazu Hisamatsu","doi":"10.1007/s00535-026-02399-0","DOIUrl":"10.1007/s00535-026-02399-0","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"692"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645344","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":"Extracellular vesicle-encapsulated microRNA-425 promotes tumor development and serves as a biomarker for pancreatic ductal adenocarcinoma.","authors":"Kazuya Koyama, Kenji Takahashi, Yusuke Ono, Kyohei Oyama, Nobue Tamamura, Hiroki Tanaka, Fumi Asai, Yukino Kobayashi, Chiho Maeda, Yu Ohtaki, Hiroki Sato, Tetsuhiro Okada, Hidemasa Kawabata, Hidetaka Iwamoto, Yohei Kitano, Taito Itoh, Akiko Matsuda, Tatsutoshi Inuzuka, Kenzui Taniue, Koh Nakayama, Mikihiro Fujiya, Toshikatsu Okumura, Yusuke Mizukami","doi":"10.1007/s00535-026-02382-9","DOIUrl":"10.1007/s00535-026-02382-9","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) enclosed within extracellular vesicles (EVs) have emerged as crucial players in carcinogenesis and are increasingly recognized as potential cancer biomarkers. However, their significance in pancreatic ductal adenocarcinoma (PDAC) and their utility for early detection remain unclear.</p><p><strong>Methods: </strong>We utilized microarray analysis to identify the miRNAs highly expressed in PDAC cells compared to immortalized pancreatic ductal cells. Functional studies investigated the effect of miRNA overexpression and inhibition on PDAC cells invasion/migration and associated signaling pathways. Additionally, we examined the transfer of miRNA via EVs and their potential impact on the recipient PDAC cells. Serum samples from 30 healthy individuals, 30 patients with intraductal papillary mucinous neoplasm, and 30 PDAC were analyzed for EV miRNA expression using digital PCR.</p><p><strong>Results: </strong>MiR-425 emerged as an oncogenic miRNA upregulated in PDAC, suppressing phosphatase and tensin homolog (PTEN) while activating phosphatidylinositol 3-kinase (PI3K)/Akt and epithelial-to-mesenchymal transition (EMT) pathways. Treatment with miR-425-enriched EVs induced EMT in PDAC cells by suppressing PTEN, enhancing invasion and migration. Serum EV miR-425 levels tended to be higher in PDAC patients, particularly in Stage I/II compared to Stage III/IV, although the difference was not statistically significant. Combining EV miR-425 with CA19-9 improved diagnostic performance over CA19-9 alone, achieving a sensitivity 93%, specificity 91%, and AUC of 0.98.</p><p><strong>Conclusion: </strong>Our finding suggested the role of intercellular transfer of EV miR-425 in inducing EMT via PTEN/PI3K/Akt pathway modulation, thereby promoting invasion and migration of PDAC cells. Serum EV miR-425 holds promise as a potential biomarker for early diagnosis of PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"660-672"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433421","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":"Regional disparities in pancreaticoduodenectomy mortality: more than just rurality?","authors":"Takehiko Hanaki","doi":"10.1007/s00535-026-02436-y","DOIUrl":"https://doi.org/10.1007/s00535-026-02436-y","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816242","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":"Correction: METTL3/YTHDF1 drives M1 macrophage polarization and aggravates ulcerative colitis progression by regulating m6A modification of SerpinB5 mRNA and FBXO32-dependent NF-κB pathway.","authors":"Tian Pu, Ranran Feng, Chunru Wang, Ye Zhao","doi":"10.1007/s00535-026-02398-1","DOIUrl":"10.1007/s00535-026-02398-1","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"691"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645369","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":"Correction: Predictors of lymph node metastases, recurrence, and survival in patients with pedunculated-type T1 colorectal cancer.","authors":"Kengo Kasuga, Toshio Uraoka, Yoshiki Kajiwara, Shiro Oka, Shinji Tanaka, Takahiro Nakamura, Shoichi Saito, Yosuke Fukunaga, Manabu Takamatsu, Hiroshi Kawachi, Kinichi Hotta, Hiroaki Ikematsu, Motohiro Kojima, Yutaka Saito, Yukihide Kanemitsu, Shigeki Sekine, Shinji Nagata, Kazutaka Yamada, Jun Konishi, Soichiro Ishihara, Yusuke Saitoh, Kenji Matsuda, Kazutomo Togashi, Koji Komori, Megumi Ishiguro, Toshio Kuwai, Takashi Okuyama, Akihiro Ohuchi, Shinobu Ohnuma, Kazuhiro Sakamoto, Tamotsu Sugai, Kenji Katsumata, Hiro-O Matsushita, Hiro-O Yamano, Keisuke Nakai, Naohiko Akimoto, Hirotoshi Kobayashi, Yoichi Ajioka, Kenichi Sugihara, Hideki Ueno","doi":"10.1007/s00535-026-02397-2","DOIUrl":"10.1007/s00535-026-02397-2","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"689-690"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674128","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":"Hepatocyte-specific yes-associated protein knockout exacerbates non-alcoholic steatohepatitis by upregulating PCSK9.","authors":"Xia Sun, Yu Zhang, Xin Zhang, Qiaohong Qin, Ying Hou, Min Jia, Xingli Su, Yulong Chen","doi":"10.1007/s00535-026-02372-x","DOIUrl":"10.1007/s00535-026-02372-x","url":null,"abstract":"<p><strong>Background: </strong>No licensed drugs have been established for the treatment of nonalcoholic steatohepatitis (NASH). Therefore, we aimed to explore the effect of Yes-associated protein (YAP) on NASH to provide a therapeutic target.</p><p><strong>Methods: </strong>We constructed a mouse model of NASH, consuming either a methionine-choline deficient (MCD) or Gubra Amylin NASH (GAN) diet. Hepatocyte-specific YAP knockout (YAP^ΔHep) mice were introduced to investigate the function of hepatocyte YAP in NASH. Furthermore, detailed mechanisms were clarified using AML12 cells. Adeno-associated virus (AAV)-mediated hepatocyte YAP overexpression was used to observe the therapeutic efficacy in mice with NASH.</p><p><strong>Results: </strong>Hepatic YAP protein levels were increased in NASH models. The YAP deletion reduced hepatic steatosis and exacerbated hepatic inflammation and fibrosis. However, YAP overexpression leads to the opposite NASH phenotype. Furthermore, the MCD or GAN diet-fed YAP^ΔHep mice also exhibited a favorable hepatic steatosis phenotype with exacerbated inflammation and fibrosis in the liver. Conversely, hepatocyte-specific YAP or YAP (5S) overexpression led to an almost complete reversal of hepatic pathologies. Mechanistically, hepatocyte-specific PCSK9 knockdown effectively reversed NASH progression in YAP^ΔHep mice. Furthermore, the oncostatin M (OSM)-JAK2-STAT3 axis was involved in the YAP-mediated regulation of PCSK9. Notably, AAV8-mediated YAP overexpression in the hepatocyte improved NASH in mice.</p><p><strong>Conclusions: </strong>Our findings demonstrate that hepatocyte YAP mitigates NASH severity by increasing PCSK9 expression via the OSM-JAK2-STAT3 pathway independent of lipid accumulation. Therefore, hepatocyte YAP may be a promising target for the management of NASH.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"625-637"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306913","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":"METTL3/YTHDF1 drives M1 macrophage polarization and aggravates ulcerative colitis progression by regulating m6A modification of SerpinB5 mRNA and FBXO32-dependent NF-κB pathway.","authors":"Tian Pu, Ranran Feng, Chunru Wang, Ye Zhao","doi":"10.1007/s00535-025-02341-w","DOIUrl":"10.1007/s00535-025-02341-w","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. It has been reported that macrophages are key cells mediating inflammation. Furthermore, Serpin family B member 5 (SerpinB5) plays a role in the regulation of macrophage phenotype conversion. However, the role and underlying mechanism of SerpinB5 in UC are still unclear.</p><p><strong>Methods: </strong>Hematoxylin and eosin staining assay was used to assess colon pathological changes. GO enrichment and KEGG pathway enrichment analyses were conducted to assess the function of the DEGs from RNA-seq data. GSE224758 database, RNA-seq, and GeneCards database were applied to analyze the intersection targets. The mRNA and protein levels of the related genes were determined using RT-qPCR and western blot. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). Cell viability, proliferation, and apoptosis were determined using CCK-8, EdU, and flow cytometry. Senescence-associated β-galactosidase (SA-β-Gal) staining and senescence-related proteins p53 and p16 were detected to evaluate the endothelial cell senescence. Inflammatory cytokines and oxidative stress were detected using ELISA and kits. Flow cytometry analysis assessed the percentage of CD11b⁺CD86⁺ and CD11b⁺CD206⁺ cells in mouse-derived macrophages. A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. The interaction of SerpinB5 and F-Box Protein 32 (FBXO32) was confirmed using GST pull-down and coimmunoprecipitation assays. Besides, MeRIP-qPCR, RNA pull-down, and RIP assays were used to examine the molecular mechanism underlying METTL3/m6A/YTHDF1 signaling axis in SerpinB5 expression.</p><p><strong>Results: </strong>SerpinB5 expression was increased in UC patients, TNF-α-treated FUC cells, and a mouse model of UC. SerpinB5 silencing repressed TNF-α-induced cell apoptosis, cell senescence, inflammation response, oxidative stress, and M1 macrophage polarization. Meanwhile, SerpinB5 knockdown relieved symptoms of the mouse model of UC and repressed M1 macrophage polarization. SerpinB5 positively mediated the NF-κB pathway by regulating FBXO32. METTL3 improved the stability of SerpinB5 mRNA in an m6A-YTHDF1-dependent manner.</p><p><strong>Conclusion: </strong>METTL3/YTHDF1 aggravated UC progression through promoting M1 macrophage polarization via SerpinB5 mRNA m6A modification and FBXO32/NF-κB pathway. These findings indicated that SerpinB5 might be a good and promising therapeutic target for UC treatment.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"559-577"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900704","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":"Interpreting risk scores after gastric ESD: insights from recent validation.","authors":"Robert Bechara, Ayaka Takasu, Waku Hatta, Hirofumi Kogure, Takuji Gotoda","doi":"10.1007/s00535-026-02352-1","DOIUrl":"10.1007/s00535-026-02352-1","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"673-674"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113432","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}