Journal of Gastroenterology最新文献

{"title":"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/s00535-025-02299-9","DOIUrl":"https://doi.org/10.1007/s00535-025-02299-9","url":null,"abstract":"<p><strong>Background: </strong>Carotegrast methyl is approved for treating patients with moderately active ulcerative colitis with inadequate response to 5-aminosalicylic acid agents. However, real-world evidence to guide optimal use is limited. This retrospective study aimed to characterise suitable patient profiles, identify biomarkers predictive of carotegrast methyl efficacy, and determine the appropriate timing for treatment evaluation.</p><p><strong>Methods: </strong>We analysed data from 186 patients enrolled in a phase 3 trial of carotegrast methyl (96 carotegrast methyl, 90 placebo). We assessed biomarkers (leucine-rich α-2 glycoprotein, C-reactive protein, faecal calprotectin, and anti-integrin αvβ6 antibody titres) alongside clinical outcomes and assessed symptom diaries and maintenance therapies.</p><p><strong>Results: </strong>Low disease activity at baseline (partial Mayo score ≤ 5) was associated with higher remission rates (56.1 vs. 33.3%). Anti-integrin αvβ6 antibody titres of < 44.6 U/mL at baseline predicted higher clinical remission rates (49.1 vs. 26.8%). Symptom improvement was detectable from week 2. Faecal calprotectin correlated with the endoscopic subscore at the end of treatment (ρ = 0.566); a faecal calprotectin level of < 387.5 µg/g predicted Mayo endoscopic subscore 0/1. Most patients maintained remission with oral 5-aminosalicylic acid alone; the 1-year maintenance rate was 56.5%.</p><p><strong>Conclusions: </strong>Carotegrast methyl appears most effective in patients with moderately active ulcerative colitis with low disease activity, with week 2 and beyond as an appropriate time point for assessing efficacy. Anti-integrin αvβ6 antibody titre shows promise in predicting response to carotegrast methyl. Faecal calprotectin may serve as a non-invasive surrogate for evaluating endoscopic healing.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113201","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":"STYK1 as a targetable vulnerability enhances the efficacy of anti-PD-L1 therapy in pancreatic cancer.","authors":"Xiao Wang, Yueqin Zhang, Anan Li, Chuanzan Zhou, Sen Xu, Zongting Gu, Wei Wang, Peng Nan, Ran Tao","doi":"10.1007/s00535-025-02291-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02291-3","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited treatment options. Immunotherapy, though effective in various tumors, has limited efficacy in PDAC due to immune tolerance. Thus, identifying new targets to enhance immunotherapy response is crucial.</p><p><strong>Methods: </strong>This study used bioinformatics analysis and public database data to identify STYK1 as a potential PDAC biomarker. We analyzed STYK1 expression in PDAC tissues, its link to patient prognosis and immune cell infiltration. In vitro experiments assessed the impact of STYK1 knockdown on PDAC cell proliferation, migration, and invasion. Immunohistochemical analysis was performed on 79 PDAC tissue samples to evaluate CD8⁺ T cell infiltration. In vivo studies examined the effects of STYK1 knockdown on tumor growth, T cell infiltration and activation, especially with anti-PD-L1 antibodies. We also investigated the molecular mechanisms of STYK1's regulation of T cell infiltration, focusing on its association with CCL20 and its role beyond the PD-1/PD-L1 pathway.</p><p><strong>Results: </strong>Elevated STYK1 expression in PDAC tissue is associated with poor prognosis and reduced CD8⁺ T cell infiltration. STYK1 knockdown inhibits PDAC cell proliferation, migration, and invasion in vitro. In vivo, it decreases tumor growth and, when combined with anti-PD-L1 antibody treatment, significantly enhances T cell infiltration and activation without affecting PD-L1 expression. STYK1 regulates T cell infiltration via CCL20, independently of the PD-1/PD-L1 signaling pathway.</p><p><strong>Conclusions: </strong>STYK1 is a potential predictive biomarker for immunotherapy response in PDAC, as its regulation of T cell infiltration via CCL20, independent of the PD-1/PD-L1 pathway, may provide a strategy to potentially augment immunotherapy efficacy, pending mechanistic confirmation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085502","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":"Forecasting age-standardized incidence rates of gastric cancer from 1990-2050 in Japan according to H. pylori prevalence and eradication scenarios.","authors":"Byron Sigel, Eiko Saito, Daisuke Yoneoka, Tomohiro Matsuda, Kota Katanoda","doi":"10.1007/s00535-025-02296-y","DOIUrl":"https://doi.org/10.1007/s00535-025-02296-y","url":null,"abstract":"<p><strong>Background: </strong>This study examines the influence of H. pylori eradication policies on gastric cancer incidence rates in Japan utilizing nationally representative registry data. It evaluates the impact of the H. pylori eradication policies introduced in 2000 and 2013, along with future eradication scenarios, on age-standardized gastric cancer rates.</p><p><strong>Methods: </strong>Data from prefectural cancer registries and national health surveys were analyzed using Poisson regression and autoregressive integrated moving average models. Predictors such as H. pylori prevalence, alcohol consumption, salt intake, body mass index, and smoking prevalence were included. The study assessed past policies by comparing incidence rates with and without the policy changes of 2000 and 2013. Future policies were evaluated through five scenarios, incorporating the cumulative impact of eradication efforts from 2000 and 2013, and a projected 75% reduction by 2050. The evaluation also compared eradication targets for age groups 40-69 and 20-39.</p><p><strong>Results: </strong>Past H. pylori eradication policies were associated with decreased age-standardized gastric cancer incidence rates in Japan, reducing the rate from a projected 39.3 per 100,000 without the 2000 and 2013 policies to 24.9 per 100,000 under current policies. Future policies, integrating the cumulative effects of the 2000 and 2013 eradication efforts and projecting a 75% reduction in H. pylori prevalence, were projected to further reduce gastric cancer incidence.</p><p><strong>Conclusion: </strong>The H. pylori eradication policies of 2000 and 2013 have significantly reduced gastric cancer incidence rates in Japan. Model projections suggest that expanded eradication efforts could lead to additional reductions, further lowering the future burden of gastric cancer in Japan.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085183","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":"Ferroptosis: biology and role in liver disease.","authors":"Keisuke Hino, Sohji Nishina, Izumi Yanatori","doi":"10.1007/s00535-025-02300-5","DOIUrl":"https://doi.org/10.1007/s00535-025-02300-5","url":null,"abstract":"<p><p>Ferroptosis is a form of nonapoptotic cell death that is driven by iron-dependent lipid peroxidation and is relevant to a wide range of biological processes, such as development, aging, immunity, and cancer. Ferroptosis has also been linked to numerous hepatic metabolic pathways, including the metabolism of iron, fatty acids, and amino acids, such as cysteine. During the last decade, studies on the biology of and molecules regulating ferroptosis have shed light on the role of ferroptosis in liver disease and its implications. The susceptibility of liver cells to ferroptosis determines the extent of liver injury and affects the progression of nonneoplastic diseases, whereas liver cancer cells display intrinsic or acquired resistance to ferroptosis, which promotes cancer progression. These findings indicate that ferroptosis represents a promising target for the prevention and treatment of many forms of liver disease. In this review, we provide an update on the mechanisms regulating ferroptosis, focusing on the peroxidation of phospholipids, the antioxidant pathways that limit lipid peroxidation, and the regulation of the labile iron pool, all of which are closely connected. We also summarize the roles and importance of ferroptosis in the pathogenesis of liver disease, and the therapeutic potential of targeting ferroptosis in liver diseases.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080835","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":"Prevalence, characteristics, and screening of spondyloarthritis in Japanese patients with early inflammatory bowel diseases: a prospective multidisciplinary study.","authors":"Sho Fukui, Mitsumasa Kishimoto, Minoru Matsuura, Aika Sakamoto, Keisuke Ono, Satoshi Kobayashi, Soko Kawashima, Noriko Ikegaya, Takahisa Kawakami, Tatsuya Mitsui, Daisuke Saito, Mari Hayashida, Jun Miyoshi, Yoshinori Komagata, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02301-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02301-4","url":null,"abstract":"<p><strong>Background: </strong>The prevalence and characteristics of inflammatory bowel disease-associated spondyloarthritis (IBD-SpA) in Japan are unclear. Moreover, methods for screening SpA among IBD patients have not been established.</p><p><strong>Methods: </strong>This single-center prospective multidisciplinary study included consecutive patients with IBD, which was newly diagnosed within the past 3 years (early IBD). Board-certified rheumatologists examined the patients for disease history and musculoskeletal manifestations, with imaging studies if needed. Questionnaires assessed patient-reported outcomes and Psoriatic Arthritis Screening and Evaluation (PASE) scores.</p><p><strong>Results: </strong>We identified 85 eligible patients with early IBD, 22 (25.9%) of whom had Crohn's disease, 63 (74.1%) had ulcerative colitis, and 3 (3.5%) had IBD-SpA diagnosed prior to study enrollment. Rheumatologist evaluations identified additional seven SpA cases, resulting in a total of 10 patients (11.8%) with IBD-SpA (1: axial, 9: peripheral). IBD patients without SpA often presented with back pain (52%) and peripheral joint pain (24%), whereas arthritis, cervical and thoracic pain, and inflammatory back pain were more frequent in IBD-SpA. Newly identified IBD-SpA cases tended to have lower-limb arthritis, dactylitis, and enthesitis, compared with previously diagnosed IBD-SpA cases. For patients with active SpA symptoms in the past 6 months, PASE demonstrated that the area under the receiver operating characteristic curve was 0.87 (95% confidence interval: 0.68, 1.00). The optimal cut-off (33 points) had a sensitivity of 0.88 and specificity of 0.88.</p><p><strong>Conclusions: </strong>This prospective study found rheumatologist evaluation increased SpA diagnosis and 11.8% of Japanese early IBD patients had IBD-SpA. PASE questionnaires may be effective for screening SpA among IBD patients.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080829","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":"Development of gastric mucosa-associated microbiota in autoimmune gastritis with neuroendocrine tumors.","authors":"Koji Otani, Geicho Nakatsu, Kosuke Fujimoto, Daichi Miyaoka, Noriaki Sato, Yuji Nadatani, Yu Nishida, Hirotsugu Maruyama, Masaki Ominami, Shusei Fukunaga, Shuhei Hosomi, Fumio Tanaka, Seiya Imoto, Satoshi Uematsu, Toshio Watanabe, Yasuhiro Fujiwara","doi":"10.1007/s00535-025-02298-w","DOIUrl":"https://doi.org/10.1007/s00535-025-02298-w","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune gastritis (AIG) is a chronic atrophic gastritis that affects the gastric corpus, leading to achlorhydria, hypergastrinemia, and a precursor of neuroendocrine tumors (NETs). This study aimed to elucidate the underlying mechanisms of gastric NET formation in AIG by analyzing gastric mucosa-associated microbiota and host tissue-derived metabolite profiles.</p><p><strong>Methods: </strong>A total of 19 patients diagnosed with AIG and 12 controls uninfected with Helicobacter pylori underwent gastric mucosal biopsies for microbiome analysis using next-generation sequencing with primers targeting the V3-V4 region of the 16S rRNA gene, and metabolome analysis using capillary electrophoresis time-of-flight mass spectrometry.</p><p><strong>Results: </strong>Microbiome analysis revealed significantly reduced α-diversity indices in patients with AIG when compared with the control group. β-Diversity analysis showed distinct microbial compositions among the control, NET-negative, and NET-positive groups. The NET-positive group exhibited a significantly higher abundance of Proteobacteria and Fusobacteriota, particularly Haemophilus parainfluenzae, Fusobacterium periodonticum, and Fusobacterium nucleatum, whereas Firmicutes, including Streptococcus salivarius and Veillonella atypica, were significantly decreased compared with the NET-negative group. Metabolome analysis revealed a shift away from glycolysis and tricarboxylic acid cycle activity toward alternative metabolic pathways in patients with AIG. Integrated analysis of gastric microbiota signatures (GMS) and tissue metabotypes demonstrated significant associations among GMS, tissue metabotypes, and NET diagnosis.</p><p><strong>Conclusions: </strong>These findings highlight marked shifts in gastric mucosa-associated microbiota profiles in patients with AIG who developed gastric NETs. Tissue-specific metabolic alterations may precede mucosal dysbiosis in patients with AIG and promote the development of a microenvironment implicated in NET formation.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040260","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":"Hic-5 deficiency attenuates MAFLD by inhibiting neutrophils migration via the CXCL1-CXCR2 axis.","authors":"Bingyu Ren, Han Li, Shenglu Liu, Zhiwei Huang, Junjie Bai, Zhonghao Jiang, Tongjie Xu, Boyuan Gu, Wenhao Yu, Lei Sun, Peng Tan, Wenguang Fu","doi":"10.1007/s00535-025-02293-1","DOIUrl":"https://doi.org/10.1007/s00535-025-02293-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Inflammatory cell infiltration in the liver is a hallmark of metabolic dysfunction-associated fatty liver disease (MAFLD). However, the pathological events that trigger the infiltration of inflammatory cells to mediate MAFLD pathogenesis remains poorly understood. This study aims to investigate the function and mechanism of Hic-5 on hepatic inflammation of MAFLD.</p><p><strong>Methods: </strong>MAFLD animal models were fed a methionine- and choline-deficient (MCD) diet in Hic-5 knockout mice. Liver tissues were analyzed by immunohistochemical staining, immunofluorescence and flow cytometry, with a particular focus on the impact on the immune microenvironment.</p><p><strong>Results: </strong>Hic-5 deficiency alleviates the severity of MAFLD, particularly the inflammation response. Gain- and loss-of-function experiments revealed that Hic-5 deficiency results in decreased neutrophil proliferation and increased apoptosis, as well as impaired migration. Conversely, Hic-5 overexpression had the opposite effects. This study confirmed that METTL3-mediated methylation of m⁶A stabilizes Hic-5 mRNA and promotes its expression, which in turn regulates the infiltration of neutrophils by the CXCL1-CXCR2 axis.</p><p><strong>Conclusions: </strong>The study reveals the role of Hic-5 in regulating neutrophils and indicates that it may be a potential therapeutic target for MAFLD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023425","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":"Combination chemotherapy for older patients with unresectable biliary tract cancer: a prospective observational study using propensity-score matched analysis (JON2104-B).","authors":"Satoshi Kobayashi, Kohei Nakachi, Kouji Yamamoto, Makoto Ueno, Yuta Maruki, Kenji Ikezawa, Takeshi Terashima, Satoshi Shimizu, Kotoe Oshima, Kunihiro Tsuji, Yoshiharu Masaki, Hidetaka Tsumura, Taro Shibuki, Masato Ozaka, Naohiro Okano, Yukiyasu Okamura, Kumiko Umemoto, Tatsunori Satoh, Yasushi Kojima, Kazuhiko Shioji, Hiroko Nebiki, Toshifumi Doi, Atsushi Naganuma, Shigeki Kataoka, Emiri Kita, Hiroyuki Asama, Kaoru Tsuchiya, Michiaki Unno, Reiko Ashida, Kazuyuki Matsumoto, Izumi Ohno, Takao Itoi, Yuji Negoro, Yasunari Sakamoto, Shiho Arima, Akinori Asagi, Hiroyuki Okuyama, Yoshito Komatsu, Noritoshi Kobayashi, Hiroaki Nagano, Junji Furuse","doi":"10.1007/s00535-025-02294-0","DOIUrl":"https://doi.org/10.1007/s00535-025-02294-0","url":null,"abstract":"<p><strong>Background: </strong>Systemic chemotherapy with gemcitabine plus S-1 (GEM + S-1), GEM + CDDP plus S-1 (GEM + CDDP + S-1), or gemcitabine plus cisplatin (GEM + CDDP) is standard treatment for advanced biliary tract cancer (aBTC). We aimed to evaluate the efficacy and safety of combination chemotherapy in older patients with aBTC.</p><p><strong>Methods: </strong>This multicenter prospective observational study (JON2104-B, UMIN000045156) included patients aged ≥ 70 years with aBTC. Inverse-probability weighting propensity-score analyses (IPW) were used to compare overall survival (OS) as the primary endpoint and progression-free survival (PFS) across treatment groups.</p><p><strong>Results: </strong>This study included 305 patients between August 2021 and January 2023. Of them, 75, 131, 26, 52, and 10 received GEM + CDDP + S-1, GEM + CDDP, GEM + S-1, gemcitabine, and S-1; their median ages were 74, 75, 77.5, 80, and 80 years, and approximately 24%, 16.8%, 23.1%, 9.6%, and 0% had G-8 scores of > 14, respectively. GEM + CDDP had a safety profile comparable to that of GEM + CDDP + S-1 but was more toxic than gemcitabine. Per IPW, the hazard ratio (HR) for GEM + CDDP + S-1 versus GEM + CDDP was 0.80 for OS (95% confidence interval [CI], 0.55-1.17) and 0.55 for PFS (95% CI 0.38-0.80). The HR for GEM + CDDP versus gemcitabine was 0.74 for OS (95% CI 0.42-1.29) and 0.79 for PFS (95% CI 0.42-1.49).</p><p><strong>Conclusions: </strong>GEM + CDDP + S-1 was associated with longer PFS without additional toxicity than GEM + CDDP for fit older patients. However, the OS for both were not statistically different. The efficacies of GEM + CDDP and gemcitabine for vulnerable older patients did not also differ significantly. These findings highlight the importance of vulnerability in patients with aBTC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006261","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":"Nationwide estimates of patient numbers and prevalence rates of ulcerative colitis and Crohn's disease in Japan in 2023.","authors":"Anna Tsutsui, Yoshitaka Murakami, Yuji Nishiwaki, Keiko Asakura, Satoko Ohfuji, Wakaba Fukushima, Katsuyoshi Matsuoka, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02295-z","DOIUrl":"https://doi.org/10.1007/s00535-025-02295-z","url":null,"abstract":"<p><strong>Background: </strong>Almost a decade has passed since the previous nationwide survey on the prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in Japan was conducted in 2015. We conducted a new nationwide hospital-based survey to provide updated estimates of the patient numbers and prevalence rates of UC and CD in Japan in 2023.</p><p><strong>Methods: </strong>Stratified random sampling was used to select hospital departments (internal medicine, surgery, pediatrics, and pediatric surgery) that routinely treat UC and CD patients. We sent questionnaires to the sampled departments to request sex-specific information on their patient numbers for UC and CD in 2023. Based on the responses, we estimated the annual patient numbers and prevalence rates of UC and CD throughout Japan. The estimates were compared with those from the previous 2015 survey.</p><p><strong>Results: </strong>The overall survey response rate was 50.8% (1,798/3,538 departments). The estimated patient numbers were approximately 316,900 (95% confidence interval: 223,900-409,900) for UC and 95,700 (61,100-130,400) for CD, both of which represent a 1.4-fold increase over the 8-year period since 2015. The annual prevalence rates per 100,000 population were 254.8 (male: 297.5; female: 214.4) for UC and 77.0 (male: 112.9, female: 43.0) for CD. The male-to-female ratios were 1.31 for UC and 2.49 for CD, and the UC-to-CD ratio was 3.31.</p><p><strong>Conclusions: </strong>The patient numbers and prevalence rates of UC and CD have continued to steadily increase in Japan, suggesting the need for continued monitoring and further investigation to track the disease burden.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957101","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":"VPS45 promotes the progression of hepatocellular carcinoma by recycling β1 integrin to the cell membrane via the endocytic pathway.","authors":"Takashi Ofuchi, Hajime Otsu, Kiyotaka Hosoda, Tomohiko Ikehara, Akinori Tsujimoto, Satoshi Higuchi, Shohei Shibuta, Yuya Ono, Kosuke Hirose, Yasuo Tsuda, Yusuke Yonemura, Takaaki Masuda, Hiromitsu Hayashi, Masaaki Iwatsuki, Koshi Mimori","doi":"10.1007/s00535-025-02278-0","DOIUrl":"10.1007/s00535-025-02278-0","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis, which is often driven by chromosomal amplifications at 1q. Vacuolar sorting protein 45 (VPS45), a gene located on chromosome 1q, is involved in the endocytic recycling pathway; however, its role in HCC remains unclear. In this study, we aimed to investigate the functional significance of VPS45 in the progression of HCC.</p><p><strong>Methods: </strong>VPS45 expression was analyzed using public databases, clinical HCC samples, and cell lines. Functional assays, including VPS45 knockout and rescue experiments, were conducted to assess the effect on tumor progression in vitro and in vivo. The molecular mechanisms underlying VPS45 function, particularly its role in β1 integrin recycling and FAK-AKT signaling activation, were also explored.</p><p><strong>Results: </strong>VPS45 expression was significantly elevated in HCC owing to DNA copy number amplification and correlated with poor prognosis. Moreover, VPS45 knockout suppressed cell proliferation, migration, and invasion, while promoting apoptosis. VPS45 interacted with syntaxin16 and rabenosyn-5 to facilitate the recycling of β1 integrin to the cell membrane, thereby activating FAK-AKT signaling, which promotes oncogenic phenotypes. In xenograft models, VPS45 knockout significantly suppressed tumor growth, further supporting its role in HCC progression.</p><p><strong>Conclusions: </strong>VPS45 is a key oncogene in HCC that promotes tumor progression by enhancing β1 integrin recycling and activating FAK-AKT signaling. Given its strong association with poor prognosis and tumor malignancy, VPS45 may serve as a promising prognostic biomarker and a potential therapeutic target for HCC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"1157-1173"},"PeriodicalIF":5.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333267","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}