Journal of Gastroenterology最新文献

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Noninvasive prediction of the clinical benefit of immunotherapy in hepatocellular carcinoma. 肝细胞癌免疫治疗临床获益的无创预测。
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-30 DOI: 10.1007/s00535-025-02251-x
Atsushi Ono, C Nelson Hayes, Ryoichi Miura, Tomokazu Kawaoka, Masataka Tsuge, Shiro Oka
{"title":"Noninvasive prediction of the clinical benefit of immunotherapy in hepatocellular carcinoma.","authors":"Atsushi Ono, C Nelson Hayes, Ryoichi Miura, Tomokazu Kawaoka, Masataka Tsuge, Shiro Oka","doi":"10.1007/s00535-025-02251-x","DOIUrl":"https://doi.org/10.1007/s00535-025-02251-x","url":null,"abstract":"<p><p>Long-term survival following a diagnosis of hepatocellular carcinoma (HCC) is greatly diminished when transplantation and surgical resection are ruled out. Fortunately, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced unresectable HCC (uHCC), prolonging median survival by over a year. T lymphocytes normally eliminate neoplastic cells, but some tumors suppress this response by binding to immune checkpoint receptors. Blocking this interaction via ICIs restores immune-mediated targeting of cancer cells. While ICI-based combination immunotherapy is currently recommended as the first-line systemic therapy for uHCC, the objective radiological response rate remains limited to 20-30%, as not all tumors exploit this mechanism. Consequently, strategies are being explored to modulate the immune microenvironment into a \"hot\" environment more responsive to ICIs by combining local therapies such as transarterial chemoembolization, ablation, and radiation therapy. Therapeutic options have also expanded beyond ICIs, emphasizing the importance of selecting the most appropriate treatment. Therefore, the development of biomarkers capable of predicting the efficacy of immunotherapy is a priority. Direct evaluation of immune cell infiltration through biopsy is currently the most effective method but involves issues such as invasiveness and susceptibility to sampling bias. In this review, we aim to highlight promising non-invasive biomarkers and scoring systems that have the potential to improve treatment outcomes, including blood-based biomarkers such as lymphocyte ratios, cytokines, C-reactive protein, and alpha-fetoprotein; imaging biomarkers such as MRI, ultrasound, and contrast-enhanced CT; and other clinical indicators such as sarcopenia, grip strength, and diversity of the gut microbiome.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187137","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}
引用次数: 0
SEC61G promotes colorectal cancer progression by regulating cytosolic Ca2+ concentration. SEC61G通过调节细胞质Ca2+浓度促进结直肠癌的进展。
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-25 DOI: 10.1007/s00535-025-02259-3
Satoshi Higuchi, Hajime Otsu, Takaaki Masuda, Masahiro Hashimoto, Yusuke Nakano, Kiyotaka Hosoda, Kosuke Hirose, Tomohiko Ikehara, Takashi Ofuchi, Yasuo Tsuda, Yusuke Yonemura, Mamoru Uemura, Hidetoshi Eguchi, Yuichiro Doki, Koshi Mimori
{"title":"SEC61G promotes colorectal cancer progression by regulating cytosolic Ca<sup>2+</sup> concentration.","authors":"Satoshi Higuchi, Hajime Otsu, Takaaki Masuda, Masahiro Hashimoto, Yusuke Nakano, Kiyotaka Hosoda, Kosuke Hirose, Tomohiko Ikehara, Takashi Ofuchi, Yasuo Tsuda, Yusuke Yonemura, Mamoru Uemura, Hidetoshi Eguchi, Yuichiro Doki, Koshi Mimori","doi":"10.1007/s00535-025-02259-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02259-3","url":null,"abstract":"<p><strong>Background: </strong>Intracellular calcium (Ca<sup>2+</sup>) signaling regulates key cancer processes. Research findings suggest that the SEC61 complex, involved in protein translocation, contributes to calcium leakage from the endoplasmic reticulum. However, the mechanism by which SEC61 Translocon Subunit Gamma (SEC61G), a component of this complex, influences colorectal cancer (CRC) progression remains unclear.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed using The Cancer Genome Atlas data sets to identify candidate genes on chromosome 7p, examine their association with DNA copy number amplification. In addition, SEC61G expression in CRC cells and tissues was validated using reverse-transcription quantitative polymerase chain reaction and immunohistochemistry. Moreover, in vitro and in vivo experiments were performed to investigate the effects of SEC61G overexpression and knockdown on CRC cell proliferation. Furthermore, publicly available single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) data were used to validate the role of SEC61G in CRC.</p><p><strong>Results: </strong>SEC61G was significantly upregulated in CRC tissues and was correlated with poor prognosis in patients with CRC. SEC61G overexpression enhanced cell proliferation and activated the EGFR pathway, promoting cell cycle progression from the G1 to S phase. In addition, SEC61G overexpression increased cytosolic Ca<sup>2+</sup> levels, which activated EGFR signaling via calmodulin. Moreover, analyses of scRNA-seq and ST-seq data confirmed that SEC61G expression was higher in tumor epithelial cells and that it was co-expressed with EGFR pathway-related genes.</p><p><strong>Conclusions: </strong>SEC61G promotes CRC progression by regulating cytosolic Ca<sup>2+</sup> concentration, EGFR activation, and cell cycle progression, highlighting its potential as a prognostic biomarker and therapeutic target in CRC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142458","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}
引用次数: 0
Autoantibodies against endothelial protein C receptor and integrin αvβ6 predict the development of ulcerative colitis. 抗内皮蛋白C受体和整合素αvβ6的自身抗体预测溃疡性结肠炎的发展。
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-15 DOI: 10.1007/s00535-025-02263-7
Motoi Sawahashi, Yoichi Kakuta, Takeo Naito, Soshi Okazaki, Kinuko Ohneda, Masatsugu Orui, Taku Obara, Soichi Ogishima, Kazuki Kumada, Hisaaki Kudo, Fuji Nagami, Atsushi Hozawa, Hideya Iwaki, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Tsuyoshi Shirai, Hiroshi Fujii, Atsushi Masamune
{"title":"Autoantibodies against endothelial protein C receptor and integrin αvβ6 predict the development of ulcerative colitis.","authors":"Motoi Sawahashi, Yoichi Kakuta, Takeo Naito, Soshi Okazaki, Kinuko Ohneda, Masatsugu Orui, Taku Obara, Soichi Ogishima, Kazuki Kumada, Hisaaki Kudo, Fuji Nagami, Atsushi Hozawa, Hideya Iwaki, Hiroshi Nagai, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Yoshitaka Kinouchi, Tsuyoshi Shirai, Hiroshi Fujii, Atsushi Masamune","doi":"10.1007/s00535-025-02263-7","DOIUrl":"https://doi.org/10.1007/s00535-025-02263-7","url":null,"abstract":"<p><strong>Background: </strong>A method for predicting ulcerative colitis (UC) onset has not been established. Serum autoantibodies have been suggested as potential predictive biomarkers for UC onset. We aimed to validate the risks associated with serological and environmental factors and construct a model for predicting UC development.</p><p><strong>Methods: </strong>Using the population-based cohort studies (n > 83,000), we identified 42 individuals who were diagnosed with UC later in life and compared them with matched healthy controls. We analyzed serum anti-integrin αvβ6 antibody (anti-αvβ6) and anti-endothelial protein C receptor antibody (anti-EPCR) titers, and lifestyle and dietary habits to explore UC onset predictors. The predictive performance of the models was evaluated based on these predictors.</p><p><strong>Results: </strong>The sensitivity and specificity of anti-EPCR for predicting UC onset were 51.4% and 97.8%, respectively, comparable to those of anti-αvβ6 (52.5% and 97.6%, respectively). The proportion of individuals with insomnia was significantly higher in the preclinical UC group (adjusted odds ratio = 2.14, 95% confidence interval [CI] 1.11-4.04, p = 0.019). The predictive performance of anti-EPCR alone was high with an area under the curve (AUC) of 0.89 (95%CI 0.83-0.96), and that of anti-EPCR combined with anti-αvβ6 was even better with an AUC of 0.92 (95%CI 0.87-0.97); the lifestyle model had lower predictive accuracy (AUC = 0.65, 95%CI 0.55-0.74).</p><p><strong>Conclusions: </strong>Anti-EPCR and anti-αvβ6 each strongly predict UC onset. The combined anti-EPCR and anti-αvβ6 model had stronger predictive performance than the single models.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078105","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}
引用次数: 0
Associations between excessive supragastric belching and esophageal reflux factors in patients with PPI-refractory GERD in Japan. 日本ppi难治性胃反流患者胃上过度打嗝与食管反流因素之间的关系
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-12 DOI: 10.1007/s00535-025-02258-4
Yukihiro Shuto, Masahiro Saito, Tomoyuki Koike, Kaoru Koizumi, Yumiko Kaise, Kazuma Yachi, Yutaka Hatayama, Yohei Ogata, Xiaoyi Jin, Takeshi Kanno, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune
{"title":"Associations between excessive supragastric belching and esophageal reflux factors in patients with PPI-refractory GERD in Japan.","authors":"Yukihiro Shuto, Masahiro Saito, Tomoyuki Koike, Kaoru Koizumi, Yumiko Kaise, Kazuma Yachi, Yutaka Hatayama, Yohei Ogata, Xiaoyi Jin, Takeshi Kanno, Waku Hatta, Kaname Uno, Naoki Asano, Akira Imatani, Atsushi Masamune","doi":"10.1007/s00535-025-02258-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02258-4","url":null,"abstract":"<p><strong>Background: </strong>No studies have evaluated the prevalence of supragastric belching (SGB) in Japanese patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD) under off-PPI conditions. This study aimed to clarify the association between excessive SGB and esophageal reflux factors.</p><p><strong>Methods: </strong>Seventy-nine patients with PPI-refractory NERD under off-PPI treatment were evaluated using 24-h multichannel intraluminal impedance pH monitoring and high-resolution impedance manometry.</p><p><strong>Results: </strong>The prevalence values of excessive SGB overall and in the true NERD, reflux hypersensitivity, and function heartburn subtypes were 19.0%, 35.7%, 5.3%, and 12.5%, respectively. The monitoring results demonstrated that, compared with those without excessive SGB, patients with excessive SGB had a significantly higher total number of reflux events (63 episodes vs. 39 episodes, p = 0.01) and significantly greater acid exposure time (6.1% vs. 1.35%, p = 0.01). However, bolus exposure did not differ significantly between the groups (p = 0.09). The manometry findings showed no significant differences in lower esophageal sphincter pressure, integrated relaxation pressure, and distal contractile integral between the groups. Regarding gastroesophageal reflux, 22% of the SGB episodes were preceded by reflux, 55% occurred independently, and 23% were followed by reflux.</p><p><strong>Conclusions: </strong>The prevalence of excessive SGB in Japanese patients with PPI-refractory NERD under off-PPI conditions was 19.0% and most commonly observed in patients with true NERD (35.7%). Patients with excessive SGB exhibited increased esophageal acid exposure, and reflux events were sometimes observed before SGB episodes.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986311","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}
引用次数: 0
An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in patients with pancreatic cancer. 轴突引导相关的microRNA面板识别胰腺癌患者根治性手术后血管周围丛局部复发。
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-10 DOI: 10.1007/s00535-025-02260-w
Satoshi Nishiwada, Kota Nakamura, Naoki Ozu, Taichi Terai, Yuichiro Kohara, Minako Nagai, Takeshi Sakata, Shunsuke Doi, Yasuko Matsuo, Satoshi Yasuda, Toshihiro Tanaka, Masayuki Sho
{"title":"An axon guidance-related microRNA panel identifies perivascular plexus local recurrence following curative surgery in patients with pancreatic cancer.","authors":"Satoshi Nishiwada, Kota Nakamura, Naoki Ozu, Taichi Terai, Yuichiro Kohara, Minako Nagai, Takeshi Sakata, Shunsuke Doi, Yasuko Matsuo, Satoshi Yasuda, Toshihiro Tanaka, Masayuki Sho","doi":"10.1007/s00535-025-02260-w","DOIUrl":"https://doi.org/10.1007/s00535-025-02260-w","url":null,"abstract":"<p><strong>Background: </strong>Complete oncological local control is essential for a potential cure in patients with pancreatic ductal adenocarcinoma (PDAC), but predicting local recurrence following curative surgery remains clinically challenging. In this study, we performed comprehensive biomarker discovery to identify an Axon guidance-related miRNA panel (AGMP) for risk-stratification of perivascular plexus recurrence (PPR) following curative surgery in patients with PDAC.</p><p><strong>Methods: </strong>To identify axon guidance-related microRNAs, we performed the pathway-miRNA interaction analysis using the miRPathDB2.0. Subsequently, the predictive performance of the miRNAs was trained and validated in three independent clinical surgically resected sample cohorts and one pretreatment blood sample cohort with different disease statuses [upfront surgery cohort: n = 162 (training: n = 103, internal validation: n = 59), neoadjuvant chemoradiotherapy (NACRT) cohort: n = 217, arterial invasion cohort: n = 62, pretreatment blood sample cohort: n = 53].</p><p><strong>Results: </strong>The pathway-miRNA interaction analysis identified 13 miRNAs related to axon guidance pathway. Subsequently, we trained a 13-miRNA risk-prediction model, AGMP, which robustly distinguished PPR after surgery in the training cohort (AUC = 0.95). The AGMP was successfully validated in three independent cohorts (AUC: validation = 0.94, NACRT = 0.94, Arterial invasion = 0.90). Furthermore, we additionally validated the performance of AGMP in a pretreatment blood cohort, which again confirmed the robustness of risk-stratification for PPR (AUC = 0.86).</p><p><strong>Conclusions: </strong>We developed a novel biomarker, AGMP that demonstrated remarkable predictive performance for PPR following curative surgery in patients with PDAC; highlighting the clinical importance of the nerve-cancer cross-talk and the hopefulness as a guidepost for designing future clinical and basic research to establish individualized treatment strategies.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016717","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}
引用次数: 0
Temporal trends in obesity and its prognostic impact in Korean patients with inflammatory bowel disease. 韩国炎症性肠病患者肥胖的时间趋势及其对预后的影响
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-01 Epub Date: 2025-02-26 DOI: 10.1007/s00535-025-02230-2
Min Kyu Kim, Seung Hwan Shin, Cheol-Hyung Lee, Soyoung Kim, Jong Whan Kim, Songhyun Lee, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Sung Wook Hwang
{"title":"Temporal trends in obesity and its prognostic impact in Korean patients with inflammatory bowel disease.","authors":"Min Kyu Kim, Seung Hwan Shin, Cheol-Hyung Lee, Soyoung Kim, Jong Whan Kim, Songhyun Lee, Seung Wook Hong, Sang Hyoung Park, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Sung Wook Hwang","doi":"10.1007/s00535-025-02230-2","DOIUrl":"10.1007/s00535-025-02230-2","url":null,"abstract":"<p><strong>Background: </strong>To assess the changes in body mass index (BMI) among Korean patients with inflammatory bowel disease (IBD) over a 14-year period and to explore how BMI at diagnosis impacts prognosis.</p><p><strong>Methods: </strong>We retrospectively collected BMI and laboratory data from patients with IBD who visited the Asan Medical Center between 2008 and 2021 (Cohort 1). Clinical outcomes, including intestinal resection and medication use, were analyzed in patients with a recorded BMI at diagnosis who were followed up in a prospectively maintained cohort (Cohort 2).</p><p><strong>Results: </strong>Among 11,216 IBD patients (Cohort 1), the median BMI increased over the study period, and the disparity in the prevalence of obese individuals (BMI ≥ 25 kg/m<sup>2</sup>) between those with IBD and the general population narrowed. Serum glucose and lipid profiles showed an upward trend during the study period. In patients with recorded BMI at the time of diagnosis (Cohort 2), the odds of intestinal resection and the use of biologics/small molecules were comparable or even lower in Crohn's disease (CD) and ulcerative colitis patients who were obese compared to patients with a normal BMI. Obesity (≥ 25 kg/m<sup>2</sup>) was inversely associated with the risk of thiopurine use in CD patients (adjusted hazard ratio: 0.61, 95% confidence interval: 0.48-0.78, p < 0.001).</p><p><strong>Conclusions: </strong>During a 14-year period, Korean IBD patients showed increasing trends in the prevalence of obese individuals and metabolic syndrome-associated laboratory results. CD patients with high BMI at diagnosis exhibited a similar or lower likelihood of undergoing intestinal resection and medication use compared to those with a normal BMI.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"583-592"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501868","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}
引用次数: 0
Single-cell RNA sequencing and functional analysis reveal the role of altered glycosylation levels of hepatic macrophages in liver cirrhosis. 单细胞RNA测序和功能分析揭示了肝巨噬细胞糖基化水平改变在肝硬化中的作用。
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-01 Epub Date: 2025-01-31 DOI: 10.1007/s00535-025-02218-y
Chunmei Wen, Huihui Tao, Huaizhou Chen, Wenjun Pu, Qiang Yan, Yaoshuang Zou, Sheng Sean Su, Lingling Zhou, Yali Peng, Guoying Wang, Tiantian Xu, Xuejia Zheng, Mengyao Wu, Yong Dai
{"title":"Single-cell RNA sequencing and functional analysis reveal the role of altered glycosylation levels of hepatic macrophages in liver cirrhosis.","authors":"Chunmei Wen, Huihui Tao, Huaizhou Chen, Wenjun Pu, Qiang Yan, Yaoshuang Zou, Sheng Sean Su, Lingling Zhou, Yali Peng, Guoying Wang, Tiantian Xu, Xuejia Zheng, Mengyao Wu, Yong Dai","doi":"10.1007/s00535-025-02218-y","DOIUrl":"10.1007/s00535-025-02218-y","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis represents a critical stage of chronic liver disease, characterized by progressive liver damage, cellular dysfunction, and disrupted cell-to-cell interactions. Glycosylation, an essential post-translational modification, significantly influences cellular behavior and disease progression. Its role in cirrhosis at the single-cell level remains unclear, despite its importance.</p><p><strong>Methods: </strong>This study, based on single-cell glycosylation and transcriptome data, compared the expression of differentially expressed genes in liver tissues from cirrhotic and healthy control samples, identifying changes in glycosylation-related genes and their functional pathway enrichment characteristics. Additionally, it analyzed the composition of immune cells and intercellular interaction features, with a focus on the interaction between macrophages and other immune cells and their potential role in immune regulation.</p><p><strong>Results: </strong>The analysis revealed significant changes in immune cell composition and glycosylation patterns in cirrhotic livers. Specifically, the number of macrophages increased substantially, while overall glycosylation levels decreased. Enhanced interactions between macrophages and other cell types were observed, highlighting the central role of macrophages in reshaping the immune microenvironment during cirrhosis progression. Gene expression analysis showed a marked upregulation of FUCA1, a gene encoding a glycosylation-related hydrolase. This change was strongly associated with the observed reduction in glycosylation levels. Functional enrichment analysis further revealed that glycosylation-related genes were primarily involved in immune pathways, including antigen processing and presentation, cytokine signaling, and immune activation.</p><p><strong>Conclusions: </strong>Single-cell glycosylation analysis provides crucial insights into immune cell interactions in cirrhosis. Targeting glycosylation pathways in macrophages may offer new treatment strategies for cirrhosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"607-620"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066198","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}
引用次数: 0
Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer. 氧化亚铁纳米颗粒-二乙基二硫代氨基甲酸酯在胰腺癌共球体3D模型中的治疗作用
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-01 Epub Date: 2025-01-31 DOI: 10.1007/s00535-025-02213-3
Marwa M Abu-Serie, Ana K Gutiérrez-García, Macie Enman, Utpreksha Vaish, Huma Fatima, Vikas Dudeja
{"title":"Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer.","authors":"Marwa M Abu-Serie, Ana K Gutiérrez-García, Macie Enman, Utpreksha Vaish, Huma Fatima, Vikas Dudeja","doi":"10.1007/s00535-025-02213-3","DOIUrl":"10.1007/s00535-025-02213-3","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and exhibits a limited response to apoptosis-dependent chemotherapeutic drugs (e.g., gemcitabine, Gem). This is mainly attributed to the antioxidant defense system (glutathione and aldehyde dehydrogenase (ALDH) 1A1), which sustains stemness features of cancer stem cells (CSCs) and activated pancreatic stellate cells (PSCs)-generated excess stromal proteins. This dense stroma retards drug delivery.</p><p><strong>Methods: </strong>This study established co-spheroid model consisting of mouse PDAC cell line (KPC) and PSCs (1:5) to accurately investigate the anti-PDAC activity of nanocomplex of ferrous oxide nanoparticles-diethyldithiocarbamate (FeO NPs-DE), compared to Gem, using in vitro and in vivo 3D models.</p><p><strong>Results: </strong>In vitro and in vivo co-spheroid models demonstrated higher therapeutic efficacy of FeO NPs-DE than Gem. FeO NPs-DE induced selective accumulation of iron-dependent ferroptosis (non-apoptosis)-generated a lethal lipid peroxidation that was potentiated by DE-mediated glutathione and ALDH1A1 suppression. This led to collapse of stemness, as evidenced by down-regulating CSC genes and p-AKT protein expression. Subsequently, gene and/or protein levels of PSC activators (transforming growth factor (TGF)-β, plasminogen activator inhibitor-1, ZEB1, and phosphorylated extracellular signal-regulated kinase) and stromal proteins (collagen 1A2, smooth muscle actin, fibronectin, and matrix metalloproteinase-9) were suppressed. Moreover, DE of nanocomplex enhanced caspase 3-dependent apoptosis with diminishing the main oncogene, BCL-2.</p><p><strong>Conclusions: </strong>FeO NPs-DE had a stronger eradicating effect than Gem on primary and metastatic peritoneal PDAC tumors. This nanocomplex-mediated ferroptosis and stemness inhibition provides an effective therapeutic approach for PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"641-657"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066157","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}
引用次数: 0
Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn's disease activity in the small bowel. 血清富亮氨酸α -2糖蛋白对小肠克罗恩病活动性的诊断准确性和临界值
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-01 Epub Date: 2025-02-14 DOI: 10.1007/s00535-025-02223-1
Muneyori Okita, Kento Takenaka, Fumihito Hirai, Shinya Ashizuka, Hideki Iijima, Shigeki Bamba, Toshimitsu Fujii, Kenji Watanabe, Yosuke Shimodaira, Hisashi Shiga, Sakiko Hiraoka, Toshihiro Inokuchi, Takeshi Yamamura, Ryo Emoto, Shigeyuki Matsui
{"title":"Diagnostic accuracy and cut-off values of serum leucine-rich alpha-2 glycoprotein for Crohn's disease activity in the small bowel.","authors":"Muneyori Okita, Kento Takenaka, Fumihito Hirai, Shinya Ashizuka, Hideki Iijima, Shigeki Bamba, Toshimitsu Fujii, Kenji Watanabe, Yosuke Shimodaira, Hisashi Shiga, Sakiko Hiraoka, Toshihiro Inokuchi, Takeshi Yamamura, Ryo Emoto, Shigeyuki Matsui","doi":"10.1007/s00535-025-02223-1","DOIUrl":"10.1007/s00535-025-02223-1","url":null,"abstract":"<p><strong>Background: </strong>Small bowel (SB) lesions in Crohn's disease (CD) are often asymptomatic despite being highly active. Fecal calprotectin (FC) is the most widely used biomarker of CD activity, but its drawbacks include a large intra-individual sample variability and the burden of collecting stool samples. Meanwhile, serum leucine-rich alpha-2 glycoprotein (LRG) has recently attracted attention as a biomarker that can address the limitations of FC. This study determined the diagnostic accuracy of LRG and its cut-off values for diagnosing CD activity in SB.</p><p><strong>Methods: </strong>This was a retrospective, multi-center study of CD patients undergoing retrograde balloon-assisted endoscopy. For ileal- and ileocolonic-type patients with a colon SES-CD score of 0, we estimated the receiver operating characteristic curve of LRG and determined the cut-off value to achieve a target sensitivity level of 80%.</p><p><strong>Results: </strong>Among 285 patients with SB lesions, LRG had an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78) with a sensitivity of 80.2% and specificity of 47.2% for a cut-off value of 10.5 when diagnosing endoscopic remission (modified SES-CD ≤ 3), while it had an AUC of 0.72 (95% CI 0.65-0.78) with a sensitivity of 81.2% and specificity of 46.2% for a cut-off value of 10.1 when diagnosing complete ulcer healing (modified SES-CD ≤ 1).</p><p><strong>Conclusion: </strong>LRG was effective for diagnosing CD activity in SB, specifically with cut-off values of 10.5 and 10.1 for endoscopic remission and complete ulcer healing, respectively. A future prospective validation study will assess its clinical utility.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"573-582"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425461","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}
引用次数: 0
Persistent body-weight change on achalasia and peroral endoscopic myotomy: a multicenter cohort study. 贲门失弛缓症和经口内窥镜肌切开术的持续体重变化:一项多中心队列研究。
IF 6.9 2区 医学
Journal of Gastroenterology Pub Date : 2025-05-01 Epub Date: 2024-12-31 DOI: 10.1007/s00535-024-02205-9
Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Takuya Satomi, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue
{"title":"Persistent body-weight change on achalasia and peroral endoscopic myotomy: a multicenter cohort study.","authors":"Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Takuya Satomi, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue","doi":"10.1007/s00535-024-02205-9","DOIUrl":"10.1007/s00535-024-02205-9","url":null,"abstract":"<p><strong>Background: </strong>The distribution of body weight in patients with achalasia and after peroral endoscopic myotomy (POEM) has not been investigated. The role of body weight assessment after treatment remains unclear.</p><p><strong>Methods: </strong>Using the multicenter achalasia cohort, the frequency of underweight (body mass index [BMI] < 18.5 kg/m<sup>2</sup>) and overweight (BMI ≥ 25.0 kg/m<sup>2</sup>) and their associated clinical characteristics were analyzed. After POEM, risk factors for insufficient- (underweight persistently) and excessive- (responded to overweight) weight gainers were investigated. The correlation between BMI-increase rate and severity of esophageal symptoms post-POEM was evaluated.</p><p><strong>Results: </strong>Among 3,410 patients, 23.0% and 15.7% were underweight and overweight, respectively. Factors associated with underweight were higher age, female sex, severe symptoms, high lower esophageal sphincter (LES) pressure, and non-dilated esophagus (all p < 0.01). Longitudinal analyses revealed that weight gain post-POEM was achieved after a long duration (≥ 12 months; p < 0.01). In 528 patients post-POEM, the frequency of underweight reduced to 8.3% (p < 0.01). Risk factors for insufficient-weight gain (36.1% of underweight patients) included low BMI (p < 0.01) and high LES pressure (p = 0.03) and conversely for excessive-weight gain. Machine learning models based on patient characteristics successfully predicted insufficient- and excessive-weight gainers with an area under the curve value of 0.74 and 0.75, respectively. Esophageal symptoms post-POEM did not correlate with BMI increase.</p><p><strong>Conclusion: </strong>Underweight is not solely a condition of advanced achalasia. After POEM, insufficient- or excessive-weight gainers are not rare and can be predicted preoperatively. Body weight change is an independent nutrition parameter rather than a part of the assessment of residual esophageal symptoms.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"535-545"},"PeriodicalIF":6.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909770","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}
引用次数: 0
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