Clinical and Molecular Hepatology最新文献

{"title":"Impaired fungal surveillance with Kennedy pathway activation drives acute liver failure, validated in preclinical models.","authors":"Neha Sharma, Sushmita Pandey, Shvetank Sharma, Shiv Kumar Sarin, Jaswinder Singh Maras","doi":"10.3350/cmh.2025.0970","DOIUrl":"https://doi.org/10.3350/cmh.2025.0970","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the ASB3-CPT1A axis-a new player in combating metabolic dysfunction-associated steatotic liver disease.","authors":"Yueying Yang, Ying Yang, Yan Lu","doi":"10.3350/cmh.2025.1013","DOIUrl":"https://doi.org/10.3350/cmh.2025.1013","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAB25/GCN1 Signaling Promotes ER Stress to Mediate Alcohol-associated Liver Disease Progression.","authors":"Xue-Wen Liu, Zi-Bin Zhan, Ze-Hua Li, Yue Zhang, Xue-Yan Qiao, Xin-Ming Li, Xiang-Jing Liang, Kun-Hao Bai, Xian-Feng Xia, Fan-Hong Zeng, Yi Gao, Jun Weng","doi":"10.3350/cmh.2025.0559","DOIUrl":"https://doi.org/10.3350/cmh.2025.0559","url":null,"abstract":"<p><strong>Background/aims: </strong>Endoplasmic reticulum (ER) stress in hepatocytes plays a causative role in alcohol-associated liver disease (ALD). The incomplete inhibition of ER stress by targeting canonical ER stress sensor proteins suggests the existence of noncanonical ER stress pathways in ALD pathology. This study aimed to delineate the role of RAB25 in ALD and its regulatory mechanism in noncanonical ER stress pathways.</p><p><strong>Methods: </strong>RAB25 activation was examined in liver samples from ALD patients and ethanol-fed mice. The interaction between RAB25 and GCN1 was confirmed through mass spectrometry and co-immunoprecipitation (Co-IP) assays in vitro. The role of RAB25/GCN1 in promoting noncanonical ER stress in ALD was assessed both in vitro and in vivo.</p><p><strong>Results: </strong>RAB25 expression was upregulated and specifically accumulated on the endoplasmic reticulum in ALD. Mass spectrometry and Co-IP assays confirmed that RAB25 interacts with GCN1, thereby activating a noncanonical ER stress pathway that facilitates ALD progression. Further analysis revealed that RAB25 interaction with GCN1 inhibits K33-ubiquitination-mediated degradation of GCN1, promotes GCN2 phosphorylation, and subsequently activates ATF4-mediated ER stress. This activation modulates lipid metabolism, mitochondrial function, and inflammation, thereby facilitating ALD progression. Knockdown of RAB25 in hepatocytes inhibited ER stress activation and mitigated associated mitochondrial dysfunction, excessive lipid synthesis, and the exaggerated inflammatory response in an ALD model.</p><p><strong>Conclusions: </strong>Our findings demonstrate a causal role for RAB25-GCN1 signaling in activating the ER stress pathway, which contributes to ALD progression. This pathway may provide a proof-of-concept target for treating ALD and associated metabolic disorders.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence to editorial on \"Dysfunction in CD8+ T Cells in Early-Stage HCC\" by Qin et al.: New Insights into HCC Immunotherapy.","authors":"Yang Kong, Xiaoqian Shen, Kun Xue, Haiying Wang","doi":"10.3350/cmh.2025.0880","DOIUrl":"https://doi.org/10.3350/cmh.2025.0880","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of bile acid composition with synthetic pathways and efficacy of bezafibrate in cholestatic liver disease.","authors":"Manami Iida, Atsuko Higashida, Shuichi Ohtomo, Akihito Takeuchi, Ryo Miura, Yoshinari Asaoka, Naoshi Horiba, Akira Honda, Atsushi Tanaka","doi":"10.3350/cmh.2025.0575","DOIUrl":"https://doi.org/10.3350/cmh.2025.0575","url":null,"abstract":"<p><strong>Background & aims: </strong>Bezafibrate (BZF), a dual peroxisome proliferator-activated receptor/pregnane X receptor agonist, has demonstrated efficacy in combination with ursodeoxycholic acid (UDCA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Although one of the therapeutic effects of BZF is suppression of bile acid synthesis, its specific impact on bile acid synthesis pathways has not been thoroughly explored. This study investigated bile acid profiles, synthesis intermediates, and their associations with liver biochemistries in patients with PBC and PSC, and evaluated the impact of BZF treatment on these associations.</p><p><strong>Methods: </strong>We enrolled 30 patients with PBC, 10 with PSC, and 30 control subjects. We measured total bile acids, bile acid components, plasma levels of 7α-hydroxycholesterol (7α-OH-C), 7α-hydroxy-4-cholesten-3-one (C4), and 27-hydroxycholesterol (27-OH-C) to assess the classic and alternative bile acid synthesis pathways and analyzed the association with liver biochemistries with and without BZF treatment.</p><p><strong>Results: </strong>Total bile acid levels were elevated in PBC and PSC compared to controls, correlating significantly with liver biochemistries. BZF treatment significantly suppressed the classic pathway, as evidenced by reduced 7α-OH-C and C4 levels. However, 27-OH-C levels, possibly reflecting the alternative pathway activity, were not reduced in those with elevated liver biochemistries despite BZF treatment, suggesting incomplete suppression of alternative pathway in patients with suboptimal BZF response.</p><p><strong>Conclusions: </strong>These findings indicate that while BZF effectively suppresses the classic pathway, alternative pathway activity may compromise its therapeutic efficacy in treatment-resistant cases, highlighting the need for novel therapies inhibiting the alternative pathway in patients with inadequate response to BZF.</p>","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Letter on \"Sex-Specific Trends and Demographic vs Epidemiologic Drivers of Alcohol-Related Cirrhosis in the U.S., 2021-2040\".","authors":"Pojsakorn Danpanichkul, Luis Antonio Diaz, Juan Pablo Arab, Amit G Singal, Ju Dong Yang","doi":"10.3350/cmh.2025.0948","DOIUrl":"https://doi.org/10.3350/cmh.2025.0948","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Correspondence to \"Call for Preemptive Treatment of Cytomegalovirus in Patients with Cirrhosis and Acute Decompensation\".","authors":"Norihiro Imai","doi":"10.3350/cmh.2025.0963","DOIUrl":"https://doi.org/10.3350/cmh.2025.0963","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SAFE Score in Chronic Liver Diseases: A Tool for Risk Enrichment and Personalized Surveillance.","authors":"Tung-Hung Su, Jia-Horng Kao","doi":"10.3350/cmh.2025.0940","DOIUrl":"https://doi.org/10.3350/cmh.2025.0940","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence to the letter titled \"Beyond Diagnostic Accuracy: Economic and Clinical Considerations for NC-MRI in Late HCC Recurrence Surveillance\".","authors":"Dong Ho Lee","doi":"10.3350/cmh.2025.0945","DOIUrl":"https://doi.org/10.3350/cmh.2025.0945","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An editorial on \"Human cytomegalovirus reactivation in cirrhosis patients with acute decompensation\" by Hong et al. Title: Human cytomegalovirus reactivation in decompensated cirrhosis: marker of immunosuppression or contributor to severity?","authors":"Zhujun Cao, Richard Moreau","doi":"10.3350/cmh.2025.0962","DOIUrl":"https://doi.org/10.3350/cmh.2025.0962","url":null,"abstract":"","PeriodicalId":10275,"journal":{"name":"Clinical and Molecular Hepatology","volume":" ","pages":""},"PeriodicalIF":16.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}