Hepatology Communications最新文献

{"title":"Multiple cell-type interactions drive invariant NKT cell hepatitis.","authors":"Jiaxin Tan, Longshan Ji, Qian Li, Ruowen Guo, Yawen Hao, Peng Xiao, Qiuhong Zai, Xuewei Zhang, Yating Gao, Xin Zhang, Miao Fang, Yanhang Gao, Weidong Zhao, Yong He, Yueqiu Gao, Man Li","doi":"10.1097/HC9.0000000000000592","DOIUrl":"10.1097/HC9.0000000000000592","url":null,"abstract":"<p><strong>Background: </strong>α-Galactosylceramide (α-Galcer), a specific ligand for invariant natural killer T (NKT) cell activation, has been actively investigated in clinical trials such as antitumor therapy; however, treatment with α-Galcer is well known to induce acute hepatitis due to enriched NKT cells in the liver. The molecular mechanisms underlying NKT-mediated hepatitis still remain obscure. The object of this study was to investigate whether and how myeloid cells affect NKT-mediated hepatitis.</p><p><strong>Methods: </strong>α-Galcer-induced NKT hepatitis was used in this study. microRNA-223 (miR-223) and neutrophil cytosolic factor 1 (Ncf1)-deficent mice were generated and subjected to α-Galcer-induced NKT hepatitis.</p><p><strong>Results: </strong>In this study, we demonstrated that α-Galcer-induced NKT cell activation resulted in neutrophil and monocyte-derived macrophage accumulation in the liver. Importantly, serum levels of several hepatic myeloid cell infiltration-related cytokines and chemokines were significantly elevated after α-Galcer administration. Among these myeloid cells, blockade of neutrophil or macrophage migration through using different inhibitors of (C-X-C Motif) receptor 2, (C-C motif) receptor 2, and (C-C motif) receptor 5 signaling ameliorated α-Galcer-induced liver injury, mainly due to the decrease of reactive oxygen species production and inflammation. Depletion of neutrophils reduced α-Galcer-induced liver injury and hepatitis. Interestingly, genetic deletion of neutrophil-specific miR-223 markedly enhanced while Ncf1 deficiency significantly ameliorated liver inflammation and oxidative damage caused by α-Galcer.</p><p><strong>Conclusions: </strong>Neutrophil and macrophage infiltration through multiple inflammatory mediators is required for NKT cell activation-induced hepatitis, which sheds light on the myeloid cell infiltration-related molecular mechanisms of NKT cell-mediated liver injury. Our study may provide a novel therapeutical strategy for the treatment of NKT cell hepatitis.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRMT1-mediated modification of H4R3me2a promotes liver cancer progression by enhancing the transcriptional activity of SOX18.","authors":"Jing Ling, Siying Wang, Chenhe Yi, Xingling Zheng, Yangyang Zhou, Shunjia Lou, Haoyu Li, Ruobing Yu, Wei Wu, Qiangxin Wu, Xiaoxiao Sun, Yuanyuan Lv, Huijue Zhu, Qi Li, Haojie Jin, Jinhong Chen, Jiaojiao Zheng, Wenxin Qin","doi":"10.1097/HC9.0000000000000647","DOIUrl":"10.1097/HC9.0000000000000647","url":null,"abstract":"<p><strong>Background: </strong>HCC is one of the most prevalent and deadliest malignancies worldwide, with a poor prognosis. Altered histone modifications have been shown to play a significant role in HCC. However, the biological roles and clinical relevance of specific histone modifications, such as the asymmetric dimethylation on arginine 3 of histone H4 (H4R3me2a), remain poorly understood in HCC.</p><p><strong>Methods: </strong>In this study, immunohistochemical staining was performed to assess histone H4R3me2a modification in 32 pairs of HCC tissues and corresponding adjacent nontumor liver tissues. Cellular-level experiments and subcutaneous xenograft models in nude mice were used to investigate the effects of silencing protein arginine methyltransferase 1 (PRMT1) with shRNA or pharmacologically blocking PRMT1 activity on HCC cell proliferation, migration, and invasion. RNA-seq analysis combined with Chip-qPCR validation was employed to explore the regulatory mechanism of PRMT1 on SOX18 expression. The downstream target of SOX18 was identified using the JASPAR database and a dual-luciferase reporter system.</p><p><strong>Results: </strong>The level of histone H4R3me2a modification was significantly elevated in HCC tissues and closely associated with poor prognosis in patients with HCC. Silencing PRMT1 or pharmacologically inhibiting its activity effectively suppressed the proliferation, migration, and invasion of HCC cells. Mechanistically, PRMT1 was found to regulate SOX18 expression by modulating histone H4R3me2a modification in the SOX18 promoter region. LOXL1 was identified as a downstream target of the transcription factor SOX18.</p><p><strong>Conclusions: </strong>This study revealed the clinical relevance of histone H4R3me2a modification in HCC and demonstrated that PRMT1 promotes malignant behavior in HCC cells by modulating H4R3me2a modification in the SOX18 promoter region. The findings elucidate the role and molecular mechanism of PRMT1-mediated histone H4R3me2a modification in HCC progression and highlight the potential clinical applications of PRMT1 inhibitors. These results may provide new insights into the treatment of HCC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Pervasive role of pruritus in impaired quality of life in patients with primary biliary cholangitis: Data from the GLIMMER study.","authors":"Helen T Smith, Sugato Das, James Fettiplace, Robyn von Maltzahn, Philip J F Troke, Megan M McLaughlin, David E Jones, Andreas E Kremer","doi":"10.1097/HC9.0000000000000698","DOIUrl":"10.1097/HC9.0000000000000698","url":null,"abstract":"","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in radiation therapy for HCC: Integration with liver-directed treatments.","authors":"Orly Yariv, Neil B Newman, Mark Yarchoan, Atoosa Rabiee, Bradford J Wood, Riad Salem, Jonathan M Hernandez, Christine K Bang, Ted K Yanagihara, Freddy E Escorcia","doi":"10.1097/HC9.0000000000000653","DOIUrl":"10.1097/HC9.0000000000000653","url":null,"abstract":"<p><p>HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based criteria for identifying at-risk individuals requiring liver disease screening.","authors":"Fredrik Åberg, Ville Männistö, Juho Asteljoki, Veikko Salomaa, Antti Jula, Annamari Lundqvist, Satu Männistö, Markus Perola, Panu K Luukkonen","doi":"10.1097/HC9.0000000000000679","DOIUrl":"10.1097/HC9.0000000000000679","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis screening is recommended in at-risk groups, but a clear definition of \"at risk\" for entry criteria is lacking. We analyzed different combinations of established risk factors to define specific screening entry criteria with a prespecified sensitivity requirement.</p><p><strong>Methods: </strong>Data regarding individuals aged 40-70 years from Finnish health-examination surveys (FINRISK 2002-2012 and Health 2000, n=15,057) and the UK Biobank (n=454,990) were linked with healthcare registries for liver cirrhosis-related events (LREs; liver-related hospitalizations, cancer, or death). The predictive performance of 1919 combinations of risk factors, including alcohol consumption, metabolic disturbances, abnormal liver function tests, and Chronic Liver Disease risk score, was assessed for 10-year LRE risk requiring a minimum 90% sensitivity. Validations were performed using liver stiffness measurement (LSM) >12 kPa in the NHANES 2017-2020 sample (n=3367).</p><p><strong>Results: </strong>Optimal entry criteria for predicting 10-year LRE risk with >90% sensitivity included any one of: hazardous alcohol use, severe obesity, metabolic syndrome, an AST-to-ALT ratio >0.8 with elevated ALT, and an intermediate-to-high Chronic Liver Disease risk score. The sensitivity and specificity for this strategy were 91% and 51% for LREs, respectively, in the Finnish cohort, and 91% and 41% for LSM >12 kPa in the US sample. In the US sample, applying these entry criteria followed by fibrosis-4 ≥1.3 for predicting LSM >12 kPa reduced the sensitivity to 45% (specificity: 85%), which was attributed to the suboptimal sensitivity of fibrosis-4.</p><p><strong>Conclusions: </strong>This study identifies an inexpensive risk factor-based strategy with >90% sensitivity for predicting LRE and LSM >12 kPa, which is practical and scalable for targeted liver fibrosis screening to improve population outcomes. However, a more sensitive first-line noninvasive fibrosis test is needed.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannose reduces fructose metabolism and reverses MASH in human liver slices and murine models in vivo.","authors":"John G Hong, Joshaya Trotman, Yvette Carbajal, Poulomi Dey, Mariel Glass, Victoria Sclar, Isaac L Alter, Peng Zhang, Liheng Wang, Li Chen, Mathieu Petitjean, Dipankar Bhattacharya, Shuang Wang, Scott L Friedman, Charles DeRossi, Jaime Chu","doi":"10.1097/HC9.0000000000000671","DOIUrl":"10.1097/HC9.0000000000000671","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis drives liver-related mortality in metabolic dysfunction-associated steatohepatitis (MASH), yet we have limited medical therapies to target MASH-fibrosis progression. Here we report that mannose, a simple sugar, attenuates MASH steatosis and fibrosis in 2 robust murine models and human liver slices.</p><p><strong>Methods: </strong>The well-validated fat-and-tumor MASH murine model for liver steatosis and fibrosis was employed. Mannose was supplied in the drinking water at the start (\"Prevention\" group) or at week 6 of the 12-week MASH regimen (\"Therapy\" group). The in vivo antifibrotic effects of mannose supplementation were tested in a second model of carbon tetrachloride (CCl4)-induced liver fibrosis. A quantitative and automated digital pathology approach was used to comprehensively assess steatosis and fibrosis phenotypes. Mannose was also tested in vitro in human and primary mouse hepatocytes conditioned with free fatty acids alone or with fructose, and human precision-cut liver slices from patients with end-stage MASH cirrhosis.</p><p><strong>Results: </strong>Oral mannose supplementation improved liver fibrosis in vivo in both fat-and-tumor MASH and CCl4 mouse models, as well as in human precision-cut liver slice MASH samples. Mannose also reduced liver steatosis in fat-and-tumor MASH mice, and in human and mouse hepatocytes in vitro. Ketohexokinase, the main enzyme in fructolysis, was decreased with mannose in whole mouse liver, cultured hepatocytes, and human precision-cut liver slices. Removal of fructose or overexpression of ketohexokinase each abrogated the antisteatotic effects of mannose.</p><p><strong>Conclusions: </strong>This study identifies mannose as a novel therapeutic candidate for MASH that mitigates steatosis by dampening hepatocyte ketohexokinase expression and exerts independent antifibrotic effects in 2 mouse models and human liver tissue slices.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperbilirubinemia at hospitalization predicts nosocomial infection in decompensated cirrhosis: Data from ATTIRE trial.","authors":"Harriett Fuller, Thais H Tittanegro, Alexander A Maini, Louise China, Freya Rhodes, Natalia Becares Salles, Subhankar Mukhopadhyay, Bernadette Moore, Alastair O'Brien","doi":"10.1097/HC9.0000000000000648","DOIUrl":"10.1097/HC9.0000000000000648","url":null,"abstract":"<p><strong>Background: </strong>To identify clinical characteristics and serological biomarkers that predicted subsequent nosocomial infection in ATTIRE trial patients.</p><p><strong>Methods: </strong>We identified 360 patients at hospitalization without infection and not prescribed antibiotics and compared clinical characteristics between those who subsequently developed a nosocomial infection and not. In a 68-patient subcohort, we compared plasma biomarkers of bacterial translocation, infection, and inflammation at hospitalization between those who developed a nosocomial infection and not. In a 56-patient subcohort, we investigated plasma lipidomic profiles in those who did and did not develop nosocomial infection using Lipotype Shotgun platform analysis and multivariate statistical techniques. To further investigate lipid pathways, we compared outcomes in patients taking statins or not at hospitalization.</p><p><strong>Results: </strong>Serum bilirubin >188 µmol/L at hospitalization predicted subsequent nosocomial infection in univariate and multivariate analyses, with 80% specificity. The most common nosocomial infections were respiratory tract (29%) and those developing infection had significantly greater 28 and 90-day mortality than those not (p=9.34E-05 and 0.014). Serological biomarkers of bacterial translocation, infection, and inflammation did not predict subsequent infection. Partial least squares discriminatory analyses identified cholesterol esters (CEs) (CE.18.1.2, CE.18.1.0, and CE.16.0.0) as important predictors of infection but provided only a small improvement in predictive ability over bilirubin alone. RNA-sequencing analyses suggest this is mediated by a downregulation of the cellular cholesterol esterification enzyme sterol O-acyltransferase 1. Statin use was not associated with nosocomial infection prevention.</p><p><strong>Conclusions: </strong>In ATTIRE, elevated serum bilirubin at hospitalization was the only clinical characteristic that predicted subsequent development of nosocomial infection. Considering the rising incidence of antimicrobial resistance, these data could be used to limit antibiotic prophylaxis or aid trial design for investigating use in high-risk patients.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EBV enhances immunotherapy sensitivity in intrahepatic cholangiocarcinoma through cGAS-STING pathway activation.","authors":"Lingli Huang, Qian Zhong, Silan Huang, Kejia Yang, Yuchen Cai, Guifang Guo","doi":"10.1097/HC9.0000000000000674","DOIUrl":"10.1097/HC9.0000000000000674","url":null,"abstract":"<p><strong>Background: </strong>The absence of representative Epstein-Barr virus-associated intrahepatic cholangiocarcinoma (EBVaICC) cell lines has limited our understanding of the molecular and immunological characteristics of this cancer subtype.</p><p><strong>Methods: </strong>We reviewed patients with metastatic cholangiocarcinoma at Sun Yat-sen University Cancer Center from January 2015 to August 2023. Among them, 22 patients with EBVaICC and 66 patients with non-EBVaICC who received anti-PD1 treatment were included. Additionally, 2 EBV-positive ICC cell lines, RBE-EBV and HuH28-EBV, were developed through cell-to-cell infection. Stable EBV infection and responsiveness to viral reactivation were confirmed. Transcriptomic and bioinformatics analyses were performed, and in vitro experiments examined the immune effects of EBV-positive ICC. Key immune-related genes and cytokines were validated by reverse transcription quantitative polymerase chain reaction and ELISA in cell lines and patient plasma samples.</p><p><strong>Results: </strong>In this study, we found that patients with EBVaICC showed enhanced immune responses and improved overall and progression-free survival compared to patients with non-EBVaICC. We first successfully established and validated 2 EBV-positive ICC cell lines (RBE-EBV and HuH28-EBV). These cell lines were confirmed for stable EBV infection and displayed responsiveness to viral reactivation, making them suitable for future studies. Transcriptomic analyses and in vitro studies revealed that EBV activated the cGAS-STING pathway, resulting in MHC-I upregulation and CXCL10 secretion in ICC cells, which collectively enhanced CD8+ T cell chemotaxis and cytotoxicity. Furthermore, ELISA analysis showed higher plasma levels of CXCL10 and IFN-γ in patients with EBVaICC, suggesting a potential role for EBV in enhancing immunotherapy sensitivity in this subtype.</p><p><strong>Conclusions: </strong>The established EBV-positive ICC cell lines revealed enhanced immunogenicity driven by cGAS-STING pathway activation, providing valuable models for future research and insights into the mechanisms of improved immunotherapy sensitivity in EBVaICC.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amphisome plays a role in HBV production and release through the endosomal and autophagic pathways.","authors":"Jia Li, Thekla Kemper, Ruth Broering, Yong Lin, Xueyu Wang, Mengji Lu","doi":"10.1097/HC9.0000000000000654","DOIUrl":"10.1097/HC9.0000000000000654","url":null,"abstract":"<p><strong>Background: </strong>Autophagic and endosomal pathways coordinately contribute to HBV virions and subviral particles (SVPs) production. To date, limited evidence supports that HBV and exosomes have a common pathway for their biogenesis and secretion. The final steps of HBV production and release have not yet been well studied.</p><p><strong>Methods: </strong>We examined the production and release of HBV virions and SVPs by using GW4869 (N,N'-Bis[4-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3,3'-pht hal amide dihydrochloride), a small molecule inhibiting ceramide-mediated inward membrane budding. Neutral sphingomyelinase, the target of GW4869, and RAB27A and -B,  2 small GTPases involved in exosome release control, were silenced using gene silencing to confirm the results obtained. Western blot, immunofluorescence staining, and confocal microscopy were applied.</p><p><strong>Results: </strong>GW4869 inhibited HBV virion release, causing their accumulation along with SVPs in hepatocytes. This triggered cellular endoplasmic reticulum stress, leading to protein kinase B-mechanistic target of rapamycin kinase signaling pathway inactivation. GW4869 treatment increased autophagosome formation and impaired autophagic degradation by blocking autophagosome-lysosome fusion. Consequently, HBsAg is increasingly localized to autophagosomes and late endosomes/multivesicular bodies. Silencing neutral sphingomyelinase yielded consistent results. Similarly, RAB27A silencing inhibited HBV virion and SVP secretion, causing their accumulation within hepatoma cells. Notably, GW4869 treatment, as well as RAB27A and -B silencing, increased the presence of LC3+CD63+HBsAg+ complexes.</p><p><strong>Conclusions: </strong>Our results demonstrate the involvement of the autophagosome-late endosome/multivesicular bodies-exosome axis in regulating HBV production and release, highlighting amphisomes as a potential platform for HBV release.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 4","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second harmonic generation microscopy reveals the spatial orientation of glutamine-potentiated liver regeneration after hepatectomy.","authors":"Chih-Chieh Yen, Chia-Sheng Yen, Hung-Wen Tsai, Matthew M Yeh, Tse-Ming Hong, Wen-Lung Wang, I-Ting Liu, Yan-Shen Shan, Chia-Jui Yen","doi":"10.1097/HC9.0000000000000640","DOIUrl":"10.1097/HC9.0000000000000640","url":null,"abstract":"<p><strong>Background: </strong>Glutamine (Gln) is a critical amino acid for energy expenditure. It participates in extracellular matrix (ECM) formation and circulates in the hepatic parenchyma in a spatial-oriented manner. Posthepatectomy liver mass recovery poses a regenerative challenge. However, little is known about the role of Gln in liver regeneration, notably the spatial orientation in the remodeling process. This study aimed to elucidate Gln-potentiated liver regeneration and ECM remodeling after mass loss.</p><p><strong>Methods: </strong>We studied the regenerative process in hepatectomized mice supplemented with Gln. Second harmonic generation/two-photon excitation fluorescence microscopy, an artificial intelligence-assisted structure-based imaging, was used to demonstrate the spatial-oriented process in a hepatic acinus.</p><p><strong>Results: </strong>Gln promotes liver mass regrowth through the cell cycle, Gln metabolism, and adipogenesis pathways after hepatectomy. Ornithine transaminase, one of the upregulated enzymes, showed temporal, spatial, and functional correspondence with the regeneration process. Second harmonic generation/two-photon excitation fluorescence microscopy highlighted transient hepatic steatosis and ECM collagen synthesis, predominantly in the portal tract instead of the central vein area. Structural remodeling was also observed in the portal tract area.</p><p><strong>Conclusions: </strong>Gln promotes liver regeneration through cellular proliferation and metabolic reprogramming after hepatectomy. Using structure-based imaging, we found that Gln potentiated hepatic steatosis and ECM collagen deposition predominantly in the portal tract area. These results highlighted the spatial orientation and mechanistic implications of Gln in liver regeneration.</p>","PeriodicalId":12978,"journal":{"name":"Hepatology Communications","volume":"9 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572842","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}