Journal of Clinical and Translational Hepatology最新文献

{"title":"SCARF2 Mediates Intracellular Trafficking and Nucleocapsid Release of Hepatitis B Virus Within Hepatocytes.","authors":"Si-Yuan Chen, Fu-Sheng Wang","doi":"10.14218/JCTH.2026.00467","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00467","url":null,"abstract":"","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"992-994"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmatine Induces TNNT1 Ubiquitination and Degradation to Potentiate Ferroptosis Sensitivity in Hepatocellular Carcinoma.","authors":"Xiaokang Wang, Fanci Xie, Chunhua Wang, Shangjun Zhou, Jiayu Wang, Zhijie Xu, Zhiyang Zhou","doi":"10.14218/JCTH.2026.00215","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00215","url":null,"abstract":"<p><strong>Background and aims: </strong>Ferroptosis, an iron-dependent form of regulated cell death, serves as an important mechanism associated with cancer progression. Natural compounds, particularly alkaloids, have emerged as attractive candidates for regulating ferroptotic cell death, thereby providing a promising anticancer strategy. However, the molecular mechanisms underlying their antitumor effects remain poorly understood. In this study, we aimed to investigate the antitumor effects and underlying mechanisms of natural alkaloids against hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>An alkaloid library was used to screen alkaloids with anti-HCC activity. A combination of proteomic profiling, <i>in vitro</i> functional assays, and <i>in vivo</i> animal experiments was performed to explore the biological roles and molecular mechanisms of the lead compound.</p><p><strong>Results: </strong>Through high-throughput screening of an alkaloid library, we identified palmatine (PAL), an active component isolated from <i>Fibraurea recisa</i> Pierre, as a potential ferroptosis sensitizer in HCC cells. PAL treatment triggered typical ferroptotic features in HCC cells, including elevated ferrous iron, reactive oxygen species, and lipid peroxidation, along with decreased glutathione levels. Importantly, the pro-ferroptotic effect of PAL was significantly abolished by two ferroptosis inhibitors, ferrostatin-1 and deferoxamine. Mechanistically, PAL directly interacted with troponin T1 (TNNT1) to trigger its K48-linked polyubiquitination and subsequent protein degradation. Ectopic TNNT1 overexpression significantly rescued PAL-mediated ferroptosis and abrogated its tumor-suppressive effects. <i>In vivo</i> animal models further confirmed that PAL suppressed tumor growth by downregulating TNNT1, with a favorable safety profile.</p><p><strong>Conclusions: </strong>This study reveals a previously unrecognized role of PAL as a ferroptosis sensitizer and highlights its translational potential for anti-HCC therapy.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"937-948"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporting Completeness of Biliary Atresia Organoid Studies: A Scoping Review and Structured Audit.","authors":"Guantong Li, Dayan Sun, Dingding Wang, Shuangshuang Li, Kaiyun Hua, Yichao Gu, Yanan Zhang, Yong Zhao, Junmin Liao, Jinshi Huang","doi":"10.14218/JCTH.2026.00352","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00352","url":null,"abstract":"<p><strong>Background and aims: </strong>Biliary atresia (BA) is the leading cause of pediatric obstructive cholestasis and a major indication for liver transplantation in infants. Organoid models are increasingly used to investigate BA pathogenesis and therapeutic responses, but incomplete methodological and clinical reporting may limit cross-study comparison and translational interpretation. This study aimed to map the landscape of BA-related organoid research, identify major reporting gaps, and propose the Biliary Atresia Minimum Reporting Standard (BA-MRS) as a preliminary framework for improving reporting completeness.</p><p><strong>Methods: </strong>PubMed, Scopus, and Web of Science Core Collection were searched on March 8, 2026, in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) and the 2024 Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. Reporting completeness was assessed using a 36-item BA-MRS across six domains, scored as fully reported, partially reported, not reported, or not applicable.</p><p><strong>Results: </strong>Twenty-six studies published between 2020 and 2026 were included. Fibrosis and epithelial-mesenchymal transition were the most frequently studied themes, whereas only one study linked organoid findings to post-Kasai outcomes. BA case/model definition, ethics approval, and differentiation protocols were fully reported in all applicable studies (100%). In contrast, contamination monitoring (3.8%), core biliary function assays (34.6%), and clinical outcome linkage (26.3%) were poorly reported. Culture System and Sample Acquisition showed the lowest domain-level fully reported rates (58.1% and 63.2%, respectively).</p><p><strong>Conclusions: </strong>BA organoid research has progressed beyond early model development, but reporting remains insufficient for robust comparison, reproducibility, and clinically meaningful interpretation. BA-MRS may serve as a preliminary framework for improving standardized reporting in future studies.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"960-976"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Frequency of Circulating IL-4R⁺SELL⁺ Naïve B Cells Is Associated with Functional Cure in Chronic Hepatitis B Patients Receiving Antiviral Treatment.","authors":"Lili Tang, Chunmei Bao, Cheng Zhen, Huan Wang, Chao Zhang, Yang Zhang, Honghong Liu, Jinwen Song, Yanmei Jiao, Tao Yang, Yue Yuan, Jinhong Yuan, Yingying Gao, Yangliu Chen, Lin Cao, Jing Li, Jun-Liang Fu, Fu-Sheng Wang, Ruonan Xu","doi":"10.14218/JCTH.2026.00356","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00356","url":null,"abstract":"<p><strong>Background and aims: </strong>Although hepatitis B surface antigen (HBsAg)-specific B cells have been partially characterized in chronic hepatitis B (CHB), the role of naïve B cells and their potential relevance to functional cure remain insufficiently explored. Here, we aimed to characterize the naïve B-cell subsets in functionally cured and uncured patients with CHB.</p><p><strong>Methods: </strong>In this retrospective study, we applied single-cell RNA sequencing to compare peripheral B-cell profiles in functionally cured and uncured CHB patients. Key findings were validated by flow cytometry in an independent cohort and further supported in a nucleos(t)ide analog monotherapy cohort stratified by HBsAg levels.</p><p><strong>Results: </strong>Single-cell RNA sequencing characterized two naïve B-cell subsets, designated IL-4R⁺SELL⁺ and IL-4R^-SELL^- naïve B cells, which were differentially distributed between functionally cured and uncured patients. Functionally cured patients showed higher frequencies of total B cells and IL-4R⁺SELL⁺ naïve B cells than uncured patients. In contrast, functionally uncured patients exhibited persistent hyperactivation of type I interferon signaling in both naïve and memory B cells. The IL-4R⁺SELL⁺ subset showed a transcriptional signature associated with germinal center biology and exhibited stronger ligand-receptor interactions with CD40LG⁺CD4⁺ T cells. Notably, the frequency of the IL-4R⁺SELL⁺ subset was inversely correlated with HBsAg levels. Consistently, patients with lower HBsAg levels also exhibited significantly higher frequencies of IL-4R⁺SELL⁺ naïve B cells compared with those with high HBsAg levels.</p><p><strong>Conclusions: </strong>Collectively, these findings indicate that the IL-4R⁺SELL⁺ naïve B-cell subset is characterized by germinal center-related responses and enhanced T-cell-mediated help and may serve as an immunological component associated with functional cure in CHB.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"883-895"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CYB5R3-mARC1 Redox Axis in Metabolic Dysfunction-associated Steatotic Liver Disease: Mechanistic Basis and Therapeutic Prospects across the Steatosis-Cirrhosis-Hepatocellular Carcinoma Spectrum.","authors":"Soon Woo Nam","doi":"10.14218/JCTH.2026.00482","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00482","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease affects roughly 38% of adults, yet approved agents do not correct the upstream redox-metabolic perturbations-a depressed nicotinamide adenine dinucleotide (NAD⁺/NADH) ratio, saturated lipid excess, and endoplasmic reticulum (ER) stress-that drive hepatocyte injury. Cytochrome b5 reductase 3 (CYB5R3) couples NADH oxidation to fatty acid desaturation, nuclear factor erythroid 2-related factor 2 (NRF2)-linked antioxidant and cholesterol-handling pathways, NAD⁺/sirtuin signaling, and ER-phagy, and is the sole electron input to mitochondrial amidoxime-reducing component 1 (mARC1). This review grades every link in the axis across the steatosis-cirrhosis-hepatocellular carcinoma spectrum, reporting effect estimates with sample sizes and test statistics alongside a study-level appraisal of clinical relevance. The common MTARC1 p.A165T variant protects against all-cause cirrhosis (odds ratio, 0.91; 95% CI, 0.89-0.94; <i>P</i> = 2.3 × 10^-11; 12,361 cases, 790,095 controls), with lower hepatic fat, liver enzyme levels, and low-density lipoprotein cholesterol levels. Germline mARC1 deletion reduces picrosirius red fibrosis area by 24%-50% depending on diet, without altering histological disease activity, whereas partial protein reduction confers no protection. Critically, therapeutic hepatocyte-directed knockdown loses its anti-fibrotic effect when started at higher disease burden and in the choline-deficient model: efficacy depends on the depth, compartment, and timing of inhibition. Deep, hepatocyte-restricted mARC1 inhibition by GalNAc-conjugated oligonucleotides-which also avoids a male-predominant cardiac liability-is therefore the most credible near-term strategy, only in pre-cirrhotic F2-F3 disease. CYB5R3 activation, and its combination with mARC1 inhibition, remain unproven, and no clinical trial of this axis has been reported. Falsifiable <i>in vivo</i> and pharmacodynamic biomarker roadmaps are proposed, together with the efficacy, delivery, and safety uncertainties specific to advanced cirrhosis and a non-invasive pharmacodynamic framework.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"977-991"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological Evolution of Pyrrolizidine Alkaloid-induced Liver Injury: Transition From SOS to PSVD?","authors":"Si Zhao, Feng Zhang, Yao Liu, Shuyan Zeng, Han Zhang, Jingjing Tu, Hui Xu, Qin Yin, Wei Zhang, Bing Xu, Jiangqiang Xiao, Lei Wang, Juan Carlos García-Pagán, Jun Chen, Yuzheng Zhuge","doi":"10.14218/JCTH.2026.00077","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00077","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatic sinusoidal obstruction syndrome (SOS) is characterized by hepatic sinusoidal endothelial cell injury and detachment, hepatic sinusoidal congestion, and hepatic cell necrosis. Currently, limited data exist concerning changes during the recovery period, especially histopathological changes. The purpose of this study was to investigate the evolution of pathology in patients with pyrrolizidine alkaloid (PA)-induced SOS and in a monocrotaline-induced SOS rat model.</p><p><strong>Methods: </strong>Patients diagnosed with PA-induced SOS who underwent liver biopsy after achieving clinical remission were consecutively enrolled in this retrospective study. To compare the clinical and pathological differences between patients with acute and convalescent SOS, a 2:1 matched analysis was performed based on age, sex, treatment regimen, and baseline Drum Tower Severity Scoring (DTSS) during the acute phase. Additionally, an animal model of PA-induced SOS was established through the administration of monocrotaline.</p><p><strong>Results: </strong>Fourteen consecutive patients with SOS who had adequate liver biopsy specimens obtained during recovery were identified. During convalescence, most laboratory and imaging findings, such as the map-like enhancement observed on computed tomography, also disappeared. However, histopathological analysis revealed a distinct shift from hepatic sinusoidal endothelial cell injury in the acute phase to portal tract abnormalities, primarily characterized by portal vein stricture, in the recovery phase. These pathological changes were corroborated in our animal model.</p><p><strong>Conclusions: </strong>Our study suggests that both patients with PA-induced SOS and rats in the convalescent stage may exhibit porto-sinusoidal vascular disease-like changes. Regular follow-up and dynamic pathological assessment are therefore recommended to facilitate the early detection of potential signs of portal hypertension.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"925-936"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics-based Decoding of Metabolic Dysfunction-associated Fatty Liver Disease: From Pathogenesis to Clinical Translation.","authors":"Jinyang Zhai, Yan Lu, Jian-Gao Fan","doi":"10.14218/JCTH.2026.00153","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00153","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multifactorial disorder driven by complex interactions among genetic, epigenetic, transcriptional, proteomic, metabolic, and microbiome factors. Single-omics technologies have provided valuable insights into disease mechanisms, yet each layer captures only a partial view of MAFLD pathogenesis. Recent advances in multi-omics integration allow systematic dissection of molecular networks, cell differentiation trajectories, intercellular communication, and spatial organization, revealing causal links between molecular alterations and tissue phenotypes. Horizontal integration connects different omic layers within the same biological state, while longitudinal integration captures dynamic changes across disease stages. Emerging spatial transcriptomics, proteomics, and metabolomics techniques further enable in situ mapping of cellular and molecular heterogeneity, uncovering spatially defined pathogenic niches and regulatory hubs. Collectively, these integrated approaches offer a multidimensional framework for understanding MAFLD progression, identifying potential biomarkers, and guiding precision therapeutic strategies. Future efforts should focus on standardized multi-omics pipelines, interdisciplinary collaboration, and functional validation to translate these insights into clinical applications.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"949-959"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA Sequencing Analysis Reveals That Targeting PLG-PLGRKT Signaling-mediated Pro-fibrotic Scar-associated Macrophages Ameliorates Liver Fibrosis in Biliary Atresia.","authors":"Xin Li, Tengfei Li, Shaowen Liu, Qianhui Yang, Yuqiang Chen, Yu Meng, Xiaodan Xu, Yilin Zhao, Yanran Zhang, Jiaying Liu, Rongjuan Sun, Alimujiang Abudureyimu","doi":"10.14218/JCTH.2026.00278","DOIUrl":"https://doi.org/10.14218/JCTH.2026.00278","url":null,"abstract":"<p><strong>Background and aims: </strong>Biliary atresia (BA) is a severe pediatric cholangiopathy characterized by rapidly progressive liver fibrosis. This study aimed to characterize scar-associated macrophages and investigate the role of plasminogen (PLG)-plasminogen receptor with a C-terminal lysine (PLGRKT) signaling in BA-associated fibrogenesis.</p><p><strong>Methods: </strong>Single-cell RNA sequencing and spatial transcriptomics were applied to liver tissues from patients with BA and non-BA controls. Key findings were validated in an independent cohort using quantitative polymerase chain reaction and multiplex immunohistochemistry. The functional role of the PLGRKT pathway was further examined using primary human peripheral blood mononuclear cell-derived macrophages with small interfering RNA (siRNA)-mediated PLGRKT knockdown, together with co-culture systems involving LX-2 hepatic stellate cells and human liver organoids. <i>In vivo</i> therapeutic potential was evaluated in a murine bile duct ligation model of cholestatic liver fibrosis using macrophage-targeted <i>Plgrkt</i>-Trem2 antibody-siRNA conjugates.</p><p><strong>Results: </strong>In BA, scar-associated macrophages (SAMs) increased with fibrosis progression and co-localized with hepatic stellate cells in fibrotic areas. PLGRKT was upregulated in BA liver tissue and increased during monocyte-to-macrophage differentiation. In primary human macrophages, PLG induced a PLGRKT-dependent pro-fibrotic phenotype, and conditioned medium from these cells increased COL1A1 deposition in hepatic stellate cells and human liver organoids. <i>In vivo</i>, macrophage-targeted <i>Plgrkt</i>-Trem2 antibody-siRNA conjugates reduced SAM accumulation and attenuated bile duct ligation-induced liver fibrosis.</p><p><strong>Conclusions: </strong>These findings support a role for SAMs and the PLGRKT-SAM axis in BA-associated liver fibrosis and suggest that PLGRKT warrants further investigation as a potential macrophage-directed anti-fibrotic target.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"912-924"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Cytometry Reveals Cell Type-specific Immune Remodeling in Placentas of Women with Chronic Hepatitis B Infection.","authors":"Zirong Yang, Li Qi, Yang Bai, Weiwei Zhou, Wenjing Wang, Yunxia Zhu, Junfeng Lu","doi":"10.14218/JCTH.2026.00429","DOIUrl":"10.14218/JCTH.2026.00429","url":null,"abstract":"<p><strong>Background and aims: </strong>Hepatitis B virus (HBV) vertical transmission remains a major health challenge, and the characteristics of the placental immune microenvironment in chronic infection remain unclear. This study aimed to use mass cytometry to comprehensively analyze phenotypic changes in placental immune cell subsets.</p><p><strong>Methods: </strong>We collected placental tissues from 20 pregnant women (6 healthy controls and 14 with chronic HBV infection). CD45⁺ leukocytes were detected using a 35-marker antibody panel. Unsupervised clustering identified 14 clusters, of which 13 immune clusters were analyzed.</p><p><strong>Results: </strong>HBV mainly caused functional remodeling of placental immune cells rather than changes in cell composition (<i>P</i> > 0.05 for all subsets). In natural killer (NK) cells, CD38 (<i>P</i> = 0.015) and CD16 (<i>P</i> = 0.0020) were notably upregulated and strongly correlated (ρ = 0.872, <i>P</i> < 0.001), suggesting potentially enhanced antibody-dependent cellular cytotoxicity (ADCC) function. T cells showed upregulation of CD27, CD38, and CXCR5. Basophils exhibited the most pronounced changes: 9 differential markers (including chemokine receptors CCR4 and CCR7) were consistently downregulated. Classical monocytes showed an M1 polarization tendency (CD38↑, CD163↓). All <i>P</i>-values were raw; no markers remained significant after false discovery rate (FDR) correction at an FDR threshold of < 0.1, indicating nominal significance. In addition, the coordinated expression patterns of markers within multiple cell subsets were weakened after infection.</p><p><strong>Conclusions: </strong>These exploratory findings suggest that HBV may reshape placental immunity through enhanced NK cell activation, broad basophil suppression, and disrupted marker coordination. The sample size was limited (n = 20), so the results need to be validated in larger cohorts. These findings provide new perspectives for understanding the mechanisms of mother-to-child transmission.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 9","pages":"896-911"},"PeriodicalIF":6.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Multi-omics and Machine Learning Reveal the Therapeutic Mechanisms of Juanyu-Xiaozhi Formula in Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatic Fibrosis via the AP-1/PPARγ/SCD1 Axis.","authors":"Zhiqiang Jin, Yi Huang, Cheng Zeng, Yueting Zhang, Yu Qiu, Yang Yang, Huabao Liu","doi":"10.14218/JCTH.2026.00106","DOIUrl":"10.14218/JCTH.2026.00106","url":null,"abstract":"<p><strong>Background and aims: </strong>Despite the surging global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and related liver fibrosis, effective treatments remain limited. While the traditional Chinese medicine Juanyu-Xiaozhi Formula (JYXZF) is used against MASLD, its bioactive components and mechanisms are poorly understood. This study aimed to investigate the therapeutic effects of JYXZF and elucidate its underlying mechanisms of action.</p><p><strong>Methods: </strong>The constituents of JYXZF were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Its efficacy was evaluated in a rat model of metabolic dysfunction-associated steatohepatitis (MASH) induced by a high-fat/calorie diet with high-fructose/high-glucose water, utilizing serum biochemistry, histology, and glucose/insulin tolerance tests. Mechanistic validation was performed in free fatty acid-treated human hepatocellular carcinoma cell line HepG2 (HepG2) cells and HepG2/human hepatic stellate cell line LX-2 (LX-2) co-culture models using luciferase assays, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR), and activator protein 1 (AP-1) overexpression rescue experiments. The functional relevance of stearoyl-CoA desaturase 1 (SCD1) was further assessed <i>in vivo</i> through liver-targeted adeno-associated virus (AAV)-mediated <i>Scd1</i> overexpression.</p><p><strong>Results: </strong>Flavonoids were identified as the main bioactive constituents. JYXZF administration alleviated metabolic dysfunction, reduced hepatic lipid accumulation, and attenuated inflammation and fibrosis in MASH rats. Multi-omics integration and machine learning-assisted target prioritization identified lipid metabolic and inflammatory pathways. Among these pathways, we selected the AP-1/peroxisome proliferator-activated receptor gamma (PPARγ)/SCD1-related lipogenic pathway for functional validation. Target perturbation experiments supported the functional involvement of AP-1 in the regulation of the PPARγ/SCD1 pathway and its contribution to the anti-steatotic effects of JYXZF.</p><p><strong>Conclusions: </strong>JYXZF alleviates MASLD-associated steatosis and fibrosis via the AP-1/PPARγ/SCD1-related lipogenic axis, demonstrating its therapeutic potential for MASLD/MASH and providing a mechanistic basis for future clinical applications.</p>","PeriodicalId":15484,"journal":{"name":"Journal of Clinical and Translational Hepatology","volume":"14 8","pages":"824-841"},"PeriodicalIF":6.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}