Liver Research最新文献

{"title":"Role of myeloid cell transcription factor EB in alcohol-induced liver injury in mice","authors":"Sha Neisha Williams ,&nbsp;Kafayat Yusuf ,&nbsp;Xiaojuan Chao ,&nbsp;Hong-Min Ni ,&nbsp;Wen-Xing Ding","doi":"10.1016/j.livres.2026.01.003","DOIUrl":"10.1016/j.livres.2026.01.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide, with no currently effective treatment. ALD is caused by excessive lipid buildup, which eventually triggers inflammation and fibrosis in the liver. Activation of hepatic Kupffer cells (KCs) and macrophages drives liver inflammation, which can worsen alcohol-induced liver injury. The autophagy-lysosome system is crucial for macrophages to support their innate immune functions. Transcription factor EB (TFEB) is a key regulator of autophagy and lysosomal biogenesis, but the role of macrophage TFEB in ALD development is unknown. The aim of this study was to evaluate the effects of Gao-binge alcohol consumption on myeloid cell TFEB and elucidate the role of myeloid TFEB in ALD.</div></div><div><h3>Methods</h3><div>Two-to-three-month-old male and female LysM Cre⁻ (WT) and LysM Cre⁺ <em>Tfeb</em> ^{Flox/Flox (f/f)} (myeloid-<em>Tfeb</em> KO) mice were subjected to chronic alcohol feeding plus an acute binge following the Gao-binge model. Serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol content were determined using biochemical assays. Total hepatic protein content and messenger RNA (mRNA) levels of autophagy-related proteins and inflammatory markers were determined using immunoblotting, immunohistochemistry, and real-time quantitative polymerase chain reaction (RT-qPCR). Isolated hepatic infiltrating macrophages and KCs from mice given intragastric ethanol infusions were analyzed by Western blot for TFEB and autophagy-related protein content. Raw 264.7 macrophages were treated with ethanol, lipopolysaccharide (LPS), and LPS plus ethanol to examine nuclear TFEB translocation using immunofluorescence.</div></div><div><h3>Results</h3><div>We found that TFEB levels were higher in macrophage/KC cells than in hepatocytes and cholangiocytes. While ethanol feeding increased serum alanine aminotransferase and aspartate aminotransferase levels, as well as hepatic triglyceride levels, no significant differences were observed between WT and myeloid-<em>Tfeb</em> KO mice. The number of F4/80-positive KCs/macrophages was similar in all four experimental groups, but hepatic neutrophil infiltration increased in alcohol-fed myeloid-<em>Tfeb</em> KO mice. LPS or ethanol alone induced nuclear TFEB translocation only moderately in Raw 264.7 macrophages.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that myeloid TFEB is dispensable for alcohol-induced liver injury in mice.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 71-81"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile acid signaling, metabolism, and aging","authors":"Ji Sun ,&nbsp;Shili Zhang ,&nbsp;Lihua Jin ,&nbsp;Wendong Huang","doi":"10.1016/j.livres.2026.02.002","DOIUrl":"10.1016/j.livres.2026.02.002","url":null,"abstract":"<div><div>Bile acids (BAs) serve not only as key facilitators of lipid absorption but also as crucial signaling molecules regulating glucose and lipid metabolism, inflammation, and overall energy homeostasis. Aging profoundly alters BA metabolism, characterized by shifts in biosynthetic pathways, compositional changes, disrupted receptor-mediated signaling, and alterations in gut microbiota interactions. These age-related changes contribute to the onset and progression of metabolic conditions, including type 2 diabetes, obesity, metabolic dysfunction-associated fatty liver disease, and neurodegenerative disorders. An increased abundance of hydrophobic and cytotoxic BAs has been associated with systemic inflammation, metabolic rigidity (disruption of metabolic flexibility), and organ dysfunction. Targeting BA signaling—through pharmacological modulation of farnesoid X receptor and Takeda G protein-coupled receptor 5 or microbiota-directed therapies—offers promising strategies to mitigate aging-related metabolic decline. A deeper understanding of how BA metabolism evolves over the lifespan may unveil novel interventions to promote healthy aging and prevent age-related disease.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 1-9"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening the advantageous population for liver cancer undergoing yttrium-90 microsphere selective internal radiation therapy","authors":"Licong Liang ,&nbsp;Yuchan Liang ,&nbsp;Wensou Huang ,&nbsp;Yongjian Guo ,&nbsp;Jingjun Huang ,&nbsp;Jingwen Zhou ,&nbsp;Liteng Lin ,&nbsp;Xinxin Nie ,&nbsp;Mingyue Cai ,&nbsp;Kangshun Zhu","doi":"10.1016/j.livres.2025.12.002","DOIUrl":"10.1016/j.livres.2025.12.002","url":null,"abstract":"<div><div>Yttrium-90 microsphere selective internal radiation therapy (SIRT), also known as transarterial radioembolization, has become one of the pivotal treatments for liver cancer, particularly for selected advantageous patient groups. This review summarizes the characteristics of different patients with liver cancer that could obtain maximum benefit from SIRT and discusses key factors affecting efficacy and safety, including tumor characteristics, liver function, patient performance status, and treatment intent. In evaluating appropriate candidates, mapping serves as a crucial simulation procedure to assess tumor vascular anatomy, predict lung shunting, and guide catheter positioning and dose planning. This procedure substantially enhances therapeutic precision while minimizing the risk of nontarget radiation-related adverse events, such as radiation-induced pneumonitis and gastrointestinal toxicity. Several studies have suggested that SIRT is not only suitable for patients with early or limited hepatocellular carcinoma but can also be used as a bridging therapy for liver transplantation and conversion therapy for unresectable liver cancers. In combination with systemic treatments, SIRT has demonstrated survival benefits in patients with unresectable liver cancer. This review also highlights the importance of further optimizing patient screening through personalized dosimetry and mapping to ensure the precision and safety of treatment. A thorough review of relevant literature and clinical practice offers clinicians comprehensive suggestions on patient screening and clarifies the promise of SIRT in the liver cancer population.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 61-70"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinic acid protects against hepatic ischemia-reperfusion injury via suppressing mitochondrial damage-induced ferroptosis","authors":"Qian Zeng ,&nbsp;Yina Sun ,&nbsp;Mengzhen Lei ,&nbsp;Zihan Liu ,&nbsp;Xijing Yan ,&nbsp;Rong Li ,&nbsp;Jun Zheng ,&nbsp;Jiandong Zha ,&nbsp;Lijun Zhang ,&nbsp;Xiaoling Guan ,&nbsp;Jia Yao","doi":"10.1016/j.livres.2025.11.001","DOIUrl":"10.1016/j.livres.2025.11.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hepatic ischemia-reperfusion injury (HIRI) is a major contributor to liver dysfunction and failure, particularly in the context of liver transplantation. Its pathogenesis is primarily driven by ferroptosis, oxidative stress, and mitochondrial dysfunction. Given the interplay among these mechanisms through redox imbalance and disrupted energy metabolism, nicotinic acid (NA)—recognized for its antioxidative and metabolic regulatory properties—emerges as a promising therapeutic candidate. This study aims to investigate the protective effects of NA on HIRI and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>An HIRI model in mice and a hypoxia/reoxygenation (H/R) model in primary hepatocytes were established to evaluate the effects of NA treatment on oxidative stress. NA was administered prior to model induction. <em>N</em>-acetylcysteine (NAC) was used as a comparator. Comprehensive assessments of ferroptosis, oxidative stress, mitophagy, and mitochondrial biogenesis markers were conducted using Western blotting, immunohistochemistry, immunofluorescence, and biochemical assays.</div></div><div><h3>Results</h3><div>NA pretreatment reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (LDH) levels, suppressed inflammation by decreasing neutrophil infiltration and macrophage activation, and mitigated oxidative stress by lowering reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It enhanced antioxidant defenses, inhibited ferroptosis, and improved mitochondrial health through increased mitophagy, mitochondrial biogenesis, and mitochondrial permeability transition pore (mPTP) stabilization, leading to enhanced ATP production and mitochondrial function in HIRI.</div></div><div><h3>Conclusions</h3><div>NA improves mitochondrial function by promoting mitophagy and mitochondrial biogenesis, which reduces ferroptosis and oxidative stress, thereby alleviating HIRI.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Pages 324-337"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of miRNA-26a-encapsulated nanoparticles against hepatocellular carcinoma in a murine model","authors":"Marwa Hassan ,&nbsp;Inés Fernández-Piñeiro ,&nbsp;Iker Badiola ,&nbsp;Mohamed Elzallat ,&nbsp;Alejandro Sánchez ,&nbsp;Tarek Aboushousha ,&nbsp;Ehab Hafiz ,&nbsp;Eman El-Ahwany","doi":"10.1016/j.livres.2025.10.002","DOIUrl":"10.1016/j.livres.2025.10.002","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hepatocellular carcinoma (HCC) treatment options are limited due to the lack of effective curative therapies, and conventional chemotherapy has often demonstrated limited effectiveness and may be associated with significant toxicity. Therefore, innovative therapeutics for HCC are urgently needed. Here, we aimed to evaluate the effectiveness of microRNA (miRNA)-26a-encapsulated nanoparticles in HCC treatment.</div></div><div><h3>Methods</h3><div>Span-Oleylamine-chondroitin sulfate were prepared and eighty male BALB/c mice were divided into four groups: (i) negative control group (saline injection), (ii) HCC group (intraperitoneal injection of diethylnitrosamine (DEN), at 50 mg/kg/week for 18 weeks), (iii) miRNA-26a-treated HCC group (intrahepatical injection of 100 nmol free miRNA-26a once weekly for four weeks), and (iv) miRNA-26a-loaded nanoparticles-treated HCC group (intrahepatic injection of miRNA-26a-loaded nanoparticles once weekly for 4 weeks, starting from Week 14 of DEN induction). Then, all mice were subjected to biochemical, genetic, histopathological, and immunohistochemical examinations.</div></div><div><h3>Results</h3><div>The HCC group showed elevated serum levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha), along with upregulated hepatic expression of <em>P70S6K</em>, <em>transforming growth factor-beta</em>, <em>DNA methyltransferase 3 beta</em> (<em>DNMT3b</em>), and <em>Caspase-3</em> genes, as well as HepPar 1, Ki67, cyclin D1, and arginase 1 proteins (all <em>P</em> &lt; 0.001). miRNA-26a treatment attenuated these changes; moreover, the miRNA-26a-encapsulated nanoparticles caused a more dramatic decrease of these markers, resulting in almost complete restoration of the normal hepatic architecture.</div></div><div><h3>Conclusions</h3><div>Administration of miRNA-26a-encapsulated nanoparticles induced nearly total regression of HCC, suppression of cancer cell growth and angiogenesis, and induction of tumor necrosis. This study demonstrates the therapeutic efficacy of restoring the imbalanced expression of miRNA in the liver. Therefore, the clinical translation of this miRNA-based strategy warrants further investigation.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Pages 338-350"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in hepatic enzymes and transporters involved in pharmacokinetics","authors":"Mehak Behal,&nbsp;Zachary McCalla,&nbsp;Xinwen Wang","doi":"10.1016/j.livres.2025.10.003","DOIUrl":"10.1016/j.livres.2025.10.003","url":null,"abstract":"<div><div>Females experience adverse drug reactions at approximately twice the rate of males, contributing to drug-related morbidity and mortality in the United States. This disparity has been strongly associated with sex-based differences in pharmacokinetics. Hepatic drug-metabolizing enzymes and transporters, key regulators of pharmacokinetics, exhibit notable sex-based differences in expression and/or activity. However, findings on the sex-specific impacts of these enzymes and transporters are often scattered, highlighting the need for a comprehensive and up-to-date overview of knowledge in this area. This review compiles and analyzes existing data on sex differences in the expression and activity of clinically relevant hepatic drug-metabolizing enzymes and transporters across species, such as cytochrome P450s, UDP-glucuronosyltransferase, carboxylesterases, P-glycoprotein, breast cancer resistance protein, multidrug resistance-associated protein, organic anion-transporting polypeptides and organic cation transporters. It also summarizes how these differences influence clinical pharmacokinetics, adverse drug reactions, and drug dosing regimens. Furthermore, we explore potential underlying mechanisms, including the influence of sex hormones, sex chromosomes and lifestyle-related factors. Lastly, we discuss clinical implications and future directions in the field, highlighting the urgent need for more human-centered research to clarify the sex-specific impact on drug metabolism and transport in human. Such effort will support the development of sex-informed pharmacotherapy strategies that ultimately reduce adverse drug reactions and improve therapeutic outcomes for patients.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Pages 253-272"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal liver dynamics: How far can we take them in vitro?","authors":"Hanyang Liu","doi":"10.1016/j.livres.2025.11.002","DOIUrl":"10.1016/j.livres.2025.11.002","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Pages 359-361"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolites involvement in the growth and spread of liver cancer","authors":"Anurag Kumar Gautam ,&nbsp;Vipin Kumar ,&nbsp;Archana Bharti Sonkar ,&nbsp;Amita Singh ,&nbsp;Deepankar Yadav ,&nbsp;Nitin Rajan ,&nbsp;Pranesh Kumar ,&nbsp;Sanjay Singh ,&nbsp;Sudipta Saha ,&nbsp;Vijayakumar Mahalingam Rajamanickam","doi":"10.1016/j.livres.2025.10.005","DOIUrl":"10.1016/j.livres.2025.10.005","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a leading cause of cancer-related mortality worldwide, primarily attributed to changing lifestyles and dietary habits. HCC arises from liver cirrhosis, hepatic fibrosis, or hepatitis B virus infection, and is caused by disruptions in protein and lipid metabolism. These metabolic alterations, recognized as a hallmark of cancer, are pivotal in the progression of chronic liver disease to HCC. Due to its asymptomatic nature in early stages, HCC is often diagnosed at advanced stages when treatment options are limited. Despite being a potentially curative option, liver transplantation remains hindered by high costs and donor scarcity, further compounded by suboptimal long-term success rates. This review examines the critical metabolites that play a part in developing HCC, focusing on their roles as possible biomarkers for disease progression and therapeutic targets. Additionally, the influence of the gut microbiome on HCC development is discussed, highlighting its interplay with metabolic pathways. Understanding the roles of metabolites and the gut microbiome in HCC progression underscores the importance of their potential use in early detection and the development of targeted therapies, offering new avenues for improving patient outcomes.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Pages 286-297"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resmetirom and beyond: A new era in MASLD therapeutics","authors":"Tejona Johnson-Moore,&nbsp;Dasia Simmons,&nbsp;Alvina Okafor,&nbsp;D'Era Washington,&nbsp;Padmamalini Baskaran","doi":"10.1016/j.livres.2025.10.004","DOIUrl":"10.1016/j.livres.2025.10.004","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Pages 362-364"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function” [Liver Res. 5 (2021) 171–180]","authors":"Mohammad Mehdi Ommati ,&nbsp;Hamidreza Mohammadi ,&nbsp;Khadijeh Mousavi ,&nbsp;Negar Azarpira ,&nbsp;Omid Farshad ,&nbsp;Reyhaneh Dehghani ,&nbsp;Asma Najibi ,&nbsp;Sedigheh Kamran ,&nbsp;Hossein Niknahad ,&nbsp;Reza Heidari","doi":"10.1016/j.livres.2025.12.001","DOIUrl":"10.1016/j.livres.2025.12.001","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 4","pages":"Page 365"},"PeriodicalIF":2.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145802090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}