Liver Research最新文献

{"title":"Silencing progestagen-associated endometrial protein (PAEP) suppresses sorafenib resistance and enhances sorafenib-induced ferroptosis in hepatocellular carcinoma","authors":"Fanlin Zeng ,&nbsp;Cuifu Fang ,&nbsp;Yijiang Wu ,&nbsp;Ling Yin ,&nbsp;Yilong Ge ,&nbsp;Honghui Zhang ,&nbsp;Caixin Song ,&nbsp;Yifeng Cai ,&nbsp;Binhui Xie ,&nbsp;Jian Wu","doi":"10.1016/j.livres.2025.09.003","DOIUrl":"10.1016/j.livres.2025.09.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>As a ferroptosis inducer, sorafenib, a first-line treatment for hepatocellular carcinoma (HCC), has a significant antitumor effect. Nonetheless, HCC patients frequently develop sorafenib resistance. Here, we investigated the impacts of progestagen-associated endometrial protein (PAEP), which controls sorafenib resistance and tumorigenesis in HCC. Furthermore, we investigated the function of PAEP and the underlying molecular mechanisms that cause HCC ferroptosis when sorafenib is applied.</div></div><div><h3>Methods</h3><div>Western blot analysis, cell proliferation, colony formation and animal experiments were performed to investigate the function of PAEP in sorafenib resistance and tumorigenesis in HCC. We detected the levels of reactive oxygen species, iron, and malondialdehyde and preformed transmission electron microscopy to investigate the relationship between PAEP and ferroptosis. Co-immunoprecipitation (co-IP) assay was performed to investigate the underlying molecular mechanisms of PAEP that cause HCC ferroptosis.</div></div><div><h3>Results</h3><div>PAEP was significantly overexpressed in HCC tissues, and this was associated with a poor clinical prognosis. PAEP silencing dramatically reduced HCC cells’ malignant phenotype. We found that sorafenib-induced ferroptosis was more sensitive to HCC cells with PAEP knockdown. Furthermore, the orthotopic cell line-derived xenograft mouse model results showed that sorafenib sensitivity can be effectively increased <em>in vivo</em> by PAEP knockdown. We determined that transferrin (TF) was a PAEP target using the String database, and we further supported this finding with Co-IP analysis. Additionally, on sorafenib-induced ferroptosis in HCC cells, TF partially reversed the effects of PAEP knockdown.</div></div><div><h3>Conclusions</h3><div>Our research indicates that PAEP may be a potential biomarker for predicting sorafenib resistance in HCC and disruption of PAEP expression may be a potential cancer-directed therapeutic option for HCC.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 82-92"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147330791","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":"The role of bile acid dynamics in inflammatory bowel disease and metabolic dysfunction-associated steatotic liver disease","authors":"Si-Rui Yu ,&nbsp;Run Sun ,&nbsp;Mei-Ya Shi ,&nbsp;Mei Yang ,&nbsp;Kun Chen ,&nbsp;Qiong Pan ,&nbsp;Ling Zhao ,&nbsp;Ming-Yue Wu ,&nbsp;Jin Chai","doi":"10.1016/j.livres.2026.02.001","DOIUrl":"10.1016/j.livres.2026.02.001","url":null,"abstract":"<div><div>The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 35-50"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557095","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":"Preclinical mouse models for studying cholangiocarcinoma","authors":"Shanru Yang ,&nbsp;Chaodi Bao ,&nbsp;Yuan Li ,&nbsp;Yangxiang Ou ,&nbsp;Yifan Jiang ,&nbsp;Wenjie Xu ,&nbsp;Dongfang Zheng ,&nbsp;Na Li ,&nbsp;Mengjie Yang ,&nbsp;Fuyan Wang ,&nbsp;Xin Hou","doi":"10.1016/j.livres.2026.01.002","DOIUrl":"10.1016/j.livres.2026.01.002","url":null,"abstract":"<div><div>Cholangiocarcinoma (CCA) is a malignancy characterized by tumor cells originating in the liver or bile ducts, exhibiting features of cholangiocyte differentiation. It poses a significant clinical challenge due to the limited diagnostic and therapeutic options available. Robust animal models are essential for advancing our understanding of CCA pathogenesis and developing effective treatments. This review provides a comprehensive overview of CCA mouse models, highlighting various approaches, including chemical induction, genetically engineered models, and tumor xenografts. Each model is discussed in terms of its establishment techniques, pathological characteristics, and research significance, with a focus on intrahepatic CCA. Chemical induction models, such as diethylnitrosamine- and azoxymethane-induced models, offer insights into tumorigenesis processes, whereas genetically modified models involving alterations in key genes such as Kirsten rat sarcoma viral oncogene homolog, tumor protein 53, and isocitrate dehydrogenase serve as important tools for studying the molecular mechanisms underlying CCA. Xenograft models, including patient-derived xenografts, bridge the gap between experimental research and clinical applications, allowing for precise therapeutic evaluations. By comparing these models, this review underscores their respective advantages and limitations, paving the way for future studies aiming to optimize and innovate CCA modeling strategies.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 22-34"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557094","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":"Progress of transgenic pigs in liver xenotransplantation","authors":"Xing-Ming Xie ,&nbsp;Guo-Ying Wang","doi":"10.1016/j.livres.2026.02.004","DOIUrl":"10.1016/j.livres.2026.02.004","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 93-94"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557091","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":"Autophagy-mediated Kupffer cell polarization in liver cirrhosis reversal: Mechanistic insights and therapeutic strategies","authors":"Debjeet Sur ,&nbsp;Gargi Banik","doi":"10.1016/j.livres.2026.01.001","DOIUrl":"10.1016/j.livres.2026.01.001","url":null,"abstract":"<div><div>Liver cirrhosis, an advanced end-stage liver disease characterized by extensive hepatic fibrosis, is a leading cause of mortality and morbidity worldwide. Despite its prevalence, there is no specific treatment to prevent fibrosis progression, with liver transplantation remaining the only definitive option for patients with advanced cirrhotic liver disease. The activation of hepatic stellate cells (HSCs) by proinflammatory M1-type Kupffer cells (KCs) is a key driver of fibrosis. Activated HSCs further exacerbate fibrosis by recruiting bone marrow-derived macrophages (BMDMs) through chemokine signaling, which induces alpha-smooth muscle actin (alpha-SMA) expression. Autophagy, a cellular process responsible for degrading damaged organelles and protein aggregates, is vital for maintaining liver physiology and metabolic balance. It also plays a significant role in the pathogenesis of fibrosis. Compounds that promote KC autophagy can polarize KCs toward an anti-inflammatory M2 phenotype, disrupting signaling pathways that activate HSCs and recruit BMDMs to injured liver tissue. This approach has been identified as a promising therapeutic strategy to combat liver fibrosis. This review highlights various strategies to activate KC autophagy and modulate KC polarization, offering insights into novel therapeutic targets for treating liver fibrosis and preventing cirrhosis progression.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 51-60"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557096","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":"Hepatocyte-like cell therapy for end-stage liver disease: From basic science to clinical application","authors":"Wenwen Ge ,&nbsp;Zhoucheng Wang ,&nbsp;Yutong Chen ,&nbsp;Xiao Tang ,&nbsp;Zijian Lou ,&nbsp;Jun Chen ,&nbsp;Xiao Xu ,&nbsp;Kai Wang","doi":"10.1016/j.livres.2026.01.005","DOIUrl":"10.1016/j.livres.2026.01.005","url":null,"abstract":"<div><div>End-stage liver disease (ESLD) covers the end-stage of acute and chronic liver diseases, mainly involving decompensated cirrhosis, various types of liver failure, and advanced liver cancer. Hepatocyte transplantation has shown promise in treating ESLD, but its clinical application is hampered by the shortage of donor hepatocytes. Cell therapy, an emerging effective treatment for ESLD, faces the same limitation due to scarce hepatocyte availability. Hepatocyte-like cells (HLCs), which are terminally differentiated cells, can be induced from both stem cells and somatic cells. As HLCs exhibit the morphology and function of primary hepatocytes, they offer a promising supplementary source of hepatocytes for cell therapy. First, we provide a background for the differentiation and maturation of primary hepatocytes. Subsequently, based on the current insights into the molecular pathways that regulate hepatocyte differentiation <em>in vivo</em>, we describe a strategy for establishing HLC derived from either stem cells or somatic cells. The key characteristics of these HLCs are also detailed. Furthermore, HLC offers therapeutic potential for liver failure, and HLC-based liver organoids and bioartificial liver systems have demonstrated the ability to provide liver functions, offering an innovative approach to treating various types of ESLD. Despite their promise, challenges such as efficiency in differentiation and functional maturation need to be addressed to improve the clinical application of HLCs. This review discusses these advancements and outlines the therapeutic potential and current challenges of HLC therapy for ESLD.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 10-21"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557099","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":"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":"The emerging role of artificial intelligence in drug-induced liver injury research: Current innovations","authors":"Thanathip Suenghataiphorn,&nbsp;Kanachai Boonpiraks,&nbsp;Vitchapong Prasitsumrit,&nbsp;Narathorn Kulthamrongsri,&nbsp;Pojsakorn Danpanichkul","doi":"10.1016/j.livres.2026.02.003","DOIUrl":"10.1016/j.livres.2026.02.003","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 1","pages":"Pages 95-97"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147557092","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}