Liver Research最新文献

{"title":"Emerging role of proteomics in advancing diagnosis, prognosis, and treatment of liver cancer","authors":"Yunyang Xu,&nbsp;Jiarui Li,&nbsp;Xingyu Luo,&nbsp;Ze Xiang,&nbsp;Zhe Yang,&nbsp;Xuyong Wei,&nbsp;Xiao Xu,&nbsp;Jian Chen","doi":"10.1016/j.livres.2026.04.002","DOIUrl":"10.1016/j.livres.2026.04.002","url":null,"abstract":"<div><div>Liver cancer (LC) remains one of the most prevalent tumors globally. Despite considerable advancements in its clinical treatment in recent years, the global burden of this disease is projected to increase. According to World Health Organization statistics, the number of LC deaths worldwide in 2022 was 760,000, ranking third among all cancers. Therefore, there is an urgent need to delve deeper into the realms of LC diagnosis, prognosis, and treatment. Proteomics, as an emerging technology leveraging mass spectrometry (MS)-based protein identification, liquid chromatography separation, and bioinformatics-driven data integration, enables the systematic characterization of proteome dynamics to address critical challenges in LC research. These challenges include the discovery of diagnostic and prognostic biomarkers as well as therapeutic targets. By scrutinizing the expression of specific proteins in both normal and cancerous tissues through high-throughput protein microarrays, researchers can uncover novel biomarkers. The use of these biomarkers alone or in combination with established ones holds the potential to significantly advance the fields of LC diagnosis, prognosis, and treatment. In general, the application of proteomics has significantly promoted the development of LC research. In this review, we summarized the latest advancements in the application of proteomics in LC, with a particular focus on diagnosis, prognosis, and treatment. We also concluded selected protein markers, aiming to offer guidance for further applications and present additional therapeutic targets for LC.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 2","pages":"Pages 121-132"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving B-mode ultrasound-based techniques for assessing metabolic dysfunction-associated steatotic liver disease: Now and beyond","authors":"Walaa Abdelhamed,&nbsp;Mohamed Elbadry,&nbsp;Mohamed El-Kassas","doi":"10.1016/j.livres.2026.05.001","DOIUrl":"10.1016/j.livres.2026.05.001","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease worldwide, coinciding with the growing burden of obesity and type 2 diabetes mellitus. While liver biopsy remains the gold standard for assessing hepatic steatosis and fibrosis, its invasiveness, sampling variability, and limited feasibility have necessitated the establishment of non-invasive diagnostic alternatives. Among non-invasive alternatives, conventional B-mode ultrasound (US) has retained a central role as the first-line imaging modality owing to its wide availability, low cost, and reasonable sensitivity and specificity, particularly in moderate-to-severe steatosis. However, traditional B-mode US has several limitations, including operator dependence, poor sensitivity in mild steatosis, and reduced accuracy in obese individuals. Semi-quantitative scoring systems and emerging technologies such as attenuation imaging, shear wave elastography, and vibration-controlled transient elastography, have been recently introduced to improve diagnostic accuracy. Additionally, artificial intelligence (AI) is increasingly being integrated into US platforms to enhance image interpretation, standardize assessments, and reduce interobserver variability. This review provides a comprehensive appraisal of the diagnostic performance, strengths, and limitations of conventional B-mode US and its advanced products in the context of MASLD. US-based techniques are also compared with magnetic resonance spectroscopy and histological assessment, highlighting the evolving role of AI in US diagnostics. Given the global rise of MASLD, optimizing and standardizing US-based approaches are essential to improve early detection, risk stratification, and monitoring strategies. With continued technological refinement and integration of AI, US remains a cornerstone of MASLD diagnosis in clinical practice.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 2","pages":"Pages 109-120"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered miR-148a-3p suppresses glycolysis and amino acid homeostasis in hepatocellular carcinoma cells by regulating multiple solute carrier transporters","authors":"Su Guan,&nbsp;Xin Li,&nbsp;Yimei Wang,&nbsp;Mei-Juan Tu,&nbsp;Ai-Ming Yu","doi":"10.1016/j.livres.2026.04.001","DOIUrl":"10.1016/j.livres.2026.04.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNA^Leu/miR-148a-3p) agent produced <em>in vivo</em>.</div></div><div><h3>Methods</h3><div>BioRNA^Leu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in <em>Escherichia coli</em> (<em>E. coli</em>), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods.</div></div><div><h3>Results</h3><div>BioRNA^Leu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3′-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine.</div></div><div><h3>Conclusions</h3><div>Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"10 2","pages":"Pages 166-176"},"PeriodicalIF":2.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"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}