Liver Research最新文献

{"title":"Patients with chronic hepatitis B under nucleos(t)ide analog therapy with Omicron BA.5 infection: A retrospective study in South China","authors":"Peipei Wang ,&nbsp;Junjian Chen ,&nbsp;Dabiao Chen ,&nbsp;Ziying Lei ,&nbsp;Zhishuo Mo ,&nbsp;Ying Zhang","doi":"10.1016/j.livres.2024.11.003","DOIUrl":"10.1016/j.livres.2024.11.003","url":null,"abstract":"<div><h3>Background and aims</h3><div>Clinical data regarding patients with chronic hepatitis B (CHB) after Omicron BA.5 infection are currently limited. This study aimed to assess the clinical characteristics of patients with CHB and Omicron BA.5 infection in South China.</div></div><div><h3>Methods</h3><div>This retrospective study was conducted from January to March 2023 in a cohort of 485 healthy individuals and 553 patients with CHB. Clinical features, encompassing COVID-19-related symptoms, levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, vaccination status, liver functions, and virological markers of hepatitis B virus (HBV) infection were measured.</div></div><div><h3>Results</h3><div>COVID-19-related symptom patterns were similar in both groups, except for fever, which was notably less prevalent (85.4% <em>vs.</em> 90.4%, <em>P</em> = 0.047) among patients with CHB who experienced a significantly shorter duration of fever (median 2.2 (25th–75th percentile, 1.0–3.0) days <em>vs.</em> 2.3 (1.0–3.0) days, <em>P</em> = 0.048) and a shorter time for symptom relief (9.2 (5.0–14.0) <em>vs.</em> 11.1 (5.0–14.0) days, <em>P</em> = 0.015). The levels of SARS-CoV-2 antibodies were comparable between the two groups but increased after booster vaccinations. In patients with CHB, globulin (GLB) and hepatitis B envelope antibody levels were significantly increased after Omicron BA.5 infection, regardless of nucleos(t)ide analog regimens comparing entecavir (ETV) with tenofovir (TFV). Patients with CHB treated with TFV had significantly higher levels of SARS-CoV-2 antibodies than those treated with ETV (1065.1 (346.9–1188.5) COI <em>vs.</em> 765.5 (24.5–1119.1) COI, <em>P</em> = 0.025).</div></div><div><h3>Conclusions</h3><div>No significant exacerbation of COVID-19 symptoms was observed in conjunction with the efficacy of COVID-19 booster vaccinations. There were no notable alterations in liver functions except for GLB. HBV reactivation, as evidenced by increased HBV DNA, was observed among patients with CHB after Omicron BA.5 infection. These changes were not affected by ETV versus TFV administration; however, TFV resulted in a significant increase in SARS-CoV-2 antibody levels. Further studies are required to improve care and therapeutics for patients with CHB who contracted COVID-19.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 66-73"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679006","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":"An 82-year-old recipient of split liver transplantation worldwide: A case report","authors":"Xiao Feng ,&nbsp;Binsheng Fu ,&nbsp;Qing Yang ,&nbsp;Kaining Zeng ,&nbsp;Huimin Yi ,&nbsp;Shuhong Yi ,&nbsp;Yang Yang","doi":"10.1016/j.livres.2024.12.004","DOIUrl":"10.1016/j.livres.2024.12.004","url":null,"abstract":"<div><div>Split liver transplantation (SLT) has become an indispensable method for expanding the donor liver pool. However, advanced age in recipients can have significant adverse effects on prognosis. We report the case of an 82-year-old man with chronic liver failure and polycystic liver disease who underwent <em>in vivo</em> split right triple lobe donor liver transplantation on October 29, 2021. The patient made a remarkable recovery and was discharged 1 month after surgery. To date, he has been followed up for 32 months, with favorable laboratory and imaging test results, and no significant abnormalities or complications. Currently, this patient may be the oldest SLT recipient in the world. With comprehensive preoperative evaluation, optimized surgical techniques, and individually tailored postoperative care, older adults can safely undergo SLT. Therefore, advanced age should not be considered an absolute contraindication for this procedure.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 74-78"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679007","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":"Prognostic comparison between pulmonary metastasectomy and combination immunotherapy with targeted molecular therapies for advanced hepatocellular carcinoma with pulmonary metastasis: A propensity score matching analysis","authors":"Juxian Sun ,&nbsp;Chang Liu ,&nbsp;Xiandong Tao ,&nbsp;Yu Yang ,&nbsp;Hai Jin ,&nbsp;Shuqun Cheng ,&nbsp;Huazheng Shi ,&nbsp;Maolin Yan ,&nbsp;Jie Shi","doi":"10.1016/j.livres.2025.01.006","DOIUrl":"10.1016/j.livres.2025.01.006","url":null,"abstract":"<div><h3>Background and aims</h3><div>Advanced hepatocellular carcinoma (HCC) with pulmonary metastasis (PM) has a poor prognosis, and optimal treatment strategies remain controversial. This study aimed to compare the long-term outcomes of patients with advanced HCC with PM who were treated with resection of pulmonary metastases versus those treated with targeted therapies combined with immunotherapy.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on the medical records of HCC patients with PM who underwent either pulmonary metastasectomy or immunotherapy combined with targeted therapies at the Eastern Hepatobiliary Surgery Hospital, Changhai Hospital of Shanghai, Fujian Provincial Hospital, and West China Hospital of Sichuan University from September 2013 to October 2022. One-to-one propensity score matching (PSM) was employed to control the influence of potential confounders, and the survival outcomes were compared.</div></div><div><h3>Results</h3><div>A total of 119 HCC patients with PM were included in this study. The overall survival (OS) of patients who underwent pulmonary metastasectomy was significantly longer than that of patients who received immunotherapy targeted combinations (OS: 1-year, 80.0% <em>vs.</em> 59.3%; 2-year, 31.7% <em>vs.</em> 20.3%; 3-year, 20.0% <em>vs.</em> 0; <em>P</em> &lt; 0.001). After PSM, the long-term prognosis of the pulmonary metastasectomy group remained significantly better than that of the immunotherapy combination group (OS: 1-year, 87.0% <em>vs.</em> 69.6%; 2-year, 34.8% <em>vs.</em> 30.4%; 3-year, 21.7% <em>vs.</em> 0; <em>P</em> = 0.005). Multivariate analysis revealed that treatment allocation (hazard ratio (HR) = 2.177, 95% confidence interval (CI) = 1.068–4.439) and hepatic tumor T stage (HR = 2.342, 95% CI = 1.209–4.538) were independent risk factors for OS.</div></div><div><h3>Conclusions</h3><div>Pulmonary metastasectomy was associated with improved survival compared to immunotherapy combined with targeted therapies and may represent an optimal treatment option for highly selected HCC patients with resectable PM.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 29-35"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679726","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":"Corrigendum to “Protective effects of Longhu Rendan on chronic liver injury and fibrosis in mice” [Liver Res. 6 (2022) 93–102]","authors":"Guizhi Yang ,&nbsp;Shengwen Li ,&nbsp;Jiahua Jin ,&nbsp;Yuanyuan Xuan ,&nbsp;Liqin Ding ,&nbsp;Minxia Huang ,&nbsp;Jun Liu ,&nbsp;Biye Wang ,&nbsp;Tian Lan","doi":"10.1016/j.livres.2025.01.003","DOIUrl":"10.1016/j.livres.2025.01.003","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Page 79"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679008","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":"Probiotic Bifidobacterium reduces serum TMAO in unstable angina patients via the gut to liver to heart axis","authors":"Zhihong Zhou ,&nbsp;Lizhe Sun ,&nbsp;Wei Zhou ,&nbsp;Wen Gao ,&nbsp;Xiao Yuan ,&nbsp;Huijuan Zhou ,&nbsp;Yuzhen Ren ,&nbsp;Bihua Li ,&nbsp;Yue Wu ,&nbsp;Jianqing She","doi":"10.1016/j.livres.2025.02.001","DOIUrl":"10.1016/j.livres.2025.02.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases, and enterohepatic circulation plays an important role in this progression. This study aims to identify potential probiotics for the treatment of unstable angina (UA) and elucidate their mechanisms of action.</div></div><div><h3>Methods</h3><div>Initially, the gut microbiota from patients with UA and control was analyzed. To directly assess the effects of <em>Bifidobacterium</em> supplementation, 10 patients with UA were enrolled and administered <em>Bifidobacterium</em> (630 mg per intake twice a day for 1 month). The fecal metagenome, serum trimethylamine N-oxide (TMAO) levels, and other laboratory parameters were evaluated before and after <em>Bifidobacterium</em> supplementation.</div></div><div><h3>Results</h3><div>After supplementing with <em>Bifidobacterium</em> for 1 month, there were statistically significant differences (<em>P</em> &lt; 0.05) in TMAO, aspartate aminotransferase, total cholesterol, and low-density lipoprotein compared to before. Additionally, the abundance of <em>Bifidobacterium longum</em> increased significantly, although the overall abundance of <em>Bifidobacterium</em> did not reach statistical significance. The gut microbiota, metabolites, and gut-liver axis are involved in the progression of UA, and potential mechanisms should be further studied.</div></div><div><h3>Conclusions</h3><div>Metagenomic analysis demonstrated a reduced abundance of <em>Bifidobacterium</em> in patients with UA. Supplementation with <em>Bifidobacterium</em> restored gut dysbiosis and decreased circulating TMAO levels in patients with UA. This study provides evidence that <em>Bifidobacterium</em> may exert cardiovascular-protective effects through the gut–liver–heart axis.</div></div><div><h3>Clinical trial number</h3><div>ChiCTR2400093946.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 57-65"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679005","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 extracellular vesicles: The path to precision medicine in liver diseases","authors":"Ashmit Mittal ,&nbsp;Vibhuti R Jakhmola ,&nbsp;Sukriti Baweja","doi":"10.1016/j.livres.2025.02.002","DOIUrl":"10.1016/j.livres.2025.02.002","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are membrane-bound entities secreted by each cell, categorized as, exosomes, microvesicles or apoptotic bodies based on their size and biogenesis. They serve as promising vectors for drug delivery due to their capacity to carry diverse molecular signatures reflective of their cell of origin. EV research has significantly advanced since their serendipitous discovery, with recent studies focusing on their roles in various diseases and their potential for targeted therapy. In liver diseases, EVs are particularly promising for precision medicine, providing diagnostic and therapeutic potential in conditions such as metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, hepatocellular carcinoma, alcoholic liver disease, liver fibrosis, and acute liver failure. Despite challenges in isolation and characterization, engineered EVs have shown efficacy in delivering therapeutic agents with improved targeting and reduced side effects. As research progresses, EVs hold great promise to revolutionize precision medicine in liver diseases, offering targeted, efficient, and versatile therapeutic options. In this review, we summarize various techniques for loading EVs with therapeutic cargo including both passive and active methods, and the potential of bioengineered EVs loaded with various molecules, such as miRNAs, proteins, and anti-inflammatory drugs in ameliorating clinical pathologies of liver diseases.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 17-28"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679725","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":"Bile acids and their receptors in hepatic immunity","authors":"Stefano Fiorucci ,&nbsp;Silvia Marchianò ,&nbsp;Eleonora Distrutti ,&nbsp;Michele Biagioli","doi":"10.1016/j.livres.2025.01.005","DOIUrl":"10.1016/j.livres.2025.01.005","url":null,"abstract":"<div><div>Similarly to conventional steroids, bile acids function as signaling molecules, acting on a family of membrane and nuclear receptors. The best-characterized bile acid-regulated receptors are the farnesoid X receptor, activated by primary bile acids, and the G-protein-coupled bile acid receptor 1 (also known as Takeda G protein-coupled receptor 5), which is activated by secondary bile acids, such as lithocholic acid (LCA) and deoxycholic acid. Both the farnesoid X receptor and G-protein-coupled bile acid receptor 1 are expressed in cells of innate immunity, monocytes/macrophages, and natural killer cells. Their activation in these cells provides counter-regulatory signals that are inhibitory in nature and attenuate inflammation. In recent years, however, it has been increasingly appreciated that bile acids biotransformations by intestinal microbiota result in the formation of chemically different secondary bile acids that potently regulate adaptive immunity. The 3-oxoLCA and isoalloLCA, two LCA derivatives, bind receptors such as the retinoic acid receptor-related orphan receptor gamma t (RORγt) and the vitamin D receptor (VDR) that are expressed only by lymphoid cells, extending the regulatory role of bile acids to T cells, including T-helper 17 cells and type 3 innate lymphoid cells (ILC3). In this novel conceptual framework, bile acids have emerged as one of the main components of the postbiota, the waste array of chemical mediators generated by the intestinal microbiota. Deciphering the interaction of these mediators with the immune system in the intestine and liver is a novel and fascinating area of bile acid renaissance.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 1-16"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679724","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":"Mechanosensitive ion channel-related genes in hepatocellular carcinoma: Unraveling prognostic genes and their roles in drug resistance and immune modulation","authors":"Xinyan Huo ,&nbsp;Shiyu Jiang ,&nbsp;Sihuang Wu ,&nbsp;Qinghai Lian ,&nbsp;Hui Chen","doi":"10.1016/j.livres.2025.01.002","DOIUrl":"10.1016/j.livres.2025.01.002","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and aims&lt;/h3&gt;&lt;div&gt;Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and its etiology involves a complex interplay of genetic and environmental factors. Despite advancements in our understanding of HCC biology and the development of novel therapeutic strategies, the molecular mechanisms underlying its onset, progression, and resistance to therapy remain largely vague. This study aimed to investigate the role of mechanosensitive ion channel-related genes (MICRGs) in HCC, focusing on their potential as prognostic biomarkers and their involvement in immune modulation and drug resistance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A comprehensive analysis was conducted using The Cancer Genome Atlas database to identify MICRGs that are upregulated in HCC. Gene expression profiling, bioinformatics tools, and functional experiments were employed to elucidate the role of these channels. In addition, protein–protein interaction (PPI) network analyses and enrichment analyses were performed to explore the biological significance of these genes. An immune cell infiltration analysis was also conducted to understand MICRG-related immune landscape. Single-cell RNA sequencing (scRNA-seq) data were utilized to identify MICRGs in different cell types within the HCC tissue. Deep-learning neural network analysis across patient cohorts was conducted to identify genes associated with sorafenib resistance. Knockdown experiments, cell viability assays, and apoptosis assays on HCC cell lines were performed to examine the role of Piezo-type mechanosensitive ion channel component 1 (&lt;em&gt;PIEZO1&lt;/em&gt;) in sorafenib resistance.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The analysis identified a subset of MICRGs, including &lt;em&gt;PIEZO1&lt;/em&gt;, that were significantly upregulated in HCC and associated with poor prognosis. The PPI network analysis revealed complex interactions among these genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses proposed the involvement of these genes in calcium signaling pathways. Immune cell infiltration analysis demonstrated distinct associations between MICRGs and various immune subpopulations, highlighting their potential roles in immune modulation. scRNA-seq data indicated the upregulation of MICRGs in various cell types in HCC tissues, particularly in endothelial cells and tumor-associated macrophages. Deep-learning neural network analysis across different patient cohorts identified &lt;em&gt;PIEZO1&lt;/em&gt; as a crucial regulator of sorafenib resistance in HCC, which was further validated by functional assays on HCC cell lines.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This study provides evidence that MICRGs, particularly &lt;em&gt;PIEZO1&lt;/em&gt;, take on crucial roles in HCC progression and drug resistance. The upregulation of &lt;em&gt;PIEZO1&lt;/em&gt; in HCC cells is associated with poor prognosis and resistance to sorafenib. These findings indicate that &lt;em&gt;PIEZO1&lt;/em&gt; could serve as a p","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 36-48"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679727","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":"Combination of brefeldin A and tunicamycin induces apoptosis in HepG2 cells through the endoplasmic reticulum stress-activated PERK-eIF2α-ATF4-CHOP signaling pathway","authors":"Minghong Li ,&nbsp;Mengyi Duan ,&nbsp;Ying Yang ,&nbsp;Xingdao Li ,&nbsp;Dan Li ,&nbsp;Wenting Gao ,&nbsp;Xiaotong Ji ,&nbsp;Jianying Bai","doi":"10.1016/j.livres.2025.01.004","DOIUrl":"10.1016/j.livres.2025.01.004","url":null,"abstract":"<div><h3>Background and aims</h3><div>Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate, but there are still no effective treatments. The aim of this study was to investigate the anticancer potential of the combined use of brefeldin A (BFA) and tunicamycin (TM) in HepG2 cells, as well as the underlying mechanisms.</div></div><div><h3>Methods</h3><div>HepG2 cells were treated with different concentrations of BFA (0.1–2.5 mg/L) and TM (1–5 mg/L) for 24 h. DMSO (0.1 %, v/v) was used as a vehicle control. Cell viability and cell migration were measured using MTT assay and scratch wound assay, respectively. Apoptosis was detected using flow cytometry and acridine orange (AO) staining. The protein and mRNA levels of various factors involved in apoptosis (poly (ADP-ribose) polymerase-1 (PARP-1), caspase-12, caspase-3, and stearoyl-CoA desaturase 1) and endoplasmic reticulum (ER) stress (binding immunoglobulin protein (BiP), protein kinase R-like endoplasmic reticulum kinase (PERK), p-PERK, phosphorylation of eukaryotic translation initiation factor 2alpha (p-eIF2α), activating transcription factor (ATF) 4, and C/EBP homologous protein (CHOP)) were measured using Western blotting and qRT-PCR, respectively.</div></div><div><h3>Results</h3><div>Both BFA and TM alone significantly reduced the viability of HepG2 cells in a dose-dependent way. The co-incubation with TM (1 mg/L) further significantly reduced the viability of HepG2 cells treated with BFA (0.25 mg/L) alone (<em>P</em> &lt; 0.05). BFA significantly increased the protein and mRNA levels of caspase-3 and PARP-1 (<em>P</em> &lt; 0.05) compared to control and DMSO-treated cells, indicating that BFA induced apoptosis in HepG2 cells by increasing the expression of caspase-3 and PARP-1. The induction of apoptosis by BFA could be further significantly enhanced by co-incubation with TM. In addition, BFA significantly increased the mRNA levels of <em>BiP, PERK</em> and <em>ATF4</em> (<em>P</em> &lt; 0.05) compared to control and DMSO-treated cells. After co-incubation of BFA and TM, the protein levels of BiP, p-PERK, p-eIF2α and CHOP were significantly increased, indicating that TM could enhance BFA-induced ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.</div></div><div><h3>Conclusions</h3><div>BFA could induce apoptosis and ER stress, and TM could enhance the ability of BFA to induce apoptosis and ER stress in HepG2 cells through the PERK-eIF2ɑ-ATF4-CHOP pathway. The findings highlight the therapeutic potential of the combined use of BFA and TM in treating HCC.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"9 1","pages":"Pages 49-56"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679728","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":"Kehuang capsule inhibits MAPK and AKT signaling pathways to mitigate CCl4-induced acute liver injury","authors":"Qinyu Ni ,&nbsp;Jiacheng Lin ,&nbsp;Weifan Huang ,&nbsp;Liu Yang ,&nbsp;Ran Li ,&nbsp;Tianzhi Tu ,&nbsp;Guangfu He ,&nbsp;Yueqiu Gao ,&nbsp;Xuehua Sun ,&nbsp;Xiaoni Kong ,&nbsp;Xiaojun Zhu","doi":"10.1016/j.livres.2024.11.006","DOIUrl":"10.1016/j.livres.2024.11.006","url":null,"abstract":"<div><h3>Background and aims</h3><div>Kehuang (KH) capsule is an herbal medical product approved for the treatment of liver diseases, including liver injury, in China. However, the mechanism is still unclear. This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride (CCl₄)-induced acute liver injury (ALI) in a murine model.</div></div><div><h3>Methods</h3><div>Mice were randomly divided into control, model (CCl₄), CCl₄+KH_Low and CCl₄+KH_High group. Liver enzyme levels and histological changes were assessed to evaluate liver injury. Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured. Additionally, network pharmacology was employed to explore the potential mechanisms of KH capsule.</div></div><div><h3>Results</h3><div>KH capsule significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as the necrotic area in liver tissue. KH capsule also decreased the infiltration of macrophages and neutrophils, thereby inhibiting the expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). Furthermore, KH capsule decreased liver malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) activity. The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)-positive cells in liver tissue was also reduced. The expression of nuclear factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins was significantly elevated, while the protein expression of cytochrome P450 2E1 (CYP2E1) was significantly reduced. Mass spectrometry identified genistein, galangin, wogonin, skullcapflavone II, and hispidulin as potential active ingredients of KH capsule. Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Western blot analysis confirmed that KH capsule suppressed AKT, extracellular signal-regulated kinase (ERK), and p38 signaling.</div></div><div><h3>Conclusions</h3><div>These findings suggest that KH capsule could exert protective effects against CCl₄-induced ALI, with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mechanism of action.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 4","pages":"Pages 269-281"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143322649","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}