Hepatic Medicine : Evidence and Research最新文献

{"title":"Aldose Reductase Mediated Mitophagy Promotes Epithelial-Mesenchymal Transition of Hepatocytes.","authors":"Jingjing Yan, Wenke Zhao, Haoyu Wang, Lutan Zhou, Xianwei Li, Guannan Wang","doi":"10.2147/HMER.S546357","DOIUrl":"10.2147/HMER.S546357","url":null,"abstract":"<p><strong>Background: </strong>Recent studies suggest that impaired mitophagy leading to epithelial-mesenchymal transition (EMT) in hepatocytes plays a major role in the progression of hepatic fibrosis (HF). The authors' previous study demonstrated that aldose reductase (AR) promotes radiation-induced EMT in alveolar epithelial cells. This study aims to examine whether AR influences EMT in hepatocytes by regulating defective mitophagy.</p><p><strong>Methods: </strong>Some histological techniques, including HE staining, Masson's trichrome staining, immunohistochemistry, and transmission electron microscopy, were employed to validate the model and examine mitochondrial injury. Subsequently, EMT was induced in hepatocytes through TGF-β1 treatment. Then experiments such as siRNA-mediated gene silencing, AR inhibition, and AR overexpression were performed. Finally, the activation status of AKT and mTOR, as well as the expression levels of proteins associated with mitophagy and EMT, were evaluated using RT-qPCR, immunofluorescence staining, and Western blotting.</p><p><strong>Results: </strong>AR knockout significantly reduced AKT and mTOR phosphorylation In vivo but increased the expression of Pink1 and Parkin in CCl₄-exposed liver tissues. This was associated with an increased LC3 II/I expression ratio, decreased p62 expression, reduced mitochondrial damage, enhanced E-cadherin expression, and diminished Snail, α-SMA, and vimentin expression, which collectively alleviated HF. In vitro experiments revealed that AR knockdown significantly attenuated the activation of the TGF-β1-induced AKT/mTOR pathway, restored mitochondrial autophagy function, decreased ROS levels, increased mitochondrial membrane potential (MMP) and ATP production, and reversed EMT in hepatocytes via siRNA or pharmacological inhibition. Conversely, AR overexpression exacerbated the activation of the TGF-β1-induced AKT/mTOR pathway, impaired mitophagy efficiency, increased ROS levels, decreased MMP and ATP levels, and facilitated EMT process.</p><p><strong>Conclusion: </strong>The study findings demonstrated that AR facilitates EMT in hepatocytes and plays a major role in enhancing HF. This process may be linked to AR-induced activation of the AKT/mTOR. Consequently, this activation suppresses the expression of Pink1 and Parkin, ultimately reducing the risk of mitophagy in hepatocytes.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"141-159"},"PeriodicalIF":1.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238542","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":"Seroprevalence and Predictors of Hepatitis B and C Virus Infections Among Patients with Chronic Liver Diseases in Dodoma Region, Tanzania: A Cross-Sectional Study.","authors":"Daudi J Gyunda, James J Yahaya, Emmanuel M Sindato, Alfred J Meremo","doi":"10.2147/HMER.S533485","DOIUrl":"10.2147/HMER.S533485","url":null,"abstract":"<p><strong>Background: </strong>The known major causes of chronic liver diseases (CLDs) include, hepatitis B virus (HBV) and hepatitis C virus (HCV); however, there is scarcity of data regarding their seroprevalence in Tanzania. We aimed to evaluate the seroprevalence of HBsAg and anti-HCV and their predictors among patients with CLDs. Additionally, we also described the clinical patterns of the patients.</p><p><strong>Methods: </strong>A cross-sectional analytical study design was carried at the two referral public hospitals in Dodoma region; Dodoma referral regional hospital (DRRH) and Benjamin Mkapa hospital (BMH) among 118 patients with CLDs. Rapid test immunochromatography was used to test for HBsAg whereas anti-HCV antibody positivity was tested using lateral flow chromatographic immunoassay. Multivariable binary logistic regression was used to evaluate the predictors of HbsAg positive results, and statistical significance was set at p˂0.05.</p><p><strong>Results: </strong>The seroprevalence of HBsAg and anti-HCV antibody was 28% (33/118) and 3.4% (4/118), respectively. Having a chronic illness (AOR = 2.3, 95% CI = 1.76-7.19, p = 0.041), raised level of alanine transaminase (ALT) (AOR = 3.6, 95% CI = 1.74-8.21, p = 0.025), increased AST/ALT ratio (AOR = 2.9, 95% CI = 2.57-11.57, p = 0.039), and increased level of total bilirubin (AOR = 5.1, 95% CI = 1.09-24.39, p = 0.039) remained the predictors of HBsAg positivity.</p><p><strong>Conclusion: </strong>This study reports that almost one-third of the study subjects had positive HbsAg, and the positivity of anti-HCV antibody was quite low. The positivity of HbsAg was associated with having chronic illness, increased levels of ALT, total bilirubin, and AST/ALT ratio. Therefore, emphasis should be made to maximize the screening practices for individuals with such predictors due to high possibility of being infected with HBV.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"125-140"},"PeriodicalIF":1.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185639","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":"Linking Brain and Immune Transcriptomes to Gut-Derived Metabolites in Hepatic Encephalopathy: An Explorative Integrative Multi-Omics Approach.","authors":"Ali Sepehrinezhad, Ali Shahbazi","doi":"10.2147/HMER.S546200","DOIUrl":"10.2147/HMER.S546200","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatic encephalopathy (HE), one of the more important cerebral complications attributable to acute liver failure and more severe forms, has traditionally been associated with hyperammonemia. However, recent studies implicate gut microbiota-derived metabolites in HE pathogenesis through systemic inflammation and neurotoxicity. Despite this, the integrated molecular mechanisms linking these metabolites to HE remains poorly described. This study addresses this gap by employing a bioinformatics-based systems biology approach to identify interactions between gut metabolites and host genes, thereby identifying novel diagnostic and therapeutic targets.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) from peripheral (GSE184200: CD4⁺ T lymphocytes) and central (GSE57193: fusiform gyrus) tissues of HE patients were analyzed using GEO2R. Genes associated with five gut microbiota-derived metabolites including choline metabolites, lipid metabolites, short-chain fatty acids, tryptophan catabolites, and secondary bile acids were extracted from GeneCards. Overlapping genes between HE-related genes and gut-derived metabolites were then subjected to multi-level enrichment analyses (pathway, phenotype, cell type, and cellular component), and miRNA/drug prediction using Enrichr and ToppGene.</p><p><strong>Results: </strong>We identified nine hub genes related to gut-systemic interactions and 29 hub genes associated with gut-brain interactions in the context of HE. The most significantly impaired pathways were signaling by interleukin 24 and TP53, as well as oxidative stress, which were affected by gut metabolites and peripheral HE-related genes. Similarly, mitochondrial fatty acid β-oxidation, neuroinflammation, and glutamate tone were significantly altered by gut metabolites and central HE-related genes. Additionally, we predicted 18 miRNAs and 13 potential drugs that target both gut microbiota metabolites and HE.</p><p><strong>Conclusion: </strong>This study offers the first systems-level framework connecting gut-derived metabolites to HE through gene networks, challenging the ammonia-centric viewpoint. The predicted miRNAs and drugs offer translational potential for precision medicine in HE. Experimental validation of these targets is required to advance therapeutic strategies.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"105-124"},"PeriodicalIF":1.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112986","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":"Pharmacological Modulation of Liver and Spleen Stiffness in a Cirrhotic Rat Model.","authors":"Omar Elshaarawy, Shami Hasan M Alquzi, Felix Piecha, Vanessa Rausch, Johannes Mueller, Sebastian Mueller","doi":"10.2147/HMER.S541039","DOIUrl":"10.2147/HMER.S541039","url":null,"abstract":"<p><strong>Purpose: </strong>Liver stiffness (LS) assesses liver fibrosis, while spleen stiffness (SS) is a promising marker for portal hypertension (PH), reflecting blood flow and vascular resistance. However, the response of LS and SS to vasoactive drugs is unclear. This study evaluates the effects of various PH-lowering drugs on LS and SS in a rat cirrhosis model.</p><p><strong>Patients and methods: </strong>In this study, cirrhosis was induced in 43 male Wistar rats (8 weeks old) via intraperitoneal thioacetamide (TAA) injections (200 mg/kg, twice weekly for six weeks). Rats were divided into six groups: control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin, and carvedilol. LS and SS were measured using μFibroscan. Mean arterial pressure (MAP), heart rate (HR), and portal vein pressure (PVP) were continuously monitored. Drugs were administered systemically, with data collected at 0, 15, and 30 minutes.</p><p><strong>Results: </strong>TAA-treated rats exhibited significantly higher LS and SS compared to controls (22.1 vs 4.2 kPa and 53.7 vs 27.7 kPa; P < 0.001). Changes in LS and SS correlated with PVP (r = 0.670 for LS and r = 0.867 for SS; P < 0.01). Metoprolol, udenafil, enalapril, and carvedilol significantly reduced PVP (22-34%, P < 0.05), accompanied by decreases in LS and SS (13-37%, P < 0.05). Terlipressin did not reduce LS or SS, likely due to opposing effects of increased MAP and reduced PVP.</p><p><strong>Conclusion: </strong>In conclusion, combined LS and SS measurements may provide valuable non-invasive insights into patient responses and adherence to PH-lowering therapies.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"91-104"},"PeriodicalIF":1.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075216","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":"MAFLD: A Comprehensive Review of the Link Between Metabolic Dysfunction and Cardiovascular Risk.","authors":"Alaa M Mostafa, Ziyan Pan, Ming-Lung Yu, Necati Örmeci, Yasser Fouad, Mohammed Eslam","doi":"10.2147/HMER.S506402","DOIUrl":"10.2147/HMER.S506402","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over 30% of the global population. It is a multisystem condition with a strong association with cardiovascular disease (CVD), the leading cause of mortality worldwide. Key shared mechanisms, including insulin resistance, systemic inflammation, oxidative stress, and genetic predisposition, couple MAFLD with increased risks of coronary artery disease, ischemic heart disease, and heart failure. Early detection via non-invasive imaging and biomarkers is crucial for effective risk stratification. Management strategies emphasize lifestyle modifications and the development of targeted pharmacotherapies addressing metabolic and inflammatory pathways. Understanding the interconnected pathogenic mechanisms facilitates personalized interventions to reduce morbidity and improve long-term outcomes. A multidisciplinary approach remains essential to prevent and manage the cardiovascular implications of MAFLD.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"75-90"},"PeriodicalIF":1.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951879","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":"The Effect of Liv.52 DS in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): A Pilot, Randomized, Double-Blind, Placebo-Controlled, Clinical Study.","authors":"Umesh Jalihal, Rajesh Amarnath Nanda, Kuldeep Katariya, Balamurugan Ramanathan, Rajesh Kumawat","doi":"10.2147/HMER.S527644","DOIUrl":"10.2147/HMER.S527644","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is considered a major global health concern. Considering the preliminary trend of hepatoprotective function of Liv.52 DS, the present study was conducted to explore its role in MAFLD.</p><p><strong>Patients and methods: </strong>This randomized, double-blind, placebo-controlled, prospective, multicenter study was performed at four tertiary care hospitals in India. A total of 52 randomized subjects were administered either Liv.52 DS or placebo tablets twice daily for six months. Liver Stiffness Measurement (LSM) and Controlled Attenuated Parameter (CAP) values were compared at baseline and 6 months. After completion of the study, data from 47 subjects were available for analysis (31 in the Liv.52 DS group and 16 in the placebo group).</p><p><strong>Results: </strong>The mean LSM score, was reduced from 7.3 to 6.0 (Change From Baseline = 17.5%) in the active group with statistically significance (p = 0.007) compared to placebo group with LSM score reduction from 7.5 to 6.9 (CFB = 7.29%). A shift in the mean value from fibrosis (>6.0 kPa) to almost no significant fibrosis (<6.0 kPa), as per the Indian National Association for the Study of the Liver (INASL) cutoff, was achieved in the Liv.52 DS Group. Improvement was also observed in CAP values with Liv.52 DS, where 71% of the subjects showed an overall improvement in steatosis grade. The other liver markers like alanine transaminase (ALT) and aspartate aminotransferase (AST) were within the normal range. There were no cases of nephrotoxicity (common concern for herbal formulation), and no drug-related adverse events were reported.</p><p><strong>Conclusion: </strong>A significant improvement in LSM and improvement in CAP was observed after 6 months of treatment with Liv.52 DS using fibroscan. This suggests that Liv.52 DS should be further explored for its potential role in the treatment of unmet medical needs in MAFLD patients.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"61-73"},"PeriodicalIF":1.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12324062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788906","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":"Historical and Emerging Trends in Hepatitis B Virus Integration: A Bibliometric Visual Analysis.","authors":"Jia Liu, Longhai Xu, Xuefeng Ma, Yanzhen Bi, Yongning Xin","doi":"10.2147/HMER.S526977","DOIUrl":"10.2147/HMER.S526977","url":null,"abstract":"<p><strong>Purpose: </strong>Hepatitis B virus (HBV) infection is a global health concern, linked to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV genome integration into host DNA is critical in disease progression and oncogenesis. Despite advancements in understanding HBV pathogenesis and therapies, the mechanisms and implications of HBV integration remain unclear. This study employs bibliometric analysis to evaluate research trends and collaborations in HBV integration.</p><p><strong>Materials and methods: </strong>We utilized the Web of Science Core Collection (WOSCC) as our primary data source, meticulously screening and identifying 972 pertinent articles published between 1980 and November 30, 2024. Bibliometric tools, including VOSviewer, CiteSpace, and Bibliometrix, were employed to analyze publication trends, authorship, institutional contributions, and key research areas. Citation data and keyword clusters were examined to identify research hotspots.</p><p><strong>Results: </strong>Publications have steadily increased from 1980 to November 30, 2024, with China and the United States contributing the most studies. While China leads in publication volume, the United States has the highest citation impact. The Institut Pasteur in Paris ranks highest in publications. Hino O is the most prolific author, and Koike K the most cited. Hepatology is the most cited journal, and the article \"Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma\" is the most referenced. Cluster analysis revealed five major research themes.</p><p><strong>Conclusion: </strong>This study highlights global research trends and key contributors in HBV integration, offering insights into current hotspots and future directions. The findings provide a basis for advancing diagnostic and therapeutic strategies targeting HBV integration.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"39-59"},"PeriodicalIF":2.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698415","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":"Performance of APRI and FIB-4 Scores Compared to FibroScan: A Cross-Sectional Study in a Black Sub-Saharan African Population.","authors":"Jean-Bonny Nsumbu, Jean-Robert Makulo, Trésor Mutombo Tshiswaka, Christian Kisoka Lusunsi, Charles Nlombi Mbendi","doi":"10.2147/HMER.S533064","DOIUrl":"10.2147/HMER.S533064","url":null,"abstract":"<p><strong>Background and aim: </strong>Several non-invasive tests are used to assess liver fibrosis and cirrhosis in patients with liver disease. However, most validation studies have not included populations in sub-Saharan Africa. This study aimed to evaluate the diagnostic performance of the APRI and FIB-4 scores in a Congolese cohort.</p><p><strong>Patients and methods: </strong>A cohort of patients in Kinshasa underwent FibroScan and laboratory testing to calculate APRI and FIB-4 scores. Pearson correlation, sensitivity, specificity, and ROC curve analyses were used to evaluate the performance of these non-invasive scores against FibroScan. Cirrhosis was defined as liver stiffness ≥14 kPa by FibroScan. Thresholds for APRI and FIB-4 scores predicting cirrhosis were set at ≥ 1.5 and ≥ 2.67, respectively.</p><p><strong>Results: </strong>The study included 316 patients (mean ± SD age: 48.1 ± 14.1 years; 60.8% male; 10.1% with diabetes; 37.1% obese; 14.2% with hepatitis B; 6.7% with hepatitis C; 25.6% with a history of alcohol use). The Pearson correlation between APRI and FibroScan was r = 0.210 (p < 0.001), while the correlation between FIB-4 and FibroScan was better (r = 0.478, p < 0.001). In subgroup analyses, FIB-4 correlated with FibroScan only among patients with alcohol use or hepatitis B or C, APRI only correlated with FibroScan in alcohol dependent patients. The sensitivity and specificity of APRI were 29.7% and 97.9% respectively, compared to 60.0% and 93.3% for FibroScan. The areas under the ROC curve were 0.8462 for APRI and 0.8312 for FIB-4, with thresholds lower than those reported in the literature: 0.422 for APRI and 1.285 for FIB-4, but these varied according to the subgroup.</p><p><strong>Conclusion: </strong>APRI and FIB-4 scores demonstrate high specificity but low sensitivity for diagnosing cirrhosis in this population. Their diagnostic performance is notably better in patients with alcohol-related liver disease or viral hepatitis, but poor among those with diabetes or obesity.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"27-37"},"PeriodicalIF":2.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674557","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":"Erratum: Identification of Ferroptosis-Related Genes in MAFLD/MASH and HQHF Validation [Corrigendum].","authors":"","doi":"10.2147/HMER.S547739","DOIUrl":"https://doi.org/10.2147/HMER.S547739","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.2147/HMER.S509778.].</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"25-26"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474960","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":"Identification of Ferroptosis -Related Genes in MAFLD/MASH and HQHF Validation.","authors":"Sutong Liu, Lihui Zhang, Junjiao Xu, Qing Zhao, Dongfang Shang, Xiaoyan Liu, Qiang Zhang, Minghao Liu, Wenxia Zhao","doi":"10.2147/HMER.S509778","DOIUrl":"10.2147/HMER.S509778","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic associated fatty liver disease (MAFLD) and its progressive form, Metabolic Dysfunction-Associated Steatohepatitis(MASH), are prevalent liver disorders with significant health implications. This study aims to identify differentially expressed genes (DEGs) associated with MAFLD/MASH and explore their potential link to ferroptosis, a form of regulated cell death.</p><p><strong>Methods: </strong>We conducted differential expression analysis using two datasets from the GEO database. Genes related to ferroptosis were identified from the Genecards and FerrDb databases, and the intersection genes were obtained by intersecting the DEGs with ferroptosis-related genes. Functional enrichment was performed using GO and KEGG pathways. The clinical diagnostic value of the intersection genes was evaluated through ROC analysis. Finally, the research findings were validated using a high-fat diet (HFD) mouse model, observing the improvement in gene expression with HQHF treatment.</p><p><strong>Results: </strong>We utilized two datasets, GSE89632 and GSE63067, from the GEO database, comprising 39 samples, including 24 healthy controls. Differential expression analysis revealed significant gene expression changes in NAFLD and NASH compared to healthy controls. These DEGs were visualized using volcano plots. Ferroptosis-related genes were identified from Genecards and FerrDb databases, resulting in 1937 unique genes. Venn analysis revealed intersections between DEGs and ferroptosis genes, highlighting potential regulatory roles. Functional enrichment analysis using GO and KEGG pathways indicated significant involvement in cellular components and signaling pathways, such as PPAR and HIF-1. The clinical diagnostic value of intersecting genes was assessed using ROC analysis, demonstrating promising diagnostic potential. In addition, a high-fat diet (HFD) mouse model was used to validate the research findings, showing that HQHF treatment can alleviate lipid deposition and inflammation in the liver. Transmission electron microscopy results indicated that HQHF prevented mitochondrial damage and significantly reduced the content of Fe2+ in the liver, alleviating iron deposition. We verified the reliable genes with diagnostic value through qPCR, and the results suggested that HQHF can lower the transcription levels of P4HA1, NR4A1, and EFEMP1, while increasing the transcription levels of ENo3, GRIA3, ME1, and FADS2, confirming our ROC results.</p><p><strong>Conclusion: </strong>This study provides insights into the molecular mechanisms underlying MAFLD/MASH and suggests ferroptosis-related genes as potential diagnostic biomarkers and therapeutic targets. Further research is warranted to explore these findings in clinical settings.</p>","PeriodicalId":12917,"journal":{"name":"Hepatic Medicine : Evidence and Research","volume":"17 ","pages":"13-24"},"PeriodicalIF":2.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989005","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}