Liver Research最新文献

{"title":"Direct-acting antivirals sofosbuvir and daclatasvir attenuate CCl4-induced liver fibrosis in mice","authors":"Mayadah M. Abdelsalam, N. El-Mahdy, Sabry Abou-Saif","doi":"10.1016/j.livres.2023.02.001","DOIUrl":"https://doi.org/10.1016/j.livres.2023.02.001","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48139641","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":"A novel nomogram based on routine clinical indicators for screening for Wilson’s disease","authors":"Jiahui Pang, Shuru Chen, W. Gan, Guo-fang Tang, Y. Jie, Zhanyi Li, Y. Chong, Youming Chen, Jiao Gong, Xinhua Li, Yongyu Mei","doi":"10.1016/j.livres.2023.02.003","DOIUrl":"https://doi.org/10.1016/j.livres.2023.02.003","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55273555","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":"MUTYH is a potential prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma","authors":"Fan Yang ,&nbsp;Qinghai Lian ,&nbsp;Beibei Ni ,&nbsp;Xiusheng Qiu ,&nbsp;Yizhan He ,&nbsp;Xiaoguang Zou ,&nbsp;Fangping He ,&nbsp;Wenjie Chen","doi":"10.1016/j.livres.2022.12.002","DOIUrl":"10.1016/j.livres.2022.12.002","url":null,"abstract":"<div><h3>Background</h3><p>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The development of biomarkers for early detection and monitoring of HCC has not shown significant progress. Meanwhile, the second adenomatous polyposis-related gene, MUTYH, which encodes a DNA glycosylase, has been observed in its contribution to oxidative DNA damage repair. Abnormal expression of MUTYH can reduce cell survival rate. Therefore, this study investigated the usefulness of MUTYH in diagnosing and prognosis HCC.</p></div><div><h3>Materials and methods</h3><p>Using The Cancer Genome Atlas (TCGA) data, we analyzed the prognostic value of MUTYH in HCC. We used logistic regression, Wilcoxon signed-rank test, and Kruskal–Wallis test to examine MUTYH expression concerning clinical-pathologic characteristics. Univariate and multivariate Cox regression methods and Kaplan-Meier analysis were applied to determine the related prognostic factors of HCC. The enrichment analysis (GSEA) was used to determine the critical pathways associated with MUTYH. The single-sample gene set enrichment analysis (ssGSEA) was conducted to examine the correlation between MUTYH expression and cancer immune infiltration.</p></div><div><h3>Results</h3><p>The higher expression of MUTYH in HCC patients was associated with a poorer overall survival rate and a shorter disease-specific survival rate. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that all differentially expressed genes (DEGs) between the high and low expression levels of MUTYH significantly enriched in the trace ligand-receptor interaction, cell cycle, oocyte meiosis, gap junction, and DNA replication. Group analysis revealed the signals of their open access. The neuron system, M phase, DNA repair, Rho GTPase effector, and cell cycle checkpoints were significantly enriched. ssGSEA showed a positive correlation between MUTYH expression and the infiltration levels of Th2 cells, NK cells, and T helper cells. Moreover, a negative correlation was found between MUTYH expression and the infiltration levels of dendritic cells (DCs) and cytotoxic cells.</p></div><div><h3>Conclusions</h3><p>MUTYH expression levels were positively correlated with immune checkpoint gene expression levels in HCC tissues. The expression level of MUTYH was related to the prognosis of HCC and the immune infiltration of HCC.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 258-268"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S254256842200071X/pdfft?md5=c28db52aa58f2574000e8f47a90fce43&pid=1-s2.0-S254256842200071X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49435079","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":"Altered serotonin metabolism in Takeda G protein-coupled receptor 5 knockout mice protects against diet-induced hepatic fibrosis","authors":"Jessica M. Ferrell ,&nbsp;Matthew Dilts ,&nbsp;Zachary Stahl ,&nbsp;Shannon Boehme ,&nbsp;Sabita Pokhrel ,&nbsp;Xinwen Wang ,&nbsp;John Y.L. Chiang","doi":"10.1016/j.livres.2022.11.009","DOIUrl":"10.1016/j.livres.2022.11.009","url":null,"abstract":"<div><h3>Background and aims</h3><p>Diet-induced obesity and metabolic syndrome can trigger the progression of fatty liver disease to non-alcoholic steatohepatitis and fibrosis, which is a major public health concern. Bile acids regulate metabolic homeostasis and inflammation in the liver and gut via the activation of nuclear farnesoid X receptor (Fxr) and the membrane receptor Takeda G protein-coupled receptor 5 (Tgr5). Tgr5 is highly expressed in the gut and skeletal muscle, and in cholangiocytes and Kupffer cells of the liver. Tgr5 is implicated in the mediation of liver and gut inflammation, as well as the maintenance of energy homeostasis. Here, we used a high fat, high fructose, and high sucrose (HFS) diet to determine how bile acid signaling through Tgr5 may regulate metabolism during the progression from fatty liver to non-alcoholic steatohepatitis and fibrosis.</p></div><div><h3>Materials and methods</h3><p>Female C57BL/6J control wild type (WT) and Tgr5 knockout (<em>Tgr5</em>^−/−) mice were fed HFS (high fat (40% kcal), high fructose, and 20% sucrose water) diet for 20 weeks. Metabolic phenotypes were characterized through examination of bile acid synthesis pathways, lipid and cholesterol metabolism pathways, and fibrosis and inflammation pathways.</p></div><div><h3>Results</h3><p><em>Tgr5</em>^−/− mice were more glucose intolerant when fed HFS diet, despite gaining the same amount of weight as WT mice. <em>Tgr5</em>^−/− mice accumulated significantly more hepatic cholesterol and triglycerides on HFS diet compared to WT mice, and gene expression of lipogenic genes was significantly upregulated. Hepatic cholesterol 7alpha-hydroxylase (<em>Cyp7a1</em>) gene expression was consistently elevated in <em>Tgr5</em>^−/− mice, while oxysterol 7alpha-hydroxylase (<em>Cyp7b1</em>), sterol 27-hydroxylase (<em>Cyp27a1</em>), <em>Fxr</em>, and small heterodimer partner (<em>Shp</em>) were downregulated by HFS diet. Surprisingly, hepatic inflammation and fibrosis were also significantly reduced in <em>Tgr5</em>^−/− mice fed HFS diet, which may be due to altered serotonin signaling in the liver.</p></div><div><h3>Conclusions</h3><p><em>Tgr5</em>^−/− mice may be protected from high fat, high sugar-induced hepatic inflammation and injury due to altered serotonin metabolism.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 214-226"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000666/pdfft?md5=600911591f416a4a97daeeae4350d526&pid=1-s2.0-S2542568422000666-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46612827","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":"Liver-adipose tissue crosstalk in alcohol-associated liver disease: The role of mTOR","authors":"Yssa Rodriguez,&nbsp;Jack Dunfield,&nbsp;Tyson Roderique,&nbsp;Hong-Min Ni","doi":"10.1016/j.livres.2022.11.006","DOIUrl":"10.1016/j.livres.2022.11.006","url":null,"abstract":"<div><h3>Background</h3><p>Alcohol-associated liver disease (ALD) is a major chronic liver disease around the world without successful treatment. Acute alcoholic hepatitis is one of the most severe forms of ALD with high mortality, which is often associated with binge drinking. Alcohol drinking dysregulates lipid metabolism, increases adipose tissue lipolysis, and induces liver steatosis and adipose tissue atrophy. Increasing evidence implicates that crosstalk of liver and adipose tissue in the pathogenesis of ALD. Mechanistic target of rapamycin (mTOR) is a phosphatidylinositol 3-kinase (PI3K)-like serine/threonine protein kinase that regulates lipid metabolism, cell proliferation and autophagy. However, the role of mTOR in regulating adipose-liver crosstalk in binge drinking-induced organ damage remains unclear.</p></div><div><h3>Methods</h3><p>We generated liver-specific and adipocyte-specific regulatory-associated protein of mTOR (<em>Rptor</em>) knockout (<em>Rptor</em>^LKO and <em>Rptor</em>^AKO) as well as <em>Mtor</em> knockout (<em>Mtor</em>^LKO and <em>Mtor</em>^AKO) mice, by crossing <em>Rptor</em>^flox and <em>Mtor</em>^flox mice with albumin Cre or adiponectin Cre mice, respectively. In addition, we generated liver and adipocyte double deletion of <em>Rptor</em> or <em>Mtor</em> (<em>Mtor</em>^{<em>L</em>AKO} and <em>Rptor</em>^{<em>L</em>AKO}) mice. The knockout mice with their matched wild-type littermates (<em>Rptor</em>^WT and <em>Mtor</em>^WT) were subjected to acute gavage of 7 g/kg ethanol.</p></div><div><h3>Results</h3><p>Mice with adipocyte deletion of <em>Rptor</em> or <em>Mtor</em> developed hepatomegaly and adipose tissue atrophy. Alcohol gavage increased liver injury, hepatic steatosis and inflammation in mouse livers as demonstrated by elevated serum alanine aminotransferase activities, increased hepatic levels of triglyceride and increased hepatic numbers of CD68 positive macrophages in mouse livers after alcohol gavage. Liver injury was further exacerbated by deletion of adipocyte <em>Rptor</em> or <em>Mtor</em>. Serum adipokine array analysis revealed that increased levels of pro-inflammatory cytokines IL-6 and TNFα as well as chemokine MCP-1 following acute alcohol gavage in wild-type mice, which were further increased in adipocyte-specific <em>Mtor</em> or <em>Rptor</em> knockout mice. Conversely, levels of anti-inflammatory cytokine IL-10 decreased in adipocyte-specific <em>Mtor</em> or <em>Rptor</em> knockout mice. The levels of circulating fibroblast growth factor 21 (FGF21) increased whereas levels of circulating adiponectin and fetuin A decreased in wild-type mice after alcohol gavage. Intriguingly, adipocyte-specific <em>Mtor</em> or <em>Rptor</em> knockout mice already had decreased basal level of FGF21 which increased by alcohol gavage. Moreover, adipocyte-specific <em>Mtor</em> or <em>Rptor</em> knockout mice al","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 227-237"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/ed/nihms-1869594.PMC10134744.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9399334","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":"Prediction of effective percutaneous transhepatic biliary drainage in patients with hepatocellular carcinoma: A multi-central retrospective study","authors":"Haofan Wang ,&nbsp;Yitao Mao ,&nbsp;Chunning Zhang ,&nbsp;Xiaojun Hu ,&nbsp;Bin Chen ,&nbsp;Luwen Mu ,&nbsp;Shuyi Wang ,&nbsp;Yifen Lin ,&nbsp;Zhanwang Xiang ,&nbsp;Mingsheng Huang","doi":"10.1016/j.livres.2022.11.008","DOIUrl":"10.1016/j.livres.2022.11.008","url":null,"abstract":"<div><h3>Background and aim</h3><p>Percutaneous transhepatic biliary drainage (PTBD) does not always lead to a reduction in serum total bilirubin (TBil) level in patients with hepatocellular carcinoma and obstructive jaundice. We aimed to develop a model for pre-PTBD prediction of post-procedural TBil decrease in these patients.</p></div><div><h3>Materials and methods</h3><p>Retrospective database searches were conducted at four teaching hospitals (reference period: January 2010 to December 2018), and baseline characteristics of eligible patients were extracted. Any decrease in TBil after PTBD and the lowest level of TBil post-PTBD &lt;5 mg/dL, 3 mg/dL, and 2 mg/dL were each taken as the standard of effectiveness for computation of its own predictive nomogram. For data dimension decrease and feature selection, the least absolute shrinkage and selection operator (LASSO) regression model was used. A multivariable logistic regression analysis was used to develop nomograms. Each nomogram's performance was internally evaluated for its calibration, discriminative ability, and clinical usefulness.</p></div><div><h3>Results</h3><p>Included in the study were 138 patients. The model for end-stage liver disease (MELD) score, platelet count, and portal vein thrombosis (PVT) were predictors in the nomogram for any decrease in TBil; international normalized ratio (INR), MELD score, platelet count, and PVT were predictors for a decrease to &lt;5 mg/dL; MELD score, cholinesterase level (CHE), platelet count, and PVT were predictors for a decrease to &lt;3 mg/dL; and MELD score, CHE, platelet count, and pre-albumin level were predictors for a decrease to &lt;2 mg/dL. The clinical value of the nomograms was proven by decision curve analysis.</p></div><div><h3>Conclusions</h3><p>These models may help inform clinical decision making for performing PTBD procedures.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 269-275"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000678/pdfft?md5=9b5219078528d2251c2bba7f3789df3c&pid=1-s2.0-S2542568422000678-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48793394","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":"Effects of apical sodium-bile acid transporter inhibitor and obeticholic acid co-treatment in experimental non-alcoholic steatohepatitis","authors":"David J. Matye ,&nbsp;Xuan Qin ,&nbsp;Mohammad Nazmul Hasan ,&nbsp;Lijie Gu ,&nbsp;Yung Dai Clayton ,&nbsp;Feng Li ,&nbsp;Tiangang Li","doi":"10.1016/j.livres.2022.11.002","DOIUrl":"10.1016/j.livres.2022.11.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis (NASH) treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many patients. Recently, we have shown that combining a gut-restricted apical sodium-bile acid transporter (ASBT) inhibitor GSK2330672 (GSK) with adeno-associated virus (AAV)-mediated liver fibroblast growth factor 15 (FGF15) overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat, cholesterol, and fructose (HFCFr) diet-induced NASH mouse model. The beneficial effects of the combined treatment can be attributed to the markedly reduced bile acid pool that reduces liver bile acid burden and intestinal lipid absorption. The aim of this study is to further investigate if combining GSK treatment with the orally bioavailable obeticholic acid (OCA), which induces endogenous FGF15 and inhibits hepatic bile acid synthesis, can achieve similar anti-NASH effect as the GSK + AAV-FGF15 co-treatment in HFCFr-diet-fed mice.</p></div><div><h3>Materials and methods</h3><p>Male C57BL/6J mice were fed HFCFr diet to induce NASH and liver fibrosis. The effect of GSK, OCA, and GSK + OCA treatments on NASH development was compared and contrasted among all groups.</p></div><div><h3>Results</h3><p>Findings from this study showed that the GSK + OCA co-treatment did not cause persistent reduction of obesity over a 12-week treatment period. Neither single treatment nor the GSK + OCA co-treatment reduce hepatic steatosis, but all three treatments reduced hepatic inflammatory cytokines and fibrosis by a similar magnitude. The GSK + OCA co-treatment caused a higher degree of total bile acid pool reduction (∼55%) than either GSK or OCA treatment alone. However, such bile acid pool reduction was insufficient to cause increased fecal lipid loss. The GSK + OCA co-treatment prevented GSK-mediated induction of hepatic cholesterol 7alpha-hydroxylase but failed to induce ileal FGF15 expression. GSK did not reduce gallbladder OCA amount in the GSK + OCA group compared to the OCA group, suggesting that ASBT inhibition does not reduce hepatic OCA distribution.</p></div><div><h3>Conclusions</h3><p>Unlike the GSK + AAV-FGF15 co-treatment, the GSK + OCA co-treatment does not provide improved efficacy against NASH and liver fibrosis than either single treatment in mice. The lack of synergistic effect may be partly attributed to the moderate reduction of total bile acid pool and the lack of high level of FGF15 exposure as seen in the GSK + AAV-FGF15 co-treatment.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 276-283"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933918/pdf/nihms-1849309.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764511","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":"Prevalence, diagnosis, treatment, and associated factors of hepatitis C in the United States from 1999 to 2018: A population-based cross-sectional study","authors":"Congnan Zhang ,&nbsp;Jiahui Lu ,&nbsp;Yajing Zhang ,&nbsp;Pengyuan He ,&nbsp;Jinyu Xia ,&nbsp;Mingxing Huang","doi":"10.1016/j.livres.2022.12.003","DOIUrl":"10.1016/j.livres.2022.12.003","url":null,"abstract":"<div><h3>Background and aim</h3><p>Hepatitis C virus (HCV) infection is one of the major global health challenges, leading to a significant increase in rates of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. A comprehensive nationwide survey of trends in prevalence and associated factors could facilitate preventive behavioral interventions. Herein, we sought to determine prevalence, diagnosis, treatment, and risk factors for HCV infection in the general United States (US) population.</p></div><div><h3>Methods</h3><p>This was a secondary analysis of the publicly available data from the US National Health and Nutrition Examination Survey (NHANES). The prevalence of HCV-RNA-positive (HCV-RNA+) was weighted using patient serum sample data collected from 1999 to 2018. A propensity score matching model was used due to the imbalance in the number of HCV-RNA+ and HCV-RNA-negative (HCV-RNA−) patients. Matched variables included gender, age, educational level, marital status, language, household size, alcohol consumption, smoking, number of family members and family income to poverty ratio.</p></div><div><h3>Results</h3><p>The weighted prevalence of HCV-RNA+ was 1.11% (95% confidence interval (CI): 1.02–1.20), 1.58% (95% CI: 1.42–1.74) for men and 0.67% (95% CI: 0.57–0.77) for women aged 20 years or older in the US from 1999 to 2018. The weighted prevalence of HCV-RNA+ increased from 0.87% (95% CI: 0.62–1.12) in 2013–2014, 0.95% (95% CI: 0.68–1.22) in 2015–2016 to 1.00% (95% CI: 0.72–1.28) in 2017–2018, respectively. In propensity-matched analysis, patients with HCV-RNA+ were more likely to be non-Hispanic black, and have had drug use and blood transfusions. Meanwhile, the weighted diagnostic and treatment rates were 56.27% (95% CI: 50.90–61.64) and 35.40% (95% CI: 27.64–43.16) from 1999 to 2018, respectively.</p></div><div><h3>Conclusions</h3><p>Active HCV infection rate increased between 2013 and 2018, varied by demographic and risk variables. In the direct-acting antiviral era, affordable treatment and universal screening have the potential to improve overall national health.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 284-288"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000721/pdfft?md5=072044f4c7cd107f75e110a4bfa40c20&pid=1-s2.0-S2542568422000721-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44483873","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":"Chemical basis of pregnane X receptor activators in the herbal supplement Gancao (licorice)","authors":"Anqi Cheng ,&nbsp;Saifei Lei ,&nbsp;Junjie Zhu ,&nbsp;Jie Lu ,&nbsp;Mary F. Paine ,&nbsp;Wen Xie ,&nbsp;Xiaochao Ma","doi":"10.1016/j.livres.2022.11.007","DOIUrl":"10.1016/j.livres.2022.11.007","url":null,"abstract":"<div><h3>Background and aims</h3><p>The herbal supplement Gancao, also known as licorice, belongs to the genus <em>Glycyrrhiza</em> and has been used worldwide for its hepatoprotective effect. Recent studies have raised concerns about potential herb-drug interactions associated with Gancao via pregnane X receptor (PXR)-mediated induction of hepatic cytochrome P450 3A4 (CYP3A4). The current work aimed to determine the phytochemicals in Gancao that activate PXR and induce CYP3A4.</p></div><div><h3>Methods</h3><p>DPX2 cells were used for cell-based PXR reporter assays. The phytochemicals in Gancao extract were identified using a metabolomics approach. The effects of PXR activators identified from <em>in vitro</em> studies were further investigated in PXR- and CYP3A4-humanized mouse models.</p></div><div><h3>Results</h3><p>Gancao was verified to be a PXR-activating herb. Two major phytochemicals in Gancao, glycyrrhizin (GZ) and glycyrrhetinic acid (GA), did not activate PXR in the cell-based reporter assays. However, glabridin was shown to activate PXR in a dose-dependent manner. <em>In vivo</em> studies confirmed that GZ is not a PXR activator and glabridin is a weak PXR activator. Although GA did not active PXR <em>in vitro</em>, it induced CYP3A4 expression in a PXR-dependent manner in the PXR- and CYP3A4-humanized mice.</p></div><div><h3>Conclusions</h3><p>GZ is not a PXR activator. GA could not activate PXR in cell-based reporter assays but it could activate PXR <em>in vivo</em>. Glabridin is a weak PXR activator. This work provides novel insights into the underlying mechanisms of Gancao-related herb-drug interactions via PXR.</p></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 251-257"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S254256842200068X/pdfft?md5=bff88fec13aebaa46dadfe043b6ab64e&pid=1-s2.0-S254256842200068X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44955475","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":"Pathogenesis of fatty liver diseases and hepatocellular carcinoma","authors":"John Y.L. Chiang,&nbsp;Tiangang Li","doi":"10.1016/j.livres.2022.12.001","DOIUrl":"10.1016/j.livres.2022.12.001","url":null,"abstract":"","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"6 4","pages":"Pages 201-202"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2542568422000708/pdfft?md5=bf3f23283e024892c75b7cd184898a22&pid=1-s2.0-S2542568422000708-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44405448","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}