Article
Medicine, Research & Experimental
Shiqi Zhong, Raphael Chevre, David Castano Mayan, Maria Corliano, Blake J. Cochran, Kai Ping Sem, Theo H. van Dijk, Jianhe Peng, Liang Juin Tan, Siddesh V. Hartimath, Boominathan Ramasamy, Peter Cheng, Albert K. Groen, Folkert Kuipers, Julian L. Goggi, Chester Drum, Rob M. van Dam, Ru San Tan, Kerry-Anne Rye, Michael R. Hayden, Ching-Yu Cheng, Shaji Chacko, Jason Flannick, Xueling Sim, Hong Chang Tan, Roshni R. Singaraja
Summary: Reduced CYP8B1 activity is associated with increased insulin sensitivity in humans, possibly due to increased skeletal muscle insulin sensitivity caused by increased circulating CDCA.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Food Science & Technology
Kai-Kai Zhang, Jia-Li Liu, Li-Jian Chen, Jia-Hao Li, Jian-Zheng Yang, Ling-Ling Xu, Yu-Kui Chen, Qin-Yao Zhang, Xiu-Wen Li, Yi Liu, Dong Zhao, Xiao-Li Xie, Qi Wang
Summary: This study identified the microbial mechanism of Meth-induced hepatic inflammation and suggested its inhibition as a potential therapeutic target for treating Meth-related hepatotoxicity.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Toxicology
Tianwei Zhang, Shanshan Feng, Jiahuan Li, Zhitao Wu, Qiangqiang Deng, Wei Yang, Jing Li, Guoyu Pan
Summary: This study found that FXR agonists, obeticholic acid (OCA) and Px-102, reduced mitochondrial function in hepatocytes and promoted cell apoptosis. Inhibiting FXR or SHP genes alleviated the cytotoxic effects of OCA and Px-102. The dose-related liver damage caused by OCA and Px-102 was confirmed in a high-fat diet mouse model. OCA or Px-102 led to a decrease in hepatocyte-specific genes and augmenter of liver regeneration in the liver.
ARCHIVES OF TOXICOLOGY
(2022)
Review
Oncology
Wenyu Luo, Shiqi Guo, Yang Zhou, Junfeng Zhu, Jingwen Zhao, Mengyao Wang, Lixuan Sang, Bingyuan Wang, Bing Chang
Summary: Bile acids play an important role in cholesterol metabolism and are involved in the development of hepatocellular carcinoma (HCC) by recognizing receptors and mediating downstream pathways. Certain bile acids can delay liver injury and HCC progression. This review introduces the structure, function, metabolism, and enterohepatic circulation of bile acids, summarizes the mechanisms by which they contribute to HCC development, and suggests possible strategies for HCC treatment.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Cheng Mo, Xiaoqing Xu, Pan Zhang, Yihong Peng, Xinpeng Zhao, Shijia Chen, Fang Guo, Yating Xiong, Xin-Jie Chu, Xiaodong Xu
Summary: The farnesoid X receptor (FXR) is a ligand-activated nuclear receptor that affects the expressions of genes involved in bile acid metabolism, inflammation, fibrosis, and lipid and glucose homeostasis. Developing FXR agonists for treating NASH and other FXR-related diseases is of great interest. This study describes the design, optimization, and characterization of a series of nonbile acid FXR agonists known as N-methylene-piperazinyl derivatives. Compound 23, or HPG1860, is a potent FXR agonist with high selectivity, favorable pharmacokinetics, and in vivo activity demonstrated in animal models, and it is currently in phase II clinical development for NASH patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Arezou Azizsoltani, Behzad Hatami, Mohammad Reza Zali, Vahideh Mahdavi, Kaveh Baghaei, Effat Alizadeh
Summary: This study aimed to deliver obeticholic acid (OCA) to the liver using exosomes, and found that exosome-loaded OCA exerted anti-fibrotic effects in fibrotic mice, leading to improvements in related indicators.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Eleanna Kaffe, Manolis Roulis, Jun Zhao, Rihao Qu, Esen Sefik, Haris Mirza, Jing Zhou, Yunjiang Zheng, Georgia Charkoftaki, Vasilis Vasiliou, Daniel F. Vatner, Yuval Kluger, Richard A. Flavell
Summary: Metabolic functions of hepatocytes are regulated by non-parenchymal cells in their microenvironment, revealing the importance of microenvironmental regulation in liver metabolism.
Review
Biochemistry & Molecular Biology
Annarosa Floreani, Daniela Gabbia, Sara De Martin
Summary: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with limited treatment options. Ursodeoxycholic acid (UDCA) is the first-line therapy but is ineffective for a significant portion of patients. Obeticholic acid (OCA) is an effective second-line treatment for UDCA-non responders. Future therapies for PBC are promising.
Review
Pharmacology & Pharmacy
Stefano Fiorucci, Michele Biagioli, Monia Baldoni, Patrizia Ricci, Valentina Sepe, Angela Zampella, Eleonora Distrutti
Summary: FXR agonists show potential in treating nonalcoholic fatty liver disease, but side effects such as elevated cholesterol levels and pruritus are common. Studies are underway to evaluate the benefits and safety of combination therapies.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Medicine, Research & Experimental
Chuangzhen Lin, Bingqing Yu, Xuelian Liu, Lixin Chen, Zhaohui Zhang, Weixiang Ye, Hui Zhong, Wenke Bai, Yuping Yang, Biao Nie
Summary: Objective: This study revealed a novel mechanism by which Obeticholic acid (OCA) improves nonalcoholic fatty liver disease (NAFLD) independent of farnesoid X receptor (FXR), suggesting a potential therapeutic effect of OCA through inhibiting hepatic long-chain fatty acids uptake mediated by FATP5.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoxin X. Wang, Cen Xie, Andrew E. Libby, Suman Ranjit, Jonathan Levi, Komuraiah Myakala, Kanchan Bhasin, Bryce A. Jones, David J. Orlicky, Shogo Takahashi, Alexander Dvornikov, David E. Kleiner, Stephen M. Hewitt, Luciano Adorini, Jeffrey B. Kopp, Kristopher W. Krausz, Avi Rosenberg, James L. McManaman, Charles E. Robertson, Diana Ir, Daniel N. Frank, Yuhuan Luo, Frank J. Gonzalez, Enrico Gratton, Moshe Levi
Summary: The dual FXR-TGR5 agonist INT-767 can prevent the progression of Western diet-induced NASH in mice by modulating bile acid composition, improving liver fatty acid synthesis and uptake, reducing inflammation, and maintaining mitochondrial function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Trinh Van Le, Hong-Thuy Phan-Thi, My-Xuan Huynh-Thi, Thanh Minh Dang, Ai Xuan Le Holterman, Gabriele Grassi, Thao-Uyen Nguyen-Luu, Nhung Hai Truong
Summary: Chloroquine (CQ) treatment has been shown to prevent hepatic stellate cell (HSC) activation and autophagy, leading to a reduction in liver fibrogenesis. In both in vitro and in vivo experiments, CQ inhibited HSC activation, improved liver function, and reduced liver injury.
Article
Plant Sciences
Yuanyuan Zhai, Wenling Zhou, Xu Yan, Yuan Qiao, Lingling Guan, Zhichun Zhang, Hao Liu, Jizhi Jiang, Jiang Liu, Liang Peng
Summary: This study investigated the effect of AS-IV on NAFLD and explored the involvement of intestinal flora. AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. The changes in intestinal flora and BAs were found to play an essential role in the remission of hepatic steatosis by AS-IV.
Article
Chemistry, Multidisciplinary
Jingyi Guo, Shangyi Huang, Qincheng Yi, Naihua Liu, Tianqi Cui, Siwei Duan, Jiabing Chen, Jiayu Li, Jun Li, Lei Wang, Yong Gao, Guangning Nie
Summary: Non-alcoholic fatty liver disease (NAFLD) is a serious liver disease that is increasing globally due to high calorie and fat diets. This study analyzed the effects of calsyntenin-3 (Clstn3) on lipid metabolism in NAFLD. The results showed that overexpression of Clstn3 improved lipid metabolism disorders and reduced liver injury and inflammation in NAFLD model mice. Clstn3 was found to be closely related to lipid metabolism disorder in NAFLD and may be a potential target for treatment.
Article
Chemistry, Multidisciplinary
Zi-bo Li, Lin Jiang, Jia-dong Ni, Yuan-hang Xu, Fang Liu, Wen-ming Liu, Shao-gui Wang, Zhong-qiu Liu, Cai-yan Wang
Summary: UDP-glucose ceramide glucosyltransferase (UGCG) is over-expressed in fibrotic livers and activated hepatic stellate cells (HSCs), and its inhibition can suppress HSC activation and alleviate hepatic fibrosis. Salvianolic acid B (SAB) from Salvia miltiorrhiza is identified as an UGCG inhibitor and shows potential as a candidate drug for liver fibrosis treatment with anti-inflammatory effects.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Analytical
Ruirui Chang, Si-Tao Xu, Hao-Wen Jin, Yong-Jie Zhao, Tian-Yu Hu, Guangji Wang, Jiankun Wang, Le Zhen
Summary: A LC-MS/MS method was developed for simultaneous determination of ZL-01 and its metabolites in rat plasma, considering stability issues. The method showed good linearity, precision, and accuracy, and was successfully applied in pharmacokinetic studies. Results suggested rapid metabolism of ZL-01 and identified M8 as a main metabolite after oral absorption.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Pharmacology & Pharmacy
Jing Li, Runbin Sun, Hui Xu, Guangji Wang
Summary: The study demonstrates that mesoporous silica nanoparticles (MSNs) have substantial effects on hepatic metabolism, with intravenous injection leading to more significant impairments compared to oral administration.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Bin Wang, Zongyu Cai, Siliang Chen, Ya Chen, Shixuan Jiao, Qiang Ren, Xuekun Wang, Xinqian Geng, Zheng Li, Guangji Wang
Summary: This study successfully developed a partial agonist of the free fatty acid receptor 1 (FFA1) with reduced lipophilicity, which showed good activity in lowering blood glucose.
Article
Oncology
Mengjie Yu, Wei Wen, Xin Yi, Wei Zhu, Jiye Aa, Guangji Wang
Summary: This study found impaired oxidative stress function in ESCC patients and identified risk metabolites associated with the development of ESCC. The levels of alpha-tocopherol and cysteine decreased progressively, while the levels of aminomalonic acid increased progressively. A high level of aminomalonic acid was a risk factor for the development of ESD to ESCC and for lymphatic metastasis in ESCC patients. A low level of alpha-tocopherol was an independent risk factor for ESCC. The panel constructed by glycolic acid, oxalic acid, glyceric acid, malate, and alpha-tocopherol performed well in distinguishing ESD/ESCC from healthy controls.
FRONTIERS IN ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
Tingting Yan, Yuhong Luo, Nana Yan, Keisuke Hamada, Nan Zhao, Yangliu Xia, Ping Wang, Changdong Zhao, Dan Qi, Shoumei Yang, Lulu Sun, Jie Cai, Qiong Wang, Changtao Jiang, Oksana Gavrilova, Kristopher W. Krausz, Daxesh P. Patel, Xiaoting Yu, Xuan Wu, Haiping Hao, Weiwei Liu, Aijuan Qu, Frank J. Gonzalez
Summary: Intestinal PPAR alpha signaling modulates fatty acid uptake through regulating FABP1 expression, contributing to NASH progression. Targeting this pathway could be a potential therapeutic strategy for NASH treatment.
Article
Chemistry, Multidisciplinary
Jing Wu, Yun-ge Lou, Xu-le Yang, Rui Wang, Ran Zhang, Ji-ye Aa, Guang-ji Wang, Yuan Xie
Summary: This study found that ER stress plays a crucial role in the inhibition of P450s activity in NAFLD, and silybin regulates P450s activity by attenuating ER stress. Silybin can restore the activity of P450s in liver microsomes and may have potential benefits for the treatment of NAFLD.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Chemistry, Analytical
Xiao-Wei Xu, Ya Zhu, Jiang-Zhou Song, Gui-Qing Zou, Zhou Zhao, Qiu-Ling Zheng, Li-Juan Cao, Guang-Ji Wang, Hong Wang, Hai-Ping Hao
Summary: Investigated the expression differences of FXR in different organs and the influence of factors such as diet and circadian rhythm on FXR homeostasis. Developed a method for real-time monitoring of FXR expression in cells.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chujie Ding, Yu Hong, Yuan Che, Tianyu He, Yun Wang, Shule Zhang, Jiawei Wu, Wanfeng Xu, Jingyi Hou, Haiping Hao, Lijuan Cao
Summary: Cholestasis, a common complication of hepatitis B virus infection, has been found to negatively impact T cells response and hinder viral clearance. Bile acids disrupt calcium homeostasis, impairing T cells activation and signaling. Targeting bile acid regulation may be a therapeutic strategy for host-virus defense.
Article
Biotechnology & Applied Microbiology
Hai-Ping Hao, Fei Xia, Hong-Tong Bai, Xun-you Yan, Hong-xia Cui, Xiao-ming Xie, Lei Shi
Summary: This study investigates the effect of bio-control plant Litsea cubeba branch inter-row cover on soil bacterial community, soil-enriched metabolites, and soil mineral nutrition in tea plantation. The results show that Litsea cubeba inter-row cover can modify the soil microbial structure and diversity, antagonize the plant pathogen community, and improve the soil aluminum and phosphorus status.
ANNALS OF MICROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jiajia Shen, Huimin Guo, Shijia Liu, Wei Jin, Zhi-Wei Zhang, Yong Zhang, Keanqi Liu, Shuying Mao, Zhihao Zhou, Lin Xie, Guangji Wang, Haiping Hao, Yan Liang
Summary: This study identifies the crucial role of intestinal flora and microbiota metabolites in the occurrence and treatment of ischaemic stroke. The accumulation of branched-chain amino acids is closely associated with gut microflora dysbiosis and neuroinflammation. Lactobacillus helveticus and Lactobacillus brevis colonization exhibit neuroprotective activity and alleviate the accumulation of branched-chain amino acids.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tingting Yao, Heng Xiao, Hong Wang, Xiaowei Xu
Summary: Proteolysis-targeting chimera (PROTAC) is a promising molecule that degrades specific proteins through the ubiquitin-proteasome system. It has shown remarkable efficacy in various fields and opened up new avenues for biomedical research and development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Shuang Cui, Huijian Hu, An Chen, Ming Cui, Xiaojie Pan, Pengfei Zhang, Guangji Wang, Hong Wang, Haiping Hao
Summary: The acetylation of FXR regulates its nucleocytoplasmic shuttling and degradation under conditions of liver injury, which limits the clinical benefits of FXR agonists. SIRT1 activators can reduce FXR acetylation and prevent its cytosolic degradation, and combining SIRT1 activators with FXR agonists shows promise in treating liver diseases.
ACTA PHARMACEUTICA SINICA B
(2023)
Review
Chemistry, Medicinal
Kang Wang, Yuecan Zhang, Guangji Wang, Haiping Hao, Hong Wang
Summary: Nonalcoholic fatty liver disease is a common liver disease without approved pharmacotherapy. Farnesoid X receptor (FXR) is considered a promising therapeutic target, but currently developed drugs have shown limited efficacy in clinical trials. This review summarizes the development of the FXR agonist obeticholic acid and discusses its limitations in depth.
MEDICINAL RESEARCH REVIEWS
(2023)
Article
Psychology, Multidisciplinary
Haiping Hao, Xiaobao Li, Xi Shen, Hong Jiang, Haoyue Xiao, Houchao Lyu
Summary: This study examined the reciprocal relationship between future time perspective and self-control among adolescents. The results showed that future-negative and future-confusional were negatively related to self-control, while future-positive, future-perspicuity, future-perseverant, and future-planning were positively related to self-control. The study also found reciprocal relationships between future-confusional, future-planning, and self-control.
CURRENT PSYCHOLOGY
(2023)