Article
Biochemistry & Molecular Biology
Eun Young Kim, Jae Man Lee
Summary: In this study, it was found that activation of NRF2 in autophagy-deficient conditions inhibits the transactivation of FXR. Decreased inductions of FXR target genes were observed in liver-specific Atg7 knockout mice and with the treatment of autophagy inhibitors. Furthermore, enforced NRF2 activation using small molecules effectively reduced the pharmacological activation of FXR in cultured cells. These findings reveal a novel function of the basal autophagy-NRF2 axis in regulating FXR transactivation and provide insights for potential therapeutic strategies in metabolic diseases.
Article
Gastroenterology & Hepatology
Stefania Grimaudo, Paola Dongiovanni, Jussi Pihlajamaki, Mohammed Eslam, Hannele Yki-Jarvinen, Rosaria Maria Pipitone, Guido Baselli, Calogero Camma, Vito Di Marco, Marco Enea, Miriam Longo, Grazia Pennisi, Daniele Prati, Rossella Zito, Anna Ludovica Fracanzani, Antonio Craxi, Jacob George, Stefano Romeo, Luca Valenti, Salvatore Petta
Summary: The NR1H4 gene rs35724 C allele is protective against severity of steatosis, steatohepatitis, and liver fibrosis, but is associated with higher total circulating cholesterol levels. Patients carrying the NR1H4 rs35724 C allele show increased hepatic mRNA levels of FXR and genes involved in bile acid synthesis. This suggests that increased hepatic FXR expression due to the NR1H4 rs35724 C allele may have potential therapeutic implications for NAFLD.
LIVER INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
Kyounghwa Jung, Minwook Kim, Juhoon So, Seung-Hoon Lee, Sungjin Ko, Donghun Shin
Summary: This study identifies that activation of farnesoid X receptor (FXR) impairs biliary epithelial cell (BEC)-driven liver regeneration by enhancing PTEN activity. FXR activation reduces hepatic progenitor cell proliferation and increases cell death by inhibiting the PI3K-AKT-mTOR signaling pathway.
Article
Biochemistry & Molecular Biology
Pin-Ho Pan, Ya-Yu Wang, Shih-Yi Lin, Su-Lan Liao, Yu-Fang Chen, Wei-Chi Huang, Chun-Jung Chen, Wen-Ying Chen
Summary: 18-β-Glycyrrhetinic acid has promising hepatoprotective effects against cholestatic liver injury, improving liver histology and reducing oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis.
Review
Biochemistry & Molecular Biology
Katrin Panzitt, Martin Wagner
Summary: The liver serves as a central metabolic hub that coordinates nutritional inputs and metabolic outputs. FXR in the liver and intestine plays a crucial role in regulating postprandial nutrient disposal. Aside from classical roles, FXR also has effects on amino acid, protein metabolism, autophagic turnover, and inflammation, which are less studied. Additionally, understanding of how FXR signaling is affected by posttranslational modifications and different isoforms is important for potential pharmaceutical targeting in clinical applications.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Lidia F. Hernandez, Angie B. Dull, Soumya Korrapati, Christina M. Annunziata
Summary: Ovarian cancer, the most lethal gynecological cancer in the US, is characterized by resistance to chemotherapy. Low Caspase 8 expression levels are associated with resistance to apoptotic chemotherapy in ovarian cancers. Combination treatment with a Smac-mimetic can increase cell death in tumor cells with low Caspase 8, leading to decreased tumor growth and enhanced overall survival in mouse models. Timing of drug administration is crucial for optimizing treatment outcomes.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoying Liu, Mahmoud Khalafalla, Chuhan Chung, Yevgeniy Gindin, Susan Hubchak, Brian LeCuyer, Alyssa Kriegermeier, Danny Zhang, Wei Qiu, Xianzhong Ding, Deyu Fang, Richard Green
Summary: The hepatic XBP1 pathway is activated in older Fxr-/- mice and has a protective role.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Immunology
Zhitao Qi, Dong Yan, Lu Cao, Yang Xu, Mingxian Chang
Summary: Bid, a member of the Bcl-2 family, enhances apoptosis rate and inhibits invasion and proliferation of E. ictaluri in zebrafish. Overexpression of p53, on the other hand, increases invasion and proliferation of E. ictaluri. Interestingly, co-overexpression of Bid and p53 results in inhibition of E. ictaluri invasion and proliferation. Furthermore, treatment with Z-IETD-FMK affects the number of E. ictaluri in larvae, with Bid-FLAG significantly decreasing the number even with prior treatment.
FRONTIERS IN IMMUNOLOGY
(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
Endocrinology & Metabolism
Hao Sun, Sunmi Seok, Hyunkyung Jung, Byron Kemper, Jongsook Kim Kemper
Summary: This study found that obesity-induced miR-802 promotes NAFLD/NASH by targeting AMPK. OCA treatment reduces miR-802 levels, improves AMPK activity, and ameliorates steatosis, inflammation, and apoptosis. However, overexpression of miR-802 or downregulation of AMPK can reverse the beneficial effects of OCA on NASH pathologies, particularly reducing apoptosis.
MOLECULAR METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Heng Zhou, Feng Zhang, Fengchao Zhai, Ye Su, Ying Zhou, Zhenglin Ge, Priyadarshini Tilak, Jurgen Eirich, Iris Finkemeier, Ling Fu, Zongmin Li, Jing Yang, Wenbiao Shen, Xingxing Yuan, Yanjie Xie
Summary: Osmotic stress caused by drought and high salinity is a significant threat to plant growth. This study reveals the critical role of thiol peroxidase GPX1 in osmotic stress response in rice, functioning as a redox sensor and transducer. GPX1 is quickly oxidized under osmotic stress and forms an intramolecular disulfide bond, which activates the transcription factor bZIP68 involved in the osmotic stress response pathway. The study also highlights the coordination of protein acetylation and redox signaling in plant osmotic stress responses.
Review
Biochemistry & Molecular Biology
Zi-Lin Ren, Chang-Xiang Li, Chong-Yang Ma, Dan Chen, Jia-Hui Chen, Wen-Xiu Xu, Cong-Ai Chen, Fa-Feng Cheng, Xue-Qian Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) affects a significant population worldwide and has implications beyond the liver, including the brain. The bile acid signaling pathway plays a crucial role in the development of NAFLD and brain disorders. Bile acids can send messages to the brain through direct or indirect channels, potentially impacting brain health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Haiyan Li, Ting Guan, Shi Qin, Qihao Xu, Lina Yin, Qingzhong Hu
Summary: Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are liver diseases caused by systemic metabolic dysfunction, affecting a significant portion of the global adult population and posing high risks of progression to serious liver conditions. Current drug discovery focuses on modifying metabolic processes and inhibiting inflammation and fibrosis, with potential in natural compounds that have not been fully explored. Compounds found in healthy food could be used as adjuvants to lifestyle changes, while natural products like alkaloids and sesquiterpenoids show promise for further development through structural modifications.
DRUG DISCOVERY TODAY
(2023)
Article
Pharmacology & Pharmacy
Ankang Peng, Shunzhi Liu, Lu Fang, Zixing Zhu, Yuan Zhou, Shanshan Yue, Zejiang Ma, Xiaoang Liu, Shilin Xue, Yingkun Qiu, Rong Qi
Summary: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Inonotus obliquus (IO), a folk medicinal fungus, has shown inhibitory effects on NAFLD by attenuating hepatic lipid accumulation through regulating liver lipogenesis pathways.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jing Zeng, Jiangao Fan, Huiping Zhou
Summary: Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), gradually progress to liver fibrosis, cirrhosis, and failure. Disruption of bile acid metabolism and intrahepatic circulation plays a crucial role in accelerating the progression of cholestatic liver diseases. Bile acids not only act as detergents for nutrition absorption but also function as key signaling molecules that regulate hepatic metabolism and immune responses. This review focuses on the role of bile acid-mediated signaling in cholestatic liver disease.
CELL AND BIOSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
He Wang, Yi-sha Du, Wen-shuo Xu, Chang-jian Li, Hong Sun, Kang-rui Hu, Yuan-zhuo Hu, Teng-jie Yu, Hui-min Guo, Lin Xie, Guang-ji Wang, Yan Liang
Summary: The study demonstrates that exogenous GSH exerts a therapeutic effect on ischemic stroke by increasing intrastriatal DA levels in rats. The accumulated DA enhances the exposure of GSH and its related substances, thereby promoting the therapeutic effect of GSH.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Zongyu Cai, Bin Wang, Zongtao Zhou, Xin Zhao, Lijun Hu, Qiang Ren, Liming Deng, Zheng Li, Guangji Wang
Summary: Compound 5, a glycine-conjugated derivative of FXR agonist 4, was found to have better protective effects against APAP-induced hepatotoxicity than its parent compound, through regulating the expressions of genes related to FXR and oxidative stress. This suggests that compound 5 is a promising FXR agonist for further research.
CHEMICAL BIOLOGY & DRUG DESIGN
(2022)
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
Biochemical Research Methods
Rongfan Tang, Pengcheng Chen, Zhe Wang, Lingling Wang, Haiping Hao, Tingjun Hou, Huiyong Sun
Summary: “Drug design targeting protein-protein interactions associated with disease development is crucial. Besides interrupting interactions, stabilizing protein-protein interactions can also be beneficial for therapy. However, characterizing the stabilization effect of stabilizers is challenging, which highlights the importance of developing reliable computational strategies.”
BRIEFINGS IN BIOINFORMATICS
(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, Medicinal
Yun Wang, Yuanyuan Xu, Xiaowei Xu, Hong Wang, Dong Wang, Wenchao Yan, Jiaying Zhu, Haiping Hao, Guangji Wang, Lijuan Cao, Jun Zhang
Summary: This study confirmed the beneficial effects of Ginkgo biloba leave extract (GbE) in alleviating hypercholesterolemia, inflammation, and atherosclerosis. GbE treatment reshaped the intestinal microbiota, downregulated proinflammatory cytokines, and enhanced the expression of tight junction proteins. It also reversed the dysfunction of microbial metabolic phenotypes and reduced atherosclerotic plaque areas. These findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.
PHYTOTHERAPY RESEARCH
(2022)
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
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)
Article
Plant Sciences
Lu Zhang, Ling-Ling Wang, Hao Zeng, Bin Li, Hua Yang, Guang-Ji Wang, Ping Li
Summary: The study found that long-term CDDP treatment has prolonged and stable efficacy against AMI. Compared with short-term treatment, it specifically regulates purine and taurine and hypotaurine metabolism and systematically corrects metabolic disorders.
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)