A5064417561- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Drug Transport and Resistance Mechanisms
- Neonatal Health and Biochemistry
- Click Chemistry and Applications
- Analytical Methods in Pharmaceuticals
- Protein Degradation and Inhibitors
- Hemoglobinopathies and Related Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Organ Transplantation Techniques and Outcomes
- Amino Acid Enzymes and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- Beetle Biology and Toxicology Studies
- Cancer Research and Treatments
- Computational Drug Discovery Methods
- Potassium and Related Disorders
- Pharmacogenetics and Drug Metabolism
China Pharmaceutical University
2021-2024
State Key Laboratory of Natural Medicine
2024
Second Affiliated Hospital of Zhejiang University
2023
Tsinghua University
2003
Mixed lineage kinase domain–like pseudokinase (MLKL) initiates necroptosis and could serve as a therapeutic target related to series of human diseases. Proteolysis-targeting chimeras (PROTACs) are useful tools for degrading pathological proteins blocking disease processes. Using computer-aided modeling molecular dynamics simulations, we developed covalent MLKL PROTACs by linking optimizing theophylline derivative that covalently targets MLKL. Via structure–activity relationship studies,...
Liver injury is often associated with hepatic retinopathy, resulting from accumulation of retinal toxins due to blood–retinal barrier (BRB) dysfunction. Retinal pigment epithelium highly expresses MRP1/Mrp1. We aimed investigate whether liver affects the function and expression Mrp1 using bile duct ligation (BDL) rats. distributions fluorescein 2,4-dinitrophenyl-S-glutathione were used for assessing function. BDL significantly increased two substrates bilirubin, downregulated protein,...
Aim: Hepatic ischemia-reperfusion (HIR) induces remote organs injury, including the brain. The homeostasis of brain is maintained by blood-brain barrier (BBB); thus, we aimed to investigate whether HIR impaired BBB and attempted elucidate its underlying mechanism. Methods: Cell viability human cerebral microvascular endothelial cells (hCMEC/D3) was measured following 24 h incubation with a serum rat undergoing 1 ischemia 4 reperfusion, liver homogenate, or lysate primary hepatocytes rat....
Polypharmacological drugs are of great value for treating complex human diseases by the combinative modulation several biological targets. However, multitarget drug design with more than two targets is challenging and generally discovered serendipity. Herein, a restricted fragment docking (RFD) computational method combined phenotypic discovery approach was developed rational polypharmacological design. Via genetic combination studies in microglial phenotype, we first identified novel...
The lethality of torsades de pointes (TdP) by drugs is one main reasons that some were withdrawn from the market. In order to assess drug-induced TdP risks, a model cardiac ionic current suppression in human ventricular myocytes (ToR-ORd model), combined with maximum effective free therapeutic plasma concentration or myocyte was often used, latter proved be more relevant and accurate. We aimed develop whole-body physiologically-based pharmacokinetic (PBPK) model, incorporated cardiomyocyte...