A5060156606- Berberine and alkaloids research
- Hepatitis C virus research
- Cancer therapeutics and mechanisms
- Antibiotic Resistance in Bacteria
- Viral Infections and Immunology Research
- Liver Disease Diagnosis and Treatment
- Drug Transport and Resistance Mechanisms
- Alkaloids: synthesis and pharmacology
- Synthesis and biological activity
- Hepatitis B Virus Studies
- Bioactive natural compounds
- Autophagy in Disease and Therapy
- Synthesis and Biological Activity
- interferon and immune responses
- Carbohydrate Chemistry and Synthesis
- Liver physiology and pathology
- RNA and protein synthesis mechanisms
- Phytochemistry and biological activities of Ficus species
- Synthesis and Biological Evaluation
- Influenza Virus Research Studies
- Traditional and Medicinal Uses of Annonaceae
- Natural Antidiabetic Agents Studies
- HIV/AIDS drug development and treatment
- Cytomegalovirus and herpesvirus research
- Chemical Synthesis and Analysis
Chinese Academy of Medical Sciences & Peking Union Medical College
2016-2025
Institute of Medicinal Plant Development
2005-2025
National Health and Family Planning Commission
2025
South China University of Technology
2023
Tsinghua University
2022-2023
State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering
2022
Xi'an Polytechnic University
2022
London School of Economics and Political Science
2022
Academy of Medical Sciences
2021
Academia Sinica
2021
Programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), proven anti-inflammation drug, as negative regulator PD-L1 from set traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity tumour cells to co-cultured T-cells by...
Berberine (BBR), a traditional Chinese medicine, has therapeutic effects on variety of inflammation-related diseases, but its direct proteomic targets remain unknown. Using activity-based protein profiling, we first demonstrated that BBR directly the NEK7 via hydrogen bond between 2,3-methylenedioxy and 121-arginine (R121) residues. The fact R121 is located precisely within key domain involved in NEK7–NLRP3 interaction allows to specifically block successively inhibit IL-1β release,...
Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, regulates several key inflammatory pathways through indicating dominant role EIF2AK2. Also, could subtly inhibit dimerization rather than enzyme activity, to selectively modulate downstream including JNK, NF-κB, AKT NLRP3, an advantage good safety...
Abstract Background Berberine (BBR) is a drug with multiple effects on cellular energy metabolism. The present study explored answers to the question of which CYP450 (Cytochrome P450) isoenzymes execute phase-I transformation for BBR, and what are bioactivities its metabolites pathways. Methods BBR were detected using LC-MS/MS. Computer-assistant docking technology as well bioassays recombinant CYP450s employed identify responsible transformation. Bioactivities in liver cells examined real...
To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty-five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure-activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial potency. Among them, compounds 2f, 2i, 2n, 2o 8b exhibited increased activities, inhibition...
Nineteen new quinoline derivatives were prepared via the Mannich reaction and evaluated for their antibacterial activities against both Gram-positive (G+) Gram-negative (G−) bacteria, taking compound 1 as lead. Among target compounds, quinolone coupled hybrid 5d exerted potential effect most of tested G+ G− strains with MIC values 0.125–8 μg/mL, much better than those 1. Molecular-docking assay showed that might bacterial LptA Top IV proteins, thereby displaying a broad-spectrum effect. This...
Programmed death-ligand 1 (PD-L1) is a T-cell inhibitory checkpoint molecule that suppresses antitumor immunity. Anti-PD-L1 antibodies have shown remarkable promise in treating tumors, but the patient response rate low. Therefore, small-molecule inhibitors blocking PD-L1 function are urgently needed.Changes of protein expression and phosphorylation levels were determined by immunoblotting. The level Membrane was examined flow cytometer. Cytotoxicity T cells NK toward tumor detected using LDH...
The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an candidate phase III trials, decreases efficiency programmed –1 ribosomal frameshifting coronaviruses thus impedes viral replication fashion. Carrimycin binds directly to coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting protein...
Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) methylenedioxy group at 2- 3-position is an essential element to keep activity, (ii) 7-position quaternary ammonium planar structure compound are activity-required, (iii) addition electron-donating groups 7- 13-position reduced activity. Of 1 analogues, 2...
Heat-stress cognate 70 (Hsc70) is a host protein required for hepatitis B virus (HBV) replication, and oxymatrine (1) suppresses Hsc70 expression. Taking as target against HBV, 22 analogues of 1 defined with substituents at position 1, 13, or 14 were synthesized evaluated their activity on mRNA The SAR revealed that (i) the oxygen atom 1-position was not essential, (ii) increasing electron density ring D reduced activity, (iii) introducing proper substituent 13- and/or 14-position(s),...
Abstract The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression either surface or soluble form. attachment was facilitated through direct interaction between and E1 protein, causing enhanced entry replication. co-receptor effect independent SR-BI. monoclonal antibodies neutralized the reduced inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound but not SR-BI, significantly...
Abstract Helicobacter pylori ( H. ) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training fine-tuning, was aided in predicting exploring novel against . positively predicted berberine derivative 8 3,13-disubstituted alkene exhibited a potency all tested...
Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after sustained virological response.Therefore, it great clinical importance to understand the mechanism potential factors that promote cure by treatment with DAAs.Here, we found tubulointerstitial nephritis antigen-like 1 (TINAGL1) significantly increased HCV-infected hepatocytes and patients fibrosis, higher TINAGL1...