A5102745002- Cell death mechanisms and regulation
- MicroRNA in disease regulation
- Receptor Mechanisms and Signaling
- Cancer-related molecular mechanisms research
- PI3K/AKT/mTOR signaling in cancer
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Cancer therapeutics and mechanisms
- Circular RNAs in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Melanoma and MAPK Pathways
- Gear and Bearing Dynamics Analysis
- Epigenetics and DNA Methylation
- Pain Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Spaceflight effects on biology
- Natural Compounds in Disease Treatment
- Electromagnetic Fields and Biological Effects
- Neurotransmitter Receptor Influence on Behavior
- Protein Tyrosine Phosphatases
- Computational Drug Discovery Methods
Shanxi Medical University
2018-2025
Chongqing Medical University
2012-2024
First Affiliated Hospital of Kunming Medical University
2024
Kunming Medical University
2016-2024
The Affiliated Yongchuan Hospital of Chongqing Medical University
2012-2024
Hebei University
2024
Ningxia Medical University
2024
Soochow University
2024
Yan'an Hospital Affiliated To Kunming Medical University
2016-2023
Children's Hospital of Chongqing Medical University
2022
We examined whether betulin, a naturally abundant compound, has anticancer functions in human cancer cells. The results showed that betulin significantly inhibited cell viability cervix carcinoma HeLa cells, hepatoma HepG2 lung adenocarcinoma A549 and breast MCF-7 cells with IC(50) values ranging from 10 to 15 microg/mL. While exhibited only moderate activity other such as SK-HEP-1 prostate PC-3, NCI-H460, 20 60 microg/mL, it minor growth inhibition erythroleukemia K562 (IC(50) > 100...
In our continued attempts to identify novel and effective pan-Bcl-2 antagonists, we have recently reported a series of compound 2 (Apogossypol) derivatives, resulting in the chiral 4 (8r). We report here synthesis evaluation on its optically pure individual isomers. Compound 11 (BI-97C1), most potent diastereoisomer 4, inhibits binding BH3 peptides Bcl-X(L), Bcl-2, Mcl-1, Bfl-1 with IC(50) values 0.31, 0.32, 0.20, 0.62 microM, respectively. The also potently cell growth human prostate...
We report the characterization and optimization of drug-like small molecule inhibitors tissue-nonspecific alkaline phosphatase (TNAP), an enzyme critical for regulation extracellular matrix calcification during bone formation growth. High-throughput screening (HTS) a library led to identification arylsulfonamides as potent selective TNAP. Critical structural requirements activity were determined, compounds subsequently profiled in vitro bioavailability parameters including metabolic...
Abstract Guided by a combination of nuclear magnetic resonance binding assays and computational docking studies, we synthesized library 5,5′ substituted Apogossypol derivatives as potent Bcl-XL antagonists. Each compound was subsequently tested for its ability to inhibit in an vitro fluorescence polarization competition assay exert single-agent proapoptotic activity human cancer cell lines. The most BI79D10 binds Bcl-XL, Bcl-2, Mcl-1 with IC50 values 190, 360, 520 nmol/L, respectively,...
Aberrant AKT activation is prevalent across human cancer lineages, providing an important therapeutic target. comprises three isoforms that mediate critical non-redundant, even opposing functions in pathophysiology. Therefore, targeting specific particular cancers may be more effective than pan-AKT inhibition while avoiding disadvantages of inhibition. Currently, isoform-specific expression and are not clearly characterized. We systematically characterized 211 cell lines derived from...
Guided by nuclear magnetic resonance (NMR) binding assays and computational docking studies, a series of 5,5′ substituted apogossypol derivatives was synthesized that resulted in potent pan-active inhibitors antiapoptotic Bcl-2 family proteins. Compound 8r inhibits the BH3 peptides to Bcl-XL, Bcl-2, Mcl-1, Bfl-1 with IC50 values 0.76, 0.32, 0.28, 0.73 μM, respectively. The compound also potently cell growth human lung cancer BP3 B-cell lymphoma lines EC50 0.33 0.66 shows little cytotoxicity...
The modification of 3′-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing cyclopentyl moiety led to development new mGluR2 positive allosteric modulators (PAMs) with optimized potency superior druglike properties. These analogues are more potent than 1 in vitro highly selective for vs other mGluR subtypes. They have significantly improved pharmacokinetic (PK) properties,...
We report the discovery and validation of a series benzoisothiazolones as potent inhibitors phosphomannose isomerase (PMI), an enzyme that converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P) and, more importantly, competes with phosphomannomutase 2 (PMM2) for Man-6-P, diverting this substrate from critical protein glycosylation events. In congenital disorder type Ia, PMM2 activity is compromised; thus, PMI inhibition potential strategy development therapeutics....
Our focus in the past several years has been on identification of novel and effective pan-Bcl-2 antagonists. We have recently reported a series Apogossypolone (ApoG2) derivatives, resulting chiral compound (+/-) BI97D6. report here synthesis evaluation its optically pure (-) (+) atropisomers. Compound BI97D6 potently inhibits binding BH3 peptides to Bcl-XL, Bcl-2, Mcl-1 Bfl-1 with IC50 values 76 ± 5, 31 2, 25 8 122 28 nM, respectively. In cellular assay, effectively cell growth PC-3 human...
As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 PAMs and no at mGlu3. Compound optimization led to the identification potent mGlu2/3 selective with in vitro mGlu1,4-8 or 45 other CNS receptors. In pharmacological characterization representative compound 44 indicated...
Abstract It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy shown to influence apoptosis. In previous studies, we reported anti-β 1 -adrenergic receptor autoantibodies (β -AABs) decreased autophagy, but role cardiomyocyte remains unclear. present study, used a β -AAB-immunized rat model investigate We level autophagic flux increased early then an actively model. Rapamycin, mTOR inhibitor, restored presence -AABs....
The rising incidence and complications of diabetes constitutes a major public health issue. mortality rate diabetes-induced myocardial ischemia/reperfusion (I/R) injury is significantly elevated. Resveratrol (RSV) naturally occurring polyphenol considered to be potent cardioprotective compound. aim the present study was explore function molecular mechanism RSV on I/R injury. Left anterior descending coronary artery ligation performed stimulate in streptozotocin-induced diabetic rats. Heart...
Anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein, is one of the receptors that facilitates entrance anthrax into cells. Previous studies have confirmed pivotal role ANTXR1 in progression and tumorigenesis diverse cancer types. However, biological function gastric (GC) still unknown. The present study aimed to investigate GC illuminate potential molecular mechanisms. Bioinformatics analysis found expression was significantly upregulated tissue its overexpression associated...
Abstract Heparan sulfate proteoglycan 2 (HSPG2), also known as perlecan, is a large multi-domain extracellular matrix proteoglycan, which contributes to the invasion, metastasis and angiogenesis of solid tumor. However, very little about effect HSPG2 on acute myeloid leukemia (AML). This study aims investigate prognostic value gene in terms overall survival leukemia-free patients with AML. Bone marrow mononuclear cells (BMMCs) from 4 AML 3 healthy controls were processed for RNA-Sequencing...
Abstract Objective To examine the effect of spinal cord adenosine (Ado) receptor stimulation on rat adjuvant‐induced arthritis (AIA). Methods Long‐term intrathecal (IT) catheters were implanted into rats to provide access for drug delivery. Animals immunized with complete Freund's adjuvant at tail base. Eight days later and every other day thereafter until 20, treated IT selective Ado A1 agonist cyclohexyladenosine (CHA) or vehicle. In some experiments, animals received an additional daily...
Overexpression of antiapoptotic Bcl-2 family proteins is commonly related with tumor maintenance, progression, and chemoresistance. Inhibition these an attractive approach for cancer therapy. Guided by nuclear magnetic resonance (NMR) binding assays, a series 5,5′ substituted compound 6a (Apogossypolone) derivatives was synthesized identified pan-active antagonists proteins, potency in the low micromolar to nanomolar range. Compound 6f inhibits BH3 peptides Bcl-XL, Bcl-2, Mcl-1 IC50 values...
Aim. To investigate the effect of Ginsenoside Rb1 (GS-Rb1) on hypoxia/ischemia (H/I) injury in cardiomyocytes vitro and mitochondrial apoptotic pathway mediated mechanism. Methods. Neonatal rat (NRCMs) for H/I groups were kept DMEM without glucose serum, placed into a hypoxic jar 24 h. GS-Rb1 at concentrations from 2.5 to 40 µM was given during period NRCMs determined by MTT lactate dehydrogenase (LDH) leakage assay. Cell apoptosis, ROS accumulation, membrane potential (MMP) assessed flow...
Heart failure may be linked to fluctuations in the rhythm of autophagy cardiomyocytes throughout day. Circadian rhythms depend on regulation core biological clock proteins, with PER2 playing a crucial role. Our previous research confirmed that presence β 1-adrenergic receptor autoantibodies (β 1-AAs) could inhibit myocardial autophagy, leading cell death and heart failure. However, it remains unclear whether 1-AA induces cardiac disorders by affecting expression. In this study, we find...