A5018492075- Cancer Mechanisms and Therapy
- Spaceflight effects on biology
- RNA Interference and Gene Delivery
- Ion channel regulation and function
- Cancer Research and Treatments
- Phytochemical compounds biological activities
- Multiple Myeloma Research and Treatments
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Receptor Mechanisms and Signaling
- Animal Virus Infections Studies
- Ginkgo biloba and Cashew Applications
- Nicotinic Acetylcholine Receptors Study
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- Enzyme Structure and Function
- Heat shock proteins research
- Cardiac electrophysiology and arrhythmias
- Protein Structure and Dynamics
- Synthesis and biological activity
- Autophagy in Disease and Therapy
- Pain Mechanisms and Treatments
- Chronic Myeloid Leukemia Treatments
The People's Hospital of Guangxi Zhuang Autonomous Region
2024
China Astronaut Research and Training Center
2010-2024
Amgen (United States)
2012-2024
Indiana University School of Medicine
2024
Third Affiliated Hospital of Sun Yat-sen University
2024
Sun Yat-sen University
2024
Nantong University
2024
Indiana University – Purdue University Indianapolis
2024
Wuhan Third Hospital
2020
China Pharmaceutical University
2003-2017
Abstract Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic loss in combination with glucagon-like peptide-1 agonists preclinical models. Based on genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body improved multiple metabolic parameters. This work reconciles similar effects antagonists...
A universal and promising route for screening of high-quality enzyme inhibitors from herbal medicines.
Identification of voltage-gated sodium channel NaV1.7 inhibitors for chronic pain therapeutic development is an area vigorous pursuit. In effort to identify more potent leads compared our previously reported GpTx-1 peptide series, electrophysiology screening fractionated tarantula venom discovered the inhibitory JzTx-V from Chinese earth tiger Chilobrachys jingzhao. The parent displayed nominal selectivity over skeletal muscle NaV1.4 channel. Attribute-based positional scan analoging...
The phosphoinositide 3-kinase family catalyzes the phosphorylation of phosphatidylinositol-4,5-diphosphate to phosphatidylinositol-3,4,5-triphosphate, a secondary messenger which plays critical role in important cellular functions such as metabolism, cell growth, and survival. Our efforts identify potent, efficacious, orally available phosphatidylinositol (PI3K) inhibitors potential cancer therapeutics have resulted discovery...
This study examined whether, and by what signaling ionic mechanisms, pyrimidine nucleotides constrict rat cerebral arteries. Cannulated arteries stripped of endothelium pressurized to 15 mmHg constricted in a dose-dependent manner UTP. constriction was partly dependent on the depolarization smooth muscle cells activation voltage-operated Ca(2+) channels. The induced UTP were unaffected bisindolylmaleimide I, PKC inhibitor that abolished phorbol ester (PMA)-induced In contrast, Rhokinase...
Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of Jak2 gain-of-function mutation majority patients with myeloproliferative disorders (MPD). Here, we describe thienopyridine series that culminates compounds showing 100- >500-fold selectivity over related Jak family kinases enzyme assays. Selectivity was also observed TEL-Jak cellular assays, as well cytokine-stimulated peripheral...
The high expression of proviral insertion site Moloney murine leukemia virus kinases (Pim-1, -2, and -3) in cancers, particularly the hematopoietic malignancies, is believed to play a role promoting cell survival proliferation while suppressing apoptosis. three isoforms Pim protein appear largely redundant their oncogenic functions. Thus, pan-Pim kinase inhibitor highly desirable. However, active inhibitors have proven difficult develop because Pim-2 has low Km for ATP therefore requires...
Inhibitors of the voltage-gated sodium channel NaV1.7 are being investigated as pain therapeutics due to compelling human genetics. We previously identified NaV1.7-inhibitory peptides GpTx-1 and JzTx-V from tarantula venom screens. Potency selectivity were modulated through attribute-based positional scans native residues via chemical synthesis. Herein, we report lead optimization identify a pharmacodynamically active peptide variant. Molecular docking ensembles NMR into homology...
It was confirmed that simulated microgravity (SMG) led to ultrastructural alterations and apoptosis in many types of microvascular endothelial cells. However, whether SMG would also affect choroidal vascular cells (CVECs) remains unknown. This study designed investigate the effects on ultrastructure CVECs.The rotary cell culture system (RCCS) utilized simulate condition. Human CVECs were cultured under normal gravity (NG) or condition for 3 days. The viewed transmission electron microscopy,...
The identification of Pim-1/2 kinase overexpression in B-cell malignancies suggests that Pim inhibitors will have utility the treatment lymphoma, leukemia, and multiple myeloma. Starting from a moderately potent quinoxaline-dihydropyrrolopiperidinone lead, we recognized potential for macrocyclization developed series 13-membered macrocycles. structure-activity relationships macrocyclic linker were systematically explored, leading to 9c as potent, subnanomolar inhibitor Pim-1 -2. This...
Understanding small interfering RNA (siRNA) fraction unbound (<i>f</i><sub>u</sub>) in relevant physiologic compartments is critical for establishing pharmacokinetic-pharmacodynamic relationships this emerging modality. In our attempts to isolate the equilibrium free of <i>N</i>-acetylgalactosamine–conjugated siRNA using classic small-molecule vitro techniques, we found that hydrodynamic radius was determining size exclusion limit requirements <i>f</i><sub>u</sub> isolation, largely...
Pim kinases are a family of constitutively active serine/threonine that partially redundant and regulate multiple pathways important for cell growth survival. In human disease, high expression the three isoforms has been implicated in progression hematopoietic solid tumor cancers, which suggests kinase inhibitors could provide patients with therapeutic benefit. Herein, we describe structure-guided optimization series quinazolinone-pyrrolodihydropyrrolone analogs leading to identification...
Purpose: Homer1a is a member of the post-synaptic density protein family that plays an important role in neuronal synaptic activity and extensively involved neurological disorders. The aim this study to investigate modulating survival using vitro traumatic injury model.Materials methods: Neurons were extracted from rats identifited. Then, cells treated with Homerla overexpression or interference vectors. Western blot was performed evaluate expression Homerla, apoptosis-related...
Human genome wide association studies confirm the of rs738409 single nucleotide polymorphism (SNP) in gene encoding protein patatin like phospholipase domain containing 3 (PNPLA3) with nonalcoholic fatty liver disease (NAFLD); presence resulting mutant PNPLA3 I148M is a driver steatohepatitis (NASH). While Pnpla3-deficient mice do not display an adverse phenotype, safety knocking down endogenous wild type humans remains unknown. To expand scope potential targeted NAFLD therapeutic to both...
The Escherichia coli grpE gene (along with dnaK, dnaJ, groEL, and groES) was originally identified as one of the host factors required for phage lambda growth. classical grpE280 mutation only that resulted from initial screen shown to specifically block initiation DNA replication. Here we report isolation several new missense mutations, again using resistance a selection. All mutants fall into two groups based on their temperature-dependent phenotype Members first group (I), including grpE17...
To better understand the contribution of dysregulated DNA methyltransferase 1 (DNMT1) expression to progression and biology clear cell renal carcinoma (ccRCC).We examined differences in DNMT1 89 ccRCC 22 normal tissue samples by immunohistochemistry. In addition, changes viability, apoptosis, colony formation invading ability lines (786-0 Caki-1) were assessed after transfection with siRNA.We found protein was significantly higher expressed than that no-tumor tissues (56.2% 27.3%,...
There has been a renewed interest in therapeutic small interfering RNAs (siRNAs) over the past few years. This is particularly result of successful and efficient delivery N-acetylgalactosamine (GalNAc)-conjugated siRNAs to liver. In general, lead selection process for siRNA drugs faster more straightforward than traditional molecules. Nevertheless, many different sequences chemical modification patterns must still be evaluated before arriving at final candidate. One major difficulties...