A5100733091- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Cancer Mechanisms and Therapy
- MicroRNA in disease regulation
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Circular RNAs in diseases
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- Drug Transport and Resistance Mechanisms
- Polyamine Metabolism and Applications
- Computational Drug Discovery Methods
- Ion Channels and Receptors
- Cancer-related Molecular Pathways
- Drug Solubulity and Delivery Systems
- Autophagy in Disease and Therapy
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
Nanjing Agricultural University
2025
Huanggang Central Hospital
2022-2024
Yangtze University
2024
Guilin Medical University
2018-2022
Northwest Women's and Children's Hospital
2022
Southern Medical University
2022
Huazhong University of Science and Technology
2020-2021
University of Michigan
2016-2020
Academy of Military Medical Sciences
2020
Hubei Cancer Hospital
2019
Proteins of the bromodomain and extra-terminal (BET) family are epigenetics "readers" promising therapeutic targets for cancer other human diseases. We describe herein a structure-guided design [1,4]oxazepines as new class BET inhibitors our subsequent design, synthesis, evaluation proteolysis-targeting chimeric (PROTAC) small-molecule degraders. Our efforts have led to discovery extremely potent degraders, exemplified by QCA570, which effectively induces degradation proteins inhibits cell...
Abstract Chemotherapy resistance is the major cause of nasopharyngeal carcinoma (NPC) treatment failure. Tripartite motif-containing protein (TRIM) family members play important roles in tumor development and chemotherapy Here, based on a screening analysis 71 TRIM by qRT-PCR, we first confirmed that TRIM11 levels were significantly higher drug-resistant NPC cells than non-drug-resistant cells, high expression predicted poor overall survival (OS) progression-free (PFS). N(6)-Methyladenosine...
Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cells and chemoresistance; however, which isoform preferentially expressed varies between cell lines. We sought explore the structural determinants of selectivity series small-molecule inhibitors support research into role stem An SAR campaign guided by cocrystal structure HTS hit CM39 (7) with ALDH1A1 afforded...
Abstract Histone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated our previous microarray screen. However, the role HDAC4 dysregulation mechanisms underlying growth metastasis nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that levels primary metastatic NPC tissues were significantly increased compared with those...
It is well established that epidermal growth factor (EGF) induces the cytoskeleton reorganization and cell migration through two major signaling cascades: phospholipase C-gamma1 (PLC-gamma1) Rho GTPases. However, little known about cross talk between PLC-gamma1 Here we showed forms a complex with Rac1 in response to EGF. This interaction direct mediated by Src homology 3 (SH3) domain (106)PNTP(109) motif. critical for EGF-induced activation vivo, SH3 actually potent specific guanine...
As an orally administered, locally acting gastrointestinal drug, mesalamine products are designed to achieve high local drug concentration in the (GI) tract for treatment of ulcerative colitis. The aim this study was directly measure and compare dissolution three formulations human GI correlate their with plasma. Healthy subjects were administered Pentasa, Apriso, or Lialda. fluids aspirated from stomach, duodenum, proximal jejunum, mid distal jejunum regions. Mesalamine (5-ASA) its primary...
Store-operated Ca2+ entry (SOCE) is a critical signaling pathway in many cell types. After sensing store depletion the endoplasmic reticulum (ER) lumen, STIM1 (STromal Interaction Molecule 1) oligomerizes and then interacts with activates Orai1 calcium channel. Our previous research has demonstrated that inhibitory helix (IH) adjacent to first coiled-coil region (CC1) of may keep whole C-terminus an inactive state. However, specific conformational change CC1-IH drives transition from resting...
We have designed and synthesized 9H-pyrimido[4,5-b]indole-containing compounds to obtain potent orally bioavailable BET inhibitors. By incorporation of an indole or a quinoline moiety the 9H-pyrimido[4,5-b]indole core, we identified series small molecules showing high binding affinities proteins low nanomolar potencies in inhibition cell growth acute leukemia lines. One such compound, 4-(6-methoxy-2-methyl-4-(quinolin-4-yl)-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethylisoxazole (31) has...
We report the structure-based discovery of CF53 (28) as a highly potent and orally active inhibitor bromodomain extra-terminal (BET) proteins. By incorporation NH-pyrazole group into 9H-pyrimido[4,5-b]indole core, we identified series compounds that bind to BRD4 BD1 protein with Ki values <1 nM achieve low nanomolar potencies in cell growth inhibition leukemia breast cancer cells. The most-promising compound, CF53, possesses excellent oral pharmacokinetic properties achieves significant...
Here, we describe a method for the comparative analysis of ribonucleic acids (RNAs). This allows sequence or modification information from previously uncharacterized RNA to be obtained by direct comparison with reference RNA, whose is known. simple and rapid enabled differential labeling two samples. One sample, labeled (16)O during enzymatic digestion. The second candidate unknown (18)O. By combining digests, digestion products that share same post-transcriptional modification(s) between...
The comparative analysis of ribonucleic acid digests (CARD) approach for sequencing transfer acids (tRNAs) is described. This method enabled by the differential labeling two tRNA populations. A set reference tRNAs, whose complete sequences including modifications are known, labeled with 16O during enzymatic digestion. second (candidate) sequence information desired, 18O. By combining digests, digestion products that share same between and candidate will appear as doublets separated 2 Da....
Plakoglobin is a tumor suppressor gene in lung cancer; however, the mechanism by which it downregulated cancer largely unknown. The aim of present study was to investigate whether histone deacetylases (HDACs) regulate plakoglobin expression cancer. effects overexpression or knockdown HDAC7 on were determined using stably transfected cell lines. Chromatin immunoprecipitation assays performed elucidate mechanisms underlying HDAC7‑induced suppression plakoglobin. A Cell Counting Kit‑8 and...
Aging is a predominant risk factor for many chronic conditions. Stem cell dysfunction plays pivotal role in the aging process. Prelamin A, an abnormal processed form of nuclear lamina protein lamin has been reported to trigger premature senescence. However, mechanism driving stem still unclear. In this study, we found that while passaging subchondral bone mesenchymal cells (SCB-MSCs) vitro, prelamin A accumulation occurred concomitantly with increase senescence-associated β-galactosidase...
Intensity interrogation-based surface plasmon resonance imaging (ISPRi) sensing has a simple schematic design and is the most widely used technology at present. In this study, we report successful development of novel high-sensitivity ISPRi biosensor its application for apoptosis detection in cancer cells. By optimizing excitation wavelength angle, achieved refractive index resolution (RIR) 5.20 × 10−6 RIU. Importantly, been tested validated high-throughput label-free activated caspase-3...
Mapping, sequencing, and quantifying individual noncoding ribonucleic acids (ncRNAs), including post-transcriptionally modified nucleosides, by mass spectrometry is a challenge that often requires rigorous sample preparation prior to analysis. Previously, we have described simplified method for the comparative analysis of RNA digests (CARD) applicable relatively complex mixtures ncRNAs. In CARD approach transfer (tRNA) analysis, two complete sets digestion products from total tRNA are...
Oxymatrine (OMT) has exhibited an anti-cancer role in human cancers, including cervical cancer (CC). The dysregulated circular RNAs (circRNAs) are key regulators biology, and circ_0008460 was upregulated CC. This study performed to investigate the circRNA-based molecular mechanism for OMT RNA detection circ_0008460, microRNA-197-3p (miR-197-3p), or ribonucleotide reductase subunit M2 (RRM2) completed using reverse transcription-quantitative polymerase chain reaction assay. Cell behaviors...
Circular RNAs (circRNAs) are a form of that lack coding potential. The role such circRNAs in dental pulp stem cell (DPSC) osteo/odontogenic differentiation remains to be determined. In this study, circRNA expression profiles DPSC process were analyzed by RNA-seq. qRT-PCR was used confirm the differential circ_0005044, miR-296-3p, and FOSL1 osteogenic process. Circ_0005044, knocked down or overexpressed. Osteoblastic activity associated mineral monitored via alkaline phosphatase (ALP)...