A5011482917- Dementia and Cognitive Impairment Research
- Histone Deacetylase Inhibitors Research
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Health, Environment, Cognitive Aging
- Nanocluster Synthesis and Applications
- Selenium in Biological Systems
- Cholinesterase and Neurodegenerative Diseases
- Trace Elements in Health
- Crystallization and Solubility Studies
- Phosphodiesterase function and regulation
- Nanoparticle-Based Drug Delivery
- 14-3-3 protein interactions
- Birth, Development, and Health
- Retinal Diseases and Treatments
- Graphene and Nanomaterials Applications
- Inflammasome and immune disorders
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Pregnancy and preeclampsia studies
Cangzhou Central Hospital
2025
Institute of Clinical Research
2019-2024
Hangzhou First People's Hospital
2020-2023
Washington Center
2023
The Affiliated Yongchuan Hospital of Chongqing Medical University
2019
Chongqing Medical University
2019
Health Biomed (China)
2019
Dart NeuroScience (United States)
2017
Scripps (United States)
2017
Scripps Institution of Oceanography
2017
Huntington's disease (HD) is an inherited, progressive neurological disorder that caused by a CAG/polyglutamine repeat expansion and for which there no effective therapy. Recent evidence indicates transcriptional dysregulation may contribute to the molecular pathogenesis of this disease. Supporting view, administration histone deacetylase (HDAC) inhibitors has been shown rescue lethality photoreceptor neurodegeneration in Drosophila model polyglutamine To further explore therapeutic...
Suberoylanilide hydroxamic acid (SAHA) is a potent inhibitor of histone deacetylases (HDACs) that causes growth arrest, differentiation, and/or apoptosis many tumor types in vitro and vivo . SAHA clinical trials for the treatment cancer. HDAC inhibitors induce expression less than 2% genes cultured cells. In this study we show induces vitamin D-up-regulated protein 1/thioredoxin-binding protein-2 (TBP-2) transformed As TBP-2 mRNA increased, second gene, thioredoxin, decreased. transient...
Histone deacetylase (HDAC) catalyzes the removal of acetyl group from lysine residues in N-terminal tails nucleosomal core histones. Eight human HDACs have been identified so far. Here, we report identification a ninth member HDAC family, designated HDAC9. HDAC9 is class II and its gene resides on chromosome 7. has several alternatively spliced isoforms. One these isoforms histone deacetylase-related protein or myocyte enhancer-binding factor 2-interacting transcriptional repressor that...
Alzheimer's disease (AD), the most common neurodegenerative disease, is caused by an accumulation of amyloid-β (Aβ) plaque deposits in brains. Evidence increasingly showing that epigallocatechin-3-gallate (EGCG) can partly protect cells from Aβ-mediated neurotoxicity inhibiting Aβ aggregation. In order to better understand process aggregation and amyloid fibril disaggregation reduce cytotoxicity EGCG at high doses, we attached onto surface selenium nanoparticles (EGCG@Se). Given low delivery...
Frameshift and nonsense mutations within the gene for human triosephosphate isomerase (TPI) that generate a codon first three-fourths of protein coding region have been found to reduce abundance product mRNA copurifies with nuclei. The cellular process location codon-mediated reduction proven difficult elucidate technical reasons. We show here, using electron microscopy judge purity isolated nuclei, previously established 25% normal level is evident nuclei are free detectable cytoplasmic...
The translation of human triosephosphate isomerase (TPI) mRNA normally terminates at codon 249 within exon 7, the final exon. Frameshift and nonsense mutations type that cause to terminate prematurely or upstream 189 6 reduce level nuclear TPI 20 30% normal by a mechanism is not function distance from either initiation termination codon. In contrast, frameshift another downstream 208, also 6, have no effect on mRNA. this work, quantitations RNA derived alleles in which codons had been...
Histone deacetylase 4 (HDAC4) is a member of family enzymes that catalyze the removal acetyl groups from core histones, resulting in compact chromatin structure generally associated with repressed gene transcription. Protein phosphorylation has been implicated regulation corepressor activity deacetylase. Here we report serine/threonine kinases are found association HDAC4 and phosphorylate vitro , phosphorylated cells. The extracellular signal-regulated 1 2 (ERK1/2), also known as p44 MAPK...
Histone deacetylases (HDACs) are involved in regulating transcription by modifying the core histones of nucleosome. To date, six HDACs have been identified mammalian cells: yeast RPD3 homologs HDAC1, 2, and 3 HDA1 HDAC4, 5, 6. HDAC4 HDAC5 contain a noncatalytic N-terminal domain. Herein, we report identification protein HDRP (HDAC-related protein) that shares 50% identity deduced amino acid sequence to domain 5. The steady-state levels mRNA high human brain, heart, skeletal muscle low...
The translation of human triosephosphate isomerase (TPI) mRNA normally terminates at codon 249 within exon 7, the final exon. Frameshift and nonsense mutations type that cause to terminate prematurely or upstream 189 6 reduce level nuclear TPI 20 30% normal by a mechanism is not function distance from either initiation termination codon. In contrast, frameshift another downstream 208, also 6, have no effect on mRNA. this work, quantitations RNA derived alleles in which codons had been...
A series of potent thienotriazolopyrimidinone-based PDE1 inhibitors was discovered. X-ray crystal structures example compounds from this in complex with the catalytic domain PDE1B and PDE10A were determined, allowing optimization potency PDE selectivity. Reduction hERG affinity led to greater than a 3000-fold selectivity for over hERG. 6-(4-Methoxybenzyl)-9-((tetrahydro-2H-pyran-4-yl)methyl)-8,9,10,11-tetrahydropyrido[4′,3′:4,5]thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one...
A series of potent and selective [1,2,4]triazolo[1,5-a]pyrimidine PDE2a inhibitors is reported. The design improvement the binding properties this was achieved using X-ray crystal structures in conjunction with careful analysis electronic structural requirements for enzyme. One lead compounds, compound 27 (DNS-8254), identified as a highly enzyme inhibitor favorable rat pharmacokinetic properties. Interestingly, increased potency facilitated by formation halogen bond oxygen Tyr827 present...
A valid, reliable, accessible, engaging, and affordable digital cognitive screen instrument for clinical use is in urgent demand. To assess the utility of MemTrax memory test early detection impairment a Chinese cohort. The 2.5-minute Montreal Cognitive Assessment (MoCA) were performed by 50 clinically diagnosed cognitively normal (CON), mild due to AD (MCI-AD), Alzheimer's disease (AD) volunteer participants. percentage correct responses (MTx-% C), mean response time (MTx-RT), composite...
Wang et al. analyze Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment accuracy as screening tests for detecting dementia associated with Alzheimer's disease (AD). Such are at the center of controversy regarding recognition treatment AD. The continued widespread use tools such MMSE (1975) underscores failure advancing cognitive assessment, which has hampered development evaluation AD treatments. It is time to employ readily available, efficient computerized measures...
Protein methylation is a posttranslational modification that can potentially regulate signal transduction pathways in similar manner as protein phosphorylation. The role of NGF signaling was examined by metabolic labeling PC12 cell proteins with l-[methyl-3H]methionine and vitro l-[methyl-3H]S-adenosylmethionine. Effects were detected within 15 min. Methyl-labeled resolved one two dimensional SDS-PAGE. affected the several 68–60-kD (pI 5.8–6.4) 50-kD (isoelectric point pH 6.7–6.8 5.8–6.2)....
ABSTRACT Cardiovascular disease is a major health concern, with cardiac hypertrophy (CH) leading to heart failure and increased mortality. Although kallistatin has shown protective effect against cardiovascular diseases, its role in CH remains unclear. The effects of on myocardial lipid metabolism, inflammation, via the SIRT1/PPARα pathway both animal model cell culture were assessed. rat was induced by Angiotensin II (Ang II). Plasma inflammatory indicators (IL‐6, TNF‐α, MCP‐1) measured...
Frameshift and nonsense mutations within the gene for human triosephosphate isomerase (TPI) that generate a codon first three-fourths of protein coding region have been found to reduce abundance product mRNA copurifies with nuclei. The cellular process location codon-mediated reduction proven difficult elucidate technical reasons. We show here, using electron microscopy judge purity isolated nuclei, previously established 25% normal level is evident nuclei are free detectable cytoplasmic...
Chiral molecules, which selectively target and inhibit amyloid β-peptide (Aβ) aggregation, have potential use as therapeutic agents for the treatment of Alzheimer's disease (AD).
Human islet amyloid polypeptide (hIAPP) was found as aggregate deposits in the pancreatic islets of patients with type-2 diabetes and studies showed that insulin its derivatives were potent inhibitors hIAPP aggregation. However, several emerging therapies this goal limited success due to instability inefficiency derivatives. Nanosized graphene oxide (nGO) possesses high stability affinity toward aromatic rings. In study, an insulin-derived peptide, EALYLV, stabilized by loading on nGO@PEG...
Background: The widespread incidence and prevalence of Alzheimer’s disease mild cognitive impairment (MCI) has prompted an urgent call for research to validate early detection screening assessment. Objective: Our primary aim was determine if selected MemTrax performance metrics relevant demographics health profile characteristics can be effectively utilized in predictive models developed with machine learning classify (normal versus MCI), as would indicated by the Montreal Cognitive...
The ability of a novel class hybrid polar compounds (HPCs) to induce differentiation and consequent cessation proliferation transformed cells has led their development as potential chemotherapeutic agents in the treatment cancer. Suberoylanilide hydroxamic acid (SAHA) is prototype family based (SAHA-like HPCs) that can, at micromolar concentrations, variety cell lines differentiate. mechanism action HPCs not entirely understood. Searching for cellular target SAHA-like HPCs, we synthesized...