HDAC4 gene silencing alleviates epilepsy by inhibition of GABA in a rat model.

OBJECTIVES: Despite the availability of effective antiepileptic drugs, epileptic patients still suffer from intractable seizures and adverse events. Better control of both seizures and fewer side effects is needed in order to enhance the patient's quality of life. We performed the present study with an attempt to explore the effect that HDAC4 gene silencing would have on epilepsy simulated by model rats. Furthermore, the study made additional analysis on the relativity of the HDAC4 gene in regard to its relationship with the gamma-aminobutyric acid (GABA) signaling pathway. MATERIALS AND METHODS: Tremor rats were prepared in order to establish the epilepsy model. The rats would go on to be treated with si-HDAC4 in order to identify roles of the HDAC4 in levels of GABAARα1, GABAARα4, GAD65, GAT-1, and GAT-3. Finally, both electroencephalogram behavior and cognitive function of the rats following the treatment of si-HDAC4 were observed. RESULTS: Levels of the GABAARα1 and GABAARα4 showed an evident increase, while GAD65, GAT-1, and GAT-3 displayed a decline in the epilepsy rats treated with the aforementioned si-HDAC4 when compared with the epilepsy rats. After injection of si-HDAC4, the epilepsy rats presented with a reduction in seizure degree, latency and duration of seizure, amount of scattered epileptic waves, and occurrence of epilepsy, with an improvement in their cognitive function. CONCLUSION: The study highlighted the role that HDAC4 gene silencing played in easing the cases of epilepsy found in the model rats. This was shown to have occurred through the upregulation of both GABAARα1 and GABAARα4 levels, as well as in the downregulation of GAD65, GAT-1, and GAT-3 levels. The evidence provided shows that the HDAC4 gene is likely to present as a new objective in further experimentation in the treatment of epilepsy.

Identification of genes associated with castration­resistant prostate cancer by gene expression profile analysis.

Prostate cancer (CaP) is a serious and common genital tumor. Generally, men with metastatic CaP can easily develop castration­resistant prostate cancer (CRPC). However, the pathogenesis and tumorigenic pathways of CRPC remain to be elucidated. The present study performed a comprehensive analysis on the gene expression profile of CRPC in order to determine the pathogenesis and tumorigenic of CRPC. The GSE33316 microarray, which consisted of 5 non­castrated samples and 5 castrated samples, was downloaded from the gene expression omnibus database. Subsequently, 201 upregulated and 161 downregulated differentially expressed genes (DEGs) were identified using the limma package in R and those genes were classified and annotated by plugin Mcode of Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology Based Annotation System 2.0 online tools to investigate the function of different gene modules. The BiNGO tool was used to visualize the level of enriched GO terms. Protein­protein interaction network was constructed using STRING and analyzed with Cytoscape. In conclusion, the present study determined that aldo­keto reductase 3, cyclin B2, regulator of G protein signaling 2, nuclear factor of activated T­cells and protein kinase C a may have important roles in the development of CRPC.