Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression. Epigenetic mechanisms involve in the regulation of miRNAs expression. Therefore we speculated that miRNAs may be important factors during the promotion of neuronal differentiation by VPA. Here, after selecting appropriate concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on the treatment of 1 mM VPA or vehicle. After validation, we obtained 5 significantly upregulated miRNAs (miR-29a-5p, miR-674-5p, miR-155-5p, miR-652-3p, and miR-210-3p) in VPA group compared with control. We predicted the target genes of these miRNAs on the website. Through gene ontology (GO) and pathway analyses, we obtained preliminary comprehension of the function of these genes. The bioinformatics analyses indicated the involvement of them during neurogenesis. In addition, we observed high expression of miR-210-3p, miR-29a-5p, and miR-674-5p in central nervous system, which suggested that they were likely to play crucial roles in neuronal differentiation. We then defined the upregulation of Map2 by transfecting mimic of miR-674-5p, which indicated the promotion of miR-674-5p on NSCs differentiation. The present study explored the miRNAs potentially mediated the function of VPA on promoting NSCs to differentiate into neurons.

ConclusionsLysophosphatidic acid receptor is a promising indicator for pancreatic cancer, and our findings suggested that lpar2 might be a potential target for clinical treatment of pancreatic cancer.

This study aimed to investigate the dose-volume effects of γ-ray stereotactic body radiotherapy (SBRT) on clinical outcomes of patients with huge-size (≥10 cm) unresectable hepatocellular carcinoma (HCC). A total of 59 patients with huge-size unresectable HCC were treated with SBRT following TACE between May 2006 and Dec. 2009. The analyzed parameters included fractional dose, marginal dose, maximal dose, and mean dose that the target received, as well as percentages of tumor volume encompassed by 60% (P 60), 70% (P 70), and 80% (P 80) of isodose curves in entire tumor. The clinical outcomes included objective response rate (ORR), disease-free survival (DFS), overall survival (OS), and adverse event (AE). During median follow-up of 18.4 months, 81.4% of ORR (8.5% CR and 72.9% PR) was achieved, higher than 28.9% of ORR recently reported for TACE alone. 1-and 3-year DFS rates were 31.1% and 2.6% with median DFS of 8.7 months; 1-, 3-, and 5-year OS rates were 46.5%, 13.7%, and 2.9%, with median OS of 11.8 months. P 70 was the only factor significantly correlating to DFS (P = 0.009) and OS (P = 0.01). Neither severe radiation-related liver disease nor > grade 3 AE was observed. In conclusion, SBRT was a safe and effective option for treatment of huge-size unresectable HCC. P 70 represented a parameter for predicting DFS and OS, and high dose-volume (e.g., P 70) might be required to achieve improved clinical outcomes of patients with this type of HCC.