Mechanism of Suoquanwan on Enuresis Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

Objective:To explore the targets and relevant signaling pathways of Suoquanwan in the treatment of enuresis using network pharmacology，and animal expriments are applied to further define its mechanism of action. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database was used to screen out active chemical components of Suoquanwan，varieties of systematic biological databases were integrated to construct the "active component-disease-target" network relationship，and the common protein protein interaction network（PPI） network genes were functionally enriched. Quantitative real time polymerase chain reaction（Real-time PCR） and Western blot were used to verify the effect of Suoquanwan on AVPR2 and DRD2 gene. Result:A total of 32 active ingredients were screened from Suoquanwan. These active ingredients were interacted with 131 potential targets relating to Enuresis，which contained 14 core target genes，namely arginine vasopressin receptor 2 （AVPR2）， neurotrophic receptor tyrosine kinase 1（NTRK1）， dopamine receptor D2（DRD2）， opioid receptor mu 1（OPRM1）， 5-hydroxytryptamine receptor 1A（HTR1A）， 5-hydroxytryptamine receptor 1B（HTR1B），solute carrier family 6 member 4（SLC6A4），Adrenoceptor Alpha 2A（ADRA2A）， prostaglandin-endoperoxide synthase 2（PTGS2）， cholinergic receptor muscarinic 2（CHRM2）， solute carrier family 6 member 3 （SLC6A3）， 5-hydroxytryptamine receptor 6（HTR6）， solute carrier family 6 member 2（SLC6A2）， cytochrome P450 family 2 subfamily C member 19（CYP2C19）. Gene enrichments mainly involved to G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and neuroactive ligand-receptor interaction. Real-time PCR and Western blot results showed that Suoquanwan could enhance the expression of AVPR2 in rat kidney，and weaken the expression of DRD2 in rat adrenal. Conclusion:The main chemical constituents in Suoquanwan may alleviate enuresis by regulating AVPR2 and DRD2 and then participating in the G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and other biological processes.

Association of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms with the risk of glioma

Several previous studies have reported the role variant of ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms in the risk of glioma, but the results of these studies are inconsistent. Therefore, we aimed to conduct a meta-analysis to investigate the role of ERCC1 rs3212986 and ERCC2 rs13181 on the risk of glioma. A comprehensive research was conducted through the databases of Pubmed, EMBASE and the China National Knowledge Infrastructure [CNKI] platforms until June 1, 2014, including 14 eligible case-control studies. Our meta-analysis found that ERCC1 rs3212986 AA genotype was significantly associated with increased risk of glioma compared with CC genotype, and the pooled OR [95%CI] was 1.29[1.07-1.55]. By subgroup analysis, ERCC1 rs3212986 AA genotype was found to be significantly correlated with increased glioma risk in Chinese population [OR=1.37, 95%CI=1.07, 1.55], Similarly, we found that ERCC2 rs13181 GT and TT genotypes were significantly associated with increased risk of glioma in Chinese population, with ORs [95%CI] of 1.47[1.17-1.85] and 1.50[1.02-2.22]. But ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms had no significant association with glioma risk in Caucasian populations. By begg's funnel plot, we found that no publication bias was existed in this meta-analysis. Our meta-analysis suggested that ERCC1 rs3212986 and ERCC2 rs13181 polymorphism play an important risk factor for brain tumor development in Chinese population, but no association in Caucasian populations

MicroRNA-184 promotes proliferation ability of glioma cells by regulating FOXO3

OBJECTIVES@#To investigate the effect of microRNA (miR-184) on regulating the genesis, development and proliferation of glioma cells.@*METHODS@#Lipidosome was used to transfect miR-184 mimic and inhibitor to glioma cell line, and the cell proliferation ability changes were determined by MTT and plate cloning experiment after the transfection. WB test was used to measure the levels of cyclinD1, p27 and FOXO3. Meanwhile, QPCR was used to detect miR-184 expression in glioma cell line, glioma tissues and adjacent tissues. Luciferase experiment was used to test 3'UTR gene targeting regulation of miR-184 and FOXO3.@*RESULTS@#QPCR results showed a significant lower miR-184 expression level in glioma cell line and glioma tissues than that in juxtacancerous tissue. MTT and plate cloning experiments have shown that after over-expressing of miR-184, the cell proliferation capacity of glioma U87 and T98G was significantly increased, which was significantly inhibited after the inhibition of miR-184. WB results showed a lower expression level of p27 in U87 and T98G cells, and a higher expression level of cyclinD1 after over-expressing of miR-184 was observed. However, a lower expression level of cyclinD1 and a higher expression level of p27 after the inhibition of miR-184. The luciferase activity was inhibited after the over-expressing of miR-184.@*CONCLUSIONS@#MiR-184 can affect the proliferation abilities of glioma cells and regulate the cell cycle related protein. It plays an important role in the occurrence and development of gliomas.