MiR-484 suppressed proliferation, migration, invasion and induced apoptosis of gastric cancer via targeting CCL-18.

Gastric cancer is a common and high-incidence malignant gastro-intestinal cancer that seriously threatens human life. Evidence suggests that microRNAs (miRNAs) play an essential role in regulating the occurrence and development of gastric cancer, but the possible mechanisms and effects remain to be further explored. In the present study, a new tumour suppresser function of miR-484 was identified in gastric cancer. The expression of miR-484 was obviously decreased, and the expression of CCL-18 was obviously increased in gastric cancer tissues and cell lines. In addition, upregulation of miR-484 suppressed cell proliferation, migration and invasion, and induced cell cycle arrest in G1 phase and cell apoptosis in gastric cancer cells. Besides, miR-484 mimics could block the PI3K/AKT signalling pathway. Moreover, CCL-18 was confirmed as a direct target of miR-484 by binding its 3'-UTR, and over-expression of CCL-18 could restore the effects of miR-484 on the growth and metastasis of gastric cancer. Finally, in vivo experiments showed that over-expression of miR-484 inhibited the subcutaneous tumorigenicity of gastric cancer cells, and the inhibition was blocked after over-expression of CCL-18. To conclude, miR-484 expression was downregulated in gastric cancer tissues and cells and played an anti-cancer role in the occurrence and development of gastric cancer, which may be achieved by inhibiting the expression of transcription factor CCL-18 and blocking the PI3K/AKT pathway.

Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

Influence of Chitosan Nanoparticles as the Absorption Enhancers on Salvianolic acid B In vitro and In vivo Evaluation.

BACKGROUND: Salvianolic acid B (SalB) represents the most abundant and bio-active phenolic constituent among the water-soluble compounds of Salvia miltiorrhiza. But the therapeutic potential of SalB has been significantly restricted by its poor absorption. METHODS: In this study, chitosans (CS) and CS nanoparticles (NPs) with different molecular weights (MWs), which have influence on the absorption of SalB, was also investigated. RESULTS: As a preliminary study, water-soluble CS with various MWs (3, 30, 50, and 100 kDa) was chosen. We investigated the MW-dependent Caco-2 cell layer transport phenomena in vitro of CS and NPs at concentrations (4 µg/ml, w/v). SalB, in presence CS or NPs has no significant toxic effect on Caco-2 cell. As the MW increases, the absorption enhancing effect of CS increases. However, as the MW decreases, the absorption enhancing effect of NPs increases. The AUC0-∞ of the SalB-100 kDa CS was 4.25 times greater than that of free SalB. And the AUC0-∞ of the SalB-3 kDa NPs was 16.03 times greater than that of free SalB. CONCLUSION: CS and NPs with different MWs as the absorption enhancers can promote the absorption of SalB. And the effect on NPs is better than CS. SUMMARY: Formation mechanism for NPs.

Identification of Candidate Genes for Seed Glucosinolate Content Using Association Mapping in Brassica napus L.

Rapeseed contains glucosinolates, a toxic group of sulfur-containing glucosides, which play critical roles in defense against herbivores and microbes. However, the presence of glucosinolates in rapeseed reduces the value of the meal as feed for livestock. We performed association mapping of seed glucosinolate (GS) content using the 60K Brassica Infinium single nucleotide polymorphism (SNP) array in 520 oilseed rape accessions. A total of 11 peak SNPs significantly associated with GS content were detected in growing seasons of 2013 and 2014 and were located on B. napus chromosomes A08, A09, C03, and C09, respectively. Two associated regions of GS content covered by these markers were further verified, and three B. napus homologous genes involved in the biosynthesis and accumulation of GS were identified. These genes were multigene family members and were distributed on different chromosomes. Moreover, two genes (BnGRT2 and BnMYB28) associated with GS content were validated by the qRT-PCR analysis of their expression profiles. The further identification and functionalization of these genes will provide useful insight into the mechanism underlying GS biosynthesis and allocation in B. napus, and the associated SNPs markers could be helpful for molecular maker-assisted breeding for low seed GS in B. napus.