Staphylococcus aureus, like other gram-positive pathogens, has evolved a large repertoire of virulence factors as a powerful weapon to subvert the host immune system, among which alpha-hemolysin (Hla), a secreted pore-forming cytotoxin, plays a preeminent role. We observed a concentration-dependent reduction in Hla production by S. aureus in the presence of sub-inhibitory concentrations of isorhamnetin, a flavonoid from the fruits of Hippophae rhamnoides L., which has little antibacterial activity. We further evaluate the effect of isorhamnetin on the transcription of the Hla-encoding gene hla and RNAIII, an effector molecule in the agr system. Isorhamnetin significantly down-regulated RNAIII expression and subsequently inhibited hla transcription. In a co-culture of S. aureus and lung cells, topical isorhamnetin treatment protected against S. aureus-induced cell injury. Isorhamnetin may represent a leading compound for the development of anti-virulence drugs against S. aureus infections.
Glutathione S-transferase (GST) genetic polymorphisms has been reported to be associated with osteosarcoma; however, the results of previous studies are conflicting. Thus, in the present study, a meta-analysis was conducted to investigate the effects of GSTM1 and GSTT1 polymorphisms on osteosarcoma risk. A literature search was performed in the PubMed, Cochrane Library and China National Knowledge Infrastructure databases to identify case-control studies published prior to March 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In addition, Begg’s test was used to measure publication bias. Sensitivity analysis were performed to ensure the accuracy of the results. The meta-analysis results demonstrated no significant association between the null genotype of GSTM1 and osteosarcoma risk (OR=0.83; 95% CI, 0.37–1.85). By contrast, the results revealed a significant association for the comparison of null vs. non-null genotypes of GSTT1 (OR=1.54; 95% CI, 1.09–2.19). In conclusion, the GSTT1 null genotype may be associated with an increased risk of developing osteosarcoma. Further studies with larger sample sizes and well-designed methodologies are required to verify these conclusions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.