چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| صنم نامی | اول |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Background: RNA interference (RNAi) is a post-transcriptional gene silencing (PTGS) phenomenon by which RNA molecules knock down essential genes responsible for vital as well as virulence factors. Lately, Asian patients with Invasive aspergillosis (IA) develop resistance to azole as a result of a long term exposure to this drug as a treatment. On the basis of recent studies, roughly 40% of voriconazole-resistant Aspergillus flavus demonstrates a wide range of MDR1overexpression compared with the wild-type strain. Thus, this study is an endeavor to delve into the silencing potentials of siRNA on MDR1 in voriconazole-resistant Aspergillus flavus strains as the target gene. Methods: In this study, four voriconazole-resistant Aspergillus flavus strains and four voriconazole-susceptible strains were used (These isolates were identified previously and were stored in the culture collection of the Medical Mycology Laboratory, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran). We designed three MDR1-specific siRNAs and after the co-transfection of siRNA into Aspergillus flavus strains, using lipofectamine, we investigated the effect of different siRNA concentrations (5, 15, 25, 50nM) on MDR1 expression by qRT-PCR. Finally, the Minimum Inhibitory Concentrations (MICs) of voriconazole for isolates were determined by the broth dilution method. Results: MDR1 siRNA induced 2, 4, 8, 17-fold reductions in MDR1 mRNA expres¬sion in voriconazole-resistant strains following the treatment of the cells with concentrations of 5, 15, 25, 50nM siRNA, respectively. The results demonstrated the MIC values of voriconazole were significantly reduced in the treated groups with MDR1-specific siRNA, both at concentrations of 25nM (1, 2, 4, 4µg per ml) and 50nM (0.5, 2, 4, 4µg per ml), when compared to the untreated groups (4, 8, 16, 16µg per ml). Conclusion: In this study, we suggested that siRNA-mediated specific inhibition of MDR1 gene can play role in voriconazole-resistant Aspergillus flavus strains and this could be one of the target genes for inactivation. However, we recommend evaluating various multidrug resistance efflux pumps (MDR-EPs) and performing experiments on the effect of siRNA on human cells in the future studies. The current study promises a bright prospect for the treatment of invasive aspergillosis through the effective deployment of RNAi and gene therapy. |
| کلمات کلیدی | MDR1 gene, RNA silencing, voriconazole, Aspergillus flavus. |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| abstract.pdf | 1398/02/31 | 1843127 | دانلود |
| 1.pdf | 1398/02/31 | 993406 | دانلود |
