The possible role of NS3 protease activity of hepatitis C virus on fibrogenesis and miR-122 expression in hepatic stellate cells.

The various roles of hepatitis C virus (HCV) NS3 protein in viral pathogenesis are emphasized, especially in the progression of fibrosis and tumors. The levels of miR-122 have been widely accepted as a critical factor in viral pathogenesis and disease progression. However, the possible correlation between miR-122 levels and fibrosis state has been less investigated. Therefore, in this study, plasmids expressing protease competent and protease mutated non-structural proteins 3 (NS3) were transfected into LX-2 cell line. Subsequently, the total RNA was extracted and real-time PCR was performed to measure the expression level of miR-122, collagen type 1 alpha 1 (COL1A1), alpha smooth muscle actin (α-SMA), and tissue inhibitor of metaloproteinase 1 (TIMP-1). Moreover, the transforming growth factor beta (TGF-ß) levels in the supernatants of transfected cells were evaluated by ELISA. The gene expression analysis of fibrotic genes and TGF-ß cytokine in LX-2 cells showed that protease competent NS3 had a significant fibrogenic impact when compared to protease defective NS3 or GFP control plasmids (P <0.001). The results also demonstrated that the expression of miR-122 was downregulated in both versions of the cells transfected with NS3 plasmids (P <0.01) irrespective of protease function. These results suggested that the protease function of NS3 protein is a crucial factor for the induction of hepatic fibrosis but it doesn't play a complete role in the expression of miR-122.

Emergence of Multidrug Resistance and Metallo-beta-lactamase Producing Acinetobacter baumannii Isolated from Patients in Shiraz, Iran.

BACKGROUND: Metallo-beta-lactamase (MßL) enzymes production is one of the most important resistance mechanisms against carbapenems in some bacteria including Acinetobacter baumannii. AIMS: This study was aimed to determine the antimicrobial susceptibility and the prevalence of MßL among carbapenem-resistant isolates of A. baumannii. MATERIALS AND METHODS: In this cross-sectional study from October 2012 to April 2013, 98 isolates were identified as A. baumannii using Microgen™ kits and confirmed by molecular method. These isolates were tested for antimicrobial susceptibilities by disk diffusion method according to the Clinical and Laboratory Standards Institute guidelines. Carbapenem-resistant isolates were further detected phenotypically by MßL minimal inhibitory concentration (MIC)-test strips, and subsequently positive MßL isolates were confirmed by polymerase chain reaction (PCR). RESULTS: Overall, 98% (96/98) of A. baumannii isolates were detected as carbapenem-resistant by MIC test. Highest sensitivity to the tested antibiotic with 42.9% (42/98) was observed to colistin. Of 96 carbapenem-resistant isolates, 43 were phenotypically positive for MßL; out of 43 isolates, 37 were confirmed for the presence of MßL genes by PCR. CONCLUSION: The frequency of drug resistance among the clinical samples of A. baumannii isolated in our study against most of the antibiotics was very high. Moreover, all MßL producing isolates were multidrug resistance. Therefore, systematic surveillance to detect MßL producing bacteria and rational prescription and use of carbapenems could be helpful to prevent the spread of carbapenem resistance.

TNF-alpha, TNF-beta and IL-4 gene polymorphisms in Iranian patients with multiple sclerosis.

OBJECTIVES: To investigate the association between tumor necrosis factor-alpha (TNF-alpha) G-308A, tumor necrosis factor-beta (TNF-beta) G+252A and interleukin-4 (IL-4) C-590T polymorphisms and susceptibility to multiple sclerosis (MS) development and clinical course of the disease. MATERIALS AND METHODS: Two hundred and seventy patients with MS and 542 sex and ethnic matched controls were enrolled in the present study. An allele-specific oligonucleotide polymerase chain reaction was used to detect the polymorphism at position -308 of the TNF-alpha gene. The genotypes of TNF-beta and IL-4 were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Allelic and genotypic frequencies for these polymorphisms were similar in patients with MS and population controls or among different types of the disease. CONCLUSION: The results of the present study suggest that the three mentioned functional polymorphisms are not likely to cause susceptibility to MS in the Iranian population.