TGF-ß1-stimulation of matrix metalloproteinase-13 expression by down-regulation of miR-203a-5p in rat osteoblasts.

Transforming growth factor-beta1 (TGF-ß1) is a pleiotropic and ubiquitous cytokine involved in bone development and bone remodeling. Matrix metalloproteinase-13 (MMP13) plays a role in the degradation of the extracellular matrix (ECM), and the regulation of this gene is critical in bone remodeling. We previously reported that TGF-ß1 stimulates MMP13 expression in rat osteoblasts. Recently, studies have examined the regulation of bone metabolism by microRNAs (miRNAs) to determine their therapeutic potential in osteogenesis. Here, we assessed the effect of TGF-ß1 on down-regulation of miRNAs that target MMP13 and stimulation of MMP13 expression in osteoblasts. We used in silico analysis and identified 11 specific miRNAs which directly target rat MMP13. Among these miRNAs, miR-203a-5p expression was significantly decreased by TGF-ß1-treatment in rat osteoblasts. Transient transfection of a miR-203a-5p mimic into rat osteoblasts reduced MMP13 expression. A luciferase reporter assay confirmed a direct targeting of miR-miR-203a-5p with the 3' untranslated regions of the MMP13 gene. Hence, we suggest that TGF-ß1 stimulated down-regulation of miR-203a-5p, resulting in the stimulation of MMP13 expression in rat osteoblasts. Thus, identification of the role of miR-203a-5p via TGF-ß1 and MMP13 in bone remodeling indicated its potential as a biomarker or therapeutic agent for treating bone and bone-related diseases.

Prediction of drug-resistance using genotypic and docking analysis among anti-retroviral therapy naïve and first-line treatment failures in Salem, Tamil Nadu, India.

The emergence of drug resistance among HIV-positive patients undergoing Anti- Retroviral Therapy (ART) with poor adherence to the HAART is a major concern in India. As the HIV accumulates the key mutations, the drug resistance occurs, that pose challenges to the ART regimens currently being used. Thus, the present study was carried out among the ART- naïve patients attending ART Centre at Salem district, Tamil Nadu, India. The mutations that concern the drug resistance were discriminated by determining the viral load before and after 6 months. The drug resistance was analyzed by HIV genotyping from the patients possessing a viral load of >1000 copies/mL after 6 months of ART. The mutations pertaining to drug resistance were analyzed by the online Stanford HIV Database. The 3D structures of the RT were modeled and the drugs used in the first-line regimens were docked to explore the effect of mutations on the binding pattern of the drugs. Among the 250 patients, the viral load data were obtained for 213 patients. The study found 23 patients with both virological and immunological failures and HIV drug mutations were also revealed by genotyping. The mutations of I135R/T/V/X, L178 I/M, M184V/I, D67N, K70R, and K103N were the most common among these 23 patients. The present study revealed that the NACO recommended first-line ART regimen is efficient in most of the patients attending ART center. The emergence of drug resistance of HIV variant is common even under the best circumstance of ART. This study reveals that there is a necessity for the implementation of improved and economically systematic attempt that allows the clinicians to make a rational choice of therapy regimen to overcome the first-line therapy failures among the ART- naive.

Anticandidal activity of certain South Indian medicinal plants.

The anticandidal activity of 20 household South Indian medicinal plants and/or plant products was studied using 30 Candida albicans isolates obtained from vaginal candidiasis patients of Rajah Muthiah Medical College and Hospital and compared with the anticandidal activity of garlic. Water and ethanol extracts were prepared and their minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) were determined. Water extracts of three plants did not show any anticandidal activity, while Murrya koenigii did not exhibit any anticandidal activity in either extract. Other plants exhibited more activity in ethanol extracts showing that their active principle is more soluble in a non-polar solvent.