Mahnaz Ghowsi; Nazli Khajehnasiri; Sajjad Sisakhtnezhad
Abstract
Connexin-43 (Cx-43) plays axial roles in the propagation of action potentials and contractile coupling in heart. Down-regulation of Cx-43 in heart is associated with arrhythmia, dilated cardiomyopathy and heart failure. To date, no studies have examined the effects of androgen deprivation therapy (ADT)-induced ...
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Connexin-43 (Cx-43) plays axial roles in the propagation of action potentials and contractile coupling in heart. Down-regulation of Cx-43 in heart is associated with arrhythmia, dilated cardiomyopathy and heart failure. To date, no studies have examined the effects of androgen deprivation therapy (ADT)-induced hypogonadism on the expression of Cx-43 in heart. This study investigated the effects of testosterone deprivation and its replacement with testosterone on the expression of Cx-43 mRNA and muscle-specific miRNAs miR-206 and miR-1, as two potential regulators of the Cx-43 protein expression in the ventricular tissue. Accordingly, 21 male Wistar rats were divided into three groups: Ι) Normal control, П) ORX-S: castrated rats serving as animal models for ADT and receiving the sesame oil as a solvent of testosterone enanthate for 10 weeks, and Ш) ORX-T: these animals were castrated, receiving testosterone enanthate (25 mg/kg) for 10 weeks. The relative expression of Cx-43 mRNA, miR-206 and miR-1 was determined by qRT-PCR. Cx-43 mRNA was found to be decreased in the ORX-S group. The Cx-43 mRNA was up-regulated after the administration of testosterone enanthate. There were no significant changes in miR-206 and miR-1 levels in the ORX-S and ORX-T groups when compared to the controls. Our results indicated that testosterone should be regarded as an important factor in the regulation of the Cx-43 mRNA expression in heart, and testosterone deprivation may down-regulate the Cx-43 mRNA expression; however, it doesn’t alter miR-1 and miR-206 levels. These results suggest that ADT-induced hypogonadism may put males at risk for cardiac dysfunctions.
Maryam Yazdani; Ali Bidmeshkipour; Sajjad Sisakhtnezhad
Abstract
The immunomodulation ability of mesenchymal stem cells (MSCs) has attracted interest as a unique property that makes them interesting tools for the treatment of inflammatory and autoimmune diseases. Eugenol is a volatile compound from the phenylpropanoids class of chemical compounds. Despite extensive ...
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The immunomodulation ability of mesenchymal stem cells (MSCs) has attracted interest as a unique property that makes them interesting tools for the treatment of inflammatory and autoimmune diseases. Eugenol is a volatile compound from the phenylpropanoids class of chemical compounds. Despite extensive investigations on the biological and pharmacological properties of Eugenol, its effect on the MSCs characteristics remains to be clarified. Therefore, this study was designed to evaluate the effect of Eugenol on the expression of genes (Tlr3, Tlr4, Ccl2, and Ccl3) involved in immunomodulation potency of MSCs by quantitative real-time PCR (qRT-PCR). To do so, MSCs were isolated from 4-8 weeks old mouse bone marrow (BM). The effect of Eugenol on the viability of BM-MSCs was evaluated by MTT assay at 24, 48, and 72h after treatment. The results showed that Eugenol reduced the number of BM-MSCs in a dose- and time-dependent manner. In addition, the half maximum inhibitory concentration of Eugenol on MSCs was 400μg/ml at 24 and 48h and 200μg/ml at 72h after treatment. Moreover, about 90% of MSCs were alive at the concentration of 12.5μg/ml 24h after treatment. The qRT-PCR results indicated that Tlr3, Tlr4, Ccl2, and Ccl3 genes up-regulated 1.6-, 1.8-, 1.3-, 2.2-fold, respectively, in Eugenol-treated BM-MSCs compared to untreated controls. In conclusion, we declare that Eugenol may somewhat regulate the immunomodulation potency of MSCs and this study provides a background for further studies on the effect of Eugenol on MSCs characteristics and functions, which may finally improve their potency for cell-based therapy applications.
