The long-term effects of Δ9-tetrahydrocannabinol on microtubule dynamicity in rats.

Studies reported that Δ9-tetrahydrocannabinol (Δ9-THC) is an essential drug as an anti-cancer, neuroprotective, anti-inflammatory, and immune-modulatory agent. However, the mechanism by which Δ9-THC causes these events remains to be elucidated. We attempted to investigate the in vivo studies of Δ9-THC on brain microtubule dynamicity, and acetylcholinesterase (AChE) activity. The microtubule polymerization, secondary and tertiary structures of α/ß-tubulins, as well as the AChE activity, were evaluated in the experimental groups. The significantly lowest optical density and initial rate of polymerization was observed in THC 3 mg/kg, THC 9 mg/kg, and THC 18 mg/kg treated groups. The content of secondary and tertiary structures of α/ß-tubulins was significantly affected in treated groups. The AChE activity was significantly lower in treated groups in a dose-dependent manner. These data highlight the microtubule dynamicity as a molecular target for Δ9-THC, which affects memory dysfunction. However, Δ9-THC can be inhibited the AChE activity and provide an improved therapeutics for neurodegenerative diseases.

Immune Modulatory Effects of Hypercholesterolemia: Can Atorvastatin Convert the Detrimental Effect of Hypercholesterolemia on the Immune System?

Many observations showed that hypercholesterolemia can disrupt immune response. Statin drugs that were used for the treatment of hypercholesterolemia patients can interfere in the regulation of the immune response and cytokine secretion. The primary aim of the current study was to investigate the immune response among treatment-naïve patients with hypercholesterolemia and healthy subjects. The secondary goal of the study was to determine whether atorvastatin can reverse the detrimental effect of hypercholesterolemia on the immune system. Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients afflicted with hypercholesterolemia who were treatment-naïve along with 50 sex/age-matched hypercholesterolemia patients receiving atorvastatin, and 50 sex/age-matched healthy subjects. Quantitative PCR and ELISA methods were used for gene and protein expression analysis of T helper 1 (Th1) and Th2 related cytokines. Additionally, the expression of the cluster of differentiation (CD) markers on T, B, and natural killer (NK) cells was measured by flow cytometry method. The results showed that hypercholesterolemia and atorvastatin down-regulated the expression of Th1-related cytokines and elevated the levels of Th2-related cytokines. The expression of cell surface markers, CD25 and CD69, was significantly decreased in the treatment-naïve, and atorvastatin groups. It seems that atorvastatin is not able to repair the deleterious effects of hypercholesterolemia on the immune system. Moreover, elevated levels of cholesterol along with the administration of atorvastatin tilt the Th1/Th2 balance in favor of Th2 and reduce T cell activation.

Improving the thermostability of Serratia marcescens B4A chitinase via G191V site-directed mutagenesis.

Chitinases with high thermostability are important for many industrial and biotechnological applications. This study was conducted to enhance the stability of Serratia marcescens B4A chitinase by site directed mutagenesis of G191 V. Further characterization showed that the thermal stability of the mutant showed marked increase of about 5 and 15 fold at 50 and 60 °C respectively, while the optimum temperature and pH was retained. Kinetic analysis showed decreased Km and Vmax of the mutant in comparison with the wild type chitinase of about 1.3 and 3 fold, respectively. Based on structural prediction, it was speculated that this replacement shortened an important loop concomitant with the extension of adjacent ß sheets. Accordingly, a higher thermostability of G191 V up to 90 °C supporting the decreased flexibility of unfolded state was also indicated. Finally, a practical proof of kinetic and thermal stabilization of chitinase was provided through decreased flexibility and entropic stabilization of its surface loops.