Pharmaceutical Potential of a Novel Chitosan Derivative Schiff Base with Special Reference to Antibacterial, Anti-Biofilm, Antioxidant, Anti-Inflammatory, Hemocompatibility and Cytotoxic Activities.

PURPOSE: Chitosan and its derivatives possess several unique properties relevant in the field of pharmaceutics and medicinal chemistry. This study aimed to evaluate the pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base. METHODS: The antibacterial activity of MA*CS*pNBA was tested against multi-drug resistant (MDR) Gram-negative and Gram-positive bacteria using agar-well diffusion method. Anti-biofilm formation was analyzed using a microtitre plate. Antioxidant assays were performed to assess the scavenging activity of MA*CS*pNBA using DPPH, hydrogen peroxide, superoxide together with its reducing power activity. Anti-inflammatory activity was evaluated by albumin denaturation, membrane stabilization, and proteinase inhibition methods. MA*CS*pNBA was tested for its hemolytic efficiency on human erythrocytes. Cytotoxicity of MA*CS*pNBA was evaluated by MTT assay. RESULTS: MA*CS*pNBA showed a significant performance as an antibacterial candidate against MDR bacteria, anti-biofilm, antioxidant and anti-inflammatory biomaterial, evidencing hemocompatibility and no cytotoxicity. It exhibited a significant negative correlation with biofilm formation by the MDR-PA-09 strain. Biological activities were found to be significantly concentration-dependent. CONCLUSIONS: the newly chitosan derivative MA*CS*pNBA showed to be promising for pharmaceutical applications, expanding the treatment ways toward skin burn infections since it allied excellent antibacterial, anti-biofilm, antioxidant, anti-inflammatory, hemocompatibility and absence of cytotoxic activities.

MiR-484 Protects Rat Myocardial Cells from Ischemia-Reperfusion Injury by Inhibiting Caspase-3 and Caspase-9 during Apoptosis

BACKGROUND AND OBJECTIVES: To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury.METHODS: Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis.RESULTS: Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1β in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484.CONCLUSIONS: MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1β in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.

MiR-484 Protects Rat Myocardial Cells from Ischemia-Reperfusion Injury by Inhibiting Caspase-3 and Caspase-9 during Apoptosis

BACKGROUND AND OBJECTIVES@#To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury.@*METHODS@#Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis.@*RESULTS@#Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1β in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484.@*CONCLUSIONS@#MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1β in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.