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Heat shock proteins (Hsps) have been reported to be dominant antigens for the host immune response to various pathogens and thus, have great potential for use in vaccination. In the present study, we evaluated the immunogenicity and protective efficacy of GroEL of Salmonella enterica serovar Typhi against lethal infection by S. typhi Ty2 in mice with or without adjuvants. Anti GroEL-IgG titers were significantly higher in mice immunized with either GroEL-alone or in combination with alum/Complete Freund's adjuvant (CFA) as compared to the control. Analysis of antibody isotypes suggested predominance of Th2 type immune response in GroEL + alum immunized animals as revealed by higher IgG1/IgG2a ratio. Whereas, immunization of animals with GroEL + CFA or GroEL-alone shifted the immune response toward Th1 phenotype. Mice immunized with GroEL with or without adjuvants, showed a significant increase in lymphocyte proliferation and cytokine levels. The animals immunized with GroEL + CFA or GroEL-alone showed higher IFN-gamma and IL-2 levels than alum group, indicating Th1 response whereas IL-4 levels (Th2 response) were found to be highest in alum group as compared to other two immunized groups. Immunization of mice with GroEL-alone, GroEL + alum, and GroEL + CFA provided 70, 50 and 80% protection, respectively, against lethal challenge by S. typhi in mice. The differences in the percentage protection among various groups were attributed to the differences in the immune responses generated by respective immunizations. The present study shows that GroEL forms an ideal candidate molecule to develop a recombinant protein based vaccine against human typhoid.

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The objective of the study was to find out the prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. Male SD rats received different doses of quercetin @ 25mg, 50mg, 100mg and 200mg/Kg BW, 1h prior to hypobaric hypoxia exposure (7,620m, for 6h). Quercetin 50 mg/kg BW supplemented orally 1h prior to hypoxia exposure was considered to be the optimum dose, due to significant reduction (p<0.001) in lung water content and lung transvascular leakage compared to control (hypoxia, 6h). Further, biochemical analysis (ROS, MDA, GSH, GPx, LDH, and albumin) and differential expressions of proteins (IKK-α/β, NFĸB, Nrf-2,TNF-α, ICAM-1, VCAM, P-selectin, Hif-1α, VEGF, TNF-α, TGF-β, INF-γ and IL-4) were determined by western blotting and ELISA. Changes in lung parenchyma were assessed by histopathology. Quercetin (50 mg/kg BW) prophylaxis under hypoxia showed significant reduction in oxidative stress (ROS and MDA), concomitant increase in antioxidants (GSH, GPx and SOD) followed by decreased LDH and albumin extravasation in BAL fluid over hypoxia. Quercetin prophylaxis significantly down regulated hypoxia induced increase in IKKα/β and NFĸB expressions leading to reduction in the levels of pro-inflammatory cytokines (TNF-α and INF-γ) followed by up regulation of anti-inflammatory cytokines (IL-4 and INF-γ) in lungs. Further, hypoxia mediated increase in HIF-1α was stabilized and VEGF levels in lungs were significantly down regulated by quercetin supplementation, leading to reduction in vascular leakage in lungs of rats under hypoxia. However, Quercetin has also enacted as Nrf-2 activator which significantly boosted up the synthesis of GSH under hypoxic condition compared to hypoxia. Histopathological observations further confirmed that quercetin preconditioning has an inhibitory effect on progression of oxidative stress and inflammation via attenuation of NFκB and stabilization HIF-1α in lungs of rats under hypoxia.These studies indicated that quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced pulmonary edema in rats.

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