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Microbes Infect,
2012]
Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine candidate because it is present in all the major life stages of parasite, but is absent in mammals. We have previously cloned, purified and biochemically characterized Bm-TPP. In the present study, we investigated the cross-reactivity of recombinant Bm-TPP (r-Bm-TPP) with the sera of human bancroftian patients belonging to different disease categories. In silico study using bioinformatics tool demonstrated that Bm-TPP is highly immunogenic in nature. BALB/c mice administered with r-Bm-TPP alone or in combination with Freund's complete adjuvant (FCA) generated a strong IgG response. Further investigations on the antibody isotypes showed generation of a mixed T helper cell response which was marginally biased towards Th1 phenotype. r-Bm-TPP with or without adjuvant lead to significantly increased accumulation of CD4+ and CD8+ T cells in the spleen of infected mice and increased the activation of peritoneal macrophages. Additionally, r-Bm-TPP enhanced the production of both proinflammatory (IL-2, IFN-) and anti-inflammatory (IL-4, IL-10) cytokines and mice immunized with r-Bm-TPP alone or in combination with FCA showed 54.5% and 67% protection respectively against B. malayi infective larvae challenge. Taken together, our findings suggest that Bm-TPP is protective in nature and might be a potential candidate for development of vaccine against lymphatic filarial infections.
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Parasite Immunol,
2012]
Withania somnifera is an ayurvedic Indian medicinal plant whose immunomodulatory activities have been widely used as a home remedy for several ailments. We recently observed immunostimulatory properties in the root extracts of chemotypes NMITLI-101, NMITLI-118, NMITLI-128 and pure withanolide, withaferin A. In the present study, we evaluated the potential immunoprophylactic efficacies of these extracts against an infective pathogen. Our results show that administration of aqueous ethanol extracts (10 mg/kg) and withaferin A (0-3 mg/kg), 7 days before and after challenge with human filarial parasite Brugia malayi, offers differential protection in Mastomys coucha with chemotype 101R offering best protection (53-57%) as compared to other chemotypes. Our findings also demonstrate that establishment of B. malayi larvae was adversely affected by pretreatment with withaferin A as evidenced by 63-6% reduction in adult worm establishment. Moreover, a large percentage of the established female worms (66-2%) also showed defective embryogenesis. While the filaria-specific immunological response induced by withaferin A and NMITLI-101 showed a mixed Th1/Th2 phenotype, 118R stimulated production of IFN- and 128R increased levels of IL-4. Taken together, our findings reveal potential immunoprophylactic properties of W. somnifera, and further studies are needed to ascertain the benefits of this plant against other pathogens as well.
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Front Nutr,
2022]
The beneficial effects of vitamin K (VK) on various chronic age-related syndromes have generally been considered dependent on its antioxidant effects. However, due to the distinct bioavailability and biological activities of VKs, exactly which of these activities and by what mechanisms they might act still need to be elucidated. In this study, we found that VK2 can extend the lifespan of C. elegans and improve the resistance to pathogen infection, heat stress and H2O2-induced inner oxidative stress. Importantly, the roles of VK2 on aging and stress resistance were shown to be dependent on enhanced fat metabolism and not due to its antioxidant effects. Moreover, the genes related to fat metabolism that were up-regulated following VK2 treatment play key roles in improving survival. Obesity is a leading risk factor for developing T2DM, and taking VKs has been previously considered to improve the insulin sensitivity associated with obesity and T2DM risk. However, our results showed that VK2 can significantly influence the expression of genes related to fat metabolism, including those that regulate fatty acid elongation, desaturation, and synthesis of fatty acid-CoA. VK2 enhanced the fatty acid β-oxidation activity in peroxisome to degrade and digest fatty acid-CoA. Our study implies that VK2 can enhance fat degradation and digestion to improve survival, supporting the effectiveness of VK2-based medical treatments. VK2 is mainly produced by gut bacteria, suggesting that VK2 might facilitate communication between the gut microbiota and the host intestinal cells to influence fat metabolism.