RESUMEN
The control and eradication of any infectious disease is only possible with a potential vaccine, which has not been accomplished for human visceral leishmaniasis (VL). The lack of vaccines may increase the risk of VL outbreaks periodically in endemic zones. Identifying a reliable vaccine candidate for Leishmania is a major challenge. Here, we considered Leishmania donovani ascorbate peroxidase (LdAPx) for its in vitro evaluation with the hope of future vaccine candidates for VL. LdAPx was selected based on its unique presence in Leishmania and virulence in VL pathogenesis. Initially, we found antibodies against recombinant LdAPx (rLdAPx) in the serum of VL patients. Therefore, using bioinformatics, we predicted and selected ten (MHC class I and II) peptides. These peptides, evaluated in vitro with PBMCs from healthy, active VL, and treated VL individuals induced PBMC proliferation, IFN-γ secretion, and Nitric Oxide (NO) production, indicating host-protective immune responses. Among them, three peptides (PEP6, PEP8, and PEP9) consistently elicited a Th1-type immune response in PBMCs. Treated VL individuals showed a stronger Th1 response compared to active VL patients and healthy subjects, highlighting these peptides' potential as vaccine candidates. Further studies are on the way toward evaluating the LdAPx-derived peptides or sub-unit vaccine in animal models against the L. donovani challenge.
RESUMEN
MicroRNAs are small ribonucleic acid that act as an important regulator of gene expression at the molecular level. However, there is no comparative data on the regulation of microRNAs (miRNAs) in visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). In this current study, we compared the expression miRNA profile in host cells (GTHP), with VL strain (GVL) and PKDL strain-infected host cell (GPKDL). Normalized read count comparison between different conditions revealed that the miRNAs are indeed differentially expressed. In GPKDL with respect to GVL and GTHP, a total of 798 and 879 miRNAs were identified, out of which 349 and 518 are known miRNAs, respectively. Comparative analysis of changes in miRNA expression suggested that the involvement of differentially expressed miRNAs in various biological processes like PI3K pathway activation, cell cycle regulation, immunomodulation, apoptosis inhibition, different cytokine production, T-cell phenotypic transitions calcium regulation, and so on. A pathway enrichment study using in silico predicted gene targets of differentially expressed miRNAs showed evidence of potentially universal immune signaling pathway effects. Whereas cytokine-cytokine receptor interaction, phagocytosis, and transforming growth factor beta (TGF-ß) signaling pathways were more highly enriched using targets of miRNAs upregulated in GPKDL. These findings could contribute to a better understanding of PKDL pathogenesis. Furthermore, the identified miRNAs could also be used as biomarkers in diagnosis, prognosis, and therapeutics of PKDL infection control.
RESUMEN
Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin's potentials as an antioxidant, immune-modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community.