In silico analysis and molecular docking studies of natural compounds of Withania somnifera against bovine NLRP9.

CONTEXT: NLRP9 is a member of nucleotide-binding domain leucine-rich repeat-containing receptors and is found to be associated with many inflammatory diseases. In the current scenario, the identification of promising anti-inflammatory compounds from natural sources by repurposing approach is still relevant for the early prevention and effective management of the disease. METHODS: In the present study, we docked bioactives of Ashwagandha (Withanoside IV, Withanoside V, Withanolide A, Withanolide B, and Sitoindoside IX) and two control drugs against bovine NLRP9 protein. ADME/T analysis was used to determine the physiochemical properties of compounds and standard drugs. Molecular modeling was used to evaluate the correctness and quality of protein structures. In silico docking analysis revealed Withanolide B had the highest binding affinity score of -10.5 kcal/mol, whereas, among control drugs, doxycycline hydrochloride was most effective (-10.3 kcal/mol). The results of this study revealed that bioactives of Withania somnifera could be promising inhibitors against bovine NLRP9. In the present study, molecular simulation was used to measure protein conformational changes over time. The Rg value was found to be 34.77A°. RMSD and B-factor were also estimated to provide insights into the flexibility and mobile regions of protein structure. A functional protein network interaction was constructed from information collected from non-curative sources as protein-protein interactions (PPI) that play an important role in determining the function of the target protein and the ability of the drug molecule. Thus, in the present situation, it is important to identify bioactives with the potential to combat inflammatory diseases and provide strength and immunity to the host. However, there is still a need to study in vitro and in vivo to further support these findings.

Comparative transcriptome analysis reveals the genetic basis of coat color variation in Pashmina goat.

The genetics of coat color variation remains a classic area. Earlier studies have focused on a limited number of genes involved in color determination; however, the complete set of trait determinants are still not well known. In this study, we used high-throughput sequencing technology to identify and characterize intricate interactions between genes that cause complex coat color variation in Changthangi Pashmina goats, producer of finest and costly commercial animal fiber. We systematically identified differentially expressed mRNAs and lncRNAs from black, brown and white Pashmina goat skin samples by using RNA-sequencing technique. A pairwise comparison of black, white and brown skin samples yielded 2479 significantly dysregulated genes (2422 mRNA and 57 lncRNAs). Differentially expressed genes were enriched in melanin biosynthesis, melanocyte differentiation, developmental pigmentation, melanosome transport activities GO terms. Our analysis suggested the potential role of lncRNAs on color coding mRNAs in cis and trans configuration. We have also developed online data repository as a component of the study to provide a central location for data access, visualization and interpretation accessible through http://pcd.skuastk.org/ .

LncRNAs and immunity: watchdogs for host pathogen interactions.

Immune responses combat various infectious agents by inducing inflammatory responses, antimicrobial pathways and adaptive immunity. The polygenic responses to these external stimuli are temporally and coordinately regulated. Specific lncRNAs are induced to modulate innate and adaptive immune responses which can function through various target interactions like RNA-DNA, RNA-RNA, and RNA-protein interaction and hence affect the immunogenic regulation at various stages of gene expression. LncRNA are found to be present in various immune cells like monocytes, macrophages, dendritic cells, neutrophils, T cells and B cells. They have been shown to be involved in many biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but the knowledge how lncRNAs are regulated and how they alter cell differentiation/function is still obscure. Further dysregulation of lncRNA has been seen in many diseases, but as yet very less research has been carried out to understand the role of lncRNAs in regulation during host-pathogens interactions. In this review, we summarize the functional developments and mechanism of action of lncRNAs, in immunity and defense of host against pathogens.