Search

Background Visceral leishmaniasis (VL) is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations. Methodology All the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India. Result and Discussion Our analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR) and rs3024498 (5311 A>G, 3’ UTR). Of these, a variant g.5311A is significantly associated with VL (χ2=18.87; p =0.00001). In silico approaches have shown that a putative micro RNA binding site (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL (‘A’ of rs3024498); and high frequency of leprosy (‘T’ of rs1554286), and Behcet’s (‘A’ of rs1518111) associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet’s disease. This study has potential implications in counseling and management of VL and other infectious diseases.

Cellular signaling plays an important role in alteration of cellular physiology and initiation of pharmacological response. Cells usually communicate with each other through extracellular messenger molecules called ligand which can travel a short distance and stimulate cells with the release of second messenger molecule by a cell that is engaged in sending messages to the downward in same cell or to the other cells in the body. Cells can only respond to a particular extracellular message if they express receptors for that ligand specifically recognize and bind that messenger molecule and the interaction between the ligand and receptor induces a conformational change in the receptor that causes the signal to be relayed across the membrane to the receptor’s cytoplasmic domain. A signaling pathway is activated by a diffusible second messenger and another in which a signaling pathway is activated by recruitment of proteins to the plasma membrane. Most signal transduction pathways involve a combination of these mechanisms. In this review we have tried to elaborate diagrammatically the details about the various pathways responsible for signaling for easy understanding for the future research.

Imbalances in normal regulation of food intake can cause obesity and related disorders. Pancreatic polypeptide (PP) share considerable amino acid sequence homology act as a robust anorexigenic hormone effectively modulates food intake and energy homeostasis, thus potentially aiding anti-obesity therapeutics. They are found in widely disparate locations, including the pancreas (PP), the distal gut (PYY), and the central nervous system (NPY). Intra-gastric and intra-intestinal infusion of nutrients stimulate PP secretion from the gastrointestinal tract, in turn that causes vagal stimulation and exerts complex actions via the neuropeptide Y4 receptor (Family of G-protein coupled Receptors) in arcuate nucleus of the hypothalamus, there by subsequently activating key hypothalamic nuclei and dorsal vagal complex of the brainstem to influence energy homeostasis and body composition. In this review our efforts have been devoted to summarize the detail about the pancreatic polypeptide their functions and mechanisms.