ABSTRACT
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tb), and it remains one of the major bacterial infections worldwide. Innate immunity is an important arm of antimycobacterial host defence mechanism that senses various pathogen-associated molecular patterns (PAMP) of microbes by a variety of pattern recognition receptors (PRRs). As per the recent discovery, Toll-like receptors (TLRs) play a crucial role in the recognition of M. tb, this immune activation occurs only in the presence of functional TLRs. Variants of TLRs may influence their expression, function and alters the recognition or signalling mechanism, which leads to the disease susceptibility. Hence, the identification of mutations in these receptors could be used as a marker to screen the individuals who are at risk. In this review, we discuss TLR SNPs and their signalling mechanism to understand the susceptibility to TB for better therapeutic approaches.
Subject(s)
Immunity, Innate/genetics , Mycobacterium tuberculosis/immunology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Tuberculosis/immunology , Genetic Predisposition to Disease , Humans , Myeloid Differentiation Factor 88/metabolism , Polymorphism, Single Nucleotide , Signal Transduction/immunology , Toll-Like Receptors/metabolism , Tuberculosis/geneticsABSTRACT
Erythropoietin is a hematopoietic cytokine factor with various biological effects and its receptors are expressed in the central nervous system, which helps in normal brain development and exerts neuroprotection in different models of brain injury. The present study was designed to evaluate the neuroprotective role of erythropoietin in Aroclor 1254 induced oxidative stress in mice. Neurotoxicity was induced by Aroclor 1254 (10 mg/kg bw/day). Erythropoietin was administered simultaneously with Aroclor 1254 for 14 days in co-treatment groups and administered before induction of neurotoxicity for 7 days in case of pretreatment groups. To assess the behavioural parameters in observation with learning and memory, open field and Y-maze were employed. Acetylcholinesterase, glutamate, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) were estimated in brain tissue and corticosterone in plasma to evaluate the intensity of oxidative signalling in brain. Triglycerides and total cholesterol were estimated in plasma. Both doses of erythropoietin (500 and 1000 IU/kg) pretreatment and co-treatment, (i) significantly increased the habituation memory and percentage alteration which are indicative of the cognitive improvement, (ii) attenuated the Aroclor 1254 induced rise in acetylcholinesterase activity, corticosterone, triglycerides and total cholesterol, (iii) increased the glutamate and antioxidant enzyme levels. These results indicate that erythropoietin protects against Aroclor 1254 induced neurotoxicity and improves the cognitive function and that this cytokine could be a promising therapeutic agent for stress induced neurodegeneration.
Subject(s)
/toxicity , Erythropoietin/pharmacology , Neurotoxicity Syndromes/prevention & control , Oxidative Stress/drug effects , Animals , Antioxidants/metabolism , Behavior, Animal/drug effects , Brain/drug effects , Brain/pathology , Cholesterol/blood , Cognition Disorders/chemically induced , Cognition Disorders/prevention & control , Dose-Response Relationship, Drug , Erythropoietin/administration & dosage , Glutamic Acid/metabolism , Male , Maze Learning/drug effects , Memory/drug effects , Mice , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Neurotoxicity Syndromes/etiology , Triglycerides/bloodABSTRACT
Humans appear to have spread to several parts of the Indian subcontinent by the middle Paleolithic period. It also provided a major passage for the distribution of modern humans. For the first time generic human leucocyte antigen (HLA) class II (DRB1) genotyping was performed using polymerase chain reaction-sequence-specific primer (PCR-SSP) (low-resolution) technique in two endogamous groups (Hindu-Brahmins and Sunni-Muslims) from the southern state of Andhra Pradesh in order to decipher the genetic affinity between them and with other populations. Calculation of genetic distances, construction of neighbour-joining dendograms and principal-component (P-C) maps were executed using HLA allelic frequencies. The present study reveals the genetic affinity of the Brahmin and Muslim populations from the state of Andhra Pradesh. The dendograms demonstrated that Indian populations form a separate cluster with oriental populations on one side and the eastern and the western Mediterranean populations on the other side. The principal component maps showed the clustering of Indian populations in the lower-right quadrant, where in the Sunni-Muslims occupied a position more closely to the north Indian Brahmins and the Bhargavas than to the geographically related south Hindu-Brahmin group. The study hypothesizes that unlike Brahmins who can be considered as an immediate stock of the Caucasians, the ancestors of Muslims might have been the result of an admixture between the Indo-Europeans and proto-Dravidians.
