IMPACT OF DELETERIOUS NON-SYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS OF CYTOKINE GENES ON NON-CLASSICAL HYDROGEN BONDS PREDISPOSING TO CARDIOVASCULAR DISEASE: AN IN SILICO APPROACH

  Objective: Cardiovascular disease (CVD) is a leading cause of death worldwide. Malfunctioning of genes that are responsible for several inflammatory processes is the major cause for its initiation. Cytokine genes are one such group of genes that are involved in the development of CVD. Hence, the prediction of potential point mutations in these genes is important for diagnostic purposes. Such mutations result in altered protein structure and function when compared to neutral ones.Methods: In this study, interleukin factor 6 (IL6), tumor necrosis factor α (TNF-α), interleukin factor 4 (IL4), and interferon gamma have been analyzed using sorting intolerant from tolerant and PolyPhen 2.0 tools.Results: Several single nucleotide polymorphisms (SNPs), in IL6, TNF-α, and IL4, are found to be potentially deleterious. In addition, bond analysis has also been performed on these SNPs. It has been predicted that L119P and R196H of IL6 as well as K87T and T181N of TNF-α are potential ns-SNP's that may cause structural and functional variations in the corresponding proteins. The hydrogen and Cation-Pi bond analysis performed in this study provides molecular-based evidence that support the predicted deleterious potential of such SNPs for these CVD candidate genes along with other conventional in silico tools.Conclusion: The study testifies the importance of adopting a computational approach to narrow down potential point mutants for disease predictions

Investigation on the role of nsSNPs in HNPCC genes – a bioinformatics approach

<p>Abstract</p> <p>Background</p> <p>A central focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations not only provides insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. Missense mutations are nucleotide substitutions that change an amino acid in a protein, the deleterious effects of these mutations are commonly attributed to their impact on primary amino acid sequence and protein structure.</p> <p>Methods</p> <p>The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols. To explore possible relationships between genetic mutation and phenotypic variation, we employed different bioinformatics algorithms like Sorting Intolerant from Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen), and PupaSuite to predict the impact of these amino acid substitutions on protein activity of mismatch repair (MMR) genes causing hereditary nonpolyposis colorectal cancer (HNPCC).</p> <p>Results</p> <p>SIFT classified 22 of 125 variants (18%) as 'Intolerant." PolyPhen classified 40 of 125 amino acid substitutions (32%) as "Probably or possibly damaging". The PupaSuite predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Based on the PolyPhen scores and availability of three-dimensional structures, structure analysis was carried out with the major mutations that occurred in the native protein coded by <it>MSH2 and MSH6 </it>genes. The amino acid residues in the native and mutant model protein were further analyzed for solvent accessibility and secondary structure to check the stability of the proteins.</p> <p>Conclusion</p> <p>Based on this approach, we have shown that four nsSNPs, which were predicted to have functional consequences (<it>MSH2</it>-Y43C, <it>MSH6</it>-Y538S, <it>MSH6</it>-S580L, <it>and MSH6</it>-K854M), were already found to be associated with cancer risk. Our study demonstrates the presence of other deleterious mutations and also endorses with <it>in vivo </it>experimental studies.</p

Comparative Estimation of Arginine Content in Peanuts: An Analytical Study

Introduction: Arginine is an amino acid that has several positive effects on human health and peanut seeds are the richest source of it. Peanuts are the store houses loaded with proteins, fatty acids, vitamins, fiber and other phytochemicals. It has been shown that the intake of arginine at the concentration of 3-6 g/day has been found to improve the cardiovascular system, reduce intestinal permeability and activate the immune system that aids in early recovery of tuberculosis patients. Aim: To evaluate the variation of arginine content in raw, boiled, soaked, soaked and boiled type of peeled and unpeeled peanuts Materials and Methods: The analytical study on various groups of peanuts (raw, boiled, soaked, soaked and boiled peanuts of both peeled and unpeeled varieties) was conducted at Gayatri Vidya Parishad Institute of Health Care and Medical Technology at Visakhapatnam, Andhra Pradesh, India, in December 2019. The arginine content was estimated in peanut seeds using the Sakaguchi method by Spectrophotometry at wavelength of 520 nm. Descriptive statistics were done for all 12 groups and were represented with mean, standard deviation and standard error. Analysis of Variance (ANOVA), Post-hoc Tukey’s were applied to find statistical significance. The p-value <0.05 was considered as statistically significant. Statistical Package for Social Sciences (SPSS) version 25.0 was used for analysis. Results: Concentration of arginine was recorded for each type in triplicate considering the mean. The raw soaked peeled peanuts had the lowest concentration of arginine (31.82 μg/g) and the soaked boiled for 15 minutes, unpeeled peanuts had the highest amount of arginine (1438.18 μg/g). Significant difference was found among the twelve groups by using ANOVA test p<0.001. Soaked and boiled 15 min peeled peanuts, soaked unpeeled, soaked and boiled 15 min unpeeled and soaked and boiled 30 min unpeeled were significantly different when compared to the remaining groups using Post hoc Tukey’s test p<0.05. Conclusion: Soaked, boiled and unpeeled peanuts were the best types with the highest amounts of arginine which could be chosen as adjuvant nutritional therapeutic supplement to aid in the recovery of certain diseases

AKT Kinase Pathway: A Leading Target in Cancer Research

AKT1, a serine/threonine-protein kinase also known as AKT kinase, is involved in the regulation of various signalling downstream pathways including metabolism, cell proliferation, survival, growth, and angiogenesis. The AKT kinases pathway stands among the most important components of cell proliferation mechanism. Several approaches have been implemented to design an efficient drug molecule to target AKT kinases, although the promising results have not been confirmed. In this paper we have documented the detailed molecular insight of AKT kinase protein and proposed a probable doxorubicin based approach in inhibiting miR-21 based cancer cell proliferation. Moreover, the inhibition of miR-21 activation by raising the FOXO3A concentration seems promising in reducing miR-21 mediated cancer activation in cell. Furthermore, the use of next generation sequencing and computational drug design approaches will greatly assist in designing a potent drug molecule against the associated cancer cases