Association of APOA1-75G/A and +83C/T polymorphic variation with acute coronary syndrome patients in Kashmir (India)

Introduction: Acute coronary syndrome (ACS) comes under the ambit of cardiovascular disease.APOA-1 gene plays a vital role in lipid metabolism and has been observed to have plausible role in ACS. This cross sectional case-control study was conducted to evaluate association between APOA1-75G/A(rs1799837), +83C/T (rs5069) genotypes and risk for ACS. Methods: The current case-control study that included confirmed 90 ACS cases and 150 healthy controls were genotyped for APOA1-75 G/A and +83 C/T by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLF) method. Results: APOA1-75G/A distribution of genotypes/alleles among cases and controls was seen proportionally same with no association to ACS (P = 0.5). APOA1+83 C/T variants showed protective effect with ACS where variant TT genotype presented more in controls (12%) than cases (1.6%) (P = 0.004) and likewise variant ‘T’ allele was found more in controls than ACS cases (9.4% vs.28.5% respectively: P < 0.05). Further, significantly high difference of CT genotype was seen among cases and controls 15% vs. 33% respectively (P = 0.002). The overall distribution of different haplotypes showed a marked difference in GT when compared with GC between cases and controls (P = 0.0001). Conclusion: The study shows that TT genotype and variant T allele of APOA1 +83 C/T depicted a protective role with respect to ACS whereas APOA1-75G>A showed no relation. Haplotype GT was observed to significantly over-represent in controls with its protective effect in ACS as against wild type haplotype GC

Implications of risk conferred by 5p15.33 loci genetic variants; human telomerase reverse transcriptase rs2736098 and rs2736100 in predisposition of bladder cancer

Background: The polymorphic variations of human telomerase reverse transcriptase (hTERT) gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of hTERT gene. Materials and methods: Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of hTERT rs2736098 and rs2736100. Results: hTERT rs2736098 homozygous variant AA genotype frequency was observed to significantly differ 2-fold between cases and controls (26.15% vs. 13.5%) (p = 0.02). In addition, rare ‘A’ allele significantly differed among two groups (cases: 47% versus controls: 39%: p = 0.03). hTERT rs2736098 was observed to be presented significantly more in high stage tumors (p = 0.02). hTERT rs2736100 genotype AA or variant allele A showed no significant difference between cases and controls. Haplotype CA displayed significantly different pattern of frequency as 0.5 in cases as compared to 0.16 in controls (p < 0.0001). Combination of variant A/G haplotype frequency implicated more in cases than in controls (0.34 vs. 0.16, p = 0.001). Conclusions: It is concluded that hTERT rs2736098 polymorphic variant has a vital role to confer a strong risk to bladder cancer in our population. Further, hTERT haplotypes CA and AG inhTERT could prove to be a promising tool to screen the risk for bladder cancer

CALLUS INDUCTION AND DIRECT ORGANOGENESIS IN SAFFRON CALLUS BY USING PLANT EXTRACT AS AN ALTERNATIVE TO PHYTOHORMONES

Objectives: Saffron (Crocus sativus) is mostly propagated vegetatively. Therefore, cost-effective methods need to be developed, in order to multiply and increase the yield of saffron. The aim of present study was to use plant extract as an alternative to phytohormones for regeneration of saffron corms in in-vitro conditions.Methods: Tiny slices or fragments of saffron corms were used as explants and cultured on Murashige and Skoog (MS) media supplemented with plant extract to obtain the callus.Results: Callus initiation was observed in all concentrations of plant extract. However, the callus grown in 20% plant extract resulted in direct organogenesis. But callus growth was slow at 40% concentration of plant extract.Conclusion: Our results showed that plant extract can be used as an efficient alternative source to phyto- hormones.Â

Prevalence and survival in patients with bladder cancer: a study in high cancer incidence zone

Background: Bladder cancer (BC) is the most common malignancy of the urinary tract caused by the uncontrollable division of cells lining the bladder. The clinicopathological characteristics of BC determine largely the prognosis and aid in the treatment and management of disease. Aim: The aim of the study was to analyze the incidence of BC in our region. Materials and methods: The study prospectively screened all the patients who were diagnosed with BC between 2018 and 2020. Detailed history of 235 patients was taken and Kaplan-Meier survival analysis of 137 BC patients was also performed to evaluate any possible association between various clinico-pathological characteristics, with respect to overall survival (OS) and recurrence in terms of disease free survival (DFS). Results: Among BC cases, 78.72% (185) patients were males and 21.27% (50) were females with a male: female ratio of 3.7:1. The frequency of BC was observed to be 36.17% (85) in cases that belonged to the age group of <50 years whereas 63.82% (150) cases belonged to ≥50 years. Of all cases 67.65% (159) patients were active smokers. The pathological characteristics of BC cases included 59.14% (139) cases of low stage (pTa/pT1) versus 40.86% (96) of the high stage (pT2/higher). Moreover, non-smokers, females and patients exhibiting low grade and stage had significant and better OS and DFS than the rest (Log rank P < 0.05). Conclusion: BC remains one of the leading cancers in our region despite absence of many occupational exposures except smoking

Brain Metabolite, Myo-inositol, Inhibits Catalase Activity: A Mechanism of the Distortion of the Antioxidant Defense System in Alzheimer’s Disease

A strong correlation between brain metabolite accumulation and oxidative stress has been observed in Alzheimer’s disease (AD) patients. There are two central hypotheses for this correlation: (i) coaccumulation of toxic amyloid-β and Myo-inositol (MI), a significant brain metabolite, during presymptomatic stages of AD, and (ii) enhanced expression of MI transporter in brain cells during oxidative stress-induced volume changes in the brain. Identifying specific interactive effects of MI with cellular antioxidant enzymes would represent an essential step in understanding the oxidative stress-induced AD pathogenicity. This study demonstrated that MI inhibits catalase, an essential antioxidant enzyme primarily inefficient in AD, by decreasing its kcat (turnover number) and increasing Km (Michaelis–Menten constant) values. This inhibition of catalase by MI under in vivo studies increased cellular H2O2 levels, leading to decreased cell viability. Furthermore, MI induces distortion of the active heme center with an overall loss of structure and stability of catalase. MI also alters distances of the vital active site and substrate channel residues of catalase. The present study provides evidence for the involvement of MI in the inactivation of the antioxidant defense system during oxidative stress-induced pathogenesis of AD. Regulation of MI levels, during early presymptomatic stages of AD, might serve as a potential early-on therapeutic strategy for this disease

Cytokine Gene Polymorphism and Cancer Risk: A Promising Tool for Individual Susceptibility and Prognostic Implications

Cytokines are potent molecules produced mainly by specific activated immune cells to control inflammatory responses besides other biologic processes. Although active participation of cytokines provides defense against carcinogenesis on the other hand, deregulation at the genetic level influences their activity to promote tumor development. Among many aspects, constitutional polymorphic sequence variations are key factors that derange the cytokine expression to lead an individual’s propensity to risk for different cancers. Cytokine polymorphisms are now believed to alter these critical molecules that have a dual face in carcinogenesis as, when implicated in the activation of the immune response, these molecules check the cancer development while their persistent inflammatory reaction can envisage the development of malignancy and tumor growth. We have given ample evidence of case-control studies in a range of cancers where substantial evidence, as reported in this chapter, links polymorphism of cytokine gene susceptibility with numerous cancers. Cytokine gene polymorphism is vital to be significant bimolecular genetic determinants of susceptibility and prognosis of cancer. A strong need is felt for more case-control association studies in cytokine candidate genes involved in specific pathways for particular cancer in bigger powered sample sizes involving additional variables to disclose their factual risk for cancer