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Purpose: Lymphotoxin alpha (LTA), a proinflammatory cytokine, plays an important role in promoting atherosclerosis which is an independent risk factor for stroke. Recent genetic studies have suggested that polymorphisms in the LTA gene, which affect its expression and biological function, may contribute to the development of stroke. The aim of this case-control study was to determine the association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke.Methods: Genotyping was determined by using SNaPshot method for 250 ischemic stroke (IS) patients, 250 age and sex matched IS free controls, 100 intracerebral hemorrhage (ICH) patients and 100 age and sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. The linkage disequilibrium (LD) was analyzed by using HaploView 4.2 software.Results: The distribution of LTA (-252 A/G and -804 C/A) genotypes was consistent with Hardy–Weinberg equilibrium. Adjusted conditional logistic regression analysis showed no significant association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of both IS and ICH. Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, a significant association between LTA -252 A/G gene polymorphism and small vessel disease subtype of IS under dominant model (OR, 2.06; 95% CI, 1.03–4.12;pvalue 0.04) with the risk of IS was observed. No LD was observed for both single nucleotide polymorphisms (SNPs) in north Indian population.Conclusion: Neither -252 G/A nor -804 C/A polymorphism of the LTA gene was found to be associated with overall stroke as well as any subtype of IS excluding SVD in North Indian population. [ABSTRACT FROM PUBLISHER]

Introduction: Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS. Methods: A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs) with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests. Results: A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC+CT vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99), recessive (CC vs. CT+TT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87), and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86). Conclusion: This meta-analysis showed that TGF-β1-509C/T gene polymorphism has no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β1 (TGF-β1) is a multifunctional pro-inflammatory cytokine involved in inflammation and pathogenesis of cerebrovascular disease. As per our knowledge, there is no published study investigating the association between variations within the TGF-β1 gene polymorphisms and risk of intracerebral hemorrhage (ICH). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A and T869C) polymorphisms, and their haplotypes with the risk of ICH in North Indian population. 100 ICH patients and 100 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of ICH. Hypertension, diabetes, dyslipidemia, low socioeconomic status, smoking, physical activity were found to be associated with the risk of ICH. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium (HWE) in the ICH and control group. Adjusted conditional logistic regression analysis showed an independent association of TGF-β1 G800A (OR 9.07; 95% CI 2.3-35.6; P = 0.002) and T869C (OR 5.1; 95 % CI 1.9-13.2; P = 0.001) with the risk of ICH under dominant model. Haplotype analysis showed that C509-G800-C869 and C509-A800-C869 haplotypes were significantly associated with the increased risk of ICH. C509T and T869C were in strong linkage disequilibrium (D' = 0.53, r(2) = 0.23). Our results suggest that TGF-β1 (G800A, T869C) gene polymorphisms and their haplotypes are significantly associated with the risk of ICH in North Indian population. Further prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing ICH. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors may play a role in the susceptibility of intracerebral hemorrhage (ICH). The present case-control study hypothesized that genetic polymorphisms in tumor necrosis factor- α (TNF-α) gene may affect the risk of ICH.Materials and Methods: In this study, we investigated the association of four single nucleotide polymorphisms (-308G/A, +488G/A, -857C/T, and -1031T/C) within TNF-α gene promoter and their haplotypes with the risk of ICH in a North Indian population. Genotyping was determined by using the SNaPshot method for 100 ICH patients and 100 age and sex-matched ICH-free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between TNF-α gene polymorphisms and risk of ICH. Haplotypes were reconstructed using PHASE 2.0, and patterns of linkage disequilibrium (LD) analysis were performed using Haploview version 4.2 software.Results: TNF-α +488G/A gene polymorphism was found to be independently associated with the risk of ICH under dominant [GG + GA vs. AA] (OR = 3.1; 95% CI = 1.2-8.2; P = 0.001) and allelic [G vs. A] (OR = 2.2; 95% CI = 1.2-4.2; P = 0.007) models. However, no significant association between -308G/A, -857C/T, and -1031T/C gene polymorphisms and risk of ICH was observed. Haplotype analysis showed that 308A-488G-857C-1031T and 308G-488A-857T-1031T haplotypes were significantly associated with an increased risk of ICH. Strong LD was observed for + 488G/A and -857C/T TNF-α polymorphisms (D' = 0.72, r2= 0.01).Conclusion: Our findings suggest that the TNF-α +488G/A polymorphism may be an important risk factor for ICH, whereas -308G/A, -857C/T, and -1031T/C gene polymorphisms may not be associated with risk of ICH in North Indian population. [ABSTRACT FROM AUTHOR]

Background: The lack of vaccines and limitations of currently available strategies demand a need to develop safe and efficacious immunomodulators. Phyllostachys bambusoides is traditionally used for various autoimmune and infectious disorders, a property possibly attributable to presence of flavonoids like orientin and iso-orientin. Objective: the objective of this study was, to search a potent immunomodulator which elicit both Th1 and Th2 immune response. Methods: The animals were (Balb/c) treated with the bioactive fraction (PBC) from P. bambusoides (100 and 200 mg/kg body weight) for 14 days with SRBC (Sheep Red Blood Cells) as an antigen. Haemagglutination antibody (HA) titre, delayed type hypersensitivity (DTH) reaction, phagocytic index, NO production, analysis of cytokines in serum and CD80/ CD86 population in spleen. Results: PBC significantly enhanced the expression of IgM and IgG titre and DTH response in a dose dependant manner after 24 and 48 h in BALB/c mice with a maximum response at 200 mg/Kg. Besides humoral and cell mediated immunity, it also enhanced phagocytic index, nitric oxide production, which further leads to protection against Candida albicans infection. It also, enhanced the expression of CD80 and CD86 in splenic cells. Conclusion: Taken together these in vitro and in vivo data, our results suggest that PBC acts as an effective immunostimulator which specially enhances macrophage function during infection. This further supports the role of PBC in immunopharmacologic applications. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. Methods: A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. Results: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2–3.8; P = 0.006), G800A (OR, 4.4; 95% CI; 2.1–9.3; P < 0.001) and T869C (OR, 2.6; 95% CI; 1.5–4.5; P = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D’ =0.51, r2 = 0.23). Conclusion: Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population. [ABSTRACT FROM AUTHOR]

Background: Interleukin-6 (IL-6), as one of the most typical pro-inflammatory and immunoregulatory cytokines, is believed to be associated with the genesis and maintenance of inflammatory response. Genetic association studies (GAS) that have investigated the association between Interleukin 6 (G174C and G572C) promoter gene polymorphisms and susceptibility to ischemic stroke (IS) which have produced contradictory and unconvincing results. Purpose: The aim of this meta-analysis is to provide a relatively comprehensive account of the association of IL-6 (G174C and G572C) polymorphisms with susceptibility to IS. Methods: A literature search was conducted using electronic database PubMed, Medline, and Trip database for all case-control studies investigating for association of IL-6 genetic polymorphisms with ischemic stroke published till August 30, 2014. The following combinations of main keywords were used: ('Interleukin- 6' or 'IL-6') and ('ischaemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for IL-6 gene-disease association. Meta-analysis was carried out using Revman 5.3 software. Results: 16 case-control studies involving a total of 3,317 IS patients and 3,432 healthy controls for G174C polymorphism and 3 case-control studies with a total of 2,001 IS patients and 2,027 healthy controls for G572C IL-6 gene polymorphisms were included in a meta-analysis. For IL-6 G174C gene polymorphisms, no significant association was observed under dominant [GC + CC vs. GG: OR = 1.01, 95% CI: 0.77-1.34, P = 0. 92], recessive [CC vs. GG + GC: OR = 0.82, 95% CI: 0.40-1.70, P = 0. 59] and allelic model [C vs. G Allele: OR = 0.99, 95% CI: 0.74-1.31, P = 0. 93]. For IL-6 G572C, no significant association was observed under dominant [CC vs. GG + GC: OR = 0.99, 95% CI: 0.57-1.71, P = 0. 97], recessive [CC vs. GG + GC: OR = 0.93, 95% CI: 0.60-1.45, P = 0. 75] and allelic model [C vs. G Allele: OR = 0.95, 95% CI: 0.66-1.36, P = 0. 76]. Conclusion: This meta-analysis shows that IL-6 (G174C) and IL-6 (G572C) gene polymorphisms may not be associated with an increased susceptibility to IS. Further studies are required for confirmatory results. [ABSTRACT FROM AUTHOR]

Melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24), a secreted protein of the IL-10 family, was first identified more than two decades ago as a novel gene differentially expressed in terminally differentiating human metastatic melanoma cells. MDA-7/IL-24 functions as a potent tumor suppressor exerting a diverse array of functions including the inhibition of tumor growth, invasion, angiogenesis, and metastasis, and induction of potent "bystander" antitumor activity and synergy with conventional cancer therapeutics. MDA-7/IL-24 induces cancer-specific cell death through apoptosis or toxic autophagy, which was initially established in vitro and in preclinical animal models in vivo and later in a Phase I clinical trial in patients with advanced cancers. This review summarizes the history and our current understanding of the molecular/biological mechanisms of MDA-7/IL-24 action rendering it a potent cancer suppressor. [ABSTRACT FROM AUTHOR]