Genetic polymorphism of glutathione S-transferases: Relevance to neurological disorders.

Glutathione S-tranferases (GSTs) are phase II drug metabolizing enzymes, they play crucial role in detoxification of environmental pollutants, carcinogens, drugs, xenobiotics and oxidative stress products. Genetic differences in expression and activity of GSTs are due to the existence of polymorphic alleles which encode them. Because of genetic polymorphism the GST activity has altered that lead to the increased susceptibility for toxic chemical compounds. GST genetic polymorphism is the main reason for many neurological dysfunctions. GST has over expressed in epileptic brain and pi (π) GST has used to predict stroke; mu (µ) and pi (π) GST are over expressed in Alzheimer's disease (AD). Null and single nucleotide polymorphism of GST has associated with many neurodisorders. Over all, it can be concluded that the GST genetic polymorphism has associated with neurodegenerative diseases.

Elevated levels of the circulatory ischemia-modified albumin in patients with polycystic ovary syndrome: a meta-analysis.

Oxidative stress (OS) has been reported to be associated with the pathogenesis of polycystic ovary syndrome (PCOS). Ischemia-modified albumin (IMA) levels in the circulation have been recently studied as a novel marker of OS. The studies in the literature on IMA levels in PCOS are inconsistent. This meta-analysis was conducted to compare circulatory IMA levels between PCOS patients and non-PCOS controls. Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. The funnel plot analysis with Begg's and Egger's tests was used for publication bias. A total of nine studies were included in this meta-analysis. The results indicated that the serum IMA levels were significantly elevated in PCOS patients as compared to non-PCOS controls (SMD = 0.49, 95% CI = 0.23-0.75, Z = 3.75, p = .0002). A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the good validity and stability of these meta-analytic results. There was no evidence of publication bias as evidenced by the Egger (p = .28) and Begg's tests (p = .21). The present meta-analysis suggests that IMA might be considered as a reliable and novel marker reflecting increased OS in PCOS.

Biogenesis of silver nanoparticles using leaf extract of Indigofera hirsuta L. and their potential biomedical applications (3-in-1 system).

The present study reports the biosynthesis of silver nanoparticles (IH-AgNPs) using aqueous leaf extract of Indigofera hisruta L. The biosynthesized IH-AgNPs were found to be FCC crystals, 5-10 nm in size, spherical in shape and stable. The biosynthesized IH-AgNPs showed dose-dependant cytotoxicity against prostate cancer (PC3) (IC50 = 68.5 µg/mL), colon cancer (COLO205) (IC50 = 85.2 µg/mL), and mouse melanoma (B16F10) (IC50 = 80.9 µg/mL). IH-AgNPs were found to be nontoxic towards normal CHO (Chinese hamster ovary) cells. The biosynthesized IH-AgNPs showed effective in vitro antioxidant activity against DPPH (IC50 = 63.43 µg/mL) and H2O2 (IC50 = 89.93 µg/mL) radicals. IH-AgNPs exhibited effective antibacterial activity against both Gram+ve and Gram-ve bacteria. MIC values of IH-AgNPs against S. aureus, B. subtilis, P. aeruginosa and E. coli were found to be 7.8 µg/mL, 3.9 µg/mL, 15.6 µg/mL and 15.6 µg/mL respectively. IH-AgNPs also showed inhibitory activity against fungal pathogens including C. albicans, C. nonalbicans and C. tropicalis. Considering the results together, we demonstrate that IH-AgNPs exhibits three different bioactivities (3-in-1 system) and they could be employed as future antimicrobial, antioxidant and anticancer agents/drug delivery vehicles in the field of biomedicine.

A systematic review and meta-analysis of the circulatory, erythrocellular and CSF selenium levels in Alzheimer's disease: A metal meta-analysis (AMMA study-I).

BACKGROUND: Available studies in the literature on the selenium levels in Alzheimer's disease (AD) are inconsistent with some studies reporting its decrease in the circulation, while others reported an increase or no change as compared to controls. AIM: The objective of this study was to perform a meta-analysis of circulatory (plasma/serum and blood), erythrocyte and cerebrospinal fluid (CSF) selenium levels in AD compared controls. We also performed a meta-analysis of the correlation coefficients (r) to demonstrate the associations between selenium and glutathione peroxidase (GPx) in AD patients. METHODS: All major databases were searched for eligible studies. We included 12 case-control/observational studies reporting selenium concentrations in AD and controls. Pooled-overall effect size as standardized mean difference (SMD) and pooled r-values were generated using Review Manager 5.3 and MedCalc 15.8 software. RESULTS: Random-effects meta-analysis indicated a decrease in circulatory (SMD=-0.44), erythrocellular (SMD=-0.52) and CSF (SMD=-0.14) selenium levels in AD patients compared to controls. Stratified meta-analysis demonstrated that the selenium levels were decreased in both the subgroups with (SMD=-0.55) and without (SMD=-0.37) age matching between AD and controls. Our results also demonstrated a direct association between decreased selenium levels and GPx in AD. CONCLUSION: This meta-analysis suggests that circulatory selenium concentration is significantly lower in AD patients compared to controls and this decrease in selenium is directly correlated with an important antioxidant enzyme, the GPx, in AD.

A meta-analysis of the association of serum ischaemia-modified albumin levels with human hypothyroidism and hyperthyroidism.

Serum levels of ischaemia-modified albumin (IMA) have been studied as a novel and simple measure of oxidative stress (OXS) in different thyroid pathologies. However, results of available studies in the literature were not consistent. This meta-analysis was attempted to quantify the overall effect size for serum IMA levels in human hypothyroidism (HT) and hyperthyroidism (HYT) and to study its associations with the thyroid profile. Databases of PubMed/Medline, EMBASE, Google Scholar, Web of Science and Science Direct were searched for articles. Data on serum IMA levels in HT, HYT patients and euthyroid controls were extracted to compute standardized mean differences (SMD) by the random-effects model. The associations between IMA and thyroid profile were computed by the meta-analysis of correlation coefficients. IMA levels in HT patients (SMD=1.12; Z=2.76; P=0.006) and HYT patients (SMD=1.64; Z=2.57; P=0.01) were significantly higher than in euthyroid controls and the thyroid treatment showed a favourble effect on serum IMA levels. There were strong and significant correlations between IMA and hormonal status in HT and HYT groups. This meta-analysis showing increased IMA level in both HT and HYT patients and its association with thyroid profile suggests that serum IMA could be used as a simple measure of increased OXS in thyroid dysfunction.

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs (spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYP-induced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYP-induced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action.

This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs (spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYP-induced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYP-induced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases.