Mangiferin: A xanthone attenuates mercury chloride induced cytotoxicity and genotoxicity in HepG2 cells

Mangiferin (MGN), a dietary C-glucosylxanthone present in Mangifera indica, is known to possess a spectrum of beneficial pharmacological properties. This study demonstrates antigenotoxic potential of MGN against mercuric chloride (HgCl2)-induced genotoxicity in HepG2 cell line. Treatment of HepG2 cells with various concentrations of HgCl2 for 3 h caused a dose-dependent increase in micronuclei frequency and elevation in DNA strand breaks (olive tail moment and tail DNA). Pretreatment with MGN significantly (p < 0.01) inhibited HgCl2 -induced (20 μM for 30 h) DNA damage. An optimal antigenotoxic effect of MGN, both in micronuclei and comet assay, was observed at a concentration of 50 μM. Furthermore, HepG2 cells treated with various concentrations of HgCl2 resulted in a dose-dependent increase in the dichlorofluorescein fluorescence, indicating an increase in the generation of reactive oxygen species (ROS). However, MGN by itself failed to generate ROS at a concentration of 50 μM, whereas it could significantly decrease HgCl2 -induced ROS. Our study clearly demonstrates that MGN pretreatment reduced the HgCl2-induced DNA damage in HepG2 cells, thus demonstrating the genoprotective potential of MGN, which is mediated mainly by the inhibition of oxidative stress.     

Specific elimination of effector memory CD4+ T cells due to enhanced Fas signaling complex formation and association with lipid raft microdomains

Elimination of autoreactive CD4⁺ T cells through the death receptor Fas/CD95 is an important mechanism of immunological self-tolerance. Fas deficiency results in systemic autoimmunity, yet does not affect the kinetics of T-cell responses to acute antigen exposure or infection. Here we show that Fas and TCR-induced apoptosis are largely restricted to CD4⁺ T cells with an effector memory phenotype (effector memory T cells (T_EM)), whereas central memory and activated naïve CD4⁺ T cells are relatively resistant to both. Sensitivity of T_EM to Fas-induced apoptosis depends on enrichment of Fas in lipid raft microdomains, and is linked to more efficient formation of the Fas death-inducing signaling complex. These results explain how Fas can cull T cells reactive against self-antigens without affecting acute immune responses. This work also identifies Fas-induced apoptosis as a possible immunotherapeutic strategy to eliminate T_EM linked to the pathogenesis of a number of autoimmune diseases.     

Decolorization of Synthetic Dyes by Aspergillus flavus

A problem of paramount importance that has attracted the attention of environmental biologists is the discharge of highly colored effluents into the environment by various industries, which use a wide range of synthetic dyes. The existing chemical methods for dye degradation are not only expensive but also contributes to secondary pollution due to high dose of the chemicals used. Hence an alternative is to exploit the potential of microorganisms to alleviate this problem. The current paper deals with the isolation, characterization, and sugar utilization for better growth of Aspergillus flavus, a marine fungus from the Bay of Bengal. The goal is to assess the bioremediation potential of a variety of synthetic, paper mill, and color photography dyes. A correlation between the amount of sugar used, biomass, and quality of protein produced was observed. This fungus is capable of reducing between 80% and 90% of synthetic dyes and 100% color photography effluents within 3 to 7 days, and 8 days, respectively. Significant effect of carbon sources was observed in the decolorization of the synthetic dye crystal violet, up to 90% in 3 to 7 days, by Aspergillus flavus. The organism showed better growth with fructose as the sole carbon source for the least sugar consumption. Therefore, this fungus can be used as an economical and eco-friendly tool to minimize the pollution by industries to a significant extent.     

Regulation between survival, persistence, and elimination of intracellular mycobacteria: a nested equilibrium of delicate balances

This review elaborates on recent insights gained on the dynamic aspects of interactions between pathogen and the host intracellular machinery in tuberculosis infection. In addition we will also discuss the utility of adopting a systems biology approach, both for a better understanding of TB biology, and for the development of more effective ways for disease management.     

Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via,mitochondrial mediated caspase-dependent mechanism

Okadaic acid (OA) is a specific and potent protein phosphatase inhibitor and tumor promoter. The present study establishes the role of reactive oxygen species (ROS) and mitogen activated protein kinases in cell death induced by okadaic acid. The study showed that okadaic acid is cytotoxic at 10 nM with an IC50 of 100 nM in U-937 cells. The CVDE assay and mitochondrial dehydrogenase assay showed a time dependent cytotoxicity. The phase contrast visualization of the OA treated cells showed the apoptotic morphology and was confirmed with esterase staining for plasma membrane integrity. OA activated caspases-7, 9 and 3, PARP cleavage and induced nuclear damage in a time and dose dependent manner. Compromised mitochondrial membrane potential, release of cytochrome-c and apoptosis inducing factor confirms the involvement of mitochondria. A time dependent decrease in glutathione levels and a dose dependent increase in ROS with maximum at 30 min were observed. ROS scavenger-N-acetyl cysteine, mitochondrial stabilizer-cyclosporin-A, and broad spectrum caspase inhibitor Z-VAD-FMK inhibited the OA induced caspase-3 activation, DNA damage and cell death but caspase-8 inhibitor had no effect. OA activated p38 MAPK and JNK in a time dependent manner, but not ERK½. MAP kinase inhibitors SB203580, SP600125 and PD98059 confirm the role of p38 MAPK and JNK in OA induced caspase-3 activation and cell death. Over all, our results indicate that OA induces cell death by generation of ROS, and activation of p38 MAPK and JNK, and executed through mitochondrial mediated caspase pathway.     

datPAV--an online processing, analysis and visualization tool for exploratory investigation of experimental data

SUMMARY: Data processing, analysis and visualization (datPAV) is an exploratory tool that allows experimentalist to quickly assess the general characteristics of the data. This platform-independent software is designed as a generic tool to process and visualize data matrices. This tool explores organization of the data, detect errors and support basic statistical analyses. Processed data can be reused whereby different step-by-step data processing/analysis workflows can be created to carry out detailed investigation. The visualization option provides publication-ready graphics. Applications of this tool are demonstrated at the web site for three cases of metabolomics, environmental and hydrodynamic data analysis. AVAILABILITY: datPAV is available free for academic use at http://www.sdwa.nus.edu.sg/datPAV/.     

p53基因多态性和脑外伤预后及临床意义

目的：研究颅脑外伤患者中P53等位基因与基因型的频率分布,探讨其与脑损伤预后的关联性,为脑损伤患者预后提供部分参数依据。方法：选择各型颅脑损伤患者141例,正常对照者144人,患者按GCS格拉斯哥评分法进行分类;采用PCR基因型检测法检测P53等位基因,基因计数法计算等位基因频率;统计学分析等位基因和基因型在脑外伤组与正常对照组、预后良好组与预后不良组的频率分布的差异,并综合分析患者年龄、性别、GCS以及P53各等位基因等因素对脑外伤患者预后的影响。结果：在颅脑外伤患者和正常对照者中P53等位基因和基因型的频率分布,差异均无统计学意义（P〉0.05）;等位基因Arg相对于Pro的OR为1.140,基因型Arg/Pro、Arg/Arg相对于Pro/Pro的OR分别为0.890和1.170。在重型脑外伤患者（3≤GCS≤8分）86例中,预后良好31例,预后不良55例,基因型对预后不良的影响：非Pro/Pro相对于Pro/Pro的OR为0.417,非Arg/Pro相对于Arg/Pro的OR为0.419,非Arg/Arg相对于Arg/Arg的OR为3.667。在所有脑外伤患者中,预后良好组和预后不良组的患者年龄、性别差异均无统计学意义（P〉0.05）;GCS、P53等位基因差异具有显著统计学意义（P〈0.01）。结论：在重型颅脑患者中,基因型Arg/Arg有增加预后不良的风险;脑外伤预后与患者的年龄、性别无关联,与GCS、P53基因密切相关。