1,476 research outputs found

    Association between GSTM1, GSTT1, and GSTP1 variants and the risk of end stage renal disease

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    Introduction: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD.Materials and methods: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC).Results: We found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of ESRD by 1.8 times (p<0.001) and the increased risk of ESRD for GSTM-null (T1+-M1-) genotype was 3.04 times (p=0.002). ESRD patients carriers the GST (GSTM1-null+GSTT1-null+GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p<0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA.Conclusion: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases

    Generalized Chaplygin gas model: Cosmological consequences and statefinder diagnosis

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    The generalized Chaplygin gas (GCG) model in spatially flat universe is investigated. The cosmological consequences led by GCG model including the evolution of EoS parameter, deceleration parameter and dimensionless Hubble parameter are calculated. We show that the GCG model behaves as a general quintessence model. The GCG model can also represent the pressureless CDM model at the early time and cosmological constant model at the late time. The dependency of transition from decelerated expansion to accelerated expansion on the parameters of model is investigated. The statefinder parameters rr and ss in this model are derived and the evolutionary trajectories in srs-r plane are plotted. Finally, based on current observational data, we plot the evolutionary trajectories in srs-r and qrq-r planes for best fit values of the parameters of GCG model. It has been shown that although, there are similarities between GCG model and other forms of chaplygin gas in statefinder plane, but the distance of this model from the Λ\LambdaCDM fixed point in srs-r diagram is shorter compare with standard chaplygin gas model.Comment: 10 pages, 5 figures, accepted in Astrophys Space Sci. (2011

    MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

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    Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

    Nucleocytoplasmic transport: a thermodynamic mechanism

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    The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include
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