11,534 research outputs found

    Microparticles-Mediated Vascular Inflammation and its Amelioration by Antioxidant Activity of Baicalin.

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    Microparticles (MPs) are extracellular vesicles (0.1-1.0 μm in size), released in response to cell activation or apoptosis. Endothelial microparticles (EC-MP), vascular smooth muscle cell microparticles (VSMC-MP), and macrophage microparticles (MØ-MP) are key hallmarks of atherosclerosis progression. In our current study, we investigated the potent antioxidant activity of baicalin to ameliorate MP-induced vascular smooth muscle cell (VSMC) dysfunction and endothelial cell (EC) dysfunction, as well as the production of inflammatory mediators in macrophage (RAW264.7). In our study, baicalin suppressed the apoptosis, reactive oxygen species (ROS) generation, NO production, foam cell formation, protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in MØ-MP-induced RAW264.7. In addition, VSMC migration induced by VSMC-MP was dose-dependently inhibited by baicalin. Likewise, baicalin inhibits metalloproteinase-9 expression and suppresses VSMC-MP-induced VSMC proliferation by down-regulation of mitogen-activated protein kinase and proliferating cell nuclear antigen protein expressions. Baicalin also inhibited ROS production and apoptosis in VSMC. In EC, the marker of endothelial dysfunction (endothelial senescence, upregulation of ICAM, and ROS production) induced by EC-MP was halted by baicalin. Our results suggested that baicalin exerts potent biological activity to restore the function of EC and VSMC altered by their corresponding microparticles and inhibits the release of inflammation markers from activated macrophages

    Electrochemical Investigation of Exchange Current Density of Uranium and Rare-earths Couples (M3+/M0) in LiCl-KCl Eutectic Electrolyte

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    The objective of this work is to use electrochemical techniques to quantify the electrode reaction rate of some rare-earth elements and uranium in a LiCl-KCl eutectic electrolyte at 500oC. The exchange current densities of the oxidation-reduction couples of M3+/M0 (La3+/La0, Ce3+/Ce0, Pr3+/Pr0, Nd3+/Nd0,Gd3+/Gd0, Y3+/Y0, U3+/U0) on a tungsten electrode were measured by applying a linear polarization resistance technique. A region of linear dependence of potential on applied current could be found to describe the reaction rate of oxidation-reduction system. From these measurements, the estimated exchange current density was 0.38 mA/cm2 for uranium, and was within the range of 0.27 to 0.38mA/cm2 for rare-earth elements.open0

    Role of sea ice on satellite-observed chlorophyll-a concentration variations during spring bloom in the East/Japan sea

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    The relationship between the spring bloom along the Primorye coast and the sea ice of the Tatarskiy Strait in the northern region of the East/Japan Sea, a semi-enclosed marginal sea in the North Pacific, was investigated using the ten-year SeaWiFS chlorophyll-a concentration data and DMSP/SSMI sea ice concentration data from 1998 to 2007. Year-to-year variations in the chlorophyll-a concentrations in the spring were positively correlated with those of the sea ice concentrations in the Tatarskiy Strait in the previous winter with a correlation coefficient of 0.77. Abrupt increases in nutrients, essential for the spring bloom in the upper ocean during spring, were supplied from sea ice-melted waters. Time series of vertical distributions of the nutrients indicated that phosphate concentrations were extremely elevated in the upper ocean (less than 100 m) without any connection to high concentrations in the deep waters below. The water mass from sea ice provided preferable conditions for the spring bloom through changes in the vertical stratification structure of the water columns. Along-coast ratios of stability parameters between two neighboring months clearly showed the rapid progression of the generation of a shallow pycnocline due to fresh water originating from sea ice. This study addressed the importance of the physical environment for biogeochemical processes in semi-enclosed marginal seas affected by local sea ice. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.1166Ysciescopu

    Maximizing total job value on a single machine with job selection

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    This paper describes a single machine scheduling problem of maximizing total job value with a machine availability constraint. The value of each job decreases over time in a stepwise fashion. Several solution properties of the problem are developed. Based on the properties, a branch-and-bound algorithm and a heuristic algorithm are derived. These algorithms are evaluated in the computational study and the results show that the heuristic algorithm provides effective solutions within short computation times

    Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats

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    © 2016 Hyun-Ho Lee et al. Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: 100, 400, and 800 mg·kg-1·day-1 (CJF 100, 400, and 800, resp.). Our results showed that CJF possessed strong cholesterol-lowering potency as indicated by the decrease in serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), accompanied by an increase in serum high-density lipoprotein (HDL). Furthermore, CJF reduced serum lipid peroxidation by suppressing the formation of thiobarbituric acid reactive substance. In addition, oil red O (ORO) staining of rat arteries showed decreased lipid-positive staining in the CJF-treated groups compared to the control HFD group. Taken together, these results suggest that CJF could be a potent herbal therapeutic option and source of a functional food for the prevention and treatment of atherosclerosis and other diseases associated with hypercholesterolemia

    Prediction of Inflammatory Breast Cancer Survival Outcomes Using Computed Tomography-Based Texture Analysis

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    Background: Although inflammatory breast cancer (IBC) has poor overall survival (OS), there is little information about using imaging features for predicting the prognosis. Computed tomography (CT)-based texture analysis, a non-invasive technique to quantify tumor heterogeneity, could be a potentially useful imaging biomarker. The aim of the article was to investigate the usefulness of chest CT-based texture analysis to predict OS in IBC patients. Methods: Of the 3,130 patients with primary breast cancers between 2006 and 2016, 104 patients (3.3%) with IBC were identified. Among them, 98 patients who underwent pre-treatment contrast-enhanced chest CT scans, got treatment in our institution, and had a follow-up period of more than 2 years were finally included for CT-based texture analysis. Texture analysis was performed on CT images of 98 patients, using commercially available software by two breast radiologists. Histogram-based textural features, such as quantification of variation in CT attenuation (mean, standard deviation, mean of positive pixels [MPP], entropy, skewness, and kurtosis), were recorded. To dichotomize textural features for survival analysis, receiver operating characteristic curve analysis was used to determine cutoff points. Clinicopathologic variables, such as age, node stage, metastasis stage at the time of diagnosis, hormonal receptor positivity, human epidermal growth factor receptor 2 positivity, and molecular subtype, were assessed. A Cox proportional hazards model was used to determine the association of textural features and clinicopathologic variables with OS. Results: During a mean follow-up period of 47.9 months, 41 of 98 patients (41.8%) died, with a median OS of 20.0 months. The textural features of lower mean attenuation, standard deviation, MPP, and entropy on CT images were significantly associated with worse OS, as was the M1 stage among clinicopathologic variables (all P-values < 0.05). In multivariate analysis, lower mean attenuation (hazard ratio [HR], 3.26; P = 0.003), lower MPP (HR, 3.03; P = 0.002), and lower entropy (HR, 2.70; P = 0.009) on chest CT images were significant factors independent from the M1 stage for predicting worse OS. Conclusions: Lower mean attenuation, MPP, and entropy on chest CT images predicted worse OS in patients with IBC, suggesting that CT-based texture analysis provides additional predictors for OS

    Cytosolic targeting factor AKR2A captures chloroplast outer membrane-localized client proteins at the ribosome during translation

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    In eukaryotic cells, organellar proteome biogenesis is pivotal for cellular function. Chloroplasts contain a complex proteome, the biogenesis of which includes post-translational import of nuclear-encoded proteins. However, the mechanisms determining when and how nascent chloroplast-targeted proteins are sorted in the cytosol are unknown. Here, we establish the timing and mode of interaction between ankyrin repeat-containing protein 2 (AKR2A), the cytosolic targeting factor of chloroplast outer membrane (COM) proteins, and its interacting partners during translation at the single-molecule level. The targeting signal of a nascent AKR2A client protein residing in the ribosomal exit tunnel induces AKR2A binding to ribosomal RPL23A. Subsequently, RPL23A-bound AKR2A binds to the targeting signal when it becomes exposed from ribosomes. Failure of AKR2A binding to RPL23A in planta severely disrupts protein targeting to the COM; thus, AKR2A-mediated targeting of COM proteins is coupled to their translation, which in turn is crucial for biogenesis of the entire chloroplast proteome.open1178Ysciescopu

    Generating mice with targeted mutations.

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    Journal ArticleMutational analysis is one of the most informative approaches available for the study of complex biological processes. It has been particularly successful in the analysis of the biology of bacteria, yeast, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Extension of this approach to the mouse, through informative, was far less successful relative to what has been achieved with these simpler model organisms. This is because it is not numerically practical in mice to use random mutagenesis to isolate mutations that affect a specified biological process of interest. Nonetheless, biological phenomena such as a sophisticated immune response, cancer, vascular disease or higher-order cognitive function, to mention just a few, must analyzed in organisms that show such phenomena, and for this reason geneticists and other researchers have turned to the mouse. Gene targeting, the means for creating mice with designed mutations in almost any gene, was developed as an alternative to the impractical use of random mutgenesis for pursing genetic analysis in the mouse. Now gene targeting has advanced the genomic manipulations possible in mice to a level that can be matched only in far simple organisms such as bacteria and yeast

    Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines

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    BACKGROUND: MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation. METHODS: Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed. RESULTS: Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells. CONCLUSION: Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease
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