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Monoatomic Platinum-Embedded Heptagonal Close-Packed Impeccable Anisotropic Superstructures as Remarkably Efficient Hydrogen Advancement Catalyst.
Using the same start structures and same computational demand regular MD simulations sampled near native complex structures only for one case. The method showed also improved results for the refinement of docked structures in the vicinity of the native binding geometry compared to regular MD refinement. © 2020 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.Exendin-4, a glucagon-like peptide-1 receptor agonist, was shown to prtect against cardiac ischemia/reperfusion (I/R) injury by suppressing oxidative stress. p66 Shc, a pro-oxidant and aapoptotic protein, is activated in the infarcted left ventricles (LVs) after induction of I/R. This study investigated if the cardiac protective effect of Exendin-4 against I/R injury in rats involves inhibition of p66 Shc and to determine the underlying mechanisms behind this. Adult male rats (n=12/group) were divided into 4 groups as a sham, a sham + Exendin-4, an I/R, and an I/R + Exendin-4. Exendin-4 was administered to rats 7 days before the induction of I//R. Ischemia was induced by ligating the left anterior descending coronary (LAD) for 40 minutes followed by reperfusion for 10 min. The infarct myocardium was used for further analysis. Exendin-4 significantly reduced infarct area (by 62%), preserved LV function and lowered serum levels of LDH and CK-MB in I/R-induced rats. Also, it significantly reduced LV levels of ROS and MDA and protein levels of cytochrome-c and cleaved caspase-3 but significantly increased levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD) in LVs of I/R rats indicating antioxidant and anti-apoptotic effects. Furthermore, it inhibited JNK and p66 Shc activation and downregulated protein levels of p66 Shc and NADPH oxidase with no effect on protein levels /activity of p53 and PKCβII. Of note, Exendin-4 also increased GSH and MnSOD in LVs of control rats. In conclusion, Exendin-4 cardioprotective effect in I/R hearts is mediated mainly by antioxidant effect and inhibition of JNK/P66 Shc/NADPH oxidase. GNE 390 This article is protected by copyright. All rights reserved.We previously published about cross reactive soya allergy in patients with peanut and other nut allergy1 . In the UK around 1 in 20 patients who are allergic to peanut are also soya allergic. An unknown number of patients with other nut allergies are also allergic to soya. Both isotretinoin and alitretinoin contain soya oil. This article is protected by copyright. All rights reserved.A series of cationic gold(I)-carbene complexes with various 4,5-diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. major amastigotes and T. gondii and distinct selectivity for T. gondii cells when compared with the activity against nonmalignant Vero cells. The ferrocene derivatives 1a-c are generally more active against the L. major amastigotes and the T. gondii tachyzoites than the other tested anisyl gold complexes and the approved drugs atovaquone and amphotericin B. Compounds 1a and 1e showed the highest selectivities for L. major amastigotes. Compounds 1d and 1f showed the highest selectivities for L. major promastigotes; 1f was the most active compound against L. major promastigotes of this series of compounds. The 3,4,5-trimethoxyphenyl analog 1b also exhibited a much greater selectivity for T. b. brucei cells when compared with its activity against human HeLa cells. © 2020 The Authors. Archiv der Pharmazie published by Wiley-VCH Verlag GmbH & Co. KGaA on behalf of Deutsche Pharmazeutische Gesellschaft.Mitochondria house anabolic and catabolic processes that must be balanced and adjusted to meet cellular demands. The RNA-binding protein CLUH (clustered mitochondria homolog) binds mRNAs of nuclear-encoded mitochondrial proteins and is highly expressed in the liver, where it regulates metabolic plasticity. Here, we show that in primary hepatocytes, CLUH coalesces in specific ribonucleoprotein particles that define the translational fate of target mRNAs, such as Pcx, Hadha, and Hmgcs2, to match nutrient availability. Moreover, CLUH granules play signaling roles, by recruiting mTOR kinase and the RNA-binding proteins G3BP1 and G3BP2. Upon starvation, CLUH regulates translation of Hmgcs2, involved in ketogenesis, inhibits mTORC1 activation and mitochondrial anabolic pathways, and promotes mitochondrial turnover, thus allowing efficient reprograming of metabolic function. In the absence of CLUH, a mitophagy block causes mitochondrial clustering that is rescued by rapamycin treatment or depletion of G3BP1 and G3BP2. Our data demonstrate that metabolic adaptation of liver mitochondria to nutrient availability depends on a compartmentalized CLUH-dependent post-transcriptional mechanism that controls both mTORC1 and G3BP signaling and ensures survival. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.Previous investigations showed inconsistent results for comparison in renal recovery, in-hospital, and in-intensive care unit (ICU) mortalities between acute kidney injury (AKI) patients treated with continuous renal replacement therapy (CRRT) and some kinds of intermittent renal replacement therapies (IRRTs). We systematically searched for articles published in the databases (PubMed, Web of Science, EMBASE, Medline, and Google Scholar) until June 2019. We made all statistical analysis using STATA 12.0 software. In the present meta-analysis, relative risks with 95% confidence intervals were calculated for binary outcomes (renal recovery status or mortality). The present study indicated no significant differences in renal recovery, in-hospital mortality, and in-ICU mortality between AKI patients given CRRT and those given sustained low-efficiency dialysis (SLED). Additionally, the study showed no significant difference in in-hospital mortality between AKI patients given CRRT and those given intermittent hemodialysis (IHD), whereas elevated in-ICU mortality was detected in AKI patients given CRRT, compared to those given IHD. The three modalities (CRRT, IHD, and SLED) have their own advantages and disadvantages. More rigorous trials design with large cohort should be made to explore the differences in renal recovery, in-hospital, and in-ICU mortalities between different kinds of RRTs. © 2020 Wiley Periodicals, Inc.
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