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Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
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Animals , Alzheimer Disease/metabolism , Amyloid beta-Peptides , Amyloid beta-Protein Precursor/metabolism , Drosophila/physiology , Drosophila Proteins/metabolism , Resveratrol/pharmacology , Sirtuin 1 , SleepABSTRACT
Objective To evaluate the effect of different anticoagulant therapy regimens in patients with atrial fibrillation and stable coronary artery disease.Methods This was a retrospective cohort study.Patients with coronary artery disease and atrial fibrillation undergoing percutaneous coronary intervention(PCI) in our hospital from January 2014 to January 2017 were involved.Based on the anticoagulant regimen,all patients were divided into two groups.:dual antiplatelet anticoagulant group(treated with aspirin and clopidogrel,as DT group),warfarin and one antiplatelet drug group (treated with warfarin and aspirin,or warfarin and clopidogrel,as WS group).We compared the safety (risk of bleeding)and efficacy(major adverse cardiac and cerebrovascular event)between groups after 12-month follow-up.Results 329 patients were included,with 173 males and mean age of(70.1± 9.3)years.There were 82 patients in the DT group,and 247 patients in the WS group.Patients in the WS group were older,and with significantly higher rates of diabetes,higher levels of creatine kinase-MB(CK-MB)and thrombosis risk compared with WS group(all P<0.05),though the anticoagulant duration,bleeding risk,data about coronary artery and peak value of CK-MB 24 h post-PCI were similar between groups.After(11.7 ± 1.5) months follow-up,the rates of bleeding was comparable between the two groups (P > 0.05).The rates of major adverse cardiacand cerebrovascular events (MACCE)were similar between groups(P >0.05),though there was a trend of increased risk of ischemic stroke in the DT group.Conclusions For patients with coronary artery disease and atrial fibrillation undergoing PCI,dual antiplatelet therapy is a safe and effective anticoagulant regimen.However,there is a trend of increased rate of ischemic stroke,which is needed to explore.
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Objective To evaluate the clinical curative effect and safety of Shenqifuzheng injection in the treatment of elderly patients with chronic heart failure.Methods 58 cases of elderly patients with chronic heart failure were selected from September 2014 to September 2015 in our hospital and randomly divided into the control group and treatment group,29 cases in each group.The control group was given conventional therapy,on the basis of the control group,the experimental group was treated with Shenqifuzheng injection,250mL,one time a day,intravenous drip;Before and after treatment,compared between the two groups of patients with serum tumor necrosis factorα(TNF-α),interleukin 1β levels,efficiency of treatment and safety.Results After treatment,compared with the control group,the serum levels of TNF-α and IL-1β were lower in the experimental group(P<0.05); the treatment efficiency of the experimental group(93.11%)was significantly higher than that of the control group(65.52%,P<0.05).Conclusion The Shenqifuzheng injection can significantly reduce the serum levels of TNF-α and IL-1βin elderly patients with chronic heart failure,reduce inflammatory reaction,improve clinical efficacy,and safety was high.
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BACKGROUND:Titanium ions have been proved to stimulate the secretion of bone remodeling-related factors from T lymphocytes;however, the effects of titanium ions on the early activation, intermediate activation, and cel cycle of T lymphocytes remain unclear. OBJECTIVE:To investigate the effects of titanium ions on the proliferation and activation of T lymphocytes in vitro. METHODS:Cel proliferation and cycle test:Jurkat E6-1 T lymphocytes in logarithmic phase were col ected and cultured in the medium containing 0 (control), 25 (low concentration), 50 (middle concentration), and 100μmol/L (high concentration) titanium ions for 24 hours to detect the cel relative proliferation rate and cel cycle. Cel activation trial:Jurkat E6-1 T lymphocytes were divided into two groups that were subdivided into four groups containing 0, 25, 50, and 100μmol/L titanium ions, respectively with or without phytohemagglutinin (PHA) pre-stimulation. The expressions of CD69 and CD25 were measured after cultured for 24 hours. RESULTS AND CONCLUSION:Titanium ions enhanced T lymphocytes proliferation in a concentration-dependent manner (P<0.05). Compared with the control group, the percentages of G0/G1 phase decreased and the proportions of cel s in S and G2/M phase increased significantly in the low, middle and high concentration groups (P<0.05). The proportion of G0/G1-phase cel s in the high concentration group was less and the proportion of G2/M phase cel s was higher than those in the middle and low concentration groups (P<0.05). With PHA pre-stimulation, the expression of CD69 in the high concentration group was higher than that in the middle and low concentration groups (P<0.05);whereas the difference of CD25 expression was not significant among four subgroups. Titanium ions promoted the expression of CD69 in a concentration-dependent manner (P<0.05), but there was no CD25 expression in each subgroup without PHA pre-stimulation. To conclude, titanium ions can significantly promote T lymphocyte proliferation and early activation in vitro, and moreover, induce S and G2/M phase arrest in T lymphocytes.
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Objective To construct and identify retroviral-mediated short hairpin RNA ( shRNA ) expression vectors of ERβ419, and explore ERβ419 unknown biological function in beagles in future.Methods To screen out the most effective gene silencing sequence of beagle ERβ419 mRNA using qRT-PCR and Western Blot assays, imitate beagle estrogen target cells.Results qRT-PCR results showed, ERβ419-shRNA1 ( P <0.01 ) and ERβ419-shRNA3 ( P <0.01)differed significantly, Western Blot result as same as qRT-PCR,ERβ419-shRNA3 is the best choice.Conclusion Beagles ERβ419-shRNA3 retrain most effectively target gene repression. It is applied to explore ERβ419 unknown biological function in beagles reproductive system, and to prevent and treat beagles reproductive function diseases.