258 research outputs found

    Elevated Serum NOX2 Levels Contribute to Delayed Cerebral Ischemia and a Poor Prognosis After Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study

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    Xiaoyu Wu,1,* Danfei Ji,1,* Zefan Wang,1,* Wenhua Yu,2 Quan Du,2 Wei Hu,3 Yongke Zheng,3 Xiaoqiao Dong,2 Fanghui Chen4 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Neurosurgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Intensive Care Unit, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Emergency Department, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiao Dong; Fanghui Chen, Email [email protected]; [email protected]: NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH.Methods: Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls. World Federation of Neurological Surgeons scale (WFNS) score and modified Fisher (mFisher) score were utilized to assess disease severity. Modified Rankin scale (mRS) score was used to evaluate the clinical prognosis at 90 days after aSAH. Relations of serum NOX2 levels to DCI and 90-day poor prognosis (mRS score of 3– 6) were analyzed using multivariate analysis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability.Results: Serum NOX2 levels in aSAH patients, compared with healthy controls, were significantly increased, and were independently correlated with WFNS score, mFisher score and post-stroke 90-day mRS score. Patients with poor prognosis or DCI had significantly higher serum NOX2 levels than other remainders, and serum NOX2 levels independently predicted 90-day poor prognosis and DCI. Serum NOX2 had high prognosis and DCI predictive abilities, and their areas under ROC curve were similar to those of WFNS score and mFisher score.Conclusion: Serum NOX2 levels are significantly associated with hemorrhage severity, poor 90-day prognosis and DCI in aSAH patients. Hence, complement NOX2 may serve as a potential prognostic biomarker after aSAH.Keywords: NADPH oxidase 2, biomarker, aneurysmal subarachnoid hemorrhage, disease severity, delayed cerebral ischemia, prognosi

    Protective effects of pioglitazone on vascular endothelial cell dysfunction induced by high glucose via an inhibition of IKKα/β-NFκB signaling mediated by PPARγ in vitro

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    Pioglitazone (PIO), a synthetic ligand for peroxisome proliferator activated receptor γ (PPARγ), is clinically used to treat type 2 diabetes mellitus. However, little is known on its endothelial protective effects and the underlying mechanisms. In this study, we sought to investigate PIO’s endothelial protective effects and its likely mechanisms. 95% confluent high glucose concentration (HG, 33 mM)-injured WT-HUVECs and PPARγLow-HUVECs were first pretreated with 10 μM of GW9662 for 30 minutes, and then treated with various concentrations of PIO (5, 10, 20 μM) for 24 hours. Finally, the levels of NO, endothelin 1(ET1), tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6) were detected. The cells were utilized to determine the cell viability, caspase3 activity, the levels of inhibitory κB kinase α/β (IKKα/β) mRNA, IKKα/β, and nuclear factor κB (NFκB) p65. Severe dysfunction and activation of IKKα/β-NFκB signaling occurred after exposure of HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKKα/β-NFκB signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPARγ. Taken together, PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKKα/β-NFκ B signaling mediated by PPARγ.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
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