Role of the OTUB1/IRF7/NOX4 axis in oxidative stress injury and inflammatory responses in mice with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is one of the most devastating neurodegenerative disorders and is associated with oxidative stress injury (OSI) and inflammatory responses. This study sought to investigate the mechanism of ovarian tumour domain-containing ubiquitin aldehyde binding 1 (OTUB1) in OSI and inflammatory responses in PD, providing a theoretical foundation for PD treatment. METHODS: The PD mouse model was established by an intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, followed by behavioural tests, observation of brain pathological changes, and quantification of inflammatory (TNF-α, IL-1ß, and IL-10) and OS (ROS, SOD, and MDA) factors. Next, the expression levels of OTUB1, interferon regulatory factor 7 (IRF7), and NADPH oxidase 4 (NOX4) levels were determined by real-time quantitative polymerase chain reaction and western blot assay, the binding of OTUB1 to IRF7 was analysed by co-immunoprecipitation, and the ubiquitination level of IRF7 and the enrichment and binding of IRF7 and the NOX4 promoter were measured by chromatin immunoprecipitation and dual-luciferase assays. Afterwards, rescue experiments were performed with IRF7 or NOX4 overexpression in OTUB1 knockout PD mice. RESULTS: OTUB1 was upregulated in brain tissues of PD mice. Inhibition of OTUB1 alleviated PD progression, OSI, and inflammatory responses. OTUB1 stabilized IRF7 through deubiquitination, and IRF7 bound to the NOX4 promoter to promote NOX4 expression. IRF7 or NOX4 overexpression reversed the effects of silencing OTUB1 on OSI and inflammatory responses in PD mice. CONCLUSION: OTUB1-mediated deubiquitination stabilized IRF7 and upregulated NOX4 expression, thereby promoting OSI and inflammatory responses in PD mice.

Risk factors and functional outcome were associated with hemorrhagic transformation after mechanical thrombectomy for acute large vessel occlusion stroke.

BACKGROUND: Risk factors and functional outcome of hemorrhagic transformation (HT) after mechanical thrombectomy (MT) are to be elucidated in patients with acute large vessel occlusion stroke. METHODS: We retrospectively analyzed data from 88 patients who underwent MT treatment. Independent risk factors of hemorrhagic infarction (HI), parenchymal hematoma (PH) and symptomatic intracranial hemorrhage (sICH) were implemented to determine. Association between HI, PH, sICH and mortality at 90 days after treatment were analyzed. RESULTS: Of 88 patients, 44.3%had HT (N.=39). 64.1% had HI (N.=25), 35.9% had PH (N.=14) and 12.5% had sICH (N.=11). Independent risk factors for HI were associated with higher NIHSS Score (OR 1.190; 95% CI 1.073~1.319, P=0.001, per 1 score increase), history of coronary heart disease (OR 4.645; 95% CI 1.092~19.758, P=0.038), and use of intravenous thrombolysis (OR 3.438; 95% CI 1.029~11.483, P=0.045). Independent risk factors for PH were associated with higher NIHSS Score (OR 1.227; 95% CI 1.085~1.387, P=0.001, per 1 score increase) and history of oral antiplatelet and/or anticoagulation drugs (OR 6.694; 95% CI 1.245~35.977, P=0.027). Independent risk factors for sICH were associated with higher NIHSS Score (OR 1.393; 95% CI 1.138~1.704, P=0.001, per 1 score increase), increased systolic blood pressure (OR 1.061; 95% CI 1.006~1.120, P=0.030, per 1 mmHg increase) and history of coronary heart disease (OR 13.699; 95% CI 1.019~184.098, P=0.048). Patients who had PH were more likely to cause mortality at 90 days (OR 10.15; 95% CI 1.455~70.914, P=0.019). CONCLUSIONS: Higher NIHSS Score was associated with HI, PH, and sICH. History of coronary heart was associated with HI and sICH. Use of intravenous thrombolysis was associated with HI. History of oral antiplatelet and/or anticoagulation drugs was associated with PH. Increased systolic blood pressure was associated with sICH. PHs was remarkably associated with mortality at 90 days.

Cryptogenic Stroke Secondary to Rare Carotid Web?

Understanding the pathogenesis and the typical imaging features of carotid artery web, and accurately diagnosing the carotid artery web will help to implement targeted intervention for cryptogenic stroke and reduce the recurrence of stroke events. Carotid web (CW) can be defined as an endoluminal shelf-like projection often noted at the origin of the internal carotid artery just beyond the bifurcation. It is recognized as a possible cause of ischemic stroke in young adults. We describe here a case of ischemic stroke caused by a CW in a healthy man. Detection of this vascular abnormality required the use of computed tomography angiography. CW is a specific anatomical structure. Its imaging and clinical manifestations are different from atherosclerosis. It's also is a latent etiology to cryptogenic stroke. CW should be considered in patients with otherwise cryptogenic stroke, otherwise healthy patients presenting with stroke and without the typical risk factors for atherosclerotic carotid disease and stroke.