Weiting Yang

This study set out to investigate the potential association between Parkinsons Disease (PD) and the Oxidative Balance Score (OBS), a measure used to evaluate the systemic level of oxidative stress.

Background: Parkinson’s disease (PD) is a common selective and progressive neurodegenerative disorder of nigrostriatal dopaminergic (DA) neurons. Quercetin is a bioflavonoid with antioxidant, anti-inflammatory, anti-aging and anti-cancer properties. However, the exact mechanism by which quercetin exerts its protective effect on DAergic neurons remains unclear. Purpose: To investigate the underlying molecular mechanism of quercetin’s protective effect on DA neurons using 1-methyl-4-phenylpyridinium (MPP+)-induced PD ferroptosis model in vitro. Methods: MPP+ was used to induce cytotoxicity in SH-SY5Y/primary neurons. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The expression levels of ferroptosis-related proteins (NCOA4, SLC7A11, Nrf2, and GPX4) were determined by Western blotting. Malondialdehyde (MDA), iron, and GPX4 levels were assesed using corresponding assay kits. Lipid peroxidation was assessed by C11-BODIPY staining. Results: In the MPP+-induced ferroptosis model of SH-SY5Y cells, the expressions of SLC7A11 and GPX4 were inhibited, and the expression of NCOA4 protein was increased, causing the overproduction of MDA and lipid peroxidation. Quercetin can reduce the above changes caused by MPP+, that is, reduce the protein expression of NCOA4 in SH-SY5Y cells, increase SLC7A11 and GPX4 partially inhibited by MPP+, and reduce MDA overproduction and lipid peroxidation to protect DA neurons. Nrf2 inhibitor ML385 could inhibit quercetin-induced increase of GPX4 and SLC7A11 protein expression, indicating that the protective effect of quercetin was mediated through Nrf2. Conclusions: The results of this study suggest that quercetin regulates ferroptosis through Nrf2-dependent signaling pathways, thereby inhibiting MPP+-induced neurotoxicity in SH-SY5Y/primary neurons.

Purpose: The aim of our study was to determine whether delta red blood cell distribution (ΔRDW) improves neurological outcomes in acute ischemic stroke (AIS) patients 2 years after intravenous thrombolysis (IVT) therapy.Methods: AIS patients who received IVT between January 2013 and December 2019 were retrospectively analyzed. In accordance with their mRS scores, the patients were divided into two groups. A binary logistic regression analysis was conducted to determine the influencing factors of adverse functional outcomes. It was decided to evaluate the variables' the predictive ability by using the area under the receiver operating characteristic. For the poor neurological recovery risk model, features were selected using the LASSO regression model. We also developed a predictive model based on logistic regression analysis, which combined the features selected in the minimum absolute contraction and selection operator regression models. An evaluation of the discrimination, calibration, and clinical applicability of the predictive model was conducted using the C index, calibration chart, and decision curve analysis. Internal validation was evaluated via bootstrapping.Results: Binary logistic regression analysis showed that ΔRDW was an independent influencing factor for poor neurofunctional outcomes. The most appropriate ΔRDW cut-off value for predicting the recovery of poor neurological outcomes was 18.9% (sensitivity: 89.9%, specificity: 78.6%, p < 0.001). The predictive factors included in the nomogram were age, the occurrence of CHD, stroke, AF, ΔRDW, NIHSS score at onset, interval time from onset to IVT, and whether there were indwelling urine catheters and gastric tubes. The model has not only a good discrimination ability, which was indicated by an overall C index of 0.891 (95% confidence interval: 0.829–0.953), but also a considerable calibration ability. Decision curve analysis showed that the nomogram of adverse neurological outcomes recovery was useful in the clinical practice when intervention was implemented above the threshold of 1% possibility of adverse neurological outcomes recovery.Conclusion: In patients with AIS after thrombolysis, the ΔRDW is a potential influencing factor that can be readily used to predict the likelihood of poor neurological function recovery.

Parkinson’s disease (PD) is a progressive age-related movement disorder caused by dopaminergic neuron loss in the substantia nigra. Diffusion-based magnetic resonance imaging (MRI) studies—namely, diffusion tensor imaging (DTI)—have been performed in the context of PD, either with or without the involvement of sleep disorders (SDs), to deepen our understanding of cerebral microstructural alterations. Analyzing the clinical characteristics and neuroimaging features of SDs in early PD patients is beneficial for early diagnosis and timely invention. In our present study, we enrolled 36 early PD patients (31 patients with SDs and 5 patients without) and 22 healthy controls. Different types of SDs were assessed using the Rapid Eye Movement Sleep Behavior Disorder Questionnaire—Hong Kong, Epworth Sleepiness Scale, International Restless Legs Scale and PD Sleep Scale-2. Brain MRI examinations were carried out in all the participants, and a region-of-interest (ROI) analysis was used to determine the DTI-based fractional anisotropy (FA) values in the substantia nigra (SN), thalamus (Thal) and hypothalamus (HT). The results illustrate that SDs showed a higher prevalence in the early PD patients than in the healthy controls (86.11% vs. 27.27%). Early PD patients with nighttime problems (NPs) had longer courses of PD than those without (5.097 ± 2.925 vs. 2.200 ± 1.095; p < 0.05), and these patients with excessive daytime sleepiness (EDS) or restless legs syndrome (RLS) had more advanced Hoehn and Yahr stages (HY stage) than those without (1.522 ± 0.511 and 1.526 ± 0.513, respectively; both p < 0.05). Compared with the early PD patients without probable rapid eye movement sleep behavior disorder (pRBD), those with pRBD had longer courses, more advanced HY stages and worse motor and non-motor symptoms of PD (course(years), 3.385 ± 1.895 vs. 5.435 ± 3.160; HY stages, 1.462 ± 0.477 vs. 1.848 ± 0.553; UPDRS, 13.538 ± 7.333 vs. 21.783 ± 10.766; UPDRS, 6.538 ± 1.898 vs. 7.957 ± 2.345; all p < 0.05). In addition, the different number of SD types in early PD patients was significantly inversely associated with the severity of damage in the SN and HT. All of the early PD patients with various SDs had injuries in the SN, in whom the damage was more pronounced in patients with NP than those without. Moreover, early PD patients with NP, RLS or pRBD had worse degrees of HT damage than those without. The current study demonstrated the pathophysiological features and neuroimaging changes in early PD patients with various types of sleep disorders, which will help in early diagnosis and therapy.