No abstract

Loss-of-function mutations in the parkin gene have recently been shown to be responsible for autosomal recessive juvenile Parkinsonism. However, the exact mechanism of pathogenesis remains unclear. This study explores the effect of Parkin downregulation on dopaminergic cells in Parkinson's disease. We generated small interfering RNA plasmids that target the parkin gene and transfected them into PC12 cells to mimic in vivo loss-of-function. We found that these small plasmids were able to effectively inhibit endogenous Parkin expression in PC12 cells. Downregulation of Parkin decreased the amount of glutathione and superoxide dismutase activity without affecting the amount of malondialdehyde. Moreover, Parkin knockdown rendered PC12 cells more susceptible to cell death induced by the proteasome inhibitor lactacystin. These results indicate that downregulation of Parkin may damage the antioxidation defenses of dopaminergic cells and increase their susceptibility to proteasome inhibitor-induced toxicity.

No abstract

Ischemic stroke is the most common type of stroke, ranked as the second leading cause of death worldwide. The Alberta Stroke Program Early CT Score (ASPECTS) is considered as a systematic method of assessing ischemic change on non-contrast CT scans (NCCT) of acute ischemic stroke (AIS) patients, while still suffering from the requirement of experts' experience and also the inconsistent results between readers.In this study, we proposed an automated ASPECTS method to utilize the powerful learning ability of neural networks for objectively scoring CT scans of AIS patients.First, we proposed to use the CT perfusion (CTP) from one-stop stroke imaging to provide the golden standard of ischemic regions for ASPECTS scoring. Second, we designed an asymmetry network to capture features when comparing the left and right sides for each ASPECTS region to estimate its ischemic status. Third, we performed experiments in a large main dataset of 870 patients, as well as an independent testing dataset consisting of 207 patients with radiologists' scorings.Experimental results show that our network achieved remarkable performance, as sensitivity and accuracy of 93.7 and 92.4% in the main dataset, and 95.5 and 91.3% in the independent testing dataset, respectively. In the latter dataset, our analysis revealed a high positive correlation between the ASPECTS score and the prognosis of patients in 90DmRs. Also, we found ASPECTS score is a good indicator of the size of Zehong Cao, Jiaona Xu, and Bin Song contributed equally to this work.