The purpose of the current study was to demonstrate the neuroprotective effect of protodioscin (Prot) in an in vitro model of ischemia/reperfusion (I/R) and investigate the underlying molecular mechanism. After PC12 cells were exposed to oxygen and glucose deprivation (OGD) reperfusion, PI staining by flow cytometry was used to quantify the rate of apoptosis. The levels of hypoxia-inducible factor 1-alpha (HIF-1α), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were determined using commercially available kits. Intracellular reactive oxygen species (ROS) level was detected using the 20,70-dichlorodihy-drofluorescein diacetate (DCFH-DA) fluorescence assay. The expression levels of heat-shock proteins (HSP), PI3K, AKT, Nrf2, and miR-124 were tested by western blot or quantitative PCR. Prot significantly attenuated oxygen-glucose deprivation/reperfusion (OGD/R)-induced apoptotic death. Prot also reduced the oxidative stress as revealed by increasing the activities of SOD and GSH-Px, decreasing the levels of ROS and MDA. Moreover, mechanism investigations suggested that Prot prevented the decrease of HSP70, HSP32 (hemeoxygenase-1, HO-1), and PI3K protein expression, phosphorylation of AKT, and the accumulation of nuclear Nrf2. The level of miR-124 was decreased in PC12 cells, which was also effectively reversed by Prot treatment. Prot protected PC12 cells against OGD/R-induced injury through inhibiting oxidative stress and apoptosis, which could be associated with increasing HSP proteins expression via activating PI3K/AKT/Nrf2 pathway and miR-124 modulation.
AIm:The role of statins for treating aneurysmal subarachnoid hemorrhage (aSAH) remains uncertain. In this study, the relevance of different end points was evaluated in order to clarify the action and efficacy of statins. mAterIAl and methOds: A systematic literature retrieval was carried out to obtain randomized controlled trials (RCTs) from before March 2013 on the use of statins for aSAH. Data extraction and quality evaluation of the studies were performed by 2 investigators. A meta-analysis was performed using Review Manager (RevMan) software version 5.2.3. results:Seven randomized controlled trials comprising 347 patients that met the inclusion criteria were included in this meta-analysis. Results showed that, in aSAH, statins did not reduce vasospasm on transcranial Doppler (RR=0.80; 95% CI, 0.53-1.21; p=0.29) or improve outcomes (RR=0.92; 95% CI, 0.71-1.20; p=0.54). However, statins were able to decrease delayed ischemic neurological deficits (RR=0.56; 95% CI, 0.41-0.75; p=0.0001) and mortality (RR=0.54; 95% CI, 0.32-0.91; p=0.02) compared with placebo.COnClusIOn: Acute statin treatment might not be a good choice for cerebral vasospasm after aSAH. Further large-scale, well-designed RCTs on this topic are still needed. BulGulAr: Bu meta analize çalışmaya alma kriterlerini karşılayan 347 hastalık yedi randomize kontrollü çalışma dahil edilmiştir. Sonuçlar aSAK durumunda statinlerin transkraniyal Doppler'de vazospazmı azaltmadığını (RR=0,80; %95 GA, 0,21; p=0,29) veya sonuçları daha iyi hale getirmediğini (RR=0,92; %95CI, 0,20; p=0,54) göstermiştir. Ancak statinler plaseboyla karşılaştırıldığında gecikmiş iskemik nörolojik defisitleri (RR=0,56; %95 GA, 0,41-0,75; p=0,0001) ve mortaliteyi (RR=0,54; %95 GA, 0,32-0,91; p=0,02) azaltmıştır. sOnuÇ: Akut statin tedavisi aSAK sonrasında serebral vazospazm için iyi bir tercih olmayabilir. Bu konuda daha büyük ölçekli ve iyi tasarlanmış randomize kontrollü çalışmalar gereklidir.
This study aims to explore factors affecting passenger car and truck driver injury severity in passenger car-truck crashes. Police-reported crash data from 2007 to 2017 in Canada are collected. Twovehicle crashes involving one truck and one passenger car are extracted for modeling. Different injury severities are not equally represented. To address the data imbalance issue, this study applies four different data imbalance treatment approaches, including over-sampling, under-sampling, a hybrid method, and a cost-sensitive learning method. To test the performances of different classifiers, five classification models are used, including multinomial logistic regression, Naive Bayes, Classification and Regression Tree, support vector machine, and eXtreme Gradient Boosting (XGBoost). In both the passenger car driver and truck driver injury severity analysis, XGBoost combined with cost-sensitive learning generates the best results in terms of G-mean, area under the curve, and overall accuracy. Additionally, the Shapley Additive Explanations (SHAP) approach is adopted to interpret the result of the best-performing model. Most of the explanatory variables have similar effects on passenger car and truck driver fatality risks. Nevertheless, six variables exhibit opposite effects, including the age of the passenger car driver, crash hour, the passenger car age, road surface condition, weather condition and the truck age. Results of this study could provide some valuable insights for improving truck traffic safety. For instance, properly installing traffic control devices could be an effective way to reduce fatality risks in passenger car-truck crashes. Besides, passenger car drivers should be extremely cautious when driving between midnight to 6 am on truck corridors.
Background: Pregnant female rats exposed to lead may give birth to offspring with learning and memory disorders. Many studies have shown that there are many mechanisms that cause learning and memory impairment. Epigenetic mechanisms may play an important function in the learning and memory impairment.Methods: We examined DNA methylation changes in the hippocampus of rats with learning and memory disorder that were the offsprings of rats exposed to lead during pregnant and lactation period. The Morris Water Maze was applied as a learning and memory test, and a Roche NimbleGen's rat DNA methylation 385K Promoter Plus CpG Island Array was used for array hybridization. Results:The results of the integrated navigation and spacial exploration test showed that until 21 days after birth and the lactation period, the learning and memory abilities of offsprings with lead exposure during pregnant and lactation period were significantly lower than those of the control group. The hippocampus DNA methylation levels of the three types of promoters increased compared with those of the control group.According to the Gene Ontology (GO) terms, metal ion transport, cell connections, the lamellar body, the axon bulge, and methylation of various metal transporters were found to be significantly enriched. Pathway analysis showed that the hedgehog signaling pathway, neuroactive receptor-ligand interaction with the ligase pathway, and interaction between cytokines had high methylation.Conclusions: DNA methylation of the whole genome in the hippocampus of the rats with learning and memory impairment induced by perinatal lead contact showed a lot of changes compared with that in the group of control.
How to improve the collision process of safety performance has become one of the most important issue in the automobile manufacturing enterprises. This paper using LS-DYNA made a security analyses about former girders, based in half vehicle model, analyzing the security of the front side member to reflect the vehicle’s performance. At the same time, through the front side member’s assembly structure’s contrast with the modified ones, the result has proved the improvement is more effective.
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