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Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. HPN (4'-hydroxyl-2-substituted phenyl nitronyl nitroxide), a stable nitronyl nitroxide, has excellent free radical scavenging properties. The purpose of this study was to investigate the protective effects of HPN on hypoxia-induced damage inPC12 cells. It was shown that HPN significantly attenuated hypoxia-induced loss of cell viability, release of lactate dehydrogenase (LDH), and morphological changes in PC12 cells. Moreover, hypoxic PC12 cells had increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), and expression of HIF-1[alpha] and VEGF, but had reduced levels of superoxide dismutase (SOD) and catalase (CAT), and HPN reversed these changes. HPN also inhibited hypoxia-induced cell apoptosis via suppressing the expression of Bax, cytochrome c, and caspase-3, and inducing the expression of Bcl-2. These results indicate that the protective effects of HPN on hypoxia-induced damage in PC12 cells is associated with the suppression of hypoxia-induced oxidative stress and cell apoptosis. HPN could be a promising candidate for the development of a novel neuroprotective agent. Key words: nitronyl nitroxide, hypoxia, PC12 cells, oxidative stress, apoptosis. L'hypoxie provoque un stress oxydant cellulaire qui est associe aux maladies neurodegeneratives. Le 4'-hydroxyl-2-phenyl nitronyl-nitroxyde substitue (HPN), un nitronyl-nitroxyde stable, presente une excellente activite de piegeur de radicaux libres. L'objectif de cette etude consistait a examiner les effets protecteurs du HPN sur le dommage induit aux cellules PC12 par l'hypoxie. Il s'est avere que le HPN attenuait significativement la perte de viabilite cellulaire, la liberation de LDH et les changements morphologiques induits par l'hypoxie chez les cellules PC12. De plus, les cellules PC12 hypox-iques presentaient une elevation des contenus en derives reactifs de l'oxygene (DRO) et en malonaldehyde (MDA), ainsi que de l'expression de HIF-1[alpha] et du VEGF, mais une diminution de la superoxyde dismutase (SOD) et de la catalase (CAT), alors que le HPN pouvait renverser ces changements. Le HPN inhibait aussi l'apoptose induite par l'hypoxie en reprimant l'expression de Bax, du cytochrome c et de la caspase-3 et en induisant l'expression de Bcl-2. Ces resultats indiquent que la protection conferee par le HPN envers les dommages provoques par l'hypoxie chez les cellules PC12 est associee a la suppression du stress oxydant et de l'apoptose induits par l'hypoxie. Le HPN pourrait constituer un candidat prometteur dans le cadre du developpement d'un nouvel agent neuroprotecteur. [Traduit par la Redaction] Mots-cles: nitronyl-nitroxyde, hypoxie, cellules PC12, stress oxydant, apoptose., Introduction Oxygen ([O.sub.2]) is essential for aerobic organisms to produce energy (Majmundar et al. 2010). When the supply of oxygen does not meet demand from the cells, this leads to [...]

In the originally published article, a funding partner Guizhou Province Science and Technology Plan Project [Qian ke He support [2020] 4Y128] was missing from the acknowledgement. The correct statement is [...]

Introduction: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. Aims: Our study aimed to investigate how deficiency of PGAM5‐mediated depressive behavior. Results: We firstly discovered that PGAM5 knockout (PGAM5−/−) mice generated depressive‐like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)‐induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5−/− mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1F0 synthase without influencing the interaction between ATP F1F0 synthase and Bcl‐xl. We then conducted ATP administration to PGAM5−/− mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5−/− mice. Conclusions: Our findings provide convincing evidence that PGAM5 ablation generates depressive‐like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the protect effect of moslosooflavone against brain injury induced by hypobaric hypoxia (HH) in mice. Methods: Protective effects of moslosooflavone in oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis were studied in HH-induced brain damage mice. The pathological morphology in the cortex of mice was determined by hematoxylin and eosin staining. The related protein expressions were detected by western blot. Key findings: Moslosooflavone improved HH-induced brain histopathological changes, reduced the contents of ROS and MDA, and elevated the levels of antioxidant enzymes and GSH in HH-exposed brains of mice. Moslosooflavone also markedly enhanced the ATPase activities and PK, ATP contents, while reducing LDH activity and the LD, TNF-α, IL-1β, and IL-6 contents HH-exposed brains of mice. In addition, moslosooflavone notably decreased the expression of HIF-1α, VEGF, Bax, and cleaved caspase-3 dramatically increasing the expression of Bcl-2, Nrf2, and HO‑1 in HH-exposed brains of mice. Conclusions: Our current studies indicate that moslosooflavone protects HH-induced brain injury possibly through alleviating oxidative stress and neuroinflammation, maintaining the balance of energy metabolism, and inhibiting cell apoptosis. [ABSTRACT FROM AUTHOR]

Studies that measure individual differences leading to risky driving behaviors in pre-crash phase will make contributions to accidents prevention. The primary concern here is what induces drivers to engage in risky behaviors. In this research, 441 valid questionnaires were distributed to examine the impact of risk preference, risk perception, and their interaction on risky driving behaviors, and the moderating effects of gender, age, and driving experience were measured accordingly. Results from the ordered logit regression model analysis demonstrate that the data fit well with our theoretical model. Risk preference and risk perception both predict risky driving behaviors with risk perception having greater predictability, and their interaction significantly affects risky driving behaviors when gender and age variables were added to the model separately. Gender and driving experience moderate the influence of risk perception on risky driving behaviors. The predictive effect of risk perception on risky driving behaviors was more significant for females than males. The effect of risk perception on risky driving behaviors was more pronounced for drivers with 1-3 years of driving experience compared with others. These interesting findings suggest that interventions need to be directed to all parts of the causal chain. [ABSTRACT FROM AUTHOR]

The government plays an important role in road safety. However, the effectiveness of the government in the context of road traffic accidents (RTAs) is rarely measured quantitatively. This study aims to quantitatively examine the effects of government regulation on human and organizational factors. A contributing factors classification framework of RTAs is presented based on the human factors analysis and classification system, one of the most popular systems approaches. A total of 405 major RTAs was collected over a 20-year period (1997–2017) in China and analyzed through the structural equation model. The results lead to two main conclusions: the frequency of inadequate regulation, which has reached 343, is the highest frequency among all contributing factors; government regulation exhibits significant effects on organizational influences, unsafe supervision and unsafe behaviors. These findings provide a new perspective for accident prevention that can be initiated by the government in policy-making and regulatory activities. [ABSTRACT FROM AUTHOR]