Oxidative stress activates Ryr2-Ca2+ and apoptosis to promote PM2.5-induced heart injury of hyperlipidemia mice.

The increased cases of hyperlipemia in China and the crucial role of PM2.5 in inducing and promoting cardiovascular diseases have attracting more and more researchers' attention. However, the effects and mechanisms of PM2.5 on cardiovascular system of hyperlipidemia people are still unclear. In this study, hyperlipidemia mice model was established by high-fat diet. Then we exposed these mice to PM2.5 or saline to explore the underling mechanism of cardiac injury in hyperlipidemia mice. The hyperlipemia mice are more susceptible to heart damage caused by PM2.5 exposure. The participation of oxidative stress, cell apoptosis and Ca2+ related mechanism could be observed in this model. After NAC (N-acetyl-L-cysteine) treatment, the oxidative stress level induced by PM2.5 exposure significantly decreased in hyperlipemia mice. NAC effectively alleviated cardiac injury, improved the imbalance of calcium and attenuated apoptosis induced by PM2.5 exposure in hyperlipemia mice. The strong oxidative stress in hyperlipemia mice could lead to calcium homeostasis imbalance and activation of apoptosis-related pathways. This mechanism of PM2.5-induced myocardial injury was also verified in vitro. In our present study, we demonstrated the contribution of the PM2.5-ROS-Ryr2-Ca2+ axis in PM2.5-induced heart injury of hyperlipidemia mice, offering a potential therapeutical target for related pathology.

Oxidative stress activates the TRPM2-Ca2+-NLRP3 axis to promote PM2.5-induced lung injury of mice.

PM2.5, a main particulate air pollutant, poses a serious hazard to human health. The exposure to PM2.5 increases mortality and morbidity of many respiratory diseases such as asthma, chronic obstructive pulmonary diseases and even lung cancer. The contribution of reactive oxygen species (ROS) in the PM2.5-induced acute lung injury process was confirmed in our previous research, but the molecular mechanism based for it remains unclarified. In this research, ROS-induced lung injury after exposure to PM2.5 was explored in vivo and in vitro. The in vivo study indicated that N-acetyl-L-cysteine (NAC) could attenuate the accumulation of inflammatory cells, the thickening of alveolar wall and the degree of lung injury. Furthermore, we found ROS could regulate the intracellular Ca2+ level, expression of the Transient Receptor Potential Melastatin 2 (TRPM2), NLRP3 and its downstream inflammatory factors in vivo. In vitro experiments with A549 cells and primary type II alveolar epithelium cells (SD cells) showed that ROS induced by PM2.5 exposure could mediate intracellular Ca2+ mobilization via TRPM2, with a subsequent activation of NLRP3. In our present study, we demonstrated the contribution of the ROS-TRPM2-Ca2+-NLRP3 pathway in PM2.5-induced acute lung injury and offered a potential therapeutical target valid for related pathology.

The harmful effects of acute PM2.5 exposure to the heart and a novel preventive and therapeutic function of CEOs.

Epidemiological researches have demonstrated the relationship between PM2.5 exposure and increased morbidity and mortality of cardiovascular injury. However, no effective therapeutic method was established. The purpose of this study is to investigate the effect of acute PM2.5 exposure on the mice heart tissue and explore the therapeutic effects of compound essential oils (CEOs) in this model. In this study, after mice were exposed to PM2.5 intratracheally, some obvious histopathological changes as well as some great alterations of proinflammatory cytokines were observed in the heart tissue. The imbalance of oxidative stress, the altered Ca2+ channel related proteins and the increased intracellular free Ca2+ were all involved in the heart impairment and would also be investigated in this model. The CEOs alleviated the heart impairment via its antioxidant effect rather than its anti-inflammatory function because our results revealed that oxidative stress related indicators were restored after CEOs administration. At the same time, increased concentration of intracellular free Ca2+ and ROS induced by PM2.5 were reduced after NAC (N-Acetyl-L-cysteine) administration. These data suggested that the acute PM2.5 exposure would damage heart tissue by inducing the inflammatory response, oxidative stress and intracellular free Ca2+ overload. PM2.5-induced oxidative stress probably increase intracellular free Ca2+ via RYR2 and SERCA2a. CEOs have the potential to be a novel effective and convenient therapeutic method to prevent and treat the acute heart impairment induced by PM2.5 via its antioxidant function.

A Weighted Spatial-Spectral Kernel RX Algorithm and Efficient Implementation on GPUs.

The kernel RX (KRX) detector proposed by Kwon and Nasrabadi exploits a kernel function to obtain a better detection performance. However, it still has two limits that can be improved. On the one hand, reasonable integration of spatial-spectral information can be used to further improve its detection accuracy. On the other hand, parallel computing can be used to reduce the processing time in available KRX detectors. Accordingly, this paper presents a novel weighted spatial-spectral kernel RX (WSSKRX) detector and its parallel implementation on graphics processing units (GPUs). The WSSKRX utilizes the spatial neighborhood resources to reconstruct the testing pixels by introducing a spectral factor and a spatial window, thereby effectively reducing the interference of background noise. Then, the kernel function is redesigned as a mapping trick in a KRX detector to implement the anomaly detection. In addition, a powerful architecture based on the GPU technique is designed to accelerate WSSKRX. To substantiate the performance of the proposed algorithm, both synthetic and real data are conducted for experiments.

Using aripiprazole to reduce antipsychotic-induced hyperprolactinemia: meta-analysis of currently available randomized controlled trials.

BACKGROUND: Hyperprolactinemia (HPL) is a common side effect of antipsychotic medications. Recent reports suggest that aripiprazole can ameliorate antipsychotic-induced HPL, but results are inconsistent and the single available systematic review only considered five studies. AIM: Conduct an updated meta-analysis of all randomized controlled trials (RCTs) about the efficacy and safety of aripiprazole as an adjunctive treatment for antipsychotic-induced hyperprolactinemia. METHODS: English and Chinese databases were searched for RCTs about the use of aripiprazole in treating antipsychotic-induced HPL published by January 20, 2015. Studies were selected using pre-defined inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate risk of biases, the Cochrane GRADE measure was used to assess the quality of evidence, and Review Manager 5.3 software was used for data analysis. RESULTS: A total of 21 studies, 19 of which were conducted in mainland China, were included in the analysis. Meta-analysis of data from 8 of the studies with a pooled sample of 604 individuals found that compared to the control condition adjunctive aripiprazole significantly increased the proportion of participants who experienced HPL recovery (risk ratio [RR]=19.2, 95%CI=11.0-33.5). The proportion who experienced any adverse effect during follow-up did not differ between the two groups, but the aripiprazole group was more likely to report somnolence (RR=2.76, 95%CI=1.34-5.69) and headaches (RR=2.31, 95%CI=1.08-4.92). High-dose aripiprazole (>5mg/day) was more effective than low-dose (<5mg/day) aripiprazole (RR=30.0, 95%CI=10.2-120.7 v. RR=15.1, 95%CI=8.1-28.1), but this difference was not statistically significant. The risk of bias in the studies was rated as 'high' in 6 of the studies and 'unclear' in 15 studies, and the quality of evidence was rated as 'high' for only 7 of the 57 outcome measures assessed. CONCLUSIONS: This study systematically reviewed and evaluated all relevant RCTs and found that adjunctive aripiprazole is effective and safe to use in the treatment of antipsychotic-induced HPL. However, the low quality of some of the studies, the incomplete methodological information provided for most of the studies, and the relatively short follow-up time of the studies raises question about the validity of the results. Further work that resolves these methodological and reporting issues is needed.