Bisphenol S impairs mitochondrial function by targeting Myo19/oxidative phosphorylation pathway contributing to axonal and dendritic injury.

Exposure to bisphenol S (BPS) is known to adversely affect neuronal development. As pivotal components of neuronal polarization, axons and dendrites are indispensable structures within neurons, crucial for the maintenance of nervous system function. Here, we investigated the impact of BPS exposure on axonal and dendritic development both in vivo and in vitro. Our results revealed that exposure to BPS during pregnancy and lactation led to a reduction in the complexity, density, and length of axons and dendrites in the prefrontal cortex (PFC) of offspring. Employing RNA sequencing technology to elucidate the underlying mechanisms of axonal and dendritic damage induced by BPS, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted a significant alteration in the oxidative phosphorylation (OXPHOS) pathway, essential for mitochondrial function. Subsequent experiments demonstrate BPS-induced impairment in mitochondrial function, including damaged morphology, decreased adenosine triphosphate (ATP) and superoxide dismutase (SOD) levels, and increased reactive oxygen species and malondialdehyde (MDA). These alterations coincided with the downregulated expression of OXPHOS pathway-related genes (ATP6V1B1, ATP5K, NDUFC1, NDUFC2, NDUFA3, COX6B1) and Myosin 19 (Myo19). Notably, Myo19 overexpression restored the BPS-induced mitochondrial dysfunction by alleviating the inhibition of OXPHOS pathway. Consequently, this amelioration was associated with a reduction in BPS-induced axonal and dendritic injury observed in cultured neurons of the PFC.

Yttrium chloride-induced cytotoxicity and DNA damage response via ROS generation and inhibition of Nrf2/PPARγ pathways in H9c2 cardiomyocytes.

Increasing exploration of rare-earth elements (REEs) has resulted in a high REEs' exposure risk. Owing to their persistence and accumulation of REEs in the environment, their adverse effects have caused widespread concern. However, limited toxicological data are available for the adverse effects of yttrium (Y) and its underlying mechanisms of action. In the present study, H9c2 cardiomyocytes were used in vitro model to investigate the cardiotoxicity of yttrium chloride (YCl3). Results show that YCl3 treatment resulted in reactive oxygen species (ROS) overproduction, decrease in ∆Ψm, and DNA damage. Mechanistically, we detected expression levels of protein in response to cellular DNA damage and antioxidative defense. Results indicated that the phosphorylation of histone H2AX remarkably increased in a dose-dependent manner. At a high YCl3-exposure concentration (120 µM), specific DNA damage sensors ATM/ATR-Chk1/Chk2 were significantly decreased. The protein levels of key antioxidant genes Nrf2/PPARγ/HO-1 were also remarkably inhabited. Additionally, the antioxidant N-acetyl-L-cysteine (NAC) pretreatment promoted the activation of antioxidative defense Nrf2/PPARγ signaling pathways, and prevented the production of cellular ROS, thus protecting the DNA from cleavage. Altogether, our findings suggest that YCl3 can induce DNA damage through causing intracellular ROS overproduction and inhibition of antioxidative defense, leading to cytotoxicity in H9c2 cardiomyocytes.

Extreme temperatures and cardiovascular mortality: assessing effect modification by subgroups in Ganzhou, China.

BACKGROUND: Many people die from cardiovascular diseases each year, and extreme temperatures are regarded as a risk factor for cardiovascular deaths. However, the relationship between temperature and cardiovascular deaths varies in different regions because of population density, demographic inequality, and economic situation, and the evidence in Ganzhou, China is limited and inconclusive. OBJECTIVE: This study aimed to assess extreme temperature-related cardiovascular mortality and identify the potential vulnerable people. METHODS: After controlling other meteorological measures, air pollution, seasonality, relative humidity, day of the week, and public holidays, we examined temperature-related cardiovascular mortality along 21 lag days by Poisson in Ganzhou, China. RESULTS: A J-shaped relationship was observed between mean temperature and cardiovascular mortality. Extremely low temperatures substantially increased the relative risks (RR) of cardiovascular mortality. The effect of cold temperature was delayed by 2-6 days and persisted for 4-10 days. However, the risk of cardiovascular mortality related to extremely high temperatures was not significant (p > 0.05). Subgroup analysis indicated that extremely low temperatures had a stronger association with cardiovascular mortality in people with cerebrovascular diseases (RR: 1.282, 95% confidence interval [CI]: 1.020-1.611), males (RR: 1.492, 95% CI: 1.175-1.896), married people (RR: 1.590, 95% CI: 1.224-2.064), and people above the age of 65 years (RR: 1.641, 95% CI: 1.106-2.434) than in people with ischemic heart disease, females, unmarried people, and the elderly (≥65 years old), respectively. CONCLUSIONS: The type of cardiovascular disease, sex, age, and marital status modified the effects of extremely low temperatures on the risk of cardiovascular mortality. These findings may help local governments to establish warning systems and precautionary measures to reduce temperature-related cardiovascular mortality.