Polystyrene microplastics induce anxiety via HRAS derived PERK-NF-κB pathway.

Exposure to environmentally hazardous substances is recognized as a significant risk factor for neurological associated disorders. Among these substances, polystyrene microplastics (PS-MPs), widely utilized in various consumer products, have been reported to exhibit neurotoxicity. However, the potential association of PS-MPs with abnormal anxiety behaviors, along with the underlying molecular mechanisms and key proteins involved, remains insufficiently explored. Here, we delineated the potential mechanisms of PS-MPs-induced anxiety through proteomics and molecular investigations. We characterized the PS-MPs, observed their accumulation in the brain, leading to anxiety-like behavior in mice, which is correlated with microglia activation and pro-inflammatory response. Consistent with these findings, our studies on BV2 microglia cells showed that PS-MPs activated NF-κB-mediated inflammation resulting in the upregulation of pro-inflammatory cytokines such as TNFα and IL-1ß. Of particular significance, HRAS was identified as a key factor in the PS-MPs induced pro-inflammatory response through whole proteomics analysis, and knockdown of H-ras effectively inhibited PS-MPs induced PERK-NF-κB activation and associated pro-inflammatory response in microglia cells. Collectively, our findings highlight that PS-MPs induce anxiety of mice via the activation of the HRAS-derived PERK-NF-κB pathway in microlglia. Our results contribute valuable insights into the molecular mechanisms of PS-MPs-induced anxiety, and may offer implications for addressing neurotoxicity and prevention the adverse effects of environmentally hazardous substances, including microplastics.

Metabolism of hibernating myocardium and regulation of uncoupling protein 2 / 中国药理学通报

HM(hibernating myocardium)is an adaptive phenome-non of myocardium against sustained ischemia,which maintains its tissue vitality through balancing energy supply and demand.It widely exists in patients suffering from coronary heart disease. HMhas its own metabolic pattern,instead of regular FAO(fatty acid β-oxidation)-based metabolism,glycolysis became main pro-cedure.Reduction of FAO,TCA (tricarboxylic cacidcycle),ETC (electron transport chain)enzyme has been observed,ROS(reac-tive oxygen species)and UCP2(uncoupling protein 2)have been up-regulated.UCP2,which promotes proton leak across innermembrane of mitochondrial and leads to ATP reduction,has e-merged as an important regulator of the energy production.It is regulated by up-stream proteins such as AMPK,PPARs,PGC-1α,and other factors like FFA(free fat acid),ROS and purine nucleotide.HM has potential function of ischemic myocardium, which can improve cardiac function through reasonable interven-tion.Modulation of UCP2 can optimize energy production,and is essential to HM metabolism.