Realistic Nanoplastics Induced Pulmonary Damage via the Crosstalk of Ferritinophagy and Mitochondrial Dysfunction.

The smaller size fraction of plastics may be more substantially existing and detrimental than larger-sized particles. However, reports on nanoplastics (NPs), especially their airborne occurrences and potential health hazards to the respiratory system, are scarce. Previous studies limit the understanding of their real respiratory effects, since sphere-type polystyrene (PS) nanoparticles differ from NPs occurring in nature with respect to their physicochemical properties. Here, we employ a mechanical breakdown method, producing NPs directly from bulk plastic, preserving NP properties in nature. We report that among four relatively high abundance NP materials PS, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polyethylene (PE) with a size of 100 nm, PVC induced slightly more severe lung toxicity profiles compared to the other plastics. The lung cytotoxicity of NPs is higher than that of commercial PS NPs and comparable to natural particles silicon dioxide (SiO2) and anatase titanium dioxide (TiO2). Mechanistically, BH3-interacting domain death agonist (Bid) transactivation-mediated mitochondrial dysfunction and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy or ferroptosis are likely common mechanisms of NPs regardless of their chemical composition. This study provides relatively comprehensive data for evaluating the risk of atmospheric NPs to lung health.

Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis.

Fine particulate matter (PM2.5) has been widely reported to contribute to the pathogenesis of pulmonary diseases. The direct hazardous effect of PM2.5 on the respiratory system at high concentrations in vitro and in vivo have been well identified. However, its effect on the pre-existing respiratory diseases of patients at environment-related concentrations remains unclear. Diesel exhaust PM2.5 as a primary representative of ambient PM2.5 fine particles were used to investigated the effect of PM2.5 on the fibrosis progression of existing pulmonary fibrosis disease models. This study reported that PM2.5 could result in the enhanced sensitivity to fibrotic response, which may be ascribed to ferroptosis induced by PM2.5 in damaged lung areas. Proteomic analysis revealed that the upregulation of HO-1 as a key mechanism in the ferroptosis and exacerbation of pulmonary fibrosis induced by PM2.5. As a result, HO-1 degraded heme-containing protein and released iron in fibrotic cells, leading to generation of mitochondrial ROS and impaired mitochondrial function. Transmission electron microscopic assay verified that PM2.5 entered the mitochondria of fibrotic cells and was accompanied by significant mitochondrial morphological changes characterized by increased mitochondrial membrane density and reduced mitochondrial size. The HO-1 inhibitor zinc protoporphyrin and mitochondrion-targeted antioxidant Mito-TEMPO significantly attenuated PM2.5-induced ferroptosis and exacerbation of fibrosis. In addition, AMPK-ULK1 axis-triggered autophagy activation and NCOA4-mediated degradation of ferritin by autophagy were found to be related to the PM2.5-induced ferroptosis of fibrotic cells. As evidenced by the inhibition of autophagy with 3-methyladenine or AMPK inhibitor, NCOA4 knockdown decreased intracellular iron accumulation and lipid peroxidation, thereby relieving PM2.5-induced epithelial-mesenchymal transition and cell death in fibrotic cells. Overall, this study provided experimental support for the idea that PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis, and HO-1-mediated mitochondrial dysfunction and NCOA4-mediated ferritinophagy are jointly required for the PM2.5-induced ferroptosis and enhanced fibrosis effects.

Myocardial infarction after near drowning.

During summer, near drowning is a common accident in Taiwan. It may lead to multiple organ damages in cases where severe hypothermia and hypoxemia occur. We present a case of myocardial infarction after near drowning. The patient was sent to our ED by the emergency medical services called by the witness. On arrival to our ED, hypothermia and hypoxemia overcame him. Endotracheal intubation and warm intravenous fluid were applied at once owing to drowsy consciousness, respiratory distress, and hypothermia. Electrocardiogram showed diffuse ST-segment elevation over the precordial leads V2-V6. The initial level of cardiac enzymes was within normal limit but elevated in troponin I on the second day after hospitalization. We presumed that the possibility of myocardial infarction resulted from near drowning-related hypoxemia. To our knowledge, this is the first case describing myocardial injury with electrocardiogram changes after near drowning.