Toxicology letters
-
Blast lung injury is associated with high morbidity and mortality. Vaporized perfluorocarbon (PFC) inhalation has been reported to attenuate acute respiratory distress syndrome in humans and animal models. However, the effect of vaporized PFC on blast lung injury is still unknown. ⋯ PFC treatment downregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), and upregulated superoxide dismutase (SOD) activity. PFC also suppressed expression of MAPK/NF-κB and Nrf2 protein levels. Our results suggest that PFC attenuated blast-induced acute lung injury by inhibiting MAPK/NF-κB activation and inducing Nrf2 expression in dogs.
-
The chemical warfare agent sulfur mustard (SM) affects all cells in the epidermis including melanocytes which are responsible for melanin synthesis. After exposure to SM, pigment abnormalities like hypo- and hyperpigmentation can occur. The underlying molecular pathomechanisms of SM exposure on human melanogenesis have not been elucidated so far. ⋯ Our findings demonstrated that exposure to low SM concentrations increased melanin synthesis accompanied with an increase in protein expression. In contrast, high SM concentrations led to decreased melanin content and a downregulation in expression of all investigated melanogenesis-associated proteins. We concluded that low SM concentrations may cause hyperpigmentation while high SM concentrations decreased melanin content which may explain hypopigmented skin areas in SM exposed patients.
-
In 2017, the U. S. Department of Health and Human Services and the White House declared a public health emergency to address the opioid crisis (Hargan, 2017). ⋯ These kits were designed to dramatically increase laboratory capability to confirm which opioids are on the streets and causing deaths. The kits are free to U. S based laboratories in the public, private, clinical, law enforcement, research, and public health domains.
-
Epidemiological studies have established the correlations between PM2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM2.5 exposure (50 μg/ml) for 30 passages. ⋯ Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions.
-
Carfentanil (CRF) is an extremely potent opioid capable of inducing fatal respiratory depression. Naloxone (NX) and naltrexone (NTX) are opioid antagonists for which the efficacy against CRF remains largely unexplored. In this study, the effects of aerosolized CRF on respiratory function were investigated using adult male CD-1 mice. ⋯ Despite improvements in MV, treatment administration did not reverse changes in DC, a measure of respiratory timing. Overall, NX and NTX administration alleviated volumetric aspects of opioid-induced respiratory toxicity, while changes in respiratory timing remained unresolved throughout post-exposure observation. These sustained changes and differences in recovery between two aspects of respiratory dynamics may provide insights for further exploration into the underlying mechanism of action of opioids and opioid antagonists.