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Air pollution is a public health threat and global epidemiological studies have shown that ambient air pollutants are closely related to various poor health conditions, including neurodegenerative diseases. Here, we evaluated the toxic effects and the underlying mechanisms of fine airborne particulate matter (PM 2.5 ) on human glioblastoma LN-229 cells. Our results showed that exposure of LN-229 cells to PM 2.5 (≥ 200 μg/mL) significantly reduced cell viability. PM 2.5 exposure increased autophagy, apoptosis, and ROS production in the cells. Pre-treatment with a ROS scavenger, catalase, or depletion of mtDNA (ρ 0 cells) abolished PM 2.5 -induced autophagy and apoptosis. PM 2.5 exposure also activated MAPK signals in cells, which were blocked by catalase pre-treatment or mtDNA depletion. Furthermore, inhibition of JNK, but not ERK1/2 or p38, attenuated PM 2.5 -induced autophagy and apoptosis in cells. Finally, suppression of autophagy with Bafilomycin A1 or Beclin 1 siRNA exacerbated PM 2.5 -induced apoptosis, indicating a protective role of autophagy against PM 2.5 -induced apoptosis. Our results demonstrated that exposure of LN-229 cells to PM 2.5 caused autophagy and apoptosis through PM 2.5 -induced ROS generation, mainly by mitochondria, and JNK activation. Autophagy may have a transient protective response in PM 2.5 -induced apoptosis. These findings have important implications for understanding the potential neurotoxicity of PM 2.5 ., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We and others have previously demonstrated that exposure to nickel nanoparticles (Nano-Ni) caused fibrogenic and carcinogenic effects; however, the underlying mechanisms are still not fully understood. This study aimed to investigate the effects of Nano-Ni on epithelial-mesenchymal transition (EMT) in human bronchial epithelial cells (BEAS-2B) and its underlying mechanisms since EMT is involved in both cancer pathogenesis and tissue fibrosis. Our results showed that exposure to Nano-Ni, compared to the control Nano-TiO2, caused a remarkable decrease in the expression of E-cadherin and an increase in the expression of vimentin and α-SMA, indicating an inducible role of Nano-Ni in EMT development in human bronchial epithelial cells. HIF-1α nuclear accumulation, HDAC3 upregulation, and decreased histone acetylation were also observed in the cells exposed to Nano-Ni, but not in those exposed to Nano-TiO2. Pretreatment of the cells with a specific HIF-1α inhibitor, CAY10585, or HIF-1α-specific siRNA transfection prior to Nano-Ni exposure resulted in the restoration of E-cadherin and abolished Nano-Ni-induced upregulation of vimentin and α-SMA, suggesting a crucial role of HIF-1α in Nano-Ni-induced EMT development. CAY10585 pretreatment also attenuated the HDAC3 upregulation and increased histone acetylation. Inhibition of HDAC3 with specific siRNA significantly restrained Nano-Ni-induced reduction in histone acetylation and restored EMT-related protein expression to near control levels. In summary, our findings suggest that exposure to Nano-Ni promotes the development of EMT in human bronchial epithelial cells by decreasing histone acetylation through HIF-1α-mediated HDAC3 upregulation. Our findings may provide information for further understanding of the molecular mechanisms of Nano-Ni-induced fibrosis and carcinogenesis. [ABSTRACT FROM AUTHOR]

Silicosis is one of the typical forms of pneumoconiosis characterized by abnormal proliferation of fibroblasts and deposition of extracellular matrix. Recent findings have shown that microRNAs and circular RNAs (circRNAs) are implicated in many diseases. However, the function of noncoding RNAs in pulmonary fibrosis remain to be elucidated. Here, miR-7 was found significantly decreased in silica-treated pulmonary epithelial cells as well as in fibrotic lung tissues of mice. Elevated expression of miR-7 via agomir injection relieved lung fibrosis in vivo. Further molecular study showed that miR-7 played its role against pulmonary fibrosis by blocking epithelial-mesenchymal transition (EMT) progression of human bronchial epithelial cells and A549 cells. Notably, transforming growth factor beta receptor 2 (TGFBR2) was identified as a target gene of miR-7 with bioinformatics tools, which was verified by dual luciferase receptor gene assay in human bronchial epithelial cells and A549 cells. Silica induced elevation of TGFBR2 could be abolished by exogenous expression of miR-7. Furthermore, bioinformatics software indicated that circRNA CDR1as had several binding sites for miR-7. The inhibitory effects of miR-7 on EMT and its target TGFBR2 were suppressed by circRNA CDR1as, which contributed to pulmonary fibrosis. Our studies also revealed overexpressed miR-7 could repress fibrogenesis of lung fibroblasts induced by TGF-β1. Collectively, circRNA CDR1as stimulated by silica could sponge miR-7 to release TGFBR2, plays an important role during pulmonary fibrosis by promoting EMT process. These results indicated that the interaction between miR-7 and circRNA CDR1as may exert important functions and provide potential therapeutic targets in lung fibrotic diseases. [ABSTRACT FROM AUTHOR]

With the rapid development of nanotechnology, the potential adverse health effects of nanoparticles have been caught more attention and become global concerns. However, the underlying mechanisms in metal nanoparticle-induced toxic effects are still largely obscure. In this study, we investigated whether exposure to nickel nanoparticles (Nano-Ni) and titanium dioxide nanoparticles (Nano-TiO 2) would alter autophagy and apoptosis levels in normal human bronchial epithelial BEAS-2B cells and the underlying mechanisms involved in this process. Our results showed that the expressions of autophagy- and apoptosis-associated proteins were dysregulated in cells exposed to Nano-Ni. However, exposure to the same doses of Nano-TiO 2 had no significant effects on these proteins. In addition, exposure to Nano-Ni, but not Nano-TiO 2 , led to nuclear accumulation of HIF-1α and decreased phosphorylation of mTOR in BEAS-2B cells. Inhibition of HIF-1α by CAY10585 abolished Nano-Ni-induced decreased phosphorylation of mTOR, while activation of mTOR by MHY1485 did not affect Nano-Ni-induced nuclear accumulation of HIF-1α. Furthermore, both HIF-1α inhibition and mTOR activation abolished Nano-Ni-induced autophagy but enhanced Nano-Ni-induced apoptosis. Blockage of autophagic flux by Bafilomycin A1 exacerbated Nano-Ni-induced apoptosis, while activation of autophagy by Rapamycin effectively rescued Nano-Ni-induced apoptosis. In conclusion, our results demonstrated that Nano-Ni exposure caused increased levels of autophagy and apoptosis via the HIF-1α/mTOR signaling axis. Nano-Ni-induced autophagy has a protective role against Nano-Ni-induced apoptosis. These findings provide us with further insight into Nano-Ni-induced toxicity. [Display omitted] • Nano-Ni, but not Nano-TiO 2 , caused increased autophagy and apoptosis in BEAS-2B cells. • Nano-Ni led to HIF-1α nuclear accumulation and decreased mTOR phosphorylation. • HIF-1α may negatively regulate mTOR. • Nano-Ni-induced autophagy has a protective role against apoptosis via HIF-1α/mTOR signaling. [ABSTRACT FROM AUTHOR]

Silica-induced pulmonary fibrosis is a kind of worldwide occupational disease, and there is no effective treatment at present. Peptide therapy has attracted significant attention due to its simple structure, high selectiveness, strong bioactivity, relative safety, and high patient tolerance. In this study, we first confirmed that M10, a 10 amino acid peptide, has anti-fibrotic effects during the early and late stages of silica-induced fibrosis in mouse models and then partly explored the underlying mechanisms in vitro. M10 was detected in both the cell cytoplasm and nuclei. M10 showed no cytotoxicity to pulmonary epithelial cells and fibroblasts at the given concentrations. Functionally, M10 can reverse the silica-induced EMT process in epithelial cells and decrease TGF-β1-stimulated fibroblast activation. Further mechanism investigations supported that M10 can block TGF-β1 signalling by inhibiting phosphorylation of Smad2 protein in vitro and in vivo. All of the results indicate that M10 peptide may be a new method for the treatment of silica-induced pulmonary fibrosis. • M10 peptide prevents silica-induced pulmonary fibrosis in the early fibrotic stage. • M10 attenuates silica-induced pulmonary fibrosis in the late fibrotic stage. • M10 suppresses silica-induced EMT process of the pulmonary epithelial cells. • M10 inhibits TGF-β1-stimulated pulmonary fibroblast activation. • M10 downregulates the expression of phosphorylated Smad2 both in vitro and in vivo. [ABSTRACT FROM AUTHOR]