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Methylmercury (MeHg) is an environmental neurotoxic substance, which can easily cross the blood–brain barrier, causing irreversible damage to the human central nervous system. Reactive oxygen species (ROS) are involved in various ways of intracellular physiological or pathological processes including neuronal apoptosis. This study attempted to explore the role of ROS‐mediated poly ADP‐ribose polymerase (PARP)/apoptosis‐inducing factor (AIF) apoptosis signaling pathway in the process of MeHg‐induced cell death of human neuroblastoma cells (SH‐SY5Y). Here, we found that SH‐SY5Y cells underwent apoptosis in response to MeHg, which was accompanied by the increased levels of ROS and calcium ion, and the activation of caspase cascades and PARP. Inhibiting the production of ROS can reduce the apoptosis rate to a certain extent. PARP/AIF apoptotic pathway is independent of caspase dependent signaling pathway and regulates it. In conclusion, these results suggest that ROS mediated activation of caspase pathway and PARP/AIF signaling pathway are involved in MeHg induced apoptosis, and these two pathways interact with each other. [ABSTRACT FROM AUTHOR]

The mechanism of the sterile inflammatory response in the respiratory tract induced by exposure to sterile particles has not been fully elucidated. The aim of our study is to explore the earlier events in initiating inflammatory response at molecular and cellular level in primary cultured human airway epithelial cells (AEC) exposed to silica particles in order to provide information for earlier diagnosis and prevention of silica particle‐induced toxicity as well as possible information on the genesis of silicosis. We isolated primary AEC from three healthy adults and treated them with silica particles at different concentrations for 48 h. We found evidence for silica‐induced inflammasome activation by the co‐localization of Caspase‐1 and NLRP3, as well as increased levels of IL‐1β and IL‐18. Lactate dehydrogenase and NucGreen analysis proved the occurrence of pyroptosis. High throughput mRNA sequencing showed that the inflammatory response and NF‐κB signaling pathways were significantly enriched in gene ontology and Kyoto encyclopedia of genes and genomes analysis, and pyroptosis‐related genes were up‐regulated. The miR‐455‐3p and five lncRNAs (LOC105375913, NEAT1, LOC105375181, LOC100506098, and LOC105369370) were verified as key factors related to the mechanism by ceRNA network analysis. LOC105375913 was first discovered to be associated with inflammation in AEC. These data suggest that microcrystalline silica can induce significant inflammation and pyroptosis in human primary AEC through NLRP3 inflammasome pathway and NF‐κB signaling pathway at both the gene and protein levels, and the possible mechanism could be miR‐455‐3p mediated ceRNA hypothesis. Our data provide a method for the studies of the respiratory toxicity of fine particulate matter and the pathogenesis of early silicosis. The miR‐455‐3p and five lncRNAs related ceRNA network might be the toxicity mechanism of microcrystalline silica particles to AEC. [ABSTRACT FROM AUTHOR]

The application of silica nanoparticles (SiNPs) in areas of agriculture and medicine has raised great concerns for the potential adverse effects of SiNPs. The increasing toxicological studies focused mainly on the lung and cardiovascular system, but the adverse effects of SiNPs on nervous system have not been well explored. This study aimed to evaluate the role and mechanism of unfolded protein reaction (UPR) in SiNPs‐induced cell injury on nerve cells in vitro. We investigated the UPR‐mediated apoptosis caused by SiNPs in human neuroblastoma (SH‐SY5Y) cell line. The size of SiNPs and its effect on cell ultrastructure were observed by transmission electron microscopy (TEM). Cell growth, mitochondrial membrane potential (MMP), calcium ion (Ca2+), apoptosis rate, and the expression level of related proteins were evaluated using MTT, flow cytometry, and western blot in SH‐SY5Y cells exposed to SiNPs. The results showed that with the increase of SiNPs concentration, cell viability decreased, MMP decreased, active oxygen (ROS), and Ca2+ levels increased in a dose‐dependent manner. In addition, protein expression of PERK, GRP78, and other related proteins in the unfolded protein response increased in a dose‐response manner together with the expression of apoptosis proteins. Conclusively, this study confirmed that SiNPs can affect the neural system by interfering structure and functional and inducing apoptosis in nerve cells through unfolded protein response. [ABSTRACT FROM AUTHOR]

As a consequence of recent progression in biomedicine and nanotechnology, nanomedicine has emerged rapidly as a new discipline with extensive application of nanomaterials in biology, medicine, and pharmacology. Among the various nanomaterials, silica nanoparticles (SNPs) are particularly promising in nanomedicine applications due to their large specific surface area, adjustable pore size, facile surface modification, and excellent biocompatibility. This paper reviews the synthesis of SNPs and their recent usage in drug delivery, biomedical imaging, photodynamic and photothermal therapy, and other applications. In addition, the possible adverse effects of SNPs in nanomedicine applications are reviewed from reported in vitro and in vivo studies. Finally, the potential opportunities and challenges for the future use of SNPs are discussed. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]