Particulate matter, polycyclic aromatic hydrocarbons and metals, platelet parameters and blood pressure alteration: Multi-pollutants study among population.

Epidemiological findings have determined the linkage of fine particulate matter (PM2.5) and the morbidity of hypertension. However, the mode of action and specific contribution of PM2.5 component in the blood pressure elevation remain unclear. Platelets are critical for vascular homeostasis and thrombosis, which may be involved in the increase of blood pressure. Among 240 high-PM2.5 exposed, 318 low-PM2.5 exposed workers in a coking plant and 210 workers in the oxygen plant and cold-rolling mill enrolled in present study, both internal and external exposure characteristics were obtained, and we performed linear regression, adaptive elastic net regression, quantile g-computation and mediation analyses to analyze the relationship between urine metabolites of polycyclic aromatic hydrocarbons (PAHs) and metals fractions with platelets indices and blood pressure indicators. We found that PM2.5 exposure leads to increased systolic blood pressure (SBP) and pulse pressure (PP). Specifically, for every 10 µg/m3 increase in PM2.5, there was a 0.09 mmHg rise in PP. Additionally, one IQR increase in urinary 1-hydroxypyrene (1.06 µmol/mol creatinine) was associated with a 3.43 % elevation in PP. Similarly, an IQR increment of urine cobalt (2.31 µmol/mol creatinine) was associated with a separate 1.77 % and 4.71 % elevation of SBP and PP. Notably, platelet-to-lymphocyte ratio (PLR) played a mediating role in the elevation of SBP and PP induced by cobalt. Our multi-pollutants results showed that PAHs and cobalt were deleterious contributors to the elevated blood pressure. These findings deepen our understanding of the cardiovascular effects associated with PM2.5 constituents, highlighting the importance of increased vigilance in monitoring and controlling the harmful components in PM2.5.

Proteomics revealed composition- and size-related regulators for hepatic impairments induced by silica nanoparticles.

Along with the growing production and application of silica nanoparticles (SiNPs), increased human exposure and ensuing safety evaluation have progressively attracted concern. Accumulative data evidenced the hepatic injuries upon SiNPs inhalation. Still, the understanding of the hepatic outcomes resulting from SiNPs exposure, and underlying mechanisms are incompletely elucidated. Here, SiNPs of two sizes (60 nm and 300 nm) were applied to investigate their composition- and size-related impacts on livers of ApoE-/- mice via intratracheal instillation. Histopathological and biochemical analysis indicated SiNPs promoted inflammation, lipid deposition and fibrosis in the hepatic tissue, accompanied by increased ALT, AST, TC and TG. Oxidative stress was activated upon SiNPs stimuli, as evidenced by the increased hepatic ROS, MDA and declined GSH/GSSG. Of note, these alterations were more dramatic in SiNPs with a smaller size (SiNPs-60) but the same dosage. LC-MS/MS-based quantitative proteomics unveiled changes in mice liver protein profiles, and filtered out particle composition- or size-related molecules. Interestingly, altered lipid metabolism and oxidative damage served as two critical biological processes. In accordance with correlation analysis and liver disease-targeting prediction, a final of 10 differentially expressed proteins (DEPs) were selected as key potential targets attributable to composition- (4 molecules) and size-related (6 molecules) liver impairments upon SiNPs stimuli. Overall, our study provided strong laboratory evidence for a comprehensive understanding of the harmful biological effects of SiNPs, which was crucial for toxicological evaluation to ensure nanosafety.

Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress.

The metabolic associated fatty liver disease (MAFLD) is a public health challenge, leading to a global increase in chronic liver disease. The respiratory exposure of silica nanoparticles (SiNPs) has revealed to induce hepatotoxicity. However, its role in the pathogenesis and progression of MAFLD was severely under-studied. In this context, the hepatic impacts of SiNPs were investigated in vivo and in vitro through using ApoE-/- mice and free fatty acid (FFA)-treated L02 hepatocytes. Histopathological examinations and biochemical analysis showed SiNPs exposure via intratracheal instillation aggravated hepatic steatosis, lipid vacuolation, inflammatory infiltration and even collagen deposition in ApoE-/- mice, companied with increased hepatic ALT, AST and LDH levels. The enhanced fatty acid synthesis and inhibited fatty acid ß-oxidation and lipid efflux may account for the increased hepatic TC/TG by SiNPs. Consistently, SiNPs induced lipid deposition and elevated TC in FFA-treated L02 cells. Further, the activation of hepatic oxidative stress was detected in vivo and in vitro, as evidenced by ROS accumulation, elevated MDA, declined GSH/GSSG and down-regulated Nrf2 signaling. Endoplasmic reticulum (ER) stress was also triggered in response to SiNPs-induced lipid accumulation, as reflecting by the remarkable ER expansion and increased BIP expression. More importantly, an UPLC-MS-based metabolomics analysis revealed that SiNPs disturbed the hepatic metabolic profile in ApoE-/- mice, prominently on amino acids and lipid metabolisms. In particular, the identified differential metabolites were strongly correlated to the activation of oxidative stress and ensuing hepatic TC/TG accumulation and liver injuries, contributing to the progression of liver diseases. Taken together, our study showed SiNPs promoted hepatic steatosis and liver damage, resulting in the aggravation of MAFLD progression. More importantly, the disturbed amino acids and lipid metabolisms-mediated oxidative stress was a key contributor to this phenomenon from a metabolic perspective.

Trend Analysis of Occupational Lung Cancer from Coke Oven Emission Exposure - China, 2008-2019.

What is already known about this topic?: Coke oven emissions are a complex mixture of particulate matter and gases, some with carcinogenicity, released during coke production. Lung cancer caused by coke oven emissions has been listed as a statutory occupational cancer in China and many countries. What is added by this report?: In this study, coke oven emissions-induced lung cancer was mainly found in the manufacturing industries. Coke oven workers exposed to higher levels of polycyclic aromatic hydrocarbons in different workplaces had a high risk of occupational lung cancer. What are the implications for public health practice?: It is necessary to take efforts to greatly reduce emissions from coke production and effectively monitor the health of workers.

Lysosomal impairment-mediated autophagy dysfunction responsible for the vascular endothelial apoptosis caused by silica nanoparticle via ROS/PARP1/AIF signaling pathway.

Understanding the underlying interactions of nanoparticles (NPs) with cells is crucial to the nanotoxicological research. Evidences suggested lysosomes as a vital target upon the accumulation of internalized NPs, and lysosomal damage and autophagy dysfunction are emerging molecular mechanisms for NPs-elicited toxicity. Nevertheless, the interaction with lysosomes, ensuing adverse effects and the underlying mechanisms are still largely obscure, especially in NPs-induced vascular toxicity. In this study, silica nanoparticles (SiNPs) were utilized to explore the adverse effects on lysosome in vascular endothelial cells by using in vitro cultured human endothelial cells (HUVECs), and in-depth investigated the mechanisms involved. Consequently, the internalized SiNPs accumulated explicitly in the lysosomes, and caused lysosomal dysfunction, which were prominent on the increased lysosomal membrane permeability, decline in lysosomal quantity, destruction of acidic environment of lysosome, and also disruption of lysosomal enzymes activities, resulting in autophagy flux blockage and autophagy dysfunction. More importantly, mechanistic results revealed the SiNPs-caused lysosomal impairments and resultant autophagy dysfunction could promote oxidative stress, DNA damage and the eventual cell apoptosis activated by ROS/PARP1/AIF signaling pathway. These findings improved the understanding of SiNPs-induced vascular injury, and may provide novel information and warnings for SiNPs applications in the fields of nanomedicine.

Oxidative stress- and mitochondrial dysfunction-mediated cytotoxicity by silica nanoparticle in lung epithelial cells from metabolomic perspective.

Quantities of researches have demonstrated silica nanoparticles (SiNPs) exposure inevitably induced damage to respiratory system, nonetheless, knowledge of its toxicological behavior and metabolic interactions with the cellular machinery that determines the potentially deleterious outcomes are limited and poorly elucidated. Here, the metabolic responses of lung bronchial epithelial cells (BEAS-2B) under SiNPs exposure were investigated using ultra performance liquid chromatography-mass spectrum (UPLC-MS)-based metabolomics research. Results revealed that even with low cytotoxicity, SiNPs disturbed global metabolism. Five metabolic pathways were significantly perturbed, in particular, oxidative stress- and mitochondrial dysfunction-related GSH metabolism and pantothenate and coenzyme A (CoA) biosynthesis, where the identified metabolites glutathione (GSH), glycine, beta-alanine, cysteine, cysteinyl-glycine and pantothenic acid were included. In support of the metabolomics profiling, SiNPs caused abnormality in mitochondrial structure and mitochondrial dysfunction, as evidenced by the inhibition of cellular respiration and ATP production. Moreover, SiNPs triggered oxidative stress as confirmed by the dose-dependent ROS generation, down-regulated nuclear factor erythroid 2-related factor 2 (NRF2) signaling, together with GSH depletion in SiNPs-treated BEAS-2B cells. Oxidative DNA damage and cell membrane dis-integrity were also detected in response to SiNPs exposure, which was correspondingly in agreed with the elevated 8-hydroxyguanosine (8-OHdG) and decreased phospholipids screened through metabolic analysis. Thereby, we successfully used the metabolomics approaches to manifest SiNPs-elicited toxicity through oxidative stress, mitochondrial dysfunction, DNA damage and rupture of membrane integrity in BEAS-2B cells. Overall, our study provided novel insights into the mechanism underlying SiNPs-induced pulmonary toxicity.

Disturbed mitochondrial quality control involved in hepatocytotoxicity induced by silica nanoparticles.

The extensive application of silica nanoparticles (SiNPs) brings about inevitable occupational, environmental, and even iatrogenic exposure for human beings. The liver, which is rich in mitochondria, is one of the target organs of SiNPs, but the underlying mechanisms by which these nanoparticles (NPs) interact with liver mitochondria and affect their functions still remain unclear. In the present study, we examined silicon nanoparticle (SiNP)-induced mitochondrial dysfunction, and further revealed its negative effects on mitochondrial quality control (MQC) in the human liver cell line L-02, including mitochondrial dynamics, mitophagy and biogenesis. Consequently, SiNPs induced cellular injury, accompanied by mitochondrial dysfunction, including mitochondrial reactive oxygen generation and mitochondrial membrane potential collapse. In line with the transmission electron microscopy (TEM)-observed abnormalities in the mitochondrial morphology and length distribution, a fission phenotype was manifested in the mitochondria of SiNP-exposed cells, and up-regulated DRP1 and FIS1, and down-regulated MFN1, were detected. Furthermore, the enhanced LC3II level, colocalization of the mitochondria and lysosomes, activated PINK1/Parkin signaling, and accumulated p62 in the SiNP-exposed cells suggested mitophagy disorder triggered by SiNPs. In addition, SiNPs inhibited mito-biogenesis, as evidenced by the reduced mitochondrial mass and mtDNA copy number, as well as the suppressed PGC1α-NRF1-TFAM signaling pathway. Overall, the study demonstrates that SiNPs trigger hepatocytotoxicity through interfering with the MQC process, bringing in excessive mitochondrial fission, mitophagy disorder and suppressed mito-biogenesis, leading to mitochondrial dysfunction and ensuing cell damage, and ultimately contributing to the occurrence and development of liver diseases. Our research could provide important experimental evidence related to safety assessments of SiNPs, especially in the field of biomedical applications.

PM2.5 triggered apoptosis in lung epithelial cells through the mitochondrial apoptotic way mediated by a ROS-DRP1-mitochondrial fission axis.

Epidemiological studies revealed a sharp increase in respiratory diseases attributed to PM2.5. However, the underlying mechanisms remain unclear. Evidence suggested mitochondrion as a sensitive target upon the stimulus of PM2.5, and the centrality in the pathological processes and clinical characterization of lung diseases. To investigate cell fate and related mechanisms caused by PM2.5, we exposed human lung epithelial cells (BEAS-2B) to PM2.5 (0-100 µg/mL). Consequently, PM2.5 components were found in cytoplasm, and morphological and functional alterations in mitochondria occurred, as evidenced by loss of cristae, vacuolization and even the outer mitochondrial membrane rupture, mitochondrial membrane potential collapse, enhanced reactive oxygen species (ROS)/mtROS level, calcium overload, suppressed cellular respiration and ATP production in PM2.5-treated cells. Further, disturbed dynamics toward fission was clearly observed in PM2.5-treated mitochondria, associated with DRP1 mitochondrial translocation and phosphorylation. Besides, PM2.5 induced mitochondria-mediated apoptosis. More importantly, mechanistic results revealed ROS- and DRP1-mediated mitochondrial fission in a reciprocal way, and DRP1 inhibitor (Mdivi-1) significantly alleviated the pro-apoptotic effect of PM2.5 through reversing the activated mitochondrial apoptotic pathway. In summary, our results firstly revealed PM2.5 induced apoptosis in lung epithelial cells through a ROS-DRP1-mitochodrial fission axis-mediated mitochondrial apoptotic pathway, ultimately contributing to the onset and development of pulmonary diseases.