Inhalation exposure to fine particulate matter (PM₂.₅) represents a global concern due to the adverse effects in human health. In the last years, scientific community has been adopted the assessment of the PM₂.₅-bound pollutant fraction that could be released (bioaccessible fraction) in simulated lung fluids (SLFs) to achieve a better understanding of PM risk assessment and toxicological studies. Thus, bioaccessibility of 49 organic pollutants, including 18 polycyclic aromatic hydrocarbons (PAHs), 12 phthalate esters (PAEs), 11 organophosphorus flame retardants (OPFRs), 6 synthetic musk compounds (SMCs) and 2 bisphenols in PM₂.₅ samples was evaluated. The proposed method consists of a physiologically based extraction test (PBET) by using artificial lysosomal fluid (ALF) to obtain bioaccessible fractions, followed by a vortex-assisted liquid-liquid microextraction (VALLME) and a final analysis by programmed temperature vaporization-gas chromatography-tandem mass spectrometry (PTV-GC-MS/MS). The highest inhalation bioaccessibility ratio was found for bisphenol A (BPA) with an average of 83%, followed by OPFRs, PAEs and PAHs (with average bioaccessibilities of 68%, 41% and 34%, respectively). Correlations between PM₂.₅ composition (major ions, trace metals, equivalent black carbon (eBC) and UV-absorbing particulate matter (UVPM)) and bioaccessibility ratios were also assessed. Principal Component Analysis (PCA) suggested that PAHs, PAES and OPFRs bioaccessibility ratios could be positively correlated with PM₂.₅ carbonaceous content. Furthermore, both inverse and positive correlations on PAHs, PAEs and OPFRs bioaccessibilites could be accounted for some major ions and metal (oid)s associated to PM₂.₅, whereas no correlations comprising considered PM₂.₅ major ions and metal (oid)s contents and BPA bioaccessibility was observed. In addition, health risk assessment of target PM₂.₅-associated PAHs via inhalation was assessed in the study area considering both total and bioaccessible concentrations, being averaged human health risks within the safe carcinogenic and non-carcinogenic levels.

Fine particulate matter 2.5 (PM2.5) exposure leads to the progress of pulmonary disease. It has been reported that N6-methyladenosine (m6A) modification was involved in various biological processes and diseases. However, the critical role of m6A modification in pulmonary disease during PM2.5 exposure remains elusive. Here, we revealed that lung inflammation and mucus production caused by PM2.5 were associated with m6A modification. Both in vivo and in vitro assays demonstrated that PM2.5 exposure elevated the total level of m6A modification as well as the methyltransferase like 3 (METTL3) expression. Integration analysis of m6A RNA immunoprecipitation-seq (meRIP-seq) and RNA-seq discovered that METTL3 up-regulated the expression level and the m6A modification of Interleukin 24 (IL24). Importantly, we explored that the stability of IL24 mRNA was enhanced due to the increased m6A modification. Moreover, the data from qRT-PCR showed that PM2.5 also increased YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) expression, and the up-regulated YTHDF1 augmented IL24 mRNA translation efficiency. Down-regulation of Mettl3 reduced Il24 expression and ameliorated the pulmonary inflammation and mucus secretion in mice exposed to PM2.5. Taken together, our finding provided a comprehensive insight for revealing the significant role of m6A regulators in the lung injury via METTL3/YTHDF1-coupled epitranscriptomal regulation of IL24.

Size segregated samples (<0.49, 0.49–0.95, 0.95–1.5, 1.5–3.0, 3.0–7.2 and > 7.2 μm) of atmospheric particulate matter (APM) were collected at a traffic site in the urban agglomeration of Thessaloniki, northern Greece, during the cold and the warm period of 2020. The solvent-extractable organic matter was analyzed for selected organic contaminants including polycyclic aromatic hydrocarbons (PAHs), and their nitro- and oxy-derivarives (NPAHs and OPAHs, respectively). Mean concentrations of ∑₁₆PAHs, ∑₆NPAHs and ∑₁₀OPAHs associated to total suspended particles (TSP) were 18 ng m⁻³, 0.2 ng m⁻³ and 0.9 ng m⁻³, respectively, in the cold period exhibiting significant decrease (6.4, 0.2 and 0.09 ng m⁻³, respectively) in the warm period. The major amount of all compounds was found to be associated with the alveolar particle size fraction <0.49 μm. The inhalation bioaccessibility of PAHs and O/N PAHs was measured in vitro using two simulated lung fluids (SLFs), the Gamble's solution (GS) and the artificial lysosomal fluid (ALF). With both SLFs, the derived bioaccessible fractions (BAFs) followed the order PAHs > OPAHs > NPAHs. Although no clear dependence of bioaccessibility on particle size was obtained, increased bioaccessibility of PAHs and PAH derivatives in coarse particles (>7.2 μm) was evident. Bioaccessibility was found to be strongly related to the logKOW and the water solubility of individual compounds hindering limited mobilization of the most hydrophobic and less water-soluble compounds from APM to SLFs. The lifetime cancer risk due to inhalation exposure to bioaccessible PAHs, NPAHs and OPAHs was estimated and compared to those calculated from the particulate concentrations of organic contaminants.

Air pollution exposure is a public health emergency, which attributes globally to an estimated seven million deaths on a yearly basis We are all exposed to air pollutants, varying from ambient air pollution hanging over cities to dust inside the home. It is a mixture of airborne particulate matter and gases that can be subdivided into three categories based on particle diameter. The smallest category called PM₀.₁ is the most abundant. A fraction of the particles included in this category might enter the blood stream spreading to other parts of the body. As air pollutants can enter the body via the lungs and gut, growing evidence links its exposure to gastrointestinal and respiratory impairments and diseases, like asthma, rhinitis, respiratory tract infections, Crohn's disease, ulcerative colitis, and abdominal pain. It has become evident that there exists a crosstalk between the respiratory and gastrointestinal tracts, commonly referred to as the gut-lung axis. Via microbial secretions, metabolites, immune mediators and lipid profiles, these two separate organ systems can influence each other. Well-known immunomodulators and gut health stimulators are probiotics, prebiotics, together called synbiotics. They might combat air pollution-induced systemic inflammation and oxidative stress by optimizing the microbiota composition and microbial metabolites, thereby stimulating anti-inflammatory pathways and strengthening mucosal and epithelial barriers. Although clinical studies investigating the role of probiotics, prebiotics, and synbiotics in an air pollution setting are lacking, these interventions show promising health promoting effects by affecting the gastrointestinal- and respiratory tract. This review summarizes the current data on how air pollution can affect the gut-lung axis and might impact gut and lung health. It will further elaborate on the potential role of probiotics, prebiotics and synbiotics on the gut-lung axis, and gut and lung health.

Silicosis is a disease mainly caused by pulmonary interstitial fibrosis caused by long-term inhalation of dust with excessively high content of free SiO₂. Transdifferentiation of lung fibroblasts into myofibroblasts is an important cellular basis for silicosis, but the key transcription factors (TFs) involved in this process are still unclear. In order to explore the biological regulation of transcription factor PPARγ/LXRα in silica-induced pulmonary fibrosis, this study explored the molecular mechanism of PPARγ/LXRα involved in regulating transcription factors related to SiO₂-induced lung injury at the cellular level and in animal models. ChIP-qPCR detected that PPARγ directly regulated the transcriptional activity of the LXRα gene promoter, while the PPARγ agonist RSG increased the expression of LXRα. In addition, we demonstrated in the cell model that upregulation of LXRα can inhibit silica-mediated fibroblast transdifferentiation, accompanied by an increase in the expression of SREBF1, PLTP and ABCA1. The results of LXRα silencing experiment matched those of overexpression experiment. These studies explored the role of LXRα in plasticity and phenotypic transformation between lung fibroblasts and myofibroblasts. Therefore, inhibiting or reversing the transdifferentiation of lung fibroblasts to myofibroblasts by intervening PPARγ/LXRα may provide a new therapeutic target for the treatment of silicosis.

Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1–100 μg/ml, 24–72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity.

The development of urbanised areas together with the growing transport infrastructure and traffic volume are the main cause of air quality deterioration due to the increasing concentrations of particulate matter. Dust pollution is a threat to human health. It can cause the development of lung, larynx or circulatory system cancer. Due to the ability to accumulate dust particles on the leaf surface, the contribution of trees in the process of phytoremediation of air pollution has started to be appreciated. An analysis of the elemental composition of particulate matter (PM) stored on the leaves surface was also carried out, which showed high average concentration of: C > O > Si > Fe (above 8wt.%). It was also observed single particles with a high concentration of heavy metals: Ti, Mn, Ba, Zn, Cr, Pb, Sn, Ni and REE (rare earth elements). The major origin of PM are vehicular emissions, soil and re-suspended road dust. This paper presents also a comparison of selected tree, shrub and vine species differing in their ability to accumulate particulate matter. It was experimentally determined the average leaf surface of individual plant species and established the amount of particulate matter with aerodynamic diameter between 10 and 100 μm, 2.5 and 10 μm, and 0.2 and 2.5 μm deposited on the leaf surface and in waxes.Some species of vines (Parthenocissus quinquefolia), shrubs (Forsythia x intermediata) and coniferous trees, such as Betula pendula ‘Youngii’, Quercus rubra, Cratageus monogyna, Acer pseduoplatanus, Tilia cordata Mill. or Platanus orientalis turned out to be the most efficient in the process of phylloremediation.

The number of deaths from air pollution worldwide is estimated at 8.8 million per year, more than the number of deaths from smoking. Air pollutants, such as PM₂.₅, are known to induce respiratory and cardiovascular diseases by inducing oxidative stress. Thioredoxin (Trx) is a 12-kDa endogenous protein that exerts antioxidant activity by promoting dithiol disulfide exchange reactions. We previously synthesized human serum albumin-fused thioredoxin (HSA-Trx), which has a longer half-life in plasma compared with Trx, and demonstrated its efficacy against various diseases including respiratory diseases. Here, we examined the effect of HSA-Trx on urban aerosol-induced lung injury in mice. Urban aerosols induced lung injury and inflammatory responses in ICR mice, but intravenous administration of HSA-Trx markedly inhibited these responses. We next analyzed reactive oxygen species (ROS) production in murine lungs using an in vivo imaging system. The results show that intratracheal administration of urban aerosols induced ROS production that was inhibited by intravenously administered HSA-Trx. Finally, we found that HSA-Trx inhibited the urban aerosol-induced increase in levels of neutrophilic extracellular trap (NET) indicators (i.e., double-stranded DNA, citrullinated histone H3, and neutrophil elastase) in bronchoalveolar lavage fluid (BALF). Together, these findings suggest that HSA-Trx prevents urban aerosol-induced acute lung injury by suppressing ROS production and neutrophilic inflammation. Thus, HSA-Trx may be a potential candidate drug for preventing the onset or exacerbation of lung injury caused by air pollutants.

Arsenic is a potent toxicant, and long-term exposure to inorganic arsenic causes lung damage. M2 macrophages play an important role in the pathogenesis of pulmonary fibrosis. However, the potential connections between arsenic and M2 macrophages in the development of pulmonary fibrosis are elusive. C57BL/6 mice were fed with drinking water containing 0, 10 and 20 ppm arsenite for 12 months. We have found that, in lung tissues of mice, arsenite, a biologically active form of arsenic, elevated H19, c-Myc, and Arg1; decreased let-7a; and caused pulmonary fibrosis. For THP-1 macrophages (THP-M) and bone-marrow-derived macrophages (BMDMs), 8 μM arsenite increased H19, c-Myc, and Arg1; decreased let-7a; and induced M2 polarization of macrophages, which caused secretion of the fibrogenic cytokine, TGF-β1. Down-regulation of H19 or up-regulation of let-7a reversed the arsenite-induced M2 polarization of macrophages. Arsenite-treated THP-M and BMDMs co-cultured with MRC-5 cells or primary lung fibroblasts (PLFs) elevated levels of p-SMAD2/3, SMAD4, α-SMA, and collagen I in lung fibroblasts and resulted in the activation of lung fibroblasts. Knockout of H19 or up-regulation of let-7a in macrophages reversed the effects. The results indicated that H19 functioned as an miRNA sponge for let-7a, which was involved in arsenite-induced M2 polarization of macrophages and induced the myofibroblast differentiation phenotype by regulation of c-Myc. In the sera of arseniasis patients, levels of hydroxyproline and H19 were higher, and levels of let-7a were lower than levels in the controls. These observations elucidate a possible mechanism for arsenic exposure-induced pulmonary fibrosis.

Indium tin oxide (ITO) is an important semiconductor material, because of increasing commercial products consumption and potentially exposed workers worldwide. So, urgently we need to assess and manage potential health risks of ITO. Although the Occupational Exposure Limit (OEL) has been established for ITO exposure, there is still a lack of distinguishing the risks of exposure to particles of different sizes. Therefore, obtaining toxicological data of small-sized particles will help to improve its risk assessment data. Important questions raised in quantitative risk assessments for ITO particles are whether biodistribution of ITO particles is affected by particle size and to what extent systematic adverse responses is subsequently initiated. In order to determine whether this toxicological paradigm for size is relevant in ITO toxic effect, we performed comparative studies on the toxicokinetics and sub-acute toxicity test of ITO in mice. The results indicate both sized-ITO resided in the lung tissue and slowly excreted from the mice, and the smaller size of ITO being cleared more slowly. Only a little ITO was transferred to other organs, especially with higher blood flow. Two type of ITO which deposit in the lung mainly impacts respiratory system and may injure liver or kidney. After sub-acute exposure to ITO, inflammation featured by neutrophils infiltration and fibrosis with both dose and size effects have been observed. Our findings revealed toxicokinetics and dose-dependent pulmonary toxicity in mice via oropharyngeal aspiration exposure, also replenish in vivo risk assessment of ITO. Collectively, these data indicate that under the current OEL, there are potential toxic effects after exposure to the ITO particles. The observed size-dependent biodistribution patterns and toxic effect might be important for approaching the hazard potential of small-sized ITO in an occupational environment.