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.

We aimed to investigate whether exposure to low-molecular-weight saturated aliphatic aldehydes induces an airway inflammation related to lung toxicity. In previous studies, we identified that several aldehydes induced inflammatory responses through the secretion of pro-inflammatory cytokines.Here, we elucidate on whether hexanal exposure induces the lung inflammatory response through the secretion of cytokines. Hexanal is one of the aldehydes, which are major components of indoor environmental irritants. Based on a multiplexed cytokine antibody array, we investigated the cytokine expression profiles to identify the significant biomarkers of hexanal exposure and to predict the possibility of adverse effects on pulmonary toxicity using in vitro and in vivo model systems. We identified the cytokines as biomarkers involved in LEPTIN, Interleukin(IL)-10, MCP-1, and VEGF that showed similar expression patterns in both in vitro and in vivo models under hexanal exposure. These cytokines are known to be associated with diverse lung diseases, such as lung fibrosis, chronic obstructive pulmonary disease (COPD), and non-small cell lung cancer.Although further studies are needed to identify the mechanisms that underlie hexanal pulmonary toxicity, these results provide the key cytokine biomarkers in response to hexanal exposure and indicate meaningful mechanistic previewing that can be indirectly attributed to lung disease.

The current was conducted to evaluate the ameliorating effect of Chlorella vulgaris (CV) extract against sodium nitrite-induced hepatotoxicity in rats. Forty-five rats were allocated randomly into 5 groups (n = 9). Group I (GI), control group: orally gavaged with normal saline daily. Group II (GII): orally gavaged with CV extract (70 mg/kg BW) for 3 months. Group III (GIII): orally gavaged with sodium nitrite (80 mg/kg BW) for 3 months. Group IV (GIV): received sodium nitrite as GIII and CV extract as GII simultaneously for 3 months. Group V (GV): received CV extract as GII and then, sodium nitrite as in GIII from the end of first month until the end of the experiment. Sodium nitrite significantly increased the activities of serum alanine aminotransferase, aspartate aminotransferase, and serum concentrations of tumor interleukin 1-β and necrosis factor α. In addition, it increased concentrations of malondialdehyde and nitric oxide and expression level of caspase-3 in the hepatic tissue. However, it decreased activities of hepatic glutathione peroxidase, catalase, and superoxide dismutase and induced degenerative and necrotic changes in hepatic tissues. In contrast, CV extract administration modulated sodium nitrite-induced inflammation, oxidative stress, and alteration in hepatic tissue function and architecture. This study indicated that CV extract modulated sodium nitrite-induced hepatic toxicity through decreasing oxidative stress and inflammation and enhancing antioxidant enzyme activities in hepatic tissue of rats.

In the current report, we examined the potential beneficial role of soursop fruit extract (SSFE) on liver injury induced by a single paracetamol (APAP) overdose (2000 mg/kg). Thirty-five Wistar albino rats were randomly divided into five groups as follows: control, SSFE, APAP, SSFE+APAP, and silymarin (SIL)+APAP. APAP intoxication was found to elevate alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels. Moreover, it increased the levels of malondialdehyde, nitrites, and nitrates and depleted glutathione, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. APAP intoxication inactivated the nuclear factor erythroid 2-related factor 2 (Nrf2) defense pathway and upregulated the expression of heme oxygenase-1 (HO-1). APAP administration enhanced the activation of nuclear factor-kappa B (NF-κB), the elevation of tumor necrosis factor-alpha and interleukin 1-beta levels, and the upregulation of inducible nitric oxide synthase mRNA expression. In addition, APAP activated the overexpression of Bax protein, increased release of cytochrome c, and the downregulation of Bcl-2 protein. Finally, APAP-induced overexpression of transforming growth factor-beta (TGF-β) further suggested enhanced liver damage. On the other hand, SSFE pretreatment attenuated these biochemical, molecular, and histopathological alterations in the liver, which might be partially due to the regulation of hepatic Nrf2/HO-1 and downregulation of NF-κB and TGF-β.

Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions. Air pollutions in Lanzhou and Lintao, Gansu Province, were measured from December 2015 to June 2016. Healthy children were recruited from both cities and enrolled in this pilot study. Demographic information was collected by questionnaires. Blood samples were collected. Peripheral blood Treg cells were analyzed for Treg cells percentage by flow cytometry. Gene expression of forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), and interleukin 35 (IL35) were examined by reverse transcription-polymerase chain reaction (RT-PCR). The results indicated PAH concentration (as sum of 16 PAHs) in Lintao was over two times higher than that was in Lanzhou (707 vs. 326 ng/m³), whereas PM₂.₅ concentration was comparable in two cities (55.3 in Lintao vs. 65.7 μg/m³ in Lanzhou). Notably, we observed lower gene expressions for Foxp3 (P < 0.05), IL35 (P < 0.05), and TGF-β, in children living in Lintao, suggesting an impairment of Treg cells function potentially associated with higher PAH exposure in Lintao. However, no significant difference was observed in Treg cells % among CD4⁺ T cells between Lanzhou and Lintao groups.

Endosulfan, a persistent organic pollutant, is widely used in agriculture as a pesticide. The aim of the present study was to evaluate the blood toxicity of different doses of endosulfan in Wistar rats. The experimental sample was composed of four groups, a control group that did not receive endosulfan and three endosulfan-exposed groups that respectively received 1, 5, or 10 mg/kg/day (doses below LD₅₀), of endosulfan for 21 days. The results showed that endosulfan significantly decreased the prothrombin time (PT) and upregulated the activated coagulation factors VIIa, Xa, and XIIIa; thrombin-antithrombin complex (TAT); and P-selectin. Plasma levels of tissue factor (TF) and malondialdehyde (MDA) were increased in the endosulfan groups. The activated partial thromboplastin time (APTT) and the level of activated coagulation factor IXa showed no obvious changes. Immunohistochemical results showed increased expression of von Willebrand factor (vWF) and the inflammatory cytokine interleukin (IL)-1β in the groups exposed to endosulfan. The pathology and electron microscopy results showed impaired vascular tissue accompanied by the exfoliation of endothelial cells and mitochondrial damage in the endosulfan-exposed groups. In summary, our results suggest that endosulfan damages endothelial cells via oxidative stress and the inflammatory response, leading to the release of TF and vWF into the blood. The TF and vWF in the blood may activate extrinsic coagulation factors and platelets, thus triggering the extrinsic coagulation pathway. There were no obvious effects on the intrinsic coagulation pathway.