There are many hypotheses about the mechanism of the emission of fine particulate EPFRs, including oxidative damage, inflammatory damage and mitochondrial damage 37. The smoke from burning tobacco also has health effects. Oxidative damage refers to a series of reactions in which EPFRs formed on the surface of fine particles enter the cell, stimulating the body to produce a large amount of ROS, destroying the body's redox equilibrium state 9, 38, thereby causing lipid peroxidation of the cell membrane, accelerating protein hydrolysis or damage oxidation, resulting in cell damage and even apoptosis 10. Inflammatory injury means that the body stimulates the transcription level of related inflammatory factors in the body under external stimulation, thereby inducing inflammatory cells to produce many inflammatory factors or adhesion factors. Such as interleukins, interferons, growth factors, tumor necrosis factors, etc., the body producing inflammatory response and ultimately cause inflammatory damage 39, 40.
Inflammation is a common pathological process in the clinic. It can be produced in tissues and organs of various parts of the body, such as pneumonia, hepatitis, and nephritis 41–43. The production of inflammation is essentially a reflection of the body's resistance to inflammatory factors. This divergence struggles throughout the inflammatory process. After acting on the body, the inflammatory factor causes damage to the tissue cells, causing local tissue cells to show degeneration and necrosis. On the other hand, it induces an increase in the body's resistance to disease, which is beneficial to clearing the inflammatory factors and repairing the damaged tissue 44. The fine particles enter the bronchus, causing the body to produce excessive inflammatory factors, breaking this balance and causing a series of adverse reactions. The fine particles exposed below PM10 are related to the poor health of human body, which will lead to respiratory diseases such as chronic obstructive pulmonary disease and asthma 45. Study have verified that short term exposure to concentrations below the EPA standard (PM2.5 < 12 ug/m3) can lead to decreased lung function 46. Long-term exposure to particulate matter below PM10 is associated with the occurrence and mortality of lung diseases, and the incidence increases with the longer exposure time 47.
At present, there are also some studies on the regulatory effect between the relevant environmental fine particles and miRNA in human disease. Studies have found that the longer exposure to PM2.5, the more it can inhibit the expression of some miRNAs (miR-21-5p, miR-187-3p, miR-1-3p, miR-146a-5p and miR-199a-5p) and promote the expression of inflammatory factors such as IL1 and TNF 48. Zhang et al. demonstrated that when HBE cells are exposed to PM2.5, miR-382-5p triggers lung inflammation through the targeting relationship with CXCL12 49. Li et al. showed that overexpression of miR-224 inhibited the airway epithelial cell inflammation and airway remodeling induced by PM2.5 in asthmatic mice by reducing the expression of TLR2 50. However, more in-depth studies are needed on the potential biological mechanisms between exposure to air pollutants and miRNA, exploring the role of miRNA in PM2.5 between normal and cancer cells.
In this study, we used Zinc Oxide (ZnO) as raw material, respectively pumped in chlorobenzene (MCB) gas, synthesis of the persistent free radicals (ZnO/MCB) in vitro and in vivo. In vitro experiment, normal lung cells (BEAS-2B) and lung cancer cells (H1299 and A549) as the research object, researched the cell toxicity difference and its precursor mechanism between ZnO and ZnO-EPFRs. In vivo experiments, BALB/c mice as the research object, explore the chronic toxicity difference between ZnO and ZnO-EPFRs.
In conclusion, our findings have showed that ZnO/MCB EPFRs promote cell proliferation and migration, impedes cell apoptosis in NSCLC. ZnO/MCB EPFRs make the expression of miR-18a up-regulate and down-regulates the expression of miR-34a. Besides, exposure to ZnO/MCB EPFRs in NSCLC, miR-18a promotes cell proliferation. Furthermore, our results showed that the EPFRs reduce the body weight and survival rate of male mice was greater than female mice in vivo experiments, which also caused lung lesions. Overall, our findings provide evidence for assessing the potential health risks of persistent free radicals on fine particles within the regulation network (Fig. 5). Nevertheless, fine particulate stimulation of the body's production and secretion of chemokines and cytokines are important steps in inflammatory damage, and their combination can affect the strength of the inflammatory response.