The effects of air pollution on health have been generating attention for years. A large number of pulmonologists have recently expressed concerns about this in an open letter to Dutch Members of Parliament. Air pollution arises mainly in all kinds of combustion processes; in addition, atmospheric chemical reactions play a role in the formation of ozone and particulate matter. Health effects are both acute (increase in daily mortality and morbidity after days with increased concentrations of air pollution) as well as chronic (shortened life span and increased incidence of respiratory and cardiovascular diseases in areas with elevated concentrations of air pollution). These effects already occur at concentrations that are clearly lower than those currently observed in the Netherlands.

Air pollution and health

Asthma is a chronic inflammatory disease of the airway with extensive airway remodeling. The ethical issues associated with the studies in asthmatic patients, required development of animal model of asthma. Animal models of asthma can provide valuable information on several features of asthma pathogenesis and treatment. Although these models cannot carry out all clinical features, they are valuable to understand mechanisms of the disease and curative access. Related articles were searched in different databases from September 1994 to April 2016 using; animal model of asthma, animal sensitization, allergen-induced asthma in animals terms. Although there are several reviews on this topic, in the present article, induction of animal model of asthma in different animals, various methods used for this purpose, measured parameters and research purposes were reviewed, which will help investigators to use the appropriate animal, methods, and evaluating parameters depending on their study design. In this study various method used for induction of animal model of asthma in different animals and measured parameters were described, which will help investigators to use the appropriate animal, method and evaluating parameters depending on their study design.

/pdf/animal-model-of-asthma-various-methods-and-measured-v8ufnd2lnw.pdf

Animal Model of Asthma, Various Methods and Measured Parameters: A Methodological Review

Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation

Air pollution has become one of the most serious issues for human health and has been shown to be particularly concerning for neural and cognitive health. Recent studies suggest that fine particulate matter of less than 2.5 (PM2.5), common in air pollution, can reach the brain, potentially resulting in the development and acceleration of various neurological disorders including Alzheimer's disease, Parkinson's disease, and other forms of dementia, but the underlying pathological mechanisms are not clear. Astaxanthin is a red-colored phytonutrient carotenoid that has been known for anti-inflammatory and neuroprotective effects. In this study, we demonstrated that exposure to PM2.5 increases the neuroinflammation, the expression of proinflammatory M1, and disease-associated microglia (DAM) signature markers in microglial cells, and that treatment with astaxanthin can prevent the neurotoxic effects of this exposure through anti-inflammatory properties. Diesel particulate matter (Sigma-Aldrich) was used as a fine particulate matter 2.5 in the present study. Cultured rat glial cells and BV-2 microglial cells were treated with various concentrations of PM2.5, and then the expression of various inflammatory mediators and signaling pathways were measured using qRT-PCR and Western blot. Astaxanthin was then added and assayed as above to evaluate its effects on microglial changes, inflammation, and toxicity induced by PM2.5. PM2.5 increased the production of nitric oxide and reactive oxygen species and upregulated the transcription of various proinflammatory markers including Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptor 2/4 (TLR2/4), and cyclooxygenase-2 (COX-2) in BV-2 microglial cells. However, the mRNA expression of IL-10 and arginase-1 decreased following PM2.5 treatment. PM2.5 treatment increased c-Jun N-terminal kinases (JNK) phosphorylation and decreased Akt phosphorylation. Astaxanthin attenuated these PM2.5-induced responses, reducing transcription of the proinflammatory markers iNOS and heme oxygenase-1 (HO-1), which prevented neuronal cell death. Our results indicate that PM2.5 exposure reformulates microglia via proinflammatory M1 and DAM phenotype, leading to neurotoxicity, and the fact that astaxanthin treatment can prevent neurotoxicity by inhibiting transition to the proinflammatory M1 and DAM phenotypes. These results demonstrate that PM2.5 exposure can induce brain damage through the change of proinflammatory M1 and DAM signatures in the microglial cells, as well as the fact that astaxanthin can have a potential beneficial effect on PM2.5 exposure of the brain.

https://www.mdpi.com/1422-0067/21/19/7227/pdf

Astaxanthin Suppresses PM2.5-Induced Neuroinflammation by Regulating Akt Phosphorylation in BV-2 Microglial Cells.

Circular RNA 406961 interacts with ILF2 to regulate PM2.5-induced inflammatory responses in human bronchial epithelial cells via activation of STAT3/JNK pathways.

Fine particulate matter (PM2.5) aggravates apoptosis of cigarette-inflamed bronchial epithelium in vivo and vitro

Identification of long non-coding RNA and circular RNA in mice after intra-tracheal instillation with fine particulate matter.

Background: Fine particulate matter (PM2.5) exposure is proved to be associated with illnesses, but the mechanism is not clear. Potential effects of PM2.5 on innate immunity have become a hotspot recently. Confronting PM2.5, macrophages are able to be activated and induce inflammatory responses. Whether PM2.5 exposure affects macrophage polarization and associated mechanisms remains to be further explored. Afterwards, whether Sirtuin1 (SIRT1) an important intermediate regulator in various physiological processes takes part in the macrophage polarization induced by PM2.5 is unknown. MiRNAs are acknowledged as key regulator in posttranscriptional modification and our previous study found that miR-146a is a novel biomarker of PM2.5 exposure. Thus, we propose a hypothesis, PM2.5 exposure induces M1 polarization and miR-146a-3p is a potential upstream regulator by targeting SIRT1. Methods: RAW264.7 cells were treated with different concentrations of PM2.5 for 24h. The expressions of cytokines and key molecular markers were detected by qRT-PCR, Western blotting and ELISA. The activation degree of TLRs and NF-κB was assessed by Western blotting. The specific agonist and antagonist of SIRT1 were used to explore the potential role of SIRT1 in M1 polarization induced by PM2.5. MiR-146a-3p mimic and inhibitor were pre-transfected into RAW264.7 cells and the effects on M1 polarization induced by PM2.5 were evaluated. Luciferase analysis was used to identify the binding site of miR-146a-3p and SIRT1. Results: PM2.5 increased the mRNA and protein expression of M1 markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in RAW264.7 cells. The protein level of TLR4 was significantly increased and the ratio of phosphorylated NF-κB p65 versus p65 subunit was also elevated in PM2.5 group. PM2.5 decreased the protein level of SIRT1 but not the mRNA expression in vitro and in vivo experiments. Pre-treatment with SIRT1 agonist SRT1720 rescued the PM2.5 induced M1 response. Whereas, SIRT1 antagonist EX527 augment the effect. MiR-146a-3p was upregulated in PM2.5 treated RAW264.7 cells. Luciferase experiments reported that SIRT1 was directly targeted by miR-146a-3p. Overexpression of miR-146a-3p downregulated the expression of SIRT1 protein in untreated RAW264.7 cells. Importantly, inhibition of miR-146a-3p upregulated SIRT1 protein and suppressed M1 polarization in PM2.5 treated RAW264.7 cells. Conclusions: These results suggested that PM2.5 induces the inflammatory M1 polarization and TLR4/NF-κB signal transduction pathway might be involved in the process. MiR-146a-3p is a novel regulator of PM2.5 exerted M1 polarization by targeting SIRT1.

/pdf/pm2-5-upregulates-microrna-146a-3p-and-induces-m1-2ewc2rg5fj.pdf

PM2.5 Upregulates MicroRNA-146a-3p and Induces M1 Polarization in RAW264.7 Cells by Targeting Sirtuin1.

Background Nitrous oxide (N2O) has gained increasing popularity as a recreational drug, causing hallucinations, excitation, and psychological dependence. However, side effects have been reported in recent years. Our case report proposes a correlation among N2O, pulmonary embolism (PE), and deep vein thrombosis (DVT) and emphasizes the role of homocysteine (Hcy) in thrombotic events. Case summary A 29-year-old man with long-term N2O abuse sought evaluation after acute chest pain. A diagnostic workup revealed PE, DVT, and hyperhomocysteinemia. The patient was successfully treated with thrombolytic and anticoagulant therapy. Moreover, his Hcy level decreased and returned to normal after Hcy-lowering therapy. Conclusion Chronic N2O abuse might increase the risk of PE and DVT, although there have been few studies previously.

Pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: A case report

Objective To synthesize evidence regarding the relationship between outdoor air pollution and risk of asthma exacerbations in single lag0 and lag1 exposure patterns.Methods We performed a systematic literature search using PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials, China National Knowledge Internet, Chinese BioMedical, and Wanfang databases. Articles published until August 1, 2020 and the reference lists of the relevant articles were reviewed. Two authors independently evaluated the eligible articles and performed structured extraction of the relevant information. Pooled relative risks (RRs) and 95% confidence intervals (CIs) of lag0 and lag1 exposure patterns were estimated using random-effect models.Results: Eighty-four studies met the eligibility criteria and provided sufficient information for meta-analysis. Outdoor air pollutants were associated with increased risk of asthma exacerbations in both single lag0 and lag1 exposure patterns [lag0: RR (95% CI) (pollutants), 1.057(1.011, 1.103) (air quality index, AQI), 1.007 (1.005, 1.010) (particulate matter of diameter ≤2.5 μm, PM2.5), 1.009 (1.005, 1.012) (particulate matter of diameter, PM10), 1.010 (1.006, 1.014) (NO2), 1.030 (1.011, 1.048) (CO), 1.005 (1.002, 1.009) (O3); lag1:1.064(1.022, 1.106) (AQI), 1.005 (1.002, 1.008) (PM2.5), 1.007 (1.004, 1.011) (PM10), 1.008 (1.004, 1.012) (NO2), 1.025 (1.007, 1.042) (CO), 1.010 (1.006, 1.013) (O3)], except SO2 [lag0: RR (95% CI), 1.004 (1.000, 1.007); lag1: RR (95% CI), 1.003 (0.999, 1.006)]. Subgroup analyses revealed stronger effects in children and asthma exacerbations associated with other events (including symptoms, lung function changes, and medication use).Conclusion Outdoor air pollution increases the asthma exacerbation risk in single lag0 and lag1 exposure patterns.Trial registration: PROSPERO, CRD42020204097. https://www.crd.york.ac.uk/PROSPERO.

Yan Hu

Papers

Fine particulate matter (PM2.5) aggravates apoptosis of cigarette-inflamed bronchial epithelium in vivo and vitro

Identification of long non-coding RNA and circular RNA in mice after intra-tracheal instillation with fine particulate matter.

PM2.5 Upregulates MicroRNA-146a-3p and Induces M1 Polarization in RAW264.7 Cells by Targeting Sirtuin1.

Pulmonary embolism and deep vein thrombosis caused by nitrous oxide abuse: A case report

Outdoor air pollution and the risk of asthma exacerbations in single lag0 and lag1 exposure patterns: a systematic review and Meta-analysis.