Does ambient particulate matter 1 increase the risk of gastric cancer in the northwest of China?

Gastric cancer (GC) remains a significant health concern in Gansu province, China, with morbidity and mortality rates surpassing national averages. Despite the recognized health risks associated with ambient particulate matter with an aerodynamic diameter <1 µm (PM1), the relationship between PM1 exposure and GC incidence has not been extensively studied. Data on GC cases from 2013 to 2021 were gathered from 262 hospitals in Gansu, China. Concurrently, data on the normalized vegetation index (NDVI), gross domestic product (GDP), drinking and smoking behavioral index (DSBI), PM1, PM2.5, and PM2.5-1 were collected. Utilizing a Bayesian conditional autoregressive (CAR) combined generalized linear model (GLM) with quasi-Poisson regression, we evaluated the impact of PM1, PM2.5, PM2.5-1, NDVI, DSBI, and GDP on GC morbidity while adjusting for potential confounders. Our analysis indicated that exposure to PM1 (µg/m3) is significantly positively correlated with GC incidence in regions with an overall age-standardized incidence rate (ASIR) >40 (relative risks [RR]: 1.023, 95% confidence intervals [CI, 1.007, 1.039]), male ASIR >50 (RR: 1.014, 95% CI [1.009, 1.019]), and female ASIR >20 (RR: 1.010, 95% CI [1.002, 1.018]). PM2.5, PM2.5-1, DSBI, and GDP were positively correlated with GC incidence, while NDVI was negatively correlated in the study regions. Our findings provided evidence of a positive correlation between PM1 exposure and GC incidence in high-risk areas of GC within arid regions. Further research is warranted to elucidate the complex nonlinear relationships between environmental factors and GC. These insights could inform strategies for improving the control and prevention of GC in Gansu and similar regions.

Particulate matter 2.5 induces the skin barrier dysfunction and cutaneous inflammation via AhR- and T helper 17 cell-related genes in human skin tissue as identified via transcriptome analysis.

Particulate matter (PM2.5) is an environmental pollutant causing skin inflammatory diseases via epidermal barrier damage. However, the mechanism and related gene expression induced by PM2.5 remains unclear. Our aim was to determine the effect of PM2.5 on human skin tissue ex vivo, and elucidate the mechanism of T helper 17 cell-related inflammatory cytokine and skin barrier function. We verified the expression levels of gene in PM2.5-treated human skin tissue using Quantseq (3' mRNA-Seq), and Gene Ontology (GO) terms and protein-protein interaction (PPI) networks were performed. The PM2.5 treatment significantly enhanced the expression of Th 1, 2, 17 and 22 cell-related genes (cut-off value: │1.2 │ > fold change and p < 0.05). Most of all, Th17 cell-related genes are upregulated and those genes are associated with skin epidermal barrier function and Aryl hydrocarbon receptor (AhR), a xenobiotic receptor, pathway. In human keratinocyte cell lines, AhR-regulated genes (e.g. AhRR, CYP1A1, IL6 and IL36G), Th17 cell-related genes (e.g. IL17C) and epidermal barrier-related genes (e.g. SPRR2A and KRT71) are significantly increased after PM2.5. In the protein level, the secretion of IL-6 and IL-36G was increased in human skin tissue following PM2.5 treatment, and the expression of SPRR2A and KRT71 was significantly increased. PM2.5 exposure could ruin the skin epidermal barrier function via AhR- and Th17 cell-related inflammatory pathway.

Selenomethionine mitigate PM2.5-induced cellular senescence in the lung via attenuating inflammatory response mediated by cGAS/STING/NF-κB pathway.

Particulate matter 2.5 (PM2.5) is a widely known atmospheric pollutant which can induce the aging-related pulmonary diseases such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF). In recent years, with the increasing atmospheric pollution, airborne fine PM2.5, which is an integral part of air pollutants, has become a thorny problem. Hence, this study focused on the effect of PM2.5 on cellular senescence in the lung, identifying which inflammatory pathway mediated PM2.5-induced cellular senescence and how to play a protective role against this issue. Our data suggested that PM2.5 induced time- and concentration-dependent increasement in the senescence of A549 cells. Using an inhibitor of cGAS (PF-06928215) and an inhibitor of NF-κB (BAY 11-7082), it was revealed that PM2.5-induced senescence was regulated by inflammatory response, which was closely related to the cGAS/STING/NF-κB pathway activated by DNA damage. Moreover, our study also showed that the pretreatment with selenomethionine (Se-Met) could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway in A549 cells exposed to PM2.5. Furthermore, in vivo C57BL/6J mice model demonstrated that aging of mouse lung tissue caused by PM2.5 was attenuated by decreasing cGAS expression after Se-Met treatment. Our findings indicated that selenium made a defense capability for PM2.5-induced cellular senescence in the lung, which provided a novel insight for resisting the harm of PM2.5 to human health.

[Effects of K-ras gene silence on the expression of oncogenes in HBE cells treated with PM(2.5)].

Objective: To explore the effects of K-ras gene on the expressions of oncogenes and cancer suppressor genes in human bronchial epithelial (HBE) cells which were exposed to PM(2.5). Methods: According to the mRNA sequence of K-ras gene provided by GenBank in September 2019, interference sequences were designed and synthesized, and the recombinant lentiviral vector was transfected into HBE cell to construct the K-ras gene-silenced cells. HBE cells and K-ras gene-silenced cells were exposed to 10 µg/ml, 50 µg/ml PM(2.5) suspension and 10 µmol/L Cr(6+). Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of c-myc, c-fos, N-ras, cyclin-D1, p16 and p53 genes, the expression levels of p53 and c-myc proteins were detected by Western blot. Results: In K-ras silenced cell group, K-ras mRNA expression level decreased (80.5%±3.6%) and K-ras protein level decreased (58.9%±4.7%) when compared with the control group (P<0.01) . Compared with the correspoding cell control group without exposure, the mRNA expression levels of c-myc, c-fos, N-ras and cyclin-D1 genes in HBE cell group exposed to different concentrations of PM(2.5), K-ras silenced cell group exposed to different concentrations of PM(2.5), HBE cell group exposed to 10 µmol/L Cr(6+) and K-ras silenced cell group exposed to 10 µmol/L Cr(6+) were increased, the mRNA expressions of p16 and p53 genes were decreased (P<0.01) . Compared with HBE cell group exposed to 10 µg/ml PM(2.5), the mRNA expressions of c-myc, c-fos and p16 genes in K-ras silenced cells exposed to 10 µg/ml PM(2.5) were decreased, and the p53 mRNA level was increased (P<0.01) . Compared with HBE cell group exposed to 50 µg/ml PM(2.5), the mRNA expression levels of c-fos, N-ras, cyclin-D1, p16 and p53 genes in K-ras silenced cell group exposed to 50 µg/ml PM(2.5) were decreased (P<0.01) . Compared with the HBE cell group without exposure, c-myc protein increased and p53 protein decreased in HBE cells exposed to 50 µg/ml PM(2.5) (P<0.05) . Compared with the K-ras silenced cell group without exposure, c-myc protein increased in K-ras silenced cells exposed to 50 µg/ml PM(2.5) (P<0.05) . Conclusion: PM(2.5) can increase the expression levels of oncogenes in HBE cells, and K-ras gene silencing can inhibit the expression levels of oncogenes in HBE cells treated with PM(2.5).

Extract of Cornus officinalis Protects Keratinocytes from Particulate Matter-induced Oxidative Stress.

The skin is one of the large organs in the human body and the most exposed to outdoor contaminants such as particulate matter < 2.5 µm (PM2.5). Recently, we reported that PM2.5 induced cellular macromolecule disruption of lipids, proteins, and DNA, via reactive oxygen species, eventually causing cellular apoptosis of human keratinocytes. In this study, the ethanol extract of Cornus officinalis fruit (EECF) showed anti-oxidant effect against PM2.5-induced cellular oxidative stress. EECF protected cells against PM2.5-induced DNA damage, lipid peroxidation, and protein carbonylation. PM2.5 up-regulated intracellular and mitochondrial Ca2+ levels excessively, which led to mitochondrial depolarization and cellular apoptosis. However, EECF suppressed the PM2.5-induced excessive Ca2+ accumulation and inhibited apoptosis. The data confirmed that EECF greatly protected human HaCaT keratinocytes from PM2.5-induced oxidative stress.

Copper-dependent biological effects of particulate matter produced by brake systems on lung alveolar cells.

Road traffic is one of the main sources of particulate emissions into the environment and has an increasing, negative impact on the release of potentially dangerous materials. Vehicle brakes release a significant amount of wear particles, and knowledge regarding their possible adverse effects is limited. One of the most dangerous elements contained in brake pads is copper (Cu), known to be toxic for human health. Therefore, our aim was to study the cell toxicity of particulate matter (PM) produced by different combinations of braking discs and pads containing different amounts of Cu. We investigated whether brake-derived microparticles have toxic effects on lung cells proportionally to their Cu content. Analyte content was measured in friction materials by XRFS and in PM2.5 captured during braking tests using SEM/EDX. The biological impact of brake-derived PM2.5 was investigated on a human epithelial alveolar cell line (A549). Cell viability, oxidative stress, mitochondrial membrane potential, apoptosis, and the pro-inflammatory response of the cells, as well as gene expression, were assessed following exposure to increasing PM2.5 concentrations (1, 10, 100, 200, and 500 µg/ml). The brake debris with the lowest Cu content did not induce significant changes in biological effects on A549 cells compared to normal controls, except for ROS production and IL6 gene expression. PM2.5 containing higher Cu quantities induced cell toxicity that correlated with Cu concentration. Our data suggest that the toxicity of PM2.5 from the brake system is mainly related to Cu content, thus confirming that eliminating Cu from brake pads will be beneficial for human health in urbanized environments.

Particulate matter 2.5 induced bronchial epithelial cell injury via activation of 5'-adenosine monophosphate-activated protein kinase-mediated autophagy.

The impact of particulate matter 2.5 (PM2.5) on the respiratory system is a worldwide concern. However, the mechanisms by which PM2.5 causes disease are still unclear. In this study, we investigated the effect of PM2.5 on autophagy and studied the effect of PM2.5-induced autophagy and 5'-adenosine monophosphate-activated protein kinase (AMPK) on cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS), and airway inflammation using human bronchial epithelial cells 16HBE140 cells. Results showed that exposure of cells to PM2.5 at a concentration of 100 µg/mL for 24 hours was most effective for inhibiting cell viability. PM2.5 induced cell arrest in the G0/G1 phase and increased mitochondrial membrane potential, ROS, and cell apoptosis with increasing concentration. PM2.5 downregulated cyclin D and matrix metallopeptidase-9 (MMP-9) expression but upregulated tissue inhibitor of metalloproteinases-1 (TIMP-1) expression, significantly promoted interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and enhanced the level and activation of AMPK. The levels of autophagy-related protein 5 (ATG5), Beclin-1, and LC3II/I were significantly increased by PM2.5. The activation of Unc-51-like autophagy activating kinase 1 was significantly inhibited by PM2.5. Moreover, ATG5 knockdown inhibited PM2.5-induced autophagy, ROS, and cell apoptosis significantly. The expression of cyclin D, MMP-9, and TIMP-1 was reversed by ATG5 suppression. PM2.5-induction of IL-6 and TNF-α was significantly inhibited by knockdown of ATG5. Thus, inhibition of autophagy protected the cells from PM2.5-induced injury. PM2.5 induced injury in human bronchial epithelial cells via activation of AMPK-mediated autophagy, suggesting possible therapeutic targets for the treatment of respiratory diseases.

Integrative analysis of mRNA and microRNA expression of a human alveolar epithelial cell(A549) exposed to water and organic-soluble extract from particulate matter (PM)2.5.

MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in toxicity. In this study, we assessed the effects of particulate matter 2.5 (PM2.5 ), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] and performed miRNA microarray analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3-fold in W-PM2.5 and O-PM2.5 , respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W-PM2.5 and O-PM2.5 exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W-PM2.5 target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O-PM2.5 target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM2.5 -induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 302-310, 2017.

Epidermal growth factor receptor (EGFR)-MAPK-nuclear factor(NF)-κB-IL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity.

Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2.5 and three cytokines with O-PM2.5 . Among them, epidermal growth factor (EGF) was commonly up-regulated by W-PM2.5 and O-PM2.5 . Then, in both groups, we can identify the increase in EGF receptor protein levels. Likewise, increases in the phosphorylation of ERK1/2 MAP kinase and acetylation of nuclear factor(NF)-κB were detected. We also detected an increase in IL-8 that was related to inflammatory response. And using the erlotinib as an inhibitor of EGFR, we identified the erlotinib impaired the phosphorylation of EGFR, ERK1/2, acetylation of NF-κB proteins and decreased IL-8. Furthermore, at in vivo model, we were able to identify similar patterns. These results suggest that PM2.5 may contribute to an abnormality in the human respiratory system through EGFR, MAP kinase, NF-κB, and IL-8 induced toxicity signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1628-1636, 2017.

PM2.5 induces lung inflammation and fibrosis via airway smooth muscle cell expression of the Wnt5a/JNK pathway.

Background: In recent years, particulate matter 2.5 (PM2.5) exposure has been considered a key dangerous factor in chronic obstructive pulmonary disease (COPD). The dysfunction of airway smooth muscle cells (ASMCs) facilitates lung inflammation and fibrosis in COPD. Therefore, we explored whether PM2.5 could promote the inflammatory response and fibrosis in ASMCs in vivo and in vitro via the wingless-related integration site 5a (Wnt5a)/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Methods: Wnt5a expression in the bronchoalveolar lavage fluid (BALF) of COPD patients exposed to PM2.5 was measured by enzyme-linked immunosorbent assay (ELISA). Mice were intratracheally injected with PM2.5 and a Wnt5a antagonist (BOX5). ASMCs were transfected with Wnt5a small interfering RNA (siRNA), BOX5 and the JNK inhibitor SP600125 before PM2.5 stimulation. Hematoxylin and eosin (H&E) staining was performed to measure the inflammatory response and airway fibrosis. The production of Wnt5a/JNK/NF-KB pathway factors was analyzed by Western blotting. The secretion of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) was measured by ELISA. The expression levels of alpha smooth muscle actin (α-SMA), collagen I and collagen III were assessed by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. Results: We found that the increase in Wnt5a expression in the BALF of COPD patients was positively correlated with the levels of PM2.5 exposure. The Wnt5a/JNK/NF-κB pathway was activated in the lung samples of PM2.5-induced model mice and PM2.5-exposed ASMCs, which promoted the production of α-SMA, collagen I and collagen III and increased the secretion of IL-6, IL-8 and TNF-α. Furthermore, our results showed that BOX5 could prevent these effects. Wnt5a siRNA blocked the activation of the Wnt5a/JNK/NF-κB pathway and inhibited the effects of PM2.5 on fibrosis and inflammation in ASMCs. SP600125 blocked the phosphorylation of NF-κB and inhibited inflammation and fibrosis in PM2.5-exposed ASMCs. Conclusions: These findings suggest that PM2.5 stimulation of ASMCs induces pulmonary inflammatory factor expression and collagen deposition during COPD via the Wnt5a/JNK pathway, which indicates that modulating the Wnt5a/JNK pathway could be a promising therapeutic strategy for PM2.5-induced COPD.

Adenophora Stricta Root Extract Protects Lung Injury from Exposure to Particulate Matter 2.5 in Mice.

Chronic exposure of particulate matter of less than 2.5 µm (PM2.5) has been considered as one of the major etiologies for various respiratory diseases. Adenophora stricta Miq. is a medicinal herb that has been used for treating respiratory diseases in East Asia. The present study investigated the effect of A. stricta root extract (AsE) on PM2.5-induced lung injury in mice. Oral administration of 100-400 mg/kg AsE for 10 days significantly reduced the PM2.5-mediated increase in relative lung weight, but there was no difference in body weight with AsE administration. In addition, AsE dose-dependently decreased congested region of the lung tissue, prevented apoptosis and matrix degradation, and alleviated mucus stasis induced by PM2.5. Moreover, cytological analysis of bronchioalveolar lavage fluid revealed that AsE significantly inhibited the infiltration of immune cells into the lungs. Consistently, AsE also decreased expression of proinflammatory cytokines and chemokines in lung tissue. Furthermore, AsE administration blocked reactive oxygen species production and lipid peroxidation through attenuating the PM2.5-dependent reduction of antioxidant defense system in the lungs. Therefore, A. stricta root would be a promising candidate for protecting lung tissue from air pollution such as PM2.5.

Ambient fine particulate pollution hysteresis triggers wake-up stroke and rapidly triggers non-wake-up stroke: a case-crossover study.

Atmospheric pollutants increase the risk of acute ischemic stroke (AIS) which has been widely reported. However, little is known about the relationships between air pollution and specific subsets of AIS, such as wake-up stroke (WUS) and non-wake-up stroke (non-WUS). This study aimed to explore the relationship between WUS and non-WUS and atmospheric pollutants. A total of 1432 patients (331 WUS patients and 1101 non-WUS patients) were admitted to a tertiary hospital from 2016 to 2019. A time-stratified case-crossover design and a conditional logistic regression model to study the associations of change in pollutant concentration with WUS and non-WUS events were constructed. Data analysis revealed that WUS-related risks increased 48 to 72 h after the increase in the PM2.5 concentration (each 10 µg/m3 increase, lag 0-72 h) [threshold OR (95% CI):18 µg/m3 1.03 (0.94-1.11), 35 µg/m3 1.01 (0.92-1.12), 50 µg/m3 1.04 (0.91-1.19)]; the non-WUS-related risk increased 1 to 6 h after the increase in the PM2.5 concentration (each 10 µg/m3 increase, lag 0-1 h) [threshold OR (95% CI):18 µg/m3 1.01 (0.98-1.03), 35 µg/m3 1.00 (0.97-1.04), 50 µg/m3 1.01 (0.96-1.05)] (lag 0-6 h) [threshold OR (95% CI): 18 µg/m3 1.00 (0.97-1.03), 35 µg/m3 1.00 (0.97-1.04), 50 µg/m3 1.01 (0.97-1.06)]; O3 exposure was related to WUS events, and its impact on WUS events was stronger and longer-lasting (1-96 h) than its impact on non-WUS events (1-6 h). Greater than or equal to 65 years of age, overweight (BMI ≥ 25), and diabetes had a significantly greater risk of WUS associated with increased PM2.5 concentration in the previous 12-96 h than patients without these conditions. Patients with hypertension and smoking had a significant risk of non-WUS associated with increased PM2.5 concentration in the previous 1-6 h. The increase in PM2.5 concentration in the cold season increased the risk of both WUS and non-WUS events. Ambient air pollution hysteresis triggers WUS and rapidly triggers non-WUS, even if the degree of pollutant is relatively low. Patients with elderly, overweight, and diabetes appeared particularly susceptible to WUS, and patients with hypertension and smoking history were susceptible to non-WUS. We need to expand the sample for further investigation into mechanisms by which environmental pollutants trigger WUS or non-WUS.

Air Pollution and Cognitive Impairment across the Life Course in Humans: A Systematic Review with Specific Focus on Income Level of Study Area.

Cognitive function is a crucial determinant of human capital. The Lancet Commission (2020) has recognized air pollution as a risk factor for dementia. However, the scientific evidence on the impact of air pollution on cognitive outcomes across the life course and across different income settings, with varying levels of air pollution, needs further exploration. A systematic review was conducted, using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Guidelines to assess the association between air pollution and cognitive outcomes across the life course with a plan to analyze findings as per the income status of the study population. The PubMed search included keywords related to cognition and to pollution (in their titles) to identify studies on human participants published in English until 10 July 2020. The search yielded 84 relevant studies that described associations between exposure to air pollutants and an increased risk of lower cognitive function among children and adolescents, cognitive impairment and decline among adults, and dementia among older adults with supportive evidence of neuroimaging and inflammatory biomarkers. No study from low- and middle-income countries (LMICs)was identified despite high levels of air pollutants and high rates of dementia. To conclude, air pollution may impair cognitive function across the life-course, but a paucity of studies from reLMICs is a major lacuna in research.

Ambient PM2.5 caused cardiac dysfunction through FoxO1-targeted cardiac hypertrophy and macrophage-activated fibrosis in mice.

Plenty of epidemiological evidences have shown that ambient particulate matter (PM2.5) exposure increased the prevalence of cardiovascular disease, but the potential mechanism has not been known clearly. We established mice models by ambient PM2.5 exposure system to explore the adverse effects of PM2.5 on cardiac function in mice. Forty-eight C57BL/6 mice were randomly divided into 3 groups and exposed to filtered air (FA), unfiltered air (UA) and concentrated PM2.5 air (CA) for 8 or 16 weeks, 6 hours per day, 7 days per week, respectively. The changes of cardiac structure and function, histological analysis and related mechanism were investigated. The main manifestations of cardiac structure were cardiac hypertrophy and fibrosis in a dose- and time-dependent manner after PM2.5 exposure, which led to the decrease of cardiac systolic function. Cardiac hypertrophy in mice might be regulated by PI3K/Akt/FoxO1 signal. Cardiac fibrosis might be attributed to inflammatory infiltration caused by macrophage activation. Consequently, our data indicated that cardiac hypertrophy and fibrosis might be important factors of PM2.5-induced cardiac dysfunction in mice.

CircRNA104250 and lncRNAuc001.dgp.1 promote the PM2.5-induced inflammatory response by co-targeting miR-3607-5p in BEAS-2B cells.

Long-term exposure to particulate matter 2.5 (PM2.5) is closely related to the occurrence and development of airway inflammation. Exploration of the role of PM2.5 in inflammation is the first step towards clarifying the harmful effects of particulate pollution. However, the molecular mechanisms underlying PM2.5-induced airway inflammation are yet to be fully established. In this study, we focused on the specific roles of non-coding RNAs (ncRNAs) in PM2.5-induced airway inflammation. In a human bronchial epithelial cell line, BEAS-2B, PM2.5 at a concentration of 75 µg/mL induced the inflammatory response. Microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analyses revealed significant upregulation of circRNA104250 and lncRNAuc001.dgp.1 during the PM2.5-induced inflammatory response in this cell line. Data from functional analyses further showed that both molecules promote an inflammatory response. CircRNA104250 and lncRNAuc001.dgp.1 target miR-3607-5p and affect expression of interleukin 1 receptor 1 (IL1R1), which influences the nuclear factor κB (NF-κB) signaling pathway. In summary, we have uncovered an underlying mechanism of airway inflammation by PM2.5 involving regulation of ncRNA for the first time, which provides further insights into the toxicological effects of PM2.5.

Exposure Assessment of Environmental Tobacco Aerosol from Heated Tobacco Products: Nicotine and PM Exposures under Two Limited Conditions.

It is too early to provide a clear answer on the impact of exposure to the second-hand aerosol of heated tobacco products (HTPs) in the planning of policy for smoke-free indoors legislation. Here, we conducted a preliminary study to evaluate indoor air quality with the use of HTPs. We first measured the concentration of nicotine and particulate matter (PM2.5) in the air following 50 puffs in the use of HTPs or cigarettes in a small shower cubicle. We then measured these concentrations in comparison with the use equivalent of smoking 5.4 cigarettes per hour in a 25 m3 room, as a typical indoor environment test condition. In the shower cubicle test, nicotine concentrations in indoor air using three types of HTP, namely IQOS, glo, and ploomTECH, were 25.9-257 µg/m3. These values all exceed the upper bound of the range of tolerable concentration without health concerns, namely 3 µg/m3. In particular, the indoor PM2.5 concentration of about 300 to 500 µg/m3 using IQOS or glo in the shower cubicle is hazardous. In the 25 m3 room test, in contrast, nicotine concentrations in indoor air with the three types of HTP did not exceed 3 µg/m3. PM2.5 concentrations were below the standard value of 15 µg/m3 per year for IQOS and ploomTECH, but were slightly high for glo, with some measurements exceeding 100 µg/m3. These results do not negate the inclusion of HTPs within a regulatory framework for indoor tolerable use from exposure to HTP aerosol, unlike cigarette smoke.

Ambient fine particulate matter induce toxicity in lung epithelial-endothelial co-culture models.

Epidemiological and toxicological studies have reported that ambient fine particulate matter (PM2.5) exposure are linked to adverse effects of cardiopulmonary system. An in vitro suitable model that assesses the interaction among various cell types should be developed to explain the toxic mechanisms occurred in cardiopulmonary system. The Transwell culture method was used to establish bi-culture consisting of A549 alveolar epithelial cells monoculture in apical chamber and EA.hy926 endothelial cells in the basolateral chamber, while tri-culture systems consisting of co-culture (A549 cells and THP-1 differentiated macrophages) in the apical chamber and also EA.hy926 endothelial cells in the basolateral chamber. Ambient PM2.5 collecting from Shanghai city in China was used for experiments. Our results showed that apical exposure of co-cultured cells to PM2.5 (20, 60, 180 µg/ml) for 24 h elicited stronger inflammatory responses than apical exposure of monocultured A549. Endothelial function was assessed via detecting gene expression in EA.hy926 cells, exposure of co-cultured cells induced more vigorous ICAM-1 and caveolin-1 mRNA expression in the tri-culture model than monocultured cells at the same dose of PM2.5 in the bi-culture model. Particles uptake were observed in both epithelial cells and endothelial cells according to TEM images. In conclusion, PM2.5 were able to pass through epithelial barrier and deposited in endothelium to further induce direct effect on endothelium function. The tri-culture system was more realistic and sensitive model to evaluate the impact of particles on the cardiopulmonary system than the bi-culture system. Therefore, the tri-culture system will contribute to explaining of the relationships between PM2.5 and cardiopulmonary diseases.

Effects of PM2.5 on Cardio-Pulmonary Function Injury in Open Manganese Mine Workers.

Exposure to fine particulate matter 2.5 (PM2.5) is associated with adverse health effects, varying by its components. The health-related effects of PM2.5 exposure from ore mining may be different from those of environment pollution. The aim of this study was to investigate the effects of different concentrations of PM2.5 exposure on the cardio-pulmonary function of manganese mining workers. A total of 280 dust-exposed workers who were involved in different types of work in an open-pit manganese mine were randomly selected. According to the different concentrations of PM2.5 in the working environment, the workers were divided into an exposed group and a control group. The electrocardiogram, blood pressure, and multiple lung function parameters of the two groups were measured and analyzed. The PM2.5 exposed group had significantly lower values in the pulmonary function indexes of forced expiratory volume in one second (FEV1.0), maximum mid expiratory flow (MMEF), peak expiratory flow rate (PEFR), percentage of peak expiratory flow out of the overall expiratory flow volume (PEFR%), forced expiratory flow at 25% and 75% of forced vital capacity (FEF 25, FEF75), forced expiratory flow when 25%, 50%, and 75% of forced vital capacity has been exhaled (FEF25%,FEF50%, FEF75%), and FEV1.0/FVC% (the percentage of the predicted value of forced vital capacity) than the control group (all p < 0.05). Both groups had mild or moderate lung injury, most of which was restrictive ventilatory disorder, and there was significant difference in the prevalence rate of restrictive respiratory dysfunction between the two groups (41.4% vs. 23.6%, p = 0.016). Electrocardiogram (ECG) abnormalities, especially sinus bradycardia, were shown in both groups, but there was no statistical difference of the prevalence rate between the two groups (p > 0.05). Also, no significant difference of the prevalence rate of hypertension was observed between the PM2.5 exposure and control groups (p > 0.05). PM2.5 exposure was associated with pulmonary function damage of the workers in the open-pit manganese mine, and the major injury was restrictive ventilatory disorder. The early effect of PM2.5 exposure on the cardiovascular system was uncertain at current exposure levels and exposure time.

Histological and Endocrine Effects of Chronic Exposure to MP2.5 Derived from Wood Smoke in the Uterus of Nulliparous Adult Rats

SUMMARY: The study explores the relationship between chronic exposure to fine particulate matter (PM2.5), sourced from wood smoke, and the histological structure and endocrine function of the uterus in nulliparous adult rats. It assesses potential structural changes in the uterus that could impact reproductive health, viewing PM2.5 exposure as a possible risk factor. A controlled experiment was conducted in a city known for high air pollution levels, exposing rats to filtered and unfiltered air conditions, thus mimicking human PM2.5 exposure. Histological findings indicated a significant increase in collagen density and uterine wall thickness in PM2.5 exposed subjects, suggesting a reproductive function risk. However, no significant differences were observed in progesterone and estradiol hormone levels, pointing to the complex relationship between PM2.5 exposure and its endocrine impact, and emphasizing the need for further studies for a deeper understanding. This work highlights the importance of thoroughly investigating the long-term effects of PM2.5 pollution on reproductive health, underlining the significance of considering environmental exposure as a critical factor in reproductive health research.

El estudio explora la relación entre la exposición crónica a partículas finas (PM2,5), procedentes del humo de leña, y la estructura histológica y la función endocrina del útero en ratas adultas nulíparas. Evalúa posibles cambios estructurales en el útero que podrían afectar la salud reproductiva, considerando la exposición a PM2,5 como un posible factor de riesgo. Se llevó a cabo un experimento controlado en una ciudad conocida por sus altos niveles de contaminación del aire, exponiendo ratas a condiciones de aire filtrado y sin filtrar, imitando así la exposición humana a PM2,5. Los hallazgos histológicos indicaron un aumento significativo en la densidad del colágeno y el grosor de la pared uterina en sujetos expuestos a PM2,5, lo que sugiere un riesgo para la función reproductiva. Sin embargo, no se observaron diferencias significativas en los niveles de las hormonas progesterona y estradiol, lo que apunta a la compleja relación entre la exposición a PM2,5 y su impacto endocrino, y enfatiza la necesidad de realizar más estudios para una comprensión más profunda. Este trabajo destaca la importancia de investigar a fondo los efectos a largo plazo de la contaminación por PM2,5 en la salud reproductiva, subrayando la importancia de considerar la exposición ambiental como un factor crítico en la investigación de la salud reproductiva.

Activated iRhom2 drives prolonged PM2.5 exposure-triggered renal injury in Nrf2-defective mice.

Research suggests that particulate matter (PM2.5) is a predisposing factor for metabolic syndrome-related systemic inflammation and oxidative stress injury. TNF-α as a major pro-inflammatory cytokine was confirmed to participate in various diseases. Inactive rhomboid protein 2 (iRhom2) was recently determined as a necessary regulator for shedding of TNF-α in immune cells. Importantly, kidney-resident macrophages are critical to inflammation-associated chronic renal injury. Podocyte injury can be induced by stimulants and give rise to nephritis, but how iRhom2 contributes to PM2.5-induced renal injury is unclear. Thus, we studied whether PM2.5 causes renal injury and characterized iRhom2 with respect to TNF-α release in mice macrophages and renal tissues in long-term PM2.5-exposed mouse models. After long-term PM2.5 exposures, renal injury was confirmed via inflammatory cytokine, chemokine expression, and reduced antioxidant activity. Patients with kidney-related diseases had increased TNF-α, which may contribute to renal injury. We observed up-regulation of serum creatinine, serum urea nitrogen, kidney injury molecule 1, uric acid, TNF-α, MDA, H2O2, and O2- in PM2.5-treated mice, which was greater than that found in Nrf2-/- mice. Meanwhile, increases in metabolic disorder-associated indicators were involved in PM2.5-induced nephritis. In vitro, kidney-resident macrophages were observed to be critical to renal inflammatory infiltration and function loss via regulation of iRhom2/TACE/TNF-α signaling, and suppression of Nrf2-associated anti-oxidant response. PM2.5 exposure led to renal injury partly by inflammation-mediated podocyte injury. Reduced SOD1, SOD2, Nrf2 activation, and increased XO, NF-κB activity, TACE, iNOS, IL-1ß, TNF-α, IL-6, MIP-1α, Emr-1, MCP-1, and Cxcr4, were also noted. Long-term PM2.5 exposure causes chronic renal injury by up-regulation of iRhom2/TACE/TNF-α axis in kidney-resident macrophages. Overexpression of TNF-α derived from macrophages causes podocyte injury and kidney function loss. Thus, PM2.5 toxicities are related to exposure duration and iRhom2 may be a potential therapeutic renal target.