RESUMEN

Airborne particulate matter (PM) contains polycyclic aromatic hydrocarbons (PAHs) as primary toxic components, causing oxidative damage and being associated with various inflammatory skin pathologies such as premature aging, atopic dermatitis, and psoriasis. Coffee cherry pulp (CCS) extract, rich in chlorogenic acid, caffeine, and theophylline, has demonstrated strong antioxidant properties. However, its specific anti-inflammatory effects and ability to protect macrophages against PAH-induced inflammation remain unexplored. Thus, this study aimed to evaluate the anti-inflammatory properties of CCS extract on RAW 264.7 macrophage cells exposed to atmospheric PAHs, compared to chlorogenic acid (CGA), caffeine (CAF), and theophylline (THP) standards. The CCS extract was assessed for its impact on the production of nitric oxide (NO) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that CCS extract exhibited significant antioxidant activities and effectively inhibited protease and lipoxygenase (LOX) activities. The PAH induced the increase in intracellular reactive oxygen species, NO, TNF-α, IL-6, iNOS, and COX-2, which were markedly suppressed by CCS extract in a dose-dependent manner, comparable to the effects of chlorogenic acid, caffeine, and theophylline. In conclusion, CCS extract inhibits PAH-induced inflammation by reducing pro-inflammatory cytokines and reactive oxygen species (ROS) production in RAW 264.7 cells. This effect is likely due to the synergistic effects of its bioactive compounds. Chlorogenic acid showed strong antioxidant and anti-inflammatory activities, while caffeine and theophylline enhanced anti-inflammatory activity. CCS extract did not irritate the hen's egg chorioallantoic membrane. Therefore, CCS extract shows its potential as a promising cosmeceutical ingredient for safely alleviating inflammatory skin diseases caused by air pollution.

Asunto(s)

Antiinflamatorios , Estrés Oxidativo , Extractos Vegetales , Hidrocarburos Policíclicos Aromáticos , Animales , Ratones , Células RAW 264.7 , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hidrocarburos Policíclicos Aromáticos/toxicidad , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/metabolismo , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Óxido Nítrico/metabolismo , Contaminación del Aire/efectos adversos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ácido Clorogénico/farmacología , Administración Tópica , Factor de Necrosis Tumoral alfa/metabolismo , Coffea/química , Cafeína/farmacología , Material Particulado/toxicidad

RESUMEN

BACKGROUND: Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. RESULTS: In this study, we examine the effect of ß-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. CONCLUSIONS: This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Asunto(s)

Encéfalo , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Material Particulado , Animales , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Material Particulado/toxicidad , Ratones , Enfermedades Neuroinflamatorias/inducido químicamente , Enfermedades Neuroinflamatorias/metabolismo , Suplementos Dietéticos , Contaminantes Atmosféricos/toxicidad , Lipidómica

RESUMEN

BACKGROUND: Existing epidemiological studies have indicated a correlation between air pollutants and the occurrence of mental disorders. However, it is difficult to estimate the causal relationship between the two because of the limitations of traditional epidemiological research. In our study, we aimed to extensively explore the causal relationship between five types of air pollutants and four types of mental disorders. METHODS: Based on the IEU OPEN GWAS database, we performed a two-sample MR analysis. The primary analysis method utilized was the inverse variance weighted (IVW) method, supplemented by the MR-Egger method and the weighted median method. Additionally, we conducted sensitivity analyses with the Cochran's Q statistic method, the leave-one-out method, and the MR-Egger intercept. We chose at least 4 GWAS datasets for each of the four psychiatric diseases and conducted a meta-analysis of our results of the MR analysis. RESULTS: The meta-analysis's findings demonstrated a causal link between depression and PM2.5 (OR=1.020, 95 %CI: (1.010,1.030), P=0.001). PM10 and schizophrenia are also causally related (OR=1.136, 95 %CI: (1.034,1.248), P=0.008). Nitrogen oxides and bipolar disorder have a causal relationship (OR=1.002, 95 %CI: (1.000,1.003), P=0.022). Nitrogen oxides and schizophrenia have a high causal association (OR=1.439, 95 %CI: (1.183,1.752), P<0.001). CONCLUSION: This study observed a causal association between increased concentrations of PM2.5, PM10, and nitrogen oxides and the occurrence of depression, schizophrenia, and bipolar disorder. Our research findings have certain guiding implications for treating and preventing mental disorders.

Asunto(s)

Contaminantes Atmosféricos , Análisis de la Aleatorización Mendeliana , Trastornos Mentales , Material Particulado , Humanos , Contaminantes Atmosféricos/toxicidad , Trastornos Mentales/genética , Trastornos Mentales/epidemiología , Trastornos Mentales/inducido químicamente , Material Particulado/toxicidad , Esquizofrenia/genética , Exposición a Riesgos Ambientales/efectos adversos , Estudio de Asociación del Genoma Completo , Contaminación del Aire/efectos adversos

RESUMEN

Climate change and air pollution are major challenges facing the world today. Cold waves and air pollution significantly impact ischemic heart disease (IHD), but the extent of these effects at different altitudes remains unclear, especially their interactions. We collected daily meteorological, pollutant, and IHD hospitalization data from Xining and Xinxiang from 2016 to 2021. Using a time-stratified case-crossover approach, we fitted conditional Poisson regression models to assess the association between cold waves, PM2.5, and IHD hospitalizations and quantified their interactions. Additionally, we calculated the attributable fraction (AF) and attributable number (AN) of hospitalizations due to exposure to cold waves and medium to high-level PM2.5. We also performed stratified analyses by altitude, gender, and age. Both cold waves and PM2.5 were positively associated with IHD hospitalization rates in Xining and Xinxiang, but the differences between the two regions were not significant. The relative risk of cold waves was 1.15 (1.07, 1.24) in Xining and 1.16 (1.11, 1.21) in Xinxiang. In Xining, there was an interaction between cold waves and different levels of PM2.5. We estimated the attributable fraction due to the joint exposure of cold waves and PM2.5 to be 0.14-0.49 in Xining and 0.26-0.36 in Xinxiang. Older adults and males faced higher risks. This study highlights the importance of reducing PM2.5 exposure and optimizing extreme weather warning systems and suggests further exploration of the impacts of individual behaviors and regional characteristics on IHD.

Asunto(s)

Contaminantes Atmosféricos , Contaminación del Aire , Altitud , Hospitalización , Isquemia Miocárdica , Material Particulado , Material Particulado/análisis , Material Particulado/toxicidad , Humanos , Hospitalización/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Anciano , China/epidemiología , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/efectos adversos , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/inducido químicamente , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/efectos adversos , Adulto , Cambio Climático , Frío/efectos adversos

RESUMEN

The presented research introduces the "Cells-on-Particles" integrated aerosol sampling and cytotoxicity testing in vitro platform, which allows for the direct assessment of the biological effects of captured aerosol particles on a selected cell type without the need for extraction or resuspension steps. By utilizing particles with unaltered chemical and physical properties, the method enables simple and fast screening of biological effects on specific cell types, making it a promising tool for assessing the cytotoxicity of particulate matter in ambient and occupational air. Platforms fabricated from cellulose acetate (CA) and poly[ε]caprolactone (PCL) were proven to be biocompatible and promoted the attachment and growth of the human bronchial epithelial cell line BEAS-2B. The PCL platforms were exposed to simulated occupational aerosols of silver, copper, and graphene oxide nanoparticles. Each nanoparticle type exhibited different and dose-dependent cytotoxic effects on cells, evidenced by reduced cell viability and distinct, particle type-dependent gene expression patterns. Notably, copper nanoparticles were identified as the most cytotoxic, and graphene oxide the least. Comparing the "Cells-on-Particles" and submerged exposure ("Particles-on-Cells") testing strategies, BEAS-2B cells responded to selected nanoparticles in a comparable manner, suggesting the developed testing system could be proposed for further evaluation with more complex environmental aerosols. Despite limitations, including particle agglomeration and the need for more replicates to address variability, the "Cells-on-Particles" platform enables effective detection of toxicity induced by relatively low levels of nanoparticles, demonstrating good sensitivity and a relatively simpler procedure compared to standard 2D cell exposure methods.

Asunto(s)

Aerosoles , Supervivencia Celular , Pruebas de Toxicidad , Humanos , Supervivencia Celular/efectos de los fármacos , Línea Celular , Pruebas de Toxicidad/métodos , Cobre/toxicidad , Grafito/toxicidad , Nanopartículas del Metal/toxicidad , Células Epiteliales/efectos de los fármacos , Nanopartículas/toxicidad , Tamaño de la Partícula , Plata/toxicidad , Material Particulado/toxicidad , Poliésteres/toxicidad , Poliésteres/química

RESUMEN

Biomass-related airborne fine particulate matter (PM2.5) is an important risk factor for chronic obstructive pulmonary disease (COPD). Macrophage polarization has been reported to be involved in PM2.5-induced COPD, but the dynamic characteristics and underlying mechanism of this process remain unclear. Our study established a PM2.5-induced COPD mouse model and revealed that M2 macrophages predominantly presented after 4 and 6 months of PM2.5 exposure, during which a notable increase in MMP12 was observed. Single cell analysis of lung tissues from COPD patients and mice further revealed that M2 macrophages were the dominant macrophage subpopulation in COPD, with MMP12 being involved as a hub gene. In vitro experiments further demonstrated that PM2.5 induced M2 polarization and increased MMP12 expression. Moreover, we found that PM2.5 increased IL-4 expression, STAT6 phosphorylation and nuclear translocation. Nuclear pSTAT6 then bound to the MMP12 promoter region. Furthermore, the inhibition of STAT6 phosphorylation effectively abrogated the PM2.5-induced increase in MMP12. Using a coculture system, we observed a significantly reduced level of E-cadherin in alveolar epithelial cells cocultured with PM2.5-exposed macrophages, while the decrease in E-cadherin was reversed by the addition of an MMP12 inhibitor to the co-culture system. Taken together, these findings indicated that PM2.5 induced M2 macrophage polarization and MMP12 upregulation via the IL-4/STAT6 pathway, which resulted in alveolar epithelial barrier dysfunction and excessive extracellular matrix (ECM) degradation, and ultimately led to COPD progression. These findings may help to elucidate the role of macrophages in COPD, and suggest promising directions for potential therapeutic strategies.

Asunto(s)

Interleucina-4 , Macrófagos , Metaloproteinasa 12 de la Matriz , Material Particulado , Enfermedad Pulmonar Obstructiva Crónica , Factor de Transcripción STAT6 , Regulación hacia Arriba , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Metaloproteinasa 12 de la Matriz/metabolismo , Animales , Material Particulado/toxicidad , Factor de Transcripción STAT6/metabolismo , Ratones , Macrófagos/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad

RESUMEN

BACKGROUND: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. RESULTS: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 µg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM2.5 (4.76 µg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM10 (4.30 µg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively. CONCLUSION: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.

Asunto(s)

Contaminantes Atmosféricos , Contaminación del Aire , Epigénesis Genética , Material Particulado , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Contaminantes Atmosféricos/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Material Particulado/toxicidad , Niño , Masculino , Epigénesis Genética/efectos de los fármacos , Contaminación del Aire/efectos adversos , Estudios de Cohortes , Envejecimiento , Monóxido de Carbono/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Ozono/toxicidad , Dióxido de Nitrógeno/toxicidad , Metilación de ADN/efectos de los fármacos , Exposición Materna/efectos adversos , China

RESUMEN

Innate lymphoid cells (ILCs) are a heterogeneous population that play diverse roles in airway inflammation after exposure to allergens and infections. However, how ILCs respond after exposure to environmental toxins is not well understood. Here we show a novel method for studying the heterogeneity of rare lung ILC populations by magnetic enrichment for lung ILCs followed by particle-templated instant partition sequencing (PIP-seq). Using this method, we were able to identify novel group 1 and group 2 ILC subsets that exist after exposure to both fungal allergen and burn pit-related constituents (BPC) that include dioxin, aromatic hydrocarbon, and particulate matter. Toxin exposure in combination with fungal allergen induced activation of specific ILC1/NK and ILC2 populations as well as promoted neutrophilic lung inflammation. Oxidative stress pathways and downregulation of specific ribosomal protein genes (Rpl41 and Rps19) implicated in anti-inflammatory responses were present after BPC exposure. Increased IFNγ expression and other pro-neutrophilic mediator transcripts were increased in BPC-stimulated lung innate lymphoid cells. Further, the addition of BPC induced Hspa8 (encodes HSC70) and aryl hydrocarbon transcription factor activity across multiple lung ILC subsets. Overall, using an airway disease model that develops after occupational and environmental exposures, we demonstrate an effective method to better understand heterogenous ILC subset activation.

Asunto(s)

Inmunidad Innata , Pulmón , Linfocitos , Animales , Inmunidad Innata/efectos de los fármacos , Pulmón/inmunología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones , Linfocitos/inmunología , Linfocitos/metabolismo , Linfocitos/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Ratones Endogámicos C57BL , Material Particulado/efectos adversos , Material Particulado/toxicidad , Alérgenos/inmunología , Neumonía/inmunología , Neumonía/genética

RESUMEN

Fine inhalable particulate matter (PM) triggers an inflammatory response in the airways and activates mononuclear cells, mediators of tissue homeostasis, and tumour-promoting inflammation. We have assessed ex vivo responses of human monocytes and monocyte-derived macrophages to standardised air pollutants: carbon black, urban dust, and nanoparticulate carbon black, focusing on their pro-inflammatory and DNA-damaging properties. None of the PM (100 µg/mL/24 h) was significantly toxic to the cells, aside from inducing oxidative stress, fractional DNA damage, and inhibiting phagocytosis. TNFα was only slightly increased. PM nanoparticles increase the expression and activate DNA-damage-related histone H2A.X as well as pro-inflammatory NF-κB. We have shown that the urban dust stimulates the pathway of DNA damage/repair via the selective post-translational phosphorylation of H2A.X while nanoparticulate carbon black increases inflammation via activation of NF-κB. Moreover, the inflammatory response to lipopolysaccharide was significantly stronger in macrophages pre-exposed to urban dust or nanoparticulate carbon black. Our data show that airborne nanoparticles induce PM-specific, epigenetic alterations in the subsets of cultured mononuclear cells, which may be quantified using binary fluorescence scatterplots. Such changes intercede with inflammatory signalling and highlight important molecular and cell-specific epigenetic mechanisms of tumour-promoting inflammation.

Asunto(s)

Contaminantes Atmosféricos , Inflamación , FN-kappa B , Nanopartículas , Neoplasias , Material Particulado , Transducción de Señal , Hollín , Humanos , Inflamación/patología , Inflamación/metabolismo , Transducción de Señal/efectos de los fármacos , Nanopartículas/química , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/efectos adversos , Material Particulado/toxicidad , Hollín/toxicidad , Hollín/efectos adversos , FN-kappa B/metabolismo , Neoplasias/patología , Neoplasias/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Histonas/metabolismo , Daño del ADN , Estrés Oxidativo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

BACKGROUND: Diesel exhaust particles (DEP), which contain hazardous compounds, are emitted during the combustion of diesel. As approximately one-third of the vehicles worldwide use diesel, there are growing concerns about the risks posed by DEP to human health. Long-term exposure to DEP is associated with airway hyperresponsiveness, pulmonary fibrosis, and inflammation; however, the molecular mechanisms behind the effects of DEP on the respiratory tract are poorly understood. Such mechanisms can be addressed by examining transcriptional and DNA methylation changes. Although several studies have focused on the effects of short-term DEP exposure on gene expression, research on the transcriptional effects and genome-wide DNA methylation changes caused by long-term DEP exposure is lacking. Hence, in this study, we investigated transcriptional and DNA methylation changes in human adenocarcinoma alveolar basal epithelial A549 cells caused by prolonged exposure to DEP and determined whether these changes are concordant. RESULTS: DNA methylation analysis using the Illumina Infinium MethylationEPIC BeadChips showed that the methylation levels of DEP-affected CpG sites in A549 cells changed in a dose-dependent manner; the extent of change increased with increasing dose reaching the statistical significance only in samples exposed to 30 µg/ml DEP. Four-week exposure to 30 µg/ml of DEP significantly induced DNA hypomethylation at 24,464 CpG sites, which were significantly enriched for DNase hypersensitive sites, genomic regions marked by H3K4me1 and H3K27ac, and several transcription factor binding sites. In contrast, 9,436 CpG sites with increased DNA methylation levels were significantly overrepresented in genomic regions marked by H3K27me3 as well as H3K4me1 and H3K27ac. In parallel, gene expression profiling by RNA sequencing demonstrated that long-term exposure to DEP altered the expression levels of 2,410 genes, enriching 16 gene sets including Xenobiotic metabolism, Inflammatory response, and Senescence. In silico analysis revealed that the expression levels of 854 genes correlated with the methylation levels of the DEP-affected cis-CpG sites. CONCLUSIONS: To our knowledge, this is the first report of genome-wide transcriptional and DNA methylation changes and their associations in A549 cells following long-term exposure to DEP.

Asunto(s)

Metilación de ADN , Transcriptoma , Emisiones de Vehículos , Humanos , Metilación de ADN/efectos de los fármacos , Emisiones de Vehículos/toxicidad , Células A549 , Transcriptoma/efectos de los fármacos , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/efectos de los fármacos , Islas de CpG , Material Particulado/toxicidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/metabolismo

RESUMEN

Inhaled particulate matter (PM) is a key factor in millions of yearly air pollution-related deaths worldwide. The oxidative potential of PM indicates its ability to promote an oxidative environment. Excessive reactive oxygen species (ROS) can cause cell damage via oxidative stress, leading to inflammation, endoplasmic reticulum stress, airway remodeling, and various cell death modes (apoptosis, ferroptosis, pyroptosis). ROS can also interact with macromolecules, inducing DNA damage and epigenetic modifications, disrupting homeostasis. These effects have been studied extensively in vitro and confirmed in vivo. This review explores the oxidative potential of airborne particles and PM-induced ROS-mediated cellular damage observed in vitro, highlighting the link between oxidative stress, inflammation, and cell death modes described in the latest literature. The review also analyzes the effects of ROS on DNA damage, repair, carcinogenicity, and epigenetics. Additionally, the latest developments on the potential of antioxidants to prevent ROS's harmful effects are described, providing future perspectives on the topic.

Asunto(s)

Antioxidantes , Daño del ADN , Estrés Oxidativo , Material Particulado , Especies Reactivas de Oxígeno , Estrés Oxidativo/efectos de los fármacos , Material Particulado/toxicidad , Humanos , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Daño del ADN/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad , Epigénesis Genética/efectos de los fármacos

RESUMEN

Exposure to traffic-related air pollution and ultrafine particles (<100 nm; UFP) is linked with neurodegeneration. However, the impact of the aromatic content in fuels and the contribution of different fractions of UFP, i.e., solid UFP vs SVOC UFP, on neuronal function is unknown. We therefore studied effects on neuronal activity and viability in rat primary cortical cells exposed for up to 120 h to copper oxide particles (CuO) or UFP (solid and SVOC) emitted from a heavy-duty diesel engine fueled with petroleum diesel (A20; 20 % aromatics) or Hydrotreated Vegetable Oil-type fuel (A0; 0.1 % aromatics), or solid UFP emitted from a non-road Kubota engine fueled with A20. Moreover, effects of UFP and CuO upon simulated inhalation exposure were studied by exposing an lung model (Calu-3 and THP-1 cells) for 48 h and subsequently exposing the cortical cells to the medium collected from the basal compartment of the lung model. Additionally, cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress were studied in the lung model after 48 h exposure to UFP and CuO. Compared to control, direct exposure to CuO and SVOC UFP decreased neuronal activity, which was partly associated with cytotoxicity. Effects on neuronal activity upon direct exposure to solid UFP were limited. A20-derived UFP (solid and SVOC) were more potent in altering neuronal function and viability than A0 counterparts. Effects on neuronal activity from simulated inhalation exposure were minor compared to direct exposures. In the lung model, CuO and A20-derived UFP increased cytokine release compared to control, whereas CuO and SVOC A20 altered gene expression indicative for oxidative stress. Our data indicate that SVOC UFP exhibit higher (neuro)toxic potency for altering neuronal activity in rat primary cortical cells than the solid fraction. Moreover, our data suggest that reducing the aromatic content in fuel decreases the (neuro)toxic potency of emitted UFP.

Asunto(s)

Contaminantes Atmosféricos , Exposición por Inhalación , Material Particulado , Emisiones de Vehículos , Emisiones de Vehículos/toxicidad , Emisiones de Vehículos/análisis , Material Particulado/toxicidad , Ratas , Animales , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Neuronas/efectos de los fármacos , Tamaño de la Partícula , Cobre/toxicidad , Supervivencia Celular/efectos de los fármacos

RESUMEN

Ultrafine particles (UFP) are the smallest atmospheric particulate matter linked to air pollution-related diseases. The extent to which UFP's physical and chemical properties contribute to its toxicity remains unclear. It is hypothesized that UFP act as carriers for chemicals that drive biological responses. This study explores robust methods for generating reference UFP to understand these mechanisms and perform toxicological tests. Two types of combustion-related UFP with similar elemental carbon cores and physical properties but different organic loads were generated and characterized. Human alveolar epithelial cells were exposed to these UFP at the air-liquid interface, and several toxicological endpoints were measured. UFP were generated using a miniCAST under fuel-rich conditions and immediately diluted to minimize agglomeration. A catalytic stripper and charcoal denuder removed volatile gases and semi-volatile particles from the surface. By adjusting the temperature of the catalytic stripper, UFP with high and low organic content was produced. These reference particles exhibited fractal structures with high reproducibility and stability over a year, maintaining similar mass and number concentrations (100 µg/m3, 2.0·105 #/cm3) and a mean particle diameter of about 40 nm. High organic content UFP had significant PAH levels, with benzo[a]pyrene at 0.2 % (m/m). Toxicological evaluations revealed that both UFP types similarly affected cytotoxicity and cell viability, regardless of organic load. Higher xenobiotic metabolism was noted for PAH-rich UFP, while reactive oxidation markers increased when semi-volatiles were stripped off. Both UFP types caused DNA strand breaks, but only the high organic content UFP induced DNA oxidation. This methodology allows modification of UFP's chemical properties while maintaining comparable physical properties, linking these variations to biological responses.

Asunto(s)

Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Humanos , Material Particulado/toxicidad , Hollín/toxicidad , Tamaño de la Partícula , Pruebas de Toxicidad , Exposición por Inhalación

RESUMEN

Micro-nanoplastic particulates (MNPs) have been identified in both indoor and outdoor environments. From these real-world exposures, MNPs have been identified in human fluids and organ tissues, including the placenta and breastmilk. Laboratory studies have identified MNPs are capable of crossing the placental barrier and depositing in fetal tissues; however, it remained unclear if MNPs persist in offspring tissues after birth. Six pregnant Sprague-Dawley rats were divided equally into two groups: control and exposed to polyamide-12 (PA-12) MNP aerosols (11.46 ± 3.78 mg/m3) over an average of 4.35 h ± 0.39 for 10 non-consecutive days between gestational day (GD) 6 - GD 19, in our custom rodent exposure chamber, allowing for whole-body inhalation. Two-weeks after delivery in-house, offspring tissues (i.e. lung, liver, kidney, heart, brain) from 1 male and 1 female pup per litter were fixed in 4 % paraformaldehyde, sectioned, stained with hematoxylin and eosin, and assessed using hyperspectral dark-field microscopy. PA-12 MNPs were identified in all offspring tissues of the exposed dams. No MNPs were visualized in control tissues. These findings have important implications for human MNPs translocation, deposition, maternal/fetal health, and the developmental origins of health and disease. Further research is warranted to quantify MNPs mass deposition, biological accumulation, and systemic toxicity.

Asunto(s)

Exposición por Inhalación , Exposición Materna , Ratas Sprague-Dawley , Animales , Femenino , Embarazo , Ratas , Masculino , Contaminantes Atmosféricos/toxicidad , Microplásticos/toxicidad , Aerosoles , Material Particulado/toxicidad

RESUMEN

The aggregation and prion-like propagation of tau are the hallmarks of Alzheimer's disease (AD) and other tauopathies. However, the molecular mechanisms underlying the assembly and spread of tau pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk of AD. However, the molecular mechanisms remain unknown. Here, we showed that PM2.5 triggered the aggregation of tau and promoted the formation of tau fibrils. Injection of PM2.5-induced tau preformed fibrils (PFFs) into the hippocampus of tau P301S transgenic mice promoted the aggregation of tau and induced cognitive deficits and synaptic dysfunction. Furthermore, intranasal administration of PM2.5 exacerbated tau pathology and induced cognitive impairment in tau P301S mice. In conclusion, our results indicated that PM2.5 exposure promoted tau pathology and induced cognitive impairments. These results provide mechanistic insight into how PM2.5 increases the risk of AD.

Asunto(s)

Modelos Animales de Enfermedad , Hipocampo , Ratones Transgénicos , Material Particulado , Tauopatías , Proteínas tau , Animales , Material Particulado/toxicidad , Proteínas tau/metabolismo , Ratones , Tauopatías/metabolismo , Tauopatías/patología , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/efectos de los fármacos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/etiología , Agregación Patológica de Proteínas/metabolismo , Humanos , Masculino

RESUMEN

Fine particulate matter (PM2.5) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM2.5 on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (Isc) and airway surface liquid (ASL) significantly decreased after PM2.5 exposure. In addition, PM2.5 exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM2.5 exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM2.5. Together, our study reveals that PM2.5 impairs the ATP-induced transepithelial anion Isc through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM2.5-mediated airway epithelial injury.

Asunto(s)

Asma , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Material Particulado , Receptores Purinérgicos P2Y2 , Animales , Ratones , Receptores Purinérgicos P2Y2/metabolismo , Receptores Purinérgicos P2Y2/genética , Asma/metabolismo , Asma/patología , Asma/tratamiento farmacológico , Asma/inducido químicamente , Asma/inmunología , Material Particulado/efectos adversos , Material Particulado/toxicidad , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Humanos , Adenosina Trifosfato/metabolismo , Ovalbúmina/inmunología , Transducción de Señal/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología

RESUMEN

A key challenge in oxidative potential (OP) assays is to accurately assess the cumulative impact of redox-active aerosol species rather than only their individual effects. This study investigates the OP of single and combined mixtures of 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ), 9,10-phenanthrenequinone (9,10-PQ), 1,4-benzoquinone (1,4-BQ), Cu, Fe, Mn, and Zn in standard ascorbic acid (OPAA) and the synthetic respiratory tract lining fluid (OPRTLF) assays. In both OPAA and OPRTLF, binary mixtures showed additive and synergistic effects in the presence of 1,2-NQ. The mixture of Cu and Zn showed substantial synergisms in both assays, while the mixtures in the absence of 1,2-NQ primarily induced antagonistic effects. For the first time, we propose linear equations to improve the prediction of OP values by considering the impacts of synergistic and antagonistic effects. Under this approach, we observed that the potential effects caused by binary mixtures in ambient particulate matter (PM) samples could account for up to 68 % of the PM-OP values in Fez, Morocco (OPmAA: 0.34 nmol min-1 µg-1 and OPmRTLF: 0.18 nmol min-1 µg-1). The present study improves the understanding of effects of chemical interaction of potentially toxic substances that are important in the understanding of PM-induced oxidative stress in the human body.

Asunto(s)

Ácido Ascórbico , Oxidación-Reducción , Quinonas , Ácido Ascórbico/farmacología , Ácido Ascórbico/química , Quinonas/química , Metales/toxicidad , Material Particulado/toxicidad , Material Particulado/análisis

RESUMEN

Air pollution exposure has been linked with coagulation function. However, evidence is limited for the relationships between air pollution, coagulation function and metabolomics in humans. We recruited a panel of 130 rural elderly from the Chayashan township in China, all of whom were free of pre-existing cardiovascular diseases and had provided residential address information. We conducted clinical examinations and collected blood samples from these rural elderly for the detection of coagulation biomarkers (e.g, activated partial thromboplastin time, fibrinogen, thrombin time, and prothrombin time) and untargeted metabolites in both December 2021 and August 2022. We used mini ambient air quality monitor to measure the mean levels of five air pollutants (e.g., PM2.5, SO2, NO2, CO and O3) during 1 to 2 weeks before blood sample collection. The Mummichog pathway analysis was used to identified potential metabolic features and pathways. In this study, we identified 5 pathways associated with both air pollution and coagulation function, and further pinpointed eight metabolic features within these pathways. The majority of these features were lipids, including arachidonic acid and linoleic acid. Overall, the findings of this study offer insights into potential mechanisms, particularly lipid metabolism, that may underlie the association between air pollution and coagulation function.

Asunto(s)

Contaminantes Atmosféricos , Coagulación Sanguínea , Población Rural , Humanos , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Anciano , Masculino , Coagulación Sanguínea/efectos de los fármacos , Femenino , China , Exposición a Riesgos Ambientales/análisis , Material Particulado/análisis , Material Particulado/toxicidad , Redes y Vías Metabólicas/efectos de los fármacos , Biomarcadores/sangre , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Anciano de 80 o más Años , Persona de Mediana Edad

RESUMEN

Li et al. [1] have commented on our recent paper investigating the association between exposure to fine particulate matter (PM2.5) constituents and the risk of cognitive impairment [2]. They provided a Mendelian randomization (MR) analysis using large-scale genome-wide association study (GWAS) datasets from the European population, confirming a causal relationship between PM2.5 exposure and cognitive performance. In our reply, we employed three causal inference models, including a generalized propensity score (GPS) adjusted Cox model, an inverse-probability weights (IPW) weighted Cox model, and a trimmed IPW-weighted Cox model, to confirm the relationship of PM2.5 and cognitive impairment in our study cohort.

Asunto(s)

Cognición , Análisis de la Aleatorización Mendeliana , Material Particulado , Material Particulado/toxicidad , Humanos , Cognición/efectos de los fármacos , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Atmosféricos/toxicidad , Estudio de Asociación del Genoma Completo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/genética , Modelos de Riesgos Proporcionales

RESUMEN

PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.

Asunto(s)

Neoplasias Pulmonares , Material Particulado , ARN Interferente Pequeño , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/patología , Material Particulado/toxicidad , Humanos , Contaminantes Atmosféricos/toxicidad