Nano-sized Particulate Matter Research Articles

Genetic background modulates the sensitivity of Caenorhabditis elegans to the toxic effects of vehicular air pollution.

Vehicular air pollution is an environmental toxicant that can have several health consequences, such as decreased respiratory and cardiovascular function and an increased incidence of age-related dementia and neurodegenerative diseases such as Alzheimer’s disease. C. elegans has been previously shown to be a valuable animal model to study the effects of air pollution due to its tendency to respond to acute exposure to nano-sized particulate matter (nPM) produced by vehicular emissions. Specifically, nPM causes delayed development resulting in smaller animal size and induction of the SKN-1-mediated oxidative stress response. Here we show that various wild isolates demonstrate differential susceptibility to nPM, as measured by body size. Specifically, the Hawaiian isolate, CB4856, displayed the highest sensitivity, equivalent to its sensitivity to the potent oxidant paraquat. The findings described herein suggest that C. elegans may be a useful genetic tool for identifying nPM-susceptibility loci.

Cerebral cortex and blood transcriptome changes in mouse neonates prenatally exposed to air pollution particulate matter

BackgroundPrenatal exposure to air pollutants is associated with increased risk for neurodevelopmental and neurodegenerative disorders. However, few studies have identified transcriptional changes related to air pollutant exposure.MethodsRNA sequencing was used to examine transcriptomic changes in blood and cerebral cortex of three male and three female mouse neonates prenatally exposed to traffic-related nano-sized particulate matter (nPM) compared to three male and three female mouse neonates prenatally exposed to control filter air.ResultsWe identified 19 nPM-associated differentially expressed genes (nPM-DEGs) in blood and 124 nPM-DEGs in cerebral cortex. The cerebral cortex transcriptional responses to nPM suggested neuroinflammation involvement, including CREB1, BDNF, and IFNγ genes. Both blood and brain tissues showed nPM transcriptional changes related to DNA damage, oxidative stress, and immune responses. Three blood nPM-DEGs showed a canonical correlation of 0.98 with 14 nPM-DEGS in the cerebral cortex, suggesting a convergence of gene expression changes in blood and cerebral cortex. Exploratory sex-stratified analyses suggested a higher number of nPM-DEGs in female cerebral cortex than male cerebral cortex. The sex-stratified analyses identified 2 nPM-DEGs (Rgl2 and Gm37534) shared between blood and cerebral cortex in a sex-dependent manner.ConclusionsOur findings suggest that prenatal nPM exposure induces transcriptional changes in the cerebral cortex, some of which are also observed in blood. Further research is needed to replicate nPM-induced transcriptional changes with additional biologically relevant time points for brain development.

Urban Air Pollution Nanoparticles from LosAngeles: Recently Decreased Neurotoxicity.

Air pollution is widely associated with accelerated cognitive decline at later ages and risk of Alzheimer's disease (AD). Correspondingly, rodent models demonstrate the neurotoxicity of ambient air pollution and its components. Our studies with nano-sized particulate matter (nPM) from urban Los Angeles collected since 2009 have shown pro-amyloidogenic and pro-inflammatory responses. However, recent batches of nPM have diminished induction of the glutamate receptor GluA1 subunit, Iba1, TNFα, Aβ42 peptide, and white matter damage. The same methods, materials, and mouse genotypes were used throughout. Expand the nPM batch comparisons and evaluate archived brain samples to identify the earliest change in nPM potency. Batches of nPM were analyzed by in vitro cell assays for NF-κB and Nrf2 induction for comparison with in vivo responses of mouse brain regions from mice exposed to these batches, analyzed by PCR and western blot. Five older nPM batches (2009-2017) and four recent nPM batches (2018, 2019) for NF-κB and Nrf2 induction showed declines in nPM potency after 2017 that paralleled declines of in vivo activity from independent exposures in different years. Transcription-based in vitro assays of nPM corresponded to the loss of in vivo potency for inflammatory and oxidative responses. These recent decreases of nPM neurotoxicity give a rationale for evaluating possible benefits to the risk of dementia and stroke in Los Angeles populations.

Adult mouse hippocampal transcriptome changes associated with long-term behavioral and metabolic effects of gestational air pollution toxicity

Gestational exposure to air pollution increases the risk of autism spectrum disorder and cognitive impairments with unresolved molecular mechanisms. This study exposed C57BL/6J mice throughout gestation to urban-derived nanosized particulate matter (nPM). Young adult male and female offspring were studied for behavioral and metabolic changes using forced swim test, fat gain, glucose tolerance, and hippocampal transcriptome. Gestational nPM exposure caused increased depressive behaviors, decreased neurogenesis in the dentate gyrus, and increased glucose tolerance in adult male offspring. Both sexes gained fat and body weight. Gestational nPM exposure induced 29 differentially expressed genes (DEGs) in adult hippocampus related to cytokine production, IL17a signaling, and dopamine degradation in both sexes. Stratification by sex showed twofold more DEGs in males than females (69 vs 37), as well as male-specific enrichment of DEGs mediating serotonin signaling, endocytosis, Gαi, and cAMP signaling. Gene co-expression analysis (WCGNA) identified a module of 43 genes with divergent responses to nPM between the sexes. Chronic changes in 14 DEGs (e.g., microRNA9-1) were associated with depressive behaviors, adiposity and glucose intolerance. These genes enriched neuroimmune pathways such as HMGB1 and TLR4. Based on cerebral cortex transcriptome data of neonates, we traced the initial nPM responses of HMGB1 pathway. In vitro, mixed glia responded to 24 h nPM with lower HMGB1 protein and increased proinflammatory cytokines. This response was ameliorated by TLR4 knockdown. In sum, we identified transcriptional changes that could be associated with air pollution-mediated behavioral and phenotypic changes. These identified genes merit further mechanistic studies for therapeutic intervention development.

Particulate matter as a possible reservoir of multidrug-resistant microorganisms in surgical healthcare settings

Aim. To study the microbial diversity and dust organic component in surgical healthcare settings and to assess the risk of dust-mediated transmission of healthcare-associated infections. Materials and Methods . Dust sampling (n = 41) was carried out using sterile gloves and containers from ventilation grilles and adjacent air ducts of the exhaust ventilation systems in various healthcare settings. Size and shape of dust particles were studied by means of scanning electron microscopy and dynamic light scattering. Elemental analysis (CHNSO) was conducted employing high temperature catalytic oxidation. Bacterial composition of the dust was investigated using a VITEK 2 Compact biochemical analyzer while viral diversity was screened by polymerase chain reaction. Results. Dust in healthcare units consisted of globular particles and/or microsized fibers. Regardless of the healthcare setting, globular particles prevailed in the dust structure. Dust nanoparticles was characterised by an average first size peak of 85.6 ± 12.6 nm and an average second peak of 307.1 ± 76.2 nm. Dust collected in non-surgical units contained a higher nitrogen content than surgical settings (p < 0.001). Proportions of hydrogen, carbon, and sulfur did not differ between non-surgical and surgical units. The dust collected from healthcare settings in different cities also varied in nitrogen content (p = 0.033). A wide microbial diversity was detected in dust samples and a high frequency (46.34%) of its contamination was found. In surgical departments, dust contamination was notable for multidrug-resistant bacteria (28.57%), while viruses prevailed in non-surgical departments (23.3%). Conclusions. Dust generated in surgical departments contains nanosized particulate matter, multidrug-resistant microorganisms, and a prominent organic component all defining it as a possible reservoir of multidrug-resistant microorganisms which may potentially cause healthcare-associated infections via airborne transmission.

Cell-based assays that predict in vivo neurotoxicity of urban ambient nano-sized particulate matter

Exposure to urban ambient particulate matter (PM) is associated with risk of Alzheimer's disease and accelerated cognitive decline in normal aging. Assessment of the neurotoxic effects caused by urban PM is complicated by variations of composition from source, location, and season. We compared several in vitro cell-based assays in relation to their in vivo neurotoxicity for NF-κB transcriptional activation, nitric oxide induction, and lipid peroxidation. These studies compared batches of nPM, a nanosized subfraction of PM2.5, extracted as an aqueous suspension, used in prior studies. In vitro activities were compared with in vivo responses of mice chronically exposed to the same batch of nPM.The potency of nPM varied widely between batches for NF-κB activation, analyzed with an NF-κB reporter in human monocytes. Three independently collected batches of nPM had corresponding differences to responses of mouse cerebral cortex to chronic nPM inhalation, for levels of induction of pro-inflammatory cytokines, microglial activation (Iba1), and soluble Aβ40 & −42 peptides. The in vitro responses of BV2 microglia for NO-production and lipid peroxidation also differed by nPM batch, but did not correlate with in vivo responses. These data confirm that batches of nPM can differ widely in toxicity. The in vitro NF-κB reporter assay offers a simple, high throughput screening method to predict the in vivo neurotoxic effects of nPM exposure.

Effect of operating conditions and speed on nanoparticle emission from diesel and gasoline driven light duty vehicles

A comparative assessment is presented for nano-sized particulate matter emission from diesel and gasoline driven light duty cars. Measurements are reported for particle size range of 10–420 nm considering the health hazard associated with the smallest diameter particles. Analysis is carried out in laboratory condition by varying engine load. For stationary car, nanoparticle emission and dispersion phenomena are examined for idling and throttling condition at various revolutions per minutes (RPM). For moving vehicle the influence of vehicle speed, acceleration/deceleration on nanoparticle size distribution of gasoline and diesel cars are reported. Measurements presented in this paper reveal that number concentration of gasoline vehicle increases with load and for all loads maximum number concentration is associated with the smallest sized particles. On the other hand particle number concentration increase is negligible for diesel cars beyond a certain load with peak shifting to larger size. The number concentration increases with acceleration of the gasoline vehicle, the number being significantly high when the vehicle is accelerated at a faster rate. On the other hand for diesel vehicle, the total number concentration shows an increase even for sudden deceleration of the vehicle.

Air Pollution Alters Caenorhabditis elegans Development and Lifespan: Responses to Traffic-Related Nanoparticulate Matter.

Air pollution is a heterogeneous environmental toxicant that impacts humans throughout their life. We introduce Caenorhabditis elegans as a valuable air pollution model with its short lifespan, medium-throughput capabilities, and highly conserved biological pathways that impact healthspan. We exposed developmental and adult life stages of C. elegans to airborne nano-sized particulate matter (nPM) produced by traffic emissions and measured biological and molecular endpoints that changed in response. Acute nPM did not cause lethality in C. elegans, but short-term exposure during larval stage 1 caused delayed development. Gene expression responses to nPM exposure overlapped with responses of mouse and cell culture models of nPM exposure in previous studies. We showed further that the skn-1/Nrf2 antioxidant response has a role in the development and hormetic effects of nPM. This study introduces the worm as a new resource and complementary model for mouse and cultured cell systems to study air pollution toxicity across the lifespan.

Nanoparticulate matter exposure results in neuroinflammatory changes in the corpus callosum.

Epidemiological studies have established an association between air pollution particulate matter exposure (PM2.5) and neurocognitive decline. Experimental data suggest that microglia play an essential role in air pollution PM-induced neuroinflammation and oxidative stress. This study examined the effect of nano-sized particulate matter (nPM) on complement C5 deposition and microglial activation in the corpus callosum of mice (C57BL/6J males). nPM was collected in an urban Los Angeles region impacted by traffic emissions. Mice were exposed to 10 weeks of re-aerosolized nPM or filtered air for a cumulative 150 hours. nPM-exposed mice exhibited reactive microglia and 2-fold increased local deposition of complement C5/ C5α proteins and complement component C5a receptor 1 (CD88) in the corpus callosum. However, serum C5 levels did not differ between nPM and filtered air cohorts. These findings demonstrate white matter C5 deposition and microglial activation secondary to nPM exposure. The C5 upregulation appears to be localized to the brain.

On-field and laboratory measurement of nanoparticle emission in the wake of gasoline vehicle

Nanoparticle emission from gasoline driven vehicles is reported to be significantly lower compared to diesel vehicles. Accordingly, there is no threshold limit implemented by the regulatory authorities in India for gasoline driven vehicles. Recent studies however indicate that this is true as far as the mass concentration of the nanoparticles is concerned. The number concentration of nanoparticles particularly of smaller dimensions is reported to be significantly higher for gasoline driven vehicles under certain operating range of speed and load. Smaller the dimension of the particles more are their residence time in environment and more susceptible are these particles to be inhaled by human respiratory and cardiovascular system. Thus an estimate of the size distribution of nano-sized particulate matter emission from gasoline driven vehicle is of immense importance in context to Indian urban population. In this direction, laboratory measurements are reported for the nanoparticle size distribution emitted from a gasoline engine under different loading conditions. On-field measurements are carried out in the wake of a stationary vehicle under idling and throttling condition. Simultaneous measurement of vehicular acceleration and deceleration is also reported along with nanoparticle distribution in the wake of a moving vehicle. The measurements reported in this paper reveal the need for deciding threshold value of number concentration to be implemented for gasoline vehicles by the Indian regulatory authorities.

Differential pattern of deposition of nanoparticles in the airways of exposed workers

Ultrafine particles (UFP) have been postulated to significantly contribute to the adverse health effects associated with exposure to particulate matter (PM). Due to their extremely small size (aerodynamic diameter <100 nm), UFP are able to deposit deep within the lung after inhalation and evade many mechanisms responsible for the clearance of larger particles. There is a lack of biologically relevant personal exposure metrics for exposure to occupational- and environmental-related micro- and nano-sized PM. The aim of the present study is to assess UFP in induced sputum (IS) and exhaled breath condensate (EBC) as possible biomarkers for assessing lung function impairment. Sputum induction and EBC testing were performed by conventional methods. UFP particles were assessed with the NanoSight LM20 (NanoSight Ltd, London, UK). The subjects included 35 exposed and 25 non-exposed workers. There were no group differences in pulmonary function test results and differential cell counts, but 63.6% of the exposed subjects had a higher percentage of neutrophils (OR3.28 p = 0.03) compared to the non-exposed subjects. The exposed subjects had higher percentages of UFP between 10 and 50 nm (69.45 ± 18.70 vs 60.11 ± 17.52 for the non-exposed group, p = 0.004). No differences were found in the IS samples. Years of exposure correlated positively to UFP content (r = 0.342 p = 0.01) and macrophage content (r = −0.327 p = 0.03). The percentage of small fraction of UFP in EBC, but not IS, is higher in exposed workers, and EBC may be a sensitive biomarker to assess exposure to nanoparticles.

Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models

Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer’s disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women’s Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.

Urban air pollutants reduce synaptic function of CA1 neurons via an NMDA/NȮ pathway in vitro

Airborne particulate matter (PM) from urban vehicular aerosols altered glutamate receptor functions and induced glial inflammatory responses in rodent models after chronic exposure. Potential neurotoxic mechanisms were analyzed in vitro. In hippocampal slices, 2 h exposure to aqueous nanosized PM (nPM) selectively altered post-synaptic proteins in cornu ammonis area 1 (CA1) neurons: increased GluA1, GluN2A, and GluN2B, but not GluA2, GluN1, or mGlur5; increased post synaptic density 95 and spinophilin, but not synaptophysin, while dentate gyrus (DG) neurons were unresponsive. In hippocampal slices and neurons, MitoSOX red fluorescence was increased by nPM, implying free radical production. Specifically, NȮ production by slices was increased within 15 min of exposure to nPM with dose dependence, 1-10 μg/mL. Correspondingly, CA1 neurons exhibited increased nitrosylation of the GluN2A receptor and dephosphorylation of GluN2B (S1303) and of GluA1 (S831 & S845). Again, DG neurons were unresponsive to nPM. The induction of NȮ and nitrosylation were inhibited by AP5, an NMDA receptor antagonist, which also protects neurite outgrowth in vitro from inhibition by nPM. Membrane injury (EthidiumD-1 uptake) showed parallel specificity. Finally, nPM decreased evoked excitatory post-synaptic currents of CA1 neurons. These findings further document the selective impact of nPM on glutamatergic functions and identify novel responses of NMDA receptor-stimulated NȮ production and nitrosylation reactions during nPM-mediated neurotoxicity. We present three new findings of rapid hippocampal slice responses to nPM (nano-sized particulate matter from urban traffic): increased NȮ production within 15 min; nitrosylation of glutamatergic NMDA receptors; and, reduced excitatory postsynaptic currents in CA1 neurons. AP5 (NMDA receptor antagonist) blocked nPM-mediated NȮ and receptor nitrosylation. Ca(2+) influx is a likely mechanism.

Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction

Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) regulated expression of multiple antioxidant and cytoprotective genes through the electrophile responsive element (EpRE) is well established, interaction of Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well understood. Due to either proteolysis or alternative translation, Nrf1 has been found as proteins of varying size, p120, p95, and p65, which have been described as either activators of EpRE or competitive inhibitors of Nrf2. We investigated the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and modifier subunits of glutamate cysteine ligase (GCLC and GCLM) as models and explored the potential role of Nrf1 in altering their expression in aging and upon chronic exposure to airborne nano-sized particulate matter (nPM). Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1) cells. Overexpression Nrf2 in combination with either p120 or p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase activity. All known forms of Nrf1 protein, remained unchanged in the lungs of mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE activity in vitro, whereas the precise role of Nrf1 in vivo requires further investigations. We conclude that Nrf1 may not be directly responsible for the loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes observed in aged animals.

Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments

Many xenobiotic detoxifying (phase II) enzymes are induced by sublethal doses of environmental toxicants. However, these adaptive mechanisms have not been studied in response to vehicular-derived airborne nano-sized particulate matter (nPM). Because aging is associated with increased susceptibility to environmental toxicants, we also examined the expression of Nrf2-regulated phase II genes in middle-aged mice and their inducibility by chronic nPM. The nPM from vehicular traffic was collected in urban Los Angeles and reaerosolized for exposure of C57BL/6J male mice (3 and 18months old) for 150h over 10weeks. Brain (cerebellum), liver, and lung were assayed by RT-PCR and/or Western blots for the expression of phase II enzymes, glutamate cysteine ligase (catalytic GCLC, and modifier GCLM subunits), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), and relevant transcription factors, NF-E2-related factor 2 (Nrf2), c-Myc, Bach1. Chronic nPM exposure induced GCLC, GCLM, HO-1, NQO1 mRNA, and protein similarly in cerebellum, liver, and lung of young mice. Middle-aged mice had elevated basal levels, but showed impaired further induction by nPM. Similarly, Nrf2 increased with age and was induced by nPM in young but not old. c-Myc showed the same age and induction profile while the age increase in Bach1 was further induced by nPM. Chronic exposure to nanoparticles induced Nrf2-regulated detoxifying enzymes in brain (cerebellum), liver, and lung of young adult mice, indicating a systemic impact of nPM. In contrast, middle-aged mice did not respond above their elevated basal levels except for Bach1. The lack of induction of phase II enzymes in aging mice may be a model for the vulnerability of elderly to air pollution.

Si3N4 with comparable permeability to SiC

Abstract Porous sintered reaction-bonded silicon nitrides (SRBSNs) with comparable permeability to SiC were fabricated using presintered Si-additive mixture granules. By increasing the granule strength through the adjustment of the presintering conditions, the strengthened sturdiness of the granules led to an increase in the pore channel size. Porous SRBSNs with ≥60% porosity were achieved without employing a pore former due to the formation of intragranular narrow pore channels as well as intergranular wide pore channels. As the specific pore area of the developed SRBSN is nearly 26 times that of SiC with similar permeability, superior filtering efficiency for nano-sized particulate matter is expected.

Emission characteristics of exhaust gases and nanoparticles from a diesel engine with biodiesel-diesel blended fuel (BD20)

This experimental study sought to investigate the characteristics of the exhaust emissions, and nanoparticle size distribution of particulate matter (PM) emitted from diesel engines fueled with 20% biodiesel-diesel blended fuel (BD20). The study also investigated the conversion efficiency of the warm-up catalytic converter (WCC). The emission characteristics of HC, CO, NOx and nano-sized PM were also observed according to engine operating conditions with and without exhaust gas recirculation (EGR). The study revealed that the maximum torque achievable with the biodieseldiesel blended fuel was slightly lower than that achievable with neat diesel fuel at high-load conditions. Smoke was decreased by more than 20% in all 13 modes. While the CO and THC emissions of BD20 slightly decreased, the NOx emission of BD20 increased by 3.7%. Measured using the scanning mobility particle sizer (SMPS), the total number and total mass of the nanoparticles in the size range between 10.6nm and 385nm were reduced by about 10% and 25%, respectively, when going from D100 to BD20. The particle number and mass for both fuels were reduced by about 43% when going from with EGR to without EGR. When EGR was applied in the engine system, the particle number and mass were reduced by 24%, and 16%, respectively, when going from D100 to BD20.

Nanoparticulate-induced toxicity and related mechanism in vitro and in vivo

In urban areas, the quantity of exhaust particles from vehicle emissions is tremendous and has been regarded as the main contributor to particulate matter (PM) pollution. Recently, the nano-sized PM on public health has begun to raise the attention. The increased toxicity of nanoparticulate can be largely explained by their small size, high airborne concentration, extensive surface area and high content of organic carbon and transition metals. We have attempted to address the toxicity of nano sized-particlulate matter by comparing various particulates including micro-SiO2 (mSiO2), nano-SiO2 (nSiO2), micro-TiO2 (mTiO2), and nano-TiO2 (nTiO2) in RAW264.7 cells and in vivo. The cell viability of all particulates decreased dose dependently. 24-h incubation with nSiO2 demonstrated apoptosis in RAW264.7 using Annexin-V binding immunofluorescent microscopy, but not in any other particulates. In vivo, cytotoxicity of nanosized was higher than micro-sized particulates. As higher the concentration of particulates, the more pulmonary injury and neutrophilic infiltration were observed in nano-sized than micro-sized particulates, respectively. Particularly, 5.0 mg/kg of mTiO2 never shows any increase of neutrophile even with high cellularity of total cells and macrophages. From these results, we suggested that particulate-induced respiratory toxicity be influenced by component, size, and dose of particulates including the characteristic nature of the target cells in vitro and in vivo.