measuring-carbon-content-airway-macrophages-exposed-to-carbon

Measuring Carbon Content in Airway Macrophages Exposed to Carbon-Containing Particulate Matters

Pulmonary macrophages exhibit a dose-dependent pattern in phagocytizing particles. Following engulfment, these macrophages are subsequently excreted with ...

Qingdao University

Carbon black (CB) particulates as virtually pure elemental carbon can deposit deep in the lungs of humans. International Agency for Research on Cancer classified CB as a Group 2B carcinogen due to inconclusive human evidence. A molecular epidemiological study was conducted in an established cohort of CB packers (CBP) to assess associations between CB exposure and genomic instability in peripheral lymphocytes using cytokinesis-block micronucleus assay (CBMN). Carbon content in airway macrophages (CCAM) was quantified as a bio-effective dosimeter for chronic CB exposure. Dose-response observed in CBPs was compared to that seen in workers exposed to diesel exhaust. The association between CB exposure status and CBMN endpoints was identified in 85 CBPs and 106 non-CBPs from a 2012 visit and replicated in 127 CBPs and 105 non-CBPs from a 2018 visit. The proportion of cytoplasm area occupied by carbon particles in airway macrophages was over fivefold higher in current CBPs compared to non-CBPs and was associated with CBMN endpoints in a dose-dependent manner. CB aerosol and diesel exhaust shared the same potency of inducing genomic instability in workers. Circulatory pro-inflammatory factors especially TNF-α was found to mediate associations between CB exposure and CBMN endpoints. In vitro functional validation supported the role of TNF-α in inducing genomic instability. An estimated range of lower limits of benchmark dose of 4.19-7.28% of CCAM was recommended for risk assessment. Chronic CB exposure increased genomic instability in human circulation and this provided novel evidence supporting its reclassification as a human carcinogen.

Carbon content in airway macrophages and genomic instability in Chinese carbon black packers.

Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments.

Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay.

Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation.

The combination of layered nanorod arrays with unique core-shell structure and transition metal layered double hydroxide (LDH) is considered as a feasible solution to improve the electrochemical performances of capacitor electrode. In this study, layered ZnNiFe-LDH@Cu(OH)/CF core-shell nanorod arrays, which consist of ultrathin ZnNiFe-LDHs nanosheet shells and ordered Cu(OH) nanorod inner cores, are successfully designed and fabricated by a typical hydrothermal way and a simple in situ oxidation reaction. The electrode prepared using ZnNiFe-LDH@Cu(OH)/CF nanomaterial reveals an remarkable area capacitance of 6100 mF cm at 3 mA cm current density, which is excellently superior than those of ZnFe-LDH@Cu(OH)/CF, NiFe-LDH@Cu(OH)/CF, Cu(OH)/CF and CF. Additionally, the capacitance retention remains as high as 83.4% after 5000 cycles and a very small Rs (0.567 Ω) can be observed. In addition, an asymmetric supercapacitor device is successfully fabricated employing ZnNiFe-LDH@Cu(OH)/CF. Meanwhile, the ZnNiFe-LDH@Cu(OH)/CF//AC device can achieve an energy density of 44 Wh kg and a corresponding power density of 720 W kg and possess the capability to light up a multi-function monitor for 33 min just using two ASC equipments connected in series. Therefore, the prepared ZnNiFe-LDH@Cu(OH)/CF composite materials with unique structure has great application potential in energy storage devices.

Origami and layered-shaped ZnNiFe-LDH synthesized on Cu(OH) nanorods array to enhance the energy storage capability.

The excellent electrical conductivity of graphene is due to its highly-conjugated structures. Manipulation of the electronic and mechanical properties of graphene can be achieved by controlling the destruction of its in-sheet conjugation system. Herein, we report the preparation of CoCeS -SA@BPMW@RGO through π-π stacking interactions at the molecular level. In this study, sodium alginate was reacted with Co and Ce , and the composite was loaded onto a graphene surface. The graphene sheets were prepared using a bi-pyrene terminated molecular wire (BPMW) to avoid re-stacking of the grapheme sheets, thereby forming nanoscale spaces between sheets. The angle between the BPMW coplanar pyrene group and the phenyl group was 33.2°, and the graphene layer is supported in an oblique direction. Finally, a three-dimensional porous composite was obtained after annealing and vulcanization. The obtained CoCeS -SA@BPMW@RGO exhibited excellent electrical conductivity and remarkable cycle stability. When the current density was 1 A g , its specific capacitance was as high as 1004 F g . BPMW modifies graphene through the synergistic effect of π-π stacking interaction and special structure to obtain excellent electrochemical performance. Moreover, a solid-state asymmetric supercapacitor device was fabricated based on the synthesized CoCeS -SA@BPMW@RGO hybrid, which exhibited a power density of 979 W kg at an energy density of 23.96 Wh kg .

In Situ Synthesis of CoCeS Bimetallic Sulfide Nanoparticles on a Bi-Pyrene Terminated Molecular Wire Modified Graphene Surface for Supercapacitors.

Growing evidence has indicated that air pollution is associated with depression, and damage of olfactory bulb (OB) is regarded as an early marker for depression. However, the toxicity of fine particulate matter (PM) on OB and underlying mechanisms remains to be elucidated. In our study, a real-ambient PM exposure system was applied to explore the effects of PM on OB in C57BL/6 mice for 4 or 8 weeks. After 8 weeks exposure, the mice emerged potential depressive-like responses with reduction and disorder of cells in olfactory bulb tissues. Apoptosis and ultra-microstructure analysis indicated that the real-ambient PM exposure caused the neuronal death of OB. The immunofluorescence observation and KEGG pathway analysis revealed the real-ambient PM exposure induced microglia activation along with tumor necrosis factor α (TNFα)-mediated signaling enriched in OB of mice with depression-like behaviors. Moreover, results from ex vivo biosensor assay exhibited that PM might trigger systemic inflammation with increased levels of various proinflammatory factors to activate microglia. Further in vitro co-culture model identified that the PM evoked microglia cells activation with TNFα secretion and induced neuronal cells apoptosis via classical caspase3 signaling. Our findings provide new insights that PM induced microglia activation characterized by the release of TNFα to cause neurotoxicity either by direct action or by circulatory inflammation, resulting in OB damage, which may play a critical role in early diagnosis and pathogenic mechanisms for PM to cause depression.

Olfactory bulb microglia activation mediated neuronal death in real-ambient particulate matter exposure mice with depression-like behaviors.

Chronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown.

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust.

As a widely used pure elemental carbon in colloidal particles, carbon black was listed as a group 2B carcinogen by IARC in 2010. The most available mechanism information about carbon black and carcinogenesis are from in vivo or in vitro studies. However, few studies concerned the nanoparticle's real-ambient exposure causing systemic change and further affecting the target organ. Herein, we used an ex vivo biosensor assay to investigate the transcriptome change of primary bronchial epithelial cells after treatment with the plasma from workers with long-term occupational carbon black exposure history. Based on ex vivo biosensor assay and transcriptome sequencing, we found the effect of internal systemic environment on epithelial cells after carbon black exposure was an inflammatory response, which mainly activates cell cycle-related pathways. After exposure to carbon black, the internal systemic environment could activate cancer-related pathways like epithelial-mesenchymal transition, hypoxia, TNF-α signaling via NF-κB. The hub genes in the carbon black group (CDC20 and PLK1) and their correlation with the systemic environment were uncovered by constructing the protein-protein interaction network. Inflammatory cytokines, especially CRP, were strongly correlated with the expression of CDC20 and PLK1. Besides, we also find a strong correlation between CDC20 and cytokinesis-block micronucleus endpoints in peripheral blood (rho = 0.591, P < 0.001). Our results show that long-term carbon black exposure might activate cell cycle-related pathways through circulating inflammation and increase the risk of cancer, while the oxidative stress caused by diesel exhaust particles are mainly related to PAHs exposure. After exposure to carbon black, the systemic environment could activate cancer-related pathways like diesel exhaust particles, increasing the risk of lung cancer. These attempts might provide a further understanding of the indirect effect of chronic occupational inhaled carbon black exposure on pulmonary carcinogenesis.

Chronic carbon black nanoparticles exposure increases lung cancer risk by affecting the cell cycle via circulatory inflammation.

Plenty of rural populations still chronically exposed to indoor coal burning, which tremendously raises the risk of cardiovascular disease, in China. This study aimed to further investigate the association between indoor coal burning exposure and atherosclerotic cardiovascular diseases to search for relevant markers for disease prevention. Herein, we conducted a cross-sectional study, carried out on 752 local long-term residents with or without bituminous coal for cooking and heating indoor, in Nangong County, Hebei Province, China. We utilized a nearest neighbor propensity score match (PSM) with a caliper distance equal to 0.001 to eliminate bias caused by confounding factors. The expression of genes associated with endothelial activation (CCL2, CCL5, CXCL8, CXCL12, VCAM, ICAM, SELP) in primary human coronary artery endothelial cells (HCAECs) were quantified through ex vivo biosensor assay. Multiple linear regression models with stratification analyses by gender and binary logit regression models were used to evaluate the association between mRNA expression of biosensor genes and indoor coal burning pollution or carotid atherosclerosis, respectively. Protein secretion level was detected by enzyme-linked immunosorbent assay (ELISA). The prevalence of carotid atherosclerosis in exposure group was higher than control (P = 0.023), before PSM. The gene expression of CCL2 in exposure group was significantly higher than control (P = 0.002). Indoor coal burning exposure was correlated with gene expression of CCL2 (β = 3.45, 95 % CI: 0.04-6.87, P = 0.047) and CXCL8 (β = 1.25, 95 % CI: 0.02-2.49, P = 0.046) in female. A higher risk of carotid atherosclerosis was observed in the same as the increase expression of CCL2 (OR = 1.07, 95 % CI: 1.01-1.14, P = 0.020). In conclusion, prolonged exposure to indoor coal burning could elevate the gene expression of CCL2 by activating vascular endothelial cells and was relative to the initiation of carotid atherosclerosis.

Ex vivo coronary endothelial cell activation associated with indoor coal combustion initiated atherosclerosis.

Three-dimensional (3D) structured organoids have become increasingly promising and effective  models, and there is an urgent need for reliable models to assess health effects of inhaled pollutants on the human airway. In our study, we conducted a toxicity assessment of human airway organoids (hAOs) for tire wear particles (TWPs) as an emerging inhaled pollutant. We induced primary human bronchial epithelial cells (HBECs) to generated human airway organoids, which recapitulated the key features of human airway epithelial cells including basal cells, ciliated cells, goblet cells, and club cells. TWPs generated from the wearing of tire treads were considered a major source of emerging inhaled road traffic-derived non-exhaust particles, but their health effect on the lungs is poorly understood. We used human airway organoids to assess the toxicology of tire wear particles on the human airway. In an exposure study, the inhibitory effect of TWPs on the growth of human airway organoids was observed. TWPs induced significant cell apoptosis and oxidative stress in a dose-dependent manner. From the qPCR analysis, TWPs significantly up-regulated the expression pf genes involved in the inflammation response. Additionally, the exposure of TWPs reduced  gene expression associated with the function of the club cell and  gene expression related to the function of basal cells. In conclusion, this was first study using human airway organoids for a toxicological assessment of TWPs, and our findings revealed that human airway organoids provide an evaluation model of inhaled pollutants potentially affecting the lungs.

Human airway organoids as 3D  models for a toxicity assessment of emerging inhaled pollutants: Tire wear particles.

Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6 J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.

Wenting Cheng

Department of Environmental and Occupational Health,
School of Public Health,
Department of Environmental and Occupational Health, School of Public Health

Qingdao University

Measuring Carbon Content in Airway Macrophages Exposed to Carbon-Containing Particulate Matters

Wenting Cheng

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Environmental and Occupational Health,School of Public Health,Department of Environmental and Occupational Health, School of Public Health

Qingdao University

Measuring Carbon Content in Airway Macrophages Exposed to Carbon-Containing Particulate Matters

Department of Environmental and Occupational Health,
School of Public Health,
Department of Environmental and Occupational Health, School of Public Health