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Cadmium exposure induces osteoporosis through cellular senescence, associated with activation of NF-κB pathway and mitochondrial dysfunction
2021
Luo, Huigen | Gu, Renjie | Ouyang, Huiya | Wang, Lihong | Shi, Shanwei | Ji, Yuna | Bao, Baicheng | Liao, Guiqing | Xu, Baoshan
Cadmium (Cd) is a heavy metal toxicant as a common pollutant derived from many agricultural and industrial sources. The absorption of Cd takes place primarily through Cd-contaminated food and water and, to a significant extent, via inhalation of Cd-contaminated air and cigarette smoking. Epidemiological data suggest that occupational or environmental exposure to Cd increases the health risk for osteoporosis and spontaneous fracture such as itai-itai disease. However, the direct effects and underlying mechanism(s) of Cd exposure on bone damage are largely unknown. We used primary bone marrow-derived mesenchymal stromal cells (BMMSCs) and found that Cd significantly induced BMMSC cellular senescence through over-activation of NF-κB signaling pathway. Increased cell senescence was determined by production of senescence-associated secretory phenotype (SASP), cell cycle arrest and upregulation of p21/p53/p16ᴵᴺᴷ⁴ᵃ protein expression. Additionally, Cd impaired osteogenic differentiation and increased adipogenesis of BMMSCs, and significantly induced cellular senescence-associated defects such as mitochondrial dysfunction and DNA damage. Sprague-Dawley (SD) rats were chronically exposed to Cd to verify that Cd significantly increased adipocyte number, and decreased mineralization tissues of bone marrow in vivo. Interestingly, we observed that Cd exposure remarkably retarded bone repair and regeneration after operation of skull defect. Notably, pretreatment of melatonin is able to partially prevent Cd-induced some senescence-associated defects of BMMSCs including mitochondrial dysfunction and DNA damage. Although Cd activated mammalian target of rapamycin (mTOR) pathway, rapamycin only partially ameliorated Cd-induced cell apoptosis rather than cellular senescence phenotypes of BMMSCs. In addition, a selective NF-κB inhibitor moderately alleviated Cd-caused the senescence-related defects of the BMMSCs. The study shed light on the action and mechanism of Cd on osteoporosis and bone ageing, and may provide a novel option to ameliorate the harmful effects of Cd exposure.
Mostrar más [+] Menos [-]Exploring the external exposome using wearable passive samplers - The China BAPE study
2021
Koelmel, Jeremy P. | Lin, Elizabeth Z. | Guo, Pengfei | Zhou, Jieqiong | He, Jucong | Chen, Alex | Gao, Ying | Deng, Fuchang | Dong, Haoran | Liu, Yuanyuan | Cha, Yu’e | Fang, Jianlong | Beecher, Chris | Shi, Xiaoming | Tang, Song | Godri Pollitt, Krystal J.
Environmental exposures are one of the greatest threats to human health, yet we lack tools to answer simple questions about our exposures: what are our personal exposure profiles and how do they change overtime (external exposome), how toxic are these chemicals, and what are the sources of these exposures? To capture variation in personal exposures to airborne chemicals in the gas and particulate phases and identify exposures which pose the greatest health risk, wearable exposure monitors can be deployed. In this study, we deployed passive air sampler wristbands with 84 healthy participants (aged 60–69 years) as part of the Biomarkers for Air Pollutants Exposure (China BAPE) study. Participants wore the wristband samplers for 3 days each month for five consecutive months. Passive samplers were analyzed using a novel gas chromatography high resolution mass spectrometry data-processing workflow to overcome the bottleneck of processing large datasets and improve confidence in the resulting identified features. The toxicity of chemicals observed frequently in personal exposures were predicted to identify exposures of potential concern via inhalation route or other routes of airborne contaminant exposure. Three exposures were highlighted based on elevated toxicity: dichlorvos from insecticides (mosquito/malaria control), naphthalene partly from mothballs, and 183 polyaromatic hydrocarbons from multiple sources. Other exposures explored in this study are linked to diet and personal care products, cigarette smoke, sunscreen, and antimicrobial soaps. We highlight the potential for this workflow employing wearable passive samplers for prioritizing chemicals of concern at both the community and individual level, and characterizing sources of exposures for follow up interventions.
Mostrar más [+] Menos [-]Hydroquinone exposure alters the morphology of lymphoid organs in vaccinated C57Bl/6 mice
2020
Fabris, André Luis | Nunes, Andre Vinicius | Schuch, Viviane | de Paula-Silva, Marina | Rocha, GHO | Nakaya, Helder I. | Ho, Paulo Lee | Silveira, Eduardo L.V. | Farsky, Sandra Helena Poliselli
The influenza is a common viral infection that can be fatal, especially in high-risk groups such as children, pregnant women, elderly, and immune-deficient individuals. Vaccination is the most efficient approach to prevent the spreading of viral infection and promote individual and public health. In contrast, exposure to environmental pollutants such as cigarette smoke reduces the efficacy of vaccination. We investigated whether chronic exposure to hydroquinone (HQ), the most abundant compound of the tobacco particulate phase, could impair the adaptive immune responses elicited by influenza vaccination. For this, adult male C57BL/6 mice were daily exposed to either nebulized HQ or PBS for 1 h for a total of eight weeks. At weeks 6 and 8, the mice were primed and boosted with the trivalent influenza vaccine via IM respectively. Although the HQ exposure did not alter the body weight of the mice and the biochemical and hematological parameters, the pollutant increased the oxidative stress in splenocytes of immunized animals, modified the morphology of spleen follicles, and augmented the size of their lymph nodes. The lymphoid organs of HQ-exposed mice presented a similar number of vaccine-specific IgG-secreting cells, titers of vaccine-specific total IgG, and respective subclasses. Transcriptome studies with HQ, benzene, or cigarette smoke exposure were also analyzed. The genes up-regulated upon pollutant exposure were associated with neutrophil migration and were shown to be co-expressed with antibody-secreting cell genes. Therefore, these findings suggest that HQ exposure may trigger an immune-compensatory mechanism that enhances the humoral responses induced by influenza vaccination.
Mostrar más [+] Menos [-]Associations of annual ambient PM2.5 components with DNAm PhenoAge acceleration in elderly men: The Normative Aging Study
2020
Wang, Cuicui | Koutrakis, Petros | Gao, Xu | Baccarelli, Andrea | Schwartz, Joel
Current studies indicate that long-term exposure to ambient fine particulate matter (PM₂.₅) is related with global mortality, yet no studies have explored relationships of PM₂.₅ and its species with DNAm PhenoAge acceleration (DNAmPhenoAccel), a new epigenetic biomarker of phenotypic age. We identified which PM₂.₅ species had association with DNAmPhenoAccel in a one-year exposure window in a longitudinal cohort. We collected whole blood samples from 683 elderly men in the Normative Aging Study between 1999 and 2013 (n = 1254 visits). DNAm PhenoAge was calculated using 513 CpGs retrieved from the Illumina Infinium HumanMethylation450 BeadChip. Daily concentrations of PM₂.₅ species were measured at a fixed air-quality monitoring site and one-year moving averages were computed. Linear mixed-effect (LME) regression and Bayesian kernel machine (BKM) regression were used to estimate the associations. The covariates included chronological age, body mass index (BMI), cigarette pack years, smoking status, estimated cell types, batch effects etc. Benjamini-Hochberg false discovery rate at a 5% false positive threshold was used to adjust for multiple comparison. During the study period, the mean DNAm PhenoAge and chronological age in our subjects were 68 and 73 years old, respectively. Using LME model, only lead and calcium were significantly associated with DNAmPhenoAccel. For example, an interquartile range (IQR, 0.0011 μg/m³) increase in lead was associated with a 1.29-year [95% confidence interval (CI): 0.47, 2.11] increase in DNAmPhenoAccel. Using BKM model, we selected PM₂.₅, lead, and silicon to be predictors for DNAmPhenoAccel. A subsequent LME model showed that only lead had significant effect on DNAmPhenoAccel: 1.45-year (95% CI: 0.46, 2.46) increase in DNAmPhenoAccel following an IQR increase in one-year lead. This is the first study that investigates long-term effects of PM₂.₅ components on DNAmPhenoAccel. The results demonstrate that lead and calcium contained in PM₂.₅ was robustly associated with DNAmPhenoAccel.
Mostrar más [+] Menos [-]Characteristics of environmentally persistent free radicals in PM2.5: Concentrations, species and sources in Xi'an, Northwestern China
2019
Chen, Qingcai | Sun, Haoyao | Mu, Zhen | Wang, Yuqin | Li, Yanguang | Zhang, Lixin | Wang, Mamin | Zhang, Zimeng
Environmentally persistent free radicals (EPFRs) are a new class of environmental risk substances that can stably exist in atmospheric particles and pose a potential threat to human health. In this study, electron paramagnetic resonance (EPR) spectroscopy was used to study the concentration levels, species characteristics, and sources of EPFRs in PM₂.₅ in Xi'an in 2017. The results showed that the concentrations of EPFRs in PM₂.₅ in Xi'an in 2017 ranged from 9.8 × 10¹¹ to 6.9 × 10¹⁴ spins/m³. The highest concentration of EPFRs occurred in winter when the average concentration was 2.1 × 10¹⁴ spins/m³. The lowest concentration of EPFRs occurred in autumn when the average concentration was 7.0 × 10¹³ spins/m³. According to the annual average atmospheric concentration of EPFRs, the amount of EPFRs inhaled by people in Xi'an is equivalent to approximately 5 cigarettes per person per day and approximately 23 cigarettes per person per day in winter when haze occurs. The results of the study on the EPFR characteristics show that the EPFRs in PM₂.₅ in Xi'an are mainly C-center organic radicals that are primarily non-decaying types, accounting for approximately 75% and 85% of total concentration of EPFRs in autumn and winter, respectively. Finally, a correlation analysis was used to explore the origins of EPFRs in PM₂.₅. Significant positive correlations were found between EPFRs and SO₂, NO₂ and the thermally derived OC3 and OC4 carbonaceous components. The results suggested that coal-fired and traffic may be important sources of EPFRs in PM₂.₅ in Xi'an. In addition, EPFRs are significantly positively correlated with O₃ in summer, suggesting that some EPFRs may also originate from secondary processes. This study provides important basic data and evidence for further assessments of the potential health risks of EPFRs in PM₂.₅ and the development of effective air pollution control measures.
Mostrar más [+] Menos [-]Aerosol deposition doses in the human respiratory tree of electronic cigarette smokers
2015
Manigrasso, Maurizio | Buonanno, Giorgio | Fuoco, Fernanda Carmen | Stabile, Luca | Avino, Pasquale
Aerosols from eight e-cigarettes at different nicotine levels and flavoring were characterized as particle number size distributions in the range 5.6–560 nm by FMPS and CPC. Results were used to provide dosimetry estimates applying the MMPD model.Particle number concentrations varied between 3.26 × 109 and 4.09 × 109 part cm−3 for e-liquids without nicotine and between 5.08 × 109 and 5.29 × 109 part cm−3 for e-liquids with nicotine. No flavor effects were detected on particle concentration data. Particle size distributions were unimodal with modes between 107–165 nm and 165–255 nm, for number and volume metrics, respectively.Averagely, 6.25 × 1010 particles were deposited in respiratory tree after a single puff. Highest deposition densities and mean layer thickness of e-cigarette liquid on the lung epithelium were estimated at lobar bronchi.Our study shows that e-cigarette aerosol is source of high particle dose in respiratory system, from 23% to 35% of the daily dose of a no-smoking individual.
Mostrar más [+] Menos [-]Early-life exposure to tobacco smoke alters airway signaling pathways and later mortality in D. melanogaster
2022
Sirocko, Karolina-Theresa | Angstmann, Hanna | Papenmeier, Stephanie | Wagner, Christina | Spohn, Michael | Indenbirken, Daniela | Ehrhardt, Birte | Kovacevic, Draginja | Hammer, Barbara | Svanes, Cecilie | Rabe, Klaus F. | Röder, Thomas | Uliczka, Karin | Krauss-Etschmann, Susanne
Early life environmental influences such as exposure to cigarette smoke (CS) can disturb molecular processes of lung development and thereby increase the risk for later development of chronic respiratory diseases. Among the latter, asthma and chronic obstructive pulmonary disease (COPD) are the most common. The airway epithelium plays a key role in their disease pathophysiology but how CS exposure in early life influences airway developmental pathways and epithelial stress responses or survival is poorly understood. Using Drosophila melanogaster larvae as a model for early life, we demonstrate that CS enters the entire larval airway system, where it activates cyp18a1 which is homologues to human CYP1A1 to metabolize CS-derived polycyclic aromatic hydrocarbons and further induces heat shock protein 70. RNASeq studies of isolated airways showed that CS dysregulates pathways involved in oxidative stress response, innate immune response, xenobiotic and glutathione metabolic processes as well as developmental processes (BMP, FGF signaling) in both sexes, while other pathways were exclusive to females or males. Glutathione S-transferase genes were further validated by qPCR showing upregulation of gstD4, gstD5 and gstD8 in respiratory tracts of females, while gstD8 was downregulated and gstD5 unchanged in males. ROS levels were increased in airways after CS. Exposure to CS further resulted in higher larval mortality, lower larval-pupal transition, and hatching rates in males only as compared to air-exposed controls. Taken together, early life CS induces airway epithelial stress responses and dysregulates pathways involved in the fly's branching morphogenesis as well as in mammalian lung development. CS further affected fitness and development in a highly sex-specific manner.
Mostrar más [+] Menos [-]Evaluating the applicability of the ratio of PM2.5 and carbon monoxide as source signatures
2022
Xiu, Meng | Jayaratne, Rohan | Thái Phong, | Christensen, Bryce | Zing, Isak | Liu, Xiaoting | Morawska, L. (Lidia)
Air pollution is among the top risk faced by people around the world, and therefore combating it is among the top priorities. It begins with identifying the sources that contribute the most to local air pollution to prioritize their control. There are advanced methods for source identification and apportionment, but such methods are not available in many low-income countries and not everywhere in all high-income countries. We propose a simplified method by using source the signatures to help obtain information about the local source contribution if no other methods are available. Using low-cost monitors, particle mass (PM₂.₅) and carbon monoxide (CO) concentrations were measured and the ratio of CO/PM₂.₅ was determined. We investigated outdoor and indoor sources, including vehicular exhaust, combustion of biomass, incense and mosquito coil burning, and cigarette smoking. The results show that the ratios differed significantly between certain pollutant sources. Compressed natural gas (CNG) engines have a high ratio (mean value of 972 ± 419), which is attributed to relatively low PM₂.₅ emissions, while ship emissions and cigarette smoke recorded a relatively low ratio. Most traffic emissions recorded higher ratios than those of bushfire emissions, and ratios of most outdoor pollutant sources were much higher than those of indoor pollutant sources. There is a clear trend for ratios to decrease from high to low for CNG, petrol, diesel for buses, and fuel for ships. Our results suggest that the ratio of CO/PM₂.₅ can be used as an effective method to identify pollution sources.
Mostrar más [+] Menos [-]The role of hydrodynamic fluctuations and wind intensity on the distribution of plastic debris on the sandy beaches of Paraná River, Argentina
2021
Garello, Nicolás | Blettler, Martín C.M. | Espínola, Luis A. | Wantzen, Karl M. | González-Fernández, Daniel | Rodrigues, Stéphane
Plastic in the environment is considered an emerging pollutant of global concern. In spite of intensive research, many questions remain open, such as the processes that drive the deposition and remobilization of plastic debris on river beaches. The objectives of this study were: i) to analyze the influence of the natural hydrological fluctuations and wind intensity on the distribution of mesoplastic (0.5–2.5 cm) and macroplastic (>2.5 cm) debris in beach sediments of a large river, ii) to describe the type of plastic debris found and iii) to explore potential relations between the number of items and weight of macro- and mesoplastics. Our results suggest that, during lowering water levels, flow removes the plastic debris and transports it further downstream. Conversely, when the beach sediments remain exposed during long periods, the plastic debris accumulates considerably. Nevertheless, the influence of wind intensity on plastic debris transport was comparatively negligible. In other words, in our study the water flow had a greater capacity to remobilize and transport plastic debris than the wind. The most abundant mesoplastic items were foam, hard plastic, film and small fragments of fishing line. The dominant macroplastic items recorded were pieces of fishing line (nylon) and cigarette filters (cellulose acetate), typically discarded by beach users. Other items found in large quantities were soft packaging elements (expanded polystyrene), hard plastic containers (polystyrene, polyethylene terephthalate) and beverage bottles (polyethylene terephthalate), typical items of domestic use in the Paraná River region. Finally, we found that the density of macroplastic items is highly correlated to the density of mesoplastic items, serving as surrogate for further estimations. Our results could help to develop better mitigation strategies in seasonal riverscapes, based on the influence of the hydrological cycle and the characteristics of the most abundant meso- and macroplastics.
Mostrar más [+] Menos [-]Phenotypic and transcriptomic changes in the corneal epithelium following exposure to cigarette smoke
2021
Jin, Mengyi | Wang, Yanzi | An, Xiaoya | Kang, Honghua | Wang, Yixin | Wang, Guoliang | Gao, Yang | Wu, Shuiping | Reinach, Peter S. | Liu, Zuguo | Xue, Yuhua | Li, Cheng
Cigarette smoke extract (CSE), a complex mixture of compounds, contributes to a range of eye diseases; however, the underlying pathophysiological responses to tobacco smoke remain ambiguous. The purpose of the present study was to evaluate the cigarette smoke-induced phenotypic and transcriptomic changes in the corneal epithelium with a view to elucidating the likely underlying mechanism. Accordingly, for the first time, we characterized the genome-wide effects of CSE on the corneal epithelium. The ocular surface of the mice in the experimental groups was exposed to CSE for 1 h per day for a period of one week, while mice in the control group were exposed to preservative-free artificial tears. Corneal fluorescein staining, in vivo confocal microscopy and scanning electron microscopy were performed to examine the corneal ultrastructure. Transcriptome sequencing and bioinformatics analysis were performed followed by RT-qPCR to validate gene expression changes. The results indicate that CSE exposure disrupted the structural integrity of the superficial epithelium, decreased the density of microvilli, and compromised the corneal epithelial barrier intactness. RNA-seq revealed 667 differentially expressed genes, and functional analysis highlighted the enhancement of several biological processes such as antioxidant activity and the response to oxidative stress. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that glutathione metabolism and drug metabolism cytochrome P450 were the most relevant pathways contributing to the effects of CSE on the corneal epithelium. Protein–protein interaction (PPI) network analysis illustrated that GCLC, NQO1, and HMOX1 were the most relevant nodes. In conclusion, the present study indicates that CSE exposure induces changes in the phenotype and genotype of the corneal epithelium. The antioxidant response element is essential for counteracting the effects of cigarette smoke on this tissue layer. These results shed novel insights into how cigarette smoke damages this ocular surface.
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