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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.
显示更多 [+] 显示较少 [-]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.
显示更多 [+] 显示较少 [-]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.
显示更多 [+] 显示较少 [-]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.
显示更多 [+] 显示较少 [-]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.
显示更多 [+] 显示较少 [-]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.
显示更多 [+] 显示较少 [-]Amount, composition and sources of macrolitter from a highly frequented roadway
2022
Ledieu, L. | Tramoy, R. | Ricordel, S. | Astrie, D. | Tassin, B. | Gasperi, J.
Many researches mention the need to identify the land-based sources of riverine macrolitter but few field data on litter amount, composition and sources are available in the scientific literature. Describing macrolitter hotspot dynamics would actually allow a better estimation of fluxes in the receiving environments and a better identification of the more appropriate mitigation strategies. This study provides new insights in roadway macrolitter production rates, typologies and input sources (i.e. deliberate or accidental). The macrolitter from an 800 m portion of a highly frequented roadway (around 90,000 vehicles per day) was collected during almost one year. Typologies were defined using the OSPAR/TGML classification. Results show high annual loads of macrolitter (42.8 kg/yr/ha), suggesting significant contributions of the road runoff to the litter fluxes in urban stormwater. Over the course of a year, 88.5 kg of debris were collected, including 53.2 kg (60%) of plastic debris. In total, 36,439 items were characterized, of which 84% were plastics. The macrodebris collected present a low diversity of components with Top 10 items accounting for 92% by count and a majority of small and lightweight items like plastic fragments (31%) or cigarette butts (18%). Input sources were estimated for 43% of the mass collected in which 37.2% were deliberately littered and 62.8% were accidental leaks, illustrating a major contribution of uncovered trucks and unsecured loads. The accumulation rates show a linear correlation with the road traffic. Such data are of prime interest since they enable to determine the potential contribution of road traffic to plastic fluxes to the environment.
显示更多 [+] 显示较少 [-]Spatio-temporal characterization of litter at a touristic sandy beach in South Brazil
2021
de Ramos, Bruna | Alencar, Melanie Vianna | Rodrigues, Fábio Lameiro | Lacerda, Ana Luzia de Figueiredo | Proietti, Maíra Carneiro
Litter is an ecological, economic, and social problem that impacts marine environments around the world. To create prevention and mitigation measures to solve this issue, it is necessary to understand the amounts and sources of this type of pollution. Cassino Beach is an extensive sandy beach located in South Brazil (∼220 km in length) that presents multiple uses, such as touristic, portuary and fishery activities. In order to evaluate the spatial and seasonal variation of litter amounts, types and sources at Cassino Beach, litter (>2.5 cm) was collected over 27 months at two urban and two non-urban sites. At each site, the litter present in three 200 m² areas was sampled and evaluated. A total of 19,457 items were collected, mostly composed by plastic (∼88%). Paper, metal, and cloth items were also present, but in low amounts. Fragments and cigarette butts were the major types of plastic litter, with abundances of 28.4% and 17.0%, respectively. Urban sites presented higher amounts of litter, with those related to beach use being more common, emphasizing the contribution of beachgoers to litter input at these sites. During the summer season, when beach use increases, the highest total litter concentration was found. Undefined and/or beach use-related sources were dominant in all sites and seasons. Mapping the predominant materials, types and potential sources of litter creates important baseline data that can contribute not only to beach monitoring, but also to the development of litter reduction strategies.
显示更多 [+] 显示较少 [-]Immunotoxic mechanisms of cigarette smoke and heat-not-burn tobacco vapor on Jurkat T cell functions
2021
Scharf, Pablo | da Rocha, Gustavo H.O. | Sandri, Silvana | Heluany, Cintia S. | Pedreira Filho, Walter R. | Farsky, Sandra H.P.
Cigarette smoke (CS) affects immune functions, leading to severe outcomes in smokers. Robust evidence addresses the immunotoxic effects of combustible tobacco products. As heat-not-burn tobacco products (HNBT) vaporize lower levels of combustible products, we here compared the effects of cigarette smoke (CS) and HNBT vapor on Jurkat T cells. Cells were exposed to air, conventional cigarettes or heatsticks of HNBT for 30 min and were stimulated or not with phorbol myristate acetate (PMA). Cell viability, proliferation, reactive oxygen species (ROS) production, 8-OHdG, MAP-kinases and nuclear factor κB (NFκB) activation and metallothionein expression (MTs) were assessed by flow cytometry; nitric oxide (NO) and cytokine levels were measured by Griess reaction and ELISA, respectively. Levels of metals in the exposure chambers were quantified by inductively coupled plasma mass spectrometry. MT expressions were quantified by immunohistochemistry in the lungs and liver of C57Bl/6 mice exposed to CS, HNBT or air (1 h, twice a day for five days: via inhalation). While both CS and HBNT exposures increased cell death, CS led to a higher number of necrotic cells, increased the production of ROS, NO, inflammatory cytokines and MTs when compared to HNBT-exposed cells, and led to a higher expression of MTs in mice. CS released higher amounts of metals. CS and HNBT exposures decreased PMA-induced interleukin-2 (IL-2) secretion and impaired Jurkat proliferation, effects also seen in cells exposed to nicotine. Although HNBT vapor does not activate T cells as CS does, exposure to both HNBT and CS suppressed proliferation and IL-2 release, a pivotal cytokine involved with T cell proliferation and tolerance, and this effect may be related to nicotine content in both products.
显示更多 [+] 显示较少 [-]Bioassay-based ecotoxicological investigation on marine and freshwater impact of cigarette butt littering
2021
Oliva, M. | De Marchi, L. | Cuccaro, A. | Pretti, C.
Despite representing an extremely relevant portion (20–40%) of worldwide coastal litter, cigarette butts are still an underestimate environmental issue of limited scientific interest. Public authorities of different countries promote active removal of cigarette butts, but the issue remains problematic in terms of aesthetic, environmental and health-related impacts. There are few studies on the environmental side-effects of smoked cigarette butt litter despite being a worldwide issue. In this work, two ecotoxicological bioassay batteries were adopted to evaluate the environmental consequences of cigarette butt water-soluble ingredient release in both marine water and freshwater. Marine assays were generally more affected compared to freshwater. Interesting outcomes were observed with crustacean tests, showing a lower effect of smoked cigarette butt leachate when tested at maximum concentration. This finding were supported by heartbeat measures of Daphnia magna, which were accelerated at 100% of smoked cigarette butt leachate.
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