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ALS risk factors: Industrial airborne chemical releases
2022
Andrew, Angeline | Zhou, Jie | Gui, Jiang | Shi, Xun | Li, Meifang | Harrison, Antoinette | Guetti, Bart | Nathan, Ramaa | Butt, Tanya | Peipert, Daniel | Tischbein, Maeve | Pioro, Erik P. | Stommel, Elijah | Bradley, Walter
Most amyotrophic lateral sclerosis (ALS) cases are sporadic (∼90%) and environmental exposures are implicated in their etiology. Large industrial facilities are permitted the airborne release of certain chemicals with hazardous properties and report the amounts to the US Environmental Protection Agency (EPA) as part of its Toxics Release Inventory (TRI) monitoring program. The objective of this project was to identify industrial chemicals released into the air that may be associated with ALS etiology. We geospatially estimated residential exposure to contaminants using a de-identified medical claims database, the SYMPHONY Integrated Dataverse®, with ∼26,000 nationally distributed ALS patients, and non-ALS controls matched for age and gender. We mapped TRI data on industrial releases of 523 airborne contaminants to estimate local residential exposure and used a dynamic categorization algorithm to solve the problem of zero-inflation in the dataset. In an independent validation study, we used residential histories to estimate exposure in each year prior to diagnosis. Air releases with positive associations in both the SYMPHONY analysis and the spatio-temporal validation study included styrene (false discovery rate (FDR) 5.4e-5), chromium (FDR 2.4e-4), nickel (FDR 1.6e-3), and dichloromethane (FDR 4.8e-4). Using a large de-identified healthcare claims dataset, we identified geospatial environmental contaminants associated with ALS. The analytic pipeline used may be applied to other diseases and identify novel targets for exposure mitigation. Our results support the future evaluation of these environmental chemicals as potential etiologic contributors to sporadic ALS risk.
显示更多 [+] 显示较少 [-]Dose-response relationship between polycyclic aromatic hydrocarbon metabolites and risk of diabetes in the general Chinese population
2014
Yang, Liangle | Zhou, Yun | Sun, Huizhen | Lai, Hanpeng | Liu, Chuanyao | Yan, Kai | Yuan, Jing | Wu, Tangchun | Chen, Weihong | Zhang, Xiaomin
The incidence of diabetes is increasing rapidly in Chinese population, and it has been postulated that environmental factors may play a role in the etiology of diabetes. Therefore, we aimed to investigate the association between PAHs exposure and risk of diabetes in a community-based population of 2824 participants with completed questionnaires, measurements of biochemical indices, and urinary PAHs metabolites. We found that elevated urinary PAHs metabolites were associated, in a dose-dependent manner, with increased risk of diabetes. Particularly, these associations were more evident in subjects who were female, less than 55 years old, nonsmokers, and normal weight. In addition, there was a modest improvement in diabetes discrimination of prediction models when incorporating certain PAHs metabolites into conventional risk factors (CRF). Overall, our data suggested that there may be a dose-dependent relationship between PAHs metabolites and risk of diabetes among general Chinese population.
显示更多 [+] 显示较少 [-]Chronic exposure to volcanogenic air pollution as cause of lung injury
2013
Camarinho, Ricardo | Garcia, Patrícia Ventura | Rodrigues, Armindo Santos
Few studies were made regarding the pulmonary effects of exposure to volcanogenic air pollution, representing an unrecognized health risk for humans inhabiting non-eruptive volcanically active areas (10% of world human population). We tested the hypothesis whether chronic exposure to air pollution of volcanogenic origin causes lung injury, using wild mice (Mus musculus) as model. Lung injury was determined using histological morphometric parameters, inflammatory status (InfS) and the amount of black silver deposits (BSD). Mice exposed to volcanogenic air pollution have decreased percentage of alveolar space, alveolar perimeter and lung structural functionality (LSF) ratio and, increased alveolar septal thickness, amount of BSD and InfS. For the first time it is evidenced that non-eruptive active volcanism has a high potential to cause lung injury. This study also highlights the usefulness of M. musculus as bioindicator species, and of the developed biomarker of effect LSF ratio, for future animal and/or human biomonitoring programs.
显示更多 [+] 显示较少 [-]Urban social stress – Risk factor for mental disorders. The case of schizophrenia
2013
Living in an urban environment is associated with an increased prevalence of specific mental health disorders, particularly schizophrenia. While many factors have been discussed as possible mediators of this association, most researchers favour the hypothesis that urban living stands as a proxy for an increased exposure to social stress. This factor has been recognized as one of the most powerful causes for the development of mental disorders, and appears to correlate with the markedly increased incidence of schizophrenia in urban minority groups. However, the hypothesis that the general urban population is exposed to increased levels of social stress has to be validated. Pursuing the goal of understanding how social stress acts as a risk factor for mental disorder in urban populations must include factors like social conditions, environmental pollutants, infrastructure and economic issues.
显示更多 [+] 显示较少 [-]Household prallethrin-based insecticide toxicity on different C. elegans life stage: A possible sign of Huntington Disease
2022
Tamagno, Wagner Antonio | Alves, Carla | Pompermaier, Aline | Vanin, Ana Paula | Barcellos, Leonardo José Gil
Household insecticide is largely used for insect and ectoparasite control, in city centers as well as in the countryside. The pyrethroids are the most used class of insecticide, these compounds in low doses have low toxicity for mammalians, in comparison to other compounds, with insecticide effects. The contact of these compounds in sublethal doses begins in early life and many cases, in intrauterine life. Considerable diseases still with undefined etiology, such as neurodegenerative conditions, and Huntington's Disease (HD) is one of them. HD is related to overexpression of Polyglutamine (PolyQ40), its aggregation, and non-solubilization, which leads to neural, behavioral, and cognitive damage. In our study, we evaluate the effect of two sublethal doses of a prallethrin-based insecticide (P-BI), in three different Caenorhabditis elegans life stages transgenerational, neonatal, and lifespan. We evaluated the Body bends and pharyngeal pumping rate, and social feeding as behavioral biomarkers. As well as acetylcholinesterase activity (AChE), PolyQ40 aggregation, antioxidant enzymes, and heat shock protein (HSP) expression. We observe that the toxic effect of P-BI is more pronounced on transgenerational and lifespan exposure. Both sublethal doses of P-BI decreased the AChE activity and retard the HSP expression as well as increased the PolyQ40 aggregates indicating a clear biomarker for possible effect in the progression of the HD, by the environmental contamination.
显示更多 [+] 显示较少 [-]Endocrine disrupting chemicals impact on ovarian aging: Evidence from epidemiological and experimental evidence
2022
Ding, Ting | Yan, Wei | Zhou, Ting | Shen, Wei | Wang, Tian | Li, Milu | Zhou, Su | Wu, Meng | Dai, Jun | Huang, Kecheng | Zhang, Jinjin | Chang, Jiang | Wang, Shixuan
Endocrine-disrupting chemicals (EDCs) are ubiquitous in daily life, but their harmful effects on the human body have not been fully explored. Recent studies have shown that EDCs exposure could lead to infertility, menstrual disorder and menopause, resulting in subsequent effects on female health. Therefore, it is of great significance to clarify and summarize the impacts of EDCs on ovarian aging for explaining the etiology of ovarian aging and maintaining female reproductive health. Here in this review, we focused on the impacts of ten typical environmental contaminants on the progression of ovarian aging during adult exposure, including epidemiological data in humans and experimental models in rodents, with their clinical phenotypes and underlying mechanisms. We found that both persistent (polychlorinated biphenyls, perfluoroalkyl and polyfluoroalkyl substances) and non-persistent (phthalates) EDCs exposure could increase an overall risk of ovarian aging, leading to the diminish of ovarian reserve, decline of fertility or fecundity, irregularity of the menstrual cycle and an earlier age at menopause, and/or premature ovarian insufficiency/failure in epidemiological studies. Among these, the loss of follicles can also be validated in experimental studies of some EDCs, such as BPA, phthalates, parabens and PCBs. The underlying mechanisms may involve the impaired ovarian follicular development by altering receptor-mediated pro-apoptotic pathways, inducing signal transduction and cell cycle arrest and epigenetic modification. However, there were inconsistent results in the impacts on fertility/fecundity, menstrual/estrous cycle and hormone changes response to different EDCs, and differences between human and animal studies. Our review summarizes the current state of knowledge on ovarian disrupters, highlights their risks to ovarian aging and identifies knowledge gaps in humans and animals. We therefore propose that females adopt healthy lifestyle changes to minimize their exposure to both persistent and non-persistent chemicals, that have the potential damage to their reproductive function.
显示更多 [+] 显示较少 [-]DEHP-elicited small extracellular vesicles miR-26a-5p promoted metastasis in nearby normal A549 cells
2021
Qin, Yifei | Zhang, Jing | Avellán-Llaguno, Ricardo David | Zhang, Xu | Huang, Qiansheng
Small extracellular vesicles (sEV) are small lipid bilayer particles released by cells. sEV have been shown to play critical roles in intercellular communication. Di (2-ethylhexyl) phthalate (DEHP), widely used as plasticizers, has been detected in the environment and human beings. DEHP was found to exist in the air particles and showed pulmonary toxicity. However, there’s little knowledge about the role of sEV in mediating the toxicity of DEHP-induced lung toxicity. We hypothesized that sEV mediated the toxicity of DEHP through their cargo. To validate this, lung epithelial cells (A549) were exposed to various concentrations (0, 0.2, 2 and 20 μM) of DEHP for 48 h. sEV extracted from DEHP-exposed A549 cells were cultured with unexposed A549 cells. Results showed that DEHP induced the epithelial-mesenchymal transition (EMT) and promoted the migration and invasion ability of A549 cells. The number of released sEV significantly increased in the culture media in DEHP-exposed groups compared to unexposed groups. The sEV can enter the unexposed A549 cells and enhance its EMT and the ability of migration and invasion. Treatment with GW4869 in DEHP-exposed A549 cells almost blocked the effects of DEHP-elicited sEV in normal A549 cells. Sequencing and functional analysis showed that the enrichment of significantly differentially expressed sEV miRNAs were related to tumor etiology. MiR-26a-5p was significantly enriched in DEHP-elicited sEV. Inhibition of miR-26a-5p in DEHP-exposed cells led to the downregulation of miR-26a-5p in sEV, and thus abolished the effects of DEHP-elicited sEV in normal A549 cells, whereas overexpression of miR-26a-5p restored the effects. The transcription factors twist is one of the downstream targets in the effects of sEV-miR-26a-5p on EMT process. In all, our results showed that DEHP exposure promoted the secretion of miR-26a-5p in sEV, which subsequently enhanced the EMT, migration and invasion ability in neighboring normal cells via the twist.
显示更多 [+] 显示较少 [-]Ambient fine particulate matter disrupts hepatic circadian oscillation and lipid metabolism in a mouse model
2020
Li, Ran | Wang, Yixuan | Chen, Rucheng | Gu, Weijia | Zhang, Lu | Gu, Jinge | Wang, Ziyao | Liu, Ying | Sun, Qinghua | Zhang, Kezhong | Liu, Cuiqing
Emerging evidence has shown that exposure to ambient fine particulate matter (PM₂.₅) is associated with hepatic lipid accumulation. However, the underlying mechanism is not fully characterized yet. Autonomous circadian clock in the liver plays a fundamental role in maintaining lipid metabolism homeostasis. In this study, we evaluated the effects of ambient PM₂.₅ exposure on the expression of hepatic circadian clock genes and expression rhythm of genes associated with lipid metabolism in mice liver. Male C57BL/6 mice were randomly assigned to ambient PM₂.₅ or filtered air for 10 weeks via a whole body exposure system. We found that the liver mass was reduced significantly at zeitgeber time (ZT) 8 in mice exposed to PM₂.₅ but not levels or circadian rhythm of hepatic triglycerides or free fatty acid (FFA). In addition, exposure to PM₂.₅ led to enhanced expression of bmal1 at ZT0/24, cry1 at ZT16 and rev-erbα at ZT4 and ZT8. Furthermore, the expression of pparα was enhanced in mice liver at ZT4 and ZT8 after PM₂.₅ exposure, with upregulation of pparα-mediated genes responsible for fatty acid transport and oxidation. Finally, the expression of rate-limiting enzymes for lipid synthesis was all significantly increased in the liver of PM₂.₅ exposed mice at ZT12. Therefore, the present study provides new perspectives for revealing the etiology of hepatic lipid metabolism abnormality from PM₂.₅-induced circadian rhythm disorder.
显示更多 [+] 显示较少 [-]Long-term exposure to environmental levels of phenanthrene induces emaciation-thirst disease-like syndromes in female mice
2022
Fang, Lu | Ou, Kunlin | Huang, Jie | Zhang, Shenli | Zhang, Ying | Zhao, Hezhen | Chen, Meng | Wang, Chonggang
Phenanthrene (Phe) is a polycyclic aromatic hydrocarbon widely present in foods and drinking water. To explore the detrimental effects of Phe on body metabolism, female Kunming mice were treated with Phe in drinking water at concentrations of 0.05, 0.5 and 5 ng/mL. After exposure for 270 d, the animals exhibited dose-dependent reduced body weight and increased water consumption. The dose-dependent accumulation of Phe in the brain decreased hypothalamic neuron numbers, upregulated hypothalamic expression of anaplastic lymphoma kinase, elevated norepinephrine levels in white adipose tissue (WAT) and further activated lipolysis in WAT, leading to a reduction in fat mass. Brown adipose tissue formation was reduced, accompanied by the inhibition of the bone morphogenetic protein signaling pathway. A simultaneous reduced serum levels of antidiuretic hormone (arginine vasopressin) might be one of the reasons for increased water consumption. The present results indicate an environmental etiology and prevention way for the development of emaciation-thirst disease.
显示更多 [+] 显示较少 [-]Associations of exposure to multiple trace elements with the risk of goiter: A case-control study
2021
He, Jia-liu | Li, Guo-ao | Zhu, Zhen-yu | Hu, Ming-jun | Wu, Hua-bing | Zhu, Jin-liang | Zhao, Huan-huan | Zhang, Han-Shuang | Huang, Fen
Goiter is one of common endocrine diseases, and its etiology has not been fully elucidated. The changes in trace elements' levels have an important impact on the thyroid. We designed a case-control study, which involved 383 goiter cases and 383 matched controls. We measured these elements in the urine of participants by inductively coupled plasma optical emission spectrometry (ICP-OES), graphite furnace atomic absorption spectrometry (GFAAS) and As³⁺-Ce⁴⁺ catalytic spectrophotometry. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the elements into multi-element models, conditional logistic regression models were applied to analyze the association between elements and goiter risk. Bayesian kernel machine regression (BKMR) model was used to depict elements’ mixtures and evaluate their joint effects. Finally, 7 elements were included in the multi-element model. We found that the concentrations of lithium (Li), strontium (Sr) and barium (Ba) had a negative effect with goiter risk, and lead (Pb) and iodine (I) showed an extreme positive effect. Additionally, compared with the lowest levels, patients with highest quartiles of I and Pb were 6.49 and 1.94 times more likely to have goiter, respectively. On the contrary, in its second and third quartiles, arsenic (As) showed a negative effect (both OR<1). BKMR model showed a certain interaction among Pb, As, Sr and Li on goiter risk. Further large sample studies are needed to confirm these findings in the future.
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