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.

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.

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.

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.

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.

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.

Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary.To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain).In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals’ residences to the 106 industries located in the study areas were computed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industries, adjusting for matching variables and potential confounders.Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at ≤2.5 km) to 0.93 (at ≤1.5 km). However, by industrial sector, excess risks (OR; 95%CI) were found near organic chemical industry (3.51; 1.42–8.69 at ≤2 km), inorganic chemical industry (3.33; 1.12–9.85 at ≤2 km), food/beverage sector (2.48; 1.12–5.50 at ≤2 km), and surface treatment using organic solvents (3.59; 1.40–9.22 at ≤3 km). By specific pollutant, a statistically significant excess risk (OR; 95%CI) was found near (≤3 km) industries releasing nonylphenol (6.43; 2.30–17.97) and antimony (4.82; 1.94–12.01).The results suggest no association between risk of gastric cancer and living in the proximity to the industrial facilities as a whole. However, a few associations were detected near some industrial sectors and installations releasing specific pollutants.

MicroRNAs (miRNAs) are a class of small, non-coding RNAs with a post-transcriptional regulatory function on gene expression and cell processes, including proliferation, apoptosis and differentiation. In recent decades, miRNAs have attracted increasing interest to explore the role of epigenetics in response to air pollution. Air pollution, which always contains kinds of particulate matters, are able to reach respiratory tract and blood circulation and then causing epigenetics changes. In addition, extensive studies have illustrated that miRNAs serve as a bridge between particulate matter exposure and health-related effects, like inflammatory cytokines, blood pressure, vascular condition and lung function. The purpose of this review is to summarize the present knowledge about the expression of miRNAs in response to particulate matter exposure. Epidemiological and experimental studies were reviewed in two parts according to the size and source of particles. In this review, we also discussed various functions of the altered miRNAs and predicted potential biological mechanism participated in particulate matter-induced health effects. More rigorous studies are worth conducting to understand contribution of particulate matter on miRNAs alteration and the etiology between environmental exposure and disease development.

PM₂.₅ exposure is an emerging environmental concern and severe health insult closely related to psychological conditions such as anxiety and depression in adolescence. Adolescence is a critical period for neural system development characterized by continuous brain maturation, especially in the prefrontal cortex. The etiology of these adolescent conditions may derive from fetal origin, probably attributed to the adverse effects induced by intrauterine environmental exposure. Anxiety- and depression-like behavior can be induced by gestational exposure to PM₂.₅ in mice offspring which act as a useful model system. Recent studies show that B-vitamin may alleviate PM₂.₅-induced hippocampal neuroinflammation- and function-related spatial memory impairment in adolescent mice offspring. However, cortical damage and related neurobehavioral defects induced by gestational PM₂.₅ exposure, as well as the potential reversibility by interventions in mice offspring require to be elucidated. Here, we aimed to investigate whether B-vitamin would protect mice offspring from the adverse effects derived from gestational exposure to urban PM₂.₅ on cortical areas to which anxiety and depression are closely related. Pregnant mice were divided into three groups: control group (treated with PBS alone), model group (treated with both PM₂.₅ and PBS), and intervention group (treated with both PM₂.₅ and B-vitamin), respectively. The mice offspring were then applied to comprehensive neurobehavioral, ultrastructural, biochemical, and molecular biological analyses. Interestingly, we observed that gestational PM₂.₅ exposure led to neurobehavioral defects including anxiety- and depression-like behavior. In addition, neuroinflammation, oxidative damage, increased apoptosis, and caspase-1-mediated inflammasome activation in the prefrontal cortex were observed. Notably, both behavioral and molecular changes could be significantly alleviated by B-vitamin treatment. In summary, our results suggest that the anxiety- and depression-like behavior induced by gestational PM₂.₅ exposure in mice offspring can be ameliorated by B-vitamin supplementation, probably through the suppression of apoptosis, oxidative damage, neuroinflammation, and caspase-1-mediated inflammasome activation.

Exposure to ultrafine particulate matter (PM0.1) is positively associated with the etiology of different acute and chronic disorders; however, the in-depth biological imprints that link these submicron particles with the disturbances in the epigenomic machinery are not well defined. Earlier, we showed that exposure to these particles causes significant disturbances in the mitochondrial machinery and triggers PI-3-kinase mediated DNA damage responses. In the present study, we aimed to further understand the epigenomic insights of the ultrafine PM exposure. The higher levels of intracellular reactive oxygen species and depleted Nrf-2 in ultrafine PM exposed cells reconfirmed its potential to induce oxidative stress. Importantly, the observed increase in the levels of NF-κβ and associated cytokines among exposed cells suggested the activation of NF-κβ mediated inflammatory loop which potentially serves as a platform for initiating epigenetic insinuations. This fact was strongly supported by the altered miRNA expression profile of the ultrafine PM exposed cells. These NF-κβ induced miRNA alterations were also found to be associated with other epigenetic targets as the exposed cells showed higher expression levels of DNA methyltransferases which positively corresponded with the global changes in DNA methylation levels. Upon further analysis, significant alterations in histone code were also reported in ultrafine PM exposed cells. Conclusively our results suggested that NF-κβ acts as an inflammatory switch that possesses the potential to induce genome-wide epigenetic modification upon ultrafine PM exposure.