Traffic-related air pollution in marginalized neighborhoods: a community perspective.

OBJECTIVES: Marginalized communities are exposed to higher levels of traffic-related air pollution (TRAP) than the general population. TRAP exposure is linked to pulmonary toxicity, neurotoxicity, and cardiovascular toxicity often through mechanisms of inflammation and oxidative stress. Early life exposure to TRAP is also implicated in higher rates of asthma in these same communities. There is a critical need for additional epidemiological, in vivo, and in vitro studies to define the health risks of TRAP exposure affecting the most vulnerable groups to set strict, protective air pollution standards in these communities. MATERIALS AND METHODS: A literature review was conducted to summarize recent findings (2010-2024) concerning TRAP exposure and toxic mechanisms that are relevant to the most affected underserved communities. CONCLUSIONS: Guided by the perspectives of NYC community scientists, this contemporary review of toxicological and epidemiological studies considers how the exposome could lead to disproportionate exposures and health effects in underserved populations.

E-Cigarette Exposure Alters Neuroinflammation Gene and Protein Expression in a Murine Model: Insights from Perinatally Exposed Offspring and Post-Birth Mothers.

The use of E-cigarettes, often considered a safer alternative to traditional smoking, has been associated with high rates of cellular toxicity, genetic alterations, and inflammation. Neuroinflammatory impacts of cigarette smoking during pregnancy have been associated with increased risks of adverse childhood health outcomes; however, it is still relatively unknown if the same propensity is conferred on offspring by maternal vaping during gestation. Results from our previous mouse inhalation studies suggest such a connection. In this earlier study, pregnant C57BL/6 mice were exposed daily to inhaled E-cig aerosols (i.e., propylene glycol and vegetable glycerin, [PG/VG]), with or without nicotine (16 mg/mL) by whole-body inhalation throughout gestation (3 h/d; 5 d/week; total ~3-week) and continuing postnatally from post-natal day (PND) 4-21. As neuroinflammation is involved in the dysregulation of glucose homeostasis and weight gain, this study aimed to explore genes associated with these pathways in 1-mo.-old offspring (equivalent in humans to 12-18 years of age). Results in the offspring demonstrated a significant increase in glucose metabolism protein levels in both treatment groups compared to filtered air controls. Gene expression analysis in the hypothalamus of 1 mo. old offspring exposed perinatally to E-cig aerosols, with and without nicotine, revealed significantly increased gene expression changes in multiple genes associated with neuroinflammation. In a second proof-of-principal parallel study employing the same experimental design, we shifted our focus to the hippocampus of the postpartum mothers. We targeted the mRNA levels of several neurotrophic factors (NTFs) indicative of neuroinflammation. While there were suggestive changes in mRNA expression in this study, levels failed to reach statistical significance. These studies highlight the need for ongoing research on E-cig-induced alterations in neuroinflammatory pathways.

In vivo exposure to electronic waste (e-waste) leachate and hydraulic fracturing fluid adversely impacts the male reproductive system.

Human health effects can arise from unregulated manual disassembly of electronic waste (e-waste) and/or hydraulic fracturing fluid spills. There is limited literature on the effects of e-waste and hydraulic fracturing wastewater exposure on the male reproductive system. Thus, this proof-of-concept study begins to address the question of how wastewater from two potentially hazardous environmental processes could affect sperm quality. Therefore, three groups of eight-week-old adult mice were exposed (5 d/wk for 6 wks) via a mealworm (Tenebrio molitor and Zophabas morio) feeding route to either: (1) e-waste leachate (50% dilution) from the Alaba Market (Lagos, Nigeria); (2) West Virginia hydraulic fracturing flowback (HFF) fluid (50% dilution); or, (3) deionized water (control). At 24-hours (hr), 3 weeks (wk), or 9-wk following the 6-wk exposure period, cohorts of mice were necropsied and adverse effects/persistence on the male reproductive system were examined. Ingestion of e-waste leachate or HFF fluid decreased number and concentration of sperm and increased both chromatin damage and numbers of morphological abnormalities in the sperm when compared to control mice. Levels of serum testosterone were reduced post-exposure (3- and 9-wk) in mice exposed to e-waste leachate and HFF when compared to time-matched controls, indicating the long-term persistence of adverse effects, well after the end of exposure. These data suggest that men living around or working in vicinity of either e-waste or hydraulic fracturing could face harmful effects to their reproductive health. From both a human health and economic standpoint, development of prevention and intervention strategies that are culturally relevant and economically sensitive are critically needed to reduce exposure to e-waste and HFF-associated toxic contaminants.

Adverse Effects of Black Carbon (BC) Exposure during Pregnancy on Maternal and Fetal Health: A Contemporary Review.

Black carbon (BC) is a major component of ambient particulate matter (PM), one of the six Environmental Protection Agency (EPA) Criteria air pollutants. The majority of research on the adverse effects of BC exposure so far has been focused on respiratory and cardiovascular systems in children. Few studies have also explored whether prenatal BC exposure affects the fetus, the placenta and/or the course of pregnancy itself. Thus, this contemporary review seeks to elucidate state-of-the-art research on this understudied topic. Epidemiological studies have shown a correlation between BC and a variety of adverse effects on fetal health, including low birth weight for gestational age and increased risk of preterm birth, as well as cardiometabolic and respiratory system complications following maternal exposure during pregnancy. There is epidemiological evidence suggesting that BC exposure increases the risk of gestational diabetes mellitus, as well as other maternal health issues, such as pregnancy loss, all of which need to be more thoroughly investigated. Adverse placental effects from BC exposure include inflammatory responses, interference with placental iodine uptake, and expression of DNA repair and tumor suppressor genes. Taking into account the differences in BC exposure around the world, as well as interracial disparities and the need to better understand the underlying mechanisms of the health effects associated with prenatal exposure, toxicological research examining the effects of early life exposure to BC is needed.

Ex vivo toxicity of E-cigarette constituents on human placental tissues.

Globally, ∼50 % of women smoke during pregnancy and the prevalence of vaping is increasing among women of reproductive age. However, the health effects of vaping during pregnancy are largely unknown. This study examined the effects of e-cig constituents alone and in combination (propylene glycol [PG], vegetable glycerin [VG], and nicotine) on human placental tissue viability (MTT assay) and immunoassayed levels of placenta-derived biomarkers, i.e., 8-isoprostane (8-IsoP), heme oxygenase-1 (HO-1), interleukin-6 (IL-6), ß-estradiol (E2), progesterone (P4), allopregnanolone (AP), and brain-derived neurotrophic factor (BDNF). Placental explant cultures were exposed ex vivo for 24 h to media-containing either nicotine (0-5000 nM), PG/VG (0-8 % v/v at 50/50 ratio), or a combination of both. No effects on tissue viability were observed at PG/VG concentrations < 8 % (v/v), while viability significantly reduced at PG/VG concentrations ≥ 10 % (v/v); biomarker studies employed only non-cytotoxic doses. Exposure to PG/VG decreased levels of 8-IsoP, IL-6, and E2, and treatment with 2 % or 8 % PG/VG significantly reduced HO-1 levels, compared to non-treated controls. Exposure to nicotine alone at 2,500 nM and 5,000 nM reduced MTT activity by 20 % (P = 0.04) and 70 % (P < 0.001), respectively, and significantly increased (P < 0.001) levels of HO-1 and BDNF, compared to controls. Treatment with nicotine alone and in combination with PG/VG reduced IL-6 and E2 levels. Interestingly, nicotine-induced toxicity was attenuated by PG/VG addition to nicotine-treated groups. These studies demonstrate that e-cig constituents negatively impact the human placenta and alters production of critical placental biomarkers, suggesting that vaping is an unsafe alternative for pregnant women or their unborn fetus.

Downregulation of Stem-Loop Binding Protein by Nicotine via α7-Nicotinic Acetylcholine Receptor and Its Role in Nicotine-Induced Cell Transformation.

The use of electronic-cigarettes (e-cigs) has increased substantially in recent years, particularly among the younger generations. Liquid nicotine is the main component of e-cigs. Previous studies have shown that mice exposed to e-cig aerosols developed lung adenocarcinoma and bladder hyperplasia. These findings implicated a potential role for e-cig aerosols and nicotine in cancer development, although the underlying mechanisms are not fully understood. Here we report that exposure to liquid nicotine or nicotine aerosol generated from e-cig induces downregulation of Stem-loop binding protein (SLBP) and polyadenylation of canonical histone mRNAs in human bronchial epithelial cells and in mice lungs. Canonical histone mRNAs typically do not end in a poly(A) tail and the acquisition of such a tail via depletion of SLBP has been shown to causes chromosome instability. We show that nicotine-induced SLBP depletion is reversed by an inhibitor of α7-nicotinic acetylcholine receptors (α7-nAChR) or siRNA specific for α7-nAChR, indicating a nAChR-dependent reduction of SLBP by nicotine. Moreover, PI3K/AKT pathway is activated by nicotine exposure and CK2 and probably CDK1, 2 kinases well known for their function for SLBP phosphorylation and degradation, are shown to be involved, α7-nAChR-dependently, in nicotine-induced SLBP depletion. Importantly, nicotine-induced anchorage-independent cell growth is attenuated by inhibition of α7-nAChR and is rescued by overexpression of SLBP. We propose that the SLBP depletion and polyadenylation of canonical histone mRNAs via activation of α7-nAChR and a series of downstream signal transduction pathways are critical for nicotine-induced cell transformation and potential carcinogenesis.

Longitudinal Impact of WTC Dust Inhalation on Rat Cardiac Tissue Transcriptomic Profiles.

First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.

Building Environmental Health and Genomics Literacy among Healthcare Providers Serving Vulnerable Communities: An Innovative Educational Framework.

This study addresses healthcare providers' knowledge deficits in environmental health and genetics, and primarily focuses on student nurses and nurses serving marginalized, low-income communities frequently exposed to environmental toxicants. Our approach to improve public health is unique, combining hands-on modeling exercises with case-based lessons in addition to three targeted 40 min lectures on toxicology. These lectures included the team's community-based environmental health research among Indigenous peoples of the U.S. The hands-on approach employed DNA and protein molecular models designed to demonstrate normal and dysfunctional molecules, as well as genetic variants in world populations. The models provided learners with visuals and an experience of "learning by doing." Increased awareness of the effects of environmental toxicants is the first step toward improving health care for exposed communities. We measured knowledge gains by pre- and post-tests among student nurses and nurses serving Native Americans living both in urban and rural areas of the U.S. (n = 116). The modeling lessons illustrated genetic variants in liver proteins common in Native peoples and their resulting health vulnerabilities. Participants were engaged and enthusiastic; and pre- and post-test results reported substantial knowledge gains and a greater understanding of genetic susceptibility (p < 0.0001). Our study demonstrates the utility of this framework across diverse populations and remote communities.

A contemporary review of electronic waste through the lens of inhalation toxicology.

Inhalation is a significant route of exposure to toxic chemicals for electronic waste (e-waste) workers, especially for those whose activities take place in the informal sector. However, there remains a dearth of research on the health effects produced by the hazardous dismantling of e-waste and associated outcomes and biological mechanisms that occur as a result of inhalation exposure. This contemporary review highlights a number of the toxicological and epidemiological studies published on this topic to bring to light the many knowledge gaps that require further research, including in vitro and ex vivo investigations to address the health outcomes and underlying mechanisms of inhaled e-waste-associated pulmonary disease.

Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.

Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.

Pyridoxine deficiency modulates benzene inhalation-induced hematotoxicity associated with hepatic CYP2E1 activity in B6C3F1 mice.

Pyridoxine is a co-factor in many enzymatic reactions and impacts of deficiency have been observed in affected populations. A possible modifying effect of pyridoxine deficiency on benzene toxicity was assessed in male B6C3F1 mice fed either a pyridoxine-deficient diet or a control diet. This treatment was combined with benzene inhalation exposure (100 ppm) or no benzene treatment. Pyridoxine-deficient mice exposed to 100 ppm benzene had significantly lower body, thymus and spleen weights. While total white blood cell counts, percentage of lymphocytes, hematocrit and hemoglobin levels were lower, the percentage of neutrophils was significantly higher in deficient and benzene-exposed mice compared to non-exposed controls. Hepatic CYP2E1 protein expression and activity in the deficient and exposed mice were also significantly higher compared to the non-exposed controls. A significant correlation between CYP2E1 activity and several hematological parameters was observed. These results demonstrated that pyridoxine deficiency significantly impacted benzene-induced hematotoxicity. Moreover, the observed agonistic effect of pyridoxinedeficiency and benzene inhalation exposure on CYP2E1 would seem to indicate an involvement of metabolism, but this needs to be further assessed.

Plant-Derived Food Grade Substances (PDFGS) Active Against Respiratory Viruses: A Systematic Review of Non-clinical Studies.

Human diet comprises several classes of phytochemicals some of which are potentially active against human pathogenic viruses. This study examined available evidence that identifies existing food plants or constituents of edible foods that have been reported to inhibit viral pathogenesis of the human respiratory tract. SCOPUS and PUBMED databases were searched with keywords designed to retrieve articles that investigated the effect of plant-derived food grade substances (PDFGS) on the activities of human pathogenic viruses. Eligible studies for this review were those done on viruses that infect the human respiratory tract. Forty six (46) studies met the specified inclusion criteria from the initial 5,734 hits. The selected studies investigated the effects of different PDFGS on the infectivity, proliferation and cytotoxicity of different respiratory viruses including influenza A virus (IAV), influenza B virus (IBV), Respiratory syncytial virus (RSV), human parainfluenza virus (hPIV), Human coronavirus NL63 (HCoV-NL63), and rhinovirus (RV) in cell lines and mouse models. This review reveals that PDFGS inhibits different stages of the pathological pathways of respiratory viruses including cell entry, replication, viral release and viral-induced dysregulation of cellular homeostasis and functions. These alterations eventually lead to the reduction of virus titer, viral-induced cellular damages and improved survival of host cells. Major food constituents active against respiratory viruses include flavonoids, phenolic acids, tannins, lectins, vitamin D, curcumin, and plant glycosides such as glycyrrhizin, acteoside, geniposide, and iridoid glycosides. Herbal teas such as guava tea, green and black tea, adlay tea, cistanche tea, kuding tea, licorice extracts, and edible bird nest extracts were also effective against respiratory viruses in vitro. The authors of this review recommend an increased consumption of foods rich in these PDFGS including legumes, fruits (e.g berries, citrus), tea, fatty fish and curcumin amongst human populations with high prevalence of respiratory viral infections in order to prevent, manage and/or reduce the severity of respiratory virus infections.

Particulate Matter and Associated Metals: A Link with Neurotoxicity and Mental Health.

Particulate air pollution (PM) is a mixture of heterogenous components from natural and anthropogenic sources and contributes to a variety of serious illnesses, including neurological and behavioral effects, as well as millions of premature deaths. Ultrafine (PM0.1) and fine-size ambient particles (PM2.5) can enter the circulatory system and cross the blood-brain barrier or enter through the optic nerve, and then upregulate inflammatory markers and increase reactive oxygen species (ROS) in the brain. Toxic and neurotoxic metals such as manganese (Mn), zinc (Zn), lead (Pb), copper (Cu), nickel (Ni), and barium (Ba) can adsorb to the PM surface and potentially contribute to the neurotoxic effects associated with PM exposure. Epidemiological studies have shown a negative relationship between exposure to PM-associated Mn and neurodevelopment amongst children, as well as impaired dexterity in the elderly. Inhaled PM-associated Cu has also been shown to impair motor performance and alter basal ganglia in schoolchildren. This paper provides a brief review of the epidemiological and toxicological studies published over the last five years concerning inhaled PM, PM-relevant metals, neurobiology, and mental health outcomes. Given the growing interest in mental health and the fact that 91% of the world's population is considered to be exposed to unhealthy air, more research on PM and PM-associated metals and neurological health is needed for future policy decisions and strategic interventions to prevent public harm.