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

Goriainova, Viktoriia; Awada, Christina; Opoku, Florence; Zelikoff, Judith T.
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.
ISSN: 2305-6304
CID: 5407312

A Research Agenda for the Chemistry of Fires at the Wildland-Urban Interface: A National Academies Consensus Report

Harries, Megan E; Allen, David T; Adetona, Olorunfemi; Bell, Michelle L; Black, Marilyn S; Burgess, Jefferey L; Dryer, Frederick L; Holder, Amara L; Mascareñas, Ana; Rosario-Ortiz, Fernando L; Stec, Anna A; Turpin, Barbara J; Zelikoff, Judith T
PMID: 36288208
ISSN: 1520-5851
CID: 5359472

Downregulation of Stem-loop binding protein by nicotine via α7-nicotinic acetylcholine receptor and its role in nicotine-induced cell transformation

Sun, Qi; Chen, Danqi; Raja, Amna; Grunig, Gabriele; Zelikoff, Judith; Jin, Chunyuan
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, two 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.
PMID: 35929799
ISSN: 1096-0929
CID: 5288342

A contemporary review of nephrotoxicity and e-cigarette use

Raja, Amna; Zelikoff, Judith T.; Jaimes, Edgar A.
Since the advent of e-cigarettes (e-cigs) as alternatives to conventional cigarette smoking, there has been a dramatic increase in their use especially among adolescents and young adults. Vaping aerosols produced by e-cigs contain a variety of toxic and carcinogenic compounds, such as volatile organic compounds (VOCs), formaldehyde and acrolein, and metals including lead and nickel. General health effects of e-cig use range from respiratory health issues, hypertension and cardiovascular disease, as well as gastrointestinal problems and cognitive and nervous system decline. Unfortunately, there remains very limited information about e-cig use and its association with renal health, despite the fact that chronic kidney disease (CKD) affects about 37 million Americans. It has been reported that cigarette smoking causes the progression of CKD, and that nicotine, a constituent of both conventional cigarettes and e-cig devices, causes renal toxicity by promoting inflammation and injury through oxidative stress-mediated pathways. This contemporary review will discuss the results of current epidemiological and experimental toxicology literature (2016"“2022), as well as possible mechanisms of e-cig-induced renal injury.
ISSN: 2468-2020
CID: 5316922

The Chemistry and Health Outcomes of Electronic Waste (E-Waste) Leachate: Exposure to E-Waste Is Toxic to Atlantic Killifish (Fundulus heteroclitus) Embryos

Igbo, Juliet Kelechi; Chukwu, Lucian Obinna; Oyewo, Emmanuel Olusegun; Blum, Jason L.; Schanzer, Ariana; Wirgin, Isaac; Meltzer, Gabriella Y.; Roy, Nirmal K.; Zelikoff, Judith T.
Although there is rising global concern over the environmental, ecological, and human health risks associated with the discharge of leachates from e-waste dumpsites into the aquatic ecosystems, little is known in this research area. Thus, for this study, we first defined the chemistry of the test leachate, followed by assessment of the leachate on the development of a model aquatic organism (Fundulus heteroclitus) used extensively as a bioassay organism in pollution studies. Chemical analyses revealed that levels of phosphate (20.03 mg/L), cadmium (Cd) (0.4 mg/L), lead (Pb) (0.2 mg/L), and chromium (Cr) (0.4 mg/L) were higher than the 2009 US EPA and the 2009 National Environmental Standards and Regulations Enforcement Agency (NESREA) permissible limits. Polycyclic aromatic hydrocarbon (PAH) burdens were dominated mainly by the high molecular weight congeners, specifically the ∑4rings (73 µg/L). Total polychlorinated biphenyls (PCB) levels ranged from 0.00 to 0.40 µg/L with the ∑deca PCBs reaching the highest concentration. For the biological studies, F. heteroclitus embryos (48-h post-fertilization) were divided randomly into groups and exposed to one of six e-waste leachate concentrations (10, 1, 0.1, 0.01, 0.001, 0.0001%). Significant differences (p ≤ 0.05) between treated and control groups were observed in standard and total length, and head size. Further analysis using Duncan"™s post-hoc test of multiple comparison also revealed specific differences within and between specific treatment groups. We conclude that e-waste leachate arising from indiscriminate dumping into aquatic ecosystems in Nigeria contains mixtures of toxic constituents that can threaten ecosystem and public health.
ISSN: 2071-1050
CID: 5349092

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

Potter, Nicole A; Arita, Yuko; Peltier, Morgan R; Zelikoff, Judith T
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), β-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.
PMID: 36084357
ISSN: 1872-7603
CID: 5337322

E-Cigarette Exposure During Fetal Development Alters Protein Transporters and Gene Expression Activity in Neural Pathways Associated With Obesity in Mice [Meeting Abstract]

Awada, C; Blum, J L; Klein, C B; Zelikoff, J T
Electronic cigarettes (E-cigs), battery-powered devices containing vegetable glycerin and propylene glycol (PG/VG) as humectants, along with nicotine and flavors, are the most commonly used nicotine product amongst adolescents and young adults. Despite the lack of safety data, pregnant cigarette smokers are also turning to e-cigs as a 'safer' smoking alternative. This study hypothesized that like cigarette smoking, maternal vaping during pregnancy increases the risk of childhood obesity in the offspring. Thus, C57BL/6 mice were exposed both prenatally (3h/d; 5d/wk for ~3-wk) and postnatally from PND 4-21 to e-cig aerosols (50:50 PG/VG) with and without nicotine (16 mg/mL) and alterations in transcriptional and inflammatory activity in hypothalamic metabolic pathways associated with obesity were investigated. At 1-mo-of-age, offspring from filtered air (FA) control and both treatment groups were sacrificed, the hypothalami collected and expression of transporters associated with obesity (i.e., Glucose 1,2,3,4, PPARgamma, and Leptin) analyzed by Western blot. Results here demonstrated a significant increase in glucose transporter 1-4 expression in both the PG/VG alone and PG/VG plus nicotine treatment groups compared to control levels. In addition, gene expression of PPARgamma, LepRb, MC4R, SLC2A1 were significantly increased (p<0.01) in these same 1-moold offspring compared to matched FA controls. Alternatively, no significant changes in AMPK and POMC expression was observed between and amongst treatment groups. These findings suggest that like traditional cigarettes, early life exposure to vaping aerosols (with and without nicotine) predispose the young offspring to obesity later in life via e-cig-induced alterations in the neural-obesity pathways
ISSN: 1098-2280
CID: 5365932

Per- and Polyfluoroalkyl substances (PFAS) in our environment-What's their story?

Lyons, Shannon Doherty; Zelikoff, Judith T
PMID: 35120848
ISSN: 1878-7541
CID: 5153982

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

Park, Sung-Hyun; Lu, Yuting; Shao, Yongzhao; Prophete, Colette; Horton, Lori; Sisco, Maureen; Lee, Hyun-Wook; Kluz, Thomas; Sun, Hong; Costa, Max; Zelikoff, Judith; Chen, Lung-Chi; Gorr, Matthew W; Wold, Loren E; Cohen, Mitchell D
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.
PMID: 35055737
ISSN: 1660-4601
CID: 5131772

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

Vandiver, Kathleen Mead; Erdei, Esther; Mayer, Amanda G; Ricciardi, Catherine; O'Leary, Marcia; Burke, Kathleen; Zelikoff, Judith T
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.
PMID: 35055751
ISSN: 1660-4601
CID: 5131782