DNA methylation is the most well studied of the epigenetic regulators in relation to environmental exposures. To date, numerous studies have detailed the manner by which DNA methylation is influenced by the environment, resulting in altered global and gene-specific DNA methylation. These studies have focused on prenatal, early-life, and adult exposure scenarios. The present review summarizes currently available literature that demonstrates a relationship between DNA methylation and environmental exposures. It includes studies on aflatoxin B, air pollution, arsenic, bisphenol A, cadmium, chromium, lead, mercury, polycyclic aromatic hydrocarbons, persistent organic pollutants, tobacco smoke, and nutritional factors. It also addresses gaps in the literature and future directions for research. These gaps include studies of mixtures, sexual dimorphisms with respect to environmentally associated methylation changes, tissue specificity, and temporal stability of the methylation marks.
Exposure to cigarette smoke is known to result in impaired host defense responses and immune suppressive effects. However, the effects of new and emerging tobacco products, such as e-cigarettes, on the immune status of the respiratory epithelium are largely unknown. We conducted a clinical study collecting superficial nasal scrape biopsies, nasal lavage, urine, and serum from nonsmokers, cigarette smokers, and e-cigarette users and assessed them for changes in immune gene expression profiles. Smoking status was determined based on a smoking history and a 3- to 4-wk smoking diary and confirmed using serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) levels. Total RNA from nasal scrape biopsies was analyzed using the nCounter Human Immunology v2 Expression panel. Smoking cigarettes or vaping e-cigarettes resulted in decreased expression of immune-related genes. All genes with decreased expression in cigarette smokers (n = 53) were also decreased in e-cigarette smokers. Additionally, vaping e-cigarettes was associated with suppression of a large number of unique genes (n = 305). Furthermore, the e-cigarette users showed a greater suppression of genes common with those changed in cigarette smokers. This was particularly apparent for suppressed expression of transcription factors, such as EGR1, which was functionally associated with decreased expression of 5 target genes in cigarette smokers and 18 target genes in e-cigarette users. Taken together, these data indicate that vaping e-cigarettes is associated with decreased expression of a large number of immune-related genes, which are consistent with immune suppression at the level of the nasal mucosa.
Atmospheric oxidation of isoprene in the presence of acidic sulfate aerosol leads to secondary organic aerosol (SOA) that substantially contributes to the mass of outdoor fine particulate matter (PM2.5). The potential adverse health effects resulting from exposure to this PM type are largely unknown. Isoprene-derived epoxides, isoprene epoxydiols (IEPOX) and methacrylic acid epoxide (MAE), have recently been identified as key gaseous intermediates leading to isoprene SOA formation through acid-catalyzed multiphase chemistry. Altered expression of oxidative stress-associated genes was assessed from exposure to laboratory-generated IEPOX- and MAE-derived SOA in an in vitro model of human airway epithelial cells (BEAS-2B). Exposure to SOA filter extracts is associated with an increased level of expression of oxidative stress response genes in human lung cells under noncytotoxic conditions, with MAE-derived SOA extracts showing greater potency than IEPOX-derived SOA extracts. Our findings highlight the importance of future work aimed at linking PM source, composition, exposure biomarkers, and health outcomes.
Friedreich's ataxia (FRDA) is the most common inherited human ataxia and results from a deficiency of the mitochondrial protein, frataxin (FXN), which is encoded in the nucleus. This deficiency is associated with an iron-sulfur (Fe-S) cluster enzyme deficit leading to progressive ataxia and a frequently fatal cardiomyopathy. There is no cure. To determine whether exogenous replacement of the missing FXN protein in mitochondria would repair the defect, we used the transactivator of transcription (TAT) protein transduction domain to deliver human FXN protein to mitochondria in both cultured patient cells and a severe mouse model of FRDA. A TAT-FXN fusion protein bound iron in vitro, transduced into mitochondria of FRDA deficient fibroblasts and reduced caspase-3 activation in response to an exogenous iron-oxidant stress. Injection of TAT-FXN protein into mice with a conditional loss of FXN increased their growth velocity and mean lifespan by 53% increased their mean heart rate and cardiac output, increased activity of aconitase and reversed abnormal mitochondrial proliferation and ultrastructure in heart. These results show that a cell-penetrant peptide is capable of delivering a functional mitochondrial protein in vivo to rescue a very severe disease phenotype, and present the possibility of TAT-FXN as a protein replacement therapy.
Aim: Sex-based differences in response to adverse prenatal environments and infant outcomes have been observed, yet the underlying mechanisms for this are unclear. The placental epigenome may be a driver of these differences. Methods: Placental DNA methylation was assessed at more than 480,000 CpG sites from male and female infants enrolled in the extremely low gestational age newborns cohort (ELGAN) and validated in a separate US-based cohort. The impact of gestational age on placental DNA methylation was further examined using the New Hampshire Birth Cohort Study for a total of n = 467 placentas. Results: A total of n = 2745 CpG sites, representing n = 587 genes, were identified as differentially methylated (p < 1 × 10 -7 ). The majority (n = 582 or 99%) of these were conserved among the New Hampshire Birth Cohort. The identified genes encode proteins related to immune function, growth/transcription factor signaling and transport across cell membranes. Conclusion: These data highlight sex-dependent epigenetic patterning in the placenta and provide insight into differences in infant outcomes and responses to the perinatal environment.
Rationale: Exposure to particulates from burning biomass is an increasing global health issue. Burning biomass, including wood smoke, is associated with increased lower respiratory infections.Objectives: To determine whether acute exposure to wood smoke modifies nasal inflammatory responses to influenza.Methods: Healthy young adults (n = 39) were randomized to a 2-hour controlled chamber exposure to wood smoke, where exposure levels were controlled to particulate number (wood smoke particles [WSP]; 500 mg/cm 3 ) or filtered air, followed by nasal inoculation with a vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed before exposure (Day 0) and on Days 1 and 2 after exposure. Nasal lavage fluid cells were analyzed for inflammatory gene expression profiles, and cell-free fluid was assayed for cytokines.Measurements and Main Results: Only IP-10 protein levels were affected, suppressed, by WSP exposure in aggregate analysis. Subsequent analysis indicated an exposure 3 sex interaction, prompting additional analyses of WSP-and LAIV-induced changes in males and females. Inflammation-related gene expression profiles differed between the sexes, at baseline (males greater than females), after LAIV inoculation (females greater than males), and after WSP exposure (increase in males and decrease in females), demonstrating that WSP-and LAIV-induced changes in antiviral defense responses in the nasal mucosa occur in a sex-specific manner.Conclusions: WSP exposure resulted in minimal modification of LAIV-induced responses in aggregate analysis. In contrast, analyzing WSP-induced modification of LAIV responses in the sexes separately unmasked sex-specific differences in response to exposure. These data highlight the need for additional studies to understand sexspecific pollutant-induced effects.Clinical trial registered with www.clinicaltrials.gov (NCT02183753).
Exposure to environmental contaminants during pregnancy has been linked to adverse outcomes at birth and later in life. The link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Toxic metals and endocrine disruptors are two major classes of contaminants that are ubiquitously present in the environment and represent threats to human health. In this review, we present evidence that prenatal exposures to these contaminants result in fetal epigenomic changes, including altered global DNA methylation, gene-specific CpG methylation and microRNA expression. Importantly, these changes may have functional cellular consequences, impacting health outcomes later in life. Therefore, these epigenetic changes represent a critical mechanism that warrants further study.
Aims The objective of this study was to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic resistant Staphylococcus aureus strains. Methods and Results Inhibitory effect of commercial orange essential oil (EO) against six S. aureus strains was tested by disc diffusion and agar dilution methods. The mechanism of EO action on MRSA was analyzed by transcriptional profiling. Morphological changes of EO treated S. aureus were examined by transmission electron microscopy. Results showed that 0.1% of cold pressed terpeneless Valencia orange oil (CPV) induced the cell wall stress stimulon consistent with inhibition of cell wall synthesis. Transmission electron microscopic observation revealed cell lysis and suggested a cell wall-lysis related mechanism of CPV. Conclusions CPV inhibits the growth of S. aureus, causes gene expression changes consistent with inhibition of cell wall synthesis and triggers cell lysis. Significance and Impact of the Study Multiple antibiotics resistance is becoming a serious problem in the management of S. aureus infections. In this study the altered expression of cell wall associated genes and subsequent cell lysis in MRSA caused by CPV suggests that it may be a potential antimicrobial agent to control antibiotic resistant S. aureus.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.