Second Skin as Self-Protection Against γ-Hydroxybutyrate.

γ-Hydroxybutyrate (GHB), a date-rape drug, causes certain symptoms, such as amnesia, confusion, ataxia, and unconsciousness, when dissolved in beverages and consumed by a victim. Commonly, assailants use GHB in secret for the crime of drug-facilitated sexual assault because it is tasteless, odorless, and colorless when dissolved in beverages. Generally, GHB detection methods are difficult to use promptly and secretly in situ and in real life because of the necessary detection equipment and low selectivity. To overcome this problem, we have developed a fast, simple, and easy-to-use second skin platform as a confidential self-protection platform that can detect GHB in situ or in real life without equipment. The second skin platform for naked-eye detection of GHB is fabricated with poly(vinyl alcohol) (PVA), polyurethane (PU), and polyacrylonitrile (PAN) included in the chemical receptor 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI). PAN conjugated with BHEI nanofibers (PB NFs) has various characteristics, such as ease of use, high sensitivity, and fast color change. PB NFs rapidly detected GHB at 0.01 mg/mL. Furthermore, the second-skin platform attached to the fingertip and wrist detected both 1 and 0.1 mg/mL GHB in solution within 50 s. The color changes caused by the interaction of GHB and the second skin platform cannot be stopped due to strong chemical reactions. In addition, a second skin platform can be secretly utilized in real life because it can recognize fingerprints and object temperatures. Therefore, the second skin platform can be used to aid daily life and prevent drug-facilitated sexual assault crime when attached to the skin because it can be exposed anytime and anywhere.

Effect of Oxyfluorination of PFA-Coated Metal Mesh with Superhydrophobic Properties on the Filtration Performance of SiO2 Microparticles.

Recently, semiconductor wastewater treatment has received much attention due to the emergence of environmental issues. Acid-resistant coatings are essential for metal prefilters used in semiconductor wastewater treatment. Perfluoroalkoxy alkane is mainly used as an acid-resistant coating agent, since PFA has inherent superhydrophobicity, water permeability is lowered. To solve this problem, the surface of the PFA-coated metal mesh was treated via an oxyfluorination method in which an injected mixed gas of fluorine and oxygen reacted with the surface functional groups. Surface analysis, water contact angle measurement, and water permeability tests were performed on the surface-treated PFA-coated mesh. Consequently, the superhydrophobic surface was effectively converted to a hydrophobic surface as the PFA coating layer was surface-modified with C-O-OH functional groups via the oxyfluorination reaction. As a result of using simulation solutions that float silica particles of various sizes, the permeability and particle removal rate of the surface-modified PFA-coated stainless-steel mesh were improved compared to those before surface modification. Therefore, the oxyfluorination treatment used in this study was suitable for improving the filtration performance of SiO2 microparticles in the PFA-coated stainless-steel mesh.

DNA methylome signatures as epigenetic biomarkers of hexanal associated with lung toxicity.

BACKGROUND: Numerous studies have investigated the relationship of environmental exposure, epigenetic effects, and human diseases. These linkages may contribute to the potential toxicity mechanisms of environmental chemicals. Here, we investigated the epigenetic pulmonary response of hexanal, a major indoor irritant, following inhalation exposure in F-344 rats. METHODS: Based on DNA methylation profiling in gene promoter regions, we identified hexanal-characterized methylated sites and target genes using an unpaired t-test with a fold-change cutoff of ≥ 3.0 and a p-value < 0.05. We also conducted an integrated analysis of DNA methylation and mRNA expression data to identify core anti-correlated target genes of hexanal exposure. To further investigate the potential key biological processes and pathways of core DNA methylated target genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. RESULTS: Thirty-six dose-dependent methylated genes and anti-correlated target genes of DNA methylation and mRNA in lung tissue of hexanal exposed F-344 rats were identified. These genes were involved in diverse biological processes such as neuroactive ligand-receptor interaction, protein kinase cascade, and intracellular signaling cascade associated with pulmonary toxicity. These results suggest that novel DNA methylation-based epigenetic biomarkers of exposure to hexanal and elucidate the potential pulmonary toxicological mechanisms of action of hexanal.

The genome of the giant Nomura's jellyfish sheds light on the early evolution of active predation.

BACKGROUND: Unique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column and were some of the first animals to become free-swimming. The class Scyphozoa, or true jellyfish, are characterized by a predominant medusa life-stage consisting of a bell and venomous tentacles used for hunting and defense, as well as using pulsed jet propulsion for mobility. Here, we present the genome of the giant Nomura's jellyfish (Nemopilema nomurai) to understand the genetic basis of these key innovations. RESULTS: We sequenced the genome and transcriptomes of the bell and tentacles of the giant Nomura's jellyfish as well as transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of the Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains, possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation). CONCLUSIONS: Taken together, the Nemopilema jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits, which may have contributed to the success of jellyfish as early multi-cellular predators.

Effect of particulate matter 2.5 on gene expression profile and cell signaling in JEG-3 human placenta cells.

Particulate matter the environmental toxicant, with a diameter less than or equal to 2.5 µm (PM2.5 ) is a common cause of several respiratory diseases. In recent years, several studies have suggested that PM2.5 can influence diverse diseases, such as respiratory diseases, cardiovascular diseases, metabolic diseases, dementia, and female reproductive disorders, and unhealthy birth outcomes. In addition, several epidemiological studies have reported that adverse health effects of PM2.5 can differ depending on regional variations. In the present study, to evaluate specific adverse health effects of PM2.5 , we collected two different PM2.5 samples from an underground parking lot and ambient air, and we evaluated cytotoxicity with eight different cell lines originating from human organs. Then, we selected JEG-3 human placenta cells, which show high cytotoxicity to both PM samples. Through RNA sequencing, gene expression profiling, and a gene ontology (GO) analysis of JEG-3 after exposure to two different PM2.5 samples, we identified 1021 commonly expressed genes involved in immune responses, the regulation of apoptosis, and so forth, which are known to induce several adverse health effects. In addition, we identified genes related to the calcium-signaling pathway, steroid hormone biosynthesis, and the cytokine-cytokine receptor interaction through a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, we confirmed these gene expressions using qRT-PCR, and the protein levels of mitogen-activated protein kinases and COX-2 with progesterone decreased using western blotting and enzyme-linked immunosorbent assay. In conclusion, this study suggests the possible toxic mechanism of human placenta that might be associated with PM2.5 -induced female reproductive disorders.

DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity.

Recent studies have investigated the epigenetic effects of environmental exposure to chemicals on human health. The associations of DNA methylation, environmental exposure and human diseases have been widely demonstrated. However, the use of gene methylation patterns as a predictive biomarker for exposure to environmental toxicants is relatively poorly understood. Here, we focused on low-molecular-weight saturated aliphatic aldehydes (LSAAs), which are important environmental risk factors in humans as major indoor air pollutants. Based on DNA methylation profiling in gene promoter regions, we analysed DNA methylation profiles following exposure of A549 cells to seven LSAAs (propanal, butanal, pentanal, hexanal, heptanal, octanal, and nonanal) to identify LSAA-characterized methylated sites and target genes, as well as to investigate whether exposure to LSAAs contributes to inducing of pulmonary toxicity. Additionally, by integrating DNA methylation and mRNA expression profile analyses, we identified core anti-correlated target genes. Gene ontology analysis of these target genes revealed several key biological processes. These findings suggest that alterations in DNA methylation by exposure to LSAAs provide novel epigenetic biomarkers for risk assessments. This DNA methylation-mRNA approach also reveals potential new mechanistic insights into the epigenetic actions of pulmonary toxicity.

Identification of novel cytokine biomarkers of hexanal exposure associated with pulmonary toxicity.

We aimed to investigate whether exposure to low-molecular-weight saturated aliphatic aldehydes induces an airway inflammation related to lung toxicity. In previous studies, we identified that several aldehydes induced inflammatory responses through the secretion of pro-inflammatory cytokines. Here, we elucidate on whether hexanal exposure induces the lung inflammatory response through the secretion of cytokines. Hexanal is one of the aldehydes, which are major components of indoor environmental irritants. Based on a multiplexed cytokine antibody array, we investigated the cytokine expression profiles to identify the significant biomarkers of hexanal exposure and to predict the possibility of adverse effects on pulmonary toxicity using in vitro and in vivo model systems. We identified the cytokines as biomarkers involved in LEPTIN, Interleukin(IL)-10, MCP-1, and VEGF that showed similar expression patterns in both in vitro and in vivo models under hexanal exposure. These cytokines are known to be associated with diverse lung diseases, such as lung fibrosis, chronic obstructive pulmonary disease (COPD), and non-small cell lung cancer. Although further studies are needed to identify the mechanisms that underlie hexanal pulmonary toxicity, these results provide the key cytokine biomarkers in response to hexanal exposure and indicate meaningful mechanistic previewing that can be indirectly attributed to lung disease.

Comparative analysis of microRNA and mRNA expression profiles in cells and exosomes under toluene exposure.

Recent studies have illustrated the growing importance of exosomes (small extracellular vesicles) and their constituent microRNAs (miRNAs) in the fields of toxicology and pathology. The mechanism of toxicity of toluene, a highly-prevalent and volatile organic compound, is largely unknown. To examine the role of miRNAs in toluene-induced toxicity, we investigated miRNAs and toluene-induced gene expression in HL-60 human promyelocytic leukemia cells and exosomes using microarrays. A total of 54 miRNAs were differentially expressed in HL-60 cell lines exposed to toluene and exosomes from the cells. Four out of the 54 miRNAs (hsa-miR-1290, hsa-miR-718, hsa-miR-3663-3p, and hsa-miR-320c) were subsequently validated by qRT-PCR. Integrated analysis of miRNA and mRNA expression profiles identified 8 miRNA-mRNA correlations. By performing Comparative Toxicogenomics Database analysis, we found that the eight putative target genes of the differentially expressed miRNAs under toluene exposure (EXOSC6, RHOH, GFER, HERC2, GOLGA4, SLC7A11, GCLM, and BACH1) are related to diverse disease categories such as nervous system disease, cancer, cardiovascular disease, and respiratory tract disease. In conclusion, our data demonstrated that miRNA-mRNA networks provide a better understanding of toxicological mechanism caused by environmental pollutants in vitro using HL-60 cells and exosomes.

Epidermal growth factor receptor (EGFR)-MAPK-nuclear factor(NF)-κB-IL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity.

Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2.5 and three cytokines with O-PM2.5 . Among them, epidermal growth factor (EGF) was commonly up-regulated by W-PM2.5 and O-PM2.5 . Then, in both groups, we can identify the increase in EGF receptor protein levels. Likewise, increases in the phosphorylation of ERK1/2 MAP kinase and acetylation of nuclear factor(NF)-κB were detected. We also detected an increase in IL-8 that was related to inflammatory response. And using the erlotinib as an inhibitor of EGFR, we identified the erlotinib impaired the phosphorylation of EGFR, ERK1/2, acetylation of NF-κB proteins and decreased IL-8. Furthermore, at in vivo model, we were able to identify similar patterns. These results suggest that PM2.5 may contribute to an abnormality in the human respiratory system through EGFR, MAP kinase, NF-κB, and IL-8 induced toxicity signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1628-1636, 2017.

Integrative analysis of mRNA and microRNA expression of a human alveolar epithelial cell(A549) exposed to water and organic-soluble extract from particulate matter (PM)2.5.

MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in toxicity. In this study, we assessed the effects of particulate matter 2.5 (PM2.5 ), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] and performed miRNA microarray analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3-fold in W-PM2.5 and O-PM2.5 , respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W-PM2.5 and O-PM2.5 exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W-PM2.5 target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O-PM2.5 target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM2.5 -induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 302-310, 2017.

Toxicogenomic analysis of the pulmonary toxic effects of hexanal in F344 rat.

Hexanal is a major component of indoor air pollutants and is a kind of aldehydes; it has adverse effects on human health. We performed an in vivo inhalation study and transcriptomic analysis to determine the mode of toxic actions in response to hexanal. Fischer 344 rats of both sexes were exposed by inhalation to hexanal aerosol for 4 h day-1 , 5 days week-1 for 4 weeks at 0, 600, 1000, and 1500 ppm. Throughout our microarray-based genome-wide expression analysis, we identified 56 differentially expressed genes in three doses of hexanal; among these genes, 11 genes showed dose-dependent expression patterns (10 downregulated and 1 upregulated, 1.5-fold, p < 0.05). Through a comparative toxicogenomics database (CTD) analysis of 11 genes, we determined that five genes (CCL12, DDIT4, KLF2, CEBPD, and ADH6) are linked to diverse disease categories such as cancer, respiratory tract disease, and immune system disease. These diseases were previously known for being induced by volatile organic compounds (VOCs). Our data demonstrated that the hexanal-induced dose-dependent altered genes could be valuable quantitative biomarkers to predict hexanal exposure and to perform relative risk assessments, including pulmonary toxicity. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 382-396, 2017.

Application of carbon foam for heavy metal removal from industrial plating wastewater and toxicity evaluation of the adsorbent.

Electroplating wastewater contains various types of toxic substances, such as heavy metals, solvents, and cleaning agents. Carbon foam was used as an adsorbent for the removal of heavy metals from real industrial plating wastewater. Its sorption capacity was compared with those of a commercial ion-exchange resin (BC258) and a heavy metal adsorbent (CupriSorb™) in a batch system. The experimental carbon foam has a considerably higher sorption capacity for Cr and Cu than commercial adsorbents for acid/alkali wastewater and cyanide wastewater. Additionally, cytotoxicity test showed that the newly developed adsorbent has low cytotoxic effects on three kinds of human cells. In a pilot plant, the carbon foam had higher sorption capacity for Cr (73.64 g kg(-1)) than for Cu (14.86 g kg(-1)) and Ni (7.74 g kg(-1)) during 350 h of operation time. Oxidation pretreatments using UV/hydrogen peroxide enhance heavy metal removal from plating wastewater containing cyanide compounds.

MicroRNA response of inhalation exposure to hexanal in lung tissues from Fischer 344 rats.

In previous studies, we have investigated the relationships between environmental chemicals and health risk based on omics analysis and identified significant biomarkers. Our current findings indicate that hexanal may be an important toxicant of the pulmonary system in epigenetic insights. MicroRNA (miRNA) is an important indicator of biomedical risk assessment and target identification. Hexanal is highly detectable in the exhaled breath of patients with chronic obstructive pulmonary disease (COPD) and chronic inflammatory lung disease. In this study, we aimed to identify hexanal-characterized miRNA-mRNA correlations involved in lung toxicity. Microarray analysis identified 56 miRNAs that commonly changed their expression more than 1.3-fold in three doses (600, 1000, and 1500 ppm) within hexanal-exposed Fischer 344 rats by inhalation, and 226 genes were predicted to be target genes of miRNAs through TargetScan analysis. By integrating analyses of miRNA and mRNA expression profiles, we identified one anti-correlated target gene (Chga; chromogranin A; parathyroid secretory protein 1). Comparative toxicogenomics database (CTD) analysis of this gene showed that Chga is involved with several disease categories such as cancer, respiratory tract disease, nervous system disease, and cardiovascular disease. Further research is necessary to elucidate the mechanisms of hexanal-responsive toxicologic pathways at the molecular level. This study concludes that our integrated approach to miRNA and mRNA enables us to identify molecular events in disease development induced by hexanal in an in vivo rat model. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1909-1921, 2016.

Blood miRNAs as sensitive and specific biological indicators of environmental and occupational exposure to volatile organic compound (VOC).

To date, there is still shortage of highly sensitive and specific minimally invasive biomarkers for assessment of environmental toxicants exposure. Because of the significance of microRNA (miRNA) in various diseases, circulating miRNAs in blood may be unique biomarkers for minimally invasive prediction of toxicants exposure. We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis. We identified 467 miRNAs for TOL, 211 miRNAs for XYL, and 695 miRNAs for XYL as characteristic discernible exposure indicator, which could discerned each VOC from the control group with higher accuracy, sensitivity, and specificity than urinary biomarkers. Current observations from this study point out that the altered levels of circulating miRNAs can be a reliable novel, minimally invasive biological indicator of occupational exposure to VOCs.

Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity.

We have shown that aldehydes impact the bronchial airway gene expression associated with inflammatory responses. In this study, we sought to determine whether microRNA (miRNA) plays a role in regulating the airway gene expression response to aldehyde exposure. We analyzed the whole genome miRNA and mRNA expression profiles of human alveolar epithelial cells exposed to 3 aldehydes (propanal, butanal, and pentanal) to identify aldehyde-sensitive miRNAs and to characterize the relationships between miRNAs and the expression of candidate cytokine-related genes, which are activated in response to inflammatory signals. Microarray analysis identified 15 miRNAs for propanal, 25 miRNAs for butanal, and 10 miRNAs for pentanal, which were differentially expressed in A549 human alveolar epithelial cells compared with vehicle control samples. Integrated analyses of miRNA and mRNA expression profiles identified significant miRNA-mRNA correlations. Gene ontology (GO) analysis of putative target genes (443 genes for propanal, 2166 genes for butanal, and 364 genes for pentanal) showed that the biological category "cytokine-cytokine receptor interaction" was prominently annotated. Moreover, we detected increased levels of interleukin (IL)-6 and IL-8 released in the 3 aldehyde exposure groups. Through an integrated analysis of the miRNA and mRNA expression profiles of aldehydes, we provide evidence that aldehyde can affect cytokine-induced toxicity signaling. Therefore, this study demonstrates the added value of an integrated miRNA-mRNA approach for identifying molecular events altered by environmental pollutants in an in vitro human model.

Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity.

In the current study, we aimed to investigate the transcriptomic responses and identify specific molecular signatures of low-molecular-weight saturated aliphatic aldehydes (LSAAs). To evaluate the change in gene expression levels, A549 human alveolar epithelial cells were exposed to six LSAAs (propanal, butanal, pentanal, hexanal, heptanal, and octanal) for 48 h. Clustering analysis of gene expression data show that the low carbon number group (LCG; propanal, butanal, and pentanal) was distinguished from the high carbon number group (HCG; hexanal, heptanal, and octanal). Also, transcriptomic profiling indicates that the LCG exposure group was more sensitive in gene alterations than the HCG group. Supervised analysis revealed 703 LCG specific genes and 55 HCG specific genes. After gene ontology (GO) analysis on LCG specific genes, we determined several key pathways which are known as being related to increase pulmonary toxicity such as cytokine-cytokine receptor interaction and chemokine signaling pathway. However, we did not find pulmonary toxicity-related pathways through GO analysis on HCG specific genes. Genes that are expressed in only the low carbon LSAA exposure group were regarded as biomarkers of aldehyde-induced pulmonary toxicity. In conclusion, this study describes changes in gene expression profiles in the in vitro respiratory system in response to exposure to 6 LSAAs with different carbon numbers and relates these gene alterations to pulmonary toxicity-related pathways. Moreover, novel carbon number-specific genes and pathways can be more widely implemented in combination with the traditional technique for assessment and prediction of exposure to environmental toxicants.

Modified composites based on mesostructured iron oxyhydroxide and synthetic minerals: a potential material for the treatment of various toxic heavy metals and its toxicity.

The composites of mesostructured iron oxyhydroxide and/or commercial synthetic zeolite were investigated for use in the removal of toxic heavy metals, such as cadmium, copper, lead and arsenic, from aqueous solution. Four types of adsorbents, dried alginate beads (DABs), synthetic-zeolite impregnated beads (SZIBs), meso-iron-oxyhydroxide impregnated beads (MIOIBs) and synthetic-zeolite/meso-iron-oxyhydroxide composite beads (SZMIOIBs), were prepared for heavy metal adsorption tests. Laboratory experiments were conducted to investigate the removal efficiencies of cations and anions of heavy metals and the possibility of regenerating the adsorbents. Among these adsorbents, the MIOIBs can simultaneously remove cations and anions of heavy metals; they have high adsorption capacities for lead (60.1mgg(-1)) and arsenic (71.9mgg(-1)) compared with other adsorbents, such as DABs (158.1 and 0.0mgg(-1)), SZIB (42.9 and 0.0mgg(-1)) and SZMIOIB (54.0 and 5.9mgg(-1)) for lead and arsenic, respectively. Additionally, the removal efficiency was consistent at approximately 90%, notwithstanding repetitive regeneration. The characteristics of meso-iron-oxyhydroxide powder were confirmed by X-ray diffraction, Brunauer-Emmett-Teller and transmission electron microscopy. We also performed a comparative toxicity study that indicated that much lower concentrations of the powdered form of mesostructured iron oxyhydroxide had stronger cytotoxicity than the granular form. These results suggest that the granular form of meso iron oxyhydroxide is a more useful and safer adsorbent for heavy metal treatment than the powdered form. This research provides promising results for the application of MIOIBs as an adsorbent for various heavy metals from wastewater and sewage.

Discovery of characteristic molecular signatures for the simultaneous prediction and detection of environmental pollutants.

Gene expression data may be very promising for the classification of toxicant types, but the development and application of transcriptomic-based gene classifiers for environmental toxicological applications are lacking compared to the biomedical sciences. Also, simultaneous classification across a set of toxicant types has not been investigated extensively. In the present study, we determined the transcriptomic response to three types of ubiquitous toxicants exposure in two types of human cell lines (HepG2 and HL-60), which are useful in vitro human model for evaluation of toxic substances that may affect human hepatotoxicity (e.g., polycyclic aromatic hydrocarbon [PAH] and persistent organic pollutant [POP]) and human leukemic myelopoietic proliferation (e.g., volatile organic compound [VOC]). The findings demonstrate characteristic molecular signatures that facilitated discrimination and prediction of the toxicant type. To evaluate changes in gene expression levels after exposure to environmental toxicants, we utilized 18 chemical substances; nine PAH toxicants, six VOC toxicants, and three POP toxicants. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxicant group, and combination analysis of two separate multi-classifications indicated 265 genes as surrogate markers for predicting each group of toxicants with 100 % accuracy. Our results suggest that these expression signatures can be used as predictable and discernible surrogate markers for detection and prediction of environmental toxicant exposure. Furthermore, this approach could easily be extended to screening for other types of environmental toxicants.

Analysis of microRNA and mRNA expression profiles highlights alterations in modulation of the MAPK pathway under octanal exposure.

Previous environmental microRNA (miRNA) studies have investigated a limited number of candidate miRNAs and have not evaluated functional effects on gene expression. In this study, we aimed to identify octanal (OC)-sensitive miRNAs and to characterize the relationships between miRNAs and expression of candidate genes involved in OC-induced toxicity. Microarray analysis identified 15 miRNAs that were differentially expressed in OC-exposed A549 human alveolar cells. Integrated analyses of miRNA and mRNA expression profiles identified significant miRNA-mRNA anti-correlations. GO analysis of 101 putative target genes showed that the biological category 'MAPK signaling pathway' was prominently annotated. Moreover, we detected increased phosphorylation of p38 MAPK in the OC-exposed group. By integrating the transcriptome and microRNAome, we provide evidence that OC can affect MAPK-induced toxicity signaling. Therefore, this study demonstrates the added value of an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model.