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.

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.

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.

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.

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.

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.

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.

Polycyclic aromatic hydrocarbon (PAH)-mediated upregulation of hepatic microRNA-181 family promotes cancer cell migration by targeting MAPK phosphatase-5, regulating the activation of p38 MAPK.

Growing evidence indicates that changes in microRNA (miRNA) expression in cancer induced by chemical carcinogens play an important role in cancer development and progression by regulating related genes. However, the mechanisms underlying miRNA involvement in hepatocarcinogenesis induced by polycyclic aromatic hydrocarbons (PAHs) remain unclear. Thus, the identification of aberrant miRNA expression during PAH-induced cancer cell migration will lead to a better understanding of the substantial role of miRNAs in cancer progression. In the present study, miRNA expression profiling showed significant upregulation of miR-181a, -181b, and -181d in human hepatocellular carcinoma cells (HepG2 line) exposed to benzo[a]anthracene (BA) and benzo[k]fluoranthene (BF). MAPK phosphatase-5 (MKP-5), a validated miR-181 target that deactivates MAPKs, was markedly suppressed while phosphorylation of p38 MAPK was increased after BA and BF exposure. The migration of HepG2 cells, observed using the scratch wound-healing assay, also increased in a dose-dependent manner. Depletion of miR-181 family members by miRNA inhibitors enhanced the expression of MKP-5 and suppressed the phosphorylation of p38 MAPK. Furthermore, the depletion of the miR-181 family inhibited cancer cell migration. Based on these results, we conclude that the miR-181 family plays a critical role in PAH-induced hepatocarcinogenesis by targeting MKP-5, resulting in the regulation of p38 MAPK activation.

Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells.

Iodothyronine deiodinase types I, II, and III (D1, D2, and D3, respectively), which constitute a family of selenoenzymes, activate and inactivate thyroid hormones through the removal of specific iodine moieties from thyroxine and its derivatives. These enzymes are important in the biological effects mediated by thyroid hormones. The expression of activating and inactivating deiodinases plays a critical role in a number of cell systems, including the neuronal system, during development as well as in adult vertebrates. To investigate deiodinase-disrupting chemicals based on transcriptomic responses, we examined differences in gene expression profiles between T3-treated and deiodinase-knockdown SH-SY5Y cells using microarray analysis and quantitative real-time RT-PCR. A total of 1,558 genes, consisting of 755 upregulated and 803 downregulated genes, were differentially expressed between the T3-treated and deiodinase-knockdown cells. The expression levels of 10 of these genes (ID2, ID3, CCL2, TBX3, TGOLN2, C1orf71, ZNF676, GULP1, KLF9, and ITGB5) were altered by deiodinase-disrupting chemicals (2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyls, propylthiouracil, iodoacetic acid, methylmercury, ß-estradiol, methimazole, 3-methylcholanthrene, aminotriazole, amiodarone, cadmium chloride, dimethoate, fenvalerate, octylmethoxycinnamate, iopanoic acid, methoxychlor, and 4-methylbenzylidene-camphor). These genes are potential biomarkers for detecting deiodinase deficiency and predicting their effects on thyroid hormone production.

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.

Changes in thyroid peroxidase activity in response to various chemicals.

Thyroperoxidase (TPO) is a large heme-containing glycoprotein that catalyzes the transfer of iodine to thyroglobulin during thyroid hormone (TH) synthesis. Previously, we established an in vitro assay for TPO activity based on human recombinant TPO (hrTPO) stably transfected into human follicular thyroid carcinoma (FTC-238) cells. It is important to determine whether environmental chemicals can disrupt TPO activity because it is an important factor in the TH axis. In this study, we used our assay to examine the changes in TPO activity in response to various chemicals, including benzophenones (BPs), polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs). Overall, BPs, PAHs, and POPs slightly altered TPO activity at low doses, as compared with the positive controls methimazole (MMI), genistein, and 2,2',4,4'-tetrahydroxy BP. Benzophenone, benzhydrol, 3-methylchloranthracene, pyrene, benzo(k)fluoranthene, benzo(e)pyrene, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and heptachlor decreased TPO activity, while 2,4-dihydroxy BP, 2,2'-dihydroxy-4-methoxy BP, and dibenzo(a,h)anthracene increased TPO activity. From these data, we can predict the disruption of TPO activity by various chemicals as a sensitive TH end point. TPO activity should be considered when enacting measures to regulate environmental exposure to thyroid-disrupting chemicals.

Polycyclic aromatic hydrocarbons induce migration in human hepatocellular carcinoma cells (HepG2) through reactive oxygen species-mediated p38 MAPK signal transduction.

Although polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and have been extensively studied with regard to tumor formation, few studies have investigated the involvement of these environmental chemicals in tumor migration and invasion. Polycyclic aromatic hydrocarbons induce reactive oxygen species (ROS) and activate MAPK signal transduction. The p38 signaling transduction pathway, one of the most typical MAPK pathways, plays an essential role in regulating cell migration. Therefore, we investigated whether three PAHs, benzo[a]anthracene (B[a]A), benzo[k]fluoranthene (B[k]F), and indeno[1,2,3-c,d]pyrene (IND), induce migration in human hepatocellular carcinoma cell line HepG2 through ROS-mediated p38 MAPK signal transduction. Reactive oxygen species generation and p38 MAPK activity both increased in a dose-dependent manner and were prevented by SB203580, an inhibitor of p38 MAPK, and N-acetylcysteine (NAC), a ROS scavenger. Expression of migration-related genes was also increased by B[a]A, B[k]F, and IND in a dose-dependent manner and was inhibited by SB203580 and NAC. The migration of HepG2 cells, observed using the Transwell migration assay, also increased in a dose-dependent manner and was prevented by SB203580 and NAC. Our results indicate that the ROS-mediated p38 MAPK signaling pathway plays an essential role in the PAH-induced migration of HepG2 cells.

Identification of characteristic molecular signature for volatile organic compounds in peripheral blood of rat.

In a previous report we demonstrated that the transcriptomic response of liver tissue was specific to toxicants, and a characteristic molecular signature could be used as an early prognostic biomarker in rats. It is necessary to determine the transcriptomic response to toxicants in peripheral blood for application to the human system. Volatile organic compounds (VOCs) comprise a major group of pollutants which significantly affect the chemistry of the atmosphere and human health. In this study we identified and validated the specific molecular signatures of toxicants in rat whole blood as early predictors of environmental toxicants. VOCs (dichloromethane, ethylbenzene, and trichloroethylene) were administered to 11-week-old SD male rats after 48h of exposure, peripheral whole blood was subjected to expression profiling analysis. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxicant, and supervised analysis identified 1,217 outlier genes as distinct molecular signatures discerning VOC exposure from healthy controls. Further analysis of multi-classification suggested 337 genes as early detective molecular markers for three VOCs with 100% accuracy. A large-scale gene expression analysis of a different VOC exposure animal model suggested that characteristic expression profiles exist in blood cells and multi-classification of this VOC-specific molecular signature can discriminate each toxicant at an early exposure time. This blood expression signature can thus be used as discernable surrogate marker for detection of biological responses to VOC exposure in an environment.

Identification of classifiers for increase or decrease of thyroid peroxidase activity in the FTC-238/hTPO recombinant cell line.

Thyroid peroxidase (TPO) plays an important role in thyroid hormone biosynthesis, as it catalyzes all of the essential steps in iodide organification. TPO activity can be detected using the guaiacol assay; however, this assay is complex and very time-consuming. Therefore, we focused on devising a simplified method using microarrays to detect changes in TPO activity, which is a target for disruption of the thyroid hormone axis. These experiments have systematically assessed the potential utility of transcriptomic end points as enhancements to the guaiacol assay. Previously, we demonstrated that benzophenone-2, benzophenone, perfluorooctane sulfonate, bisphenol A bis ether, and vinclozolin decreased TPO activity, and that dibutyl phthalate, carbaryl, dibenzo(a,h)anthracene, benzo(a)pyrene, and methylmercury increased TPO activity. In this work, we used human oligonucleotide chips to examine changes in the gene expression profile of FTC-238 human follicular thyroid carcinoma cells expressing human recombinant TPO, after exposure of the cells to TPO activity-disrupting agents. We identified 362 classifiers that could predict the effect of the toxicants on TPO activity with about 70% accuracy. These classifiers are potential markers for predicting the effects of chemicals on thyroid hormone production.

Molecular signature for early detection and prediction of polycyclic aromatic hydrocarbons in peripheral blood.

Whole blood is one of the most easily accessible biofluids, and circulating leukocytes would include informative transcripts as a first line of immune defense for many disease processes. To demonstrate that transcriptomic responses of circulating blood cells reflect the exposure to environmental toxicants and the characteristic molecular signatures can discriminate and predict the type of toxicant at an early exposure time, we identified and validated characteristic gene expression profiles of rat whole blood after exposure to polycyclic aromatic hydrocarbons (PAHs). At an early exposure time point, conventional toxicological analysis including changes in the body and organ weight, histopathological examination, and blood biochemical analysis did not reflect any toxicant stresses. However, unsupervised gene expression analysis of blood cells resulted in a characteristic molecular signature for each toxicant. Further analysis of multiclassification suggested 220 genes as early detective and surrogate markers for predicting each PAH with 100% accuracy. These findings suggest that the blood expression signature could be used as a predictable and discernible surrogate marker for detection and prediction of PAHs, and the use of these molecular markers may be more widely implemented in combination with more traditional techniques for assessment and prediction of toxicity exposure to PAHs from an environmental aspect.

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.

Transcriptomic configuration of mouse brain induced by adolescent exposure to 3,4-methylenedioxymethamphetamine.

The amphetamine derivative (+/-)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliative emotional response. MDMA is a potent monoaminergic neurotoxin with the potential to damage brain serotonin and/or dopamine neurons. As the majority of MDMA users are young adults, the risk that users may expose the fetus to MDMA is a concern. However, the majority of studies on MDMA have investigated the effects on adult animals. Here, we investigated whether long-term exposure to MDMA, especially in adolescence, could induce comprehensive transcriptional changes in mouse brain. Transcriptomic analysis of mouse brain regions demonstrated significant gene expression changes in the cerebral cortex. Supervised analysis identified 1028 genes that were chronically dysregulated by long-term exposure to MDMA in adolescent mice. Functional categories most represented by this MDMA characteristic signature are intracellular molecular signaling pathways of neurotoxicity, such as, the MAPK signaling pathway, the Wnt signaling pathway, neuroactive ligand-receptor interaction, long-term potentiation, and the long-term depression signaling pathway. Although these resultant large-scale molecular changes remain to be studied associated with functional brain damage caused by MDMA, our observations delineate the possible neurotoxic effects of MDMA on brain function, and have therapeutic implications concerning neuro-pathological conditions associated with MDMA abuse.

Effect of electric field on electrical conductivity of dielectric liquids mixed with polar additives: DC conductivity.

To understand the dynamics of dielectric-liquid-based colloidal systems, the effect of electric field on conductivity of dielectric liquids must be characterized. We measured dc conductivity of dielectric liquids mixed with polar additives, including surfactants, an alcohol, and an oil-soluble salt. The conductivities of the mixtures increased with the electric field and concentration of polar additives and were also affected by temperature. Conductivity increased with electric-field strength at very similar rates, almost irrespective of the kind of mixture. A simple formula derived from Onsager theory predicted the electrical conductivity under electric field fairly well.

Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway.

Methotrexate (MTX) has been widely used for the treatment of inflammatory diseases and rheumatoid arthritis (RA), as well as a variety of tumors. However, MTX-induced toxicity is a serious and unpredictable side effect of this therapy and an important clinical problem. We used microarray analysis to examine MTX-induced gene expression in a human lung epithelial cell line (BEAS-2B) and identified 10 differentially expressed genes related to the p38 mitogen-activated protein kinase (MAPK) pathway, including IL-1beta, MKK6, and MAPKAPK2. Differential gene expression was confirmed via real-time RT-PCR. To determine the functional significance of MTX-induced p38 MAPK activation, we used a p38 MAPK inhibitor (SB203580) to block the p38 MAPK cascade. We also used protein array technology to investigate the modulated expression of pro- and anti-inflammatory cytokines in BEAS-2B cells. MTX activated IL-1beta expression and induced the phosphorylation of various proteins in the p38 MAPK cascade, including TAK1, MKK3/MKK6, p38 MAPK, MAPKAPK2, and HSP27. Finally, HSP27 activation may increase IL-8 secretion, resulting in a pulmonary inflammatory response such as pneumonitis. Although IL-1beta and IL-8 expression increased, the expression of IL-4, IL-6, IL-12, TNF-alpha, MIP-1alpha, and MIP-1beta decreased in a dose-dependent manner. These results suggest that the modulation of cytokine expression may play an important role in MTX-induced pulmonary toxicity.