Published literature

Public Health (12) Products

  Mouse&Rat miRNA OneArray  
 Environmental Toxicology. 2015, 30(6):712-23. doi: 10.1002/tox.21949.
 Prenatal and neonatal exposure to perfluorooctane sulfonic acid results in aberrant changes in miRNA expression profile and levels in developing rat livers 
 Fan Wang, Yihe Jin, Faqi Wang, Junsheng Ma, Wei Liu
  Abstract
Perfluorooctane sulfonate (PFOS) is an animal carcinogen. However, the underlying mechanism in cancer initiation is still largely unknown. Recently identified microRNAs (miRNAs) may play an important role in toxicant exposure and in the process of toxicant-induced tumorigenesis. We used PFOS to investigate PFOS-induced changes in miRNA expression in developing rat liver and the potential mechanism of PFOS-induced toxic action. Dams received 3.2 mg/kg PFOS in their feed from gestational day 1 (GD1) to postnatal day 7 (PND 7). Pups then had free access to treated feed until PND 7. We isolated RNAs from liver tissues on PND 1 and 7 and analyzed the expression profiles of 387 known rat miRNAs using microarray technology. PFOS exposure induced significant changes in miRNA expression profiles. Forty-six miRNAs had significant expression alterations on PND 1, nine miRNAs on PND 7. Specifically, expression of four miRNAs was up-regulated on PND 7 but down-regulated on PND1 (p < 0.05). Many aberrantly expressed miRNAs were related to various cancers. We found oncogenic and tumor-suppressing miRNAs, which included miR-19b, miR-21*, miR-17-3p, miR-125a-3p, miR-16, miR-26a, miR-1, miR-200c, and miR-451. In addition, four miRNAs were simultaneous significantly expressed on both PND 1 and 7. Functional Annotation analysis of the predicted transcript targets revealed that PFOS exposure potentially alters pathways associated with different cancers (cancer, melanoma, pancreatic cancer, colorectal cancer, and glioma), biological processes which include positive regulation of apoptosis and cell proliferation. Results showed PFOS exposure altered the expression of a suite of miRNAs.
   

  Mouse OneArray  
 Archives of Toxicology. 2014 Oct 2.
 Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice
 
 
 Jin‑Feng Zhao, Sheng‑Huang Hsiao, Ming‑Hua Hsu, Kuan‑Chuan Pao, Yu Ru Kou, Song‑Kun Shyue, Tzong‑Shyuan Lee
  Abstract
Di-(2-ethylhexyl) phthalate (DEHP) is associated with atherosclerosis-related cardiovascular disease complications, but we lack direct evidence of its unfavorable effect on atherogenesis. In this study, we aimed to clarify in vivo and in vitro the contribution of DEHP to the development ofatherosclerosis and its underlying mechanisms. Apolipoprotein E-deficient (apoE-/-) mice chronically treated with DEHP for 4 weeks showed exacerbated hyperlipidemia, systemic inflammation, and atherosclerosis. In addition, DEHP promoted low-density lipoprotein (LDL) oxidation, which led to inflammation in endothelial cells as evidenced by increased protein expression of pro-inflammatory mediators. Furthermore, chronic DEHP treatment increased hepatic cholesterol accumulation by downregulating the protein expression of key regulators in cholesterol clearance including LDL receptor, cholesterol 7帢-hydrolase, ATP-binding cassette transporter G5 and G8, and liver X receptor 帢. Moreover, the adiposity and inflammation of white adipose tissues were promoted in DEHP-treated apoE-/- mice. In conclusion, DEHP may disturb cholesterol homeostasis and deregulate the inflammatory response, thus leading to accelerated atherosclerosis.
   

  Human OneArray  
 BioMed Research International. 2014 Sep 8.
 Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure
 
 
 Kuei-Fang Lee, Julia Tzu-Ya Weng, Paul Wei-Che Hsu, Yu-Hsiang Chi, Ching-Kai Chen, Ingrid Y. Liu, Yi-Cheng Chen, Lawrence Shih-Hsin Wu
  Abstract
Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.
   

  Human miRNA OneArray  
 BioMed Research International. 2014 Sep 16.
 MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure
 
 
 Kuei-Fang Lee, Yi-Cheng Chen, Paul Wei-Che Hsu, Ingrid Y. Liu, Lawrence Shih-Hsin Wu
  Abstract
Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE) is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs) have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.
   

  Mouse&Rat miRNA OneArray  
 Molecular BioSystems. 2014 Jan 14. doi: 10.1039/C3MB70564A .
 An increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers
 
 
 Lihua Xie, Minghua Wu, Hua Lin, Chun Liu, Honghui Yang, Juan Zhan, Shenghua Sun
  Abstract
Heavy smoking is associated with the development of chronic obstructive pulmonary disease (COPD). However, there is no valuable biomarker for evaluating COPD development in heavy smokers because they are usually asymptomatic. This study is aimed at evaluating whether the levels of serum miRNAs can serve as biomarkers for predicting the occurrence of COPD. A rat model of emphysema was induced by enforced smoking, and the dynamic miRNAs expression profile at different stages of emphysema with varying periods of smoking were analyzed by microarray and quantitative real-time polymerase chain reaction (qRT-PCR). The differentially expressing miRNAs were analyzed using Gene Ontology and the KEGG PATHWAY database. The levels of three serum candidate miRNAs were measured by qRT-PCR in 41 healthy controls (HC), 40 asymptomatic heavy smokers, and 49 COPD patients. Following smoking for varying periods, different severities of lung emphysema were observed in different groups of rats, accompanied by altered levels of some serum miRNAs associated with regulating some pathways. Furthermore, the levels of miR-21 were significantly higher in the COPD patients and asymptomatic heavy smokers than in the HC (P < 0.001), while the levels of miR-181a were significantly lower in the COPD patients and asymptomatic heavy smokers than in the HC (P < 0.001). Accordingly, the levels of serum miR-21 and miR-181a as well as their ratios had a high sensitivity (0.854) and specificity (0.850) for evaluating the development of COPD. Our data suggest that the levels of serum miR-21 and miR-181a may be valuable for evaluating the development of COPD in heavy smokers.
   

  Mouse&Rat miRNA OneArray  
 Environmental Toxicology. 2012 Jul 30. DOI: 10.1002/tox.21795.
 Modulation of microRNA expression by volatile organic compounds in mouse lung
 
 
 Fan Wang, Chonglei Li, Wei Liu, Yihe Jin
  Abstract
Volatile organic compounds (VOCs) are one of main pollutants indoors. Exposure to VOCs is associated with cancer, asthma disease, and multiple chemical allergies. Despite the adverse health effects of VOCs, the molecular mechanisms underlying VOCs-induced disease remain largely unknown. MicroRNAs (miRNAs), as key post-transcriptional regulators of gene expression, may influence cellular disease state. To investigate whether lung miRNA expression profiles in mice are modified by VOCs mixture exposure, 44 male Kunming mice were exposed in 4 similar static chambers, 0 (control) and 3 different doses of VOCs mixture (groups 13). The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 3.0 + 3.3 + 6.0 + 6.0 mg/m3, 5.0 + 5.5 + 10.0 + 10.0 mg/m3, 10.0 + 11.0 + 20.0 + 20.0 mg/m3, respectively, which corresponded to 30, 50, and 100 times of indoor air quality standard in China, after exposure to 2 weeks (2 h/day, 5 days/week). Small RNAs in lung and protein isolated from bronchoalveolar lavage fluid (BALF) were collected and analyzed for miRNA expression using microarray analysis and for interleukin-8 (IL-8) protein levels by enzyme-linked immunosorbent assay, respectively. VOCs exposure altered the miRNA expression profiles in lung in mice. Specifically, 69 miRNAs were significantly differentially expressed in VOCs-exposed samples versus controls. Functional annotation analysis of the predicted miRNA transcript targets revealed that VOCs exposure potentially alters signaling pathways associated with cancer, chemokine signaling, Wnt signaling, neuroactive ligand-receptor interaction, and cell adhesion molecules. IL-8 isolated from BALF and nitric oxide synthase of lung increased significantly, whereas GSH of lung decreased significantly in mice exposed to VOCs. These results indicate that inhalation of VOCs alters miRNA patterns that regulate gene expression, potentially leading to the initiation of cancer and inflammatory diseases.
   

  Human OneArray  
 Chemical Research in Toxicology. 2011, 24(10):1636-43. doi: 10.1021/tx200181q.
 Whole Genome Expression in Peripheral-Blood Samples of Workers Professionally Exposed to Polycyclic Aromatic Hydrocarbons.
 
 
 Wu MT, Lee TC, Wu IC, Su HJ, Huang JL, Peng CY, Wang W, Chou TY, Lin MY, Lin WY, Huang CT, Pan CH, Ho CK.
  Abstract
This study aims to examine global gene expression profiles before and after the work-shift among coke-oven workers (COWs). COWs work six consecutive days and then take two days off. Two blood and urine samples in each worker were collected before starting to work after two days off and end-of-shift in the sixth day of work in 2009. Altered gene expressions (ratio of gene expression levels between end-of-shift and preshift work) were performed by a Human OneArray expression system which probes ~30,000-transcription expression profiling of human genes. Sixteen workers, all men, were enrolled in this study. Median urinary 1-hydroxypyrene (1OHP) levels (弮mol/mol creatinine) in end-of-shift work were significantly higher than those in preshift work (2.58 vs 0.29, p = 0.0002). Among the 20,341 genes which passed experimental quality control, 26 gene expression changes, 7 positive and 19 negative, were highly correlated with across-the-shift urinary 1OHP levels (end-of-shift-preshift 1OHP) (p-value <0.001). The high and low exposure groups of across-the-shift urinary 1OHP levels dichotomized in ~2.00 弮mol/mol creatinine were able to be distinguished by these 26 genes. Some of them are known to be involved in apoptosis, chromosome stability/DNA repair, cell cycle control/tumor suppressor, cell adhesion, development/spermatogenesis, immune function, and neuronal cell function. These findings in COWs will be an ideal model to study the relationship of PAH exposure with acute changes of gene expressions.
   

  Human OneArray  
 Molecular Carcinogenesis. 2012, 51(3):280-9. doi: 10.1002/mc.20844.
 Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens
 
 
 Kusum Rathore, Hwa-Chain Robert Wang.
  Abstract
Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically achievable concentration of 2.5 弮g/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.
   

  Human OneArray  
 Libertas Academica. 2011, 6:7-16.
 Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide
 
 
 Udensi K. Udensi, Hari H.P. Cohly, Barbara E. Graham-Evans, Kenneth Ndebele, Nat?lia Garcia-Reyero, Bindu Nanduri, Paul B. Tchounwou, Raphael D. Isokpehi.
  Abstract
Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes.
   

  Human OneArray  
 Ind Health. 2011, 49(1):8-14.
 Changes in Oxidative Stress Biomarker and Gene Expression Levels in Workers Exposed to Volatile Organic Compounds.
 
 
 Kim JH, Moon JY, Park EY, Lee KH, Hong YC.
  Abstract
Exposure to volatile organic compounds (VOCs) was known to result in immunologic, respiratory, carcinogenic, reproductive, neurologic, and cardiovascular effects. However, the mechanisms by which VOCs induce these adverse health effects are not well understood. To evaluate the change of oxidative stress biomarker and gene expression levels in workers exposed to VOCs, we obtained urine and blood samples from 21 subjects before and after occupational exposure to VOCs. We measured levels of muconic acid (MuA), hippuric acid (HA), mandelic acid (MaA), and methyl hippuric acid (MHA) as urinary exposure biomarkers for benzene, toluene, ethylbenzene, and xylene (collectively BTEX), and malondialdehyde (MDA) and 8-hydroxydeoxyguanine (8-OHdG) as oxidative stress biomarkers in all subjects. We also evaluated BTEX-mediated RNA expression using cDNA microarray in 14 subjects. HA and MHA levels were higher following occupational exposure to VOCs (p < 0.01). In the linear regression analysis, HA ratios of after- and before-exposure were found to be significantly associated with increase of MDA ratios of after- and before-exposure after controlling for age, body mass index, and smoking (帣 = 0.06, p = 0.031). Evaluation of the gene expressions by HA showed that 23 gene expressions were found to be significantly associated with HA levels after adjusting for age, body mass index, and smoking (p < 0.001). In particular, expressions of ENO3 and CDNA FLJ39461 fis among the 23 genes were significantly associated with the change in MDA level (p < 0.05). Our study results suggest that exposure to VOCs, specifically toluene, induces oxidative stress and various gene expression change of which some may be responsible for oxidative stress.
   

  Mouse OneArray  
 Nanotechnology. 2010, 21(17):175101. doi: 10.1088/0957-4484/21/17/175101.
 Long-term hepatotoxicity of polyethylene-glycol functionalized multi-walled carbon nanotubes in mice.
 
 
 Zhang D, Deng X, Ji Z, Shen X, Gu T, Liu Y, Dong L, Wu M
  Abstract
The toxicity of polyethylene-glycol functionalized (PEGylated) multi-walled carbon nanotubes (MWCNTs) and non-PEGylated MWCNTs in vivo was evaluated and compared. Mice were exposed to MWCNTs by intravenous injection. The activity level of glutathione, superoxide dismutase and gene expression in liver, as well as some biochemical parameters and the tumor necrosis factor alpha level in blood were measured over 2 months. The pathological and electron micrographic observations of liver evidently indicate that the damage caused by non-PEGylated MWCNTs is slightly more severe than that of PEGylated MWCNTs, which means that PEGylation can partly, but not substantially, improve the in vivo biocompatibility of MWCNTs.
   

  Mouse OneArray  
 Environmental and Molecular Mutagenesis. 2008, 49(9):741-5. doi: 10.1002/em.20429.
 Gene Expression Changes Associated with Xenobiotic Metabolism Pathways in Mice Exposed to Acrylamide.
 
 
 Guo L, Tseng J, Dial SL, Liao W, Manjanatha MG, Mei N
  Abstract
The discovery of acrylamide (AA) in a variety of fried foods has raised public health concerns. In this study, groups of male mice were administered 500 mg/L AA in drinking water for 3 weeks, and gene expression changes were evaluated in the livers of AA-treated mice within 24 hr of the last treatment. When a two-fold cutoff value and a P-value less than 0.05 were selected, 696 genes (233 up-regulated and 463 down-regulated) were identified as differentially expressed genes in AA-treated mice when compared with the controls. Gene ontology analysis revealed that the principle pathways affected by AA were xenobiotic metabolism by cytochrome P450 (CYPs) and glutathione metabolism, suggesting that drug and/or xenobiotic metabolism is most affected by exposure. The results provide more information about AA metabolism and further insight into the molecular mechanisms involved in AA-induced toxicity.