• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.863-870
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• 2012

Though hydrogen peroxide ($H_2O_2$) causes a deleterious effect to cells with its reactive oxygen species resulting in cell death, S-allyl cysteine (SAC, a bioactive organosulfur compound of aged garlic extract) has been known to have a cytoprotective effect. Few reported profiles of gene expression of $H_2O_2$ and SAC treated human cord blood derived mesenchymal stem cells (MSC). This study revealed changes in the profile of twenty-one genes grouped by oxidative stress, antioxidant, cell death, anti-apoptosis and anti-aging by quantitative real time PCR. A concentration of $100{\mu}M$ of SAC or $50{\mu}M$ of $H_2O_2$ was applied to MSC which show moderate growth and apoptosis pattern. $H_2O_2$ treatment enhanced expression of eleven genes out of twenty-one genes compared with that of control group, on the contrary SAC suppressed expression of eighteen genes out of twenty-one genes except C ros oncogene. SAC decreased expression of oxidative stress genes such as SOD1, CAT and GPX. These results seemed consistent with reports which elucidated over-expression of NF-${\kappa}$B by $H_2O_2$, and suppression of it by SAC. This study will confer basic information for further experiments regarding the effects of SAC on gene levels.

• Toxicological Research
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• v.35 no.3
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• pp.257-270
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• 2019

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

• Journal of Periodontal and Implant Science
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• v.47 no.2
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• pp.66-76
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• 2017

Purpose: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-${\beta}1$ (TGF-${\beta}1$). Methods: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-${\beta}1$. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification. Results: We found that 5-aza enhanced TGF-${\beta}1$-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-${\beta}$ type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-${\beta}$ signaling. 5-aza moderately increased the expression of TGF-${\beta}$ type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-${\beta}1$. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation. Conclusions: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-${\beta}$-induced IL11 expression in gingival fibroblasts.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.323-330
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• 2008

Surrogate tissue analysis incorporating -omics technologies has emerged as a potential alternative method for evaluating toxic effect of the tissues which are not accessible for sampling. Among the recent applications, blood including whole blood, peripheral blood lymphocytes and peripheral blood mononuclear cells (PBMCs) was suggested as a suitable surrogate tissue in determining toxicant exposure and effect at the pre- or early clinical stage. In this application, we investigated transcriptomic profiles in astemizole treated Cynomolgus monkey's PBMCs. PBMCs were isolated from 4-6 years old male monkeys at 24 hr after administration45 Helvetica Light (10 mg/kg, 30 mg/kg). Gene expression profiles of astemizole treated monkey's PBMCs were determined using Affymetrix $GeneChip^{(R)}$ Human Genome U133 plus 2.0 arrays. The expression levels of 724 probe sets were significantly altered in PBMCs at 10 or 30 mg/kg after astemizole administration following determination of paired t-test using statistical criteria of ${\geq}$$1.5-fold changes at P<0.05. Gene expression patterns in PBMCs showed a considerable difference between astemizole 10 and 30 mg/kg administration groups in spite of an administration of the same chemical. However, close examination using Ingenuity Pathway Analysis (IPA) software revealed that several gene sets related to cardiotoxicity were deregulated at astemizole 10 and 30 mg/kg administration groups. The deregulation of cardiac hypertrophy related genes such as TXN, GNAQ, and MAP3K5 was observed at 10 mg/kg group. In astemizole 30 mg/kg group, genes involved in cardiotoxicity including cardiac necrosis/cell death, dilation, fibrosis, and hypertrophy were also identified. These results suggest that toxicogenomic approach using PBMCs as surrogate tissues will contribute to assess toxicant exposures and identify biomarkers at the pre-clinical stage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.853-860
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• 2006

This study was performed to investigate genes which are differently expressed in human blood by administrating of OLT-2. OLT-2 was medical precipitation composed of three medicinal herbs, Ginseng Radix, Astragali Radix, Glycyrrhizae Radix, and anti-leukemia effect of it was evaluated from Byung Hun Jeon of Wonkwang University this study was approved by Institutional Review Board of Korea Institute of Oriental Medicine (Taejeon, Korea) and four male subjects participated in this study. Gene expressions were evaluated by cDNA chip, in which 24,000 genes were spotted. Hierarchical cluster and biological process against the genes, which expression changes were more than 1.6 fold, were constructed by cluster 3.0 providing Stanford University and EASE(http://apps1 .maid.nih.gov/DAVID). Five groups were clustered according to their expression patterns. Group A contained gene decreased by OLT-2 and increased genes by OLT-2 were involved in Group B, C, D. In biological process, expression of genes involved in cytokine or cell calcium signaling, such as interleukin 18 and G-protein beta 4 were increased, but protein tyrosine phosphatase receptor type c, which function is cell adhesion between antigen-presenting cell and T or B-cell, was decreased by OLT-2. This study provides the most comprehensive available survey of gene expression changes in response to anti-leukemia effect of OLT-2 in human blood.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3123-3129
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• 2013

Background: The search for naturally occurring agents in routinely consumed foods that may inhibit cancer development is of high priority. [6]-Paradol is a pungent phenolic bioactive component from ginger with welldocumented health promoting antioxidant, antimutagenic, antigenotoxic and anti-inflammatory properties. However, anticarcinogenic effects have yet to be fully explored. The objectives of the present study were therefore to assess protective effects against 7,12-dimethylbenz(a)anthracene (DMBA) induced buccal pouch carcinogenesis in male golden Syrian hamsters. Methods: Oral squamous cell carcinomas developed in the left buccal pouch of hamsters on painting with 0.5% of DMBA, three times in a week. To assess the apoptotic associated gene expressing potential of [6]-paradol, it was orally administered to DMBA treated hamsters on alternate days from DMBA painting for 14 weeks. Results: We observed 100% tumor formation with marked levels of neoplastic changes and altered the expression of apoptotic associated gene (p53, bcl-2, caspase-3 and TNF-${\alpha}$) was observed in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of [6]-paradol at a dose of 30 mg/kg b.wt to DMBA treated animals on alternative days for 14 weeks significantly reduced the neoplastic changes and improved the status of apoptosis associated gene expression. Conclusion: These observations confirmed that [6]-paradol acts as a tumor suppressing agent against DMBA induced oral carcinogenesis. We also conclude that [6]-paradol also effectively enhances apoptosis- associated gene expression in DMBA treated animals.

• Environmental Mutagens and Carcinogens
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• v.26 no.1
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• pp.1-6
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• 2006

To enhance our understanding of toxicity mediated through the pathway by which TCDD stimulates gene expression, we have investigated genes whose expressions are changed after treatment with TCDD and/or MNNG in human Chang liver cell. First, we treated with MNNG and TCDD for two weeks to transform human Chang liver cell. We obtained cell looks like to be transformed and compared the differential gene expression by using cDNA chip (Macrogen) which carrys genes related with signal transduction pathways, oncogenes and tumor suppressor genes, etc. We found that TCDD up- or down-regulated 203 and 111 genes including oncogenes and tumor suppressor genes in human Chang liver cell two fold or more, respectively. Second, we compared the differential gene expression after treatment with TCDD only by using cDNA chip (Superarray) which carrys genes related with cell cycle regulations, and found that TCDD up regulated genes related with cell proliferation as well as cell growth inhibition in human Chang liver cell two fold or more, respectively. These results suggest that toxicity induced by TCDD may reflect sustained alterations in the expression of many genes and that the changes reflect both direct and indirect effects of TCDD.

• Molecules and Cells
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• v.40 no.11
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• pp.855-863
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• 2017

Adipose tissue plays a central role in regulating dynamic cross-talk between tissues and organs. A detailed description of molecules that are differentially expressed upon changes in adipose tissue mass is expected to increase our understanding of the molecular mechanisms that underlie obesity and related metabolic co-morbidities. Our previous studies suggest a possible link between endophilins (SH3Grb2 proteins) and changes in body weight. To explore this further, we sought to assess the distribution of endophilin A2 (EA2) in human adipose tissue and experimental animals. Human paired adipose tissue samples (subcutaneous and visceral) were collected from subjects undergoing elective abdominal surgery and abdominal liposuction. We observed elevated EA2 gene expression in the subcutaneous compared to that in the visceral human adipose tissue. EA2 gene expression negatively correlated with adiponectin and chemerin in visceral adipose tissue, and positively correlated with $TNF-{\alpha}$ in subcutaneous adipose tissue. EA2 gene expression was significantly downregulated during differentiation of preadipocytes in vitro. In conclusion, this study provides a description of EA2 distribution and emphasizes a need to study the roles of this protein during the progression of obesity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8553-8557
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• 2016

Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1316-1321
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• 2012

Adipokines, adipocyte-derived protein, have important roles in various kinds of physiology including energy homeostasis. Chemerin, one of adipocyte-derived adipokines, is highly expressed in differentiated adipocytes and is known to induce macrophage chemotaxis and glucose intolerance. The objective of the present study was to investigate the changes of chemerin and the chemokine-like-receptor 1 (CMKLR1) gene expression levels during differentiation of the bovine adipocyte and in differentiated adipocytes treated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), adiponectin, leptin, and chemerin (peptide analog). The expression levels of the chemerin gene increased at d 6 and 12 of the differentiation period accompanied by increased cytoplasm lipid droplets. From d 6 onward, peroxisome proliferator-activated receptor-${\gamma}2$ (PPAR-${\gamma}2$) gene expression levels were significantly higher than that of d 0 and 3. In contrast, CMKLR1 expression levels decreased at the end of the differentiation period. In fully differentiated adipocytes (i.e. at d 12), the treatment of TNF-${\alpha}$ and adiponectin upregulated both chemerin and CMKLR1 gene expression levels, although leptin did not show such effects. Moreover, chemerin analog treatment was shown to upregulate chemerin gene expression levels regardless of doses. These results suggest that the expression of chemerin in bovine adipocyte might be regulated by chemerin itself and other adipokines, which indicates its possible role in modulating the adipokine secretions in adipose tissues.