• YAKHAK HOEJI
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• v.43 no.1
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• pp.104-110
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• 1999

We investigated effects of methanol extract of Aloe vera on anticancer drugs(cisplatin, mitomycin C, 5-fluorouracil)-induced growth inhibition in p388, L1210, HCT-15, SK-HepG-1 as cancer cell lines and mouse splenocytes as a normal cell by MTT assay, respectively. We also examined the effects of aloe extract and mitomycin C on the mitogen(Con, A, LPS)-induced splenocyte proliferation. Aloe extract(0.25 mg/m , 1.25 mg/m , 2.5 mg/m , 5.0 mg/m ) showed dose-dependently selective cytotoxicity against the cancer cell lines. In contrast, Aloe extract increased the growth and proliferation of the normal mouse splenocytes. The combination of aloe extract with anticancer drugs showed an additive effect for the cytotoxicity against cancer cell lines. However, that combination reduced clealy the anticancer drugs-induced toxicity against the normal mouse splenocytes.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.477-487
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• 2022

Probiotics provide a symbiotic relationship and beneficial effects by balancing the human intestinal microbiota. The relationships between microbiota changes and various diseases may predict health abnormalities and diseases. Treatment with vitamins and probiotics is one therapeutic approach. To evaluate the effect of probiotics on vitamin absorption, we chose Lactobacillus rhamnosus CBT-LR5 treatment, which has resistance to vitamin C-inducible toxicity, with vitamins in high-fat diet (HFD)-induced obesity models. CBT-LR5 affected the absorption of micronutrients, such as ionic minerals and water-soluble vitamins. An increase in vitamin C absorption by CBT-LR5 enhanced the antioxidant response in HFD-induced obesity models. Increased vitamin B absorption by CBT-LR5 regulated lipid metabolism in HFD-induced obesity models. These favorable effects of CBT-LR5 on the absorption of vitamins should be investigated as candidate therapeutic target treatments for metabolic diseases.

• Bulletin of the Korean Chemical Society
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• v.32 no.6
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• pp.2051-2057
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• 2011

Several studies have demonstrated that nanoparticles (NPs) have toxic effects on cultured cell lines, yet there are no clear data describing the overall molecular changes induced by NPs currently in use for human applications. In this study, the in vitro cytotoxicity of three oxide NPs of around 100 nm size, namely, mesoporous silica (MCM-41), iron oxide ($Fe_2O_3$-NPs), and zinc oxide (ZnO-NPs), was evaluated in the human embryonic kidney cell line HEK293. Cell viability assays demonstrated that 100 ${\mu}g/mL$ MCM-41, 100 ${\mu}g/mL$ $Fe_2O_3$, and 12.5 ${\mu}g/mL$ ZnO exhibited 20% reductions in HEK293 cell viability in 24 hrs. DNA microarray analysis was performed on cells treated with these oxide NPs and further validated by real time PCR to understand cytotoxic changes occurring at the molecular level. Microarray analysis of NP-treated cells identified a number of up- and down-regulated genes that were found to be associated with inflammation, stress, and the cell death and defense response. At both the cellular and molecular levels, the toxicity was observed in the following order: ZnO-NPs > $Fe_2O_3$-NPs > MCM-41. In conclusion, our study provides important information regarding the toxicity of these three commonly used oxide NPs, which should be useful in future biomedical applications of these nanoparticles.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.256-261
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• 2005

The recent DNA microarray technology enables us to understand gene expression profiling in cell line and animal models. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, microarray system has been used for the prediction of toxicity through gene expression induced by toxicants. It has been shown that compounds with similar toxic mechanisms produce similar changes in gene expression in vivo system. Here we focus on the use of toxicogenomics for the determination of gene expression analysis associated with hepatotoxicity in rat liver and cell line (WB-F344). Methotrexate (MTX) is a chemotherapy agent that has been used for many years in the treatment of cancer because it affects cells that are rapidly dividing. Also it has been known the toxicity of MTX, in a MTX abortion, it stops embryonic cells from dividing and multiplying and is a non-surgical method of ending pregnancy in its early stages. We have shown DNA microarray analyses to assess MTX-specific expression profiles in vivo and in vitro. Male Sprague-Dawely VAF+ albino rats of 5-6 weeks old and WB-F344 cell line have been treated with MTX. Total RNA was isolated from Rat liver and cell line that has treated with MTX. 4.8 K cDNA microarray in house has been used for gene expression profiling of MTX treatment. We have found quite distinct gene expression patterns induced by MTX in a cell line and in vivo system.

• BMB Reports
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• v.37 no.4
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• pp.454-459
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• 2004

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% $O_2$, 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.86-92
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• 2019

Di-ethylhexyl phthalate (DEHP) is an environmental contaminant that is used as a plasticizer. Endometriosis is a complex disease with an unknown etiology that is believed to be associated with exposure to DEHP. The present study examined the potential toxicity of DEHP by exposing endometrial adenocarcinoma cells (Ishikawa cells) to DEHP. In the experiments, the cells were treated with stepwise DEHP concentrations (0, 0.01, 0.1, 1, and $5{\mu}M$) for different exposure times (24, 48, and 72 h). When the relationship between the resulting survival rate of the cells and initial inflammation was examined, the cell viability, expression of $TNF-{\alpha}$, an inflammatory mediator, and the expression of MMP-9, an ECM degradation protein, were increased remarkably when the cells were exposed to $5{\mu}M$ DEHP for 48 and 72 hours. These results suggest that the exposure of Ishikawa cells to certain concentrations of DEHP, estrogen mimics, may cause time-dependent toxicity that affects the cell viability and inflammation, implying a potential role in the etiology of endometriosis. Further research on the effects of endocrine disruptors on the pathogenesis of endometriosis may reveal strategies to prevent this disease.

• Journal of Environmental Health Sciences
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• v.49 no.2
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• pp.89-98
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• 2023

Background: Organophosphorus flame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials. Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce. Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures. Methods: Nine organophosphorus flame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea. Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours. Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2. In addition, the observed EC_x values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction. Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays. However, EC₅₀ values were derived for seven out of nine OPFRs in the HepG2 assays. In the HepG2 assays, the highest to lowest EC₅₀ were in the order of the molecular weight of the target chemicals. In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions: Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP. Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.

• Journal of Life Science
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• v.26 no.6
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• pp.633-639
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• 2016

Biomaterials including polymer, metal, ceramic, and composite have been widely applied for medical uses as medical fibers, artificial blood vessels, artificial joints, implants, soft tissue, and plastic surgery materials owing to their physicochemical properties. However, the biocompatibility and toxicity for film- and plate-form biomaterials is difficult to measure in mammalian cells because there is no appropriate incubation system. To solve these problems, we developed a novel mammalian cell culture system consisting of a silicone ring, top panel, and bottom panel and we applied two polymer films (PF) and one metal plate (MP). This system was based on the principal of sandwiching a test sample between the top panel and the bottom panel. Following the assembly of the culture system, SK-MEL-2 cells were seeded onto Styela Clava Tunic (SCT)-PF, NaHCO₃-added SCT (SCTN)-PF, and magnesium MP (MMP) and incubated at 37℃ for 24 hr and 48 hr. An MTT assay revealed that cell viability was maintained at a normal level in the SCT-PF culture group at 24 or 48 hr, although it rapidly decreased in the SCTN-PF culture group at 48 hr. Furthermore, the cell viability in the MMP culture group was very similar to that of the control group after incubation for 24 hr and 48 hr. Together, these results suggest the sandwich-type mammalian culture system developed here has the potential for the evaluation of the biocompatibility and toxicity of cells against PF- and MP-form biomaterials.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2003.10a
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• pp.66-72
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• 2003

Toxicogenomics is now emerging as one of the most important genomics application because the toxicity test based on gene expression profiles is expected more precise and efficient than current histopathological approach in pre-clinical phase. One of the challenging points in Toxicogenomics is the construction of intelligent database management system which can deal with very heterogeneous and complex data from many different experimental and information sources. Here we present a new Toxicogenomics database developed as a part of 'Toxicogenomics for Efficient Safety Test (TEST) project'. The TEST database is especially focused on the connectivity of heterogeneous data and intelligent query system which enables users to get inspiration from the complex data sets. The database deals with four kinds of information; compound information, histopathological information, gene expression information, and annotation information. Currently, TEST database has Toxicogenomics information fer 12 molecules with 4 efficacy classes; anti cancer, antibiotic, hypotension, and gastric ulcer. Users can easily access all kinds of detailed information about there compounds and simultaneously, users can also check the confidence of retrieved information by browsing the quality of experimental data and toxicity grade of gene generated from our toxicology annotation system. Intelligent query system is designed for multiple comparisons of experimental data because the comparison of experimental data according to histopathological toxicity, compounds, efficacy, and individual variation is crucial to find common genetic characteristics .Our presented system can be a good information source for the study of toxicology mechanism in the genome-wide level and also can be utilized fur the design of toxicity test chip.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3419-3424
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• 2014

Background: Our aim was to conduct a meta-analysis to compare the efficacy and safety of pemetrexed and docetaxel for non-small cell lung cancer (NSCLC). Materials and Methods: We systematically searched the Cochrane Library, PubMed, Embase, China Biology Medicine Database for randomized controlled trials (RCTs) comparing the efficacy and toxicities of pemetrexed versus docetaxel as a treatment for advanced NSCLC. We limited the languages to English and Chinese. Two reviewers independently screened articles to identify eligible trials according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. The meta-analysis was performed using STATA12.0. Results: Six RCTs involving 1,414 patients were identified. We found that there was no statistically significant differences in overall response rate, survival time, progression-free survival, disease control rate, and 1-2yr survival rate (p>0.050) but it is worthy of mention that patients in the pemetrexed arms had significantly higher 3-yr survival rate (P=0.002). With regard to the grade 3 or 4 hematological toxicity, compared with docetaxel, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, and leukocyts toxicity (p<0.001). There was no significant difference in anemia between the two arms (p=0.08). In addition, pemetrexed led to higher rate of grade 3-4 thrombocytopenia toxicity (p=0.03). As for the non-hematological toxicities, compared with docetaxel, pemetrexed group had lower rate of grade 3-4 diarrhea and alopecia. Conclusions: Pemetrexed was almost as effective as docetaxel in patients with advanced NSCLC. At the same time, pemetrexed might increase the 3-yr survival rate. As for safety, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, leukocytes, diarrhea and alopecia toxicity. However, it was associated with a higher rate of grade 3-4 thrombocytopenia.