• Toxicological Research
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• 제32권4호
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• pp.289-300
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• 2016

Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals. The model was based on short term exposure assays (3 days) and the training was limited to oxidative stressors, peroxisome proliferators and hormone modulators. Validation of the predictor was performed on independent toxicogenomic data (TG-GATEs, Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System, Osaka, Japan). To build our model we performed Random Forests together with a recursive elimination algorithm (VarSelRF). Gene set enrichment analysis was employed for functional interpretation. A total of 770 microarrays comprising 96 different compounds were analyzed and a predictor of 54 genes was built. Prediction accuracy was 0.85 in the training set, 0.87 in the test set and increased with increasing concentration in the validation set: 0.6 at low dose, 0.7 at medium doses and 0.81 at high doses. Pathway analysis revealed gene prominence of cellular respiration, energy production and lipoprotein metabolism. The biggest target of toxicogenomics is accurately predict the toxicity of unknown drugs. In this analysis, we presented a classifier that can predict non-genotoxic carcinogenicity by using short term exposure assays. In this approach, dose level is critical when evaluating chemicals at early time points.

• Molecular & Cellular Toxicology
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• 제2권4호
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• pp.273-278
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• 2006

95 squamous cell lung carcinoma samples (normal tissue: 40 samples, tumor: 55 samples) were analyzed with 8 K cDNA microarray. 1-way ANOVA test was employed to select differentially expressed genes in tumor with FDR<0.01. Among the selected 1,655 genes, final 212 genes were chosen according to the expression fold change and used for following analysis. The expression of up-regulated 64 genes was verified with Reverse Transcription PCR and 10 genes were identified as candidates for SCC markers. In our opinion, those candidates can be exploited as diagnostic or therapeutic purposes. Gene Ontology (GO) based analysis was performed using those 212 genes, and following categories were revealed as significant biological processes: Immune response (GO: 0006955), antigen processing (GO: 0030333), inflammatory response (GO: 0006954), Cell adhesion (GO: 0007155), and Epidermis differentiation (GO: 0008544). Gene set enrichment analysis (GSEA) also carried out on overall gene expression profile with 522 functional gene sets. Glycolysis, cell cycle, K-ras and amino acid biosynthesis related gene sets were most distinguished. These results are consistent with the known characteristics of SCC and may be interconnected to rapid cell proliferation. However, the unexpected results from ERK activation in squamous cell carcinoma gripped our attention, and further studies are under progress.

• 디지털콘텐츠학회 논문지
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• 제19권9호
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• pp.1795-1801
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• 2018

질환의 원인을 규명하기 위해 전장유전체 연관분석 (GWAS; Genome-Wide Association Study) 연구가 활발히 진행되고 유전체 레벨의 단일염기다형성 (SNP; Single-nucleotide polymorphism)이 많이 밝혀지고 있다. 그러나 단일염기다형성의 연관분석을 통해 질환이 발병하는 생물학적 메카니즘을 이해하기 어렵기 때문에 유전자, 생물학적 패스웨이 및 질환 등의 연관성 분석이 이전보다 더욱 중요하다. 본 논문에서는 단일염기다형성과 관련된 유전자와 패스웨이, 질환 정보를 검색하여 통합 분석하는 서비스를 제공하는 PRaDA 웹 시스템을 제안하였다. PRaDA는 사용자로부터 입력받은 유의한 몇몇의 단일염기다형성들과 관련된 유전자 및 패스웨이 뿐만 아니라, 유의하지 않은 다수의 단일염기다형성 집합의 간접적인 영향을 파악하기 위해 기능적으로 근접한 패스웨이를 검색하고 통계적 분석을 실행한다. 사용자들은 PRaDA가 제공하는 통합된 정보를 통해 질병의 전반적인 이해를 할 수 있다.

• Genomics & Informatics
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• 제8권1호
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• pp.28-33
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• 2010

Increased exposure of human to RF fields has raised concerns for its potential adverse effects on our health. To address the biological effects of RF radiation, we used genome wide gene expression as the indicator. We exposed normal WI-38 human fibroblast cells to 1763 MHz mobile phone RF radiation at a specific absorption rate (SAR) of 60 W/kg with an operating cooling system for 24 h. There were no alterations in cell numbers or morphology after RF exposure. Through microarray analysis, we identified no differentially expressed genes (DEGs) at the 0.05 significance level after controlling for multiple testing errors with the Benjaminiochberg false discovery rate (BH FDR) method. Meanwhile, 82 genes were differentially expressed between RF-exposed cells and controls when the significance level was set at 0.01 without correction for multiple comparisons. We found that 24 genes (0.08% of the total genes examined) were changed by more than 1.5-fold on RF exposure. However, significant enrichment of any gene set or pathway was not observed from the functional annotation analysis. From these results, we did not find any evidence that non-thermal RF radiation at a 60-W/kg SAR significantly affects cell proliferation or gene expression in WI-38 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4553-4557
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• 2013

Objective: The purpose of this study was to identify genes related to bladder cancer with samples from normal and disease cases by microarray chip. Methods: After downloading the gene expression profile GSE3167 from Gene Expression Omnibus database which includes 50 bladder samples, comprising 9 normal and 41 disease samples, differentially expressed genes were identified with packages in R language. The selected differentially expressed genes were further analyzed using bioinformatics methods. Firstly, molecular functions, biological processes and cell component analysis were researched by software Gestalt. Then, software String was used to search interaction relationships among differentially expressed genes, and hub genes of the network were selected. Finally, by using plugins of software Cytoscape, Mcode and Bingo, module analysis of hub-genes was performed. Results: A total of 221 genes were identified as differentially expressed by comparing normal and disease bladder samples, and a network as well as the hub gene C1QBP was obtained from the network. The C1QBP module had the closest relationship to production of molecular mediators involved in inflammatory responses. Conclusion: We obtained differentially expressed genes of bladder cancer by microarray, and both PRDX2 and YWHAZ in the module with hub gene C1QBP were most significantly related to production of molecular mediators involved in inflammatory responses. From knowledge of inflammatory responses and cancer, our results showed that, the hub gene and its module could induce inflammation in bladder cancer. These related genes are candidate bio-markers for bladder cancer diagnosis and might be helpful in designing novel therapies.

• Molecules and Cells
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• 제40권10호
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• pp.737-751
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• 2017

Histone-modifying enzymes are key players in the field of cellular differentiation. Here, we used GSK-J4 to profile important target genes that are responsible for neural differentiation. Embryoid bodies were treated with retinoic acid ($10{\mu}M$) to induce neural differentiation in the presence or absence of GSK-J4. To profile GSKJ4-target genes, we performed RNA sequencing for both normal and demethylase-inhibited cells. A total of 47 and 58 genes were up- and down-regulated, respectively, after GSK-J4 exposure at a log2-fold-change cut-off value of 1.2 (p-value < 0.05). Functional annotations of all of the differentially expressed genes revealed that a significant number of genes were associated with the suppression of cellular proliferation, cell cycle progression and induction of cell death. We also identified an enrichment of potent motifs in selected genes that were differentially expressed. Additionally, we listed upstream transcriptional regulators of all of the differentially expressed genes. Our data indicate that GSK-J4 affects cellular biology by inhibiting cellular proliferation through cell cycle suppression and induction of cell death. These findings will expand the current understanding of the biology of histone-modifying enzymes, thereby promoting further investigations to elucidate the underlying mechanisms.

• 한국식품과학회지
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• 제35권6호
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• pp.1188-1192
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• 2003

새우나 게 껍질로부터 chitin을 유일한 탄소원으로 하는 집적배양에 의하여 chitinase 활성이 우수한 균주를 2종 분리하였다. 분리균주는 형태학적, 그람염색, 16s rDNA 서열분석을 통하여 Arthrobacter nicotianae로 동정되어, 각각 Arthrobacter nicotianae CH4와 Arthrobacter nicotianae CH13으로 명명하였다. 두 종의 분리균주로부터의 chitinase는 모두 pH $3.0{\sim}9.0$에서 90% 이상의 효소활성을 유지하여 높은 pH안정성을 나타내었다. 온도의 영향은 $20{\sim}60^{\circ}C$ 구간에서 최적 효소 활성의 $70{\sim}90%$를 유지하여 열안정성도 뛰어났다. A. nicotianae CH4와 A. nicotianae CH13이 분비하는 chitinase 조효소를 0.1% colloidal chitin 기질에 반응시켜서 반응산물로 생산되는 chitin 올리고당을 HPLC를 사용하여 분석하였다. A. nicotianae CH4 조효소에 의한 효소반응산물로는 올리고머인 $(GlcNAc)_4$이, A. nicotianae CH13는 단량체인 $(GlcNAc)_1$이 전체 반응산물의 각각 98% 이상 생성되었다.

• 한국미생물·생명공학회지
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• 제43권4호
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• pp.401-404
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• 2015

Bacillus coagulans는 프로바이오틱스 및 내열성 생물소재의 생산에 활용 가능성이 높은 미생물로 주목받고 있지만, 우리나라에서는 관심의 대상이 되지 못하고 있으며 상용화된 바 없다. 따라서 기능연구를 통한 산업화 대상 균주가 국내에는 충분히 확보되지 못한 상태에 있다. 본 연구자들은 미래 활용을 위한 B. coagulans의 확보를 위하여 볏짚으로부터 B. coagulans의 빠른 분리법을 개발하였다. $50^{\circ}C$에서의 집적배양, 산 생성 확인을 통한 Bacillus 속 균주의 제거, 선택배지를 이용한 enterococci 균주의 제거는 B. coagulans 선발을 위한 빠르고 정확한 방법이 될 수 있는 것으로 확인되었다.

• Journal of Ginseng Research
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• 제43권4호
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• pp.572-579
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• 2019

Background: Panax ginseng has been used in traditional medicine to strengthen the body and mental well-being of humans for thousands of years. Many elite ginseng cultivars have been developed, and ginseng cultivation has become well established during the last century. However, heat stress poses an important threat to the growth and sustainable production of ginseng. Efforts have been made to study the effects of high temperature on ginseng physiology, but knowledge of the molecular responses to heat stress is still limited. Methods: We sequenced the transcriptomes (RNA-Seq) of two ginseng cultivars, Chunpoong (CP) and Yunpoong (YP), which are sensitive and resistant to heat stress, respectively, after 1- and 3-week heat treatments. Differential gene expression and gene ontology enrichment along with profiled chlorophyll contents were performed. Results: CP is more sensitive to heat stress than YP and exhibited a lower chlorophyll content than YP. Moreover, heat stress reduced the chlorophyll content more rapidly in CP than in YP. A total of 329 heat-responsive genes were identified. Intriguingly, genes encoding chlorophyll a/b-binding proteins, WRKY transcription factors, and fatty acid desaturase were predominantly responsive during heat stress and appeared to regulate photosynthesis. In addition, a genome-wide scan of photosynthetic and sugar metabolic genes revealed reduced transcription levels for ribulose 1,5-bisphosphate carboxylase/oxygenase under heat stress, especially in CP, possibly attributable to elevated levels of soluble sugars. Conclusion: Our comprehensive genomic analysis reveals candidate loci/gene targets for breeding and functional studies related to developing high temperature-tolerant ginseng varieties.

• Journal of Korean Neurosurgical Society
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• 제65권2호
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• pp.236-244
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• 2022

Objective : To evaluate the interactions among differentially expressed autophagy and mitophagy markers in subarachnoid hemorrhage (SAH) patients with delayed cerebral ischemia (DCI). Methods : The expression data of autophagy and mitophagy-related makers in the cerebrospinal fluid (CSF) cells was analyzed by real-time reverse transcription-polymerase chain reaction and Western blotting. The markers included death-associated protein kinase (DAPK)-1, BCL2 interacting protein 3 like (BNIP3L), Bcl-1 antagonist X, phosphatase and tensin homolog-induced kinase (PINK), Unc-51 like autophagy activating kinase 1, nuclear dot protein 52, and p62. In silico functional analyses including gene ontology enrichment and the protein-protein interaction network were performed. Results : A total of 56 SAH patients were included and 22 (38.6%) of them experienced DCI. The DCI patients had significantly increased mRNA levels of DAPK1, BNIP3L, and PINK1, and increased expression of BECN1 compared to the non-DCI patients. The most enriched biological process was the positive regulation of autophagy, followed by the response to mitochondrial depolarization. The molecular functions ubiquitin-like protein ligase binding and ubiquitin-protein ligase binding were enriched. In the cluster of cellular components, Lewy bodies and the phagophore assembly site were enriched. BECN1 was the most connected gene among the differentially expressed markers related to autophagy and mitophagy in the development of DCI. Conclusion : Our study may provide novel insight into mitochondrial dysfunction in DCI pathogenesis.