• 대한약침학회지
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• 제8권3호
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• pp.57-69
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• 2005

Objectives : Neurological disorders have been one of main therapeutic targets of acupuncture. The present study investigated the protective effects of Gwakhyangjeonggisan herbal acupuncture solution (GHAS). Methods : We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in glioblastoma cells, and did microarray analysis with cells exposed to reactive oxigen species (ROS) of hydrogen peroxide by 8.0 k Human cDNA, with cut-off level of 2-fold changes in gene expression. Results : MTT assay showed protective effect of GHAS on the glioblastoma cells exposed to hydrogen peroxide. When glioblastoma cells were exposed to hydrogen peroxide, 24 genes were downregulated. When the cells were pretreated with GHAS before exposure to hydrogen peroxide, 46 genes were downregulated. Many of the genes downregulated by hydrogen peroxide stimulation were decreased in the amount of downregulation or reversed to upregulation. Conclusions : The gene expression changes observed in the present study are supposed to be related to the protective molecular mechanism of GHAS in the glioblastoma cells exposed to ROS stress.

• Journal of Acupuncture Research
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• 제22권6호
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• pp.111-123
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• 2005

Objectives : Neurological disorders have been one of main therapeutic targets of acupuncture. The present study investigated the protective effects of Gwakhyangjeonggisan herbal acupuncture solution (GHAS). Methods : We performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in glioblastoma cells, and did microarray analysis with cells exposed to reactive oxigen species (ROS) of hydrogen peroxide by 8.0 k Human cDNA, with cut-off level of 2-fold changes in gene expression. Results : MTT assay showed protective effect of GHAS on the glioblastoma cells exposed to hydrogen peroxide. When glioblastoma cells were exposed to hydrogen peroxide, 16 genes were upregulated. When the cells were pretreated with GHAS before exposure to hydrogen peroxide, 22 genes were upregulated. Most of the genes upregulated by hydrogen peroxide stimulation were reversed to downregulation by GHAS. Conclusion : The gene expression changes observed in the present study are supposed to be related to the protective molecular mechanism of GHAS in the glioblastoma cells exposed to ROS stress.

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.1-6
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• 2009

Microglial cells constitute the first line of defense against infection and injury in the brain. This study was conducted to evaluate the protective mechanisms of Agrimonia pilosa (AP) on LPS-induced activation of BV-2 microglial cells. The effects of AP on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100 mm dish ($1{\times}10^7/mL$) for 24 hr and then pretreated with 1 g/mL AP or left untreated for 30 min. Next, 1 g/mL LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min, 3 hr and 6 hr. The gene expression profiles of the BV-2 microglial cells varied depending on the AP. The microarray analysis revealed that MAPK signaling pathway-related genes were down-regulated and IL10 gene was up-regulated in AP-treated BV-2 microglial cells. AP can affect the inflammatory response and MAPK pathway in BV-2 microglial cells.

• 환경생물
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• 제22권3호
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• pp.472-477
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• 2004

본 연구에서는 감마선으로 유도된 돌연변이체들에서 공통으로 발현되는 방사선 관련 유전자들의 발현을 연구하기 위하여, B. lentimorbus WJ5 의 방사선 유도 돌연변이체에서 발현되는 유전자를 DNA microarray로 동시에 탐색하였다. DNA microarray는 B. lentimorbus WJ5 genome을 무작위로 절단하여 2,000 단편으로 구성하였으며, 감마선 $(^{60}/Co)$으로 유도된 7 돌연변이체의 발현을 정량적으로 관찰하였다. 클러스터 분석결과 발현된 408 유전자 중 27개가 감마선 유도 돌연변이체 모두에서 유의하게 발현이 증가되었다. 특히, 복구(mutL, mutM) 에너지 대사 (acsA, sdhB, pgk, yhjB, citB), protease (npr), 산화자극에 대한 환원 (HMM)관련 유전자들이 동시에 증가되었다. 이는 감마선 유도 돌연변이체들에서 자발적인 직/간접 복구 관련 유전자의 발현 증가는 방사선 노출 직후 보이는 stress response와는 다른 현상임을 나타내는 것으로 생각된다.

• Preventive Nutrition and Food Science
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• 제8권4호
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• pp.390-394
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• 2003

In the post-genome period, the technique for identifying gene expression has been progressed to high throughput screening. In the field of molecular nutrition, the use of screening techniques to clarify molecular function of specific nutrients would be very advantageous. In this study, we have evaluated Zn-regulated gene expression in Zn-deficient, homocystein-treated EA.hy926 cells, using cDNA microarray, which can be used to screen the expression of many genes simultaneously. The information obtained can be used for preliminary assessment of molecular and signaling events modulated by Zn under pro-atherogenic conditions. EA.hy926 cells derived from human umbilical vein endothelial cells were cultured in Zn-adequate (control, 15 $\mu$M Zn) or Zn-deficient (experimental, 0 $\mu$M Zn) Dulbecco's MEM media under high homocysteine level (100 $\mu$M) for 3 days of post-confluency. Cells were harvested and RNA was extracted. Total RNA was reverse-transcribed and the synthesized cDNA was labeled with Cy3 or Cy5. Fluorescent labeled cDNA probe was applied to microarray slides for hybridization, and the slide was then scanned using a fluorescence scanner. The expression of seven genes was found to be significantly decreased, and one significantly increased, in response to treatment of EA.hy926 cells with Zn-deficient medium, compared with Zn-supplemented medium. The upregulated genes were oncogenes and tumor suppressor genes, cell cycle-related genes and transporter genes. The down-regulated gene was RelB, a component of the NF-kappaB complex of transcription factors. The results of this study imply the effectiveness of cDNA microarray for expression profiling of a singly nutrient deficiency, namely Zn. Furthur study, using tailored-cDNA array and vascular endothelial cell lines, would be beneficial to clarify the molecular function of Zn in atherosclerosis, more in detail.

• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.248-255
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• 2005

To understand the response of cancer cells to anticancer drugs at the gene expression level, we examined the gene expression changes in response to five anticancer drugs, 5-fluorouracil, cytarabine, cisplatin, paclitaxel, and cytochalasin D in NCI-H460 human lung cancer cells. Of the five drugs, 5-fluorouracil had the most distinctive gene expression signature. By clustering genes whose expression changed significantly, we identified three clusters with unique gene expression patterns. The first cluster reflected the up-regulation of gene expression by cisplatin, and included genes involved in cell death and DNA repair. The second cluster pointed to a general reduction of gene expression by most of the anticancer drugs tested. A number of genes in this cluster are involved in signal transduction that is important for communication between cells and reception of extracellular signals. The last cluster represented reduced gene expression in response to 5-fluorouracil, the genes involved being implicated in DNA metabolism, the cell cycle, and RNA processing. Since the gene expression signature of 5-fluorouracil was unique, we investigated it in more detail. Significance analysis of microarray data (SAM) identified 808 genes whose expression was significantly altered by 5-fluorouracil. Among the up-regulated genes, those affecting apoptosis were the most noteworthy. The down-regulated genes were mainly associated with transcription-and translation-related processes which are known targets of 5-fluorouracil. These results suggest that the gene expression signature of an anticancer drug is closely related to its physiological action and the response of caner cells.

• Communications for Statistical Applications and Methods
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• 제16권3호
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• pp.397-408
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• 2009

마이크로어레이 기술은 수만 개 유전자의 발현 패턴을 동시에 관찰하는 것을 가능하게 하였고, 이들을 하나씩 검정하여 찾아낸 특이발현 현상을 보이는 유전자를 중심으로 질병의 진단, 치료법 정립과 신약 개발을 위한 기본 정보를 확립하였다. 그러나 개별 유전자분석의 여러 문제점이 발견되면서 유전자들을 생물학적 대사경로나 염색체 위치가 같은 것끼리 묶은 집단을 분석하여 질병의 발생이나 생존에 영향을 미치는 집단을 찾는 방법이 제시되었다. 이러한 유전자 집단의 유의성에 대한 연구는 2002년에 MIT에서 비롯되어 GSEA, SAM-GS와 중심극한 정리의 개념을 이용한 모수적 방법인 PAGE 등이 사용되고 있다. 본 논문에서는 이들 통계량의 구조적 한계를 극복하고 계산이 간단한 새로운 모수적 방법을 제안하고 자료 분석을 통하여 효율성을 보였다.

• 한국정보과학회논문지:시스템및이론
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• 제30권10호
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• pp.544-555
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• 2003

DNA 마이크로어레이 실험으로 나오는 데이타는 아주 많은 양의 유전자 발현 정보를 담고 있기 때문에 적절한 분석 방법이 필요하다. 대표적인 분석 방법은 계층적 클러스터링(hierarchical clustering) 방법이다. 본 논문에서는 계층적 클러스터링의 결과로 나오게 되는 덴드로그램(dendrogram)에 대해서 후처리(post-Processing)를 시행함으로써 DNA 마이크로어레이 데이타 분석을 더 용이하게 해주는 리프오더링(leaf-ordering)에 대해서 연구하였다. 먼저, 기존의 리프오더링 알고리즘들을 분석하였고, 리프오더링 알고리즘의 새로운 접근 방식을 제안하였다. 또한 이에 대한 성능을 실험하고 분석하기 위해서 계층적 클러스터링과 몇 가지 리프오더링 알고리즘들, 그리고 제안된 접근 방식을 직접 구현한 HCLO (Hierarchical Clustering & Leaf-Ordering Tool)에 대해서 소개하였다.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2005년도 제5회 발생공학 국제심포지엄 및 학술대회
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• pp.108-108
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• 2005

• Journal of Acupuncture Research
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• 제23권4호
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• pp.135-148
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• 2006

Objectives : Juglandis Semen herbal acupuncture solution(JSS) has a broad array of clinical applications in oriental medicine, including treatment of chronic musculoskeletal diseases such as arthritis. This study was performed to investigate the global gene expression profiles using microarray assay in RAW 264.7 cell line treated with JSS and to advance our understanding of the pharmacologic effect of Jss. Methods : Change of the gene expression profile in RAW cell line following treatment with JSS alone, with lipopolysaccharide(LPS) alone, or with LPS plus JSS was investigated with a cut-off level of 2 fold change in the expression. Results : Of the 8170 genes profiled in this study, 95 were upragulated and 42 downregulated following JSS treatment, 51 were upragulated and 21 downregulated following LPS treatment, and 88 were upregulated and 69 downregulated following costimulation of JSS and LPS. Conclusion : JSS treatment induced upregulation of some genes including IL-10 with its possible implication in an antiinflammatory action of JSS. However, further research on expression profile changes induced by JSS treatment is expected.