• Molecules and Cells
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• 제38권4호
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• pp.304-311
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• 2015

Most follicles in the mammalian ovary undergo atresia. Granulosa cell apoptosis is a hallmark of follicle atresia. Our previous study using a microRNA (miRNA) microarray showed that the let-7 microRNA family was differentially expressed during follicular atresia. However, whether the let-7 miRNA family members are related to porcine (Sus scrofa) ovary follicular apoptosis is unclear. In the current study, real-time quantitative polymerase chain reaction showed that the expression levels of let-7 family members in follicles and granulosa cells were similar to our microarray data, in which miRNAs let-7a, let-7b, let-7c, and let-7i were significantly decreased in early atretic and progressively atretic porcine ovary follicles compared with healthy follicles, while let-7g was highly expressed during follicle atresia. Furthermore, flow cytometric analysis and Hoechst33342 staining demonstrated that let-7g increased the apoptotic rate of cultured granulosa cells. In addition, let-7 target genes were predicted and annotated by TargetScan, PicTar, gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our data provide new insight into the association between the let-7 miRNA family in granulosa cell programmed death.

• Genomics & Informatics
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• 제8권1호
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• pp.50-57
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• 2010

Mercuric chloride, a model nephrotoxicant was used to elucidate time- and dose- dependent global gene expression changes associated with proximal tubular toxicity. Rat kidney cell lines NRK-52E cells were exposed for 2, 6 and 12 hours and with 3 different doses of mercuric chloride. Cell viability assay showed that mercuric chloride had toxic effects on NRK-52E cells causing 20% cell death (IC20) at $40{\mu}M$ concentration. We set this IC20 as high dose concentration and 1/5 and 1/25 concentration of LC20 were used as mid and low concentration, respectively. Analyses of microarray data revealed that 738 genes were differentially expressed (more than two-fold change and p<0.05) by low concentration of mercuric chloride at least one time point in NRK-52E cells. 317 and 2,499 genes were differentially expressed at mid and high concentration of mercuric chloride, respectively. These deregulated genes showed a primary involvement with protein trafficking (CAV2, CANX, CORO1B), detoxification (GSTs) and immunity and defense (HMOX1, NQO1). Several of these genes were previously reported to be up-regulated in proximal tubule cells treated with nephrotoxicants and might be aid in promoting the predictive biomarkers for nephrotoxicity.

• BMB Reports
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• 제44권8호
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• pp.523-528
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• 2011

To identify novel genes that are regulated by promoter methylation, a combinational approach involving in silico mining followed by molecular assay was performed. From the expression microarray data registered in the European bioinformatics institute (EBI), genes showing downregulation in breast cancer cells were initially screened and then selected by e-Northern analysis using the Unigene database. A series of these in silico methods identified CAMK2B and ARFGEF1 as candidates, and the two genes were revealed to be hypermethylated in breast cancer cell lines and hypomethylated in normal breast cell lines. Additionally, cancer cell lines showed downregulated expression of these genes. Furthermore, treatment of the cancer cell lines with a demethylation agent, 5-Aza-2'-deoxycytidine, recovered expression of CAMK2B and ARFGEF1, implying that hypermethyaltion silenced gene activity in cancer cells. Taken together, promoter methylations of CAMK2B and ARFGEF1 are novel epigenetic markers identified in breast cancer cell lines and can be utilized for the application to clinical cancer tissues.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.836-843
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• 2004

Nontypeable H. influenzae (NTHi), a Gram-negative obligate human pathogen, causes pneumonia, chronic bronchitis, and otitis media, and the respiratory epithelium is the first line of defense that copes with the pathogen. In an effort to identify transcriptional responses of human respiratory epithelial cells to infection with NTHi, we examined its differential gene expression using high density cDNA microarrays. BEAS-2B human bronchial epithelial cells were exposed to NTHi for 3 hand 24 h, and the alteration of mRNA expression was analyzed using microarrays consisting of 8,170 human cDNA clones. The results indicated that approximately 2.6% of the genes present on the microarrays increased in expression over 2-fold and 3.8% of the genes decreased during the 24-h infection period. Upregulated genes included cytokines (granulocyte-macrophage colony stimulating factor 2, granulocyte chemotactic protein 2, IL-6, IL-10, IL-8), transcription factors (Kruppel-like factor 7, CCAAT/enhancer binding protein $\beta$, E2F-1, NF-$\kappa$B, cell surface molecules (CD74, ICAM-1, ICAM-2, HLA class I), as well as those involved in signal transduction and cellular transport. Selected genes were further confirmed by reverse-transcription-PCR. These data expand our knowledge of host cellular responses during NTHi infection and should provide a molecular basis for the study of host-NTHi interaction.

• 생명과학회지
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• 제17권5호
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• pp.678-686
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• 2007

인간중간엽줄기세포는(Human mesenchymal stem cells, hMSC) 골수, 지방, 피부, 근육, 혈액에 존재하며, 뼈, 연골, 지방, 근육, 신경세포로 분화가능성이 보고되어 손상조직의 재생을 위한 재료로서뿐만 아니라 유전자치료의 매개체로 이용될 수 있는 가능성이 제안되고 있다. 인간중간엽줄기세포의 적절한 배양조건에는 소 태아혈청(fetal bovine serum, FBS)이 요구되어지므로 세포치료에는 소 태아혈청이 다수 포함되어 있을 것이며 세포배양 배지 유래 소 태아혈청의 단백질에 의한 면역거부반응이 우려된다. 이미 앞선 연구에서 자가혈청 하에서 인체지방줄기세포 분리와 계속적인 세포배양을 실시하였을 때 인체지방줄기세포의 증식능력과 다 분화 능이 유지되며 면역결핍 생쥐에 골수의 말초혈액에서 유래된 CD34세포 이식 시 안착 능을 촉진함을 보였다. 본 연구에서 인체지방줄기세포가 인체혈청 하에서 배양되었을 때 소 태아혈청 하에서 배양할 때 발현하는 표면항원을 유지함을 확인했으며 microarray를 사용하여 유전자 발현을 비교했다. 유 세포 분석을 통하여 인체혈청 하에서 계속적으로 배양된 인체유래지방줄기세포에서 HLA-DR, CD117, CD29 와 CD44 의 발현이 소 태아혈청 하에서 배양했을 때와 비슷함을 밝혔다. 그러나 인체혈청 하에서 배양된 인체지방줄기세포의 유전자 발현형태와 소 태아혈청 하에서 배양된 세포의 유전자 발현형태 간에는 상당한 차이를 보였다. 그러므로 본 연구는 인체혈청 하에서 배양된 인체지방기질줄기세포가 임상적용을 위한 선행 데이터로써 직접적인 추정을 하기 위해서는 인체지방기질줄기세포 이식연구에 in vivo 동물실험연구가 수행되어져야 함을 제시하고 있다.

• Journal of Ginseng Research
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• 제45권1호
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• pp.183-190
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• 2021

Background: The circadian rhythm is the internal clock that controls sleep-wake cycles, metabolism, cognition, and several processes in the body, and its disruption has been associated with aging. The differentiated embryo chondrocyte (Dec) gene is related to circadian rhythm. To our knowledge, there are no reports of the relationship between dec gene expression and KRG effect. Therefore, we treated Dec gene knockout (KO) aging mice with KRG to study anti-aging related effects and possible mechanisms. Methods: We evaluated KRG and expression of Dec genes in an ototoxicity model. Dec genes expression in livers of aging mice was further analyzed. Then, we assessed the effects of DEC KO on hearing function in mice by ABR. Finally, we performed DNA microarray to identify KRG-related gene expression changes in mouse liver and assessed the results using KEGG analysis. Results: KRG decreased the expression of Dec genes in ototoxicity model, which may contribute to its anti-aging efficacy. Moreover, KRG suppressed Dec genes expression in liver of wild type indicating inhibition of senescence. ABR test indicated that KRG improved auditory function in aging mouse, demonstrating KRG efficacy on aging related diseases. Conclusion: Finally, in KEGG analysis of 238 genes that were activated and 158 that were inhibited by KRG in DEC KO mice, activated genes were involved in proliferation signaling, mineral absorption, and PPAR signaling whereas the inhibited genes were involved in arachidonic acid metabolism and peroxisomes. Our data indicate that inhibition of senescence-related Dec genes may explain the anti-aging efficacy of KRG.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2004년도 The 3rd Annual Conference for The Korean Society for Bioinformatics Association of Asian Societies for Bioinformatics 2004 Symposium
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• pp.117-123
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• 2004

마이크로어레이 (microarray) 기술이 개발된 후로 연관된 유전자 클러스터 (cluster)를 찾는 문제는 깊이 연구되어왔다. 이 문제는 핵심적인 과제 중 하나는 생물학적으로 타당한 클러스터의 수를 결정하는 데 있다. 본 논문은 최적의 클러스터 수를 결정하는 기준을 제시하고, non-negative factorization (NMF)를 이용해 클러스터 centroid의 패턴을 찾는 방법을 제안한다. NMF에 의해 발견된 각각의 패턴은 생물학적 프로세스의 특정 부분으로 해석될 수 있다. NMF는 factor matrix의 entity를 non-negative로 제약 (constraint)하고, 이 제약은 오직 additive combination만 허용하기 때문에 이러한 부분적인 패턴을 찾아낼 수 있다. NMF의 유용성은 이미지 분석과 텍스트 분석에서 이미 입증되어 있다. 본 논문에서 제안한 방법에 의해 위의패턴과 유사한 발현 패턴을 갖는 유전자를 모을 수 있었다. 제안된 방법은 human fibroblast데이터와 yeast cell cycle 데이터에 적용해 성능을 입증하였다.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2001년도 봄 학술발표논문집 Vol.28 No.1 (B)
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• pp.295-297
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• 2001

최근 생물 유전자 정보를 효과적으로 분석하기 위한 적절한 도구의 필요성이 대두되고 있다. 본 논문에서는 백혈병 환자의 골수로부터 얻어낸 DNA Microarray 유전 정보를 분류하여 환자가 가지고 있는 암의 종류를 예측하기 위한 최적의 특징추출방법과 분류 방법을 찾고자 한다. 이를 위해 피어슨 상관관계, 유클리디안 거리, 코사인 계수, 스피어맨 상관관계, 정보 이득, 상호 정보, 신호 대잡음비의 7가지 특징 추출 방법을 사용하였으며, 역전과 신경망, 의사결정 트리, 구조 적응형 자기구성 지도, $textsc{k}$-최근접 이웃 등 가지의 기계학습 분류기를 이용하여 분류 실험을 하였다. 실험결과, 피어슨 상관관계와 역전파 신경망을 이용한 분류 방법이 97.1%의 인식률을 보임을 알 수 있었다.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2004년도 가을 학술발표논문집 Vol.31 No.2 (1)
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• pp.235-237
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• 2004

Microarray 로 표현되는 유전자 발현 데이터는 일반적으로 샘플(sample) 수에 비해 많은 수의 유전자를 포함한다. 피처 추출은 이러한 데이터에 기계학습 방법론을 효과적으로 적용하기 위한 방법 중 하나로, 학습성능을 향상시키고 계산 시간을 줄일 수 있을 뿐만 아니라 중요한 피처들을 발견할 수 있다는 점에서 큰 의미를 갖는다. 본 연구에서는 베이지안 신경망(Bayesian Neural Network)에 기반 한 자동유효성탐지(Automatic Relevance Detection, ARD) 기법을 사용하여 유전자 발현 데이터에서 학습 오류를 줄이는 동시에 학습에 필요한 최소한의 유전자 집합을 추출할 수 있는 방법을 제시했다. CAMDA 2003에서 제시된 폐종양 환자의 유전자 발현 데이터에 대해 실험한 결과, 12600 개의 유전자 중에서 가장 중요하다고 여겨지는 187 개의 유전자를 발견했으며, 높은 학습성능을 달성했다.

• 동의생리병리학회지
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• 제18권2호
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• pp.468-473
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• 2004

Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels, and affects 1-3% of the world-wide population. Although many immunological and clinical reports indicate a role for the immune system in the pathogenesis of psoriasis, puzzling questions about psoriasis remain unsolved. During the several decade, immunosuppressor and PUVA treatment are ubiquitously used to psoriasis therapy. But recently, to promote terminal differentiation of keratinocytes, block either NK-Tcell or T-cell activation, and interrupting the angiogenic switch represent another therapeutic opportunity in psoriasis. To keep face with immunological therapy, the needs of newly designed prescription on the psoriasis treatments were demanded. With the object of understand the psoriasis from an orient medical point of view, patients were administrated the GY during several weeks. We investigated the changes of gene expression in involved and uninvolved skin samples during the oriental remedy. Microarray data showed several important results. First, Gene expression profiling is similar to each patient. Second, precursor proteins that organize cornified envelops are decreased at the end of remedy. But genes which related to apoptosis, G-protein signalling, and lipid metabolism are increased. Third, 68.5% of clustering genes localized on the psoriasis susceptibility locus. In our results indicated that GY influence on the keratinocytes hyperproliferation by regulating the gene, which located on the psoriasis susceptibility locus.