• 대한본초학회지
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• 제31권2호
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• pp.13-19
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• 2016

Objectives : The present study was designed to evaluate the protective effect of Allium tuberosum (AT) extract on atherosclerosis in LDL receptor knockout (LDLr KO) mouse fed western diet.Methods : The AT was extracted 70% ethanol. The experimental groups were divided with four groups of LDLr KO mice, one group fed a normal diet and the others fed a Western diets for 8weeks. Two Western diet groups were orally administered AT extract at dosage of 100 and 300 mg/kg body weight. The body weight and food intake were measured every day. We measured levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and Glucose in serum. Also, effect of AT extract performed using H&E staining.Results : The AT treatment groups showed decrease in body weight and food efficiency in comparison with control group. Blood biochemistry parameters such as TG, TC, LDL, and glucose levels were increased in control group, while AT treatment groups were reduced. Also, the increased levels of ALT and AST were improved by AT extract. We confirmed that the weights of liver, kidney, subcutaneous fat, epididymal fat, kidney leaf fat, and intraabdominal fat were change in LDLr KO mice treated AT extract. In addition, histopathological changes in liver and aorta were similar to normal group.Conclusions : Based on these results, the AT extract is considered to make prevention of atherosclerosis through reduction and functional improvement of the liver and vascular endothelial cells in the body fat accumulation and lipid content in LDLr ko mouse model.

• 한국독성학회:학술대회논문집
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• 한국독성학회 1998년도 국제심포지움 및 추계학술대회
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• pp.8-13
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• 1998

Polyoma Virus Enhancer core Binding Protein (PEBP2)는 유전자의 전사를 조절하는 hetero-dimeric transcription factor로서 $\alpha$와 $\beta$ subunit으로 구성되어 있다. $\alpha$ subunit을 coding 하는 유전자중 하나인 PEBP2aB는 급성백혈병과 관련되어있는 t(8;21) 또는 t(12;21)에 의하여 변형됨으로서 백혈병 발병의 원인이 되고 있다 (Miyoshi et al., 1993; .Romana et al., 1995). $\beta$ subunit을 coding 하는 PEBP2$\beta$도 inv(16)에 의하여 변형됨으로서 백혈병을 유도하는 주요 원인이 되고 있다 (Liu et al., 1993). 이 유전자들의 생물학적 활성을 밝히기 위한 연구가 gene targeting에 의한 knockout mouse 생산 방법으로 수행되었다. 그 결과 PEBP2$\alpha$B와 PEBP2$\beta$ 유전자가 definitive hematopoiesis에 있어서 결정적으로 중요한 역할을 하고 있음이 관찰되었다 (Okuda et al., 1996, Wang et al., 1996a, 1996b), 이는 이들 유전자가 bematopoietic master switch 유전자임을 밝힌 중요한 결과로서 이로부터 혈액학 연구 분야의 새로운 장이 열리게 되었다. 또한 이러한 연구 결과들은 PEBP2 family에 속하는 다른 유전자의 생물학적 활성의 연구를 촉진하는 계기가 되었다. 최근 PEBP2$\alpha$A 유전자가 결손된 마우스가 생산되었는데 이 유전자의 경우에는 모든 종류의 뼈의 생성이 완전히 결손됨이 관찰되었다 (Komori et al., 1997). 이는 PEBP2$\alpha$A 유전자가 뼈의 생성을 지배하는 master switch 유전자임을 보여주는 중요한 관찰로서 bone biologist 들의 큰 관심을 모으고 있다. 본 연구팀은 PEBP2 family 유전자 중 유일하게 아직 생물학적 활성이 규명되지 않은 PEBP2$\alpha$C 유전자의 활성을 knockout 마우스를 생산하는 방법에 의하여 분석하였으며 소화기관의 형성에 중요한 역할을 하고 있음을 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.233-240
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• 2020

Autophagy regulators are often effective as potential cancer therapeutic agents. Here, we investigated paclitaxel sensitivity in cells with knockout (KO) of ATG5 gene. The ATG5 KO in multidrug resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr) was generated using the CRISPR/Cas9 technology. The qPCR and LC3 immunoblot confirmed knockout of the gene and protein of ATG5, respectively. The ATG5 KO restored the sensitivity of Ras-NIH 3T3/Mdr cells to paclitaxel. Interestingly, ATG5 overexpression restored autophagy function in ATG5 KO cells, but failed to rescue paclitaxel resistance. These results raise the possibility that low level of resistance to paclitaxel in ATG5 KO cells may be related to other roles of ATG5 independent of its function in autophagy. The ATG5 KO significantly induced a G₂/M arrest in cell cycle progression. Additionally, ATG5 KO caused necrosis of a high proportion of cells after paclitaxel treatment. These data suggest that the difference in sensitivity to paclitaxel between ATG5 KO and their parental MDR cells may result from the disparity in the proportions of necrotic cells in both populations. Thus, our results demonstrate that the ATG5 KO in paclitaxel resistant cells leads to a marked G₂/M arrest and sensitizes cells to paclitaxel-induced necrosis.

• 대한본초학회지
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• 제31권1호
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• pp.17-23
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• 2016

Objectives : This study was designed to protect effect on atherosclerosis through regulation of low density lipoprotein(LDL) by 70 % ethanol extract Ganoderma lucidum (GL) in LDL receptor knockout mouse (LDLr ko mice) fed Western diet.Methods : The LDLr ko mice were divided into 3 groups ; Control, GL100, and GL300. After grouping, LDLr ko mice were fed Western diet. The GL (100 or 300 mg/kg body weight/day, p.o.) was administered every day for 8 weeks. The body weight and food intake were measured every day. The changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) in serum were analyzed after experiment.Results : The LDLr ko mice fed Western diet were increased body weight gain and blood biochemistry parameters such as ALT, AST, TG, TC, and LDL. However GL300 group significantly reduced the body weight. Also TG, TC, and LDL level did not increase. The levels of ALT, AST, HDL were not changed. Also, LDLr ko mice model liver were observed lipid drop, but GL groups did not appear. Futhermore, histological analysis of GL groups aorta tissue were similar to NOR groups.Conclusions : We confirmed that whether GL administration is protect atherosclerosis or not. As the results, blood biochemistry and histological analysis did not changed much in GL administration groups. This study provides scientific evidence that GL protect the atherosclerosis through the reduction of LDL cholesterol. Therefore GL has potential medicine inhibition of atherosclerosis.

• Journal of Korean Dental Science
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• 제9권1호
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• pp.9-18
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• 2016

Purpose: Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. Deletion of the Wntless (Wls) gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation. However, it remains unclear if autonomous Wnt ligands are necessary for differentiation of dental pulp cells into odontoblast-like cells to induce reparative dentinogenesis, one of well-known feature of pulp repair to form tertiary dentin. Materials and Methods: To analyze the autonomous role of Wls for differentiation of dental pulp cells into odontoblast-like cells, we used primary dental pulp cells from unerupted molars of Wls-floxed allele mouse after infection with adenovirus for Cre recombinase expression to knockout the floxed Wls gene or control GFP expression. The differentiation of dental pulp cells into odontoblast-like cells was analyzed by quantitative real-time polymerase chain reaction. Result: Proliferation rate was significantly decreased in dental pulp cells with Cre expression for Wls knockout. The expression levels of Osterix (Osx), runt-related transcription factor 2 (Runx2), and nuclear factor I-C (Nfic) were all significantly decreased by 0.3-fold, 0.2-fold, and 0.3-fold respectively in dental pulp cells with Wls knockout. In addition, the expression levels of Bsp, Col1a1, Opn, and Alpl were significantly decreased by 0.7-fold, 0.3-fold, 0.8-fold, and 0.6-fold respectively in dental pulp cells with Wls knockout. Conclusion: Wnt ligands produced autonomously are necessary for proper proliferation and odontoblastic differentiation of mouse dental pulp cells toward further tertiary dentinogenesis.

• 한국통신학회논문지
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• 제26권11C호
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• pp.113-122
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• 2001

위성을 기반으로 하는 ATM 스위치에서 가장 중요하게 고려할 사항은 높은 수준의 셀 손실률을 만족함으로써 재전송을 피해야함과 on-board 프로세싱과 스위칭의 복잡도이다. ATM 스위치로 잘 알려진 스위치 중에 하나인 Knockout 스위치는 트래픽 성능 면에서 뛰어난 성능을 가지지만, 많은 스위치 구성요소와 버퍼를 필요로 한다. 이는 복잡도의 주요 원인이다. 제한된 입력단 버퍼의 추가는 만족할 만한 수준으로 셀 손실률과 복잡도를 줄이고 효과적인 위성 대역폭 사용에 기여할 수 있다. 본 논문에서는 기존에 제안된 스위치에 비하여 더 나은 셀 손실률을 가질 뿐만 아니라 더 적은 스위치 구성요소와 버퍼를 가짐으로써 복잡도를 낮춘다. 시뮬레이션을 한 결과, 제안된 구조는 기존에 제안되었던 스위치 구조에 비해 우수한 셀 손실률을 보여 주었으며, 스위치 구성요소를 최대 50%이상 줄이며 최대 50% 이상의 버퍼용량을 줄일 수 있다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권7호
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• pp.1029-1036
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• 2017

Objective: In the livestock industry, the regulatory mechanisms of muscle proliferation and differentiation can be applied to improve traits such as growth and meat production. We investigated the regulatory pathway of MyoD and its role in muscle differentiation in quail myoblast cells. Methods: The MyoD gene was mutated by the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology and single cell-derived MyoD mutant sublines were identified to investigate the global regulatory mechanism responsible for muscle differentiation. Results: The mutation efficiency was 73.3% in the mixed population, and from this population we were able to establish two QM7 MyoD knockout subline (MyoD KO QM7#4) through single cell pick-up and expansion. In the undifferentiated condition, paired box 7 expression in MyoD KO QM7#4 cells was not significantly different from regular QM7 (rQM7) cells. During differentiation, however, myotube formation was dramatically repressed in MyoD KO QM7#4 cells. Moreover, myogenic differentiation-specific transcripts and proteins were not expressed in MyoD KO QM7#4 cells even after an extended differentiation period. These results indicate that MyoD is critical for muscle differentiation. Furthermore, we analyzed the global regulatory interactions by RNA sequencing during muscle differentiation. Conclusion: With CRISPR/Cas9-mediated genomic editing, single cell-derived sublines with a specific knockout gene can be adapted to various aspects of basic research as well as in functional genomics studies.

• 한국컴퓨터정보학회논문지
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• 제11권1호
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• pp.157-165
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• 2006

본 논문에서는 출력 버퍼형 탠덤크로스포인터 멀티캐스트 ATM 스위인 MTCOS 스위치를 제안한다. MTCOS 스위치는 라우팅 구조가 간단한 다수의 크로스포인터 스위치 패브릭으로 구성된 TCSF와 효율적 멀티캐스팅을 위한 집중화기 출력 버퍼로 구성된다. TCSF는 셀프 라우팅 크로스바 스위치가 갖는 셀 지연 편차 문제를 개선하고, 또한 하나의 입력에서 다수 출력 포트들로 다수의 동시 경로를 제공하며, 간단한 소프트웨어적 설정을 통해 다중 채널 스위칭을 제공하며, 확장성, 고성능, 모듈화 특성을 갖는다. MTCOS에서 제공되는 공유 트래픽 집중화 및 출력 큐잉 방식은 다양한 멀티캐스트 트래픽에 대해 낮은 셀 손실율과 낮은 지연시간을 보인다. 또한 동일 Knockout 집중화율을 달성하기 위해 SCOQ와 Knockout 멀티캐스트 스위치 보다 낮은 하드웨어 복잡도를 갖는다. 해석적 및 컴퓨터 시뮬레이션을 통해 임의의 트래픽에 대해 제안된 스위치가 높은 성능을 달성할 수 있음을 보였다.

• Toxicological Research
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• 제17권
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• pp.299-304
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• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Molecules and Cells
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• 제38권3호
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• pp.251-258
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• 2015

Germline mutations in the breast cancer type 2 susceptibility gene (BRCA2) are linked to familial breast cancer and the progressive bone marrow failure syndrome Fanconi anaemia. Established Brca2 mouse knockout models show embryonic lethality, but those with a truncating mutation at the C-terminus survive to birth and develop thymic lymphoma at an early age. To overcome early lethality and investigate the function of BRCA2, we used T cell-specific conditional Brca2 knockout mice, which were previously shown to develop thymic lymphoma at a low penetrance. In the current study we showed that the number of peripheral T cells, particularly na$\ddot{i}$ve pools, drastically declined with age. This decline was primarily ascribed to improper peripheral maintenance. Furthermore, heterozygous mice with one wild-type Brca2 allele manifested reduced T cell numbers, suggesting that Brca2 haploinsufficiency might also result in T cell loss. Our study reveals molecular events occurring in Brca2-deficient T cells and suggests that both heterozygous and homozygous Brca2 mutation may lead to dysfunction in T cell populations.