• BMB Reports
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• 제43권2호
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• pp.97-102
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• 2010

Clenbuterol, a $\beta_2$-adrenoceptor agonist, has been proven to be a powerful repartition agent that can decrease fat deposition. Based on results from our previous cDNA microarray experiment of pig clenbuterol administration, a novel up-regulated EST was full-length cloned (4859 bp encoding 1041 amino acids) and found to be the pig homolog of large tumor suppressor 2 (Lats2). We mapped pig Lats2 to chromosome 11p13-14 by using FISH, and western blotting demonstrated that pig Lats2 protein was most abundant in adipose. In Drosophila, Lats2 ortholog was reported as a key component of the Hippo pathway which regulates cell differentiation and growth. Here, we show that pig Lats2 exhibit inverted expression to YAP1, another member of the Hippo pathway which positively regulates cell growth and proliferation, during the differentiation of 3T3-L1 preadipocytes. Our results suggested that Lats2 may involve in Hippo pathway regulating the fat reduction by inhibiting adipocyte differentiation and growth.

• Toxicological Research
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• 제34권2호
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• pp.151-162
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• 2018

Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

• 한방안이비인후피부과학회지
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• 제23권2호
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• pp.81-108
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• 2010

Objective : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5, PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.

• 대한수의학회지
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• 제57권3호
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• pp.147-154
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• 2017

The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of $16{\mu}L/mL$. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol ($40.02{\pm}33.38{\mu}g/mL$, $66.01{\pm}22.04{\mu}g/mL$, respectively) and aldehyde ($5.72{\pm}0.47{\mu}g/mL$, $6.72{\pm}1.70{\mu}g/mL$, respectively) concentrations in blood compared to those in the alcohol-water group ($199.75{\pm}33.83{\mu}g/mL$, $50.43{\pm}13.88{\mu}g/mL$, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.

• 대한한방부인과학회지
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• 제23권2호
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Genomics & Informatics
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• 제6권1호
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• pp.36-43
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• 2008

Radiotherapy would be the choice of treatment for human cancers, because of high cost-effectiveness. However, a certain population of patients shows a resistance to radiotherapy and recurrence. In an effort to increase the efficacy of radiotherapy, many efforts were driven to find the genes causing the unresponsiveness to ionizing radiation. In this paper, we compared the gene expression profiles of two lung cancer cell lines, H460 and H1299, which showed differential responses to ionizing radiations. Each cell were irradiated at 2 Gy, and harvested after 0, 2, 4, 8, 12 and 24 hours to examine the expressions. Two-way ANOVA analysis on time-series experiments of two cells could select 2863 genes differentially expressed upon ionizing radiation among 32,321 genes in microarray (p<0.05). We classified these genes into 21 clusters by SOM clustering according to the interaction between cell types and time. Two SOM clusters were enriched with apoptosis-related genes in pathway analysis. One cluster contained higher levels of phosphatidyl inositol 3-phosphate kinase (PI3K) subunits in H1299, radio-resistant cells than H460, radiosensitive cells. TRAIL receptors were expressed in H460 cells while the decoy receptor for TRAIL was expressed in H1299 cells. From these results, we could characterize the differential responsiveness to ionizing radiation according to their differential expressions of apoptosis-related genes, which might be the candidates to increase the power of radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5513-5518
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• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• 정보과학회 논문지
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• 제45권1호
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• pp.61-68
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• 2018

암환자의 예후 예측에 기여하는 유전자를 찾는 것은 환자에게 보다 적합한 치료를 제공하기 위한 도전 과제 중 하나이다. 예후 유전자를 찾기 위해 유전자 발현 데이터를 이용한 분류 모델 개발 연구가 많이 이루어지고 있다. 하지만 암의 이질성으로 인해 예후 예측의 정확도 향상에 한계가 있다는 문제가 있다. 본 논문에서는 유방암을 비롯한 6개의 암에 대한 암환자의 마이크로어레이 데이터와 생물학적 네트워크 데이터를 이용하여 페이지랭크 알고리즘을 통해 예후 유전자들을 식별하고, K-Nearest Neighbor 알고리즘을 사용하여 암 환자의 예후를 예측하는 모델을 제안한다. 그리고 페이지랭크를 사용하기 전에 K-Means 클러스터링으로 유전자 발현 패턴이 비슷한 샘플들을 나누어 이질성을 극복하고자 한다. 본 논문에서 제안한 방법은 기존의 유전자 바이오마커를 찾는 알고리즘보다 높은 예측 정확도를 보여 주었으며, GO 검증을 통해 클러스터에 특이적인 생물학적 기능을 확인하였다.

• The Plant Pathology Journal
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• 제34권4호
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• pp.257-268
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• 2018

Rice blast disease, caused by Magnaporthe oryzae, results in an extensive loss of rice productivity. Previously, we identified a novel M. oryzae secreted protein, termed MSP1 which causes cell death and pathogen-associated molecular pattern (PAMP)-triggered immune (PTI) responses in rice. Here, we report the transcriptome profile of MSP1-induced response in rice, which led to the identification of 21,619 genes, among which 4,386 showed significant changes (P < 0.05 and fold change > 2 or < 1/2) in response to exogenous MSP1 treatment. Functional annotation of differentially regulated genes showed that the suppressed genes were deeply associated with photosynthesis, secondary metabolism, lipid synthesis, and protein synthesis, while the induced genes were involved in lipid degradation, protein degradation, and signaling. Moreover, expression of genes encoding receptor-like kinases, MAPKs, WRKYs, hormone signaling proteins and pathogenesis-related (PR) proteins were also induced by MSP1. Mapping these differentially expressed genes onto various pathways revealed critical information about the MSP1-triggered responses, providing new insights into the molecular mechanism and components of MSP1-triggered PTI responses in rice.

• Genomics & Informatics
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• 제4권2호
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• pp.71-76
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• 2006

We have investigated biological responses to radiofrequency (RF) radiation in in vitro and in vivo models. By measuring the levels of heat shock proteins as well as the activation of mitogen activated protein kinases (MAPKs), we could not detect any differences upon RF exposure. In this study, we used more sensitive method to find the molecular responses to RF radiation. Jurkat, human T-Iymphocyte cells were exposed to 1763 MHz RF radiation at an average specific absorption rate (SAR) of 10 W/kg for one hour and harvested immediately (R0) or after five hours (R5). From the profiles of 30,000 genes, we selected 68 differentially expressed genes among sham (S), R0 and R5 groups using a random-variance F-test. Especially 45 annotated genes were related to metabolism, apoptosis or transcription regulation. Based on support vector machine (SVM) algorithm, we designed prediction model using 68 genes to discriminate three groups. Our prediction model could predict the target class of 19 among 20 examples exactly (95% accuracy). From these data, we could select the 68 biomarkers to predict the RF radiation exposure with high accuracy, which might need to be validated in in vivo models.