• Title/Summary/Keyword: transactivation

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Water Extract of Rosa laevigata Michx. Protects Hepatocytes from Arachidonic Acid and Iron-mediated Oxidative Stress (아라키돈산과 철 유도성 산화적 스트레스에 대한 금앵자(金櫻子) 열수 추출물의 간세포 보호 효능)

  • Ko, Hae Li;Jegal, Kyung Hwan;Song, Si Yeon;Kim, Nan Ee;Kang, Jiwon;Byun, Sung Hui;Kim, Young Woo;Cho, Il Je;Kim, Sang Chan
    • The Korea Journal of Herbology
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    • v.30 no.6
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    • pp.7-15
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    • 2015
  • Objectives : Rosa laevigata Michx. has been used for the treatment of renal disease in traditional Korean medicine. In this study, we investigated cytoprotective effect of R. laevigata water extract (RLE) against oxidative stress induced by arachidonic acid (AA) + iron.Methods : To evaluate the protective effects of RLE against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The effects of RLE on reduced glutathione level, production of reactive oxygen species and mitochondrial membrane potential were also monitored. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) was examined by immunoblot analysis. Additionally, Nrf2 transactivation and its downstream target genes expression were also determined by reporter gene and realtime RT-PCR analyses.Results : RLE pretreatment (30-300 μg/ml) prevented cells from AA + iron-mediated cell death in a concentration dependent manner. In addition, 100 μg/ml RLE inhibited AA + iron-induced glutathione depletion, reactive oxygen species production and mitochondrial dysfunction. RLE accumulated nuclear Nrf2 and also transactivated Nrf2, which was evidenced by antioxidant response element- and glutathione S-transferase A2-driven luciferase activities and mRNA level of glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1 and sestrin 2. Moreover, protective effect of RLE against AA + iron was abolished in Nrf2 knockout cells.Conclusions : These results indicate that RLE has the ability to protect hepatocyte against oxidative stress through Nrf2 activation.

FMDV 2C Protein of Foot-and-mouth Disease Virus Increases Expression of Pro-inflammatory Cytokine TNFα via Endoplasmic Reticulum Stress (구제역바이러스의 FMDV 2C 단백질은 소포체 스트레스를 통해서 염증 유도 사이토카인 TNFα의 발현을 증가시킴)

  • Kang, Hyo Rin;Seong, Mi So;Nah, Jin Ju;Ryoo, Soyoon;Ku, Bok Kyung;Cheong, JaeHun
    • Journal of Life Science
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    • v.30 no.3
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    • pp.285-290
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    • 2020
  • Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • v.8 no.1
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

Effect of Maturity at Harvest on the Changes in Quality of Round Baled Rye Silage (수확시 숙기가 호밀 라운드베일 사일리지의 품질변화에 미치는 영향)

  • Kim, J.G.;Chung, E.S.;Seo, S.;Kang, W.S.;Ham, J.S.;Kim, D.A.
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.21 no.1
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    • pp.1-6
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    • 2001
  • This experiment was conducted to evaluated the effect of maturity at harvest on the changes in quality of round baled rye silage at forage experimental field of Grassland and Forage Crops Division, National Livestock Research Institute, RDA, Suwon in 1998. The experimental design was a split-plot design with three replications. The main plots were three different harvest stages : boot, heading and flowering stages, and the subplots were days after ensiling : 1, 2, 3, 5, 10, 30, 45, and 60 days. The wilting period of boot, heading and flowering stages were 1, 0.5 and 0.5 days, respectively. The final pH of rye silage was higher in the order of flowering, boot and heading stages. And pH of flowering stage began to change at early fermentation period, but that of boot and heading stages was delayed 1~2 days. Ammonia-N content of boot stage was highest. and that was increased as fermentation progressed. But Ammonia-N of heading stage was decreased to 30 days. then that was increased after 45 days fermentation. Among fermentation periods, inside temperature of deep place was not affected by external temperature. And that of deep place was increased to 3$0^{\circ}C$ at early fermentation. then decreased as fermentation progressed. However surface temperature was affected by external temperature after 10 days. Acetic acid content was not changed with 5 days by harvest stages, but that of boot stage was increased after 10 days. Butyric acid of boot stage was increased after 5 days. but that of heading stage was increased after 10 days. However lactic acid was increased from 1~2% to 6~8%. Lactic acid bacteria (LAB) of heading and flowering stages were highest at 5 days fermentation, and that of boot stage was highest at 10 days fermentation. The results of this study indicate that fermentation of round baled rye silage occur within 5 days. Therefore, any modification should be applied with an 5 days for high quality of round baled rye silage.

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Allium tuberosum Reverses PCSK9-Mediated LDLR Degradation by Inhibition of HNF1α (부추 추출물의 PCSK9 억제를 통한 LDL 콜레스테롤 저감 효능)

  • Choi, Hyo-Kyoung;Kim, Hyo Jin;Hwang, Jin-Taek;Chung, Min-Yu
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.11
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    • pp.1278-1285
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    • 2017
  • Accumulation of excess low density lipoprotein (LDL) cholesterol in the blood can initiate and accelerate atherosclerosis. Statins mediate the transactivation of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of this study was to investigate whether or not Allium tuberosum (AT) regulates LDLR and PCSK9. Mice were fed a low fat control diet (LD) or Western diet (WD) supplemented with AT (1%, w/w). AT significantly attenuated total and LDL cholesterol levels in mice fed WD (P<0.05). AT also significantly inhibited hepatic PCSK9 gene expression (P<0.05) while AT maintained hepatic LDLR gene expression. To further investigate AT-mediated PCSK9 regulation, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of AT. Non-toxic level of AT dose-dependently increased the LDLR protein level, and AT at $400{\mu}g/mL$ markedly inhibited PCSK9 protein expression. Similarly, AT significantly increased LDLR gene expression, whereas it significantly down-regulated PCSK9 gene expression. AT-mediated reduction of PCSK9 gene expression is likely due to decreased hepatic nuclear factor $1{\alpha}$ ($HNF1{\alpha}$) expression, but not SREBP2 in HepG2 cells under lipid-depleted conditions. AT-mediated PCSK9 inhibition contributed to LDLR protein stabilization via protection against LDLR lysosomal degradation in HepG2 cells under lipid-depleted conditions. Further investigation is warranted to determine the active components of AT and whether or not these components are effective in reducing hypercholesterolemia.

Research about feature selection that use heuristic function (휴리스틱 함수를 이용한 feature selection에 관한 연구)

  • Hong, Seok-Mi;Jung, Kyung-Sook;Chung, Tae-Choong
    • The KIPS Transactions:PartB
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    • v.10B no.3
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    • pp.281-286
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    • 2003
  • A large number of features are collected for problem solving in real life, but to utilize ail the features collected would be difficult. It is not so easy to collect of correct data about all features. In case it takes advantage of all collected data to learn, complicated learning model is created and good performance result can't get. Also exist interrelationships or hierarchical relations among the features. We can reduce feature's number analyzing relation among the features using heuristic knowledge or statistical method. Heuristic technique refers to learning through repetitive trial and errors and experience. Experts can approach to relevant problem domain through opinion collection process by experience. These properties can be utilized to reduce the number of feature used in learning. Experts generate a new feature (highly abstract) using raw data. This paper describes machine learning model that reduce the number of features used in learning using heuristic function and use abstracted feature by neural network's input value. We have applied this model to the win/lose prediction in pro-baseball games. The result shows the model mixing two techniques not only reduces the complexity of the neural network model but also significantly improves the classification accuracy than when neural network and heuristic model are used separately.

A Novel Glycine-Rich Region in Sox4 is a Target for the Proteolytic Cleavage in E. coli (전사활성 인자인 Sox4의 단백질 분해효소에 의한 표적 부위에 관한 연구)

  • 허은혜;최주연;장경희;김인경;임향숙
    • Korean Journal of Microbiology
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    • v.38 no.3
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    • pp.153-161
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    • 2002
  • Sox4, a transcription factor, consists of three functional domains: an HMG-box domain as a DNA binding domain, serine rich region as a transactivation domain and glycine rich region (GRR), an unknown functional domain. Although Sox4 is known to be functionally involved in heart, B-cell and reproductive system development, its physiological function remains to be elucidated. We used pGEX expression system to develop a simple and rapid method for purifying Sox4 protein in suitable forms for biochemical studies of their functions. Unexpectedly, we observed that full-length Sox4 appears to be protease-sensitive during expression and purification in E. coli. To map the protease-sensitive site in Sox4, we generated various constructs with each of functional domains of Sox4 and purified as the GST-Sox4 fusion proteins using glutathione beads. We found that the specific cleavage site for the proteolytic enzyme, which exists in E. coli, is localized within the novel GRR of Sox4. Our study suggest that the GRR of Sox4 may a target for the cellular protease action and this cleavage in the GRR may be involved in regulating physiological function of Sox4. Additionally, our study may provide a useful method for investigating the proteolytic cleavage of the target molecule in E. coli.