• Title/Summary/Keyword: Activation Strategy

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DOWN REGULATION OF TGF-$\beta$ GENE EXPRESSION BY ANTISENSE OLIGO-DEOXYNUCLEOTIDES INCREASE rIFN-${\gamma}$-INDUCED NITRIC OXIDE SYNTHESIS IN MURINE PERITONEAL MACROPHAGES

  • Jun, Chang-Duk;Kim, Su-Ung;Lee, Seong-Yong;Chung, Hun-Taeg
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.78-78
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    • 1995
  • Increasing evidence indicates that the production of nitric oxide (NO) by inducible NO synthase (NOS) is tightely regulated. Transforming growth factor-${\beta}$ (TGF-${\beta}$) is a homodimeric protein secreted during macrophage activation, but several lines of evidence suggest that TGF-${\beta}$ is selectively suppressive for macrophage NO production. We therefore reasoned that a strategy employing oligodeoxynucleotides(ODNs) complemently to TGF-${\beta}$ mRNA (antisense ODNs) might increase NO production in IFN-${\gamma}$-treated murine peritoneal macrophages. To evaluate this concept, we tested the effects of antisense ODNs targeted to TGF-${\beta}$ mRNA (25-mer ODNs complemently to TGF-${\beta}$mRNA sequences) by introducing it into the medium of cultured macrophages. Phosphorothiolation of ODNs were employed to retard their degradation. Antisense ODNs had no effect on NO production by itself, whereas IFN-${\gamma}$ alone had modest effect. When antisense ODNs were used in combination with IFN-${\gamma}$, there was a marked cooperative induction of NO production, These effects of antisense ODNs were associated with decreased TGF-${\beta}$ expression in activated macrophages. ODNs with the same nucleotides but a scrambled sequence had no effect. Adding anti-TGF-${\beta}$ antibodies to the IFN-${\gamma}$-treated macrophages mimicked the positive effect of antisense ODNs on NO production. In addition, the effects of either antisense ODNs or anti-TGF-${\beta}$ antibodies were blocked by adding TGF-${\beta}$ in cultured macrophages. These results indicate that the generation of TGF-${\beta}$ by activated macrophages provides a self-regulating mechanism by which the temporal and perhaps spatial production of NO, a reactive and potentially toxic mediator, can be finely regulated.

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Targeting Nrf2-Mediated Gene Transcription by Triterpenoids and Their Derivatives

  • Loboda, Agnieszka;Rojczyk-Golebiewska, Ewa;Bednarczyk-Cwynar, Barbara;Zaprutko, Lucjusz;Jozkowicz, Alicja;Dulak, Jozef
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.499-505
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    • 2012
  • Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor. Activation of Nrf2 by triterpenoids induces the expression of phase 2 detoxifying and antioxidant enzymes such as NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) - proteins which can protect cells or tissues against various toxic metabolites. On the other hand, inhibition of other transcription factors, like NF-${\kappa}B$ leads to the decrease in the pro-inflammatory gene expression. Moreover, the modulation of microRNAs activity may constitute a new mechanism responsible for valuable effects of triterpenoids. Recently, based on the structure of naturally occurring triterpenoids and with involvement of bioinformatics and computational chemistry, many synthetic analogs with improved biological properties have been obtained. Data from in vitro and in vivo experiments strongly suggest synthetic derivatives as promising candidates in the chemopreventive and chemotherapeutic strategies.

Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells

  • Jo, Si-Kyoung;Hong, Ji-Young;Park, Hyen Joo;Lee, Sang Kook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.513-519
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    • 2012
  • Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

Dual Inhibition of PI3K/Akt/mTOR Pathway and Role of Autophagy in Non-Small Cell Lung Cancer Cells

  • Jeong, Eun-Hui;Choi, Hyeong-Sim;Lee, Tae-Gul;Kim, Hye-Ryoun;Kim, Cheol-Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.72 no.4
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    • pp.343-351
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    • 2012
  • Background: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. Methods: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. Results: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. Conclusion: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.

A Study on the University Start-Up Activation Plan through CO-OP Education : Focused on Development of a University Education Model with linking Field Practices (코업(CO-OP) 교육을 통한 창업 활성화 방안 연구 : 현장실습연계형 대학 교육모델 개발을 중심으로)

  • Kim, Chun-Shik
    • Journal of Information Technology Applications and Management
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    • v.26 no.3
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    • pp.61-80
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    • 2019
  • The cooperation between universities and industries is already one of the most important factors driving the national economy in the knowledge-based society of the 21st century represented by the Fourth Industrial Revolution. The Korean government has also been carrying out legal and institutional re-adjustments to promote industrial-university cooperation in line with demands for such changes in the times. However, despite this industry-academic cooperation system, there is still a significant mismatch between industrial demand and the university's workforce development system. By the way, there is a Cooperative Education(CO-OP) in Canada and the United States. It's an innovative link between the university and the industry. The reason is that the CO-OP program not only allows students to gain experience with their majors in the industrial field, but also plays a positive role in improving their specialty expertise. In particular, field information, ideas, and job insights that students acquire through CO-OP also serve as motivation for starting a business beyond employment after graduation. Furthermore, CO-OP experience is an important opportunity for future researchers to come up with commercialized research results that are not separated from the field sites The purpose of this study is to overcome the gap between industrial demand and the college manpower training system, and develop a Korean-style coaching program model as a growth engine for creative talent-building policies, represented by 'creation of start-ups and new industry.' In addition, this study suggested measures that can be applied in real universities. In addition, the study also highlighted that the introduction of CO-OP programs with field practices in Korea could also boost start-ups. Based on the Korean CO-OP program model, the curricula applicable to domestic universities consisted of two types : general and research-oriented university types.

A Study on the Activation Strategy of Site-Based Experiential Environmental Education (현장체험중심의 환경교육 활성화 방안 연구 -독일의 환경교육이 주는 시사점을 중심으로-)

  • 최돈형;노경임
    • Hwankyungkyoyuk
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    • v.13 no.2
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    • pp.51-62
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    • 2000
  • This study examined the current status of school environmental education (EE) in Germany, and attempted to propose strategies to develop school EE in Korea. The study intended to accomplish the following goals: First, this study attempted to examine the developmental process of school EE in Germany. Second, exemplary cases of site-based experiential education in Germany are selected and analysed to develop pedagogical strategies in school EE in Korea. The strategies for development proposed in this study can be summarized as follows: First, the focus of EE should go beyond that of "solving or curing"environmental problems and pollutions, and need to be re-directed to pursue an "education for sustainable development", a new paradigm for future EE. Second, EE should increasingly integrate outdoor site-based, experiential programs into the currently classroom-based and knowledge-driven forms of education, not only to maximize its educational effect but also and knowledge-driven forms of education, not only to maximize its educational effect but also to coordinate the instruction of EE in the context of the educational reform agenda, currently undergoing since the late 1990s, in Korea. Third, teaching-learning materials for EE should be variously developed, and programs should be encouraged to serve local needs and circumstances for effective classroom practices, and criteria for standardization and professionalization should be sought in developing these programs. Fourth, it is recommended that the Ministry of Environment secure funds to facilitate the local school authorities at the municipal and provincial levels to operate a mobile environmental support system, equivalent to the function of the "Lumbricus"in Germany. Fifth, an external support network should be established among the support agencies for EE. Especially, a professional agency or institute to academically support school EE and a special planning committee for enhancing EE need to be established for resource and personal development. Parents′voluntary participation should also be encouraged to establish a tripartite network of "school-community-government" to support and facilitate school EE.

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A Study on Alternatives for Activating a North Corridor of the Trans Asian Railway according to The Opening of a Cross-Border Freight Railway Service between South and North Korea (남북간 화물열차 개통이후 TAR북부노선 연계.활성화를 위한 대안 연구)

  • Yun, Dong-Hee
    • Proceedings of the KSR Conference
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    • 2008.06a
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    • pp.2303-2315
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    • 2008
  • Finally, Musan-Bongdong section in Kyeong-Ui corridor opened on 11. DEC.2007, which is a historical event, because this connection means the restoration of 56 yrs' disconnection since 1951 and also starting point launching to connect china, Mongolia, Russia for continental railway logistic infrastructure. This is also one of master plans about the northern line in TAR, carried out by UNESCAP, so this study will touch up each country's railway status and the next tasks related with trans-continental railway such as North Korea, Russia, China. Also, this study reveal a mid-long term development strategy to improve the North Korea railroad for a continent rail link and international railroad transportation between China and Russia, and also checks the way of confrontation to the domestic infrastructure for the activation of the continent railway and the north and south, investigates concretely how to establish TAR northern part routes as soon as possible.

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A Study on the Development Strategies for e-commerce Innovation (e-커머스 서비스 혁신을 위한 발전전략 연구)

  • Kwon, Hyeog In;Baek, Bo Hyun;Ahn, Yea Jin;Lee, Jin Hyung
    • The Journal of the Korea Contents Association
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    • v.20 no.1
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    • pp.217-232
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    • 2020
  • The purpose of this study is to organize prior research related to e-commerce activation factors available to stakeholders in the online distribution industry, and to conduct FGI with e-commerce experts to calculate the importance of each factor in order based on the 3 Level Service Model of Kwon Hyeog-in (2010), the key factors derived through the preceding study and the FGI were structured and the weighting of each factor was derived using AHP methodology. In the higher factors, the private sector (0.542) > communes (0.237) > public (0.2222) appeared to be important. Sub-factories included 'search service development' (0.0970)', 'recommendation service development (0.0805)', 'consumer needs analysis (0.0534)', 'consumer consumption pattern analysis (0.0505)' and 'other platform-linked service development (0.0450)', in the order of weighting down, indicating each of the factors within the top 15 priority. The results of this study will be utilized throughout the e-commerce industry as well as e-commerce enterprises, providing an academic foundation for the rapidly growing e-commerce ecosystem.

An Analysis of a Strategy for the Activation of Korean Wave K-Fashion (한류 K-패션 활성화를 위한 전략 분석 연구)

  • Kim, Hee-Sun
    • Journal of the Korea Fashion and Costume Design Association
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    • v.19 no.3
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    • pp.175-192
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    • 2017
  • The purpose of this study is to provide the characteristics and development direction of K-fashion and to systematize the strategic features performed by government agencies, fashion associations, fashion companies, and other companies to activate K-fashion. This research analyzed K-fashion related articles published in major newspapers and magazines in Korea from the late 1990s to early 2017. The results of the study are as follows. 1. The characteristics of K-fashion are as follows: The first is a trendy and sophisticated design with modern sensibilities, unique designs that reinterpret the latest trends with designer creativity, practical and popular designs that ordinary people can wear comfortably in everyday life. The second is functional and trendy materials. The third is excellent sewing technology. The fourth is rapid turnover of products by quick connections among planning, production and sales. The fifth is a lower price than quality. 2. The direction for K-fashion to pursue was the continuous and ongoing development of the above characteristics and the creation of a 'design with the Korean emotion of its 5,000 year history'. 3. The following projects were carried out to promote K-fashion. 1) Utilization of K-pop, K-drama and other Korean wave content. (1) Holding a fashion concert event that combines Idol's K-Pop performances with fashion shows. (2) Hallyu (Korean wave) star's costume support and design collaboration with Hallyu stars. (3) Collaboration between entertainment companies and fashion companies. 2) Nurturing a global fashion branding project. 3) Business support for overseas expansion of the K-fashion brand. (1) Support project for foreign trade fair participation. (2) Holding a fashion brand fair in Korea. (3) Overseas business support by establishing a showroom and design center 4) Business to discover and nurture new designers

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Apoptotic Effects of A Cisplatin and Eugenol Co-treatment of G361 Human Melanoma Cells

  • Park, Jun-Young;Jo, Jae-Beom;Kim, In-Ryoung;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.36 no.3
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    • pp.155-162
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    • 2011
  • Eugenol (4-allyl-2-methoxyphenol) is a naturally occurring phenolic compound that is widely used in dentistry as a component of zinc oxide eugenol cement that is commonly applied to the mouth environment. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatments with eugenol and cisplatin on human melanoma (G361) cells. To investigate whether this co-treatment efficiently reduces the viability of G361 cells compared with each single treatment, an MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis of DNA hypoploidy. Western blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) changes were also assayed. The results indicated that a co-treatment with eugenol and cisplatin induced multiple pathways and processes associated with an apoptotic response in G361 cells including nuclear condensation, DNA fragmentation, a reduction in MMP and proteasome activity, the increase and decrease of Bax and Bcl-2, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, and the activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD). In contrast, separate treatments of 300 ${\mu}M$ eugenol or 3 ${\mu}M$ cisplatin for 24 h did not induce apoptosis. Our present data thus suggest that a combination therapy of eugenol and cisplatin is a potential treatment strategy for human melanoma.