• Title/Summary/Keyword: Action Target 3

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β-Lapachone-Induced Apoptosis is Associated with Inhibition of Cyclooxygenase-2 Activity in Human Lung Cancer A549 Cells (β-lapachone에 의한 A549 인체폐암세포의 apoptosis 유도와 cyclooxygenase-2 활성 저하)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.21 no.10
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    • pp.1494-1499
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    • 2011
  • ${\beta}$-lapachone, a quinone of lapachol extracted from the bark of the lapacho tree, has been found to induce apoptosis in various human cancer cells. In the present study, we investigated further possible mechanisms by which ${\beta}$-lapachone exerts its pro-apoptotic action in cultured human lung cancer A549 cells. ${\beta}$-lapachone treatment resulted in inhibition of growth and induction of apoptosis in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of apoptosis by ${\beta}$-lapachone was associated with up-regulation of the expression of p53 and p21 in both transcriptional and translational levels, and the phosphorylation of p53. In addition, ${\beta}$-lapachone activated caspase-3 and -9, and induced degradation of caspase-3 target proteins such as poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin. Furthermore, ${\beta}$-lapachone treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. Taken together, these results indicated that ${\beta}$-lapachone may have therapeutic potential in human lung cancer treatment.

Autogenous Shrinkage Mock-up Test of High Performance Concrete by Emulsified Refined Cooking Oil (유화처리 정제식용유를 사용한 고성능 콘크리트의 자기수축 Mock-up 실험)

  • Jo, Man-Ki;Han, Cheon-Goo
    • Journal of the Korean Recycled Construction Resources Institute
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    • v.4 no.3
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    • pp.307-315
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    • 2016
  • The aim of this research is analyzing the fundamental properties and autogenous shrinkage reducing performance of 70 and 100MPa grade high performance concrete including emusified refined cooking oil(ERCO) under the mock-up conditions. As a results of experiment, the mixture contained 0.5% of ERCO showed slightly decreased slump flow while the slump was increased and segregation resistance performance was improved as 2.5 of EIS. For air content, all mixtures satisfied target air content with increased unit weight and delayed setting time with ERCO addition. In the case of compressive strength, when ERCO was added 0.5%, the result of approximately 5 to 10% of increased compressive strength was observed. For the autogenous shrinkage, ERCO contributed on 20-30% of shrinkage reducing performance comparing to Plain mixture without ERCO. It is considered that capillary pore filling action of soap particles occurred by the reaction of ERCO in cement paste between fatty aicd and calcium hydroxide contributed the shrinkage reducing performance. Based on these mock-up test results, application of the high performance concrete mixture with ERCO on CFT actual structure was decided.

Effect of Fibroblast Growth Factor 23 on Osteoblastic Differentiation and Mineralization of D1 Mesenchymal Stem Cells (섬유모세포성장인자-23이 D1 간엽줄기세포에서 조골세포로의 분화 및 기질 광화에 미치는 영향)

  • Park, Kyeong-Lok
    • Journal of Life Science
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    • v.26 no.3
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    • pp.331-337
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    • 2016
  • Although fibroblast growth factor 23 (FGF23) is exclusively produced in osteoblasts and osteocytes, its main target is the kidney, where it decreases phosphate reabsorption by suppressing Na-phosphate cotransporters. Independently of its action on phosphate homeostasis, FGF23 also inhibits bone formation in vivo. In a calvarial osteoblastic cell model, FGF23 was shown to negatively affect extracellular matrix mineralization. This study investigated whether FGF23 had similar effects on osteoblast maturation, including differentiation and mineralization of bone marrow-derived mesenchymal stem cells (MSCs). D1 MSCs were cultured in an osteogenic medium containing β-glycerophosphate, ascorbic acid, and dexamethazone. Osteoblastic differentiation was evaluated by alkaline phosphatase (Alp) staining, and matrix mineralization was evaluated by alizarin red staining and calcium deposition. The expression of differentiation-stimulating genes Runx2, Alp, and osteocalcin and mineralization-inhibiting genes Enpp1 and Ank was analyzed using semiquantitative RT-PCR. Supraphysiological doses of FGF23 did not stimulate proliferation or osteoblastic differentiation of MSCs. Matrix mineralization 1, 2, and 3 weeks after the FGF23 treatment did not vary between control and FGF23 groups, although time-dependent enhancement of mineralization was obvious. Calcium deposition was also unchanged after the FGF23 treatment. mRNA expression levels of differentiation- and mineralization-related genes were also similar between the groups. Despite these negative findings, FGF23 signaling through FGF receptors seemed to function normally, with phosphorylation of the Erk protein more evident in the FGF23 group than in controls. These findings suggest that unlike calvarial osteoblasts, FGF23 is not likely to affect osteoblastic differentiation and mineralization of MSCs.

The Lexical Access of Regular and Irregular Korean Verbs in the Mental Lexicon (한국어 규칙 동사와 불규칙 동사의 심성 어휘집 접근 과정)

  • Park, Hee-Jin;Koo, Min-Mo;Nam, Ki-Chun
    • Korean Journal of Cognitive Science
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    • v.23 no.1
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    • pp.1-23
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    • 2012
  • This study investigated the lexical access processing of inflected Korean verbs in the mental lexicon. In Korean, verbs can be classified into two main types of inflections, which are regular and irregular inflections, which can be further divided into three types of regular inflections and two types of irregular inflections. A masked priming lexical decision task was used and the priming effects were compared. Experiments were carried out using the five different types of verbal inflections in Korean: (1) No change-regularity (regular verbs with no orthographical or phonological changes), (2) Phonological change-regularity (regular verbs with phonological changes to the stem only), (3) Orthographical change-regularity (regular verbs that only undergo orthographical changes), (4) Stem change-irregularity (the stem is omitted or alternated with the other phoneme of the stem in irregular verbs), (5) Ending change-irregularity (irregular verbs with changes in the endings by phoneme substitution). The first three types are regarded as regular verbal inflections whereas the latter two types are regarded as irregular verbal inflections. The infinitive forms of the verb were presented as target words and three different conditions were presented as prime words. The three conditions included regular verbal inflection, irregular verbal inflection, and a control condition in which morphologically and semantically unrelated primes were presented. In addition, different stimulus onset asynchrony (SOA) were manipulated (43ms, 72ms, 230ms) to examine the time frame of the morphological decomposition process in word recognition. The results revealed that there were significant priming effects in all three SOAs across conditions. Hence, there was no significant differences in priming effects between regular and irregular verbal inflection conditions. This may suggest that Korean verb processing does not adopt different processing routes for regular and irregular inflections, which can also be an indication of earlier morphological information processing for Korean verbs.

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Systemic Approaches Identify a Garlic-Derived Chemical, Z-ajoene, as a Glioblastoma Multiforme Cancer Stem Cell-Specific Targeting Agent

  • Jung, Yuchae;Park, Heejoo;Zhao, Hui-Yuan;Jeon, Raok;Ryu, Jae-Ha;Kim, Woo-Young
    • Molecules and Cells
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    • v.37 no.7
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    • pp.547-553
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    • 2014
  • Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

The Effects of Prunus Armeniaca Linne Var Fractions on Th2 Cytokine Expression and Atopic Dermatitis of NC/Nga Mouse (행인(杏仁) 분획물이 Th2 cytokine 발현과 NC/Nga mouse의 아토피 피부염에 미치는 영향)

  • Kang, Ki Yeon;Han, Jae Kyung;Kim, Yun Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.30 no.4
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    • pp.29-59
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    • 2016
  • Objectives PRAL (Prunus armeniaca Linne Var) has been known to suppress allergic reaction. However, the cellular target and its mechanism of action were unclear. This study was designed to investigate the effect of PRAL on RBL-2H3 mast cell, which is PMA-Ionomycin-induced activated in vitro and the effect of PRAL on the MNC/Nga mice that are DNCB-induced activated in vivo. Methods In this study, IL-4, IL-13 production were examined by ELISA analysis; IL-4, IL-13, IL-31, IL-31Ra, $TNF-{\alpha}$ and GM-CSF mRNA expression were examined by Real-time PCR; manifestations of AP-1 and MAPKs transcription factors were examined by western blotting in vitro. Then skin rashes have been evaluated and verified the distribution of mast cells by H&E and toluidine blue. Also, WBC, eosinophil and neutrophil, IgE level in serum, $IFN-{\gamma}$, IL-4, IL-5 in the splenocyte culture supernatant, the absolute cell numbers of $CD4^+$, $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$, $CD3^+CD69^+$ in the Axillary Lymph Node (ALN), PBMCs and dorsal skin and IL-5, IL-13, IL-31, IL-31Ra in the dorsal skin by Real-time PCR were all evaluated from the NC/BNga mice. Results As a result of this study, the mRNA expression of IL-4, IL-13, IL-31, IL-31Ra and $TNF-{\alpha}$ and IL-4, IL-13 production, shown in ELISA analysis, were suppressed by PRAL. Results from the western blot analysis showed decrease on the expression of mast-cell-specific transcription factors, including AP-1 and p-JNK, p-ERK. Histological examination showed that infiltration levels of immune cells in the skin of the AD-induced NC/Nga mice were improved by PRAL orally adminstration. Orally- administered PRAL group also showred decreased level of IgE in the serum. This group has shown decreased the level of IL-4, IL-5, but shown elevated $IFN-{\gamma}$ level in the splenocyte culture supernatant. The same group also has shown decreased cell numbers of $CD4^+$, $CD8^+$, $CD3^+CD69^+$ in the ALN, and $CD4^+$, $Gr-1^+CD11b^+$ in the dorsal skin. PRAL oral adminstration increased cell numbers of $CD4^+$, but decreased cell numbers of $CD8^+$, $Gr-1^+CD11b^+$, $B220^+CD23^+$ in the PBMCs. Conclusions Obtained results suggest that PRAL can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis (AD) induced in the NC/Nga mice. This may play an important role in recovering AD symptoms and suppressing pruritus.

Phytophthora Blight of Pepper and Genetic Control of the Disease (고추 역병과 그 유전적 방제)

  • Kim, Byung-Soo
    • Current Research on Agriculture and Life Sciences
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    • v.32 no.3
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    • pp.111-117
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    • 2014
  • Phytophthora blight caused by Phytophthora capsici Leonian is a dangerous disease threatening pepper growers worldwide. The efficacy of chemical control is generally low as the pathogen is soil-borne and rapidly spread by zoospores during the rainy season. Thus, based on the demand for resistant varieties, various good resistant sources, such as CM334, AC2258, and PI201234, have been reported and their inheritance of resistance studied by many different authorities. However, the mode of inheritance remains unclear, as 1 or 2 independent dominant genes, 3 genes, or multiple genes have all been reported as responsible for resistance. Recently, QTL mappings of the gene factors for resistance have been reported, and molecular markers for resistance used in breeding programs. With the release of many resistant commercial hybrid cultivars, differentiation of pathotypes of the pathogen is attracting interest among breeders and plant pathologists. Various authorities have already classified the pathogen strains into different races according to the inter-action between resistant host plants, including the source of resistance, such as CM334 and PI201234, and resistant commercial varieties and P. capsici isolates. However, no standard differential host sets have yet been established, so the results are good only for the pathogen strains used in the experiments. Thus, for breeding varieties with durable resist-ance, it is important to introduce resistance from different sources and use diverse local pathogen strains collected in the target area for distribution in a breeding program.

Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells

  • Choi, Youn Kyung;Kang, Jung-Il;Hyun, Jin Won;Koh, Young Sang;Kang, Ji-Hoon;Hyun, Chang-Gu;Yoon, Kyung-Sup;Lee, Kwang Sik;Lee, Chun Mong;Kim, Tae Yang;Yoo, Eun-Sook;Kang, Hee-Kyoung
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.211-219
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    • 2021
  • Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

Analysis of Expression Types of Character Animation TV Advertisements (캐릭터애니메이션 TV광고의 표현유형 분석 연구)

  • Lee, Yong-Woo
    • Archives of design research
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    • v.19 no.5 s.67
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    • pp.85-94
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    • 2006
  • In the 2000s, character animation technique is used at domestic TV character animation ads of diverse items displaying new character patterns and expression techniques of a high level. This study intends to identify the characteristics of TV character animation ads based ell character aesthetic theory and advertising rhetoric theory, and based on these findings, analyze trend and stream of expression in TV character animation ads by examining and classifying advertisements released in the past four years by items, character patterns and expression techniques. The results showed that TV character animation ads have been concentrated on confectionery, beverages and foods in the past, but the items have been diversified through the years. With reference to character patterns, personal and animal characters had made the main pattern, but recently product, virtual and composite characters are on the increase. In expression techniques, cell animation technique was found to be the most frequently used technique, which was followed by full-3D, cell and live action, cell and 3D and the clay animation technique. A trend like this suggests that TV character animation advertising items will continue to increase in line with the participation level of targets. In the meantime, personal and animal characters will continue to make the leading character pattern, while virtual and composite character patterns emerge in new forms. In expression techniques, live action combined with 30 technique and techniques using new expression materials will appear with cell animation technique as a central figure. As a whole, Korean character animation advertisement is expected to keep on growing to a new dimension in the aspect of items, character patterns and expression technique.

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Cytotoxic Mechanism of Docosahexaenoic Acid in Human Oral Cancer Cells (인체 구강암 세포주에서 Docosahexaenoic acid에 의한 세포독성 기전)

  • Hong, Tae-Hwa;Kim, Hoon;Shin, Soyeon;Jing, Kaipeng;Jeong, Soyeon;Lim, Hyun;Yun, Donghyuk;Jeong, Ki-Eun;Lee, Myung-Ryul;Park, Jong-Il;Kweon, Gi-Ryang;Park, Seung Kiel;Hwang, Byung-Doo;Lim, Kyu
    • Journal of Life Science
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    • v.23 no.5
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    • pp.689-697
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    • 2013
  • In the United States, about 40,000 new cases of oral cancer are diagnosed each year and nearly 7,800 patients died from it in 2012. Omega-3 polyunsaturated fatty acids have been found to have anticancer effects in a variety of cancer cell lines and animal models, but their effect in oral cancer remains unclear. This study was designed to examine the effect of docosahexaenoic acid (DHA, a kind of omega-3 fatty acid) on oral cancer cells and the molecular mechanism of its action. We found that exposure of squamous cell carcinoma-4 (SCC-4) and squamous cell carcinoma-9 (SCC-9) human oral cancer cells to DHA induced growth inhibition in a dose- and time-dependent manner. Meanwhile, in addition to the elevated levels of apoptotic markers, such as cleaved PARP, subG1 portion and TUNEL-positive nuclei, DHA led to autophagic vesicle formation and an increase in autophagic flux, indicating the involvement of both apoptosis and autophagy in the inhibitory effects of DHA on oral cancer cells. Further experiments revealed that the apoptosis and autophagy induced by DHA were linked to inhibition of mammalian target of rapamycin (mTOR) signaling by AKT inhibition and AMP-activated protein kinase (AMPK) activation in SCC-9 cells. Together, our results suggest that DHA induces apoptosis- and autophagy-associated cell death through the AMPK/AKT/mTOR signaling pathway in oral cancer cells. Thus, utilization of omega-3 fatty acids may represent a promising therapeutic approach for chemoprevention and treatment of human oral cancer.