• Title/Summary/Keyword: SRC

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Biapigenin, Candidate of an Agonist of Human Peroxisome Proliferator-Activated Receptor γ with Anticancer Activity

  • Kim, Jin-Kyoung;Shin, So-Young;Lee, Jee-Young;Lee, So-Jung;Lee, Eun-Jung;Jin, Qinglong;Lee, June-Young;Woo, Eun-Rhan;Lee, Dong-Gun;Yoon, Do-Young;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.8
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    • pp.2717-2721
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    • 2011
  • Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors (NRs). Human peroxisome proliferator-activated receptor gamma (hPPAR${\gamma}$) has been implicated in the pathology of numerous diseases, including obesity, diabetes, and cancer. ELISA-based hPPAR${\gamma}$ activation assay showed that biapigenin increased the binding between hPPAR${\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 3-fold. In order to confirm that biapigenin binds to hPPAR${\gamma}$, fluorescence quenching experiment was performed. The results showed that biapigenin has higher binding affinity to hPPAR${\gamma}$ at nanomolar concentrations compared to indomethacin. Biapigenin showed anticancer activity against HeLa cells. Biapigenin was noncytotoxic against HaCa T cell. All these data implied that biapigenin may be a potent agonist of hPPAR${\gamma}$ with anticancer activity. We will further investigate its anticancer effects against human cervical cancer.

The Effect of PWHT on Fracture Toughness in HAZ of Cr-Mo Steel(II) (Cr-Mo鋼 熔接熱影響部 의 破壞靭性 에 미치는 熔接後 熱處理 의 影響 II)

  • 임재규;정세희
    • Transactions of the Korean Society of Mechanical Engineers
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    • v.9 no.1
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    • pp.40-46
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    • 1985
  • Some problems such as toughness decrement and stess relief cracking (SRC), many occur when post weld heat treatment (PWHT) is applied to remove residual stress adn hydrogen. In this paper PWHT was carried out under the stress of 0, 98, 196 and 294 MPa (0, 10, 20 and 30kgf/mm$^{2}$ each) to simulate residual stress in HAZ of Cr-Mo steel. The effect of applied stress during PWHT on fracture toughness was evaluated by COD fracture toughness test, micro-hardnes test and observation of SEM. The experimental results are as follows; (1) Fracture toughness of weld HAZ was improved by PWHT, but it decreased as heat treated under the stress. (2)Hardness ratio under the stress of 294MPa (30kg/mm$^{2}$) was lower and fracture toughness was decreased than that of the no stress. (3) Applied stress in weld HAZ during PWHT assisted precipitation of over saturated alloying elements in the structure, so fracture surface at the stress of 294MPa (30kg/mm$_{2}$) appeared the grain boundary failure possibly one of the reasons for PWHT embrittlenment.

Heat Shock Protein $90{\beta}$ Inhibits Phospholipase $C{\gamma}-1$ Activity in vitro

  • Cho, Sang-Min;Kim, Sung-Kuk;Chang, Jong-Soo
    • Biomedical Science Letters
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    • v.12 no.4
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    • pp.419-425
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    • 2006
  • Phospholipase $C-{\gamma}1\;(PLC-{\gamma}1)$ is an important signaling molecule for cell proliferation and differentiation. $PLC-{\gamma}1$ contains two pleckstrin homology (PH) domains, which are responsible for protein-protein interaction and protein-lipid interaction. $PLC-{\gamma}1$ also has two Src homology (SH)2 domains and a SH3 domain, which are responsible for protein- protein interaction. To identity proteins that specifically binds to PH domain of $PLC-{\gamma}1$, we prepared and incubated the glutathione S-transferase(GST)-fused PH domains of $PLC-{\gamma}1$ with COS7 cell lysate. We found that 90 kDa protein specifically binds to PH domain of $PLC-{\gamma}1$. By matrix-assisted laser desorption ionization time of flight-mass spectrometry, the 90 kDa protein revealed to be heat shock protein (Hsp) $90{\beta}$. Hsp $90{\beta}$ is a molecular chaperone that stabilizes and facilitates the folding of proteins that are involved in cell signaling, including receptors for steroids hormones and a variety of protein kinases. To know whether Hsp $90{\beta}$ affects on $PLC-{\gamma}1$ activity, we performed $PIP_2$ hydrolyzing activity of $PLC-{\gamma}1$ in the presence of purified Hsp $90{\beta}$ in vitro. Our results show that the Hsp $90{\beta}$ dose-dependently inhibits the enzymatic activity of $PLC-{\gamma}1$ and further suggest that Hsp $90{\beta}$ regulates cell growth and differentiation via regulation of $PLC-{\gamma}1$ activity.

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Demands and distribution of hysteretic energy in moment resistant self-centering steel frames

  • Lopez-Barraza, Arturo;Ruiz, Sonia E.;Reyes-Salazar, Alfredo;Bojorquez, Eden
    • Steel and Composite Structures
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    • v.20 no.5
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    • pp.1155-1171
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    • 2016
  • Post-tensioned (PT) steel moment resisting frames (MRFs) with semi-rigid connections (SRC) can be used to control the hysteretic energy demands and to reduce the maximum inter-story drift (${\gamma}$). In this study the seismic behavior of steel MRFs with PT connections is estimated by incremental nonlinear dynamic analysis in terms of dissipated hysteretic energy ($E_H$) demands. For this aim, five PT steel MRFs are subjected to 30 long duration earthquake ground motions recorded on soft soil sites. To assess the energy dissipated in the frames with PT connections, a new expression is proposed for the hysteretic behavior of semi-rigid connections validated by experimental tests. The performance was estimated not only for the global $E_H$ demands in the steel frames; but also for, the distribution and demands of hysteretic energy in beams, columns and connections considering several levels of deformation. The results show that $E_H$ varies with ${\gamma}$, and that most of $E_H$ is dissipated by the connections. It is observed in all the cases a log-normal distribution of $E_H$ through the building height. The largest demand of $E_H$ occurs between 0.25 and 0.5 of the height. Finally, an equation is proposed to calculate the distribution of $E_H$ in terms of the normalized height of the stories (h/H) and the inter-story drift.

Effect of Rocatec system on Shear Bond Strength between Zir-Ceram and Sinfony Indirect Composite Resin (Rocatec system이 Zir-ceram과 간접복합수지간의 전단결합강도에 미치는 영향)

  • Kim, Dong-Il;Kim, Bu-Sob;Chung, In-Sung
    • Journal of Technologic Dentistry
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    • v.30 no.2
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    • pp.23-29
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    • 2008
  • The purpose of this study is to evaluate possibility of using indirect composite resin instead of porcelain through the measurement of shear bond strength between zirconia core and indirect composite resin under treatment of $Rocatec^{TM}$ system for improving the adhesion of indirect composite resin. 20 cylindrical zirconia core specimens were divided into 2 groups, according to zirconia surface treatment and attached materials: 1) treated with sandblast and attached with indirect composite resin, 2) treated with sandblast + $Rocatec^{TM}$ system and attached with indirect composite resin. The shear bond strength of each experimental group was measured by MTS and the changes of zirconia core surface according to surface treatments were obtained by SEM observation and measurements of surface roughness. The mean shear bond strength values are $0.55\;{\pm}\;0.11MPa$(Group SC) and $1.16\;{\pm}\;0.46MPa$(Group SRC). The mean Ra values for the surface treatments were follows: $0.39\;{\pm}\;0.13$($100{\beta}_{{\mu}m}$ sandblast) and $0.50\;{\pm}\;0.03$($100{\beta}_{{\mu}m}$ sandblast + $Rocatec^{TM}$ system). In the analysis of EDS, Si element was detected in the Group SC. The shear bond strength between zirconia core and indirect composite resin was improved significantly by using $Rocatec^{TM}$ system.

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Targeting SHCBP1 Inhibits Cell Proliferation in Human Hepatocellular Carcinoma Cells

  • Tao, Han-Chuan;Wang, Hai-Xiao;Dai, Min;Gu, Cheng-Yu;Wang, Qun;Han, Ze-Guang;Cai, Bing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5645-5650
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    • 2013
  • Src homology 2 domain containing (SHC) is a proto-oncogene which mediates cell proliferation and carcinogenesis in human carcinomas. Here, the SHC SH2-domain binding protein 1 (SHCBP1) was first established to be up-regulated in human hepatocellular carcinoma (HCC) tissues by array-base comparative genome hybridization (aCGH). Meanwhile, we examine and verify it by quantitative real-time PCR and western blot. Our current data show that SHCBP1 was up-regulated in HCC tissues. Overexpression of SHCBP1 could significantly promote HCC cell proliferation, survival and colony formation in HCC cell lines. Furthermore, knockdown of SHCBP1 induced cell cycle delay and suppressed cell proliferation. Furthermore, SHCBP1 could regulate the expression of activate extracellular signal-regulated kinase 1/2 (ERK1/2) and cyclin D1. Together, our findings indicate that SHCBP1 may contribute to human hepatocellular carcinoma by promoting cell proliferation and may serve as a molecular target of cancer therapy.

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

  • Liu, Ying;Liu, Chuan-Xia;Wu, Zhong-Ting;Ge, Lin;Zhou, Hong-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4621-4625
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    • 2013
  • The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

Role of Retinoic Acid in Spontaneous Apoptosis of Human Neutrophils

  • Yang, Eun-Ju;Lee, Ji-Sook;Kim, Dong-Hee;Min, Bok-Kee;Hyun, Sung-Hee;Kim, In-Sik
    • Biomedical Science Letters
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    • v.13 no.4
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    • pp.279-285
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    • 2007
  • Although retinoic acid has been known as either anti-inflammatory or pro-inflammatory molecule, depending on the cell type, its exact role in mature human neutrophils has not been fully explored. In this study, we investigate the effects of retinoic acid on neutrophil apoptosis and the associated mechanism and found that 9-cis retinoic acid (9CRA) significantly inhibits the spontaneous apoptosis of neutrophils. Its effect is increased by co-treatment with $TNF-\alpha$ (P<0.05). The 9CRA-induced inhibition is blocked by the following enzyme inhibitors: Ly 294002, phosphoinoside (PI)-3 kinase inhibitor, U73122, a phospholipase C (PLC) inhibitor, PP2, Src family protein inhibitor, SB202190, p38 MAPK inhibitor, and BAY-11-7085, NF-kB inhibitor. This study also demonstrates that all-trans retinoic acid suppresses spontaneous apoptosis, similar to the mechanism of inhibition exhibited by 9CRA. Phosphorylation of p38 MAPK decreases by 9CRA treatment. $Ik-B{\alpha}$ is degraded until 30 minutes after a time-dependent 9CRA treatment, but degradation can be inhibited by Ly 294002. These results indicate that 9CRA decreases p38 MAPK activation, induces NF-kB activation via PI-3 kinase, and also blocks cleavage of caspase 3. As these findings suggest, 9CRA has a molecular mechanism which may help pro-inflammatory response by blocking neutrophil apoptosis.

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Immunostimulatory Activities of Polysaccharides from Liquid Culture of Pine-Mushroom Tricholoma matsutake

  • Kim, Joo-Young;Byeon, Se-Eun;Lee, Yong-Gyu;Lee, Ji-Yeon;Park, Jong-Sun;Hong, Eock-Ki;Cho, Jae-Youl
    • Journal of Microbiology and Biotechnology
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    • v.18 no.1
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    • pp.95-103
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    • 2008
  • Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. Polysaccharide ${\beta}$-glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we compared the immunostimulatory potency of polysaccharide fractions, prepared from liquid culture of pine-mushroom Tricholoma matsutake, with a potent immunogen lipopolysaccharide (LPS), and their molecular mechanisms on the functional activation of macrophages. We found that fraction II (TMF-II) was able to comparably upregulate or highly enhance the phenotypic functions of macrophages such NO production and cytokine (IL-$1{\beta}$, IL-6, IL-12, and TNF-${\alpha}$) expression, to LPS. TMF-II triggered the phosphorylation of $I{\kappa}B{\alpha}$, a critical step for NF-${\kappa}B$ activation and translocation. Of the upstream signaling enzymes tested, Src and Akt were thought to be the responsible upstream signaling components in induction of NO production, although TMF-II strongly upregulated the phosphorylation of all MAPK pathways. Therefore, our data suggest that T. matsutake-derived ${\beta}$-glucan may exert its immunostimulating activities with similar potency to LPS via activation of multiple signaling pathways linked to NF-${\kappa}B$ activation.

Properties on the Freeze-Thaw of Concrete Subjected to Seawater Attack (해수의 영향을 받은 콘크리트의 동결융해 특성)

  • Park, Kwang-Pil;Kim, Seong-Soo;Lee, Seung-Tae;Kim, Jong-Pil;Jung, Ho-Seop
    • Journal of the Korea Concrete Institute
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    • v.23 no.1
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    • pp.23-30
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    • 2011
  • In this study, deterioration degrees of concrete were investigated at laboratory under seawater attack and cycling freeze-thaw, which are major durability performance deterioration factors of concrete. Deteriorations of mixed concrete using Portland & blended cement were examined by instrumental analysis of changes in relative dynamic modulus of elasticity and compressive strength. After 520 cycles of freeze-thaw, relative dynamic modulus of elasticity and compressive strength of concrete mixed with normal Portland and LHC over 75% showed relatively low resistance of approximately 44% of those values of SRC. Concrete replaced with 50% fine powder of blast furnace slag showed the most excellent freeze-thaw resistance among the tested blended cement concrete.