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Anticancer Effects of the Hsp90 Inhibitor 17-Demethoxy-Reblastatin in Human Breast Cancer MDA-MB-231 Cells

  • Zhao, Qing;Wu, Cheng-Zhu;Lee, Jae Kyoung;Zhao, Su-Rong;Li, Hong-Mei;Huo, Qiang;Ma, Tao;Zhang, Jin;Hong, Young-Soo;Liu, Hao
    • Journal of Microbiology and Biotechnology
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    • v.24 no.7
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    • pp.914-920
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    • 2014
  • Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel non-benzoquinone-type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.

Description of Cellobiohydrolases Ce16A and Ce17A from Trichoderma reesei Using Langmuir-type Models

  • Kim, Dong-Won;Hong, Young-Gwan
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.6 no.2
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    • pp.89-94
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    • 2001
  • The binding of cellobiohydrolases to cullulose is a crucial initial step in cellulose hydrolysis. In the search for a detailed understanding of the function of cellobiohydrolases, much information concerning how the enzymes and their constituent catalytic and cellulose-binding changes during hydrolysis is still needed. The adsorption of purified two cellobiohydrolases (Ce17A and Ce16A) from Trichoderma reesei cellulase to microcrystalline cellulose has been studied. Cellobiohydrolase II (Ce16A) does not affect the adsorption of cellobiohydrolase I (Ce17A) significantly, and there are specific binding sites for both Ce17A and Ce16A. The adsorption affinity and tightness of the cullulase binding domain (CBD) for Ce17A are larger than those of the CBD for Ce16A. The CBD for Ce17A binds more rapidly and tightly to Avicel than the CBD for Ce16A. The decrease in adsorption observed when the two cellobihydrolases are studied together would appear to be the result of competition for binding sites on the cellulose. Ce17A competes more efficiently for binding sites than Ce16A. Competition for binding sites is the dominating factor when the two enzymes are acting together, furthermore adsorption to sites specific for Ce17A and Ce16A, also contributes to the total adsorption.

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Insulin Resistance and Serum Levels of Interleukin-17 and Interleukin-18 in Normal Pregnancy

  • Jahromi, Abdolreza Sotoodeh;Shojaei, Mohammad;Ghobadifar, Mohamed Amin
    • IMMUNE NETWORK
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    • v.14 no.3
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    • pp.149-155
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    • 2014
  • We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked immunosorbent assay (ELISA). Insulin resistance was measured by homeostasis model assessment of insulin resistance equation. No significant differences between the demographic data of the pregnant and non pregnant groups were observed. Insulin resistant in pregnant women was significantly higher than the controls (p=0.006). Serum IL-17 concentration was significantly different in non pregnant women and pregnant women in all gestational ages (p<0.05). Serum IL-18 level was significantly lower in subjects with first, second, and third trimesters of pregnancy in compared to non pregnant women (p<0.05). No significant correlations were found between serum IL-17 and IL-18 levels with insulin resistance (r=0.08, p=0.34 vs. r=0.01, p=0.91, respectively). Our data suggested that IL-17 and IL-18 do not appear to attribute greatly to pregnancy deduced insulin resistance during normal pregnancy.

Th17 Responses Are not Induced in Dextran Sodium Sulfate Model of Acute Colitis

  • Kim, Yoon-Suk;Lee, Min-Ho;Ju, Ahn-Seung;Rhee, Ki-Jong
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.416-419
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    • 2011
  • Dextran sodium sulfate (DSS) is a widely used chemical model for inflammatory bowel disease (IBD). It is thought that imbalances in the T helper (Th) cell subsets contribute to IBD. Recent studies suggest that the acute DSS-colitis model is polarized toward a Th1/Th17 profile based on RT-PCR analysis of colonic tissues. In the current study we determined whether colonic Th cells from DSS-colitis mice were skewed toward the Th17 profile. Mice were treated with 5% DSS for 7 days and colonic T cells isolated and examined for production of IFN-${\gamma}$ (Th1 cell), IL-4 (Th2 cell) and IL-17 (Th17 cell) by intracellular flow cytometry. We found that the percentage of colonic Th17 cells were similar to non-treated controls but the percentage of Th1 cells were elevated in DSS-colitis mice. These results suggest that in the acute DSS-colitis model the colonic Th cells exhibit a Th1 profile and not a Th17 profile.

Preparation of Hard Magnetic $Sm_2Fe_{17}N_x$ Compound by Mechanical Alloying (기계적 합금화법에 의한 영구자석용 $Sm_2Fe_{17}N_x$ 화합물의 제조)

  • 이충효;김명근;석명진;김지순;윤석길;권영순
    • Journal of Powder Materials
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    • v.8 no.1
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    • pp.55-60
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    • 2001
  • Mechanical alloying technique was applied to prepare hard magnetic $Sm_2Fe_{17}N_x$ compound powders. Staring from pure Fe and Sm powders, the formation process of hard magnetic $Sm_2Fe_{17}N_x$ phase by mechanical alloying and subsequent solid state reaction was studied. As milled powders were found to consist of Sm-Fe amorphous and $\alpha$-Fe phases in all compositions of $Sm_xFe_{100-x}$(x = 11, 13, 15, 17). The effects of starting composition on the formation of $Sm_2Fe_{17}$ intermetallic compound was investigated by heat treatment of mechanically-alloyed powders. When Sm content was 15 at.%, heat-treated powders consisted of nearly $Sm_2Fe_{17}$ single phase. For preparation of hard magnetic $Sm_2Fe_{17}N_x$ powders, additional nitriding treatment was performed under $N_2$ gas flow at 45$0^{\circ}C$. The increase in the coercivity and remanence was proportional to the nitrogen content which increased drastically at first and then increased gradually as the nitriding time was extended to 3 hours.

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The Effect of Galangin on the Regulation of Vascular Contractility via the Holoenzyme Reactivation Suppressing ROCK/CPI-17 rather than PKC/CPI-17

  • Yoon, Hyuk-Jun;Jung, Won Pill;Min, Young Sil;Jin, Fanxue;Bang, Joon Seok;Sohn, Uy Dong;Je, Hyun Dong
    • Biomolecules & Therapeutics
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    • v.30 no.2
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    • pp.145-150
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    • 2022
  • In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway. Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoride-dependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.

Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation

  • Hyuk-Jun Yoon;Heui Woong Moon;Young Sil Min;Fanxue Jin;Joon Seok Bang;Uy Dong Sohn;Hyun Dong Je
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.361-367
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    • 2024
  • In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.

Monitoring Bacterial Population Dynamics Using Real-Time PCR During the Bioremediation of Crude-Oil-Contaminated Soil

  • Baek, Kyung-Hwa;Yoon, Byung-Dae;Cho, Dae-Hyun;Kim, Byung-Hyuk;Oh, Hee-Mock;Kim, Hee-Sik
    • Journal of Microbiology and Biotechnology
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    • v.19 no.4
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    • pp.339-345
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    • 2009
  • We evaluated the activity and abundance of the crude-oil-degrading bacterium Nocardia sp. H17-1 during bioremediation of oil-contaminated soil, using real-time PCR. The total petroleum hydrocarbon(TPH) degradation rate constants(k) of the soils treated with and without H17-1 were $0.103\;d^{-1}$ and $0.028\;d^{-1}$ respectively. The degradation rate constant was 3.6 times higher in the soil with H17-1 than in the soil without H17-1. In order to detect and quantify the Nocardia sp. H17-1 in soil samples, we quantified the genes encoding 16S ribosomal RNA(16S rRNA), alkane monooxygenase(alkB4), and catechol 2,3-dioxygenase(23CAT) with real-time PCR using SYBR green. The amounts of H17-1 16S rRNA and alkB4 detected increased rapidly up to 1,000-folds for the first 10 days, and then continued to increase only slightly or leveled off. However, the abundance of the 23CAT gene detected in H17-1-treated soil, where H17-1 had neither the 23CAT gene for the degradation of aromatic hydrocarbons nor the catechol 2,3-dioxygenase activity, did not differ significantly from that of the untreated soil($\alpha$=0.05,p>0.22). These results indicated that H17-1 is a potential candidate for the bioaugmentation of alkane-contaminated soil. Overall, we evaluated the abundance and metabolic activity of the bioremediation strain H17-1 using real-time PCR, independent of cultivation.

Ciglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Ligand, Inhibits Proliferation and Differentiation of Th17 Cells

  • Kim, Dong Hyeok;Ihn, Hyun-Ju;Moon, Chaerin;Oh, Sang-Seok;Park, Soojong;Kim, Suk;Lee, Keun Woo;Kim, Kwang Dong
    • Biomolecules & Therapeutics
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    • v.23 no.1
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    • pp.71-76
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    • 2015
  • Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

Projection and Burnup Trends of Spent Nuclear Fuel in Korea (국내 사용후핵연료 현황 분석)

  • 조동건;최종원;이희환
    • Proceedings of the Korean Radioactive Waste Society Conference
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    • 2004.06a
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    • pp.261-267
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    • 2004
  • Inventories, projections, and characteristics of spent nuclear fuel(SNF) generated from domestic nuclear power plants were updated to support high-level waste disposal system design. The historical and projected inventory by the end 2055 is expected to be 20,500 and 14,800MTU for PWR and CANDU spent nuclear fuel, respectively The ratio of quantity for TEX>$17{\times}17$ SNF was shown to be 0.6 as of 2003. The amount of TEX>$17{\times}17$ SNF, however, will be less than that of TEX>$16{\times}16$ KSFA after 2012, while the quantity of TEX>$16{\times}16$ KSFA will reach to 70% of the total spent fuels in the 2055. Average turnup of SNF revealed ~36GWD/MTU and ~40GWD/MTU for the period of 1994-1999 and 2000-2003, respectively. It is expected that the average burnup of SNF will exceed 45GWD/MTU at the end of 2000's. Therefore, it seems reasonable to use the TEX>$17{\times}17$ 4.5w/o, 45GWD/MTU as the Reference SNF at present state. The TEX>$16{\times}16$ KSFA 4.5w/o, 55GWD/MTU, however, should be Reference SNF after ~2010.

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