• Title/Summary/Keyword: Model compound

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Behavior of Soil-reinforced Retaining Walls in Tiered Arrangement (계단식 보강토 옹벽의 거동 특성)

  • Yoo, Choong-Sik;Kim, Joo-Suk
    • Journal of the Korean Geotechnical Society
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    • v.18 no.3
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    • pp.61-72
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    • 2002
  • This paper presents the results of investigation on the behavior of soil-reinforced segmental retaining walls in tiered arrangement using the finite element method of analysis. 2D finite element analyses were performed on tiered walls with two levels of offset distance. Cases with equivalent surcharge as suggested by the NCMA design guideline were additionally analyzed in an attempt to confirm the appropriateness of the equivalent surcharge model adopted by NCMA. Deformation characteristics of a tiered wall with small offset distance suggest a compound mode of failure and support current design approaches requiring a global slope stability analysis for design. Also revealed is that the interaction between the upper and lower walls significantly affects not only the performance of the lower wall but also the upper wall, suggesting that the upper walls should also be designed with due consideration of the interaction.

NSM00158 Specifically Disrupts the CtBP2-p300 Interaction to Reverse CtBP2-Mediated Transrepression and Prevent the Occurrence of Nonunion

  • Chen, Xun;Zhang, Wentao;Zhang, Qian;Song, Tao;Yu, Zirui;Li, Zhong;Duan, Ning;Dang, Xiaoqian
    • Molecules and Cells
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    • v.43 no.6
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    • pp.517-529
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    • 2020
  • Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.

Aquatic Toxicities of Major Antimicrobial and Anthelmintic Veterinary Pharmaceuticals and their Potential Ecological Risks

  • Oh, Su-Gene;Kim, Jung-Kon;Park, So-Young;Lee, Min-Jung;Choi, Kyung-Ho
    • Proceedings of the Korean Environmental Health Society Conference
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    • 2004.06a
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    • pp.173-177
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    • 2004
  • The acute toxicities of two major anti-pathogenic veterinary medicines, i.e., ciprofloxacin and enrofloxacin, and six benzimidazole anthelmintics, i.e., albendazole, thiabendazole, flubendazole, febantel, fenbendazole, and oxfendazole, were evaluated with a marine bacterium, Vibrio fischeri, and invertebrate Daphnia magna. These veterinary medical products have been widely used for farm animals, but their impact on aquatic fauna has seldom been investigated. In general, daphnids responded as much as 3 orders of magnitude more sensitively to the tested pharmaceuticals than the microbes. For Daphnia, the most toxic product among the tested anthelmintics was fenbendazole, followed by flubendazole > albendazole ${\approx}$ febantel > thiabendazole > oxfendazole. Daphnids' EC50 values obtained from 48 to 96 hrs of fenbendazole exposure ranged from 2.7 to 6.3 ug/L. The mixture toxicity of the test pharmaceuticals was generally additive in nature and was well predicted by a concentration addition model. Using the predicted no effect concentrations (PNECs) of the benzimidazole derivatives estimated from this study, and predicted environmental concentrations (PECs) of these pharmaceuticals, the risk quotients of each anthelmintics were calculated. Most of the test anthelmintic compounds resulted in risk quotients greater than 1. Especially, risk quotient for fenbendazole was 2,791, which strongly indicates this compound might cause severe ecological consequences, should no future action be taken. This study is the first report on the aquatic toxicities and potential ecological risk of major anthelmintic and antimicrobial veterinary products in Korea. The result of this study provides information necessary for conducting more detailed ecological risk assessment of pharmaceutical products in ambient water and guiding proper management decision.

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Action Mechanism of LB10522, a New Catechol-Substituted Cephalosporin (카테콜 치환체를 가진 세파로스포린계 항생제 LB10522의 작용기전)

  • Kim, Mu-Yong;Oh, Jeong-In;Paek, Kyoung-Sook;Kim, In-Chull;Kwak, Jin-Hwan
    • YAKHAK HOEJI
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    • v.40 no.1
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    • pp.102-111
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    • 1996
  • LB10522 is a new parenteral broad spectrum cephalosporin with a catechol moiety at C-7 position of beta-lactam ring. This compound can utilize tonB-dependent iron transp ort system in addition to porin proteins to enter bacterial periplasmic space and access to penicillin-binding proteins (PBPs) which are the lethal targets of ${\beta}$-lactam antibiotics. The chelating activity of LB10522 to metal iron was measured by spectrophotometrically scanning the absorbance from 200 to 900nm. When $FeCl_3$ was added, optical density was increased between 450 and 800nm. LB10522 was more active against gram-negative strains in iron-depleted media than in iron-replete media. This is due to the increased expression of iron transport channels in iron-depleted condition. LB10522 showed a similar activity against E. coli DC2 (permeability mutant) and E. coli DCO (wild type strain) in both iron-depleted and iron-replete media, indicating a minimal permeaility barrier for LB10522 uptake. LB10522 had high affinities to PBP 3 and PBP 1A, 1B of E. coli. By blocking these proteins, LB10522 caused inhibition of cell division and the eventual death of cells. This result was correlated well with the morphological changes in E. coli exposed to LB10522. Although the in vitro MIC of LB10522 against P. aeruginosa 1912E mutant (tonB) was 8-times higher than that of the P. aeruginosa 1912E parent strain, LB10522 showed a similar in vivo protection efficacy against both strains in the mouse systemic infection model. This result suggested that tonB mutant, which requires a high level of iron for normal growth, might have a difficulty in surviving in their host with an iron-limited environment.

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Synthesis and Crystal Structure of 1-(dimethylbromotin)-2-[(methoxyl)methly]-o-carborane $(C_{16}H_{21}B_{10}BrOSn)$ (1-(Dimethylbromotin)-2-[(methoxyl) methly]-o-carborane $(C_{16}H_{21}B_{10}BrOSn)$의 합성 및 결정 구조)

  • Cho Sung Il;Kang Sang Ook;Chang K.
    • Korean Journal of Crystallography
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    • v.15 no.2
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    • pp.88-92
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    • 2004
  • An organometallic compound, $(C_{16}H_{21}B_{10}BrOSn)$, was synthesized from o-carborane, closo-1-[(methoxyl)methyl]-o-carborane $(HCab^o)$, and $SnMe_2Br_2$. The molecular structure of this complex has been determined by X-ray diffraction. Crystallographic data: orthorhombic, space group Pna2, a = 17.9292(15)$\AA$, b= 7.2066(4)$\AA$, c=13.0582(10)$\AA$, Z=4, V=1687.2(2) $\AA^3$. The structure was solved by direct methods and refined by full-matrix least-squares methods to give a model with a reliability factor R=0.0574 for 1724 reflections.

Effects of Supercritical Fluid Extract, Shikonin and Acetylshikonin from Lithospermum erythrorhizon on Chondrocytes and MIA-Induced Osteoarthritis in Rats (지치의 초임계추출물, Shikonin 및 Acetylshikonin의 연골세포 및 MIA 유도 관절염 모델에서의 효과)

  • Kim, Geum Soog;Kim, Hwa Jin;Lee, Dae Young;Choi, Seung Min;Lee, Seung Eun;Noh, Hyung Jun;Choi, Jong Gil;Choi, Soo Im
    • Korean Journal of Medicinal Crop Science
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    • v.21 no.6
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    • pp.466-473
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    • 2013
  • This study investigates the effect of supercritical fluid extract (CMPB803-C) of Lithospermum erythrorhizon, shikonin and acetylshikonin isolated from Lithospermum erythrorhizon on IL-$1{\beta}$-induced chondrocytes and monosodium iodoacetate (MIA)-induced osteoarthritis in rat. Shikonin ($50{\mu}m$) and acetylshikonin ($3{\mu}M$) treatment reduced significantly the mRNA expression and enzyme activity of matrix metalloproteinase (MMP)-1, -3 and -13 in IL-$1{\beta}$-induced SW1353 chondrosarcoma cells. The chondro-protective effects of CMPB803-C and acetylshikonin were than analyzed in a rat OA model using a single intra-articular injection of MIA (1mg) in the right knee joint. CMPB803-C (200mg/kg) or acetylshikonin (5mg/kg) was orally administered daily for two weeks starting after 1 week of MIA injection. In the histological observation, CMPB803-C and acetylshikonin clearly improved OA lesions being comparable to or better that control group. Our results demonstrated that CMPB803-C and acetylshikonin as active compound of Lithospermum erythrorhizon have a strong chondro-protective effect in OA rats, which likely attributes to its anti-inflammatory activity and inhibition of MMPs production.

Inhibition of gene associated with Dyslipidemia and Antioxidative Effect of Artemisia iwayomogi, Curcumae Radix and Raphani Semen(ACR) on HepG2 cell model (HepG2 cell을 이용한 한인진, 울금, 나복자 복합물(ACR)의 이상지질혈증 관련 유전자 발현 억제 및 항산화 효능 평가)

  • Cha, Jiyun;Yoo, Ho-ryong;Kim, Yoon-sik;Seol, In-chan;Jo, Hyun-kyung
    • The Journal of Korean Medicine
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    • v.38 no.3
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    • pp.43-58
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    • 2017
  • Objectives: We performed this study to evaluate the antioxidative and hypolipidemic effect of Artemisia iwayomogi (韓茵蔯), Curcuma longa L. (鬱金) and Raphanus sativus L. (蘿?子) (ACR). Method: We enriched Artemisiae Capillaris, Curcumae Longae and Raphani Semen compound with alcohol. ACR extract is treated to HepG2 cell. Cell groups are devided into 3 groups: normal, control and ACR treated group. We measured polyphenol, flavonoids, DPPH and ABTS radical scavenging activity, ROS, glutathione, GSH peroxidase, GSH reductase, SOD, catalase, free fatty acid, lipid peroxidation and suppression of ACAT1 and HMG-CoA reductase expression on mRNA level. Results: 1. ACR contained polyphenol and flavonoids and increased GSH significantly in HepG2 cell. 2. ACR increased GPx, GR, and catalase activity significantly in HepG2 cell. 3. ACR increased DPPH and ABTS radical scavenging activity significantly in HepG2 cell and decreased ROS. 4. ACR decreased free fatty acid and MDA significantly in HepG2 cell. 5. ACR suppressed ACAT1 and HMG-CoA reductase expression on mRNA level in HepG2 cell. Conclusion: This study suggests that ACR has antioxidative and hypolipidemic effect and might be effective in prevention and treatment of dyslipidemia.

Control of Gaseous Styrene Using a Bioactive Foam Reactor (계면활성제 미생물반응기를 이용한 기체상 스타이렌 제어)

  • Shin, Shoung-Kyu;Song, Ji-Hyeon
    • Journal of Korean Society of Environmental Engineers
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    • v.28 no.7
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    • pp.770-775
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    • 2006
  • Biofilters packed with various materials commonly show problems such as low performance and clogging in a long-term operation. Recently, a bioactive foam reactor(BFR) using surfactants has been suggested to ensure efficient and stable VOCs removal performance. This study was mainly conducted to investigate the feasibility of the BFR system using styrene as a model compound. An abiotic md a biotic tests were conducted to estimate a mass transfer coefficient($K_La$) and a specific substrate utilization coefficient(k) for the BFR, showing the rate of mass transfer was greater in the BFR than in other diffuser systems. A dynamic loading test also indicated that the performance of the BFR was stable under a shock loading condition. Furthermore, the maximum elimination capacity of the BFR was determined to be 109 $g/m^3/hr$ for styrene, which was much higher than those for biofilter systems generally reported in the literature. Overall, the experimental results suggest that the BFR be a potential alternative to the conventional packed-bed biofilters.

The Ion Transport Phenomena through the Liquid Membrane with Macrocyclic Compound (I). Mechanism of Potassium Ion Transport through $H_2O-CHl_3-H_2O$ System with Dibenzo-18-Crown-6 (마크로고리 화합물을 운반체로 하는 액체막을 통한 이온의 운반에 관한 연구 (제1보). Dibenzo-18-Crown-6-(DBC)/$H_2O-CHCl_3-H_2O$계에서 칼륨이온의 운반 메카니즘)

  • Yoon, Chang-Ju;Lee, Shim-Sung;Koo, Chang-Hyun;Kim, Si-Joong
    • Journal of the Korean Chemical Society
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    • v.28 no.3
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    • pp.163-169
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    • 1984
  • The transport rates of $K^+$ion through CHCl$_3$ liquid membrane containing dibenzo-18-crown-6(DBC) as a carrier molecule have been determined at $25^{\circ}C$. The transport rates depend highly on the ion concentration and on the nature of anion. It is concluded that $K^+$ions are transported in the form of ion-pair. In the case of potassium picrate, however, it is found that the transport proceeds with the formation of the incomplete ion-pair in the concentration less than 1.0 ${\times}10^{-3}$M of picrate, while with the complete formation of ion-pair in the concentration more than 1.0 ${\times}10^{-3}$M of picrate. Seven steps of the transport process are suggested and they can be illustrated in terms of energy barrier model as a function of the position of ionic species in the membrane.

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Influence of Phenobarbital on the Hepatic Clearance of Organic Anionic Drugs in Rats - On the Basis of Pharmacokinetics of Indocyanine Green - (Rat에 있어서 Phenobarbital이 유기음이온성 의약품의 간클리어란스에 미치는 영향 - Indocyanine Green의 체내동태를 중심으로 -)

  • Lee, Yong-Bok;Shin, Sang-Chul;Koh, Ik-Bae
    • Korean Journal of Clinical Pharmacy
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    • v.3 no.1
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    • pp.31-43
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    • 1993
  • The influence of phenobarbital(PB) pretreatment(75mg/kg/day, Lp. for 4 days) on the hepatic clearance of indocyanine green(ICG) as a model compound of organic anionic drugs was investigated in rats in order to elucidate the relative contributions of change in the hepatic blood flow versus increase in the hepatic intrinsic activity to remove ICG due to PB pretreatment. ICG(1mg/kg) was injected single bolus via femoral or portal vein to the control and the PB-pretreated rats. The initial hepatic uptake clearance$(V_{d.c.}K_{12})$ obtained from plasma concentration-time data was increased by $38.4\% in the PB-pretreated rats, which may be due to the increased hepatic blood flow by PB pretreatment. Using a pharmacokinetic approach, hepatic blood flows were estimated of 67.5ml/min/kg in control rats and 91.9ml/min/kg in PB-pretreated rats. They were in good agreement with other's blood flow estimates observed experimentally. It may be concluded that the $38\%$ increased initial hepatic uptake clearance of ICG was due to the $36\%$ increased hepatic blood flow with phenobarbital, and that the increased hepatic blood flow and the activated hepatic intrinsic clearance with phenobarbital contributed to $49\%\;and\;51\%$ of the increased systemic clearance of ICG, respectively.

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