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Fibrinolytic and Antiplatelet Aggregation Properties of a Recombinant Cheonggukjang Kinase
Chinzorig Radnaabazar,박충무,김정환,차재호,송영선 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.6
This study characterized the efficacy of recombinant Cheonggukjang kinase (CGK) 3–5-rich fraction as a thrombolytic agent, which we overexpressed in Bacillus licheniformis ATCC10716, a strain normally lacking fibrinolytic activity. We found that CGK3-5 is a plasmin-like protease that directly degrades fibrin clots and does not activate plasminogen during fibrin clot lysis and platelet-rich clot lysis assays. We also confirmed antiplatelet and antithrombotic activity by CGK3-5-rich fraction both in vitro and in vivo. CGK3-5-rich fraction inhibited collagen-induced platelet aggregation in platelet-rich plasma in a concentration-dependent manner. The concentration of 1.5 mg/mL CGK3-5-rich fraction completely inhibited collagen-induced platelet aggregation. Furthermore, injection of CGK3-5-rich fraction into tail veins dose-dependently protected mice from death by pulmonary embolism induced by collagen and epinephrine. The survival rates were 30%, 70%, and 100%, respectively, with doses of 130 mg/kg, 260 mg/kg, and 520 mg/kg. These findings suggest that CGK3-5 holds promise as a treatment to mitigate the potentially effects of stroke and heart failure.
Hierarchical Cluster Analysis Histogram Thresholding with Local Minima
Sengee, Nyamlkhagva,Radnaabazar, Chinzorig,Batsuuri, Suvdaa,Tsedendamba, Khurel-Ochir,Telue, Berekjan Korea Multimedia Society 2017 The journal of multimedia information system Vol.4 No.4
In this study, we propose a method which is based on "Image segmentation by histogram thresholding using hierarchical cluster analysis"/HCA/ and "A nonparametric approach for histogram segmentation"/NHS/. HCA method uses that all histogram bins are one cluster then it reduces cluster numbers by using distance metric. Because this method has too many clusters, it is more computation. In order to eliminate disadvantages of "HCA" method, we used "NHS" method. NHS method finds all local minima of histogram. To reduce cluster number, we use NHS method which is fast. In our approach, we combine those two methods to eliminate disadvantages of Arifin method. The proposed method is not only less computational than "HCA" method because combined method has few clusters but also it uses local minima of histogram which is computed by "NHS".
Hye Yeon Cho,Chung Mu Park,Mi Jeong Kim,Radnaabazar Chinzorig,Chung Won Cho,Young Sun Song 한국영양학회 2011 Nutrition Research and Practice Vol.5 No.5
We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-α exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)κB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFκB transactivation might be partially related to the down-regulation of these mRNAs in TNF-α-stimulated HUVECs.
Ryoo, Soo-Ryoon,Cho, Hyun-Jeong,Lee, Hye-Won,Jeong, Hey Kyeong,Radnaabazar, Chinzorig,Kim, Yeun-Soo,Kim, Min-Jeong,Son, Mi-Young,Seo, Hyemyung,Chung, Sul-Hee,Song, Woo-Joo Blackwell Publishing Ltd 2008 Journal of Neurochemistry Vol.104 No.5
<P>Abstract</P><P>Most individuals with Down Syndrome (DS) show an early-onset of Alzheimer’s disease (AD), which potentially results from the presence of an extra copy of a segment of chromosome 21. Located on chromosome 21 are the genes that encode &bgr;-amyloid (A&bgr;) precursor protein (<I>APP</I> ), a key protein involved in the pathogenesis of AD, and dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A (<I>DYRK1A</I> ), a proline-directed protein kinase that plays a critical role in neurodevelopment. Here, we describe a potential mechanism for the regulation of AD pathology in DS brains by DYRK1A-mediated phosphorylation of APP. We show that APP is phosphorylated at Thr668 by DYRK1A <I>in vitro</I> and in mammalian cells. The amounts of phospho-APP and A&bgr; are increased in the brains of transgenic mice that over-express the human DYRK1A protein. Furthermore, we show that the amounts of phospho-APP as well as those of APP and DYRK1A are elevated in human DS brains. Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the over-expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.</P>
Cho, Hye-Yeon,Park, Chung-Mu,Kim, Mi-Jeong,Chinzorig, Radnaabazar,Cho, Chung-Won,Song, Young-Sun The Korean Nutrition Society 2011 Nutrition Research and Practice Vol. No.
We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-${\alpha}$-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-${\alpha}$ exposure significantly increased expression of monocyte chemoattractant protein (MCP)-l, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-l and VCAM-l production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-l production. The effects of genistein and daidzein on MCP-l secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-${\alpha}$ exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)${\kappa}$B activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-l and eNOS expression than that of daidzein. Additionally, NF${\kappa}$B transactivation might be partially related to the down-regulation of these mRNAs in TNF-${\alpha}$-stimulated HUVECs.
RAW264.7 Macrophage Cell에서 녹차씨껍질 에틸아세테이트 분획의 염증억제 효과 및 기전 연구
노경희(Kyung-Hee Noh),장지현(Ji-Hyun Jang),민관희(Kwan-Hee Min),친조리그 라드나바자르(Radnaabazar Chinzorig),이미옥(Mi-Ock Lee),송영선(Young-Sun Song) 한국식품영양과학회 2011 한국식품영양과학회지 Vol.40 No.5
본 연구는 녹차씨껍질 분획 추출물 중 염증 저해능이 강력한 EtOAC분획을 선정하여 대식세포주인 RAW264.7 macrophage cell에서 항염증효과의 기전을 생화학적, 분자학적 수준에서 분석하고자 하였다. 녹차씨껍질 추출물 100 ㎎당 총 페놀함량은 EtOAC분획에서 가장 높은 수준이었으며 EtOH추출물>PE분획>BuOH분획과 H₂O분획의 순으로 나타났다. 또한 EtOAC분획의 NO 억제능이 가장 강한 것으로 나타나, EtOAC분획의 polyphenol을 분석한 결과 EGC(1146.5±11.01 ㎍/g)> tannic acid(967.0±32.24 ㎍/g)> EC(70.9±4.39 ㎍/g)> gallic acid(947.6±1.03 ㎍/g)> caffeic acid(37.7±1.46 ㎍/g)> ECG(35.5±3.19 ㎍/g)> EGCG(15.5±0.09 ㎍/g)의 순으로 나타났다. 녹차씨껍질 EtOAC분획이 RAW264.7 macrophage cell에서 LPS 처리에 의한 산화적 스트레스로 발생되는 NO 생성을 농도 의존적으로 감소시키며(IC50: 80.11 ㎍/mL) PGE₂의 생성을 억제하였다. 염증생성 전사인자인 iNOS의 유전자 발현은 농도 의존적으로 억제시켰으나 COX-2의 단백질 발현에는 영향을 미치지 않았다. 녹차씨껍질 EtOAC분획은 총 항산화능과 GSH 수준을 증가시켜 산화적 스트레스를 경감시키는 역할을 하며 항산화효소계인 catalase, GSH-red 및 Mn-SOD 활성의 단백질 발현을 증가시키는 것으로 나타났다. 핵에서의 p65 농도는 대조군에 비해 녹차씨껍질 EtOAC분획을 처리한 군에서 현저하게 낮은 것으로 나타났다. 이상의 결과에서, 녹차씨껍질 EtOAC분획은 NF-κB 활성을 억제함으로써 iNOS 단백질 발현을 억제하여 NO의 생성을 감소시키고 총 항산화능과 GSH 수준을 증가시키며, 항산화 효소계를 활성화시켜 세포내 산화적 스트레스를 감소시킴으로써 LPS 자극에 의한 염증반응을 지연하거나 억제하는 것으로 사료된다. Green tea seed coat (GTSC) was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether (PE), ethyl acetate (EtOAC) and butanol (BuOH). The EtOAC fraction showed the highest level in total phenol contents and the lowest level in nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophage cell. Thus, this study was carried out to investigate the anti-inflammatory and its mechanisms of GTSC EtOAC fraction in LPS-stimulated RAW264.7 macrophage cell. GTSC EtOAC fraction contained EGC (1146.48±11.01 ㎍/g), tannic acid (966.99±32.24 ㎍/g), EC (70.88±4.39 ㎍/g), gallic acid (947.61±1.03 ㎍/g), caffeic acid (37.69±1.46 ㎍/g), ECG (35.46±3.19 ㎍/g), and EGCG (15.53±0.09 ㎍/g) when analyzed by HPLC. NO production was significantly (p<0.05) suppressed in a dose-dependent manner with an IC50 of 80.11 ㎍/mL. Also prostaglandin E₂ level was also inhibited in a dose-dependent manner. Moreover, iNOS protein expression was suppressed in dose-dependent manner but COX-2 gene expression was not affected. Total antioxidant capacity and glutathione (GSH) levels were enhanced more than the LPS-control. Expressions of antioxidative enzymes including catalase, GSH-reductase and Mn-SOD were elevated compared to LPS-control. Nuclear p65 level was decreased in the GTSC EtOAC fraction in a dose-dependent manner. These results indicate that GTSC EtOAC fraction inhibit oxidative stress and inflammatory responses through elevated GSH levels, antioxidative enzymes expressions and suppression of iNOS expression via NF-κB down-regulation.
Ryu, Young Shin,Park, So Young,Jung, Min-Su,Yoon, Song-Hee,Kwen, Mi-Yang,Lee, Sun-Young,Choi, Sun-Hee,Radnaabazar, Chinzorig,Kim, Mi-Kyoung,Kim, Hangun,Kim, Kwonseop,Song, Woo-Joo,Chung, Sul-Hee Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.115 No.3
<P><I>J. Neurochem.</I> (2010) <B>115</B>, 574–584.</P><P>Abstract</P><P>The dual-specificity tyrosine(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) gene is located on human chromosome 21 and encodes a proline-directed protein kinase that might be responsible for mental retardation and early onset of Alzheimer’s disease (AD) in Down syndrome (DS) patients. Presenilin 1 (PS1) is a key component of the &ggr;-secretase complex in the generation of &bgr;-amyloid (A&bgr;), an important trigger protein in the pathogenesis of AD. Increased Dyrk1A expression has been reported in human AD and DS brains. We previously showed that Dyrk1A increased A&bgr; production in mammalian cells and transgenic mice that over-express Dyrk1A. In this study, we describe a potential mechanism by which A&bgr; is increased in Dyrk1A-over-expressing DS and AD brains. First, we show that PS1 is phosphorylated by the Dyrk1A at Thr<SUP>354</SUP> and that this phosphorylation increases &ggr;-secretase activity. Then, using transgenic mice that over-express human Dyrk1A, we demonstrate that phospho-Thr354-PS1 (pT354-PS1) expression is enhanced when Dyrk1A level is increased. We also show that pT354-PS1 is more stable than the unphosphorylated form of PS1. These results reveal a potential regulatory link between Dyrk1A and PS1 in the A&bgr; pathway of DS and AD brains, suggesting that up-regulated Dyrk1A may accelerate AD pathogenesis through PS1 phosphorylation.</P>