• Title/Summary/Keyword: KDR

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Stimulatory Efect of Cinnamomum cassia Extract on Angiogenesis Through Regulation of VEGF (VEGF 조절을 통한 육계 추출물의 신생혈관 형성 촉진 작용)

  • Ko, Jeong-Min;Lee, Sang-Hoon;Baek, Yong-Hyeon;Choi, Do-Young
    • Journal of Acupuncture Research
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    • v.26 no.1
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    • pp.153-162
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    • 2009
  • 목적 : 한의학 분야에서 육계(CCE: Cinnamomum cassia)는 혈류 순환이 저하된 상태에 널리 쓰이는 약재이다. 이 연구에서는 CCE와 그 활성 혼합물인 cinnamic acid가 in vitro와 in vivo에서 발휘하는 신생혈관 형성 작용에 대해 알아보고자 한다. 방법 : CCE와 CA의 신생혈관형성 작용을 알아보기 위하여 Human unbilical endothelial cells(HUVECs)와 Bovine arterial endothelial cells(BAECs) 그리고 Matrigel assay를 이용하였다. 결과 : In vitro에서 CCE와 그 활성 혼합물은 HUVEC 증식, 이동, 모세혈관-유사 관 형성을 유도한다. CCE에서의 25-50% 증가(1 또는 10ng/ml 용량에서)는 CA에서 증식과 유사하게 나타났다. HUVEC에서는 증식이 뚜렷하게 나타났으나 BAEC에서는 증식이 뚜렷하게 나타나지 않아 증식 효과는 내피세포의 기원에 따라 다른 것으로 나타났다. BAEC는 CCE와 CA에서 증식은 보이지 않았지만 이동과 모세혈관-유사 관 형성 또는 분화를 보였다. 또한 CCE와 CA는 HUVEC에서 VEGF 발현과 Flk-1/KDR 발현을 각각 2.2배와 2.5배 증가시켰다. 결론 : CCE와 그 활성 혼합물은 in vivo와 in vitro에서 혈관 내피세포의 VEGF 발현을 통하여 신생혈관 형성 작용을 유도하며 이는 앞으로 다른 한약 추출물의 신생혈관형성 촉진 작용 연구에 모델을 제시할 것으로 보인다.

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Inhibitory Effects of Rehmannia glutinosa Liboschitz on Endothelial Cell Proliferation

  • Lee, Sung-Jin;Lee, Hak-Kyo
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.5
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    • pp.311-314
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    • 2007
  • Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.

Cytotoxic and Antioxidant Effects of Taraxacum coreanum Nakai. and T. officinale WEB. Extracts (흰민들레와 서양민들레 추출물의 세포독성 및 항산화 활성 비교)

  • Lee, Hyun-Hwa;Lee, Sook-Yeong
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.2
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    • pp.79-85
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    • 2008
  • Some studies of dandelion have been carried out on bioactivities, however, no comparative analysis on antioxidant and cytotoxic activities in the Korean dandelion (T. coreanum NAKAI.; KD) and dandelion (T. officinale WEB.) have been reported. In this study, the extracts of KD and dandelion analyzed relative phenolic contents and free radical scavenging, antioxidant enzyme and cytotoxic activities. The extract of Korean dandelion leaves (KDL) exhibited a higher phenolics content ($368{\pm}11.5\;mg/l00\;g$) and a strong free radical scavenging activity ($RC_{50}$value;87.89 ug/ml) than other parts and BHT (120.12 ug/ml), synthetic antioxidant. At ascorbate peroxidase (APX) activity, the dandelion root (DR) had a greater (38.8 U/mg protein) antioxidant enzyme compare to the dandelion leaves (12.2 U/mg protein). The catalase (CAT) and superoxide dismutase (SOD) followed higher enzyme activity in Korean dandelion root (KDR) than other parts. In a cytotoxic activity against human cancer cell, the extracts of KDR was found to be active against Calu-6, HCT-116, and SNU-601 cell lines, with $IC_{50}$ values of 522.34, 532.74 and 614.85 ug/ml, respectively. These results suggest that KD and dandelion would be an alternative antioxidant source, based on natural plant resources.

Development of digital excitation system in nuclear power plant (원전 발전기 디지털 제어시스템 개발 III)

  • Shin, Man-Su;Lee, Byeong-Gu;Lim, Ick-Heon;Lee, Ju-Hyun;Ryu, Ho-Seon
    • Proceedings of the KIEE Conference
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    • 2006.04a
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    • pp.237-239
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    • 2006
  • Nowadays the core control systems are made by multiple redundancy strategy. There are analog excitation systems which have been operating during more than twenty years. This project is aim to retrofit nuclear power plants, also improves the reliance, safety, faculty of nuclear generator excitation system.

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Vascular Endothelial Growth Factor Inhibits irradiation-induced Apoptosis in Human Umbilical Vein Endothelial Cells (혈관내피세포에서 Vascular Endothelial Growth Factor가 방사선에 의해 유도된 apoptosis에 미치는 영향)

  • Lee Song Jae;Kim Dong-Yun
    • The Journal of Korean Society for Radiation Therapy
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    • v.14 no.1
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    • pp.165-174
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    • 2002
  • Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we examined the effect of VEGF on radiation induced apoptosis and receptor/second messenger signal transduction pathway for VEGF effect in human umbilical vein endothelial cells (HUVECs). VEGF was found to protect HUVECs against the lethal effects of ionizing radiation by inhibiting the apoptosis induced in these cells by radiation exposure. VEGF (1-30 ng/ml) dose dependently inhibited apoptosis by irradiation. Pre-treatment with Flt-1 and Flk-l/KDR receptor blocked the VEGF-in duced antiapoptotic effect. Phosphatidylinositol 3'-kinase (PI3-kinase) specific inhibitor, Wortman in and LY294002, blocked the VEGF-induced antiapoptotic effect. These data suggest that VEGF may play an important role in survival of HUVECs due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation.

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Stage specific transcriptome profiles at cardiac lineage commitment during cardiomyocyte differentiation from mouse and human pluripotent stem cells

  • Cho, Sung Woo;Kim, Hyoung Kyu;Sung, Ji Hee;Han, Jin
    • BMB Reports
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    • v.54 no.9
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    • pp.464-469
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    • 2021
  • Cardiomyocyte differentiation occurs through complex and finely regulated processes including cardiac lineage commitment and maturation from pluripotent stem cells (PSCs). To gain some insight into the genome-wide characteristics of cardiac lineage commitment, we performed transcriptome analysis on both mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs) at specific stages of cardiomyocyte differentiation. Specifically, the gene expression profiles and the protein-protein interaction networks of the mESC-derived platelet-derived growth factor receptor-alpha (PDGFRα)+ cardiac lineage-committed cells (CLCs) and hiPSC-derived kinase insert domain receptor (KDR)+ and PDGFRα+ cardiac progenitor cells (CPCs) at cardiac lineage commitment were compared with those of mesodermal cells and differentiated cardiomyocytes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the genes significantly upregulated at cardiac lineage commitment were associated with responses to organic substances and external stimuli, extracellular and myocardial contractile components, receptor binding, gated channel activity, PI3K-AKT signaling, and cardiac hypertrophy and dilation pathways. Protein-protein interaction network analysis revealed that the expression levels of genes that regulate cardiac maturation, heart contraction, and calcium handling showed a consistent increase during cardiac differentiation; however, the expression levels of genes that regulate cell differentiation and multicellular organism development decreased at the cardiac maturation stage following lineage commitment. Additionally, we identified for the first time the protein-protein interaction network connecting cardiac development, the immune system, and metabolism during cardiac lineage commitment in both mESC-derived PDGFRα+ CLCs and hiPSC-derived KDR+PDGFRα+ CPCs. These findings shed light on the regulation of cardiac lineage commitment and the pathogenesis of cardiometabolic diseases.

Design and Synthesis of an Anticancer Diarylurea Derivative with Multiple-Kinase Inhibitory Effect

  • El-Gamal, Mohammed I.;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.33 no.5
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    • pp.1571-1576
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    • 2012
  • A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.

A Cipadesin Limonoid and a Tirucallane Triterpene from the Fruit of Sandoricum koetjape and their Inhibitory Properties against Receptor Tyrosine Kinases

  • Rachmadhaningtiyas, Dyah Ayu;Heliawati, Leny;Hermawati, Elvira;Syah, Yana Maolana
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.134-139
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    • 2021
  • A new cipadesin limonoid, i.e. 3-epi-cipadonoid C (1), and a new tirucallane triterpene, i.e. hispidol B 3-palmitate (3), have been isolated from the seeds and fruit peels extract of Sandoricum koetjape, respectively. Along with these compounds the known limonoid, cipaferen G (2), and two pentacyclic triterpenes, bryonolic (4) and bryononic (5) acids, were also isolated. The strucrures of the new compounds were elucidated by the analysis of NMR and mass spectral data. Compounds 1 - 5 were evaluated as the inhibitor of receptor tyrosine kinases (EGFR, Epidermal Growth Factor Receptor; HER2, HER4, Human Epidermal growth factor Receptor 2, -4; IGFR, Insulin-like Growth Factor Receptor; InsR, Insulin Receptor; KDR, Kinase insert Domain Receptor; PDGFRα, and PDGFRβ, Platelet-Derived Growth Factor Receptor-α and -β). The results showed only 1 and 3 that have weak activity against InsR.

Effects of Exercise on Endothelial Progenitor Cells in Cardiovascular Disease Patients: A Systematic Review (운동중재가 심혈관질환자의 혈관내피전구세포에 미치는 영향: 체계적 문헌고찰)

  • Kim, Ahrin;Yang, In-Suk
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.4
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    • pp.366-379
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    • 2017
  • In this study, we performed a systematic review and meta-analysis to identify the effects of exercise on endothelial progenitor cells (EPCs) in patients with cardiovascular disease (CVD). We conducted database searches (Cochrane Library, PubMed, EMBASE, ScienceDirect, CINAHL, Scopus, KoreaMed, KISS, RISS, KMBASE) for the effect of exercise on cardiovascular disease, using heart disease, coronary artery disease, heart failure, cardiovascular disease, exercise, motor activity, rehabilitation, and endothelial progenitor cells as the keywords. Of the 539 studies identified, 9 met the inclusion and exclusion criteria. Comprehensive Meta-Analysis version 2.0 was used to analyze the effect size and the publication bias was checked with a funnel plot. Exercise was found to improve the VEGF (vascular endothelial growth factor), CD34+KDR+, and endothelial function, assessed via FMD (flow-mediated dilation), in the exercise vs. control groups, viz. 2.008 (95% CI 0.204-3.812), 1.399 (95% CI 0.310-2.489), and 1.881 (95% CI 0.848-2.914), respectively. Exercise improved the VEGF, number of EPCs, and endothelial function in the CVD patients. Considering the increasing prevalence and mortality rates for cardiovascular disease in Korea, the findings of this study that analyzed the effects of exercise on EPCs might provide guidelines for planning exercise interventions for patients with CVD.

Forced Expression of HoxB4 Enhances Hematopoietic Differentiation by Human Embryonic Stem Cells

  • Lee, Gab Sang;Kim, Byung Soo;Sheih, Jae-hung;Moore, Malcolm AS
    • Molecules and Cells
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    • v.25 no.4
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    • pp.487-493
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    • 2008
  • HoxB4 has been shown to enhance hematopoietic engraftment by hematopoietic stem cells (HSC) from differentiating mouse embryonic stem cell (mESC) cultures. Here we examined the effect of ectopic expression of HoxB4 in differentiated human embryonic stem cells (hESCs). Stable HoxB4-expressing hESCs were established by lentiviral transduction, and the forced expression of HoxB4 did not affect stem cell features. HoxB4-expressing hESC-derived CD34+ cells generated higher numbers of erythroid and blast-like colonies than controls. The number of CD34+ cells increased but CD45+ and KDR+ cell numbers were not significantly affected. When the hESC derived CD34+ cells were transplanted into $NOD/SCID{\beta}2m-/-$ mice, the ectopic expression of HoxB4 did not alter their repopulating capacity. Our findings show that overexpression of HoxB4 in differentiating hESCs increases hematopoietic colony formation and hematopoietic cell formation in vitro, but does not affect in vivo repopulation in adult mice hosts.