• Title/Summary/Keyword: 혈관생성인자농도

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Computational analysis of cancer angiogenesis using two dimensional model (2차원 모델을 이용한 암의 혈관생성에 대한 수치적 연구)

  • Shim Eun Bo;Ko Hyung Jong;Deisboeck Thomas
    • Proceedings of the KSME Conference
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    • 2002.08a
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    • pp.709-710
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    • 2002
  • Cancer angiogenesis is simulated using a two dimensional model. Governing equation of angiogenesis is a TAE (Tumor angiogenesis factor) conservation equation in time and space. A stochastic process model is utilized to simulate vessel formation, proliferation, and migration to a cancer pellet. Numerical results are presented especially in case of growing cancer.

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Regulatory Effects of Chrysanthemi Zawadskii Herba on NO Production and Vascular Adhesion Molecule Expression (구절초(Chrysanthemi Zawadskii Herba)의 항염증 인자 생성 및 혈관부착인자 발현 억제 효과)

  • Sohn, E.S.;Kim, S.H.;Ha, C.W.;Jang, S.;Sohn, E.H.;Chae, C.J.;Koo, H.J.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.24 no.1
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    • pp.14-22
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    • 2022
  • The purpose of this study is to provide evidence for discovering functional materials through the anti-inflammatory efficacy screening of randomly selected medicinal herbs. We prepared 70% ethanol extracts from 10 herbs and evaluated for the inhibitory effect of NO production on LPS-stimulated mouse macrophage cell line Raw 264.7. As a result, it was confirmed that the Chrysanthemi Zawadskii Herba (CZ) extract had the highest effect of inhibiting NO production induced by LPS. We therefore measured and compared NO inhibitory effects at different concentrations (10, 50, 250 ㎍/mL) of 70% ethanol and water extract of CZ. It was observed that both ethanol and water treatment groups inhibited NO production in a concentration-dependent manner in both ethanol and water treatment groups. In particular, it was confirmed that the CZ 70% ethanol extract (99.97%) had a higher NO inhibitory effect than the water extract (93.32%) in the high concentration (250 ㎍/mL) treatment group. There was no effect of CZ extract on cell viability at all concentrations used in the experiment. Moreover, it was shown that CZ ethanol extract remarkably inhibited the expression of VCAM-1 induced by TNF-𝛼, and it was slightly decreased even by treatment with water extract. This study suggests that Chrysanthemi Zawadskii Herba has potential as a functional substance that regulates vascular inflammation.

Forsythiae Fructus Induces VEGF Production via p38 MAPK Activation in Human Keratinocytes (각질형성세포에서 p38 MAPK 활성을 통한 연교의 VEGF 생성 효과)

  • Kim, Mi-Sun;Choi, Yun Ho;Park, Sun Gyoo;Lee, Cheon Koo;Lee, Sang Hwa
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.329-336
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    • 2016
  • Cutaneous microvasculature plays a critical role in age-associated skin changes. A considerable reduction of number and size of vessels has been observed in the upper dermis of elderly skin. Forsythiae fructus (FF), the dried fruit of plant Forsythia suspensa (F. suspensa), has been traditionally used as an herbal medicine to treat inflammatory diseases and bacterial diseases. However, its regulatory effect on angiogenic responses has not been elucidated in skin. Therefore, we analyzed secretory profiles upon treatment of FF extract using array designed to detect angiogenesis-associated mediators in human keratinocytes. Because keratinocyte-derived VEGF (vascular endothelial growth factor) has been regarded as a potent factor for new microvasculature under the epidermis, we further investigated the effect of FF extract on VEGF production. We observed that the VEGF expression of mRNA and protein level was increased by about 2 folds in a dose-dependent manner after FF extract treatment. In signaling experiments, FF extract induced rapid p38 MAPK activation within 5 min, and the activation was totally abrogated by pretreatment with a p38 MAPK specific inhibitor. The FF-induced VEGF upregulation was also significantly attenuated by a p38 MAPK inhibition. Taken together, FF extract induces VEGF production via p38 MAPK activation in human epidermal keratinocytes. These novel findings suggest that FF is useful as a potential agent with pro-angiogenic activity and may help to improve age-dependent reduction of the microvasculature in aged skin or to heal skin wound.

7-Ketocholesterol Induces Vascular Smooth Muscle Cell Apoptosis via Akt Degradation (7-Ketocholesterol에 의한 Akt 감소와 혈관평활근세포의 세포자멸사)

  • Seo, Kyo Won;Kim, Chi Dae;Lee, Won Suk
    • Journal of Life Science
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    • v.26 no.2
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    • pp.226-233
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    • 2016
  • Vascular smooth muscle cell (VSMC) apoptosis has been identified in various vascular diseases, including atherosclerosis and restenosis after angioplasty, and has been known to precipitate atherosclerotic plaque instability and rupture. Oxysterols are known as inducers of apoptosis in VSMC, and 7-ketocholesterol (7KC) is the major nonenzymically formed oxysterol in atherosclerotic lesions. The precise mechanism underlying VSMC apoptosis is still poorly understood. In this study, we investigated whether 7KC causes apoptosis, and characterized its apoptotic mechanisms in primary cultured rat aortic VSMC. Cell viability was assessed by MTT assay and trypan blue assay. Apoptosis was assessed by flow cytometry, immunofluorescence, immunoprecipitation, and Western blot analyses. 7KC markedly decreased the VSMC viability in a time- and concentration-dependent manner, and increased the production of 4-hydroxynonenal (HNE), a major end-product of lipid peroxidation, which also decreased the VSMC viability. Pretreatment with 2,4-dinitrophenylhydrazine, a well-known reagent of lipid peroxidation-derived aldehydes, significantly restored the 7KC-decreased viability of VSMC. Furthermore, HNE, as well as 7KC, reduced the level of total Akt, a major mediator of cell survival. The 7KC-decreased level of total Akt was significantly restored by pretreatments with 2,4-dinitrophenylhydrazine and N-acetylcysteine. Lactacystin, a proteasome inhibitor, protected VSMC against apoptosis and Akt degradation, but did not inhibit HNE production. In the immunoprecipitation assay, 7KC increased HNE-modified Akt. From the results, it seems that, in atherosclerotic lesions, 7KC induces HNE production in VSMC, and this HNE binds to Akt, proceeding to proteasomal degradation of Akt, through which mechanism the atherosclerotic plaque instability may be facilitated.

Effects of Acai Berry Ethanolic Extracts on Production of Nitric Oxide and Activity of Angiotensin Converting Enzyme Related to Blood Circulation (혈액순환과 관련하여 nitric oxide 생성과 angiotensin converting enzyme 활성에 미치는 Acai berry 에탄올 추출물의 영향)

  • Nam, Hyang;Lee, Su-Gyeong;Kim, Deok Won;Kim, Joo Wan;Kim, Ki Young;Kim, Sung Goo;Kim, Moon-Moo;Chung, Kyung Tae
    • Journal of Life Science
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    • v.23 no.6
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    • pp.743-750
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    • 2013
  • The aim of this study is to develop a supplementary therapeutic agent capable of promoting vascular circulation. The effects of Acai berry ethanolic extracts (ABEE) on activity of angiotensin converting enzyme from rabbit lung, production of nitro oxide in both murine macrophage cells and vascular endothelial cells as well as antioxidant effects were investigated in this study. First of all, it was observed the direct effects of ABEE on reducing power and antioxidant effect lipid peroxidation. In addition, ABEE showed a protective effect on DNA oxidation induced by hydroxyl radical. Furthermore, ABEE at 0.01% exerted approximately 50% inhibition on activity of angiotensin converting enzyme. ABEE increased the production of nitric oxide in endothelial cells, but decreased the induction of nitric oxide stimulated by lipopolysaccharide in microphage. The expression levels of superoxide dismutase (SOD)-2 and -3 were enhanced by ABEE treatment, however, the expression level of SOD-1 remained constant. Moreover, the expression level of nitric oxide synthases-1 (NOS-1), a constitutive enzyme, was increased by ABEE, but that of NOS-2, a inducible enzyme, was constant. It was also found that the level of Nrf-2, a transcription factor of SOD, was increased by ABEE. Therefore, these results demonstrate that ABEE could promote blood circulation via above actions, suggesting that may be helpful for health of blood vessel.

NO and Cytokine Production due to Crysochroa fulgidissima (비단벌레(Crysochroa fulgidissima) 에탄올추출물의 NO 증강 및 염증인자억제활성)

  • Ahn, Mi-Young;Kim, Soon-Ja;Jeong, Hye-Kyoung;Seo, Yun-Jung;Park, Hae-Cheol;Lee, Young-Bo;Kim, Mi-Aae
    • Korean journal of applied entomology
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    • v.50 no.3
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    • pp.227-233
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    • 2011
  • Crysochroa fulgidissima (Bidan-beole, Spanish fly) is traditionally used as a crude drug and insecticide in the East Asia and Korea, respectively. This study investigated the effect of ethanol extract of C. fulgidissima on the NO production activity. The C. fulgidissima extract was a potent inducer of NO production in CPAE cells and a stimulator of endothelial nitric oxide synthase in a dose-dependent manner. This study also evaluated the anti-inflammatory activity of this extract by determining the level of ICAM-1, VCAM-1, and prostaglandin $E_2$ from HUVEC cells. Although C. fulgidissima extract was a potent inducer of NO production in the CPAE cells, it showed weak inhibitory effects on vascular endothelial growth factor (VEGF) production in HUVEC cells. HPLC and GC-MS analysis of the ethanol extract of C. fulgidissima revealed the presence of cantharidin.

Extracellular $K^+$ Effects on the Mouse Aortic Endothelial Cell Contractility (쥐 대동맥 혈관 내피세포에서 세포 외 $K^+$에 의한 혈관 수축선 조절 기전)

  • 안재호;유지영
    • Journal of Chest Surgery
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    • v.36 no.12
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    • pp.887-893
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    • 2003
  • External stimuli increases intracellular (IC) $Ca^{2+}$, which increases extracellular (EC) $K^{+}$. To verify $K^{+}$ effects on the vascular contraction, we performed an experiment using mouse aortic endothelial cell. Meterial and Method: We examined the mouse aortic contractility changes as we measured the IC $Ca^{2+}$ change and ionic current by using the voltage clamp technique under different conditions such as: increasing EC $K^{+}$, removing endothelial cell, giving L-NAME (N-nitro-L-arginine methyl ester) which suppress nitric oxide formation, Ouabain which control N $a^{+}$ - $K^{+}$ pump and N $i^{2+}$ which repress N $a^{+}$-C $a^{2+}$ exchanger Result: When we increased EC $K^{+}$ from 6 to 12 mM, there was no change in aortic contractility. Aorta contracted with more than 12 mM of EC $K^{+}$. Ace-tylcholine (ACh) induced relaxation was inhibited with EC $K^{+}$ from 6 to 12 mM, but was not found after de-endothelialization or L-NAME treatment. ATP or ACh increased IC $Ca^{2+}$ in cultured endothelium. After maximal increase of IC $Ca^{2+}$, increasing EC $K^{+}$ from 6 to 12 mM made IC $Ca^{2+}$ decrease and re-decreasing EC $K^{+}$ to 6 mM made IC $Ca^{2+}$ increase. Ouabain and N $i^{2+}$ masked the inhibitory effect of endothelium dependent relaxation by increased EC $K^{+}$. Conclusion: These data indicate that increase in EC $K^{+}$ relaxes vascular smooth muscle and reduces $Ca^{2+}$ in the endothelial cells which inhibit endothelium dependent relaxation. This inhibitory mechanism may be due to the activation of N $a^{+}$- $K^{+}$ pump and N $a^{+}$-C $a^{2+}$ exchanger. $a^{+}$-C $a^{2+}$ exchanger.r.

Dietary Fiber and Cholesterol Metabolism (식이섬유와 콜레스테롤 대사)

  • Kang, Hee-Jung;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.2
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    • pp.358-369
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    • 1997
  • Hypercholesterolemia is a main risk factor to develop cardiovascular disease, a major cause of death in Korea currently. Dietary factors which shows hypocholesterolemic effect have been reported, which includes plant proteins, unsaturated fatty acids, milk, calcium, flavonoids. Numerous animal and human studies confirmed the pronounced hypocholesterolemic effects of soluble dietary fiber, such as psyllium husk, pectin, sodium alginate, guar gum. Several hypotheses have been proposed to explain the hypocholesterolemic effect of dietary fiber, including binding of bile acids by fiber, interference of lipid absorption and reduced hepatic cholesterol synthesis by propionate, a product of soluble dietary fiber fermentation. Several other hypotheses have been proposed, and these hypotheses are not mutually exclusive.

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Prognostic Value of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) Expression in Resected Non-small Cell Lung Cancer (수술로 절제된 비소세포폐암 조직에서 예후인자로서 VEGF와 bFGF 발현의 의의)

  • Kim, Seung Joon;Lee, Jung Mi;Kim, Jin Sook;Kang, Ji Young;Lee, Sang Hak;Kim, Seok Chan;Lee, Sook Young;Kim, Chi Hong;Ahn, Joong Hyun;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak;Moon, Seok Hwan;Wang, Yeong Pil
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.3
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    • pp.200-205
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    • 2008
  • Background: Tumor angiogenesis plays an important role in tumor growth, maintenance and metastatic potential. Tumor tissue produces many types of angiogenic growth factors. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumor angiogenesis. In this study, the expression of tissue VEGF and bFGF from non-small cell lung cancer (NSCLC) patients were analyzed. Methods: We retrospectively investigated 35 patients with a histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, where the primary curative approach was surgery. An ELISA was employed to determine the expression of VEGF and bFGF in extracts prepared from 35 frozen tissue samples taken from the cancer patients. Results: VEGF and bFGF concentrations were significantly increased in lung cancer tissue as compared with control (non-cancerous) tissue. The VEGF concentration was significantly increased in T2 and T3 cancers as compared with T1 cancer. Expression of VEGF was increased in node-positive lung cancer tissue as compared with node-negative lung cancer tissue (p=0.06). VEGF and bFGF expression were not directly related to the stage of lung cancer and patient survival. Conclusion: Expression of VEGF and bFGF were increased in lung cancer tissue, and the expression of VEGF concentration in lung cancer tissue was more likely related with tumor size and the presence of a lymph node metastasis than the expression of bFGF. However, in this study, expression of both VEGF and bFGF in tissue were not associated with patient prognosis.

Development of Purification Process of Recombinant Human Vascular Endotherial Growth Factor (VEGF) using Fusion Protein (융합 단백질을 이용한 재조합 인간 혈관내피세포 성장인자의 정제공정 개발)

  • Sung, Keehyun;Kim, In Ho
    • Korean Chemical Engineering Research
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    • v.55 no.3
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    • pp.369-378
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    • 2017
  • Vascular endotherial growth factor (VEGF) is a potent mitogen that stimulates vascular permeability and angiogenesis and has a potential in therapeutic applications. An industrial production method that provides high yield as well as purity is needed. Researches for various factors of mild solubilization with combination of ubiquitin fusion protein to increase solubility were carried out as well as by changing pH and denaturant concentration. Usage of pET28-a bacteral expression vector in BL21 (DE3) host cell was capable of producing approximately 14 g/L VEGF fusion protein in 20L fermentor. A purification process consisting of four chromatography steps including refolding and digestion with UBP1 resulted in mild solublization under the conditions of 2M urea and pH 10.0 due to ubiquitin fusion tag protein that increases in solubility of target protein VEGF. High yield of refolding and dimerization could be obtained between two step Ni-affinity chromatography. Multimeric and misfolded proteins and endotoxin were removed by DEAE anion exchange chromatography. Final monomers were removed from dimers by gel filtration chromatography. Characterization analysis of purified dimeric VEGF was performed using SDS-PAGE and RP-HPLC with a purity of 97%.