• Title/Summary/Keyword: 금속단백효소

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Inhibition of Neointima Formation and Migration of Vascular Smooth Muscle Cells by Anti-vascular Endothelial Growth Factor Receptor-1 (Flt-4) Peptide in Diabetic Rats (당뇨병 쥐에서 혈관내피 성장인자 수용체-1 차단 펩타이드를 이용한 신내막 형성과 혈관평활근세포 이동의 억제)

  • Jo, Min-Seop;Yoo, Ki-Dong;Park, Chan-Beom;Cho, Deog-Gon;Cho, Kue-Do;Jin, Ung;Moon, Kun-Woong;Kim, Chul-Min;Wang, Young-Pil;Lee, Sun-Hee
    • Journal of Chest Surgery
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    • v.40 no.4 s.273
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    • pp.264-272
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    • 2007
  • Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

Matrix metalloproteinase-8 and substance P levels in root canal exudates of nonvital teeth (근관 삼출액에서의 기질금속단백분해효소-8과 substance P의 수준에 관한 연구)

  • Shin, Su-Jung;Lee, Woo-Cheol;Lee, Jae-Il;Baek, Seung-Ho;Kum, Kee-Yeon;Shon, Won-Jun;Bae, Kwang-Shik
    • Restorative Dentistry and Endodontics
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    • v.36 no.3
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    • pp.196-202
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    • 2011
  • Objectives: The aim of this study was to investigate levels of matrix metalloproteinase-8 (MMP-8) and substance P (SP) in root canal exudates during root canal treatment (RCT) of nonvital, painful teeth. Materials and Methods: Patients scheduled for nonsurgical RCT were prospectively selected; the study was performed after obtaining informed consent from the patients and was approved by the Institutional Review Board for Clinical Research of Gangnam Severance Hospital, Yonsei University (3-2008-0118). Canal exudates samples were collected using sterilized paper points from teeth scheduled for RCT across three different time periods. MMP-8 and SP levels were measured using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using a mixed model analysis and the Pearson correlation analysis (p < 0.05). Results: MMP-8 and SP levels in GCF were decreased during RCT (p < 0.0001), and they showed a weak positive correlation to each other (p < 0.05). Patients' subjective pain levels and the response from percussion test were significantly related to SP level. Conclusions: This study demonstrated that periradicular inflammation endodontic origin can elevate SP and MMP-8 levels in root canal exudates. Interestingly, SP level of canal exudates showed a possibility of being used as an indicator of pain due to periapical pathosis.

Evaluation of the Canine Stifle Joint after Transection of the Cranial Cruciate Ligament and Medial Collateral Ligament, and Medial Meniscectomy without Postoperative Exercise (앞십자인대 및 내측 곁인대 절제와 내측 반월판 절제술을 한 뒤 수술후 운동을 실시하지 않은 개의 무릎 관절의 평가)

  • Lee, Hae-Beom;Jeong, Chang-Woo;Kim, Nam-Soo
    • Journal of Veterinary Clinics
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    • v.24 no.3
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    • pp.325-330
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    • 2007
  • This study was to determine whether canine model which produce acute permanent joint instability in short period without postoperative exercise have a degenerative changes and also evaluated its suitability as an appropriate animal OA models. Ten skeletally mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and, the medial collateral ligament as well as a medial meniscectomy. The contra-lateral joint was used as control. After 12 weeks, After 12 weeks, the amount of joint damage, inflammation and biochemical change of synovial fluid was evaluated. Histological analysis showed chondrocyte clone formation, hypertrophy of the cartilage and moderate loss of proteoglycans in the experimental joints compared to control joints. In addition, the synovial inflammation in the experimental joints was observed. Biochemical analysis of SF showed significantly increased MMP (matrix metalloproteinase) -2 and -9 in experimental joints compared to control joints. This canine OA model shows the characteristics of degenerative joint disease, and may have a advantages of reducing the time and cost because postoperative exercise is not needed in this OA model.

Protective effect of Thymus quinquecostatus extracts UVB-induced matrix metalloproteinase-1 via suppressing MAPKs phosphorylation in human keratinocyte (사람의 각질세포에서 UVB 유도에 따른 MMP-1의 발현 조절과 MAPKs 인산화에 타임 추출물이 미치는 효과)

  • Jung, Hana;Jeong, Hyun Ju;Shin, Kyounghee;Kim, Yung Sun;Moon, Jae Heon;Lee, Tae Hoon
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.417-421
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    • 2018
  • Ultraviolet rays are electromagnetic waves with a shorter wavelength than visible light, and ultraviolet rays that pass through the ozone layer are the main cause of skin aging. Chronic exposure of skin tissue to ultraviolet light activates the Mitogen-activated Protein Kinases (MAPKs) signaling pathways in human keratinocytes, resulting in increased production of matrix metalloproteinases (MMPs). In this study, we investigated the herbal extracts from Jeju Island on the anti-aging effect in human keratinocytes (HaCaTs) by ultraviolet stimulation. We examined that herb extract from Jeju Island were decreased in anti-aging activity on measuring the level of MMP-1 gene and protein expression in ultraviolet-induced keratinocytes. As a result, it was confirmed that Thymus quinquecostatus extract (TQE) significantly reduced the expression of MMP-1 in a dose-dependent manner by UV irradiated HaCaTs. According to our data, TQE significantly attenuated UV-induced phosphorylation of the MAPKs signaling elements ERK1/2, JNK1/2 and p38 proteins. These results suggest that the MAPKs pathway may contribute to the inhibitory effect of TQE on UV-induced MMP-1 production in human keratinocytes. Our results suggest that TQE may be a protective agent against skin aging by preventing UV-induced MMP-1 production.

Inhibitory Substance on the Snake Venoms Produced by Penicillium sp. (사독의 조해물질에 관한 연구)

  • Seu, Jung-Hwn;Yi, Dong-Heui
    • Microbiology and Biotechnology Letters
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    • v.7 no.2
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    • pp.75-89
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    • 1979
  • One strain of Penicillium sp. (175-66-B), isolated from soil, was able to produce a substance that has a strong inibition activity against the Agkistrodon and Trimeresurus venoms. In this experiment, the chemical and biological properties of the sample were investigated. As an inhibitory substance, it was effective to the proteinase, hemorrhagic and lethal factors of Agkistrodon and Trimeresurus venoms, and also effective to several fractions of the proteinases and hemorrhagic factors of Agkistrodon halys blomhoffi venom. Moreover, in the addition of prednisotone, it was more effective for the cure of the mouse envenomated with the venom amount of two fold of MLD$_{100}$. This substance was very stable to the acid, alkali and heat. Its melting point was high enough to sublime at 222$^{\circ}C$ without any decomposition. This sample was easily dissolved only in hot water, but not in several organic solvents except for a little dissolution in elate. It did not have the chelating activity. It had very strong specificity to the snake venoms. but its activity was depressed by the addition of zinc or cupric salts. This sample had no acute toxicity to the mouse. Its chemical formula was $C_{16}$ $H_{12}$$N_2$ $O_{10}$ with the molecular weight of about 392. It has two epoxy groups and four carboxyl radicals, but amino, nitrite and nitrate radicals, unsaturated bonds and aromatic ring were not detected. Theuchemical configuration of this sample was suggested to be;

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Deterioration Diagnosis and Source Area of Rock Properties at the West Stone Pagoda, Gameunsaji Temple Site, Korea (감은사지 서탑의 풍화훼손도 진단 및 석재의 산지추정)

  • Lee Chan Hee;Lee Myeong Seong;Suh Mancheol;Choi Seok-Won;Kim Man Gap
    • Economic and Environmental Geology
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    • v.37 no.5
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    • pp.569-583
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    • 2004
  • The rock properties of the West pagoda in the Gameunsaji temple site are composed mainly of dark grey porphyritic granodiorite with medium grained equigranular texture and developed with small numerous dioritic xenoliths. These xenoliths occurred with small holes due to different weathering processes. As a weathering results, the rock properties of this pagoda occur wholly softened to physical hardness because of a complex result of petrological, meteorological and biological causes. Southeastern part of the pagoda deteriorated seriously that the surface of rock blocks showed partially exfoliations, fractures, open cavities in course of granular decomposition of minerals, sea water spray and crystallization of salt from the eastern coast. The Joint between blocks has small or large fracture cross each other, contaminated and corrupted for inserting with concrete, cement mortar, rock fragments and iron plates, and partially accelerated coloration and fractures. There are serious contamination materials of algae, fungus, lichen and bryophytes on the margin and the surface on the roof stone of the pagoda, so it'll require conservation treatment biochemically for releasing vegetation inhabiting on the surface and the discontinuous plane of the blocks because of adding the weathering activity of stones and growing weeds naturally by soil processing on the fissure zone. Consisting rock for the conservation and restoration of the pagoda would be careful choice of new rock properties and epoxy to reinforce for the deterioration surfaces. For the attenuation of secondary contamination and surface humidity, the possible conservation treatments are needed.