• Title/Summary/Keyword: tissue factor

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Local Silencing of Connective Tissue Growth Factor by siRNA/Peptide Improves Dermal Collagen Arrangements

  • Cho Lee, Ae-Ri;Woo, Inhae
    • Tissue Engineering and Regenerative Medicine
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    • v.15 no.6
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    • pp.711-719
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    • 2018
  • BACKGROUND: Collagen organization within tissues has a critical role in wound regeneration. Collagen fibril diameter, arrangements and maturity between connective tissue growth factor (CTGF) small interfering RNA (siRNA) and mismatch scrambled siRNA-treated wound were compared to evaluate the efficacy of CTGF siRNA as a future implement for scar preventive medicine. METHODS: Nanocomplexes of CTGF small interfering RNA (CTGF siRNA) with cell penetrating peptides (KALA and $MPG^{{\Delta}NLS}$) were formulated and their effects on CTGF downregulation, collagen fibril diameter and arrangement were investigated. Various ratios of CTGF siRNA and peptide complexes were prepared and down-regulation were evaluated by immunoblot analysis. Control and CTGF siRNA modified cells-populated collagen lattices were prepared and rates of contraction measured. Collagen organization in rabbit ear 8 mm biopsy punch wound at 1 day to 8 wks post injury time were investigated by transmission electron microscopy and histology was investigated with Olympus System and TS-Auto software. CONCLUSION: CTGF expression was down-regulated to 40% of control by CTGF siRNA/KALA (1:24) complexes (p<0.01) and collagen lattice contraction was inhibited. However, down-regulated of CTGF by CTGF $siRNA/MPG^{{\Delta}NLS}$ complexes was not statistically significant. CTGF KALA-treated wound appeared with well formed-basket weave pattern of collagen fibrils with mean diameter of $128{\pm}22nm$ (n = 821). Mismatch siRNA/KALA-treated wound showed a high frequency of parallel small diameter fibrils (mean $90{\pm}20nm$, n = 563). CONCLUSION: Controlling over-expression of CTGF by peptide-mediated siRNA delivery could improve the collagen orientation and tissue remodeling in full thickness rabbit ear wound.

Cyclic Aminoalcohols with C-18 Alkenyl Substituents and Their Nanomolar Level-Activities as Tissue Factor Inhibitors

  • Yoon, Ung-Chan;Kwon, Hyuk-Chul;Cho, Yong-Jin
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.234.2-234.2
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    • 2003
  • Development of new tissue factor (TF) inhibitor is still needed for improved compositions having anticoagulant activity and which can be administed orally or non-intravenously at low doses. Our studies for the development of new TF inhibitors uncovered that aminoalcohols with C-18 alkenyl group, 9-octadecenyl- or 9,12-octadecadienyl groups exhibits in vitro nanomolar level activities. (omitted)

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Syntheses of Aminoalcohols with Alkenyl Substituents for the Development of Tissue Factor Inhibitors and Their in vitro Nanomolar Level-Activities

  • Yoon, Ung-Chan;Kwon, Hyuk-Chul;Song, Kyu-Chan
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.238.1-238.1
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    • 2003
  • Tissue Factor (TF), a principal initiator of the veterbrate coagulation cascade is known to to induced in endothelial cells, monocytes and macrophages by inflammetry stimuli and in many pathological conditions. Through our synthetic efforts to develop new TF inhibitors, seventeen N-C-18 alkenyl group (9-octadecenyl or 9,12-octadecadienyl) substituted aminoalcohols (2-aminoethanol, 1-amino-2-propanol and 3-amino-1-propanol) were prepared and their in vitro TF inhibitory activities were examined. (omitted)

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Matrix Metalloproteinase Inhibitors Attenuate Neuroinflammation Following Focal Cerebral Ischemia in Mice

  • Park, Cheol-Hong;Shin, Tae-Kyeong;Lee, Ho-Youn;Kim, So-Jung;Lee, Won-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.2
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    • pp.115-122
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    • 2011
  • The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-${\alpha}$, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.

A Rapid Method for the Measurement of the Absolute Activity of Carbon-14 in Pea Plant Tissue

  • Kendall, F.H.;Park, Chang-Kyu;Mer, C.L.
    • Applied Biological Chemistry
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    • v.18 no.2
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    • pp.56-60
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    • 1975
  • A rapid method for the measurement of the absolute activity of carbon-14 in cotyledons and root of etiolated pea seedlings has been developed. Fresh tissue was frozen in liquid air, ground and suspended in gel phosphor and subjected to measurement for its radioactivity by liquid scintillation counter. Apparent activity of the suspended tissue sample calculated by counting efficiency value obtained by internal standardisation, was found to be related to absolute activity of the tissue, determined by flask combustion technique, by a constant factor. Once this factor is determined experimentally, analysis of C-14 lebelled tissue involves only fairly simple suspension counting by liquid scintillation counter. Present method appears to be applicable to other tissues tagged with C-14.

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Regulation of Skeletal Muscle Differentiation by Akt (Akt에 의한 근육세포의 분화 조절)

  • Woo, Dae-Han;Yun, Sung-Ji;Kim, Eun-Kyoung;Ha, Jung-Min;Shin, Hwa-Kyoung;Bae, Sun-Sik
    • Journal of Life Science
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    • v.22 no.4
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    • pp.447-455
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    • 2012
  • Akt plays an important role in a variety of cellular physiologies such as growth, proliferation, and differentiation. In skeletal muscle, Akt has been implicated in regulating regeneration, hypertrophy, and atrophy. In this study, the role of Akt has been examined during skeletal muscle differentiation. Culturing C2C12 myoblasts under low serum (1% horse serum) and high density converted cell morphology from a round shape to an elongated and multi-nucleated shape. Morphological changes were initiated from day 2 of differentiation. In addition, the expression of both myogenin G and myogenin D was elevated from day 2 of differentiation. Skeletal muscle differentiation was abolished by silencing Akt1 or Akt2, but was significantly enhanced by the over-expression of either Akt1 or Akt2. The activation of Akt was observed from day 2 of differentiation and disappeared after day 7. The expression of kruppel-like factor 4 was observed from day 6 of differentiation. Moreover, this expression was blocked in cells silencing either Akt1 or Akt2. In addition, the promoter activity of kruppel-like factor 4 was significantly reduced in cells silencing Akt1 or Akt2. These results suggest that Akt regulates skeletal muscle differentiation through the regulation of kruppel-like factor 4 expression.

The Study of CYFRA 21-1 and Epidermal Growth Factor Receptor Levels in Cancer Tissue of Bronchogenic Carcinoma Patients (폐암환자의 암조직내 CYFRA 21-1과 Epidermal Growth Factor Receptor의 측정치에 대한 연구)

  • 김대연;김송명
    • Journal of Chest Surgery
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    • v.30 no.9
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    • pp.854-861
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    • 1997
  • CYPRA 21-1 is known to be a cytokeratin 19 fragment, and it can be detected by using two specific monoclonal antibodies (KS 19-1 and BM 19-21) and can be clinically applied as a useful circulating tumor marker The epidermal growth factor receptor (EGF-R) expression was evaluated and characterized by its tyrosine protein kinase activity and by its ligand-stimulated autophosphorylation, a property shared with other peptide growth factor receptors. Autocrine or para'urine action was initiated by a growth factor, or by a transforming growth factor o, which had an extensive homology with EGP and which also stimulated tyrosine kinase activity on the EGF-R. The CYFRA 21-1 and the EGF-R levels in 30 patients with primary lung tumors were investigated. There were 24 patients with squamous cell carcinomas and 6 patients with adenocarcinomas. Specimen 5 mm3 in size were sampled at three different locations ; the main lesion, the boundary between the lesion and the unaffected tissue, and the unaffected tissue of the patients. The results were as follows 1. The CYPRA 21-1 concentration in the cancer boundary, the most malignant region,(348.6 : 89.9 ng/ml) was the lowest value. The CYFRA 21-1 concentration in unaffected tissue,(718.4$\pm$77.8 ng/ml) was higher than that in the main lesion. which had intact cellularity. 2. The EGF-R concentration in the main lesion was higher than that in the unaffected tissue, and the EGF-R concentration in a squamous cell cacinoma was higher than that in an adenocarcinoma. also, the EGF-R concentration in the cancer b undary was highest at stage 1, ll. The EGF-R concentration was higher in the main cancer lesion that in the unaffected tissue at stage 111, IV. 3. The CYFRA 21-1 was a cytoplasmic skeleton and the EGF-R was a cell-wall component; there was no correlation. In conclusion, CYFRA 21-1 was abundant in the cytoplasm but had a higher concentration in the unaffected tissue than in the main cancer lesion. The CYFRA 21-1 concentration of the tissue did not reflect the amount of cancer activity, the EGP-R was located in the cell membrane, the level of tissue that reflects cancer activity, so the main cancer lesion had a higher concentration than the unaffected tissue. CYFRA 21-1 is not a useful tumor maker at the tissue level. Because the EGF-R concentration re(looted the cancer activity, its a useful tumor marker for lung cancer.

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Recent Progress in Study and Development of Polymeric Scaffolds for Tissue Regeneration (조직재생을 위한 고분자 지지체의 최근 연구개발 동향)

  • Joung, Yoon-Ki;Park, Ki-Dong;Park, Kwi-Deok;Han, Dong-Keun
    • Journal of Biomedical Engineering Research
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    • v.29 no.4
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    • pp.255-266
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    • 2008
  • In tissue engineering, scaffolds play an important role in the growth of cells to 3-D organs or tissues. For the success of tissue engineering, they should be mimicked to meet the requirements of natural extracellular matrix (ECM) in the body, such as mechanical properties, adhesiveness, porosity, biodegradability, and growth factor release, etc. Contrary to other materials, polymeric materials are adequate to engineer scaffolds for tissue engineering because controlling the structure and the ratio of components and designing various shapes and size are possible. In this review, the importance, major characteristics, processes, and recent examples of polymeric scaffolds for tissue engineering applications are discussed.

Cell-Interactive Polymers for Tissue Engineering

  • Lee, Kuen Yong;Mooney, David J.
    • Fibers and Polymers
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    • v.2 no.2
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    • pp.51-57
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    • 2001
  • Tissue engineering is one exciting approach to treat patients who need a new organ or tissue. A critical element in this approach is the polymer scaffold, as it provides a space for new tissue formation and mimics many roles of natural extra-cellular matrices. In this review, we describe several design parameters of polymer matrices that can significantly affect cellular behavior, as well as various polymers which are frequently used to date or potentially useful in many tissue engineering applications. Interactions between cells and polymer scaffolds, including specific receptor-ligand interactions, physical and degradation feature of the scaffolds, and delivery of soluble factors, should be considered in the design and tailoring of appropriate polymer matrices to be used in tissue engineering applications, as these interactions control the function and structure of engineered tissues.

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Tissue Factor Inhibitory Flavonoids from the Fruits of Chaenomeles sinensis

  • Lee, Ming-Hong;Son, Yeon-Kyoung;Han, Yong-Nam
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.842-850
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    • 2002
  • Tissue factor (TF, tissue thromboplastin or coagulation factor III) accelerates the blood clotting, activating both the intrinsic and the extrinsic pathways to serve as a cofactor. In order to isolate TF inhibitors from the fruits of Chaenomeles sinensis, an activity-guided purification utilizing a bio-assay method of prothrombin time prolongation, was carried out to yield five active flavoniods such as hovetrichoside C (1) ($IC_{50}$ = 14.0 $\mu$g), luteolin-7-Ο-$\beta$-D-glucuronide (3) ($IC_{50}$ = 31.9$\mu$g), hyperin (4) ($IC_{50}$ = 20.8 $\mu$g), avicularin (6) ($IC_{50}$ = 54.8 $\mu$g) and quercitrin (10) ($IC_{50}$ = 135.7 $\mu$g), along with other inactive compounds such as ($\pm$)-(2E,4E)-Ο-$\beta$-D-glucopyranosyl-4'-hydroxy-$\beta$-ionylideneacetic acid ester (2), genistein-7-Ο-$\beta$-D-glucopyranoside (5), luteolin-3'-methoxy-4'-Ο-$\beta$-D-glucopyranoside (7), luteolin-7-Ο-$\beta$-D-glucuronide methyl ester (8), tricetin-3'-methoxy-4'-Ο-$\beta$-D-glucopyranoside (selagin-4'-Ο-$\beta$-D-glucopyranoside) (9), (-)-epicatechin (11), luteolin-4'-Ο-$\beta$-D-glucopyranoside (12) and apigenin-7-Ο-$\beta$-D-glucuronide methyl ester (13). The structures of the isolated compounds were elucidated through spectral analysis. Among them, compounds 1 to 9, 12 and 13 were isolated for the first time from the fruits of this plant and the compound 9 is a new flavonoid.