• The Korean Journal of Pain
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• v.13 no.1
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• pp.1-7
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• 2000

Background: Intraarticular local anesthetic injection has been therapeutically applied for pain control in various arthritis patients. However, little physiologic effects of local anesthetics on their tissue were known. This study was conducted to determine its effects on the cell proliferation and matrix metalloproteinases (MMP) production of cultured fibroblast like synoviocytes (FLS) derived from synovial tissues of rheumatoid arthritis patients. Methods: Bupivacaine with varying concentrations 0 (control), 0.1, 0.25, 0.5% was applied to experimental cell groups growing as monolayers in culture plates for varying durations 0 (control), 30, 90, 180 seconds in the presence and absence of interleukin-$1\beta$. Results: No statistical significances were noted in thymidine incorporation between 0, 30, 90 and 180 seconds exposure groups with 0.5% bupivacaine after 1 day and 2 days. Thymidine incorporation between 0, 0.1, 0.25, 0.5% exposure groups 1 day and 2 days after 90 seconds exposure did not show any differences. After exposure to bupivacaine, there were statistically significant increases in MMP-1 (p=0.025) and MMP-3 productions (p=0.000) of FLS in the absence of IL-$1\beta$, but no differences among the groups in the presence of IL-$1\beta$. Conclusion: We concluded that in this short-term in vitro study, bupivacaine does not have injurious effect on cultured rheumatoid arthritic joint tissues. The long-term effect cannot be known from this investigation.

• Korean Journal of Microbiology
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• v.30 no.4
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• pp.239-245
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• 1992

Buci1llr.s 11c~h~n~1rnSiSi.As 3-2MI which is responsible for the special taste of traditionalKorean soy sause produced two kinds of proteinase. The activity of the proteinasc I washigher about two fold than that of proteinase 11. The optimai, reaction pH of proteinaseI and I1 wcre found to be 7-1 1.5 and 7-9. respectively. Proteinase I1 was more stable andactive than proteinase I at pH ranges around 3 to 5. The optimal te~tlperature of proteinaseI and I1 were 502. The temperature stabilitl of proteinase I1 was Inore stable thanproteinase 1 at temperature range around 30-quot;~A. ctivities of proteinase I and I1 graduallydeclined above $30^{\circ}$C and 45C. respectively. Proteinasc 1 was more active than proteinaseI1 at salt concentration range around 25-3500. The K,,, values of casein and soy proteinfor proteinase I were 6.89 mglml and 3.98 mglml. In case of proteinase 11. they were 9.00mgiml anti 11.44 111g/ml. respectively. The activity of the crudc enzyme was increased by1 rnM Pb(CH3COO). but was decreased by 5 n1M and 10 rnM of HgS04 and ZnS04. Thetwo proteinases produced amino acids and peptides from the soybean protein. The peptideswere digested into amino acids. Both protcinases were found to be the main enzymes thatproduced amino acids which make the main taste of traditional Korean soy sauce.al Korean soy sauce.

• Restorative Dentistry and Endodontics
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• v.24 no.1
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• pp.200-211
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• 1999

The periapical response to injury is a complex interaction of inflammatory, immune, neural, vascular and synthetic activity. TGF-${\beta}$ is a potent modulator of proliferation and differentiation in various tissue, seems to lead to an increase in extracellular matrix. MMP are a family of proteolytic enzyme that mediate the degradation of extracellular matric macromolecules, but little is known about theirs possible role in periapical tissue. The purpose of this study is to investigate the differential expression of TGF-${\beta}$ and MMP-1 in tooth follicle, periapical abscess, granuloma and cyst. The expression of TGF-${\beta}$ and MMP-1 in Periapical tissue was evaluated by immunohistochemical staining and Western blot analysis. Correlationship among the periapical lesions were stastically analyzed. The degree of MMP-1 expression in periapical abscess was higher than in any other periapical lesion, and stastically significant. TGF-${\beta}$ expression is the prominent in granuloma than other periapical lesion, which was stastically significant. The increased expression of MMP and TGF-${\beta}$ was not co-related with inflammatory cell infiltration degree of the periapical cyst. The expression degree of MMP and TGF-${\beta}$ was not co-related with periapical abscess and cyst, but expression of MMP and TGF-${\beta}$ showed strong positive co-relationship with periapical granuloma, which was stastically significant. TGF-${\beta}$ expression by Western blot analysis was prominent in granuloma and cyst, and similar to the results by imunohistochemistry. MMP-1 expression is less than TGF-${\beta}$, but there is not extreme difference between periapical lesion. These results suggest that TGF-${\beta}$ and MMP may be involved in tissue remodeling and has an important role in progress or mediation of periapical lesions.

• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.38-43
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• 2005

Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

• Journal of Life Science
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• v.20 no.4
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• pp.602-606
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• 2010

Type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Proteins in the matrix metalloproteinase-3 (MMP3) family are involved in the breakdown of the extracellular matrix in normal physiological processes such as embryonic development, reproduction and tissue remodeling, as well as in disease processes. Therefore, we investigated the genotype for the A(-267)G, A658G and T813C polymorphisms in the MMP3 gene in the Korean population and compared genotypes of patients with those of the control group. 200 patients (male 108, female 92), who had previously been diagnosed with type 2 diabetes (T2DM) and 100 control subjects (male 36, female 64) participated in this study. There was a strong association between A(-267)G and A658G polymorphism in the MMP3 gene and T2DM. The present study shows that MMP3 polymorphisms (A(-267)G and A658G) may be associated with the pathogenesis of T2DM. Further studies with a larger population may be needed for the development of diagnostic methods at a genetic level, such as DNA chip.

• 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.

• 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.

• 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.

• 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.