• Journal of Applied Biological Chemistry
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• v.61 no.1
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• pp.9-15
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• 2018

We analyzed the antioxidant and anti-wrinkle activities of berberine, isolated from dried rhizome of Coptis japonica Makino, to determine its cosmetic potential. We performed the 3-[4,5-dimethylthiazol]-2-yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay to evaluate the toxicity of the berberine. We also measured the ROS and hyaluronic acid production, and expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and tumor necrosis factor-alpha ($TNF-{\alpha}$) to evaluate the antioxidant and anti-wrinkle activities of berberine, respectively. The cytotoxicity of ultraviolet light, in presence of berberine, was measured by the MTT assay using CCD-986sk fibroblasts, and no cytotoxicity was observed at concentrations less than $25{\mu}g/mL$. We also found that berberine decreased ROS production in a concentration-dependent manner and promoted the synthesis of hyaluronic acid. Further, berberine reduced the protein levels and mRNA expression of MMP-2 and MMP-9, which are associated with wrinkle formation, and increased the expression of TIMP-1 and TIMP-2. In addition, the inhibitory effect of berberine on $TNF-{\alpha}$, known as pro-inflammatory cytokine, was inhibited by $TNF-{\alpha}$ gene in a concentration-dependent manner. These results suggest that berberine holds cosmetic value owing to its antioxidant activity, by inhibiting ROS production and anti-wrinkle activity by reducing MMP-2 and MMP-9 and increasing TIMP-1 and TIMP-2 expression.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.370-378
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• 2005

The purpose of this study is that evaluate the distribution and biological roles of TNF-a, interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and tissue inhibitors of metalloproteinase-1(TIMP-1) in the synovial fliud of patients with non-inflammatory chronic temporomandibular joint(TMJ) disorders in relation to pain during joint movements and magnetic resonance imaging(MRI) findings. TMJ synovial fluids aspirates were obtained from 36 patients (36 joints) with chronic TMJ disorders and from 8 controls(8 joints). Patients were divided to four groups. The control group was from healthy volunteers(8 joints), group I(18 joints) was patients with anterior disc displacement with reduction, group II(5 joints) was patients with disc displacement without reduction and group III (5 joints) was osteoarthritis. The TNF-${\alpha}$, IL-1${\beta}$ and IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain during joint movements and MRI observations, these cytokines' level and frequencies of detection were compared. The level of IL-1${\beta}$was not significant different in all groups. but the level of TNF-${\alpha}$, IL-6 and TIMP-1 were significant different among groups. The level of IL-6 and TIMP-1 were correlated to pain during movement(p<0.01) and the level of TNF-a(p<0.05). Also, the level of IL-6 was correlated to the level of TIMP-1(p<0.01). Especially, The level of the TIMP-1 level was significantly correlated to the pain during movement and showed very high levle of Pearson's correlation coefficient (r=0.833)(p<0.001). The results indicated that the TNF-${\alpha}$, IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. Especially, IL-6 and TIMP-1 were very high levels in the patients who were degraded in the TMJ. Also, TNF-${\alpha}$, IL-6 and TIMP-1 showed the significant correlation in the chronic temporomandibular joint disorders. Therefore I suggest that these cytokines were also correlated to the pain during movement in the chronic temporomandibular joint disorders.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.123-132
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• 2005

중등도 이상의 치주염 환자에서 치은 열구액내의 MMPs 및 TIMP-1 과 치주염과의 연관성을 규명하고, 치주 수술이 MMPs 및 TIMP-1의 정량에 미치는 영향을 연구하고자 하였다. 총 14명의 치주낭 깊이 6mm 이상의 중등도 이상의 치주 질환 이환자에서 치아를 선정하여, 치주낭 심도, 치은 지수(gingival index)를 측정하고, 치은의 조직학적 염증의 정도를 측정하기 위해, 해당 치아의 치주낭 연조직을 절취하여 H-E염색을 하고, 치은 절편에서 염증세포 침윤의 정도 및 분포를 비교하였다. Perio-paper를 이용하여 치은열구액을 얻고, pyrogen-free water에서 추출하였다. 채취한 치은 열구액에서 ELISA-kit를 이용하여 MMP-1, 8, 9, 13과 TIMP-1을 측정하여 수술 전과, 수술 후, 그리고 건강한 조직인 대조군을 비교하였으며, 통계처리는 Wilcoxon 검정을 사용하였다. 또한 MMPs 혹은 TIMP-1이 치주낭 심도나 치은지수등의 임상적 지표와 가지는 연관성을 Spearman's correlation coefficient를 이용하여 알아보았다. TIMP-1을 제외한 MMP-1, 8 ,9, 13 에서 수술 전보다 수술 후에 치은 열구액 내의 양이 현저하게 줄어든 것을 관찰할 수 있었으나, MMP-1(p=0.025), MMP-9(p=0.016) 와 MMP-13(p=0.009) 에서만 통계적으로 유의성있는 차이를 보였다. 한편 MMP-9 (p=0.011) 나 MMP-13(p=0.026) 은 건강한 대조군과 수술 전 사이에도 유의성있는 차이를 보였다. 연조직의 조직학적 관찰을 통하여 치은지수의 임상적 신뢰도를 평가한 결과 통계학적으로 유의한 결과를 얻을 수 있었으며, 치주 치료 전의 치주낭 심도와 치은지수와의 관계나, 수술 전과 수술 후의 치주낭 심도등의 변화도 통계적으로 유의성있는 결과를 보였다. 하지만 치주낭 심도나 치은지수등의 임상적 지표는 MMPs나 TIMP의 정량과는 별다른 연관성을 보이지 않았다. 이 실험의 결과로 보아 MMP-1, MMP-9나 MMP-13을 치주 수술 전과 수술 후의 치주염의 심도 변화를 반영할 수 있는 지표로 생각할 수 있으며, 특히 MMP-9와 MMP-13가 치주염과 가지는 연관성은 크다고 할 수 있겠다.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.142-142
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• 2003

TGF-$\beta$ super family는 난소를 포함하여 여러 기관 및 조직의 성장에 광범위하게 영향을 미치는 것으로 알려져 있으며, TGF-$\beta$ super family는 난자의 매우 초기에 영향을 미치며, 난포의 성장을 촉진하여 초기의 난자의 형태를 이루는데 중요한 역할을 하는 것으로 알려져 있다. 한편 TIMP-1은 난관상피세포로부터 분비되는 난자의 생리활성 촉진인자로 보고되고 있다. 따라서 본 연구는 한우난포란의 체외성숙에 난자의 생리활성 촉진인자를 이용하여 한우 체외성숙 및 체외수정에 미치는 영향을 구명하고자 실시하였다. 한우 난포란은 도축암소의 난소를 채취하여 회수하였으며, 체외성숙은 HP-TCM를 기본 배양액으로 TGF-$\beta$ 0.1, 1, 10 ng/ml를 첨가하여 실시하였고, TIMP-1은 0.05, 0.5, 5ng/ml를 첨가하여 6, 12, 24시간 동안 체외성숙시켰다. 체외성숙된 난자는 체외성숙율을 검사하기 위하여, 0.1% aceto-orcein으로 염색을 실시하여 핵의 변화를 검사하였다. (중략)

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.873-876
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• 2013

Our aim was to test the hypothesis that preoperative serum levels of matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels correlate with pathological features. Serum levels of MMP-7, and MMP-9 and TIMP-1 were determined in 90 bladder cancer patients and 40 healthy controls using an enzyme linked immunosorbent assay. Preoperative serum MMP-7 and MMP-9 levels were significantly higher in cancer patients than control groups (p<0.001). In contast, serum TIMP-1 levels were lower (p<0.001). Alteration in MMP-7, and MMP-9, and TIMP-1 production may contribute to tumor angiogenesis and be associated with clinic-pathological features.

• Journal of Applied Biological Chemistry
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• v.63 no.1
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• pp.75-82
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• 2020

In this study, extracts from the Green ball apple peel (GBE) and the newly bred green ball apple from Korea showed inhibition effects on photo-aging factor regulation associated with skin aging. To investigate the inhibition effect on photo-aging factor regulation in skin, GBE was treated with UVB to induce photo-aging related factors in CCD986sk fibroblast cells. Photo-aging factor regulation effects showed that GBE inhibited UVB-stimulated matrix metalloproteinase (MMP)-1 and MMP-9 protein synthesis in collagen type I alpha 2 chain (COL1A2), MMP-1, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1 protein expression. The expression of COL1A2 and TIMP-1 protein was significantly increased. The mRNA expression levels of COL1A2, MMP-1, MMP-9, hyaluronan synthase (HAS)2, transforming growth factor (TGF)-β, and TIMP-1 were decreased by GBE. The expression of TIMP-1 and TGF-β, which are regulators involved in matrix metalloproteinase and type I procollagen expression, was found to increase with increasing expression of COL1A2. The expression of HAS2, which is involved in the production of hyaluronic acid, one of the structural proteins constituting the skin, was also confirmed. Therefore, GBE showed excellent efficacy against photo-aging factor regulation and could be used as functional material to prevent and treat skin aging.

• Restorative Dentistry and Endodontics
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• v.30 no.5
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• pp.372-384
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• 2005

The purpose of this study was to monitor the secretion of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) by human periodontal ligament (PDL) fibroblasts stimulated with Prevotella nigrescens lipopolysaccharide (LPS), and to examine the effect of calcium hydroxide treatment on P. nigrescens LPS. LPS was extracted and purified from anaerobically cultured P. nigrescens. PDL fibroblasts were stimulated by the LPS (0, 0.1, 1, 10 ${\mu}g/ml$) or LPS (10 ${\mu}g/ml$) pretreated with 12.5 mg/ml of $Ca(OH)_2$ for 3 days, for various periods of time (12, 24, 48 h). Immunoprecipitation were performed for protein level analysis of MMP-1 MMP-2 and TIMP-1. Total RNA was isolated and real-time quantitative polymerase chain reaction (PCR) was performed for quantification of MMP-1 mRNA. According to this study, the results were as follows: 1. The p개duction of MMP-1 by stimulation with P. nigrescens LPS increased in time-dependent manner, and showed maximum value at 48 h in both protein and mRNA level. But there was no dose-dependent increas. 2. MMP-2 production time-dependently increased when stimulated with 1 and 10 ${\mu}g/ml$LPS, but there was no dose-dependent increase. 3. TIMP-1 p개duction increased to 24 h, but decreased at 48 h. It increased when stimulated with 0.1 and 1${\mu}g/ml$, but suppressed at 10 ${\mu}g/ml$ .4. P. nigrescens LPS pretreated with $Ca(OH)_2$ markedly downregulated MMP-1 gene expression.

• The Journal of the Korean dental association
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• v.35 no.10 s.341
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• pp.798-799
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• 1997

• Journal of Music and Human Behavior
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• v.8 no.1
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• pp.1-16
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• 2011

This study was to investigate the influence of using Therapeutic Instrumental Music Performance (TIMP) in uninvolved hand function for children with spastic cerebral palsy. Participants were recruited from a welfare center for people with cerebral palsy(CP). Ages ranged from 11 to 12, and a total of 15 TIMP sessions were provided for 3 weeks. Hand function tests were used including Jebsen Hand Function Test for hand function, Box and Block Test for dexterity of uninvolved hand, and MIDI (Musical Instrument Digital Interface) evaluation for velocity of fingers. The TIMP program consisted of hand percussion playing and keyboard playing with changes of timbre and tempo. While the scores of Jebsen test and Box and Block test were improved for all participants, outcomes of MIDI analysis showed differences among participants. Overall, hand function improvements were observed after the completion of using the TIMP program, and the results implies that the TIMP program can be applied in upper extremity rehabilitation for children with CP.

• BMB Reports
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• v.32 no.1
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• pp.60-66
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• 1999

Matrix metalloproteinase-2 (MMP-2; 72-kDa gelatinase; 72-kDa type IV collagenase; gelatinase A) plays an important role in normal physiological processes and in many pathologic processes such as arthritis and metastasis of cancer. Tissue inhibitor of metalloproteinases-2 (TIMP-2) binds to proMMP-2 or mature MMP-2 at a 1:1 ratio and inhibits the catalytic activity of MMP-2. We demonstrated that the baculovirus/insect cell system does not have TIMP-2 activity. The human proMMP-2 free of TIMP-2 was expressed in the expression system and purified by one-step affinity chromatography using gelatin-Sepharose. The free proMMP-2 was autoactivated to the mature MMP-2 and autodegraded into smaller molecular weight forms in the absence of external activator. The activation and autodegradation of the proMMP-2 was much more rapid in the presence of 4-aminophenylmercuric acetate (APMA). Addition of TIMP-2 inhibits both APMA-induced activation and autodegradation of the free proMMP-2. However, an increasing concentration of TIMP-2 more readily inhibited activation of the free proMMP-2 than autodegradation. These results demonstrate that TIMP-2 plays roles in inhibition of both activation and autodegradation of the free proMMP-2 in addition to inhibition of the catalytic activity of MMP-2.