• The Journal of Korean Medicine
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• v.41 no.4
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• pp.12-26
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• 2020

Objectives: The aim of this study is to investigate the mechanisms involved in the anti-inflammatory and anti-tumor effects of Rhus verniciflua Stokes (RVS) on PMA-differentiated human monocytic leukemia THP-1 cells. Methods: Cells were treated with various concentrations of RVS decoction (0-300㎍/ml) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay. The expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, iNOS and COX-2 mRNA and proteins were measured using RT-PCR and western blotting, respectively. Results: RVS suppressed expression of MMP-2 and MMP-9 mRNA. It also down-regulated iNOS and COX-2 mRNA and protein expression. RVS inhibited NF-𝜅B p65 activity and the phosphorylation of Akt and MAPK (ERK and p38 MAPK). Instead, the phosphorylation of JNK is increased at a very low concentration but decreased at higher concentrations. Conclusion: RVS is regarded to inhibit the expression of MMP and TIMP as well as iNOS and COX-2 gene expression via directly inhibiting the activation of NF-𝜅B and phosphorylation of MAPK pathway in THP-1 cells. This suggests RVS have potential to be used as a therapeutic agent for acute myeloid leukemia (AML).

• Journal of Periodontal and Implant Science
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• v.38 no.4
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• pp.645-656
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• 2008

Purpose: To evaulate the effects of chlorhexidine and $H_2O_2$ on matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase(TIMP-1, TIMP-2), Type 1 collagen, fibronectin and UNCL expressions in human periodontal ligament fibroblasts (hPDLF). Materials and Methods: $1.2{\times}10^{-1}%$, $1.2{\times}10^{-2}%$ and $1.2{\times}10^{-3}%$ CHX and $3{\times}10^{-3}%$, $3{\times}10^{-4}%$ and $3{\times}10^{-5}%$ $H_2O_2$ and mixture of CHX and $H_2O_2$ were applied to hPDLF for 1 min and 30 min. The mRNA expressions of MMP-1, TIMP-1 and 2, Type 1 collagen, fibronectin and UNCL in hPDLF were analysed by RT-PCR. Results: The result were as follows: 1. The expression of UNCL mRNA was higher than that of other mRNAs. 2. $1.2{\times}10^{-3}%$ CHX increased mRNA expressions of hPDLF as application time increased. 3. $H_2O_2$ lower than $3{\times}10^{-3}%$ increased expression of UNCL mRNA, and did not decrease mRNA expression of hPDLF. 4. hPDLF treatment with $1.2{\times}10^{-1}%$ CHX (with or without $H_2O_2$) resulted in no gene expression. 5. hPDLF treatment with $1.2{\times}10^{-2}%$ CHX (with or without $H_2O_2$) for 30 minutes resulted in no gene expression. Conclusion: Because low concentration of CHX and $H_2O_2$ increased UNCL mRNA expression of hPDLF, low concentraction of CHX and $H_2O_2$ may have an antioxidative effect.

• Journal of Embryo Transfer
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• v.33 no.3
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• pp.99-105
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• 2018

To determine the differences in the in-vitro ovum maturation process of bovine, we compared the expression of MMPs in these oocytes and cumulus cell throughout oocytes maturated. In an attempt to investigate the effect of MMP activation and inhibitors in total protein of cumulus cell and, oocytes during oocytes maturation, we examined and monitored the localization and expression of MMPs (MMP-2 and MMP-9), TIMPs (TIMP-2 and TIMP-3), as well as their expression profiles (Real-time PCR, Gelatin Zymography and ELISA). Our results that the bovine oocytes MMP-2 and MMP-9 level was significantly associated with the rate of maturity of oocytes (P<0.05). In cumulus cell, MMP-2 was highly expressed in all stages of the oocyte's maturation. The final oocytes maturation exhibited strong gelatinase activity. There was no significant correlation between cumulus cell MMP-9 and the maturation rate of oocytes. However, for the oocyte cytoplasm MMP-9 expression was significant correlation to the maturation oocytes. There was no significant correlation between cumulonimbus cells MMP-9 and oocyte maturation rates; however, for oocyte cytoplasm, MMP-9 expression was significantly correlated with mature oocyte. However, the TIMP-1 and TIMP-2 protein expression patterns are not correlated with the maturation rate of the oocyte. Our results suggest that MMP different expression pattern may regulate the morphological remodeling of oocyte's in the cumulus cell. Further, the MMP-2 expression has a strong relation with a higher maturation rate of the oocyte.

• Journal of Music and Human Behavior
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• v.19 no.2
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• pp.81-103
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• 2022

The effects of therapeutic instrumental music performance (TIMP) using a ukulele were examined in adults with central nervous system damage and impaired hand functions. The participants were three adults with neurological damage who participated in 30-min sessions twice a week over 6 weeks. Changes in hand function was measured by the Box and Block Test (BBT), the 9-Hole Peg Test (9-HPT), and the Jebsen-Taylor Hand Function Test (JTHFT). Following the intervention, all three participants showed increases in the BBT and 9-HPT scores, indicating positive changes in fine motor coordination and dexterity. In terms of the JTHFT, all three participants showed increases in the "writing" and "card flipping" subtask scores, indicating that the intervention was effective in improving more coordinated finger movements. All participants reported the satisfaction with the intervention. They also pointed out that they were motivated to play the ukulele and that following the intervention used their affected hand more frequently in daily activities. These findings suggest that TIMP with a ukulele for patients with central nervous system damage can have positive effects on their functional hand movements and motivate these patients to practice their rehabilitation exercises.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.407-419
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• 2002

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method： We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result： Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group： 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion： The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.

• Journal of Korean Neurosurgical Society
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• v.55 no.5
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• pp.237-243
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• 2014

Objective : Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods : Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results : MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-$1{\beta}$ stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion : Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

• Journal of Life Science
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• v.31 no.11
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• pp.980-986
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• 2021

Natural products have always been an attractive source in terms of novel anti-metastatic compounds which can hinder MMP expression and activity. Corydalis heterocarpa is a salt marsh plant found in the seashores throughout Korea. Its yellow flowers and spikes have been an ingredient in folk medicine to treat spasm and contractions. The present study assessed the potential of different solvent-based fractions from the crude extract of Corydalis heterocarpa (CHE), a halophyte with reported bioactivities, to suppress the PMA-induced MMP expression in human fibrosarcoma HT-1080 cells. The solvent fractions which were named after the solvent used for fractionation (n-hexane, 85% aqueous (aq.) methanol (MeOH), n-butanol (BuOH), and H₂O were shown to inhibit the both elevated mRNA and protein expression levels of MMP-2 and MMP-9 and simultaneously relieved the suppression on the expression of the endogenous MMP inhibitors TIMP-1 and TIMP-2. Results indicated that the CHE fractions might intervene with the PMA-induced activation of the MAPK signaling which is the upstream activator of MMP overexpression. Among tested samples, 85% aq. MeOH and n-hexane fractions of CHE was determined to be the most active and future studies to isolate the bioactive substances responsible for the regulation of the MMP expression are, therefore, urged. In conclusion, C. heterocarpa was shown to be a potential source of anti-metastatic compounds and n-Hexane and MeOH fractions might yield lead molecules to develop novel MMP inhibitors.

• Molecules and Cells
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• v.39 no.2
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• pp.103-110
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• 2016

As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-$1{\beta}$. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-$1{\beta}$ on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-$1{\beta}$ treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-$1{\beta}$, thereby suggesting potent synergistic action. These results provided1novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4893-4896
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• 2014

Background: Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) plays an important role in metastasis. Despite a clear understanding of the protein's structure and properties, its functional role remains elusive. We conducted the present study to evaluate the expressions of CXCR4 in pancreatic cancer, and to investigate its relationship with clinicopathological parameters, especially perineural invasion(PNI). Materials and Methods: The association between CXCR4 expression and perineural invasion was determined by immunohistochemistry in pancreatic cancer patients (n=51). Results: CXCR4 expression was correlated with the existence of PNI and the type of PNI (p=0.042, p=0.040). TIMP-2 expression was also correlated with the existence, the pathway and degree of PNI (p=0.000, p=0.006, p=0.000). Conclusions: Our results suggest an association between PNI and expression of CXCR4 and TIMP-2 in pancreatic cancer. CXCR4 may promote the occurrence of PNI in pancreatic cancer cells by decreasing the inhibition of TIMPs on MMP.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.213-219
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• 2011

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.