• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.6
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• pp.499-508
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• 2007

Background and Purpose: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. Experimental Design: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2. Results: Transplantation of human ACC tumor cell $(5{\times}10^5)$ into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P<0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC. Conclusion: VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

• Molecules and Cells
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• v.41 no.6
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.90-97
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• 2009

Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation. Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface. Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-${\kappa}B$. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of $I{\kappa}B$, and nuclear translocation of NF-${\kappa}B$ p65 and p50 subunits. Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.3
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• pp.223-229
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• 2015

In this study, we investigated the effect of ethanol extracts from Gentianae scabrae bunge (GSB) on the activities of antioxidant, whitening and anti-inflammation. Viability of cells was measured by neutral red (NR) assay, and inhibitory effects of GSB on melanin synthesis was determined the melanin production in B16F10 cells. The expression level of matrix metalloproteinase-1 (MMP-1) in media was analyzed by ELISA kit, and nitric oxide (NO) production in RAW264.7 cells was monitored by measuring the nitrite content in culture medium. GSB showed highly efficacy in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and significantly reduced melanin synthesis in B16F10 cells. MMP-1 production in UVB-stimulated human dermal fibroblast (HDF) cells was inhibited by GSB treatments. NO production was suppressed by the treatment of GSB in LPS-stimulated RAW264.7 cells. From this results, it was indicated that GSB could be utilized as anti-aging and whitening cosmetic ingredients.

• Toxicological Research
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• v.28 no.4
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• pp.241-248
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• 2012

Exposure of cells to ultraviolet B (UVB) radiation can induce production of free radicals and reactive oxygen species (ROS), which damage cellular components. In addition, these agents can stimulate the expression of matrix metalloproteinase (MMP) and decrease collagen synthesis in human skin cells. In this study, we examined the anti-photoaging effects of extracts of Tetraselmis suecica (W-TS). W-TS showed the strongest scavenging activity against 2,2-difenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals, followed by superoxide anions from the xanthine/xanthine oxidase system. We observed that the levels of both intracellular ROS and lipid peroxidation significantly increased in UVB-irradiated human skin fibroblast cells. Furthermore, the activities of enzymatic antioxidants (e.g., superoxide dismutase) and the levels of non-enzymatic antioxidants (e.g., glutathione) significantly decreased in cells. However, W-TS pretreatment, at the maximum tested concentration, significantly decreased intracellular ROS and malondialdehyde (MDA) levels, and increased superoxide dismutase and glutathione levels in the cells. At this same concentration, W-TS did not show cytotoxicity. Type 1 procollagen and MMP-1 released were quantified using RT-PCR techniques. The results showed that W-TS protected type 1 procollagen against UVB-induced depletion in fibroblast cells in a dose-dependent manner via inhibition of UVB-induced MMP-1. Taken together, the results of the study suggest that W-TS effectively inhibits UVB-induced photoaging in skin fibroblasts by its strong anti-oxidant ability.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.21-29
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• 2019

The effects of Lavandula angustifolia extract fermented with Pediococcus pentosaceus DK1 on UVB-mediated MMP-1 expression and collagen decrease in human skin fibroblasts were determined, and the conversion of its components was also analyzed. Fermentation was performed at varying L. angustifolia extract and MRS medium concentrations, and optimal fermentation conditions were selected. L. angustifolia extracts showed decreased cytotoxicity after fermentation in the fibroblasts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extract showed MMP-1 expression 8.2-14.0% lower than that in UVB-irradiated fibroblasts treated with non-fermented extract. This was observed even at fermented extract concentrations lower than those of non-fermented extracts. Fibroblasts treated with fermented L. angustifolia extract showed 20% less reduction in collagen production upon UVB irradiation than those treated with non-fermented extracts. UVB-irradiated fibroblasts treated with fermented L. angustifolia extracts showed 50% higher inhibition of ROS generation than those treated with non-fermented extract. Luteolin and apigenin glycosides of L. angustifolia were converted during fermentation, and identified using RP-HPLC and LC/ESI-MS. Therefore, the effects of L. angustifolia extract on MMP-1 expression and collagen decrease in UVB-irradiated human skin fibroblasts were increased through fermentation by P. pentosaceus.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.175-184
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• 2022

Background: Post-tuberculosis (TB) sequelae is a commonly encountered clinical entity, especially in high TB burden countries. This may represent chronic anatomic sequelae of previously treated TB, with frequent symptomatic presentation. This pilot study was aimed to investigate the pulmonary functions and systemic inflammatory markers in patients with post-TB sequelae (PTBS) and to compare them with post-TB without sequelae (PTBWS) participants and healthy controls. Methods: A total of 30 participants were enrolled, PTBS (n=10), PTBWS (n=10), and healthy controls (n=10). Pulmonary function tests included spirometry and measurement of airway impedance by impulse oscillometry. Serum levels of matrix metalloproteinase (MMP)-1, transforming growth factor-β, and interferon-γ were estimated. Results: Slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), FEV₁/FVC, and peak expiratory flow were significantly lower in PTBS as compared to controls. SVC and FEV₁ were significantly less in PTBS as compared to PTBWS. Total airway impedance (Z₅), total airway resistance (R₅), central airway resistance (R₂₀), area of reactance (Ax), and resonant frequency (Fres) were significantly higher and respiratory reactance at 5 and 20 Hz (X₅, X₂₀) were significantly lower in PTBS as compared to PTBWS. Spirometry parameters correlated with impulse oscillometry parameters in PTBS. Serum MMP-1 level was significantly higher in PTBS as compared to other groups. Conclusion: Significant pulmonary function impairment was observed in PTBS, and raised serum MMP-1 levels compared with PTBWS and healthy controls. Follow-up pulmonary function testing is recommended after treatment of TB for early diagnosis and treatment of PTBS.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.640-647
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• 2023

The skin, the largest organ in the body, undergoes age-related changes influenced by both intrinsic and extrinsic factors. The primary external factor is photoaging which causes hyperpigmentation, uneven skin surface, deep wrinkles, and markedly enlarged capillaries. In the human dermis, it decreases fibroblast function, resulting in a lack of collagen structure and also decreases keratinocyte function, which compromises the strength of the protective barrier. In this study, we found that treatment with γ-aminobutyric acid (GABA) had no toxicity to skin fibroblasts and GABA enhanced their migration ability, which can accelerate skin wound healing. UVB radiation was found to significantly induce the production of matrix metalloproteinase 1 (MMP-1), but treatment with GABA resulted in the inhibition of MMP-1 production. We also investigated the enhancement of filaggrin and aquaporin 3 in keratinocytes after treatment with GABA, showing that GABA can effectively improve skin moisturization. In vivo experiments showed that oral administration of GABA significantly improved skin wrinkles and epidermal thickness. After the intake of GABA, there was a significant decrease observed in the increase of skin thickness measured by calipers and erythema. Additionally, the decrease in skin moisture and elasticity in hairless mice exposed to UVB radiation was also significantly restored. Overall, this study demonstrates the potential of GABA as functional food material for improving skin aging and moisturizing.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1484-1494
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• 2023

NUC1 (Nutraceutical compound 1) is an ethanol extract composed of a formulation based on medicinal herbs traditionally used for the treatment of arthritis in Korea and China. This study investigated the therapeutic effects of NUC1 on osteoarthritis (OA). The protective effect of NUC1 on OA was tested in a rabbit model of collagenase-induced arthritis (CIA) for 4 weeks. Results were compared among four groups (n = 9 per group): the normal group (untreated), the CIA group (vehicle control), the NUC1 group (CIA rabbits treated with 200 mg/kg NUC1), and the JOINS group (positive control, CIA rabbits treated with 200 mg/kg JOINS tablet). NUC1 significantly inhibited NO production (p < 0.05 at 125 ㎍/ml, p < 0.01 at 250 ㎍/ml, and p < 0.001 at 500 ㎍/ml) and iNOS expression in macrophages, in a concentration-dependent manner. NUC1 also inhibited the release and protein expression of MMP-1, 3, and 13, in TNF-α-induced chondrosarcoma cells in a concentration-dependent manner. In vivo, the MMP-1 and MMP-3 levels in synovial fluids were significantly (p < 0.05) lower in NUC1 group (77.50 ± 20.56 and 22.50 ± 7.39 pg/ml, respectively) than in the CIA group (148.33 ± 68.58 and 77.50 ± 20.46 pg/ml, respectively). Also, in histopathological, NUC1 ameliorated articular cartilage damage in OA by increasing the abundance of chondrocytes and proteoglycan in the articular cartilage. Thus, NUC1 showed promise as a potential therapeutic agent, and it can be generalized to a broader study population in different OA animal models.

• Journal of Ginseng Research
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• v.31 no.2
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• pp.86-92
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• 2007

This study was carried out to develop health & functional food by using Korean red ginseng for prevention of skin wrinkles. Effects of Korean red ginseng on the collagen biosynthesis and inhibition of matrix metalloproteinase-I (MMP-1) activity in human dermal fibroblast were investigated. Crude saponin contents of Korean red ginseng water extract (WE), Korean red ginseng ethanol extracts (EE) and Korean Red ginseng purified extracts (PE) were 72 mg/g, 107 mg/g and 220 mg/g, respectively. We incubated human fibroblast cell with Korean red ginseng component by addition of l ${\mu}g/ml$, 5 ${\mu}g/ml$, 10 ${\mu}g/ml$. Amount of collagen biosynthesis was 1.86 ng/ml in control sample and 2.85 ng/ml, 2.05 ng/ml and 2.58 ng/ml in retinoic acid, EE and PE respectively. Furthermore, $ginsenoside-Rg_1$ and $ginsenoside-Rb_1$ were shown 2.01 ng/ml and 3.07 ng/ml. MMP-l activities of EE, PE, $ginsenoside-Rg_1$ and $ginsenoside-Rb_1$ were decreased to 92%, 94%, 91% and 78% respectively as compared with control. Cell proliferation were showed 84-96% in the Korean red ginseng components. The antioxidative SOD activities of the Korean red ginseng components were showed 28-69%, however it was lower than that of Vitamin C. From this results, we conclude that Korean red ginseng have a anti-wrinkle effect and $ginsenoside-Rb_1$ may be considered as a more effective component.