• IMMUNE NETWORK
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• v.10 no.3
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• pp.92-98
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• 2010

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs). Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells. Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs. Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.1
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• pp.1-12
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• 2013

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

• Molecules and Cells
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• v.26 no.6
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• pp.583-589
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• 2008

In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-$1{\alpha}$ ($MIP-1{\alpha}$) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and $MIP-1{\alpha}$ induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of $NF-{\kappa}B$. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.481-491
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• 2018

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

• The Journal of Pediatrics of Korean Medicine
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• v.36 no.3
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• pp.87-96
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• 2022

Objective The purpose of this study was to confirm the effect of Sabaek-san extract on skin damage recovery and inflammation relief in atopic dermatitis-induced mice through Endocannabinoid system (ECS) control. Methods In this study, we used 6-week-old NC/Nga mice were divided into 4 group: control group (Ctrl), lipid barrier elimination group (LBEG), palmitoylethanolamide (PEA) treated group after lipid barrier elimination (PEAG), and Sabaek-san extract treatment group after lipid barrier elimination (SBSG). Each group was assigned 10 animals. After drug administration of three weeks duration following lipid barrier elimination, cannabinoid receptor (CB) 1, CB2, CD (Cluster of Differentiation) 68, phosphorylated inhibitor kappa B (p-IκB), inducible nitric oxide synthase (iNOS), Fc ε receptor, substance P and serotonin were observed to confirm the regulation of the ECS, macrophage activity and mast cell activity. Results We found that 8-hydroxydeoxyguanosine (8-OXdG) positive reaction was significantly lower in the SBST group than in LBET and PEAT groups. Both CB1 and CB2 showed higher positive reactions in the SBST group than in the LBET and PEAT. CD68, p-IκB, iNOS, Fc ε receptor, Substance P and serotonin showed lower positive reaction in the SBST compared to the LBET and PEAT. Conclusion It was confirmed that the Sabaek-san extract can reduce the inflammation of atopic dermatitis by restoring the structural damage of the skin lipid barrier through ECS activity.

• Advances in nano research
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• v.12 no.6
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

• The Korea Journal of Herbology
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• v.20 no.2
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• pp.159-169
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• 2005

Objectives : This study was carried out for the purpose of knowing the effect from anti-arthma action of the abstraction from a extract of Paridis Rhizoma(EPR). In order to know what the effect of controlling an abstraction from Paridis Rhizoma. and about the expression of B cells and Ig E cells, mast cells it was necessary for it to be activated by ovalbumin. Methods : In order to know what the effect was on the organization of cytokine gene expression from The increase and divorce of the B cells and allergic acting by EPR, we found it necessary to examine the BALF. At the same time, as we examined the histamine release by ELISA method, we also examined the effect of EPR. Results : EPR at $100\;{\mu}g/ml$, the highest concentration examined did not have any cytotoxic effects on mLFCs. In FACS analysis, number of granulocyte/lymphocyte, $CD3e^+/CCR3^+,\;CD4^+\;and\;CD23^+/B220^+$ in asthma-induced lung cells were significantly decreased by EPR treatment compared to the control group. In RT-PCR analysis, mRNA expression for CCR3, eotaxin and histamine in asthma-induced lung cells, which was induced by rIL-3 plus rmIL-5 treatments, was significantly decreased by EPR treatment. In ELISA analysis, production levels of IL-4, IL-13 and histamine in asthma-induced lung cells, which were induced by rIL-3 plus rmIL-5 co-treatment, were significantly decreased by EPR treatment. EPR treatments significantly inhibited the proliferation of eosinohils prepared from asthma-induced mouse lung tissues compared to the non-EPR treated control cells. Immunohistochemical analysis revealed that EPR treatment significantly decreased the levels of eosipnphil activation compared to non-treated cells. Conclusion : The present data suggested that Paridis Rhizoma may have an effects on the inhibition of parameters associated with asthma responses in eosinpophils, and thus implicate the possibility for the clinical application of Paridis Rhizoma.

• Journal of Dairy Science and Biotechnology
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• v.33 no.4
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• pp.271-275
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• 2015

Colloidal semiconductor CdSe-ZnS core-shell nanocrystal quantum dot (Qdot) are luminescent inorganic fluorophores that show potential to overcome some of the functional limitations encountered with organic dyes in fluorescence labeling applications. Salmonella Enteritidis has emerged as a major cause of human salmonellosis worldwide since the 1980s. A rapid, specific, and sensitive method for the detection of Salmonella Enteritidis was developed using Qdot as a fluorescence marker coupled with immunomagnetic separation. Magnetic beads coated with anti-Salmonella Enteritidis antibodies were employed to selectively capture the target bacteria, and biotin-conjugated anti-Salmonella antibodies were added to form sandwich immune complexes. After magnetic separation, the immune complexes were labeled with Qdot via biotin-streptavidin conjugation, and fluorescence measurement was carried out using a fluorescence measurement system. The detection limit of the Qdot method was a Salmonella Enteritidis concentration of $10^3$ colony-forming units (CFU)/mL, whereas the conventional fluorescein isothiocyanate-based method required over $10^5CFU/mL$. The total detection time was within 2 h. In addition to the potential for general nanotechnology development, these results suggest a new rapid detection method of various pathogenic bacteria from a complex food matrix.

• The Journal of Korean Society of Virology
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• v.30 no.3
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• pp.161-170
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• 2000

Continuous efforts are being made to find effective therapeutic agents against HIV-1, the causative agents of AIDS. In this study, we developed a cell-based assay system employing a trans-complementation for production of recombinant viruses which are capable of undergoing one round of replication in CD4+ T cells. This assay system was tested for ability to screen the agents that act at late stage of HIV-1 life cycle. The effect of a protease inhibitor on the trans-complementation assay was assessed. Recombinant HIV-1 viruses were prepared from a trans-complementation in the presence of various concentrations of protease inhibitor. Inhibition of single round infection of these recombinant viruses by protease inhibitor was observed to be a dose-dependent manner. Inhibitory effects of a protease inhibitor on HIV-1 Gag polyprotein processing by HIV-1 protease was detected at concentrations of the protease inhibitor compatible with inhibition of virus infection, confirming that the corresponding step was involved in the inhibitory mechanism of this compound. Together, these results provide evidence that a cell-based assay system established in this study can be used to screen the agents that target the late stage of HIV-1 life cycle.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.282-289
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• 2008

We evaluated the effect of SHBCS on adhesion and invasion of colon L5-26 adenocarcinoma cell line in vitro in vitro and experimental liver metastasis in vivo. SHBCS showed little inhibitory effect on colon 26-L5 cell proliferation. At the concentration of up to 500 mg/ml of SHBCS 80% of cells were viable. SHBCS showed no inhibitory effect on adhesion and invasion of colon 26-L5 cells, which were placed on matrigel. In a dose dependent manner, oral administration of SHBCS showed a significantly inhibitory effect on liver metastasis from colon 26-L5 injected mice. When mice were depleted of NK cells or macrophages before tumor inoculation, SHBCS significantly decreased liver metastasis fromf the tumor injected mice. Compared with the control mice, SHBCS increased the populations of macrophages and NK cells by 30%, 18%(10 mg/mouse, 50 mg/mouse) and 5%, 1% (10 mg/mouse, 50 mg/mouse) respectively. Compared with the control mice, SHBCS increased the populations of CD4 cells by 5%, 18% (10 mg/mouse, 50 mg/mouse) respectively. Spelenocytes from mice administerd with SHBCS were stimulated with LPS plus ConA, proliferation of splenocytes from mice administerd with SHBCS was 140%, 146%(10 mg/mouse, 50 mg/mouse) compared with th control mice. In conclusion, the present study suggests that SHBCS may have an inhibitory effect on liver metastasis through immunopotentiating activity which is associated with macrophages and NK cells.