• 동의생리병리학회지
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• 제27권2호
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• pp.212-224
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• 2013

This study intends to clarify how Sayeok-tang(here in after reffered to SYT) affect C57BL/10 mice whose osteoarthritis was induced by papain. Osteoarthritis was induced by injecting papain in the knee joint of 3 groups(n=6) of mice. Normal group was non-treatment group and was not injected papain, whereas control mice were orally administered with $200{\mu}{\ell}$ of physiological saline. Positive comparison group was medicated with 100 mg/kg of Joins$^{(R)}$ mixed with $200{\mu}{\ell}$ of physiological saline. Experimental group was medicated with 400 mg/kg of SYT mixed with $200{\mu}{\ell}$ of physiological saline. Both Positive and experimental comparison groups were orally medicated once per day for 4 weeks. After the experiment, the functions of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological changes in the knee joint structures were observed. As results, SYT had no significant effect on the liver and kidney functions. Interleukin-$1{\beta}$(IL-$1{\beta}$), interleukin-6(IL-6), monocyte chemo attractant protein-1(MCP-1) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were significantly decreased. Inflammation cytokines in joints were all significantly decreased. Prostaglandin $E_2(PGE_2)$, thromboxane $B_2(TXB_2)$ were significantly decreased. Destruction of cartilage on micro computed tomography(CT)-arthrography was meaningfully decreased. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small. Based on all results mentioned above, Sayeok-tang(SYT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• Toxicological Research
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• 제22권2호
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• 대한한의학회지
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• 제38권4호
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• pp.11-40
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• 2017

Objectives: We investigated whether a mixture of the main component of pomegranate concentrated powder (PCP) with appropriate proportions of Eucommiae Cortex (EC) and Achyranthis Radix (AR) could act synergistically as an effective treatment for osteoarthritis (OA). Methods: In order to evaluate the effects of PCP, EC, and AR against OA, knee thicknesses, maximum extension angle of each knee, anti - inflammation effects, the transcript levels of chondrogenic genes mRNA expressions in femur and tibia articular cartilage (AC) with synovial membrane (SM) were analyzed. In addition, the histopathology and immunohistochemistry of the femur and tibia AC or SM were performed. Results: The surgically-induced OA signs in rats were significantly inhibited by 28 days of continuous treatment of PCP, EC and AR single formulas, and PCP with EC:AR mixed formulas. Especially, PCP with EC:AR 4:1, 2:1 and 1:1 mixed formula treatment constantly showed significantly more favorable inhibitory activities, as compared with those of single formula of PCP, EC and AR treated rats. Conclusion: PCP and EC:AR 4:1 mixed formula showed similar OA refinement effects through potent anti-inflammatory pathways as compared with those of diclofenac treatment, and showed additional chondrocyte proliferating effects on the both femur and tibia AC.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1433-1442
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• 2018

To identify and quantify the effects of a combination of dietary $1{\times}10^8CFU/g$ Lactococcus lactis subsp. lactis I2 ($LI_2$) and 0.1% ${\beta}$-glucooligosaccharides (BGO) on the growth and immunity of olive flounder (Paralichthys olivaceus), a feeding experiment was conducted. Flounder ($14{\pm}0.5g$) were divided into two groups and fed control and synbiotic feeds for 8 weeks. Investigations were carried out on growth and feed utilization, innate immunity, serum biochemical parameters, intestinal lactic acid bacterial (LAB) viability, microvillus length, and changes in the expression levels of genes encoding pro-inflammatory cytokines (tumor necrosis factor $[TNF]-{\alpha}$, interleukin $[IL]-1{\beta}$, and IL-6). Results demonstrated the synbiotic diet had significantly better (p < 0.05) responses in terms of weight gain and specific growth rate, three innate immune parameters (respiratory burst, serum lysozyme, and superoxide dismutase), intestinal LAB viability, and the relative $TNF-{\alpha}$ expression level (p < 0.05). Moreover, after challenge with Streptococcus iniae ($1{\times}10^8CFU/ml$), the synbiotically fed group exhibited significantly higher (p < 0.05) protection against streptococcosis, validating the observed changes in immune parameters and induction of the cytokine-encoding gene. Therefore, according to the results of the present study, synbiotic feed ($LI_2+BGO$) increased growth, modulated innate immune parameters and protected olive flounder against streptococcosis.

• Journal of Microbiology and Biotechnology
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• 제30권8호
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• pp.1132-1141
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• 2020

Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.

• Journal of Microbiology and Biotechnology
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• 제30권10호
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• pp.1543-1551
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• 2020

Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPS-treated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.741-762
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• 2003

Ginsenosides, the major active ingredients of ginseng, show a variety of biomedical efficacies such as anti-aging, anti oxidation and anti-inflammatory activities. To understand the effects of compound K (20-O-D-glucopyranosyl-20 (S)-protopanaxadiol), one of the major metabolite of ginsenosides on the skin, we assessed the expression level of ∼ 100 transcripts in compound K-treated HaCaT cells using cDNA microarray analysis. Compound K treatment induced differential expression of 21 genes, which have been reported to be involved in the organization of ECM structure as well as defense responses in human skin cells. One of the most interesting findings is 2-fold increase in hyaluronan synthase2 (HAS2) gene expression by compound K. We found that change in expression of HAS2 gene represents a specific response of HaCaT cells to compound K because hyaluronan synthase 1, 3 was not changed by treatment with compound K. We also demonstrated that the compound K effectively induced hyaluronan synthesis in human skin cells and hairless mouse skin. The human clinical study indicates that topical application of compound K-containing oil-in-water emulsion showed improvement of xerosis, wrinkle and fine lines in the aged skin. We concluded that compound K has anti-aging effects by the induction of HAS2 gene expression and following hyaluronan synthase.

• Journal of Periodontal and Implant Science
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• 제50권5호
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• pp.281-290
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• 2020

Purpose: The aim of this study was to compare microRNA (miRNA) gene expression in saliva using miRNA polymerase chain reaction (PCR) arrays in healthy and aggressive periodontitis (AP) patients. Methods: PCR arrays of 84 miRNAs related to the human inflammatory response and autoimmunity from the saliva samples of 4 patients with AP and 4 healthy controls were performed. The functions and diseases related to the miRNAs were obtained using TAM 2.0. Experimentally validated targets of differentially expressed miRNAs were obtained from mirTarBase. Gene ontology terms and pathways were analyzed using ConsensusPathDB. Results: Four downregulated miRNAs (hsa-let-7a-5p, hsa-let-7f-5p, hsa-miR-181b-5p, and hsa-miR-23b-3p) were identified in patients with AP. These miRNAs are associated with cell death and innate immunity, and they target genes associated with osteoclast development and function. Conclusions: This study is the first analysis of miRNAs in the saliva of patients with AP. Identifying discriminatory human salivary miRNA biomarkers reflective of periodontal disease in a non-invasive screening assay is crucial for the development of salivary diagnostics. These data provide a first step towards the discovery of key salivary miRNA biomarkers for AP.

• International Journal of Oral Biology
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• 제39권1호
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• pp.15-22
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• 2014

Aggregatibacter actinomycetemcomitans is an important pathogen in the development of localized aggressive periodontitis. Lipopolysaccharide (LPS) is a virulent factor of periodontal pathogens that contributes to alveolar bone loss and connective tissue degradation in periodontal disease. Our present study was designed to investigate the cytokine expression and signaling pathways regulated by A. actinomycetemcomitans LPS (Aa LPS). Cytokine gene expression profiling in RAW 264.7 cells was performed by microarray analyses. The cytokine mRNA and protein levels and related signaling pathways induced by Aa LPS were measured by RT-PCR, ELISA and western blotting. Microarray results showed that Aa LPS strongly induced the expression of NF-${\kappa}B$, NF-${\kappa}B$-related genes, inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in RAW 264.7 cells. NF-${\kappa}B$ inhibitor pretreatment significantly reduced the levels of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA and protein. In addition, the Aa LPS-induced TNF-${\alpha}$ and IL-$1{\beta}$ expression was inhibited by p38/JNK MAP kinase inhibitor pretreatment. These results show that Aa LPS stimulates TNF-${\alpha}$ and IL-$1{\beta}$ expression through NF-${\kappa}B$ and p38/JNK activation in RAW 264.7 cells, suggesting the essential role of this pathway in the pathogenesis of localized aggressive periodontitis.

• International Journal of Oral Biology
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• 제38권1호
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• pp.37-42
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• 2013

Receptor activator of NF-${\kappa}B$ ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as $T_{17}$ cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.