• Radiation Oncology Journal
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• 제30권4호
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• pp.197-204
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• 2012

Purpose: To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Materials and Methods: Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were reevaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and ${\beta}$-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. Results: At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and ${\beta}$-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. Conclusion: There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and ${\beta}$-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

• 한방재활의학과학회지
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• 제24권2호
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• pp.51-64
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• 2014

Objectives This study was carried out to know the effects of Keonbodan (hereinafter referred to KBD) in osteoarthritis induced by Monosodium iodoacetate(hereinafter referred to MIA) on Wistar rat. Methods Osteoarthritis was induced by injection of MIA into left knee joint cavities of rat. Osteoarthritis rats were divided into 4 groups (normal (n=6), control (n=6), indomethacin (n=6), KBD (n=6) group). The control group was administered normal saline and indomethacin group was administered indomethacin (2 mg/kg). And the KBD group was administered KBD (142 mg/kg). Each groups were administered by orally for 4 weeks. This experiment were carried out in vivo. In vivo, at the end of the experiment (5 weeks after MIA injection), effects on hepatotoxicity and nephrotoxicity, cytokines in serum, arachidonic acid, osteocalcin, MMP-9, TIMP-1 and cartilage volume were evaluated. And histopathological examinations on the articular structures of knee joints were performed. Results 1. In weight-bearing measurement, level of weight was increased. 2. In order to hepatotoxicity and nephrotoxicity, ALT, AST, BUN and creatinine were tested. And there were no significant changes. 3. In serum, levels of TNF-$\alpha$, IL-$1{\beta}$ were significantly decreased. IL-6 was insignificantly decreased. 4. In serum, level of MMP-9 and TIMP-1 was decreased. 5. In serum, level of $LTB_4$, $PGE_2$ and osteocalcin was decreased. 6. In ${\mu}$CT-arthrography, the cartilage volume was greater than that of the control group. 7. The joint damage induced by osteoarthritis was lesser than the control group in histopathologic observation (H&E, Safranin-O staining). Conclusions These results demonstrated that KBD suppressed the osteoarthritis- inducing effects of MIA in rat. And further studies are required to find out more effective substance and anti-osteoarthritic mechanism in the future.

• 대한한방소아과학회지
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• 제30권4호
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• pp.77-86
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• 2016

Objectives Hataedock (HTD) is an oral Korean herbal medical oral treatment that removes fetal toxic heat and meconium from new born babies. The purpose of this study is to evaluate whether Hataedock treatment of Duchi extracts has anti-inflammation effects in atopic dermatitis-like skin lesions in House Dust Mite-Induced NC/Nga Mice. Methods The mice were divided into 3 groups (n=10 per group) as follows: the control group (Ctrl group), AD-induced group (AE group), AD-induced with HTD treatment group (DT group). 3-week-old NC/Nga mice were introduced to Hataedock treatment, made of Duchi extract. After 4 weeks, House Dust Mite-Induced application was used six times per week for 3 weeks to induce the first atopic dermatitis, and second AD in 7 weeks after. To examine skin injuries and anti-inflammatory effect, PKC, MMP-9, iNOS immunohistochemistry were used. Results The alleviate effect of the skin damage and angiogenesis was observed in DT group. The damage of stratum corneum, hyperplasia, edema, infiltration of lymphocytes and distribution of capillary were decreased in DT group. Also, the study results suggested that Hataedock treatment made of Duchi extracts in DT group remarkably decreased skin damages by 51% (p < 0.001), as well as PKC by 91%, MMP-9 by 48% (p < 0.001), iNOS by 51% (p < 0.001). Conclusions Based on the study results, we observed that Hataedock treatment of Duchi extracts alleviates AD by diminishing various inflammatory cytokines, initial steps of AD development, in the skin lesions. Potential applications for prevention and treatment of atopic dermatitis are expected.

• 대한한방내과학회지
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• 제37권6호
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• pp.1030-1041
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• 2016

Objectives: This study investigated the administration of Jeungmiyijin-tang (JYT) to rats with reflux esophagitis (RE) induced by pylorus and forestomach ligation operations. Methods: Twenty laboratory rats were divided into three groups with 5~7 rats in each group. The control group consisted of rats with no inflammation (CON). The RE group had rats with gastroesophageal reflux elicited by pylorus and forestomach ligation operations. The JYT group had rats that were orally administered Jeungmiyijin-tang (1.5 ml/day/300 g) once a day for 14 days before reflux esophagitis was induced by the pylorus and forestomach ligation operations. Six hours after the operations, the rats were sacrificed, morphological changes were observed, and histological examinations were done in the stomach and esophagus lesion areas. If apoptosis was observed, the apoptotic cells in the esophagus lesion areas were counted. Results: The morphological and histochemical changes consisted of various injuries from hemorrhagic erosion in the RE group, while there were significantly fewer in the JYT group. The RE group marked increases of gastric mucosa erosion and infiltration of inflammatory cells in the submucosa, as well as cell division in the epithelial layer, the proliferation and degranulation of mast cells, and increases in the IL-$1{\beta}$, TNF-${\alpha}$, and MMP-9 expressions in the esophagus of the rats. The JYT group was inhibited above expression compared with the RE group. Apoptosis was statistically significantly decreased in the JYT group compared with the RE group. Conclusions: According to the above results, it appears that Jeungmiyijin-tang inhibits the expression of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, and MMP-9) and apoptosis in the esophagus mucosa, thereby preventing esophageal mucosal damage from esophageal reflux.

• 한국수산과학회지
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• 제41권1호
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• pp.7-12
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• 2008

To develop a whitening agent, cytotoxicity of the soluble collagen isolated from Todarodes pacificus (CIT) was evaluated. CIT tested for cytotoxicity on human dermal fibroblast (CCD-986sk) was exhibited very low cytotoxicity. Because tyrosinase is the key enzyme for melanin biosynthesis, the use of various tyrosinase inhibitors is a common practice for whitening purpose in cosmetics. Tyrosinase inhibitory activity and melanin production assay were measured to confirm the whitening effect. The inhibitory effect of MMP-1 in UV-irradiated human dermal fibroblast was also performed. CIT showed strong inhibition potency on tyrosinase by 51.5% at 0.2 mg/mL which increased the inhibition by increasing the concentration of CIT, and showed 69.1% inhibition at 1.0 mg/mL. CIT showed strong inhibition effect on melanin production with 82% at 1.0 mg/mL. The CIT also reduced about 76% expression of MMP-1 in UV-irradiated CCD-986sk cell at 1.0 mg/mL. From the preliminary observations, we suggest that the collagen isolated from CIT could be a potential source of natural skin-whitening and anti-aging agents for the photo-damaged skin.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.72-78
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• 2013

This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1358-1364
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• 2005

In this study, we investigated whether a novel anti-ischemic $K_{ATP}$ opener KR-31378 [(2S,3S,4R)­N'-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2 -methly-2-dimethoxymethly-2H-benzopyran-4-yl)­N'-benzylguanidine] has protective effect against oxidative stress-induced death in heart-derived H9c2 cells. Cell death was induced by BSO, butionine sulfoximine, which inhibits GSH synthesis and subsequently increases reactive oxygen species (ROS) level. Cell death was quantitatively determined by measuring lactate dehydrogenase (LDH) activity and stained by Hoechst 33258. BSO-induced ROS production and mitochondrial membrane potential (MMP) were measured using 2',7'-dichlorofluorescein diacetate oxidation and rhodamine 123, respectively. Both the LDH release and the ROS elevation induced by treatment of H9c2 cells with 10 mM BSO, were significantly decreased by KR-31378. These protective effect and antioxidant effect of KR-31378 appeared to be independent on $K_{ATP}$ channel opening. Cells exposed to BSO showed an early reduction in MMP, and this reduction in MMP was significantly reversed by treatment with KR-31378. Caspase-3 activity in BSO treated H9c2 cells was remarkably increased, and this increased caspase-3 activity was significantly reversed by KR-31378. In conclusion, our results suggest that KR-31378 can produce cardioprotective effect against oxidative stress-induced cell death through antioxidant mechanism.

• Journal of Microbiology and Biotechnology
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• 제33권11호
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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 Chest Surgery
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• 제49권6호
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• pp.443-450
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• 2016

Background: Although unique aortic pathology related to bicuspid aortic valve (BAV) has been previously reported, clinical implications of BAV to aortopathy risk have yet to be investigated. We looked for potential differences in matrix protein expressions in the aortic wall in BAV patients. Methods: Aorta specimens were obtained from 31 patients: BAV group (n=27), tricuspid aortic valve (TAV) group (n=4). The BAV group was categorized into three subgroups: left coronary sinus-right coronary sinus (R+L group; n=13, 42%), right coronary sinus-non-coronary sinus (R+N group; n=8, 26%), and anteroposterior (AP group; n=6, 19%). We analyzed the expression of endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-2. Results: Based on the mean value of the control group, BAV group showed decreased expression of eNOS in 72.7% of patients, increased MMP-9 in 82.3%, and decreased TIMP in 79.2%. There was a higher tendency for aortopathy in the BAV group: eNOS $(BAV:TAV)=53%{\pm}7%:57%{\pm}11%$, MMP-9 $(BAV:TAV)=48%{\pm}10%:38%{\pm}1%$. The AP group showed lower expression of eNOS than the fusion (R+L, R+N) group did; $48%{\pm}5%$ vs. $55%{\pm}7%$ (p=0.081). Conclusion: Not all patients with BAV had expression of aortopathy; however, for patients who had a suspicious form of bicuspid valve, aortic wall biopsy could be valuable to signify the presence of aortopathy.

• International Journal of Oral Biology
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• 제31권2호
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• pp.53-65
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• 2006

Calcium concentration in the bone resorption lacunae is high and is in the mM concentration range. Both osteoblast and osteoclast have calcium sensing receptor in the cell surface, suggesting the regulatory role of high extracellular calcium in bone metabolism. In vitro, high extracellular calcium stimulated osteoclastogenesis in coculture of mouse osteoblasts and bone marrow cells. Therefore we examined the genes that were commonly regulated by both high extracellular calcium and $1,25(OH)_2vitaminD_3(VD3)$ by using mouse oligo 11 K gene chip. In the presence of 10 mM $[Ca^{2+}]e$ or 10 nM VD3, mouse calvarial osteoblasts and bone marrow cells were co-cultured for 4 days when tartrate resistant acid phosphatase-positive multinucleated cells start to appear. Of 11,000 genes examined, the genes commonly regulated both by high extracellular calcium and by VD3 were as follows; 1) the expression of genes which were osteoclast differentiation markers or were associated with osteoclastogenesis were up-regulated both by high extracellular calcium and by VD3; trap, mmp9, car2, ctsk, ckb, atp6b2, tm7sf4, rab7, 2) several chemokine and chemokine receptor genes such as sdf1, scya2, scyb5, scya6, scya8, scya9, and ccr1 were up-regulated both by high extracellular calcium and by VD3, 3) the genes such as mmp1b, mmp3 and c3 which possibly stimulate bone resorption by osteoclast, were commonly up-regulated, 4) the gene such as c1q and msr2 which were related with macrophage function, were commonly down-regulated, 5) the genes which possibly stimulate osteoblast differentiation and/or mineralization of extracellular matrix, were commonly down-regulated; slc8a1, admr, plod2, lox, fosb, 6) the genes which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were commonly up-regulated; s100a4, npr3, mme, 7) the genes such as calponin 1 and tgfbi which possibly suppress osteoblast differentiation and/or mineralization of extracellular matrix, were up-regulated by high extracellular calcium but were down-regulated by VD3. These results suggest that in coculture condition, both high extracellular calcium and VD3 commonly induce osteoclastogenesis but suppress osteoblast differentiation/mineralization by regulating the expression of related genes.