• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2187-2191
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• 2015

Background: Protrusive structures formed by migrating and invading cells are termed lamellipodia, filopodia, invadopodia and podosomes. Lamellipodia and filopodia appear on the leading edges of migrating cells and function to command the direction of the migrating cells. Invadopodia and podosomes are special F-actin-rich matrix-degrading structures that arise on the ventral surface of the cell membrane. Invadopodia are found in a variety of carcinomatous cells including squamous cell carcinoma of head and neck region whereas podosomes are found in normal highly motile cells of mesenchymal and myelomonocytic lineage. Invadopodia-associated protein markers consisted of 129 proteins belonging to different functional classes including WASP, NWASP, cortactin, Src kinase, Arp 2/3 complex, MT1-MMP and F-actin. To date, our current understanding on the role(s) of these regulators of actin dynamics in tumors of the orofacial region indicates that upregulation of these proteins promotes invasion and metastasis in oral squamous cell carcinoma, is associated with poor/worst prognostic outcome in laryngeal cancers, contributes to the persistent growth and metastasis characteristics of salivary gland adenoid cystic carcinoma, is a significant predictor of increased cancer risk in oral mucosal premalignant lesions and enhances local invasiveness in jawbone ameloblastomas.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7375-7379
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• 2013

The main aim of this study was to investigate the roles of GST-${\pi}$ and $pol{\beta}$ genes in the chemoresistance of esophageal carcinoma cells. Eukaryotic expression vectors containing each gene were constructed and transfected into EC9706 cells, and the biological effects of the two genes assessed based on a resistance index. We additionally investigated the in vitro and in vivo anti-resistance effects of GST-${\pi}$ and $pol{\beta}$ genes using recombinant lentiviruses carrying siRNAs against the two genes. Our results showed that upregulation of GST-${\pi}$ and $pol{\beta}$ genes suppresses chemosensitivity of esophageal carcinoma cells to cisplatin, while downregulation of these two genes with RNAi technology reverses this chemoresistance. Multi-site injection of recombinant lentivirus targeting the GST-${\pi}$ gene into transplanted cDDP tumors effectively reversed their chemoresistant phenotype. However, the same treatment against the $pol{\beta}$ gene did not lead to significant efficacy against chemoresistance.

• Journal of Applied Biological Chemistry
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• v.57 no.1
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• pp.17-22
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• 2014

Nardostachys chinensis (N. chinensis) has been used in traditional medicine as a sedative and analgesic. It has been reported that N. chinensis extract has an antioxidant activity. However, the mechanism has not been elucidated. In this study, we showed that FOXO3a was activated by N. chinensis extract. FOXO3a is a transcriptional factor that involved in cell cycle arrest, DNA repair, apoptosis, and detoxification of reactive oxygen spices (ROS). Protein level of FOXO3a was increased by N. chinensis extract whereas phospho-FOXO3a (Thr 32) was not changed. Promoter activities of target genes of FOXO3a such as MnSOD, p27, and GADD45 were increased by N. chinensis extract. Among target genes, protein level of MnSOD was increased by N. chinensis extract, and this leads to removal of ROS level in human embryonic fibroblast (HEF) cells. These results suggested that N. chinensis extract has an antioxidant activity by upregulation of MnSOD through FOXO3a activation.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.99-106
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• 2017

Obesity is a critical risk factor for the hypertension. Although angiotensin II (Ang II) in obese individuals is known to be upregulated in obesity-induced hypertension, direct evidence that explains the underlying mechanism for increased vascular tone and consequent increase in blood pressure (BP) is largely unknown. The purpose of this study is to investigate the novel mechanism underlying Ang II-induced hyper-contractility and hypertension in obese rats. Eight-week old male Sprague-Dawley rats were fed with 60% fat diet or normal diet for 4 months. Body weight, plasma lipid profile, plasma Ang II level, BP, Ang II-induced vascular contraction, and expression of regulatory proteins modulating vascular contraction with/without Ang II stimulation were measured. As a result, high fat diet (HFD) accelerated age-dependent body weight gaining along with increased plasma Ang II concentration. It also increased BP and Ang II-induced aortic contraction. Basal expression of p-CPI-17 and myosin light chain (MLC) kinase was increased by HFD along with increased phosphorylation of MLC. Ang II-induced phosphorylation of CPI-17 and MLC were also higher in HFD group than control group. In conclusion HFD-induced hypertension is through at least in part by increased vascular contractility via increased expression and activation of contractile proteins and subsequent MLC phosphorylation induced by increased Ang II.

• Nutrition Research and Practice
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• v.9 no.6
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• pp.586-591
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• 2015

BACKGROUND/OBJECTIVES: Reactive oxygen species (ROS) formation is closely related to miconazole-induced heart dysfunction. Although rhamnetin has antioxidant effects, it remained unknown whether it can protect against miconazole-induced cardiomyocyte apoptosis. Thus, we investigated the effects of rhamnetin on miconazole-stimulated H9c2 cell apoptosis. MATERIALS/METHODS: Cell morphology was observed by inverted microscope and cell viability was determined using a WelCount$^{TM}$ cell proliferation assay kit. Miconazole-induced ROS production was evaluated by fluorescence-activated cell sorting with 6-carboxy-2',7'-dichlorofluoroscein diacetate ($H_2DCF$-DA) stain. Immunoblot analysis was used to determine apurinic/apyrimidinic endonuclease 1 (APE/Ref-1) and cleaved cysteine-aspartic protease (caspase) 3 expression. NADPH oxidase levels were measured using real-time polymerase chain reaction. RESULTS: Miconazole (3 and $10{\mu}M$) induced abnormal morphological changes and cell death in H9c2 cells. Rhamnetin enhanced the viability of miconazole ($3{\mu}M$)-treated cells in a dose-dependent manner. Rhamnetin (1 and $3{\mu}M$) treatment downregulated cleaved caspase 3 and upregulated APE/Ref-1 expression in miconazole-stimulated cells. Additionally, rhamnetin significantly reduced ROS generation. CONCLUSIONS: Our data suggest that rhamnetin may have cytoprotective effects in miconazole-stimulated H9c2 cardiomyocytes via ROS inhibition. This effect most likely occurs through the upregulation of APE/Ref-1 and attenuation of hydrogen peroxide levels.

• Fisheries and Aquatic Sciences
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• v.20 no.12
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• pp.31.1-31.11
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• 2017

Background: Liver-expressed antimicrobial peptide-2 (LEAP-2) is an important component of innate immune system in teleosts. In order to understand isoform-specific involvement and regulation of LEAP-2 genes in mud loach (Misgurnus mizolepis, Cypriniformes), a commercially important food fish, this study was aimed to characterize gene structure and expression characteristics of two paralog LEAP-2 isoforms. Results: Mud loach LEAP-2 isoforms (LEAP-2A and LEAP-2B) showed conserved features in the core structure of mature peptides characterized by four Cys residues to form two disulfide bonds. The two paralog isoforms represented a tripartite genomic organization, known as a common structure of vertebrate LEAP-2 genes. Bioinformatic analysis predicted various transcription factor binding motifs in the 5'-flanking regions of mud loach LEAP-2 genes with regard to development and immune response. Mud loach LEAP-2A and LEAP-2B isoforms exhibited different tissue expression patterns and were developmentally regulated. Both isoforms are rapidly modulated toward upregulation during bacterial challenge in an isoform and/or tissue-dependent fashion. Conclusion: Both LEAP-2 isoforms play protective roles not only in embryonic and larval development but also in early immune response to bacterial invasion in mud loach. The regulation pattern of the two isoform genes under basal and stimulated conditions would be isoform-specific, suggestive of a certain degree of functional divergence between isoforms in innate immune system in this species.

• Journal of Microbiology and Biotechnology
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• v.26 no.7
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• pp.1224-1233
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• 2016

The present study assessed the effects of an aqueous extract of Acanthopanax koreanum root (AE) and of AE following fermentation by lactic acid bacteria (Lactobacillus plantarum and Bifidobacterium bifidum) (AEF) on human skin fibroblast HS68 cells exposed to ultraviolet B (UVB) irradiation and oxidative stress. AEF effectively antagonized the senescence-associated β-galactosidase staining and upregulation of p53 and p21^Cip1/WAF1 induced by UVB or H₂O₂ treatment in HS68 cells. It also exhibited excellent antioxidant activities in radical scavenging assays and reduced the intracellular level of reactive oxygen species induced by UVB or H₂O₂ treatment. The antioxidant and antisenescent activities of AEF were greater than those of nonfermented A. koreanum extract. AEF significantly repressed the UVB- or H₂O₂-induced activities of matrix metalloproteinase (MMP)-1 and -3, overexpression of MMP-1, and nuclear factor κB (NF-κB) activation. This repression of NF-κB activation and MMP-1 overexpression was attenuated by a mitogen-activated protein kinase activator, suggesting that this AEF activity was dependent on this signaling pathway. Taken together, these data indicated that AEF-mediated antioxidant and anti-photoaging activities may produce anti-wrinkle effects on human skin.

• Archives of Pharmacal Research
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• v.26 no.3
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• pp.244-251
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• 2003

Plant nutrients are believed to provide protection against various diseases including inflammation. Since interactions of the cell adhesion molecules are known to play important roles in mediating inflammation, inhibiting adhesion protein upregulation is a possible therapeutic target. In this study, the interacellular adhesion molecule-1 (ICAM-1) was induced in human umbilical endothelial cells (HUVECs) after stimulation with $TNF-{\alpha}$. In addition, alginate, ascorbic acid and allicin were demonstrated to inhibit the $TNF-{\alpha}$ induced expression of ICAM-1 on the HUVECs in a dose-dependent manner. These compounds also inhibited the production of NO and $H_2O_2$ induced by $TNF-{\alpha}$, which suggests that the inhibition of ICAM-1 expression by the three compounds may be due to the modulated production of the reactive oxygen/nitrogen components. Overall, these results indicate that these dietary components have a therapeutic potential in the treatment of various inflammatory disorders associated with an increase in endothelial leukocyte adhesion molecules.

• YAKHAK HOEJI
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• v.59 no.1
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• pp.1-5
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• 2015

Cordyceps militaris has shown to have various pharmacological activities including an immune-modulatory effect. Previously, we reported that anti-influenza effect of C. militaris in DBA/2 mice was mediated by increased IL-12 and the activation of NK cells. In this study, we investigated the effect of C. militaris on adaptive immune responses using DBA2 mice immunized with influenza vaccine. To determine the effect of C. militaris on antigen presentation capability, we treated RAW 264.7 cells with various concentrations of ethanol extract of C. militaris, which showed a significant upregulation of CD86 (B7.2), CD284 (TLR4), CD40, H-2k (MHC I) and I-Ad (MHC II). To examine the direct effect of C. militaris on adaptive immune responses, we immunized DBA2 mice with influenza vaccine in presence or absence of C. militaris. After 2 or 4 weeks, influenza-specific T cell proliferation, HAI titers and IFN-${\gamma}$ production were measured in plasma or PBMCs isolated from animals. Influenza-specific T cell proliferation and HAI titers were not considerably increased in immunized mice in presence of C. militaris. However, the production of IFN-${\gamma}$ was much greater in immunized mice with C. militaris as adjuvant than only immunized mice.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.37-42
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• 2008

Betulinic acid, a naturally occurring pentacyclic triterpenoid, is found in abundance in the outer bark of white birch (Betula alba). In this study, we investigated if betulinic acid affects cytokine expression from activated macrophage cells. ELISA result showed that stimulation of HL-60 cells with proinflammatory cytokine such as $TNF-{\alpha}$ resulted in MCP-1 release into culture medium. In addition, transcriptional upregulation of MCP-1 in response to $TNF-{\alpha}$ was observed by RT-PCR analysis. However, incubation of HL-60 cells with betulinic acid prior to $TNF-{\alpha}$ treatment abrogated MCP-1 expression in transcription and translational level. Consistent with a number of studies which reported requirement of ERK activation for $TNF-{\alpha}$ expression, Western blot analysis showed that $TNF-{\alpha}-induced$ ERK activation was suppressed by pretreatment of HL-60 cells with betulinic acid. Taken together, our data indicate that betulinic acid exerts its anti-inflammatory effect through inhibition of $TNF-{\alpha}-induced$ ERK activation which is required for the subsequent MCP-1 release.