• IMMUNE NETWORK
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• v.14 no.6
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• pp.296-306
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• 2014

There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-${\kappa}B$. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.96-102
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• 2017

Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

• YAKHAK HOEJI
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• v.22 no.3
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• pp.163-174
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• 1978

Plantaginis seed has been applied in Chinese medicine a as well as in folk remedy. It was advocated that Plantaginis S Semeη exerts good therapeutic effects as anti-inflammatory, antitussive, obstipant and diuretic agent in some cases of alimentary, respiratory a and renal disorders. This study was carried out in order to r re-evaluate the pharmacological action, especially the hypotensive a action of Plantaginis Semen and to elucidate the mechanism of its a action, making use of Plantaginis Semen methanol extract (PME), because its basic pharmacological action, i. e., hypotensive action is n not clear. 1) PME, when administered into intravenous route, elicited the h hypotensive response dependent on the dose of PME given to the rabbit anesthetized with urethane. 2) This hypotensive response of P PME was inhibited by atropine and potentiated by physostigmine, but not influ$\varepsilon$need by vagotomization. 3) Depressor effect of PME was blocked by chlorisondamine, phentolamine, and bethanicline, while not altered by cyproheptadine, diphenhydramine and propran¬olol. 4) The secondary pressor response after blocking the depressor e effect of PME by chlorisondamine was produced, but this pressor response was deminished by atropine. 5) PME augmented the pressor e effect of norepinephrine and angiotensin, on the other hand, reduced b blood pressure elevated by carotid occlusion reflex. 6) These observa¬t tions suggest that PME may induce the hypotensive response via dual mechanisms of parasympathomimetic and sympatholytic action, that the positions of this action are cholinergic peripheral site and sympathetic ganglia respectively, and that PME may possess the pressor activity caused by stimulation of "atropine-sensitive site" which seems to existsin the sympathetic ganglia.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.166-171
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• 2007

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

• The Plant Pathology Journal
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• v.33 no.4
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• pp.402-409
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• 2017

Cyclic dipeptides (CDPs) are one of the simplest compounds produced by living organisms. Plant-growth promoting rhizobacteria (PGPRs) also produce CDPs that can induce disease resistance. Bacillus vallismortis strain BS07 producing various CDPs has been evaluated as a potential biocontrol agent against multiple plant pathogens in chili pepper. However, plant signal pathway triggered by CDPs has not been fully elucidated yet. Here we introduce four CDPs, cyclo(Gly-L-Pro) previously identified from Aspergillus sp., and cyclo(L-Ala-L-Ile), cyclo(L-Ala-L-Leu), and cyclo(L-Leu-L-Pro) identified from B. vallismortis BS07, which induce disease resistance in Arabidopsis against Pseudomonas syringae infection. The CDPs do not directly inhibit fungal and oomycete growth in vitro. These CDPs require PHYTOALEXIN DEFICIENT4, SALICYLIC ACID INDUCTION DEFICIENT2, and NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 important for salicylic acid-dependent defense to induce resistance. On the other hand, regulators involved in jasmonate-dependent event, such as ETHYLENE RECEPTOR1, JASMONATE RESPONSE1, and JASMONATE INSENSITIVE1, are necessary to the CDP-induced resistance. Furthermore, treatment of these CDPs primes Arabidopsis plants to rapidly express PATHOGENESIS-RELATED PROTEIN4 at early infection phase. Taken together, we propose that these CDPs from PGPR strains accelerate activation of jasmonate-related signaling pathway during infection.

• Journal of Microbiology and Biotechnology
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• v.29 no.2
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• pp.304-310
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• 2019

Interleukin-21 is a common ${\gamma}$-chain cytokine that controls the immune responses of B cells, T cells, and natural killer cells. Targeting IL-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. However, the practical application of IL-21 is limited by the high production cost. In this study, we improved IL-21 production by codon optimization and selection of appropriate signal peptide in CHO-K1 cells. Codon-optimized or non-optimized human IL-21 was stably transfected into CHO-K1 cells. IL-21 expression was 10-fold higher for codon-optimized than non-optimized IL-21. We fused five different signal peptides to codon-optimized mature IL-21 and evaluated their effect on IL-21 production. The best result (a 3-fold increase) was obtained using a signal peptide derived from human azurocidin. Furthermore, codon-optimized IL-21 containing the azurocidin signal peptide promoted $IFN-{\gamma}$ secretion and STAT3 phosphorylation in NK-92 cells similar to codon-optimized IL-21 containing original signal peptide. Collectively, these results indicate that codon optimization and azurocidin signal peptides provide an efficient approach for the high-level production of IL-21 as a biopharmaceutical.

• ALGAE
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• v.34 no.2
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• pp.177-185
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• 2019

Ecklonia cava is popular in Korea as a marine functional materials. E. cava is generally collected and used on the coast of Jeju Island. However, the continuous use of collected natural E. cava may be limited because difficult to secure throughout the year and may be exposed to environmental pollution. Jeju magma seawater (MSW) was known to be significant advantages such as safety, cleanness, stability, and functional improvement. Attempts have been reported on application of MSW to the culturing of macro- and microalgae and showed improved results. Thus, the objective of the present study was to explore the anti-melanogenesis activity of brown seaweed E. cava (E. cava cultured with MSW [MSWE]) extract cultured in tanks with MSW of Jeju Island to evaluate the possibility of cosmeceutical industrial application. MSWE extract showed the higher polyphenolic and dieckol contents than natural E. cava (NE) extract. Anti-melanogenesis activity of MSWE extract and NE extract are tested and compared using tyrosinase and dihydroxyphenylalanine (DOPA) oxidation inhibition assay. MSWE extracts evidenced more effective tyrosinase and DOPA oxidation inhibition activity than that of the NE extracts and the commercial whitening agent, arbutin. MSWE extracts also markedly inhibited melanin synthesis and decreased the expression of melanogenesis-related protein in ${\alpha}$-melanocyte stimulating hormone-stimulated B16F10 melanoma cells without cytotoxicity. These results suggest that MSW cultivation process would be more effective in releasing bioactive compounds with whitening effect from seaweed such as E. cava at an industrial scale.

• Journal of Adhesion and Interface
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• v.19 no.4
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• pp.154-162
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• 2018

Plasma treatment and corona treatment have been used for surface modification of polydimethylsiloxane (PDMS) film by activating its surface with the -OH group. Adhesion promoter or coupling agent was also used to improve adhesion of PDMS film with various materials. However, obtained hydrophilicity onto the surface of PDMS films with those processes was transient and vulnerable. In this study, a new alkoxysilane-functionalized acrylic polymer precursor was first synthesized by copolymerization process, and then was reacted with HO-terminated PDMS through condensation reaction to prepare a new surface modifier for PDMS film. The structure and molecular weight of the prepared surface modifier were confirmed by 1H-NMR and GPC measurement. Surface properties of surface modifier-coated PDMS films were also investigated by using XPS, ATR and WCA analysis. The adhesion between the PDMS film and the surface modifier was tested using cross-cut test.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.1
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• pp.56-62
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• 2019

To investigate the effect of Bombycis Corpus on male osteoporosis, we performed Dual Energy X-Ray Absorptiometry(DEXA) and histochemical methods. The animals were used ICR-based male mice of 8 weeks and 50 weeks, respectively. ICR male mice at 8 weeks were used in the control group, and ICR male mice at 50 weeks were used in aging group and Bombycis Corpus group(BC group). In the aging group, 0.5 ml of distilled water was administered once a day for 6 months. In BC group, Bombycis Corpus(0.78g/kg) was dissolved in distilled water for 6 months once a day. As a result, Bombycis Corpus decreased bone loss, increased bone density by reducing the loss of bone matrix in the femur due to aging, and increased osteoblast - induced osteopontin(OPN) and osteocalcin(OPC) positivite reaction. In addition, administration of Bombycis Corpus decreased Reaction of activation of nuclear factor kappa B ligand(RANKL) positive reaction, increased osteoprotegerin(OPG) positive reaction, and decreased matrix metalloproteinase-3(MMP-3) and 8-hydroxy-2'-deoxyguanosine(8-OHdG) positivite reaction. Taken together, Bombycis Corpus increases the activity of osteoblasts, inhibits osteoclast function, promotes osteoblast function, inhibits bone tissue degradation, and inhibits bone loss due to oxidative stress. It was observed that Bombycis Corpus reduced bone loss and increased bone density caused by aging to improve male osteoporosis. Therefore, Bombycis Corpus may be used as a preventive and therapeutic agent for male osteoporosis.

• Journal of Rheumatic Diseases
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• v.24 no.4
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• pp.192-202
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• 2017

Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.