• Archives of Pharmacal Research
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• 제25권6호
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• pp.801-806
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• 2002

Cyclicpeptides are important targets in peptide synthesis because of their interesting biological properties. Constraining highly flexible linear peptides by cyclization is one of the mostly widely used approaches to define the bioactive conformation of peptides. Cyclic peptides often have increased receptor affinity and metabolic stability over their linear counterparts. We carried out virtual screening experiment via docking in order to understand the interaction between HLE-Human Leukocyte Elastase and ligand peptide and to identify the sequence that can be a target in various ligand peptides. We made cyclic peptides as a target base on Metlle-Phe sequence having affinity for ligand and receptor active site docking. There are three ways to cyclize certain sequences of amino acids such as Met-lie-Phe-Gly-Ile. First is head-to-tail cyclization method, linking between N-terminal and C-terminal. Second method utilizes amino acid side chain such as thiol functional group in Cys, making a thioether bond. The last one includes an application of resin-substituted amino acids in solid phase reaction. Among the three methods, solid phase reaction showed the greatest yield. Macrocyclization of Fmoc-Met-Ile-Phe-Gly-Ile-OBn after cleavage of Fmoc protection in solution phase was carried out to give macrocyclic compound 5 in about 7% yield. In the contrast with solution phase reaction, solid phase reaction for macrocyclization of Met-Ile-Phe-Gly-Ile-Asp-Tentagel in normal concentrated condition gave macrocyclic compound 7 in more than 35% yield.

• Food Science and Biotechnology
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• 제14권4호
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• pp.479-486
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• 2005

Arabinoxylan, a complex polysaccharide in cereal cell walls, has recently received research attention as a biological response modifier. The immunomodulating effect of arabinoxylans from rice bran (AXrb) was studied using a combined process of extrusion and commercial hemicellulase treatment in order to elucidate the augmentation mechanism of cell-mediated immunity in vitro. The cytotoxicity of mouse spleen lymphocytes against YAC-1 tumor cells was significantly enhanced by treatment with AXrb at $10-100\;{\mu}g/mL$. In an attempt to investigate the mechanism by which AXrb enhance NK cytotoxicity, we examined the effect of AXrb on cytokine production by spleen lymphocytes. Culture supernatants of the cells incubated with AXrb were collected and analyzed for IL-2 and IFN-${\gamma}$ synthesis by ELISA. IL-2 and IFN-${\gamma}$ production were increased significantly. These results suggest that AXrb may induce Th1 immune responses. Macrophages play an important role in host defenses against tumors by killing them and producing secretory products, which protect against bacterial, viral infection and malignant cell growth. AXrb were examined for their ability to induce secretory and cellular responses in murine peritoneal macrophages. When macrophages were treated with various concentrations ($10-100\;{\mu}g/mL$) of AXrb, AXrb induced tumoricidal activity, as well as increasing phagocytosis and the production of NO, $H_2O_2$, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results indicate that reactive oxygen species, reactive nitrogen species, and inflammatory cytokines are likely to be the major mediators of tumoricidal activity in AXrb-treated macrophages. Therefore, AXrb may be useful in cancer immunotherapy and it is anticipated that AXrb obtained using extrusion and subsequent enzyme treatment can be used as an ingredient in nutraceuticals and cereal-based functional food.

• 전기화학회지
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• 제11권3호
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• pp.176-183
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• 2008

본 연구에서는 8족 금속 원소인 osmium을 중심금속으로 4가지의 착물을 합성하였다. 합성한 착물은 ${[Os(bpy)}_2{(ap-im)Cl]}^{+/2+}$, ${[Os(dme-bpy)}_2{(ap-im)Cl]}^{+/2+}$, ${[Os(dmo-bpy)}_2{(ap-im)Cl]}^{+/2+}$, ${[Os(dcl-bpy)}_2{(ap-im)Cl]}^{+/2+}$이다. 합성된 착물을 순환전압전류법을 포함한 다양한 전기화학분석방법을 이용하여 전기적 성질을 조사하여 작용기에 따른 전위의 변화를 다음의 전위구간에서 $E_p$:$-0.06\;V{\sim}0.313\;V$ vs. Ag/AgCl 확인하였다. 합성한 화합물을 전기적 흡착방법으로 고정된 금나노입자(gold nano-particles)를 전극 위에 자기조립방식으로 고정화를 시켰다. 당과 당 분해효소(Glucose Oxidase, GOx)에 의한 촉매반응의 전류를 확인하였고, glucose농도에 따른 변화하는 전류의 양도 확인하였다. 마지막으로 고정된 4가지의 osmium complex는 서로 다른 전위로 인하여 촉매전류의 양이 달라지는 것을 알 수 있었고, 이로 인해 redox complex의 전위가 촉매반응에 미치는 영향을 확인 할 수 있었다.

• Molecules and Cells
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• 제26권2호
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• pp.158-164
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• 2008

Arsenic trioxide (ATO) affects many biological processes such as cell proliferation, apoptosis, differentiation and angiogenesis. L-buthionine sulfoximine (BSO) is an inhibitor of GSH synthesis. We tested whether ATO reduced the viability of lung cancer A549 cells in vitro, and investigated the in vitro effect of the combination of ATO and BSO on cell viability in relation to apoptosis and the cell cycle. ATO caused a dose-dependant decrease of viability of A549 cells with an $IC_{50}$ of more than $50{\mu}m$. Low doses of ATO or BSO ($1{\sim}10{\mu}m$) alone did not induce cell death. However, combined treatment depleted GSH content and induced apoptosis, loss of mitochondrial transmembrane potential (${\Delta}{\Psi}_m$) and cell cycle arrest in G2. Reactive oxygen species (ROS) increased or decreased depending on the concentration of ATO. In addition, BSO generally increased ROS in ATO-treated A549 cells. ROS levels were at least in part related to apoptosis in cells treated with ATO and/or BSO. In conclusion, we have demonstrated that A549 lung cells are very resistant to ATO, and that BSO synergizes with clinically achievable concentration of ATO. Our results suggest that combination treatment with ATO and BSO may be useful for treating lung cancer.

• BMB Reports
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• 제42권9호
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• pp.561-567
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• 2009

Although many plant-derived phenolic compounds display antioxidant effects in biological systems, their mechanism of action remains controversial. In this study, the mechanism by which p-coumaric acid (p-CA) performs its antioxidant action was investigated in bovine aortic endothelial cells under oxidative stress due to high levels of glucose (HG) and arachidonic acid (AA), a free fatty acid. p-CA prevented lipid peroxidation and cell death due to HG+AA without affecting the production of reactive oxygen species. The antioxidant effect of p-CA was not decreased by buthionine-(S,R)-sulfoximine, an inhibitor of cellular GSH synthesis. In contrast, pretreatment with p-CA caused the induction of peroxidases that decomposed t-butyl hydroperoxide in a p-CA-dependent manner. Furthermore, the antioxidant effect of p-CA was significantly mitigated by methimazole, which was shown to inhibit the catalytic activity of 'p-CA peroxidases' in vitro. Therefore, it is suggested that the induction of these previously unidentified 'p-CA peroxidases' is responsible for the antioxidant effect of p-CA.

• Asian-Australasian Journal of Animal Sciences
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• 제22권5호
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• pp.618-625
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• 2009

The objective of this work was to study the direct effects of daidzein on steroidogenesis in cultured mouse Leydig cells. Adult mouse Leydig cells were purified by Percoll gradient centrifugation, and the cell purity was determined using a $3{\beta}$-hydroxysteroid dehydrogenase ($3{\beta}$-HSD) staining method. The purified Leydig cells were exposed to different concentrations ($10^{-7}$ M to $10^{-4}$ M) of daidzein for 24 h under basal and human chorionic gonadotropin (hCG)-stimulated conditions. The cell viability and testosterone production were determined, and the related mechanisms of daidzein action were also evaluated using the estrogen receptor antagonist ICI 182,780 and measuring the mRNA levels of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc), and $3{\beta}$-HSD-1 involved in testosterone biosynthesis. The results revealed that daidzein did not influence cell viability. Daidzein increased both basal and hCG-stimulated testosterone production in a dose-dependent manner, and this effect was statistically significant at concentrations of $10^{-5}$ M and $10^{-4}$ M daidzein (p<0.05). ICI 182,780 had no influence on daidzein action. RTPCR results revealed that $10^{-5}$ M and $10^{-4}$ M daidzein did not exert any obvious influence on the mRNA level of P450scc in Leydig cells. However, in the presence of hCG, these concentrations of daidzein significantly increased the StAR and $3{\beta}$-HSD-1 mRNA levels (p<0.05), but in the absence of hCG, only $10^{-5}$ M and $10^{-4}$ M daidzein up-regulated the StAR and $3{\beta}$-HSD-1 mRNA expression (p<0.05), respectively. These results suggest that daidzein has direct effect on Leydig cells. Daidzein-induced increase of testosterone production is probably not mediated by the estrogen receptor but correlates with the increased mRNA levels of StAR and $3{\beta}$-HSD-1.

• 한국토양비료학회지
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• 제46권6호
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• pp.652-658
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• 2013

A huge number of greenhouse soils in Korea have accumulated mineral elements which induce many nutritional and pathological problems. The present study was performed to the effects of the reduced fertilization on plant growth, and uptake and partitioning of minerals (N, P, K) and soluble carbohydrates using highly minerals-accumulated farmer's greenhouse soil. On the basis of the recommended application for tomato crop, the application rates of N, P and K were 110(50%)-5.2(5%)-41.5(35%)kg $ha^{-1}$, respectively, using Hoagland's nutrient solution. Tomato growth rates during the whole experiment were not significant between treatments, but it was found that a decrease in daily growth represented after 60 days of treatment (DAT). The reduced application led to a drastic decrease in the concentration of N, P and K in fruits, and, thus, this resulted in lower uptake after 40 DAT. The lower phloem export and utilization of soluble carbohydrates caused an accumulation of extra-carbohydrates in leaves, stems and fruits in the reduced application. The reduced fertilization induced the capture of N, P and K in leaves and of soluble carbohydrates in stems compared to the conventional application. In this study, we suggest that it is possible to delay the first fertigation time in minerals-accumulated soils without an adverse impact on crop growth, but it is necessary to regularly monitor mineral status in soil to ensure a balanced uptake, synthesis and partitioning of minerals and carbohydrates.

• 대한화학회지
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• 제56권6호
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• pp.679-691
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• 2012

New series of metal complexes of Co(II), Ni(II), Cu(II), Zn(II), Pd(II) and Pt(II) with 4-(p-chlorophenyl)-1-(pyridin-2-yl)thiosemicarbazide (HCPTS) have been synthesized and characterized by elemental analyses, magnetic moment, spectra (IR, UV-Vis, $^1H$ NMR, mass and ESR) and thermal studies. The IR data suggest different coordination modes for HCPTS which behaves as a monobasic bidentate with all metal ions except Cu(II) and Zn(II) which acts as a monobasic tridentate. Based on the electronic and magnetic studies, Co(II), Cu(II), Pd(II) and Pt(II) complexes have square - planner, Ni(II) has mixed stereochemistry (tetrahedral + square planar), while Zn(II) is tetrahedral. Molar conductance in DMF solution indicates the non-ionic nature of the complexes. The ESR spectra of solid copper(II) complex show $g_{\parallel}$ (2.2221) > $g_{\perp}$ (2.0899) > 2.0023 indicating square-planar structure and the presence of the unpaired electron in the $d_x2_{-y}2$ orbital with significant covalent bond character. The thermal stability and degradation kinetics of the ligand and its metal complexes were studied by TGA and DTA and the kinetic parameters were calculated using Coats-Redfern and Horowitz-Metzger methods. The complexes have more antibacterial activity against some bacteria than the free ligand. However, the ligand has high anticancer activities against HCT116 (human colon carcinoma cell line) and HEPG2 (human liver hepatocellular carcinoma cell line) compared with its complexes.

• IMMUNE NETWORK
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• 제4권3호
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• pp.131-142
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• 2004

In recent years, adjuvants have received much attention because of the development of purified subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. Therefore, immunologic adjuvants have been developed and testing for most of this century. During the last years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS-21, MF-59 and immunostimulating complexes (ISCOMS). Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. The most common adjuvants for human use today are aluminum hydroxide and aluminum phosphate. Calcium phosphate and oil emulsions have been also used in human vaccination. The biggest issue with the use of adjuvants for human vaccines is the toxicity and adverse side effects of most of the adjuvant formulations. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The availability of hundreds of different adjuvants has prompted a need for identifying rational standards for selection of adjuvant formulations based on safety and sound immunological principles for human vaccines. The aim of the present review is to put the recent findings into a broader perspective to facilitate the application of these adjuvants in general and experimental vaccinology.

• 한국토양비료학회지
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• 제46권5호
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• pp.351-358
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• 2013

A suitable supply of mineral elements into shoot via a root system from growth media makes plants favorable growth and yield. The shortage or surplus of minerals directly affects overall physiological reactions to plants and, especially, strongly influences carbohydrate metabolism as a primary response. We have studied mineral uptake and synthesis and translocation of soluble carbohydrates in N, P or K-deficient tomato plants, and examined the interaction between soluble carbohydrates and mineral elements. Four-weeks-old tomato plants were grown in a hydroponic growth container adjusted with suboptimal N ($0.5mmol\;L^{-1}\;Ca(NO_3)2{\cdot}4H_2O$ and $0.5mmol\;L^{-1}\;KNO_3$), P ($0.05mmol\;L^{-1}\;KH_2PO_4$), and K ($0.5mmol\;L^{-1}\;KNO_3$) for 30 days. The deficiency of specific mineral element led to a significant decrease in its concentration and affected the concentration of other elements with increasing treatment period. The appearance of the reduction, however, differed slightly between elements. The ratios of N uptake of each treatment to that in NPK sufficient tomato shoots were 4 (N deficient), 50 (P deficient), and 50% (K deficient). The P uptake ratios were 21 (N deficient), 19 (P deficient), and 28% (K deficient) and K uptake ratios were 11 (N deficient), 46 (P deficient), and 7% (K deficient). The deficiency of mineral elements also influenced on carbohydrate metabolism; soluble sugar and starch was substantially enhanced, especially in N or K deficiency. In conclusion, mineral deficiency leads to an adverse carbohydrate metabolism such as immoderate accumulation and restricted translocation as well as reduced mineral uptake and thus results in the reduced plant growth.