• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.10
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• pp.2997-3003
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• 2009

The pharmacological profile of KR-31081, a nonpeptide $AT_1$ selective angiotensin receptor antagonist, was investigated by receptor binding studies, functional in vitro assays with rabbit aorta. KR-31081 inhibited the specific binding of $[^{125}I]\;[Sar^1,\;Ile^8]$-angiotensin II to human recombinant $AT_1$ receptor with an 8.6-fold greater potency than losartan ($IC_{50}$: 1.43 and 12.3 nM, respectively), but it did not inhibit the binding of [$^{125}I$] CGP 42112A to human recombinant $AT_2$ receptor ($IC_{50}$: higher than $10{\mu}M$ for both). The Hill coefficient for the competition curve of KR-31081 against $AT_1$ receptor was not significantly different from unity (0.99). Scatchard analysis showed that KR-31081 interacted with human recombinant $AT_1$ receptor in a competitive manner, as with losartan. In functional studies with rabbit aorta, KR-31081 competitively inhibited the contractile response to angiotensin II ($pK_B$ values: 8.66) with 20-70% decrease in the maximum contractile responses, unlike losartan that showed competitive antagonism without any change in the maximum contractile responses to angiotensin II ($pA_2$ values: 7.59). These results suggest that KR-31081 is a highly potent $AT_1$ selective angiotensin II receptor antagonist with a mode of insurmountable antagonism to be developed as the exploratory potential of this compound.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.201-211
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• 2016

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment ($10{\mu}M$) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-$1{\alpha}$ ($PGC1{\alpha}$) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving $PGC1{\alpha}$ during cardiac HR injuries.

• The Korean Journal of Pesticide Science
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• v.13 no.3
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• pp.185-189
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• 2009

A monoterpenoid compound, benzylideneacetone (BZA), is a metabolite of an entomopathogenic bacterium, Xenorhabdus nematophila. Its primary biological activity is an inhibitor of phospholipase $A_2$, which catalyzes the committed step of biosynthesis of various eicosanoids that are critically important to mediate insect immune responses. When BZA was applied to two-spotted spider mite, Tetranychus urticae, it exhibited a dose-dependent mortality in leaf-disc assay. Subsequently BZA was tested against T. urticae infesting apples in a field orchard, in which it showed a significant control efficacy, which was not statistically different with that of a commercial acaricide. BZA also had significant antibacterial activities against three species of plant pathogenic bacteria when it was added to the bacterial cultures, in which it showed the highest inhibitory activity against a bacterial wilt-causing pathogen, Ralstonia solanacearum. The bacterial pathogen caused significant disease symptom to young potato plants. However, BZA significantly suppressed the disease occurrence. This study suggests that BZA can be used to develop a novel crop protectant to control mite and bacterial pathogen.

• Korean Journal of Veterinary Research
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• v.58 no.2
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• pp.87-94
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• 2018

This study assessed the effects of Weissella cibaria (W. cibaria) CMU on oral health in male and female beagles (n = 18) by measuring oral malodor and periodontal disease-related parameters (calculus, plaque, and gingivitis indices). Oral malodor and indicators of periodontal disease were assessed in five treatment groups: negative control (scaling and 0.24 mg of maltodextrin, n = 3), positive control (0.24 mg of maltodextrin, n = 3), and W. cibaria CMU groups (each n = 4) at low (CMU-L, $2{\times}10^7$ colony forming unit [CFU]), medium (CMU-M, $2{\times}10^8CFU$), and high (CMU-H, $2{\times}10^9CFU$) concentrations. After feeding with W. cibaria CMU for 6 weeks, total volatile sulfur compound concentrations in the CMU-L ($2.0{\pm}1.04ng/10mL$), CMU-M ($2.4{\pm}1.05ng/10mL$), and CMU-H ($2.6{\pm}1.33ng/10mL$) groups were significantly lower than in the positive control group ($3.2{\pm}1.65ng/10mL$). Also, CMU-L ($1.4{\pm}0.83ng/10mL$) and CMU-H ($1.9{\pm}1.14ng/10mL$) groups had methyl mercaptan levels lower than that in the positive control group ($2.4{\pm}1.21ng/10mL$) at week 2. The plaque index was significantly lower in the CMU-H group ($4.5{\pm}0.28$) than in the positive control group ($5.9{\pm}1.08$) at week 6. W. cibaria CMU could be useful as a novel oral hygiene probiotics for reducing volatile sulfur compounds production and inhibiting plaque growth in companion animals.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3035-3042
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• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.118-122
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• 2016

Integrin ${\alpha}_v{\beta}_3$ plays an important role in the tumor metastases and angiogenesis. Arginine-glycine-aspartate (RGD) peptide motif binds to the integrin ${\alpha}_v{\beta}_3$. General $^{68}Ga$-labeled cyclic RGD peptides was rapidly eliminated from the circulatory system by renal excretion because of its hydrophilic property. The purpose of this study was to develop a novel $^{68}Ga$-labeled cyclic RGD peptides, which could acquire enhanced PET tumor images with improved pharmacokinetics by adopting biphenyl group between chelator and RGD peptides. $^{68}Ga$-DOTA-2P-c(RGDyK) was demonstrated a 12% higher lipophilicity level than $^{68}Ga$-DOTA-c(RGDyK) as a reference compound. In the animal PET, $^{68}Ga$-DOTA-2P-c(RGDyK) represented relatively lower blood-clearance, and an increased signal to noise ratio compared to $^{68}Ga$-DOTA-c(RGDyK). From these perspective, $^{68}Ga$-DOTA-2P-c(RGDyK) could be a good candidate for in integrin ${\alpha}_v{\beta}_3$-expressed tumor imaging.

• Korean Journal of Pharmacognosy
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• v.33 no.3 s.130
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• pp.177-181
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• 2002

This study was carried out to investigate the antioxidative activities of Rosa davurica Pall for the purpose of development of novel antioxidant from natural products. Antioxidant activities of four different parts of Rosa davurica Pall such as fruit, leaf, stem and root were examined by measuring the radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The methanol extract from the root of Rosa davurica Pall showed the highest antioxidative activity among 16 samples tested. And, we also tested radical scavenging effects of 5 different extract compartments(Hexane, $CHCl_3$, EtOAc, BuOH and $H_2O$ fraction). EtOAc and BuOH fractions from the root of Rosa davurica Pall exhibited antioxidative activities higher to those of natural, ${\alpha}-tocopherol$ or synthetic antioxidants, BHT. The antioxidative substance of EtOAc fraction from the root of Rosa davurica Pall was successively purified with silica gel adsorption column chromatography and Sephadex LH-20 column chromatography. The purified active substance was isolated as crystal and identified as (+)-catechin by $^{l}H-NMR$ and $^{13}C-NMR$. This compound exhibited DPPH radical scavenging activity with the $IC_50$ value of $1.7\;{\mu}g/ml$. In the analysis of catechin content, the leaf extracts contained the highest catechin, and fruit extracts contained the lowest catechin. Considering antioxidative activity on DPPH assay, the extracts of Rosa davurica Pall showed a possibility to be used as a new material for natural antioxidant and functional food.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2002.04b
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• pp.69-75
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were Shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

• Journal of Mushroom
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• v.16 no.3
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• pp.131-139
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• 2018

The king oyster mushroom (Pleurotus eryngii) is widely consumed because of its flavor, texture, and its functional properties such as antioxidant activity and prebiotic effects. However, long-term product storage and transportation (e.g., export) are difficult because of its limited durability. The shelf-life of king oyster mushroom is affected by environmental factors such as temperature, humidity, gas composition, and ventilation, which may affect sensory characteristics including respiration rate, texture, moisture, flavor, color, and pH. The major problems regarding storage of mushrooms are browning, flavor changes, and softening. To address these problems, novel preservation techniques were developed, and more durable variants were bred. Different drying methods, gamma irradiation, chitosan coating, modified atmosphere (MA) packaging, and controlled atmosphere (CA) storage were evaluated in order to extend the shelf-life of king oyster mushrooms. Freeze drying showed better results for the preservation of mushrooms than other drying methods. Irradiation with 1 kGy was more effective for extending mushroom shelf-life than higher doses. The preservative performance of chitosan-based films was improved by combining the compound with other hydrocolloids, such as oil, protocatechuic acid, and wax. The CA storage conditions recommended for king oyster mushrooms are 5kPa $O_2$ and 10 to 15kPa $CO_2$ at temperatures below $10^{\circ}C$. Active MA packaging with microperforated PP film was also effective for maintaining quality during storage.

• Journal of Plant Biotechnology
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• v.29 no.2
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• pp.139-144
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• 2002

Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd /dwf3 were shown to be blocked in D$^4$reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bril/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRIl could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.