• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.326-333
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• 2020

Nitrate-nitrite-nitric oxide (NO) pathway is a major alternative source of NO and is essential for NO - dependent physiological functions in body. Food supplements having nitrate/nitrite can improve metabolic syndromes including hypertension through antioxidant activity or vasodilation. The purpose of this study was to observe the effects of fermented garlic (F. garlic) having high concentration of NO2- on changes in blood flow and nitric oxide synthesis in the cerebral cortex of rodents. The generation of nitric oxide detected by a chemi-luminescence detector was higher in F. Garlic compared with NaNO2 solution under artificial gastric juice with pH 2.0. Ether F. garlic or NaNO2 diluted with artificial cerebrospinal fluid was directly applied into around the needle probe of laser Doppler flow meter that was located on epidural surface of the cortex. Direct application of F. garlic resulted in increase of cerebral blood flow detected by a laser Doppler flow meter with a dose-dependent manner. Compared with NaNO2 solution, F. garlic produced changes in cerebral blood flow at lower concentration of NO2-. Pretreatment of methylene blue, a guanylyl cyclase inhibitor prevented upregulation of cerebral blood flow by the treatment of F. garlic. In addition, the application of F. garlic with 250, 500ppm of NO2- caused significantly the production of NO in the cortical tissue but NaNO2 solution with 500ppm of NO2- did not. In summary, these results suggested that F. garlic with high content of NO2- induce increase in cerebral blood flow through nitric oxide-dependent signal pathway.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.59-59
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• 2017

Rice (Oryza sativa L.) is the most important crop and its yield must be improved to feed the increasing global population. Recently developed high-yielding varieties with extra-large sink capacity often have a problem in unstable grain-filling. Therefore, understanding limiting factors for improving grain-filling and controlling them are essential for further improvement of rice grain yield. However, since grain-filling rate was determined by complex sink-source balance, the ability of grain-filling was very difficult to evaluate. Source ability for 'grain' was not only determined by the ability of carbon assimilation in leaves, but also that of carbon translocation from leaves to panicles. Sink strength was determined by the complex carbon metabolism from sucrose degradation to starch synthesis. Hence, to evaluate the grain-filling ability and determine its regulatory steps, the whole picture of carbon flow from photosynthesis at leaves to starch synthesis at grains must be revealed in a metabolite level. In this study, the yield and grain growth rate of three high-yielding varieties, which show high sink capacity commonly, were compared. Momiroman showed lower grain filling rate and slower grain growth rate than the other varieties, Hokuriku 193 and Tequing. To clarify the limiting point in the carbon flow of Momiroman, $CO_2$ labeled by stable isotope ($^{13}C$) was fed to three varieties during ripening period. The ratio of $^{13}C$ left in the stem was higher in Momiroman 24 hours after feeding, suggesting inefficient carbon translocation of Momiroman. More interestingly, $^{13}C$ translocation from soluble fraction to insoluble one in the grain seemed to be slower in Momiroman. To get the further insight in a metabolite level, we are now trying the $^{13}C$ labeling metabolome analysis in the developing grains.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.8.1-8.14
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• 2018

We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Our screening of the CYP2J family indicated a dysregulation in the CYP system in a cerebellar-specific manner. Moreover, in Purkinje cells, CYP2J6 showed an elevated expression level compared to that of astrocytes, granule cells, and microglia. In this regard, we found that one CYP metabolite, 14,15-EET, acts as a key mediator in ameliorating cholesterol accumulation. In confirming this hypothesis, 14,15-EET treatment reduced the accumulation of cholesterol in human NPC1 patient-derived fibroblasts in vitro by suppressing cholesterol synthesis and ameliorating the impaired autophagic flux. We show that the reduced activity within the CYP system in the cerebellum could cause the neurological symptoms of NPC1 patients, as 14,15-EET treatment significantly rescued cholesterol accumulation and impaired autophagy. We also provide evidence that the intranasal administration of hUCB-MSCs is a highly promising alternative to traumatic surgical transplantation for NPC1 patients.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.143-150
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• 2001

Butyrolactone ester of ceftezole (CFZ-BL) was synthesized by esterification of ceftezole (CFZ) with ${\alpha}-bromo-{\gamma}-butyrolactone$. The synthesis was confirmed by spectroscopic analysis. CFZ-BL was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. CFZ-BL itself did not show any microbiological activity in vitro, but serums taken after oral administration of CFZ-BL showed substaintial microbiological activity indicating that CFZ-BL is converted to microbiologically active metabolite, probably CFZ, in the body. The conversion was confirmed by in vitro incubation study, in which CFZ-BL was incubated in some body tissues of rabbit. Liver homogenate showed fastest conversion of CFZ-BL among the tissues tested (blood and intestine). Thus, CFZ-BL appeares to be rapidly metabolized in the liver to CFZ following oral administration. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-BL. In vivo metabolism of CFZ-BL to CFZ was confirmed by analying CFZ by HPLC. CFZ concentration in the serum samples taken after oral administration of CFZ-BL were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-BL, a prodrug of CFZ, was 1.45-fold higher than that of CFZ in rabbits possibly due to enhanced lipophility and absorption of the prodrug.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.100-105
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• 2005

Mancozeb (MCZ) is known to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine peritoneal macrophages through evaluation of MCZ-induced alteration of nitric oxide (NO) production and tumor necrosis $factor-{\alpha}(TNF-\alpha)$ synthesis. Macrophages were examined ex vivo from mice orally treated with various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 $(TNF-{\alpha})$ or 3 days (NO) in the presence of LPS plus $IFN-{\gamma}$. Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 ${\mu}g//mIL$ in the presence of LPS plus $IFN-{\gamma}$ for 2 $(TNF-{\alpha})$ or 3 days (NO) in vitro. NO production was decreased with the in vitro exposure to all concentrations of MCZ. However, the amount of NO production by peritoneal macrophages from MCZ-subacutely exposed mice was increased in comparision with that of control group. In vitro, MCZ suppressed $(TNF-\alpha)$ secretion with significant reduction at 2 ${\mu}g/mL$ MCZ. Conversely, $(TNF-{\alpha})$ release was enhanced ex vivo. This study provides the substantial evidence on MCZ-induced alternation in macrophage activity. In order to clearly understand the contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to further investigate the influence of major metabolite of MCZ (ETU) exposure on the NO production and $(TNF-{\alpha})$ synthesis.

• Journal of the Korean institute of surface engineering
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• v.56 no.6
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• pp.393-400
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• 2023

Acetone, a metabolite detected from the exhaled breath of people doing a diet, can be used for non-invasive monitoring of diet efficiency. Thus, gas sensors with rapid response and recovery characteristics to acetone need to be developed. Herein, we report ultrafast acetone sensors using Ce-doped In₂O₃ nanoparticles prepared by the one-pot microwave-assisted hydrothermal method. The pure In₂O₃ sensor shows a high response and fast response time (τ_res = 6 s) upon exposure to 2 ppm acetone at 300 ℃, while exhibiting a relatively sluggish recovery speed (τ_recov = 1129 s). When 20 wt% Ce is doped, the τ_recov of the sensor significantly decreased to 45 s withholding the fast-responding characteristic (τ_res = 6 s). In addition, the acetone response (resistance ratio, S) of the sensor is as high as 5.8, sufficiently high to detect breath acetone. Moreover, the sensor shows similar acetone sensing characteristics even under a highly humid condition (relative humidity of 60%) in terms of τ_res (6 s), τ_recov (47 s), and S (4.7), demonstrating its high potential in real applications. The excellent acetone sensing characteristics of Ce-doped In₂O₃ nanoparticles are discussed in terms of their size, composition, phase, and oxygen adsorption on the sensing surface.

• Journal of Microbiology and Biotechnology
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• v.22 no.9
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• pp.1258-1263
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• 2012

2,3-Butanediol (2,3-BD) is a major metabolite produced by Klebsiella pneumoniae KCTC2242, which is a important chemical with wide applications. Three genes important for 2,3-BD biosynthesis acetolactate decarboxylase (budA), acetolactate synthase (budB), and alcohol dehydrogenase (budC) were identified in K. pneumoniae genomic DNA. With the goal of enhancing 2,3-BD production, these genes were cloned into pUC18K expression vectors containing the lacZ promoter and the kanamycin resistance gene to generate plasmids pSB1-7. The plasmids were then introduced into K. pneumoniae using electroporation. All strains were incubated in flask experiments and 2,3-BD production was increased by 60% in recombinant bacteria harboring pSB04 (budA and budB genes), compared with the parental strain K. pneumoniae KCTC2242. The maximum 2,3-BD production level achieved through fed-batch fermentation with K. pneumoniae SGJSB04 was 101.53 g/l over 40 h with a productivity of 2.54 g/l.h. These results suggest that overexpression of 2,3-BD synthesis-related genes can enhance 2,3-BD production in K. pneumoniae by fermentation.

• Korean Journal of Microbiology
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• v.25 no.4
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• pp.353-359
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• 1987

The aim of the present study was to investigate the effects of growth rate on the biosynthesis of tylosin in Streptomyces fradiae. In order to elucidate the relation between the growth rate and the tylosin formation rate, the activities of enzymes involved in oxaloacetate metabolism were determined using cells grown at different growth rates in chemostats. As the results, it was found that the specific rate of tylosin formation($q_{p}$) was closely related to the specific cell growth rate and the maximum value of $q_{p}$ was 1.1mg tylosin, $q_{p}$ cell, $0.013h^{-1}$ at the growth rate $0.013h^{-1}$. However further increase in the growth rate over $0.013h^{-1}$ resulted in apparent decrease of $1_{p}$. The synthesis and activities of citrate synthase, aspartate aminotransferase, and PEP carboxylase were very low at lower growth rate. On the other hand, the activity and synthesis of methylmalonyl-CoA carboxyltransferase was closely related to tylosin formation. Therefore it was concluded that tylosin formation was apparently controlled by the growth rate.

• KSBB Journal
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• v.21 no.5
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• pp.366-370
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• 2006

In this research, analysis of UDP-glucose a precursor of ${\beta}$-1,3-glucan by high performance liquid chromatography(HPLC) was established using a reversed phase system. One of key metabolite UDP-glucose was selected and its concentration changes was measured with the change of fermentation conditions. The effects of fermentation conditions with/without nitrogen source for cell growth on ${\beta}$-1,3-glucan production were dependent on the UDP-glucose concentration. The UDP-glucose was synthesized rapidly during cell exponential growth period and maintained high during ${\beta}$-1,3-glucan production period. The UDP-glucose concentration was higher for ${\beta}$-1.3-glucan production fermentor than that for cell growth fermentor. The ${\beta}$-1,3-glucan production was optimal at pH 5.5 and synthesis of ${\beta}$-1,3-glucan was greatest at pH 5.5.

• Journal of Pharmaceutical Investigation
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• v.27 no.2
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• pp.125-131
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• 1997

Ethoxycarbonyloxyethyl ester of ceftezole (CFZ-ET) was synthesized as a prodrug by esterification of ceftezole (CFZ) with ethoxycarbonyloxyethyl chloride and was confirmed by spectroscopic analyses. CFZ-ET was more lipophillic than CFZ as assessed by n-octanol and water partition coefficients at various pH. CFZ-ET itself did not show any microbiological activity in vitro, but showed substaintial microbiological activity after oral administration of CFZ-ET, indicating that CFZ-ET is converted to microbiologically active metabolite, probably CFZ, in the body. When CFZ-ET was incubated in blood, liver and intestine homogenates of rabbits, liver homogenate showed the fastest conversion of CFZ-ET. CFZ-ET appears rapidly metabolized in the liver when given orally due to the hydrolysis of the ester to CFZ, the parent drug of CFZ-ET. In vivo metabolism of CFZ-ET to CFZ was confirmed in rabbit by HPLC analysis. CFZ-ET were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-ET was 1.5-fold higher than that of CFZ in rabbits because of enhanced lipophilicity and absorption. Based on these findings, CFZ-ET appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.