• 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.

• Korean Journal of Food Science and Technology
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• v.27 no.5
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• pp.666-672
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• 1995

This study was carried out to characterize thermolabile pectinesterase (TLPE) and thermostable pectinesterase (TSPE) separated from crude PE of Valencia orange in order to investigate the preventive measures of cloudy juice clarification. The TLPE was observed to be mixture of several isoenzymes with the same molecular weight of 36 KD (37.5 KD) but different isoelectric point of pH 8.4, 8.7, 8.9, 9.8 and ${\geq}10$ which were unstable at $70^{\circ}C$, and the TSPE also was found to be mixture of two or three isoenzymes with the same molecular weight of 53 KD (50 KD) but different isoelectric point of pH 8.7, 9.2 and ${\geq}10$ which had slightly different stability from one another at $70^{\circ}C$. The TLPE and the TSPE had the optimum reaction pH of 7.0 and $7.0{\sim}8.5,\;appK_{M}$ of 1.1 and 1.7 mg/ml, appVmax of 0.53 and $1.01\;{\mu}mol/min/{\mu}g$, and the turnover number of 19.000 and 54,000 mol/mol/min toward Kodak pectin, respectively. The TSPE had higher storage stabiblity and cloud loss effect on orange juice than the TLPE. Above all, the crude PE was most effective on orange juice cloud loss among the PEs used.

• Genomics & Informatics
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• v.20 no.2
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• pp.21.1-21.14
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• 2022

The influenza A viruses have high mutation rates and cause a serious health problem worldwide. Therefore, this study focused on genome characterization of the viruses isolated from Thai patients based on the next-generation sequencing technology. The nasal swabs were collected from patients with influenza-like illness in Thailand during 2017-2018. Then, the influenza A viruses were detected by reverse transcription-quantitative polymerase chain reaction and isolated by MDCK cells. The viral genomes were amplified and sequenced by Illumina MiSeq platform. Whole genome sequences were used for characterization, phylogenetic construction, mutation analysis and nucleotide diversity of the viruses. The result revealed that 90 samples were positive for the viruses including 44 of A/H1N1 and 46 of A/H3N2. Among these, 43 samples were successfully isolated and then the viral genomes of 25 samples were completely amplified. Finally, 17 whole genomes of the viruses (A/H1N1, n=12 and A/H3N2, n=5) were successfully sequenced with an average of 232,578 mapped reads and 1,720 genome coverage per sample. Phylogenetic analysis demonstrated that the A/H1N1 viruses were distinguishable from the recommended vaccine strains. However, the A/H3N2 viruses from this study were closely related to the recommended vaccine strains. The nonsynonymous mutations were found in all genes of both viruses, especially in hemagglutinin (HA) and neuraminidase (NA) genes. The nucleotide diversity analysis revealed negative selection in the PB1, PA, HA, and NA genes of the A/H1N1 viruses. High-throughput data in this study allow for genetic characterization of circulating influenza viruses which would be crucial for preparation against pandemic and epidemic outbreaks in the future.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.1031-1040
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• 2013

Candida albicans is a dimorphic fungus that commensally colonizes human mucosal surfaces. The aim of this study was to assess the role of different C. albicans morphologies in inducing pattern recognition receptors (PRRs) and cytokines in macrophages. Macrophages may respond to pathogen-associated molecular patterns via TLR2 and TLR4 by expressing cytokines. The hyphal transition of C. albicans was induced by 20% serum (S), RPMI-1640 (R), or $39^{\circ}C$ culture (H). Macrophages were then challenged with either yeast (Y) or different hyphae cultures of C. albicans, followed by RT-PCR and FACS analysis of PRRs expression. In addition, macrophages were stimulated with either yeast or different hyphae cultures of C. albicans used by RT-PCR and Bio-Plex analysis of cytokines production. Macrophages expressed high levels of TLR4 and dectin-1 after stimulation with Y cells. In contrast, stimulation with H or R cells strongly increased the expression of TLR2 and dectin-2. Stimulation with Y cells significantly enhanced the expression of IL-$1{\beta}$ and weakly increased the expression of IL-6 and IL-12. Stimulation with hyphal cells (S, R, and H) strongly increased IL-10 expression, but weakly reduced IL-$1{\beta}$ expression. The phagocytosis activity and NO production of macrophages were decreased upon treatment with hyphal cells compared with yeast, and depended on the length of hyphae. In summary, the yeast and hyphae forms of C. albicans resulted in an induction of different PRRs, with accompanying differences in immune cell cytokine profiles.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.577-583
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• 2019

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants-including three novel variants F69S, L310V, and Q324X-that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high $k_{cat}$ values; however, their $K_m$ values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher $K_m$ and lower $k_{cat}$ values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower $k_{cat}$ and $K_m$ values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.

• Journal of the Korean Society of Clothing and Textiles
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• v.16 no.2
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• pp.237-244
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• 1992

The purpose of this study was to comparatively evaluate thermal and water transmission properties of several vapor permeable water repellent (VPWR) fabrics and synthetic battings that became available in recent years. Five VPWR fabrics evaluated were Hipora in three coating variants, $Gore-Tex^{\circledR}$ and $Aitace^{\circledR}$. Battings evaluated were $Viwarma^{\circledR}$, $Uniwarmr^{\circledR}$, $Thinsulate^{\circledR}$, and $Airseal^{\circledR}$ Thermal resistance and water vapor transmission were measured for each fabric and batting and in all combinations. Thermal resistance at zero and 37 cm/sec air velocity was determined by the Thermo Labo II technique for simultaneously measuring conduction and radiation heat transfer. Water vapor transmission over 24 hours was measured by a modified weight-gain method in a compact humid chamber at conditions simulating the clothing climate under heavy exercise ($40{\pm}1^{\circ}C$, $90{\pm}2\%$ R.H., and 0.5 m/sec air velocity). Fabric porosity was calculated from fiber density and fabric weight, thickness, and area. Thermal resistance results for the fabrics showed the effectiveness of coatings in inhibiting heat transfer. Measurements taken in wind were: $31.1\~37.6\%$ for $Hipora^{\circledR}$ variants; $31.0\%$ for $Gore-Tex^{\circledR}$; and $18.4\%$ for $Aitaca^{\circledR}$ Measurements without wind were higher but in the same order. Water vapor transmission results were in reverse order: $Aitac^{\circledR}$, $8.8 kg/m^{2};\;Gore-Tex^{\circledR}$, 6.4 kg/$m^{2}$; and $Hipora^{\circledR},\;4.4\~6.0\;kg/m^{2}$. In general thermal resistance increased with porosity. For battings, the thermal resistance with wind results were: $Viwarmu^{\circledR}$, $65.0\%;\; Thinsulate^{\circledR}$, $62.0\%$; $Uniwarm^{\circledR}$, $61.0\%$; and $Airseala^{\circledR},\;53.1\%$. Thermal resistance was proportional to thickness. Thermal resistance of fabric-batting combinations were $20\%$ higher than those of the battings only. Water vapor transmission for combinations was mainly affected by that for the VPWR fabric used.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.45-54
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• 2000

Cannabidiol derivatives (1, 2 and 3), and 5-fluorouracil (4, 5-FU) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. These compounds showed a potent inhibitory activity in vitro in the micromolar range against KB cell lines. In general, the antitumor activity of these compounds (1, 2, 3 and 4) was in a dose-dependent over the micromolar concentration ranges from $1\;{\mu}M\;to\;100\;{\mu}M$. The comparison of $IC_{50}$ values of these compounds in tumor cell lines shows that their susceptibility to these compounds decreases in the following order: CBD > 5-FU > CBDME > CBDDE by the MTT assay and SRB assay. Cannabidiol derivatives (1, 2 and 3), and 5-FU were tested for their cytotoxic effects on NIH 3T3 fibroblasts using two different MTT assay and SRB assay. These compounds exhibited potent cytotoxic activities in vitro in the micromolar range against NIH 3T3 fibroblasts. In general, the cytotoxic activities of these compounds (1, 2, 3 and 4) were in a dose-dependent over the micromolar concentration range $1\;{\mu}M\;to\;100\;{\mu}M$. The comparison of $CD_{50}$ values of these compounds on NIH 3T3 fibroblasts shows that their susceptibility to these compounds decreases in the following order; CBD > 5-FU > CBDDE > CBDME by MTT assay, CBD > 5-FU > CBDME > CBDDE by SRB assay. These results suggest that cannabidiol (1, CBD) retains the most growth-inhibitory activity against KB cell lines.

• Korean Journal of Food Science and Technology
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• v.48 no.5
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• pp.502-507
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• 2016

This study was designed to investigate the beneficial effects of fermented Rhus verniciflua stem bark extract (RVSBE) on the stomach. We evaluated RVSBE for its antimicrobial activity against Helicobacter pylori (H. pylori), along with its ability to reduce the viability of human gastric cancer AGS cells. In addition, its anti-inflammatory effect was examined by evaluating nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. RVSBE showed antimicrobial activity, as 2.0 mg of the extract produced a clear inhibition zone of 4.0 mm. RVSBE inhibited the growth of AGS cells by 20% at concentrations ranging from 0.25-1.0 mg/mL. Regarding the anti-inflammatory effects of RVSBE, at 0.1-1.0 mg/mL, the extract showed more than 75% inhibition of NO production. In addition, cells treated with 0.25 mg/mL RVSBE showed a 25% decrease in iNOS mRNA levels compared to those in the LPS-treated cells. These results suggest that RVSBE may have significant inhibitory effects on inflammatory mediators, and therefore, may be a potential anti-inflammatory candidate.

• Preventive Nutrition and Food Science
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• v.6 no.2
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• pp.126-132
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• 2001

Methanol extracts form four kinds of kimchi, which were differently prepared in kinds and levels of sub-ingredients, were given to Balb/c mice for 3 weeks (0.5 mg/kg/day). Peritoneal macrophages isolated from mice treated with kimchi extracts and saline were stimulated by lipopolysaccharide (LPS). K3 and K4 kimchis, containing more red pepper powder, garlic, Chinese pepper powder, mustard leaf and organically cultivated Korean cabbage, significantly increased NO production by the activated macrophages (p<0.05). K1, K2, K3 and K4 kimchi extracts (0.01, 0.1, 1.0 $\mu\textrm{g}$) significantly reduced the increased TGF-$\beta$1 production of H.pylori lysate (0.01 $\mu\textrm{g}$)-activated human epithelial RPMI 2650 cells (5$\times$10$^{4}$ cells/mL) at 24 and 48 hrs of treatment (p<0.01). However, the decreased TGF-$\beta$1 $\alpha$ production of RPMI 2650 cells by H. pylori lysate increased by treatment with kimchi extract for 72 hrs. Especially, K4 kimchi (containing organically cultivated Korean cabbage and more ingredients, modulated TGF-$\beta$1 production of H. pylori lysate-activated RPMI 2650 cells to the normal level (control) by treatment for 48 hrs. The treatment of K1 and K4 kimchi enhanced the LPS (0.01 $\mu\textrm{g}$/mL)-induced IL-6 production of splenocytes. The results suggest that kimchi might have an beneficial effect on cancer prevention due in part to the function enhancing NO production of activated macrophages. Our data suggest that kimchi could modulate TGF-$\beta$1 production by cancer cells and IL-6 production of splenocytes, thereby possibly contributing to control carcinogenesis and the immune system.

• Journal of Korean Neurosurgical Society
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• v.59 no.5
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• pp.466-470
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• 2016

Objective : To determine imaging features that may separate adamantinomatous and papillary variants of craniopharyngiomas given that tumors with adamantinomatous signature features are associated with higher recurrence rates, morbidity, and mortality. We specifically reviewed calcification on CT, T1 bright signal intensity, and cystic change on T2 weighted images for differentiating these two types. Methods : We retrospectively reviewed the MRI and CT studies in 38 consecutive patients with pathologically proven craniopharyngiomas between January 2004 and February 2014 for the presence of calcification on CT scans, bright signal intensity on T1 weighted images, and cystic change on T2 weighted images. Results : Of the 38 craniopharyngiomas, 30 were adamantinomatous type and 8 were papillary type. On CT scans, calcification was present in 25 of 38 tumors. All calcified tumors were adamantinomatous type. Twenty four of 38 tumors had bright signal intensity on T1 weighted images. Of these 24 tumors, 22 (91.7%) were adamantinomatous and 2 were papillary type. Cystic change on T2 weighted images was noted in 37 of 38 tumors; only 1 tumor with papillary type did not show cystic change. Conclusion : T1 bright signal intensity and calcification on CT scans uniformly favor the adamantinomatous type over papillary type of craniopharyngioma in children. However, these findings are more variable in adults where calcification and T1 bright signal intensity occur in 70.6% and 58.8% respectively of adult adamantinomatous types of craniopharyngiomas.