• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1100-1105
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• 2006

Purpose : Because NELL2 expression is strictly restricted only in neurons in developing and post-differentiated neural tissues, it is thought to be involved in the neuronal differentiation during development and in the maintenance of neuronal physiology in the post-differentiated neurons. In this study, we examined whether NELL2 is involved in the regulation of cell cycle and apoptosis in the hippocampal neuroprogenitor HiB5 cells. Methods : Effects of NELL2 on the cultured HiB5 cell numbers, DNA fragmentation, and proteins involved in the regulation of the cell cycle were measured. Results : NELL2 induced a decrease in cell numbers and an increase in G1 phase arrest. Moreover, transfection of NELL2 resulted in an increase of DNA fragmentation that shows an evidence of apoptosis. Contents of proteins involved in the regulation of cell cycle were also changed by transfection of NELL2 expression vectors. Conclusion : This study suggests that NELL2 plays an important role in the regulation of cell cycle and apoptosis of neurons.

• Journal of Life Science
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• v.11 no.2
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2006.02a
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.295-304
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• 2021

Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.

• Korean Circulation Journal
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• v.53 no.10
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• pp.693-707
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• 2023

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions: There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

• Journal of Embryo Transfer
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• v.17 no.1
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• pp.45-53
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• 2002

The main goal of this study was to produce transgenic porcine embryos by direct injection of sperm-mediated exogenous DNA. Spermatozoa (6$\times$10$^{6}$ sperms of final concentration) were mixed with pcDNA LAC Z (20 ng/$\mu$l) and subjected into electroporation (300~750 volts, 25 $\mu$F, 0.4 cm electrode). After sperm injection, the oocytes were activated electrically (1.7 KV/cm, 30$\mu$sec, single pulse) in 0.3 M mannitol solution or not. The sperm injected eggs were cultured in NCSU 23 medium (0.4% BSA) at 39$^{\circ}C$, 5% $CO_2$ in air fur 144 h. The rates of cleavage and development into blastocyst stage in activation group were significantly higher than those of non-activation group (79.6% and 24.1% vs. 46.3% and 14.4%, respectively, p<0.05). Control oocytes and shame injection were developed to blastocysts low (2.5%). Sixty five (27.1%) out of 240 embryos observed in activation and non-activation groups were showed positive by X-gal staining. However, all embryos in both groups were expressed partial or mosaic pattern. These results suggested that electrical stimulation far oocytes activation after sperm injection enhances the incidence of both fertilization and development fellowing sperm injection in the pig. Our study also suggested that sperm-mediated transfer of exogenous DNA by ICSI would be used as a valuable tool for the production of transgenic porcine embryos.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.625-634
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• 2011

Green tea seed coat (GTSC) was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether (PE), ethyl acetate (EtOAC) and butanol (BuOH). The EtOAC fraction showed the highest level in total phenol contents and the lowest level in nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophage cell. Thus, this study was carried out to investigate the anti-inflammatory and its mechanisms of GTSC EtOAC fraction in LPS-stimulated RAW264.7 macrophage cell. GTSC EtOAC fraction contained EGC ($1146.48{\pm}11.01\;{\mu}g/g$), tannic acid ($966.99{\pm}32.24\;{\mu}g/g$), EC ($70.88{\pm}4.39\;{\mu}g/g$), gallic acid ($947.61{\pm}1.03\;{\mu}g/g$), caffeic acid ($37.69{\pm}1.46\;{\mu}g/g$), ECG ($35.46{\pm}3.19\;{\mu}g/g$), and EGCG ($15.53{\pm}0.09\;{\mu}g/g$) when analyzed by HPLC. NO production was significantly (p<0.05) suppressed in a dose-dependent manner with an $IC_{50}$ of $80.11\;{\mu}g$/mL. Also prostaglandin $E_2$ level was also inhibited in a dose-dependent manner. Moreover, iNOS protein expression was suppressed in dose-dependent manner but COX-2 gene expression was not affected. Total antioxidant capacity and glutathione (GSH) levels were enhanced more than the LPS-control. Expressions of antioxidative enzymes including catalase, GSH-reductase and Mn-SOD were elevated compared to LPS-control. Nuclear p65 level was decreased in the GTSC EtOAC fraction in a dose-dependent manner. These results indicate that GTSC EtOAC fraction inhibit oxidative stress and inflammatory responses through elevated GSH levels, antioxidative enzymes expressions and suppression of iNOS expression via NF-${\kappa}B$ down-regulation.

• Journal of Animal Science and Technology
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• v.53 no.5
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• pp.389-395
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• 2011

This study was conducted to investigate the combined effect of fatty acid synthase (FASN) and Acetyl CoA Carboxylase-${\alpha}$ (ACACA) genes on carcass traits of Korean cattle (Hanwoo). A total of 1,057 commercial Hanwoo cattle provided by the NongHyup Livestock Research Center (NLRC) and Hanwoo Performance Competition (HPC) were used to analyze the effect of four single nucleotide polymorphisms (SNPs) within FASN (g.11280A>G, g.16024A>G, g.16039T>C, and g.17924A>G) and one SNP within ACACA (g.2274G>A) genes. In addition, the effect of genotypic combinations between FASN (g.17924A>G) and ACACA (g.2274G>A) SNPs has been studied with carcass traits. Significant associations were identified between g.17924A>G of FASN and carcass weight and back fat, and between the ACACA gene SNP g.2274G>A and longissimus muscle area with HPC samples. It was also found that both effects of FASN g.17924A>G and ACACA g.2274G>A polymorphisms were consistent in NLRC samples. Combined analyses of both NLRC and HPC samples also revealed the significant associations between the FASN g.17924A>G and carcass weight and back fat and between the ACACA g.2274G>A and back fat, respectively. The effect of the genotypic combination of g.17924A>G within FASN and g.2274G>A within ACACA genes showed that the combination of both GG genotypes of FASN and ACACA SNPs causes higher carcass weight and marbling score. The results of this study indicate that the two SNP markers within the FASN and ACACA genes can be utilized to select superior Hanwoo cows and calves in commercial Hanwoo farms.