• Title/Summary/Keyword: human-to-human (H2H)

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Fermentation Properties and in vitro Anticancer Effect of Young Radish Kimchi and Young Radish Watery Kimchi (열무김치 및 열무물김치의 발효특성과 in vitro 항암효과)

  • Kong, Chang-Suk;Kim, Do-Kyoung;Rhee, Sook-Hee;Rho, Chi-Woong;Hwang, Hae-Jun;Choi, Keyng-Lag;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.3
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    • pp.311-316
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    • 2005
  • Fermentation properties and in vitro anticancer effect of young radish (YR) kimchi and young radish watery (YRW) kimchi were investigated during fermentation at 5℃. The fermentation of YR kimchi during 2-3 weeks led to the decrease of pH down to pH 4.3, increased acidity, and the highest Leuconostoc sp. counts. YR kimchi showed the acidity of 1.04-1.27% at the pH 4.3, when the kimchi was ripened properly. The fermentation of YRW kimchi during 9 days led to the decrease of pH down to pH 4.3 and the acidity of 0.20%. Inhibitory effects of the juices of YR, YR kimchi, and YRW kimchi on the growth of AGS human gastric adenocarcinoma cells in MTT assay were increased with the added concentration. The juice of YR kimchi had a higher inhibitory effect on the growth of AGS human gastric adenocarcinoma cells than that of YRW kimchi at same concentration. The juice of YR kimchi showed similar inhibitory effects on the growth of AGS human gastric and HT-29 human colon adenocarcinoma cells in MTT assay to baechu kimchi, which the inhibition rates are more than 50%.

Effects of Paroxetine on a Human Ether-a-go-go-related Gene (hERG) K+ Channel Expressed in Xenopus Oocytes and on Cardiac Action Potential

  • Hong, Hee-Kyung;Hwang, Soobeen;Jo, Su-Hyun
    • International Journal of Oral Biology
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    • v.43 no.1
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    • pp.43-51
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    • 2018
  • $K^+$ channels are key components of the primary and secondary basolateral $Cl^-$ pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human $K^+$ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier $K^+$ channel ($I_{Kr}$) in the heart. Mutations in hERG reduce $I_{Kr}$ and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at $36^{\circ}C$, treatment with $0.4{\mu}M$ paroxetine for 5 min decreased the action potential duration at 90% of repolarization ($APD_{90}$) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

Suppression of Human GD3 Synthase (hST8Sia I) Expression Induced by Retinoic Acid in Human Melanoma SK-MEL-2 Cells (흑색종세포주 SK-MEL-2에서 레티노이드에 의한 GD3합성효소(hST8Sia I)의 발현억제)

  • Kwon, Haw-Young;Kang, Nam-Young;Lee, Young-Choon
    • Journal of Life Science
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    • v.20 no.5
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    • pp.655-661
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    • 2010
  • To elucidate the mechanism underlying the suppressive regulation of hST8Sia I expression in retinoic acid (RA)-induced SK-MEL-2 cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5‘-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kB, functions as the RA-repressive promoter in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analyses indicated that the NF-kB binding site at -731 to -722 is crucial for the RA-induced repression of hST8Sia I in SK-MEL-2 cells. In addition, the transcriptional activity of hST8Sia I suppressed by RA in SK-MEL-2 cells was strongly inhibited by extracellular signal-regulated protein kinase (ERK) inhibitor U0126 and protein kinase C (PKC) inhibitor GO6976, as determined by RT-PCR and luciferase assay of hST8Sia I promoter containing the -1146 to -646 regions. These results suggest that RA markedly modulates transcriptional regulation of hST8Sia I gene expression through the PKC/ERK signal pathway in SK-MEL-2 cells.

Inhibitory activities of Perilla frutescens britton leaf extract against the growth, migration, and adhesion of human cancer cells

  • Kwak, Youngeun;Ju, Jihyeung
    • Nutrition Research and Practice
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    • v.9 no.1
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    • pp.11-16
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    • 2015
  • BACKGROUND/OBJECTIVES: Perilla frutescens Britton leaves are a commonly consumed vegetable in different Asian countries including Korea. Cancer is a major cause of human death worldwide. The aim of the current study was to investigate the inhibitory effects of ethanol extract of perilla leaf (PLE) against important characteristics of cancer cells, including unrestricted growth, resisted apoptosis, and activated metastasis, using human cancer cells. MATERIALS/METHODS: Two human cancer cell lines were used in this study, HCT116 colorectal carcinoma cells and H1299 non-small cell lung carcinoma cells. Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide were performed for measurement of cell growth. Soft agar and wound healing assays were performed to determine colony formation and cell migration, respectively. Nuclear staining and cell cycle analysis were performed for assessment of apoptosis. Fibronectin-coated plates were used to determine cell adhesion. RESULTS: Treatment of HCT116 and H1299 cells with PLE resulted in dose-dependent inhibition of growth by 52-92% (at the concentrations of 87.5, 175, and $350{\mu}g/ml$) and completely abolished the colony formation in soft agar (at the concentration of $350{\mu}g/ml$). Treatment with PLE at the $350{\mu}g/ml$ concentration resulted in change of the nucleus morphology and significantly increased sub-G1 cell population in both cells, indicating its apoptosis-inducing activity. PLE at the concentration range of 87.5 to $350{\mu}g/ml$ was also effective in inhibiting the migration of H1299 cells (by 52-58%) and adhesion of both HCT116 and H1299 cells (by 25-46%). CONCLUSIONS: These results indicate that PLE exerts anti-cancer activities against colon and lung cancers in vitro. Further studies are needed in order to determine whether similar effects are reproduced in vivo.

Tanshinone IIA Protects Endothelial Cells from H2O2-Induced Injuries via PXR Activation

  • Zhu, Haiyan;Chen, Zhiwu;Ma, Zengchun;Tan, Hongling;Xiao, Chengrong;Tang, Xianglin;Zhang, Boli;Wang, Yuguang;Gao, Yue
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.599-608
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    • 2017
  • Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide ($H_2O_2$) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to $400{\mu}M$ $H_2O_2$ for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of $H_2O_2$ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against $H_2O_2$-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by $H_2O_2$ via PXR activation. In conclusion, Tan IIA protected HUVECs against $H_2O_2$-induced cell injury through PXR-dependent mechanisms.

Extracts of Aster species Inhibit Invasive Phenotype and Motility of H-ras MCF10A Human Breast Epithelial Cells Possibly via Downregulation of MMP-2 and MMP-9

  • Ahn, Seong-Min;Lee, Kang-Ro;Moon, A-Ree
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.240-245
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    • 2002
  • Cancer metastasis represents the most important cause of cancer death and antitumor agents that may inhibit this process have been extensively pursued. Invasion and metastasis of malignantly transformed cells involve degradation of the extracellular matrix (ECM) components by matrix metalloproteinases (MMP), especially MMP-2 and -9. We previously showed that H-ras-induced invasive phenotype may involve MMP-2, rather than MMP-9, in MCF10A cells. In the present study, we investigated the chemopreventive effect of Aster, a widely used culinary vegetable in Korea. We screened twelve extracts from three Aster species (Aster scaber, Aster oharai and Aster glehni) for the inhibitory effect on MMP activities of H-ras MCF10A human breast epithelial cells. All of the extracts tested in this study efficiently inhibited the gelatinolytic activities of MMP-2 and MMP-9. A more prominent inhibition was observed in MMP-2 activity compared to MMP-9. Out of twelve extracts, eight extracts showed>90% inhibition of MMP-2 activity in H-ras MCF10A cells while only one extract showed>90% inhibition of MMP-9 activity. We selected three extracts (AO-3, AG-3 and AS-EA) for further studies since they exerted a marked inhibition in the ratio of MMP-2 to MMP-9. Treatment with AO-3, AG-3 and AS-EA in H-ras MCF10A cells caused a significant inhibition of invasive phenotype and migration, proving a chemopreventive potential of these extracts. Taken together, our results demonstrate that extracts of Aster effectively inhibit invasion and migration of highly malignant human breast cells, possibly via downregulation of MMP-2 and MMP-9.

In Vitro Neural Cell Differentiation Derived from Human Embryonic Stem Cells: II. Generation of Specific Neurons from Neural Progenitor Cells Treated with BDNF and PDGF

  • Jo Hyeon-Jeong;Kim Eun-Yeong;Choe Gyeong-Hui;An So-Yeon;Park Se-Pil;Im Jin-Ho
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.84-84
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    • 2002
  • This study was to investigate generation of the specific neuronal cell in vitro from the neural progenitors derived from human embryonic stem (hES, MB03) cells. For the neural progenitor cell formation, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for 7-10 days, 20 ng/㎖ of bFGF added N2 medium) from EB. And then for the differentiation into neuronal cells, neural progenitor cells were cultured in N2 medium (without bFGF) supplemented with brain derived neurotrophic factor (BDNF, 5 ng/㎖) or platelet derived growth factor-bb (pDGF-bb, 20ng/㎖) for 2 weeks. (omitted)

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Interference of EGFP RNA in Human NT-2/D1 Cell Lines Using Human U6 Promoter-based siRNA PCR Products

  • Kwak, Young-Don;Sugaya, Kiminobu
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.3
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    • pp.273-276
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    • 2006
  • RNA interference (RNAi), a process of sequence-specific gene suppression, has been known as a natural gene regulatory mechanism in a wide range of lower organisms. Recently, we have reported that a transfection of human U6 promoter (hU6) driven hairpin small-interference RNA (siRNA) plasmid specifically knocks down the target gene by post-transcriptional gene silencing in mammalian cells. Here we report that transfection of polymerase chain reaction (PCR) products, containing human U6 promoter with hairpin siRNA, knocks down the target gene expression in human teratocarcinoma NT-2/D1 cells. Moreover, we showed 3' end termination sequence, 5 Ts, is not critical elements for knocking down in PCR-based siRNA system. Therefore, the PCR-based siRNA system is a promising tool not only for the screening but also to temporally regulate gene expression in the human progenitor cells.

Characteristics of Thiamine Uptake by the BeWo Human Trophoblast Cell Line

  • Keating, Elisa;Lemos, Clara;Azevedo, Isabel;Martel, Fatima
    • BMB Reports
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    • v.39 no.4
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    • pp.383-393
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    • 2006
  • Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

Characterization of Double Transgenic Mice Harboring Both Goat $\beta$-casein/hGH and Goat $\beta$-casein/hG-CSF Hybrid Genes

  • Oh, Keon-Bong;Lee, Chul-Sang
    • Development and Reproduction
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    • v.13 no.3
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    • pp.191-198
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    • 2009
  • In an attempt to simultaneously produce two human proteins, hGH and hG-CSF, in the milk of transgenic mice, we constructed goat $\beta$-casein-directed hGH and hG-CSF expression cassettes individually and generated transgenic mice by co-injecting them into mouse zygotes. Out of 33 transgenic mice, 29 were identified as double transgenic harboring both transgenes on their genome. All analyzed double transgenic females secreted both hGH and hG-CSF in their milks. Concentrations ranged from 2.1 to $12.4\;mg/m{\ell}$ for hGH and from 0.04 to $0.13\;mg/m{\ell}$ for hG-CSF. hG-CSF level was much lower than hGH level but very similar to that of single hG-CSF mice, which were introduced with hG-CSF cassette alone. In order to address the causes of concentration difference between hGH and hG-CSF in milk, we examined mRNA level of hGH and hG-CSF in the mammary glands of double transgenic mice and tissue specificity of hG-CSF mRNA expression in both double and single transgenic mice. Likewise protein levels in milk, hGH mRNA level was much higher than hG-CSF mRNA, and hG-CSF mRNA expression was definitely specific to the mammary glands of both double and single transgenic mice. These results demonstrated that two transgenes have distinct transcriptional potentials without interaction each other in double transgenic mice although two transgenes co-integrated into same genomic sites and their expressions were directed by the same goat $\beta$-casein promoter. Therefore goat $\beta$-casein promoter is very useful for the multiple production of human proteins in the milk of transgenic animals.

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