• Title/Summary/Keyword: Terminal differentiation

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Cytotoxicity in HL-60 cells and human lymphocytes and effect of leukemia cell differentiation induced by Saussureae Radix extract (정상사람림프구와 HL-60 cell에서 목향의 세포독성과 백혈병세포 분화효과에 관한 연구)

  • Lee, Young-Joon;Kang, Su-Jin;Ku, Sae-Kwang
    • The Korea Journal of Herbology
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    • v.26 no.2
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    • pp.31-37
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    • 2011
  • Objectives : This study was focused to investigate the toxicity of Saussurea lappa (SL) extracts in HL-60 cells and human lymphocytes. We also examined the differentiation effect of SL against leukemia cells. Methods : For examining the toxicity of SL, cytokinesis-block micronucleus (CBMN) assay and single cell gel eletrophoresis (SCGE) assay were used in present study. The cell differentiation effect of SL was evaluated by nitroblue tetrazolium (NBT) reduction assay. Results : The inhibition of cell growth in HL-60 cells was observed in a dose-dependant manner after SL treatment for 24 h. According to SCGE assay, HL-60 cells treated with SL increased DNA damage at $10{\mu}g/m{\ell}$, while DNA damage was induced by 0.1, 1, $10{\mu}g/m{\ell}$ concentration of SL in human lymphocytes. Our results indicated that SL have no genotoxic effect in HL-60 cells and human lymphocytes. Additionally, the differentiation effect was induced in $1{\mu}g/m{\ell}$ SL-treated HL-60 cells. Conclusions : From above results it is suggested that SL could be beneficial for the preparation of the useful agent for treating leukemia.

Design remaining capacity calculation system of a nickel-cadmium battery by using fuzzy logic (퍼지로직을 이용한 니켈-카드뮴 축전지의 잔존용량 산출 알고리즘 제안)

  • Jang, Woong-Sung;Jeon, Sun-Yong
    • Proceedings of the KIEE Conference
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    • 2004.11c
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    • pp.355-357
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    • 2004
  • In this paper, to calculate accurate remaining volume, it presents how to figure out nickel-cadmium battery algorithm. A nickel-cadmium battery has widely been used in industrial field and to military. Recent high demands on the battery caused 'How to calculate accurate remaining volume is very important task to be solved. In this paper, it says it is useful using the terminal voltage change of the resistance that can be connected with the battery and the differentiation of the terminal voltage to calculate remaining volume of nickel-cadmium battery. And these can be used for volume inference data so that it is fuzzy based system which can be helpful to inference the remaining volume by the resistance of terminal voltage change. Because of electrochemical complexity, the volume calculating system is inferencing undirectly by experimentally built DB where as current the existing volume models are suffering to be adapted.

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New Alternative Splicing Isoform and Identification of the Kinase Activity of N-Terminal Kinase-Like Protein (NTKL)

  • Merlin, Jayalal L.P.
    • Journal of Integrative Natural Science
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    • v.6 no.4
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    • pp.234-243
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    • 2013
  • N-terminal kinase-like (NTKL) protein was initially identified as a protein binding to protein kinase B (PKB, also known as Akt). Though NTKL-BP1 (NTKL-binding protein 1) has been identified as an NTKL binding protein, its functions related to binding have not yet been elucidated. Here, a new alternative spliced variant of NTKL and its association with integrin ${\beta}1$ is described, in addition to the kinase activity of NTKL and its substrate candidates. Although the phosphorylation of the candidates must be further confirmed using other experimental methods, the observation that NTKL can phosphorylate ROCK1, DYRK3, and MST1 indicates that NTKL may act as a signaling protein to regulate actin assembly, cell migration, cell growth, and to facilitate differentiation and development in an integrin-associated manner.

The use of culture systems for the study of oligodendrocyte development and injury: The erbB2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes

  • Park, Song-Kyu;Kim, Hwan-Mook;Vartanian, Timothy
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2002.05a
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    • pp.14-23
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    • 2002
  • Development of oligodendrocytes and the generation of myelin internodes within the spinal cord depends on regional signals derived from the notochord and axonally derived signals. Neuregulin (NRG)-1, localized in the floor plate as well as in motor and sensory neurons, is necessary for normal oligodendrocyte development. Oligodendrocytes respond to NRGs by activating members of the erbB receptor tyrosine kinase family. Here, we show that erbB2 is not necessary for the early stages of oligodendrocyte precursor development, but is essential for proligodendroblasts to differentiate into galactosylcerebroside-positive (GalC+) oligodendrocytes. In the presence of erbB2, oligodendrocyte development is normal. In the absence of erbB2 (erbB2-/-), however, oligodendrocyte development is halted at the proligodendroblast stage with a >10-fold reduction in the number of GalC+ oligodendrocytes. ErbB2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal, since there is no evidence of increased oligodendrocyte death in the absence of erbB2. Furthermore, known survival signals for oligodendrocytes increase oligodendrocyte numbers in the presence of erbB2, but fail to do so in the absence of erbB2. Of the erbB2-/- oligodendrocytes that do differentiate, all fail to ensheath neurites. These data suggest that erbB2 is required for the terminal differentiation of oligodendrocytes and for development of myelin.

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Angelica Sinensis Polysaccharide Induces Erythroid Differentiation of Human Chronic Myelogenous Leukemia K562 Cells

  • Wang, Lu;Jiang, Rong;Song, Shu-Dan;Hua, Zi-Sen;Wang, Jian-Wei;Wang, Ya-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3715-3721
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    • 2015
  • Leukemia is a clonal disorder with blocked normal differentiation and cell death of hematopoietic progenitor cells. Traditional modalities with most used radiation and chemotherapy are nonspecific and toxic which cause adverse effects on normal cells. Differentiation inducing therapy forcing malignant cells to undergo terminal differentiation has been proven to be a promising strategy. However, there is still scarce of potent differentiation inducing agents. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), has potential differentiation inducing activity in human chronic erythro-megakaryoblastic leukemia K562 cells. MTT assays and flow cytometric analysis demonstrated that ASP inhibited K562 cell proliferation and arrested the cell cycle at the G0/G1 phase. ASP also triggered K562 cells to undergo erythroid differentiaton as revealed by morphological changes, intensive benzidine staining and hemoglobin colorimetric reaction, as well as increased expression of glycophorin A (GPA) protein. ASP induced redistribution of STAT5 protein from the cytoplasm to the nucleus. Western blotting analysis further identified that ASP markedly sensitized K562 cells to exogenous erythropoietin (EPO) by activating EPO-induced JAK2/STAT5 tyrosine phosphorylation, thus augmenting the EPO-mediated JAK2/STAT5 signaling pathway. On the basis of these findings, we propose that ASP might be developed as a potential candidate for chronic myelogenous leukemia inducing differentiation treatment.

Extracellular Signal-regulated Kinase (ERK) is Required for Water Extract of Nardostachys chinersis-Induced Differentiation in HL-60 Cells

  • Yoon, Sang-Hak;Ju, Sung-Min;Kim, Nam-Su;Park, Sung-Cheol;Park, Jin-Young;Kim, Sung-Hoon;Song, Yung-Sun;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1315-1320
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    • 2006
  • The root and rhizomes of Nardostachys chinensis belonging to the family Valerianaceae has been used for medicinal therapy in Korean traditional medicine. The parts have been especially used to elicit stomachic and sedative effects. Our previous studies reported that the water extract of N. chinensis has induced granulocytic differentiation inhuman promyelocytic leukemia (HL-60) cells. The Mitogen-activated protein kinases (MAPKs) are serine/threonine kinases involved in the regulation of various cellular responses, such as cell proliferation, differentiation and apoptosis. In this study, we investigated the signaling pathways on the HL-60 cell differentiation induced by N. chinensis. Activation of extracellular signal-regulated kinase (ERK) increased time-dependently in differentiation of HL-60 cells induced by N. chinersis. Activation of p38 increased slightly at 24 h after N. chinensis treatment, but activation of c-jun N-terminal kinase (JNK) was unaffected. Inhibitor of ERK (PD98059) significantly reduced NBT reduction activity induced by N. chinensis in HL-60 cells. In contrast, p38 inhibitor (SB203580) did not inhibit the cell differentiation. These results indicated that activaiton of ERK may De involved in HL-60 cell differentiation induced by N. chinensis.

Construction of Artificial Epithelial Tissues Prepared from Human Normal Fibroblasts and C9 Cervical Epithelial Cancer Cells Carrying Human Papillomavirus Type 18 Genes

  • Eun Kyung Yang;Seu
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.3 no.1
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    • pp.1-5
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    • 1998
  • One cervical cancer cell line, C9, carrying human papillomavirus type 18 (HPV18) genes that is one of the major etiologic concoviruses for cervical cancer was characterized. This cell line was further characterized for its capacity related to the epithelial cell proliferation, stratification and differentiation in reconstituted artificial epithelial tissue. The in vitro construction of three dimensional artificial cervical opithelial tissue has been engineered using C9 epithelial cancer cells, human foreskin fibroblasts and a matrix made of type I collagen by organotypic culture of epithelial cells. The morphology of paraffin embedded artificial tissue was examined by histochemical staining. The artificial epithelial tissues were well developed having multilayer. However, the tissue morphology was similar to the cervical tissus having displasia induced by HPV infection. The characteristics of the artificial tissues were examined by determinining the expression of specific marker proteins. In the C9 derived artificial tissues, the expression of EGF receptor, as epithelial proliferation marker proteins for stratum basale was observed up to the stratum spinosum. Another epithelial proliferation marker for stratum spinosum, cytokerations 5/6/18, were observed well over the stratum spinosum. For the differentiation markers, the expression of involucrin and filaggrin were observed while the terminal differentiation marker, cytokeratins 10/13 was not detected at all. Therefore the reconstituted artificial epithelial tissues expressed the same types of differentiation marker proteins that are expressed in normal human cervical epithelial tissues but lacked the final differentiation capacity representing characteristics of C9 cell line as a cancer tissue devived cell line. Expression of HPV18 E6 oncoprotein was also observed in this artifical cervical opithelial tissue though the intensity of the staining was weak. Thus this artificial epithelial tissue could be used as a useful model system to examine the relationship between HPV-induced cervical oncogenesis and epithelial cell differentiation.

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Inhibitory Effects of Yongbu-tang on Osteoclast Differentiation and Bone Resorption (용부탕의 파골세포 분화 억제와 골 흡수 억제효과)

  • Lee, Jeong Ju;Jo, So Hyun;Park, Min Cheol;Jo, Eun Heui
    • Journal of Acupuncture Research
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    • v.32 no.3
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    • pp.27-40
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    • 2015
  • Objectives : This study was performed to evaluate the effects of water extract of Cervi Parvum Cornu(CPC), Aconiti Lateralis Radix Preparata(ALR), and Yongbu-tang(YBT) on suppression of the receptor activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation and bone resorption. Methods : The effects of CPC, ALR, YBT extracts on osteoclast differentiation were determined by culture of bone marrow macrophage(BMM). The mRNA expression levels of the nuclear factor of activated T-cells cytoplasmic 1(NFATc1), c-Fos and tartrate-resistant acid phosphatase(TRAP) in BMMs were analyzed by reverse transcriptase polymerase chain reaction(RT-PCR). Similarly, the protein expression levels of NFATc1, c-Fos, mitogen-activated protein kinase(MAPK)s and ${\beta}$-actin in cell lysates were measured by western blotting. In addition, effects of CPC, ALR and YBT extracts were determined by means of Lipopolysaccharide(LPS)-induced bone-loss with mice. Results : CPC, ALR and YBT extracts showed remarkable inhibition on RANKL-induced osteoclast differentiation without cytotoxicity. CPC and ALR extracts significantly reduced the protein expression level of NFATc1. YBT extract significantly reduced the mRNA expression levels of c-Fos, NFATc1 and the protein expression levels of c-Fos, NFATc1, AKT, p38, c-Jun N-terminal kinase(JNK). Further, YBT extract suppressed degradation of$ I-{\kappa}B$. And ALR extract significantly restored the bone erosion by LPS treatment in mice. Conclusions : YBT extract showed more remarkable inhibition on osteoclast differentiation than CPC and ALR extracts in vitro. ALR extract showed remarkable inhibition on bone resorption in vivo. Thus, YBT extract can be a useful treatment for bone-loss diseases such as osteoporosis.

Effects for the New Formulation of Daesiho-tang on adipocyte development and differentiation in 3T3-L1 (대시호탕의 새로운 제형이 3T3-L1에서 지방세포 증식과 분화 과정에 미치는 영향)

  • Choi, Hye-Min;Kim, Se-Jin;Moon, Sung-Ok;Lee, Ji-Beom;Lee, Ha-young;Kim, Jong-Beom;Lee, Hwa-Dong
    • The Korea Journal of Herbology
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    • v.33 no.2
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    • pp.69-77
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    • 2018
  • Objectives : Daesiho-tang (DSHT) has been widely used in the treatment of cerebral infarct in traditional medicine. However, there was not report on the anti-obesity-related diseases efficacy of DSHT. In this study, we investigated the effects for the new formulation of DSHT, on the adipocyte differentiation cycle in 3T3-L1 cells. Methods : 3T3-L1 cells were treated with DSHT (50, 100, $200{\mu}g/m{\ell}$) during differentiation for 6 days. Also, the inhibitory effect of DSHT against 3T3-L1 adipogenesis was evaluated in various stage of adipogenesis such as early (0-2day), intermediate (2-4day), and terminal stage (4-6day). The accumulation of lipid droplets was determined by Oil Red O staining. and, the expressions of genes related to adipogenesis were measured by RT-PCR and Western blot analyses. Results : DSHT showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affect cell toxicity as assessed by measuring fat accumulation and adipogenesis. In addition, DSHT significantly reduced the expression levels of several adipocyte marker genes including proliferator activated $receptor-{\gamma}$ ($PPAR-{\gamma}$) and CCAAT/ enhancer-binding $protein-{\alpha}$ ($C/EBP-{\alpha}$). Also, the anti-adipogenic effect of DSHT was strongly limited in the intermediate (2-4 day), terminal stage (4-6 day) of 3T3-L1 adipogenesis. In addition, the DSHT treatment down- regulated mRNA expression levels of $PPAR-{\gamma}$,, $C/EBP-{\alpha}$ in mature 3T3-L1 adipocytes. Conclusions : These results suggest that, the ability of DSHT has inhibited overall adipogenesis and lipid accumulation in the 3T3-L1 cells. The new formulation of DSHT may be a promising medicine for the treatment of obesity and related metabolic disorders.

Moderator Effects of e-Book Terminal Type on Factors Influencing Satisfaction of the e-Book User (전자책 사용자만족도 영향요인에 대한 단말기유형의 조절효과)

  • Kim, Keun Hyung;Kim, Seong In;Oh, Sung-Ryoel
    • The Journal of the Korea Contents Association
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    • v.13 no.5
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    • pp.408-419
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    • 2013
  • The terminals of e-Book(electronic Book) are classified into two types which consist of special-purpose terminal equipment and general-purpose terminal equipment. Although the terminal products inr the two types have had a strong race in the e-Book market each other, both enterprises and consumers want the two type to remain persistently with competition in good faith. Therefore, it is necessary for each type camps to find blue ocean by establishing differentiation strategies of each type. In this paper, we designed the research model that independent variables consist of hardware quality and software quality, dependent variable is user satisfaction, moderator variable is the terminal type. Through the research model, we investigated factors having a influence on the user satisfaction of the e-Book terminal that consists of hardware and software. In particular, we investigated if the degree of the influence is different between the two types. As a result, we got conclusions as followings. First, the quality of hardware and software in the terminal had significant influences on the user satisfaction. Second, the degree which the hardware quality has influenced user satisfaction was not different between the two types, but the degree which the software quality has influence on user satisfaction was different between the two types. As a implication of this result, we found that special-purpose terminal provider need to establish a strategies for raising the quality of e-Book viewer to provide different product from general-purpose terminal.