• Title/Summary/Keyword: Cycle-Dependent

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Age-Related Changes of Adult Neural Stem Cells in the MouseHippocampal Dentate Gyrus

  • Jung, Ji-Yeon;Byun, Kang-Ok;Jeong, Yeon-Jin;Kim, Won-Jae
    • International Journal of Oral Biology
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    • v.33 no.2
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    • pp.59-64
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    • 2008
  • This study was designed to investigate the changes in the properties of the neuronal setm cells or progenitor cells associated with age-related decline in neurogenesis of the hippocampal dentate gyrus (DG). Active whole cells cycle marker Ki67 (a marker of whole cell cycle)-positive and S phase marker bromodeoxyuridine (BrdU)-positive. Neural stem cells gradually were reduced in the hippocampal subgranular zone (SGZ) in an age-dependant manner after birth (from P1 month to P1 year). The ratio of BrdUpositivecells/Ki67-positive cells was gradually enhanced in an age-dependent manner. The ratio of Ki67-positive cells/accu-mulating BrdU-positive cells at 3 hrs after BrdU injection was injected once a day for consecutive 5 days gradually decreased during ageing. TUNEL- and caspase 3 (apoptotic terminal caspase)-positive cells gradually decreased in the dentate SGZ during ageing and immunohistochemical findings of glial fibrillary acid protein (GFAP) were not changed during ageing. NeuN, a marker of mature neural cells, and BrdU-double positive cells gradually decreased in an age-dependent manner but differentiating ratio and survival rate of cells were not changed at 4 wks after BrdU injection once a day for consecutive 5 days. The number of BrdU-positive cells migrated from the hippocampal SGZ into granular layer and its migration speed was gradually declined during ageing. These results suggest that the adult neurogenesis in the mouse hippocampal DG gradually decrease through reducing proliferation of neural stem cells accompanying with cells cycle change and reduced cells migration rather than changes of differentiation.

The Changes of Sleep-Wake Cycle from Jet-Lag by Age (연령에 따른 비행시차 후의 수면-각성주기 변화)

  • Kim, Leen;Lee, Seung-Hwan;Suh, Kwang-Yoon
    • Sleep Medicine and Psychophysiology
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    • v.3 no.2
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    • pp.18-31
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    • 1996
  • Jet-lag can be defined as the cumulative physiological and psychological effects of rapid air travel across multiple time zones. Many reports have suggested that age-related changes in sleep reflect fundamental changes in the circadian system and in significant declines in slow wave sleep. Jet lag is a dramatic situation in which the changes of the phase of circadian process and homeostatic process of sleep occur. Thus the authors evaluatead the changes of sleep-wake cycle from jet lag by age. Thirty-eight healthy travellers were studied for 3 days before and 7 days after jet-flights across seven to ten time zone. They were aged 19-70, They trareled eastbound, Seoul to North America (USA, Canada). Sleep onset time, wake-up time, sleep latency, awakening frequency on night sleep, awakening duration on night sleep, sleepiness at wake-up and nap length were evaluated. Our results suggest that by the 7 to 10 time zone shift, the old age group was significantly influenced in sleep-wake cycles. The date on which subjective physical condition was recovered was $6.23{\pm}83$ day after arrivals for old age group, while for young and middle age group, $4.46{\pm}1.50$ day and $4.83{\pm}1.52$ day, respectively. In old age group, sleep onset time was later than baselines and could not recover untill 7th day. But in other groups, the recovery was within 5th day. Nap dura fion was longer in old age group through jet lag than younger age group. In other parameters, there was no definite difference among three age groups. Our results suggested that the old age was significantly influenced by the disharmony between internal body clock and sleep-wake cycle needed at the travel site. Thus we proved that recovery ability from jet lag was age-dependent as well as travelling direction-dependent. To demonstrate more definite evidence, EEG monitoring and staging of sleep were funthun encouraged.

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Anti-Proliferative Effect of Polysaccharides from Salicornia herbacea on Induction of G2/M Arrest and Apoptosis in Human Colon Cancer Cells

  • Ryu, Deok-Seon;Kim, Seon-Hee;Lee, Dong-Seok
    • Journal of Microbiology and Biotechnology
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    • v.19 no.11
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    • pp.1482-1489
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    • 2009
  • In this study, we investigated the anti-proliferative effect of polysaccharides from Salicornia herbacea on HT-29 human colon cancer cells. Crude polysaccharides from S. herbacea (CS) were prepared by extraction with hot steam water, and fine polysaccharides from S. herbacea (PS) were obtained through further size exclusion chromatography. The anti-proliferative effect of CS and PS were measured using the MTS assay, apoptosis analysis, cell cycle analysis, and RT-PCR. HT-29 cells were treated with CS or PS at different dosages (0.5, 1, 2, 4 mg $ml^{-1}$) for 24 or 48 h. CS and PS inhibited proliferation and stimulated apoptosis of cells in a dose-dependent manner. Flow cytometric analysis after Annexin V-FITC and PI staining revealed that treatment with CS or PS increased total apoptotic death of cells to 24.99% or 91.59%, respectively, in comparison with the control (13.51 %). PS increased early apoptotic death substantially - up to 12 times more than the control. Treatment with CS or PS resulted in a concentration-dependent increase of the G2/M cell population of the cell cycle as determined by flow cytometry. G2/M arrest was induced significantly with the highest concentration (4 mg $ml^{-1}$) of PS. RT-PCR was performed to study the correlation between G2/M arrest and transcription of cell cycle control genes. The anti-proliferative activity of CS and PS was accompanied by inhibition of cyclin B1, and Cdc 2 mRNA. Moreover, both CS and PS induced expression of the p53 tumor suppressor gene and the Cdk inhibitor p21. These results suggest that polysaccharides from S. herbacea have anti-cancer activity in human colon cancer cells.

Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells

  • Jo, Si-Kyoung;Hong, Ji-Young;Park, Hyen Joo;Lee, Sang Kook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.513-519
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    • 2012
  • Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells

  • Han, Joo-Hui;Kim, Yohan;Jung, Sang-Hyuk;Lee, Jung-Jin;Park, Hyun-Soo;Song, Gyu-Yong;Nguyen, Manh Cuong;Kim, Young Ho;Myung, Chang-Seon
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.421-426
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    • 2015
  • The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through $G_0/G_1$ to S phase of the cell cycle, as measured by [$^3H$]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at $G_0/G_1$ phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice

  • Yang, Hyun-Jung;Joo, Yu-Young;Hong, Bo-Hyun;Ha, Sung-Ji;Woo, Ran-Sook;Lee, Sang-Hyung;Suh, Yoo-Hun;Kim, Hye-Sun
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.4
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    • pp.229-233
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    • 2010
  • Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

Optimization Study of the Compression/Absorption Hybrid Heat Pump Cycle (증기압축식/흡수식 하이브리드 히트펌프 사이클에 관한 최적화 연구)

  • 전관택;박춘건;정동수
    • Korean Journal of Air-Conditioning and Refrigeration Engineering
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    • v.13 no.1
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    • pp.48-58
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    • 2001
  • For the past few decades the vapor compression cycle with a solution circuit (VCCSC) has been known to provide high efficiency and variable capacity. In this study performance of a VCCSC cycle is examined through computer simulation. In the simulation heat exchangers were modelled by specifying UA or effectiveness values while the compressor performance was specified by an isentropic efficiency. Aqua/ammonia solution was chosen as the working fluid which can be used in the high temperature range. The results show that there exists an optimum operation condition which is dependent upon the temperatures of the external heat transfer fluids(HTFs). Besides the HTF\`s temperature, the maximum system pressure and the size of the solution heat exchanger are shown to have an influence on the optimum operation condition. Finally, as compared to a simple vapor compression heat pump with HFC134a, the COP of the VCCSC is shown to be 2∼22% higher.

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An Analysis of Financial Statement Among Urban Households Based On a System Approach (체계론에 기초한 도시가계의 재정상태 분석)

  • 양정선
    • Journal of the Korean Home Economics Association
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    • v.30 no.1
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    • pp.237-255
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    • 1992
  • The purpose of this study was to investigate relations of resources and demands, family financial management and financial statement of urban households by applying a system approach. The results of this study were as follows; Saving rate had significant differences according to resources variables such as age, family life cycle, occupation of househead and housewife, ratio of employed to family member, and to demands variabels such as subjective prospect of business cycle, and value orientation, whereas total saving amount had significant differences according to resources vaiables such as age, family life cycle, educational level, percapita income, occupation of househead, type of income and to demand variable, perception of relative income. Also average monthly saving amount had significant differences according to resources vaiables such as educational level, per capita income, occupation of housewife, housing ownership, ratio of employed to family member, ratio of dependent to employed, and to demands variable, perception of relative income. The stocks had significant differences according to resources variables such as age, family life cycle, educational level, per capita income, occupation of househead, type of income, and housing ownership. Finally, real estate had significant differences according to resources variables such as age, family life cycle, educational level, percapita income, occupation of househead, type of income, housing ownership, and to demands variable, perception of relative income. Financial Statement among urban households according to family financial management had significant differences. And among all variables affecting financial statement among urban households, per capita income had the highest effect and perception of relative income was the second.

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Oligosaccharide-Linked Acyl Carrier Protein, a Novel Transmethylase Inhibitor, from Porcine Liver Inhibits Cell Growth

  • Seo, Dong-Wan;Kim, Yong-Kee;Cho, Eun-Jung;Han, Jeung-Whan;Lee, Hoi-Young;Hong, Sungyoul;Lee, Hyang-Woo
    • Archives of Pharmacal Research
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    • v.25 no.4
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    • pp.463-468
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    • 2002
  • We have previously reported on the identification of the endogenous transmethylation inhibitor oligosaccharide-linked acyl carrier protein (O-ACP), In this study, the role of the transmethylation reaction on cell cycle progression was evaluated using various transmethylase inhibitors, including O-ACP. O-ACP significantly inhibited the growth of various cancer cell lines, including NIH3T3, ras-transformed NIH3T3, MDA-MB-231, HT-1376, and AGS. In addition, exposure of ras-transformed NIH3T3 to O-ACP caused cell cycle arrest at the $G_0/G_1$ phase, which led to a decrease in cells at the S phase, as determined by flow cytometry. In contrast, transmethylase inhibitors did not affect the expression of $p21^{WAF1/Cip1}$, a well known inhibitor of cyclin dependent kinase, indicating that the cell cycle arrest by transmethylase inhibitors might be mediated by a $p21^{WAF1/Cip1}$-independent mechanism. Therefore, O-ACP, a novel transmethylase inhibitor, could be a useful tool for elucidating the novel role of methylation in cell proliferation and cell cycle progression.

Apoptosis and Cell Cycle Arrest in Two Human Breast Cancer Cell Lines by Dieckol Isolated from Ecklonia cava

  • You, Sun Hyong;Kim, Jeong-Soo;Kim, Yong-Seok
    • Journal of Breast Disease
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    • v.6 no.2
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    • pp.39-45
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    • 2018
  • Purpose: Dieckol, a phlorotannin compound isolated from Ecklonia cava, has been reported to have antioxidant, antiviral, anti-inflammatory, and anticancer properties. The purpose of this study was to investigate its anticancer effects on human breast cancer cell lines. Methods: In this study, the viability of two human breast cancer cell lines SK-BR-3 and MCF-7 was investigated after dieckol treatment using a WST-1 assay. Apoptosis and cell cycle distribution were assayed via Annexin V-fluorescein isothiocyanate and propidium iodide staining followed by flow cytometric analysis. Immunoblotting analysis was also performed using Bax/Bcl-2 to determine whether the dieckol-induced apoptosis was mediated by the intrinsic apoptotic pathway. Results: In a dose dependent manner, dieckol reduced the number of viable cells and increased the number of apoptotic cells. The effect of dieckol on the cell cycle distribution was analyzed using flow cytometry. Dieckol treatment significantly increased the percentage of MCF-7 and SK-BR-3 in the G2/M phase. Immunoblot analysis revealed that 24 hours of dieckol exposure increased the Bax/Bcl-2 ratio. Conclusion: Dieckol induced cytotoxicity in MCF-7 and SK-BR-3 human breast cancer cells inducing apoptosis and cell cycle arrest. Therefore, it is suggested that dieckol may be a potential therapeutic agent for breast cancer.