• Title/Summary/Keyword: cellular growth

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Low-dose metronomic doxorubicin inhibits mobilization and differentiation of endothelial progenitor cells through REDD1-mediated VEGFR-2 downregulation

  • Park, Minsik;Kim, Ji Yoon;Kim, Joohwan;Lee, Jeong-Hyung;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
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    • v.54 no.9
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    • pp.470-475
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    • 2021
  • Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

In vivo protein expression changes in mouse livers treated with dialyzed coffee extract as determined by IP-HPLC

  • Yoon, Cheol Soo;Kim, Min Keun;Kim, Yeon Sook;Lee, Suk Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.40
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    • pp.44.1-44.17
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    • 2018
  • Background: Coffee extract has been investigated by many authors, and many minor components of coffee are known, such as polyphenols, diterpenes (kahweol and cafestol), melanoidins, and trigonelline, to have anti-inflammatory, anti-oxidant, anti-angiogenic, anticancer, chemoprotective, and hepatoprotective effects. Therefore, it is necessary to know its pharmacological effect on hepatocytes which show the most active cellular regeneration in body. Methods: In order to determine whether coffee extract has a beneficial effect on the liver, 20 C57BL/6J mice were intraperitoneally injected once with dialyzed coffee extract (DCE)-2.5 (equivalent to 2.5 cups of coffee a day in man), DCE-5, or DCE-10, or normal saline (control), and then followed by histological observation and IP-HPLC (immunoprecipitation high performance liquid chromatography) over 24 h. Results: Mice treated with DCE-2.5 or DCE-5 showed markedly hypertrophic hepatocytes with eosinophilic cytoplasms, while those treated with DCE-10 showed slightly hypertrophic hepatocytes, which were well aligned in hepatic cords with increased sinusoidal spaces. DCE induced the upregulations of cellular proliferation, growth factor/RAS signaling, cellular protection, p53-mediated apoptosis, angiogenesis, and antioxidant and protection-related proteins, and the downregulations of NFkB signaling proteins, inflammatory proteins, and oncogenic proteins in mouse livers. These protein expression changes induced by DCE were usually limited to the range ± 10%, suggesting murine hepatocytes were safely reactive to DCE within the threshold of physiological homeostasis. DCE-2.5 and DCE-5 induced relatively mild dose-dependent changes in protein expressions for cellular regeneration and de novo angiogenesis as compared with non-treated controls, whereas DCE-10 induced fluctuations in protein expressions. Conclusion: These observations suggested that DCE-2.5 and DCE-5 were safer and more beneficial to murine hepatocytes than DCE-10. It was also found that murine hepatocytes treated with DCE showed mild p53-mediated apoptosis, followed by cellular proliferation and growth devoid of fibrosis signaling (as determined by IP-HPLC), and subsequently progressed to rapid cellular regeneration and wound healing in the absence of any inflammatory reaction based on histologic observations.

Novel p104 protein regulates cell proliferation through PI3K inhibition and p27Kip1 expression

  • Han, Seung-Jin;Lee, Jung-Hyun;Choi, Ki-Young;Hong, Seung-Hwan
    • BMB Reports
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    • v.43 no.3
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    • pp.199-204
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    • 2010
  • The protein p104 was first isolated as a binding partner of the Src homology domain of phospholipase C$\gamma$1, and has been shown to associate with p85$\alpha$, Grb2. The ectopic expression of p104 reduced cellular growth rate, which was also achieved with the overexpression of only the proline-rich region of p104. The proline-rich region of p104 has been found to inhibit the colony formation of platelet-derived growth factor BB-stimulated NIH3T3 cells and MCF7 cancer cells on soft agar. Mutagenesis analysis showed that the second and third proline-rich regions are essential for growth control, as well as for interaction with p85$\alpha$. Overexpression of p104 increased the level of the cyclin-dependent kinase inhibitor, $p27^{Kip1}$, and inhibited the activity of phosphoinositide 3-kinase (PI3K). In summary, p104 interacts with p85$\alpha$ and is involved in the regulation of $p27^{Kip1}$ expression for the reduction of cellular proliferation.

Antibacterial Activity of Powdered Spice against Escherichia coli and Staphylococcus aureus (향신료 분말의 Esdcherichia coli 와 Staphylococcus aureus 에 대한 항균작용)

  • 김미림;최경호;박찬성
    • Food Science and Preservation
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    • v.7 no.1
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    • pp.124-131
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    • 2000
  • Antibacterial activities of powdered spices(garlic , ginger, cinnamon and clove) against pathogenic Escherichia coli )157:H7 and Staphyloccus auresus were investigated. Spice powder was added in was exponetial phase of each bacterial culture . Growth inhibition was determined by the absorbance at 660nm and morphological changes of the cells were observed by transmission electron microscope (TEM). Ginger powder has the highest antibacterial activity, following cinnamon , clove and garlic has the least activity.Growth of Escherichia coli O157:H7 and Staphyloccus aureus were completely inhibited within 5 hours after addition of 1 % of garlic , 0.3% of ginger or cinnamon , 0.5% of clove powder on the exponential phase of the cells. Spice untreated cells of E. coli and S. aureus, the cytoplasm was entirely surrounded by rigid cell wall and cell walls formed a smooth layer well attached to the plasma membrane. In the cells of E. coli and S. aureus treated with spice powder, cell wall and plasma membrane were lysed and severely damaged. E.coli cells growth in the presence of spice powder showed plammolysis, the loss of electron dense material, the formation of extra cellular blebs and cytoplasm burst out from the cell. S .sureus cells grown in the presence of spice powder showed swell of cell wall, the loss of electron dense material , coagulation of cell cytoplasm and formation of extra cellular blebs. Severely damaged cells of S. aureus lost whole cytoplasm and left as ghost of the cell. Spice powder stimulated autolyssi and induced cell death.

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Cellular Automaton Models Revealing Effects of Initial Bacterial Distribution on Biofilm Growth (생물막 성장에 대한 세균의 초기 분포영향을 나타내는 셀룰라오토마톤 모델)

  • Lee, Sang-Hee;Choi, Kyung-Hee;Chon, Tae-Soo
    • Korean Journal of Ecology and Environment
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    • v.37 no.3 s.108
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    • pp.297-303
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    • 2004
  • Two dimensional cellular automaton (CA) models were developed to investigate growth of biofilms in aquatic ecosystems. Simple local rules on CA were applied to governing growth of bacterial populations in relation to different nutrient concentrations. Initial bacterial distribution played an important role in determining population size and morphology of biofilm at low concentrations of nutrition. With clumped distribution, population size increased slowly compared with uniform and random distributions, while the porosity tented to be higher with uniform distribution compared with other initial distributions.

Growth and characterization of $Al_{2}O_{3}-based\;Y_{3}Al_5O_{12},\;ZrO_{2}$ binary and ternary eutectic fibers

  • Lee, J.H.;Yoshikawa, A.;Kaiden, H.;Fukuda, T.;Yoon, D.H.;Waku, Y.
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.11 no.4
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    • pp.170-175
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    • 2001
  • It was possible to grow the $Al_{2}O_{3}$ based $Y_{3}A_{5}O_{12}(YAG),ZrO_{2}$ binary and ternary eutectic fibers using micro-pulling down method with a growing rate of 0.1~15 mm/min. While $Al_{2}O_{3}/ZrO_{2}$ showed cellular-lamellar structure, $Al_{2}O_{3}$/YAG and $Al_{2}O_{3}$/YAG/$ZrO_{2}$ternary eutectic fibers showed homogeneous Chinese script lamellar structures. The microstructures of $Al_{2}O_{3}/ZrO_{2}$ binary eutectic fibers changed with solidification rate from lamellar pattern to cellular structure. The interlamellar spacing agreed with the inverse-square-root dependance on pulling rate according to $\lambda$=$kv_p\;{-1/2}$. $Al_{2}O_{3}/ZrO_{2}$ binary eutectic fibers recorded the highest tensile strength of about 1560MPa at room temperature. $Al_2O_3/YAG/ZrO_2$ternary eutectic fiber showed excellent thermal stability to $1200^{\circ}C$ without significant decrease. The maximum strength of ternary eutectic fibers recorded were 1100MPa at $25^{\circ}C$ and 970MPa at $1200^{\circ}C$, respectively.

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A Study on the Urban Growth Patterns Focusing on Regional Characteristics (지역적 특성을 고려한 도시 성장 패턴에 관한 연구)

  • Yun, Jeong-Mi;Lee, Sung-Ho
    • Journal of the Korean Association of Geographic Information Studies
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    • v.9 no.1
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    • pp.116-126
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    • 2006
  • The purpose of this study is to analyze the growing course of Busan, Gimhae and Jinhae and further find patterns of the urban growth. This study shows that patterns of the urban growth differ from city to city, being influenced by the city's characteristics. Acknowledging this fact would help the decision maker to determine the developing plan of the urban. The methodology for this study is as follows; Fuzzy set concept is applied to minimize the data loss. At the same time, the AHP is used to give a relative weight to each factor. In order to be able to manage the change based on the dynamic model and time, Cellular Automata is introduced to simulate the growth of urban. The results show that the pattern of Gimhae's and Jinhae's growth is the same, whereas that of Busan is different from them. That is to say, each city has regional characteristics. And the pattern of the urban growth is influenced by the regional conditions of the city.

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Altered Expression of Pyrophosphate: Fructose-6-Phosphate 1-Phosphotransferase Affects the Growth of Transgenic Arabidopsis Plants

  • Lim, Hyemin;Cho, Man-Ho;Jeon, Jong-Seong;Bhoo, Seong Hee;Kwon, Yong-Kook;Hahn, Tae-Ryong
    • Molecules and Cells
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    • v.27 no.6
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    • pp.641-649
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    • 2009
  • Pyrophosphate:fructose-6-phosphate 1-phosphotransferase (PFP) catalyzes the reversible interconversion of fructose-6-phosphate and fructose-1,6-bisphosphate, a key step in the regulation of the metabolic flux toward glycolysis or gluconeogenesis. To examine the role of PFP in plant growth, we have generated transgenic Arabidopsis plants that either overexpress or repress Arabidopsis PFP subunit genes. The overexpressing lines displayed increased PFP activity and slightly faster growth relative to wild type plants, although their photosynthetic activities and the levels of metabolites appeared not to have significantly changed. In contrast, the RNAi lines showed significantly retarded growth in parallel with the reduced PFP activity. Analysis of photosynthetic activity revealed that the growth retardation phenotype of the RNAi lines was accompanied by the reduced rates of $CO_2$ assimilation. Microarray analysis of our transgenic plants further revealed that the altered expression of $AtPFP{\beta}$ affects the expression of several genes involved in diverse physiological processes. Our current data thus suggest that PFP is important in carbohydrate metabolism and other cellular processes.

Effects of Milk Protein levels and Casein/Whey Ratios on Organ Growth and Protein Metabolism in Early Weaned Rats (조기 이유한 흰쥐에서 유단백질의 섭취수준과 조성비가 기관성장과 단백질대사에 미치는 영향)

  • 박미나
    • Journal of Nutrition and Health
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    • v.30 no.1
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    • pp.3-11
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    • 1997
  • This study was conducted to investigate the effects of protein levels and casein/whey ratios on organ growth and protein metabolism in early weaned rats. Premature rats weaned by the 17th day were fed six semipurified synthetic, isocaloric and gel diets that contained three levels (low, medium and high) and two different combinations(casein/whey ; 80 : 20 or 20 : 80) of milk protein for 8 days. On the 25th day postpartum, frest weigth and DNA, RNA and milk protein contents in brain, liver, kidney and muscle were determined to ascertain organ and cellular growth. Futher, with a view to ascertain protein metabolism and renal functions, serum total protein, $\alpha$-amino N, urea N, and creatinine and creatinine and urinary urea N, creatinine and hydroxproline were determined. Total DNA contents of brain, liver and kidney, which may represent as an index of cell numbers in those organs were significantly decreased in the rats fed diets containing low level protein regardless of casein/whey ratio. However, as fat as the rats fed high protein diets were concerned, their fresh weight, protein contents and GFR of kidney were significantly increased. Furthermore, nitrogen components, $\alpha$-amino N, urea N and creatinie in serum and urine were also increassed. Another observation was that high casein/whey ratio significantly facilitated accumulation of porteins in muscle and kidney and urinary hydorxyproline excretion, not affecting the DNA content of those organs. This study showed that low(8%) or high(32%) contents of protein had less desirable effects either on protein metabolism or on organ cellular growth in prematurely weaned rats, whereas there were no effects on general growth and bone strength.

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Effect of electromagnetic field exposure on the reproductive system

  • Gye, Myung-Chan;Park, Chan-Jin
    • Clinical and Experimental Reproductive Medicine
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    • v.39 no.1
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    • pp.1-9
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    • 2012
  • The safety of human exposure to an ever-increasing number and diversity of electromagnetic field (EMF) sources both at work and at home has become a public health issue. To date, many in vivo and in vitro studies have revealed that EMF exposure can alter cellular homeostasis, endocrine function, reproductive function, and fetal development in animal systems. Reproductive parameters reported to be altered by EMF exposure include male germ cell death, the estrous cycle, reproductive endocrine hormones, reproductive organ weights, sperm motility, early embryonic development, and pregnancy success. At the cellular level, an increase in free radicals and $[Ca^{2+}]i$ may mediate the effect of EMFs and lead to cell growth inhibition, protein misfolding, and DNA breaks. The effect of EMF exposure on reproductive function differs according to frequency and wave, strength (energy), and duration of exposure. In the present review, the effects of EMFs on reproductive function are summarized according to the types of EMF, wave type, strength, and duration of exposure at cellular and organism levels.