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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.

The Effect of SiO2 addition on Oxidation and Electrical Resistance Stability at High-temperature of P/M Fecralloy Compact (P/M Fecralloy 성형체의 고온산화 및 전기저항 안정성에 미치는 SiO2 첨가 효과)

  • Park, Jin-Woo;Ok, Jin-Uk;Jung, Woo-young;Park, Dong-kyu;Ahn, In-Shup
    • Journal of Powder Materials
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    • v.24 no.4
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    • pp.292-297
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    • 2017
  • A metallic oxide layer of a heat-resistant element contributes to the high-temperature oxidation resistance by delaying the oxidation and has a positive effect on the increase in electrical resistivity. In this study, green compacts of Fecralloy powder mixed with amorphous and crystalline silica are oxidized at $950^{\circ}C$ for up to 210 h in order to evaluate the effect of metal oxide on the oxidation and electrical resistivity. The weight change ratio increases as per a parabolic law, and the increase is larger than that observed for Fecralloy owing to the formation of Fe-Si, Fe-Cr composite oxide, and $Al_2O_3$ upon the addition of Si oxide. Si oxides promote the formation of $Al_2O_3$ and Cr oxide at the grain boundary, and obstruct neck formation and the growth of Fecralloy particles to ensure stable electrical resistivity.

Effects of In vitro Maturation Condition on Bovine IVF Embryos Development (체외성숙 조건이 소 체외수정란의 체외발달에 미치는 영향)

  • 최선호;류일선;김일화;박수봉;연성흠;진현수;서상욱;이충섭;손동수
    • Journal of Embryo Transfer
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    • v.14 no.2
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    • pp.113-119
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    • 1999
  • This study was performed to improve the development of the in vitro fertilized bovine embryos by the condition of in vitro maturation. COCs were matured in TCM 199 supplemented with 0.1% PVA, 10ng/ml EGF, Hormones (5$\mu\textrm{g}$/ml FSH, 10 IU hCG, 1 $\mu\textrm{g}$/ml estradiol 17-$\beta$) or granulsa cell+Hormones atmosphere 39$^{\circ}C$, 5% CO2, 95% air for 24hrs. Matured oocytes were fertilized with frozen-thawed semen capacitated with 5mM caffein in BO medium for 20 hrs. IVF embryos were cultured in TCM 199 containing with hormones(same as matured medium), 10% FBS and co-culture with bovine oviduct epitherial cells. Maturation rates of COCs were showed 73.8%, 78.5%, 83.2% and 87.6% respectively, and were significant differences between PVA, EGF, and Hormones, GC+Hormones(p<0.05). The cleavage rates of IVF embryos were revealed 72.5%, 78.4%, 82.3% and 84.2% and showed same tendency as maturation rates(p<0.05). The blastocysts matured by above maturation condition and cultured for 7~10 days after fertilization had 34.4, 43.6, 52.3 and 59.3 cells had no differences among the treatments. These results suggest that high molecules as a substitutes of serum and growth factor may induce nuclear resumption of COCs but we need more study to produce transferable IVF blastocysts by use of that agents.

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Effect on the Growth of Chinese Cabbage and Chemical Composition of the Liquid Piggery Slurry Digested Anaerobically in Biogas Plant (바이오가스 프랜트에서 혐기 소화시킨 돈사 Slurry의 화학적 특성 및 배추생육 시용효과에 관한 연구)

  • Jeong, Chan-Seong;Bak, Jeong-Geun;Roh, Ahn-Sung;Cho, Woong-Gi;Lee, Sung-Sill;Moon, Yea-Hwang
    • Journal of Animal Environmental Science
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    • v.20 no.3
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    • pp.125-132
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    • 2014
  • This study was conducted to investigate the effects on chemical properties of soil and yield of chinese cabbage when the piggery liquid slurry (ADS) digested anaerobically in the biogas plant was sprinkled to the soils. Treatments were composed of non-nitrogen plot (PK), chemical fertilizer plot (NPK) and ADS plot, and were arranged by randomized block design with 3 replications. The ADS was an alkali (pH 8.6) fertilizer containing 0.55% of total nitrogen, optimal levels of phosphorus, potassium and other components. When based (100%) on the yield of chinese cabbage in the NPK, those of the ADS and the PK were 114% and 43%, respectively. The nitrogen absorption of chinese cabbage at 50-d after transplant was significantly greater (p<0.05) in the ADS than other treatment. Heavy metal contents of soil were not difference between before and after experiment. With supplementing phosphorus and potassium sources in it, the ADS should be an excellent fertilizer in cabbage culture.

Physicochemical Characteristics of Dredged Soils in Reservoirs (저수지 준설대상 토양의 이화학적 특성)

  • 손재권;구자웅;최진규
    • Magazine of the Korean Society of Agricultural Engineers
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    • v.39 no.3
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    • pp.96-107
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    • 1997
  • This study was carried out to examine the physicochemical characteristics of dredged soils in reservoirs. Surveys and analyses of basic materials were made on 241 of 2,328 reservoirs in Chonbuk province through 2 years from December 1994 to November 1996. The results of this study are summarized as follows : 1. Soils were classified as 15 types according to physical properties, and some soils contain comparatively high percentage of sand and gravel. Considering only soil textures, useful and economical soils as aggregate are approximately 25% in all, and the other soils are arable for farm planting. 2. The results of chemical analyses of soils showed on the average 5.9 in pH, 1.lmmhos/cm in ECe, 14.6me/l00g in CEC, 460.0ppm in T-N, 119.0ppm in T-P, 264.9ppm in K, 134.2ppm in Na, l,335.0ppm in Ca, 575.9ppm in Mg, 486.Sppm in Fe, 57.7ppm in Mn, 3.3ppm in Cu, 21.9ppm in Zn, 0.49ppm in As, 0.34ppm in Cd, 0.O3ppm in Hg, 1.7% in OM, respectively. 3. General chemical components, heavy metals, organic matter contents were analyzed as similar to tlie mean values of common soils, therefore it was considered to be no significant effects on crop growth in the chemical properties. 4. Accodingly, the physicochemical characteristics of soils ought to be analyzed accurately before dredging for effective using of dredged soils. And it will be more effective, if the dredged soils are used with proper balance among each content of components with considering to the physicochemical properties of common soils.

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Studies on the Nutrition of Amino Acids and Vitamins in Undaria pinnatifida (Harvey) Suringar (미역의 아미노酸 및 비타민에 對한 營養學的 硏究)

  • Lee, Hyun-Ki
    • Journal of the Korean Chemical Society
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    • v.9 no.4
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    • pp.201-210
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    • 1965
  • Leuconostoc mesenteroides P-60, Lactobacillus arabinosus 17-5, Streptococcus faecalis R have been successfully used for the quantitative determination of sixteen amino acids in Undaria pinnatifida (Harvey) Suringar hydrolysate by alkaline and hydrolysis for succesive two hours from two to twelve hours, by means of microbiological assay. And thiamine and riboflavin were fluorometrically determinated by thiochrome and lumiflavin in powder (80mesh) of Undaria pinnatifida (Harvey) Suringar. The results were as follows: 1) Arginine contents was the highest in hydrolysate for two hours, but longer the hydrolysis, the more content Undaria pinnatifida was decreased. 2) The adequate contents of other amino acids were obtained by hydrolysis for six hours. 3) Growth check and improve of Lactobacillus were not identified in determination by microbiological assay for Undaria pinnatifida. 4) The following values were obtained in Undaria pinnatifida hydrolysate six hours: asparatic acid 466, arginine 230, lysine 317, histidine 74, isoleucine 242, methionine 202, phenylalanine 256, proline 231, threonine 231, tyrosine 161, valine 415, glycine 302, leucine 414, glutamic acid 625, cystine (5 hrs.) 53 and tryptophan (8 hrs.) 90mg per nitrogen one gram. 5) Protein score was 81 (limiting factor was isoleucine) and essential amino acids pattern was of satisfactory results. And methionine contained was higher than FAO value or milk value. 6) Sulphur contained amino acids (methionine plus cystine) contained in Undaria pinnatifida were 225mg/N-g. That was satisfactory results. 7) Absorption spectrum of wave length were not different 1% HAc from buffer-sol. (pH 6.8) in dilution for determination of riboflavin. Both methods might be suitable. 8) Thiamine and riboflavin contained in Undaria pinnatifida were ($B_1,\;82.51{\pm}1.1){\gamma}/N-g\;and\;(B_2,\;115.29{\pm}1.5){\gamma}/N-g.$.

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EFFECTS OF MACROPHAGE INFLAMMATORY $PROTEIN-1{\alpha}$ON THE T CELL PROLIFERATION AND THE EXPRESSION OF CD4 AND CD8 (Macrophage Inflammatory Protein $1{\alpha}$가 T세포성장 및 CD4, CD8 발현에 미치는 영향)

  • Choi, Jong-Sun;Kim, Oh-Whan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.18 no.1
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    • pp.153-163
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    • 1996
  • Macrophage inflammatory protein $(MIP)-1{\alpha}$ is a cytokine which produces wide range of bioactivities such as proinflammatory, immunomodulatory, and hematopoietic modulatory actions. To determine whether $MIP-1{\alpha}$ acts as a negative regulator on the functions of lymphocyte, $[^3H]$-thymidine incorporation test and flow cytometric analysis were performed by using human tonsil T cell, human peripheral blood T cell, and murine cytolytic T lymphocyte (CTL) line CTLL-2, The results were as follow. 1. When human tonsil T lymphocytes were stimulated with anti-CD3 monoclonal antibody (mAb), rate of T cell proliferation was about four times increased. 200ng/ml of $MIP-1{\alpha}$ inhibited anti-CD3 mAb-mediated T cell growth as much as 60% (P<0.05). 2. The suppression of human peripheral T cell proliferation produced by $MIP-1{\alpha}$ was dramatic, but variable among T cells derived from different individuals $(40%{\sim}90%)$. 3. $MIP-1{\alpha}$inhibited the proliferation of murine CTL line CTLL-2 as much as 75%(P<0.001). 4. When the $MIP-1{\alpha}$ was added to human peripheral T cell, cell proporation of $CD4^+$ helper T cell and $CD8^+$ CTL were not noticeably affected. The expression level of CD4, not of Cd8, however, was down regulated by $MIP-1{\alpha}$ treatment $(27%{\sim}82%)$.

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Isoforms of Glucose 6-Phosphate Dehydrogenase in Deinococcus radiophilus

  • Sung, Ji-Youn;Lee, Young-Nam
    • Journal of Microbiology
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    • v.45 no.4
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    • pp.318-325
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    • 2007
  • Glucose 6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in Deinococcus radiophilus, an extraordinarily UV-resistant bacterium, was investigated to gain insight into its resistance as it was shown to be involved in a scavenging system of superoxide $(O_2^{-1})$ and peroxide $(O_2^{-2})$ generated by UV and oxidative stresses. D. radiophilus possesses two G6PDH isoforms: G6PDH-1 and G6PDH-2, both showing dual coenzyme specificity for NAD and NADP. Both enzymes were detected throughout the growth phase; however, the substantial increase in G6PDH-1 observed at stationary phase or as the results of external oxidative stress indicates that this enzyme is inducible under stressful environmental conditions. The G6PDH-1 and G6PDH-2 were purified 122- and 44-fold (using NADP as cofactor), respectively. The purified G6PDH-1 and G6PDH-2 had the specific activity of 2,890 and 1,033 U/mg protein (using NADP as cofactor) and 3,078 and 1,076 U/mg protein (using NAD as cofactor), respectively. The isoforms also evidenced distinct structures; G6PDH-1 was a tetramer of 35 kDa subunits, whereas G6PDH-2 was a dimer of 60kDa subunits. The pIs of G6PDH-1 and G6PDH-2 were 6.4 and 5.7, respectively. Both G6PDH-1 and G6PDH-2 were inhibited by both ATP and oleic acid, but G6PDH-1 was found to be more susceptible to oleic acid than G6PDH-2. The profound inhibition of both enzymes by ${\beta}-naphthoquinone-4-sulfonic$ acid suggests the involvement of lysine at their active sites. $Cu^{2+}$ was a potent inhibitor to G6PDH-2, but a lesser degree to G6PDH-1. Both G6PDH-1 and G6PDH-2 showed an optimum activity at pH 8.0 and $30^{\circ}C$.

Effect of Alloying on the Microstructure and Fatigue Behavior of Fe-Ni-Cu-Mo P/M Steels

  • Bohn, Dmitri A.;Lawley, Alan
    • Proceedings of the Korean Powder Metallurgy Institute Conference
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    • 1997.04a
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    • pp.34-34
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    • 1997
  • The effect of alloying mode and porosity on the axial tension-tension fatigue behavior of a P/M steel of nominal composition Fe-4w/o Ni-1.5w/o Cu-O.5w/o Mo-O.5w/o C has been evaluated. Alloying modes utilized were elemental powder mixing, partial alloying(distaloy) and prealloying by water atomization; in each case the carbon was introduced as graphite prior to sintering. Powder compacts were sintered($1120{\circ}C$/30 min.) in 7Sv/o $H_2$/25v/o $N_2$ to densities in the range 6.77-7.2 g/$cm^3$. The dependence of fatigue limit response on alloying mode and porosity was interpreted in terms of the constituent phases and the pore and fracture morphologies associated with the three alloying modes. For the same nominal composition, the three alloying modes resulted in different sintered microstructures. In the elemental mix alloy and the distaloy, the major constituent was coarse and fine pearlite, with regions of Ni-rich ferrite, Ni-rich martensite and Ni-rich areas. In contrast, the prealloy consisted primarily of martensite by with some Ni-rich areas. From an examination of the fracture surfaces following fatigue testing it was concluded that essentially all of the fracture surfaces exhibited dimpled rupture, characteristic of tensile overload. Thus, the extent of growth of any fatigue cracks prior to overload was small. The stress amplitude for the three alloying modes at 2x$l0^6$ was used for the comparison of fatigue strengths. For load cycles <3x$l0^5$, the prealloy exhibited optimum fatigue response followed by the distaloy and elemental mix alloy, respectively. At load cycles >2x$l0^6$, similar fatigue limits were exhibited by the three alloys. It was concluded that fatigue cracks propagate primarily through pores, rather than through the constituent phases of the microstructure. A decrease in pore SIze improved the S-N behavior of the sintered steel.

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Soil Characteristics of Newly Reclaimed Tidal Land and Its Changes by Cultivation of Green Manure Crops

  • Lee, Kyeong-Bo;Kang, Jong-Gook;Lee, Kyeong-Do;Lee, Sanghun;Hwang, Seon-Ah;Hwang, Seon-Woong;Kim, Hong-Kyu
    • Korean Journal of Soil Science and Fertilizer
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    • v.46 no.2
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    • pp.129-135
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    • 2013
  • This study was conducted to investigate the soil characteristics of newly reclaimed tidal land and the effect of green manure crops on soil properties. Summer green manure crops such as sesbania (Sesbania grandiflora), barnyard grass (Echinochloa spp.) and sorghum${\times}$sudangrass hybrid (Sorghum bicolor L.) were cultivated at Hwaong, Ewon, Saemangeum and Yongsangang area. Soil pH of reclaimed tidal land was relatively high, but organic matter and available phosphorus contents were lower compared to the optimum range for common upland crops. Soil nutrient contents were unbalanced for upland crop growth. Yield of green manure crops had a wide spatial variation. Nitrogen content in green manure crops was the greater in Sesbania and it was estimated that major nutrient ($N-P_2O_5-K_2O$) supply amount were 150-40-370, 220-50-170 and 140-50-250 $kg\;ha^{-1}$ from sorghum${\times}$sudangrass hybrid, sesbania and barnyard grass, respectively. Based on these results, desalination is required to grow the upland crops at newly reclaimed tidal lands and management practices are necessary to reduce the salt damage by resalinization during the growing seasons. To improve the productivity and increase the nutrient utilization rate, soil physicochemical properties need to be improved to the level for upland crops by application of organic matter and fertilizer.