• Title/Summary/Keyword: dose control

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Presence of Leukemia-maintaining Cells in Differentiation-resistant Fraction of K562 Chronic Myelogenous Leukemia (만성 골수성 백혈병 K562세포의 분화 내성 분획에서 백혈병 유지 세포의 동정)

  • Lee, Hong-Rae;Kim, Mi-Ju;Ha, Gahee;Kim, So-Jung;Kim, Sun-Hee;Kang, Chi-Dug
    • Journal of Life Science
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    • v.23 no.2
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    • pp.197-206
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    • 2013
  • The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.

Migration of $^{99m}Tc$-Hexamethylpropylene Amino Oxime (HMPAO) Labeled Immature and Mature Dendritic Cells in the Mouse (마우스에서 Tc-99m HMPAO 표지 미성숙 및 성숙 수지상세포의 이동에 관한 연구)

  • Li, Ming-Hao;Lee, Je-Jung;Min, Jung-Joon;Heo, Young-Jun;Song, Ho-Chun;Park, Young-Kyu;Park, An-Na;Bom, Hee-Seung
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.1
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    • pp.26-33
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    • 2005
  • Purpose: The purpose of this study is to evaluate migration of technetium-99m hexamethylpropylene amine oxime ($^{99m}Tc$-HMPAO) labeled immature and mature dendritic cells (DC) in the mouse. Methods: DC were collected from bone marrow (BM) of tibiae and femurs of mice. Immature and mature DC from BM cells were radiolabeled with $^{99m}Tc$-HMPAO. To evaluate the functional and phenotypic changes of DC from radiolabeling, the allogeneic mixed lymphocyte reaction (MLR) and fluorescence-activated cell sorting (FACS) analysis were performed before and after labeling with $^{99m}Tc$-HMPAO. Migration of intravenously injected DC (iv-DC) was assessed by serial gamma camera images of mice with or without subcutaneous tumor. Percent injected dose per gram (%ID/g) was calculated in lungs, liver, spleen, kidneys, and tumor through dissection of each mice after 24 hours of injection. Results: Labeling efficiency of immature and mature DC were $60.4{\pm}5.4%\;and\;61.8{\pm}6.7%$, respectively. Iv-DC initially appeared in the lungs, then redistributed mainly to liver and spleen. Migration of mature DC to spleen was significantly higher than that of immature DC ($38.3{\pm}4.0%\;vs.\;32.2{\pm}4.1%$ in control group, $40.4{\pm}4.1%\;vs.\;35.9{\pm}3.8%$ in tumor group; p<0.05). Migration to tumor was also significantly higher in mature DC than in immature DC ($2.4{\pm}0.3%\;vs\;1.7{\pm}0.2%$; p=0.034). Conclusion: Assessment of migration pattern of DC in mice was possible using $^{99m}Tc$-HMPAO labeled immature and mature DC. Migration of mature DC to spleen and tumor was higher than that of immature DC when they were i.v. injected.

Antioxidant and Anti-adipogenic Effects of PineXol® (PineXol®의 항산화 및 지방세포 분화 억제 효과)

  • Lee, Young Jun;Han, Ohan Taek;Choi, Hyeon-Son;Lee, Boo Yong;Chung, Hyun-Jung;Lee, Ok-Hwan
    • Korean Journal of Food Science and Technology
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    • v.45 no.1
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    • pp.97-103
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    • 2013
  • Pine bark extract is made from the bark of Pinus densiflora which naturally contains occurring phytochemicals such as phenolic compounds. PineXol$^{(R)}$ from products of pine bark extract is sold under the brand name. The aim of this study was to evaluate the total phenol, total flavonoids contents and antioxidant activity of the PineXol$^{(R)}$ as well as to assess the lipid accumulation during adipogenesis of 3T3-L1 cells. Our results demonstrate that the total phenolic and flavonoids contents of the PineXol$^{(R)}$ were $717.40{\pm}6.86$ GAE mg/mL and $54.44{\pm}0.01$ RE mg/mL, respectively. The antioxidative activities of the PineXol$^{(R)}$ were significantly increased in a dose dependent manner on DPPH (1,1-Diphenyl-2-picryl hydrazyl) radical scavenging, ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) radical scavenging, FRAP (ferric reducing antioxidant power) activity, reducing power, nitrite radical scavenging activity and ORAC (Oxygen radical absorbance capacity) value. In addition, the PineXol$^{(R)}$ inhibited the adipocyte differentiation of 3T3-L1 preadipocytes. Exposure to 200 ${\mu}g/mL$, PineXol$^{(R)}$ significantly reduced lipid accumulation (~80%) in 3T3-L1 cells compared to control cells.

Inhibitory effects of heavy metals on CYP1A expression in eel hepatocyte cultures (뱀장어 배양 간세포에서의 Cytochrome P4501A (CYP1A) 유전자 발현에 대한 중금속들의 억제효과)

  • Kwon, Hyuk-Chu;Maeng, Joon-Ho;Choi, Seong-Hee
    • Journal of fish pathology
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    • v.23 no.2
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    • pp.245-254
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    • 2010
  • Effects of heavy metal ions on the gene expression of cytochrome P4501A (CYP1A) were examined in cultured eel hepatocytes. When the expression of CYP1A mRNA was measured by RT-PCR after incubation of eel hepatocytes with benzo[$\alpha$]pyrene (B[$\alpha$]P) at concentrations of 10-8~10-5 M, the CYP1A expression increased with B[$\alpha$]P treatment in a dose dependent manner, showing significant increase at concentrations more than 10-7 M. When the eel hepatocyte was treated with cadmium (10-6 and 10-5 M), the expression of CYP1A was inhibited and especially at higher concentration (10-5 M). The inhibition of CYP1A expression by cadmium was also observed in cells treated with B[$\alpha$]P. In another study, effects of heavy metal ions on the expression of CYP1A were examined in cultured hepatocytes isolated from eel which was treated previously with B[$\alpha$]P in vivo. Hepatocytes isolated from the liver of eel taken at 48 hours after injection of B[$\alpha$]P (10 mg/kg) were cultured for 2 days with cadmium, copper, lead or zinc (10-6 and 10-5 M). The expression of CYP1A was found to be suppressed by the metal ions compared with the control in which CYP1A was induced with previous treatment of B[$\alpha$]P in vivo. The present results may provide an important basic information for studying the effects of heavy metal ions on CYP1A expression in other species of fish and studying toxicological mechanisms of heavy metal ions in aquatic livings.

In Vitro Cytotoxicity, Skin Regeneration, Anti-wrinkle, Whitening and In Vivo Skin Moisturizing Effects of Oncheongeum (온청음 물 추출물의 세포독성, 피부재생, 주름개선, 미백 및 보습 효과)

  • An, Tteul-E-Bom;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.29 no.1
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    • pp.14-34
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    • 2016
  • Objectives: The objective of this study was to evaluate the effects of cytotoxicity, skin regeneration, anti-wrinkle, whitening and skin moisturizing of Oncheongeum (OCE).Methods: The cytotoxicity of OCE lyophilized aqueous extracts (yield=13.82%) was observed against human normal fibroblast cells and B16/F10 murine melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium Bromide (MTT) assay, and skin regeneration and anti-wrinkle effects were also evaluated through the assay of collagen type I synthesis compared to the transformation of the growth factor (TGF)-β1, hyaluronidase, collagenase and matrix metalloproteinase (MMP)-1 inhibitory assays compared to oleanolic acid (OA), and elastase inhibitory effects compared to phosphoramidon disodium salt (PP). In addition, OCE’s whitening effects were measured by a tyrosinase inhibitory assay and melanin formation test in B16/F10 murine melanoma cells compared to arbutin, and skin moisturizing effects were observed through a mouse skin water content test, respectively. Results: No OCE treatment-related cytotoxic effects appeared on human normal fibroblasts and B16/F10 murine melanoma cells. OCE concentration-dependently increased the collagen Type I synthesis on human normal fibroblast cells, and also effectively inhibited hyaluronidase, elastase, collagenase and MMP-1 activities. In addition, OCE inhibited melanin production of B16/F10 murine melanoma cells and activity of tyrosinase. And significant and dose-dependent increases of skin water content were detected in OCE-treated mouse skin compared to vehicle control skins. Conclusions: OCE showed favorable and sufficient effects in skin regeneration, anti-wrinkle, whitening and skin moisturizing in this experiment. But more detail mechanisms and studies on the skin protective efficiency of in vivo are needed with the screening of active biological compounds in individual OCE herbs.

Effects of Phenolic Compounds of Persimmon Leaves on Antioxidative System and Miscellaneous Enzyme Activities Related to Liver Function in Ethanol-Induced Hepatotoxicity of Rats (감잎의 Phenolic Compounds가 에탄올을 투여한 흰쥐의 항산화계 및 기타 효소활성에 미치는 영향)

  • 정창주;윤준식;이명렬
    • Food Science and Preservation
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    • v.11 no.1
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    • pp.79-87
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    • 2004
  • To investigate antioxidative effects of phenolic compounds separated from persimmon leaves(PL)(Diospyros kaki Thunb.) on the ethanol-induced hepatotoxicity in rat, Sprague-Dawley rats weighing 100-150 g were divided into 5 groups; control group(CON), PL(70 mg/kg) administered group(PEl), ethanol(5 mL/kg, 25%) administered group(ETH), PL(70 mg/kg) and ethanol administered group (PE2), and PL(140 mg/kg) and ethanol administered group(PE3), respectively. The antioxidative activity of persimmon leaves decreased in order of ethylacetate>interphase materials>n-butanol>chloroform>n-hexane>water fraction. The growth rate and feed efficiency ratio decreased by ethanol were gradually increased to the adjacent level of CON by administering PL. The serum activities of ALT, alkaline phosphatase and lactic acid dehydrogenase elevated by ethanol were decreased significantly. It was also observed that the activities of SOD, catalase, and GSH-Px of rat liver increased by ethanol were markedly decreased in PL administered group as compared to ETH. The GSH content of liver was decreased by ethanol, but that was increased in PE1 and PE2 compared with ETH as a dose-dependant manner. These results suggested that phenolic compounds separated from persimmon leaves have a possible protective and relievable effect on the ethanol-induced hepatotoxicity in rats.

Effects of Vitamin C on Residual Aflatoxin $B_1$ in Rat Sera Treated with Radiation and Aflatoxin $B_1$ (Vitamin C가 방사선과 Aflatoxin $B_1$을 투여한 흰쥐의 혈청 중 Aflatoxin $B_1$ 잔류량에 미치는 영향)

  • Chung, Do-Young;Kim, Han-Soo;Kang, Jin-Soon
    • Food Science and Preservation
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    • v.18 no.3
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    • pp.374-382
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    • 2011
  • Aflatoxin ($AFB_1$) is a potent hepatotoxic and hepatocarcinogenic mycotoxin in humans. It is also well-known to be accumulated in animal tissues via various metabolic pathways. This study was conducted to determine the effects of vitamin C on the residual $AFB_1$ in rat sera that were treated with radiation and $AFB_1$. Six week-old male Sprague-Dawley rats were randomly divided into five groups: a control group, $AFB_1$-treated group, the group treated with $AFB_1$ and vitamin C, the group treated with X-ray and AFB1, and the group treated with X-ray and $AFB_1$ with vitamin C. On the first day of the experiment, only one dose of X-rays was exposed to the entire liver at 1,500 cGy. Next, vitamin C was injected at 10 mg/kg body weight via intraperitoneal injection, followed 1 hr later by the administration of 0.4 mg/kg of $AFB_1$ via intraperitoneal injection. These treatments were then administered every three days over a period of 15 days. On the 16th day of treatments, the animals were sacrificed. The contents of $AFB_1$ in rat sera were determined via indirect competitive ELISA and HPLC method. In the quantitative analysis of $AFB_1$ in rat sera via ELISA, $5.17{\pm}0.34$ ng/mL of $AFB_1$ was detected in the $AFB_1$-treated groups, but the amount more significantly decreased to $3.23{\pm}0.76$ ng/mL in the groups treated with $AFB_1$ and vitamin C (p<0.01) than in the $AFB_1$-treated groups. The $AFB_1$ contents of the rat sera of the groups treated with X-ray and $AFB_1$ did not significantly decreased with the administration of vitamin C. The $AFB_1$ content of the rat sera that was analyzed via HPLC showed a tendency similar to that of the content that was analyzed via ELISA. With regard to these data, vitamin C was very effective in reducing $AFB_1$ residue in rat sera.

Fertility Status in Northeastern Alpine Soils of South Korea with Cultivation of Vegetable Crops (강원도 고랭지 채소 재배지의 토양 비옥도관리 현황과 전망)

  • Yang, Jae-E.;Cho, Byong-Ok;Shin, Young-Oh;Kim, Jeong-Je
    • Korean Journal of Soil Science and Fertilizer
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    • v.34 no.1
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    • pp.1-7
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    • 2001
  • Total upland area for cultivating the vegetable crops in the Alpine soils of Northeastern South Korea has been extending its limit to meet the increasing demand of vegetable food in recent decades. About 70% of these alpine soils are located in over 7% of the slope and most of vegetable crops have been cultivated intensively without practicing the best management systems. Thus, soil erosion and continuous cropping system have degenerated the soil fertility and shown detrimental effects on water quality. We initiated an intensive and extensive investigation to characterize the fertility problems encountered in these uplands. Objectives of this paper were to characterize the fertility status in the Alpine soils cultivated with vegetable crops for many years and to provide the recommendations for adequate soil management measures including fertilization and erosion control. Soils in general have good drainage with textural classes of loam or sandy loam. Their topographical characteristics tended to lead them to shallow plow layers, and the steepness of the terrain created erosion hazard. Of the soils examined, about 11% of uplands over 30% gradient was found in need of an urgent reforestation. A high content of gravel and firm hardness of soil attributed to inhibit the utilization of farm machinery and plant-root development. The average soil pH 5.6 was slightly low relative to pH 5.70 of the national average. Organic matter content was high compared with 2.0% of national average, but decreased with the prolonged cultivation periods. Available $P_2O_5$ concentration was unusually high due to the consequence of over dose application with chemical and organic fertilizers. Exchangeable cations as Ca, Mg, and K were appeared to be decreased in these regions with prolonging the cultivation periods. There were no significant differences in cation exchange capacity (CEC) and electrical conductivity (EC) among locations. Heavy metal contents were mostly lower than the threshold of danger level designated by Soil Environment Conservation Law of South Korea. Results indicated that a proper countermeasure and the best management practice should be immediately implemented to conserve the top soil and fertility in the Alpine regions.

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Toxic Evaluation of Antifouling Paint (Irgarol and Diuron) using the Population Growth Rate of Marine Diatom, Skeletonema costatum (해산 규조류(Skeletonema costatum)의 개체군 성장률 분석을 이용한 신방오도료(Irgarol, Diuron)의 독성평가)

  • Lee, Ju-Wook;Choi, Hoon;Park, Yun-Ho;Lee, Seung-Min;Choi, Yoon-Seok;Heo, Seung;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.5 no.1
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    • pp.9-16
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    • 2020
  • We evaluated the toxic effects of antifouling paint (irgarol and diuron) on the population growth rate (r) of the marine diatom, Skeletonema costatum. The r of S. costatum was determined after 96 hrs of exposure to irgarol (0, 0.31, 0.63, 1.25, 2.5 and 5 ㎍ l-1) and diuron (0, 7.81, 15.63, 31.25, 62.5 and 125 ㎍ l-1). It was observed that r in the control (absence of irgarol and diuron) were greater than 0.04, while r in the treatment groups decreased with increasing irgarol and diuron concentrations. Irgarol and diuron reduced r in a dose-dependent manner with significant decreases occurring at concentrations above 0.63 and 15.63 ㎍ l-1, respectively. The EC50 values of r in irgarol and diuron exposure were 1.09 and 45.45 ㎍ l-1. No observed effect concentration (NOEC) were 0.31 and 7.81 ㎍ l-1, the lowest observed effect concentration (LOEC) were 0.63 and 15.63 ㎍ l-1. This result indicate that a concentration of greater than 0.63 ㎍ l-1 of irgarol and 15.63 ㎍ l-1 of diuron in marine ecosystems induced to decreasing r of S. costatum. Also, these toxic values can be useful as a baseline data for the toxic evaluation of irgarol and diuron in marine ecosystems.

Anti-inflammatory Activities of Ethanol Extracts of Dried Lettuce (Lactuca sativa L.) (건조 상추 에탄올 추출물의 항염증 활성)

  • Lee, Eun-Joo;Seo, Yu-Mi;Kim, Yong-Hyun;Chung, Chungwook;Sung, Hwa-Jung;Sohn, Ho-Yong;Park, Jong-Yi;Kim, Jong-Sik
    • Journal of Life Science
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    • v.29 no.3
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    • pp.325-331
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    • 2019
  • Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including $IL-1{\alpha}$, $IL-1{\beta}$, IL-1F6, $TNF-{\alpha}$, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of $NF-{\kappa}B$ p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and $NF-{\kappa}B$ pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, $NF-{\kappa}B$, and Nrf2/HO-1 pathways.