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.
Kim, Jin-Ik;Choi, Yong-Won;Choi, Geun-June;Kang, Ji-An;Lee, In-Young;Narantuya, Nandintsetseg;Oh, Myong-Seok;Cho, Sik-Jae;Moon, Ja-Young
Journal of Life Science
/
v.31
no.1
/
pp.17-27
/
2021
This study was performed to investigate the antioxidant activities of subfractions of Peucedanum insolens Kitagawa root in various organic solvents and their anti-inflammatory effects on LPS-treated RAW264.7 cells. First, P. insolens Kitagawa roots were dried at room temperature for one week, chopped, and extracted with 70% ethanol. The resulting extracts were successively sub-fractionated with hexane, chloroform, ethyl acetate, and water. The antioxidant potential of the fractions was evaluated using a DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay and by measuring total polyphenol and flavonoid contents. The anti-inflammatory potency of the fractions was evaluated by measuring the inhibition levels of the expressions of inflammatory-mediated genes and proteins (e.g., iNOS, COX-2, IL-1β, and IL-6) in RAW264.7 cells. The results clearly showed that the ethyl acetate fraction of the P. insolens Kitagawa root contained relatively high total flavonoid (34.08±1.68 ㎍ of quercetin equivalents per mg) and total polyphenol (154.1±3.2 ㎍ of gallic acid equivalents per mg) contents. The DPPH assay results showed that the P. insolens Kitagawa root possessed strong free radical scavenging activity in the ethyl acetate fraction. Both the ethyl acetate and hexane fractions showed strong inhibitory potencies to nitric oxide production induced by lipopolysaccharide (1 ㎍/ml) treatment for 24 hr in RAW264.7 cells. The results also showed that both the hexane and ethyl acetate fractions of the P. insolens Kitagawa root strongly inhibited mRNA levels of iNOS, IL-1β, and IL-6, which were overexpressed by LPS treatment for 24 hr in the RAW264.7 cells. These results suggest that P. insolens Kitagawa root may contain compounds that possess strong potency for anti-inflammatory activity. Further studies are needed to discover more detailed modes of action of P. insolens Kitagawa root fractions against inflammation modulation, such as the regulation of cytokine signaling and inflammatory signaling pathways.
The present study was conducted to measure diurnal patterns in the flow of soluble non-ammonia nitrogen (SNAN) fractions in the liquid phase of digesta entering the omasum of cows fed grass-red clover silage supplemented with barley and rapeseed meal. Four ruminally cannulated cows were fed, in a 4×4 Latin square design, grass-red clover silage alone (GS) or supplemented with (on a DM basis) 6.0kg/d of barley grain, 2.1kg/d of rapeseed meal or 6.0kg/d of barley and 2.1kg/d rapeseed meal. Omasal digesta was taken using an omasal sampling system at 1.5h intervals during a 12h feeding cycle, and SNAN fractions (free AA, peptide and soluble protein) in the omasal digesta were assessed using ninhydrin assay. Dietary supplementation numerically increased the mean flow of SNAN fractions relative to GS diet despite the lack of statistical significance. Diurnal patterns in the flow of peptide entering the omasum during a 12h feeding cycle appeared to be highest immediately after feeding, declined by 10.0h post-feeding and slightly increased thereafter. In SNAN fractions, the flow of peptide was higher for supplemented diets than for GS diet throughout the feeding cycle. Based on the microbial contribution to total SNAN using 15N, diurnal patterns in the flow of dietary SNAN for dietary supplemented diets appeared to be higher compared with GS diets. Present results may conclude that peptide flow is quantitatively the most important N in SNAN fractions and that dietary supplementation can increase peptide flow entering the omasal canal.
The rates for the aquation of $cis-[Co(en)(NH_3)_2Cl_2]Cl in acetone-water mixtures have been measured at various pressures and temperatures by the electric conductivity method. The rate constant measured at 25$^{\circ}$C in pure water solvent is 3.47 ${\times}10^{-4}$/sec. Rate constants are increased with increasing temperature, and decreased with increasing pressure and mole fraction of acetone. Activation volumes and other activation parameters are calculated from these rate constants. The activation volumes are all positive and lie in the limited range +2.82~+$8.2cm^3$/mole. The rate constants in aqueous acetone solution are analyzed with the solvent compositions. Plots of log $k_{obs}$ vs. Grunwald-Winstein Y values show that log $k_{obs}$ varies linearly and the gradients are about 0.25. The applications of a free energy cycle relating the process initial state ${\to}$ transition state in water to that in acetone-water mixture show that the changes in solvation of the transition state have a dominant effect on the rate. From these results the aquation of this complex would be discussed in terms of dissociative mechanism ($I_d$).
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.11
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pp.1695-1700
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2014
Oriental herbal liquor (Yakju) is a type of Korean traditional alcoholic beverage that uses Nuruk and oriental herbs for fermentation. The purpose of this study was to develop cosmetic ingredients using Jubak, which is a by-product of alcoholic fermentation of oriental herbal liquor. To investigate antioxidant, whitening, and anti-aging effects of Jubak, we prepared extract of Jubak and its solvent fractions. Ethyl acetate fraction (KSD E4-3) showed the most prominent free radical [1,1-diphenyl-2-picrylhydrazyl (DPPH)] scavenging activity ($SC_{50}$: 0.75 mg/mL). KSD E4-3 significantly inhibited in vitro mushroom tyrosinase activity ($IC_{50}$: 0.82 mg/mL) and reduced the melanin contents in mouse melanoma melanocyte, B16F10 cells. KSD E4-3 down-regulated protein expression of tyrosinase related proteins (TRP)-1, -2, which play key roles in melanogenesis. For anti-aging effects, inhibition of matrix metalloproteinase (MMPs) expression was evaluated using human keratinocyte, HaCaT cells. Treatment of HaCaT cells with KSD E4-3 reduced expression of MMP-1, -2, -9 and inhibited proteolytic activities of MMP-2, -9. These results suggest that KSD E4-3 induces down-regulation of cellular melanogenesis and protects against photoaging induced by UVB-induced damage. Thus KSD E4-3 could potentially be a valuable cosmetic ingredient.
Natural gas in deep sediment may occur in three phases based on the physical and chemical conditions. If the concentration of gas in pore water is less than the solubility, gas is dissolved. If the concentration of gas is greater than its solubility (water is saturated or supersaturated with gas), gas occurs as a fee gas below the gas hydrate stability Lone (GHSZ) and is present as solid hydrate within the GHSZ. The knowledge of gas concentration in deep sediment appears critical to determine the phase of natural gases and to understand the formation and distribution of gas hydrate. However, reliable data on gas concentration are usually available only from the upper section of marine sediment by the headspace gas technique, which is widely used for sampling of gases from the sediments. The headspace gas technique represents only a fraction of gases present in situ because sediments release most of the gases during recovery and sampling. The PCS (Pressure Core Sampler) is a downhole tool developed to recover a nominal $1{\cal}m$ long, $4.32{\cal}cm$ diameter core containing $1,465cm^3$ of sediment, pore water and gas at in situ pressure up to 68.9 MPa. During Leg 204, the PCS was deployed at 6 Sites. In situ methane gas concentration and distribution of gas hydrate was measured by using PCS tool. Characteristics of methane concentration and distribution is different from site to site. Distribution of gas hydrate in the study area is closely related to characteristics of in situ gas concentration measured by PCS.
Jeon In Cheol;Jeong Jae Eun;Son In Hwan;Lee Ju Seok;Jeong Seung Won;Jang Jae Ho;Lee Seon U;Lee In;Moon Byun Soon
Journal of Physiology & Pathology in Korean Medicine
/
v.18
no.6
/
pp.1652-1660
/
2004
Apoptosis of vascular smooth muscle cells(VSMCs) is essential in atherogenesis, being a factor that modulates its early progression rather than a terminal event in the course of the disease. Various stimuli, including oxide lipoproteins, altered hemodynamic stress and free radical, can induced VSMCs apoptosis in vitro. The protective effects of Sophorae Radix (SR) on apoptotic cell death induced by H₂O₂ were investigated in VSMCs. The viability of VSMCs was markedly decreased by H₂O₂. Sophorae Radix protected the H202-induced apoptotic death of VSMCs, which was characterized as nuclear fragmentation and increase of sub-G0/G1 fraction .. Sophorae Radix decreased the activation of caspase-3 like protease induced by H₂O₂ and recovered control level from H202-induced PARP, Bak, Bcl-XL and mitochondrial membrane potential. These results suggest that Sophorae Radix protected VSMCs apoptotic death induced by H₂O₂ via inactivation of caspase-3 and modulation of mitochondrial function. Also, the expression profile of proteins by using two-dimensional (2-D) gel electrophoresis was screened. Future investigations will need to explore the use of an anti atherosclerotic therapy of Sophorae Radix, which relies on inhibition of the proapoptotic activation of the vascular smooth muscle cells.
Purpose: To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. Materials and Methods: Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors. Results: The 5-year disease-free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS. Conclusion: PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered.
Interrelation between the antioxidative activities of 70% ethanol extracts from bran fraction of 23 kinds of colored rice and chuchung as a control were examined. Antioxidative activities were evaluated by assaying reducing power, electron-donation ability to DPPH free radical, scavenging activity of hydroxy radical $({\cdot}OH)$ generated through Fenton reaction and inhibitory activity on lipid peroxidation using linoleic acid autoxidation system, respectively. Among 24 varieties of colored rice LK 1-3-6-12-1-1 had the strongest reducing power followed by Elwee, DZ 78, Jumlalocal-1 and SC-45 in decreasing order. The electron-donating ability to DPPH radical was higher in order of HP 883-1-1-1-B-1-1, HP 833-1-3-1-1-1, LK 2-7-12-1-1 and DZ 78. The hydroxy radical scavenging activity was higher in order of DK-1, IR 1544-38-2-2-1-2-2, SC-5 and SC-45 but LK 2-7-12-1-1 had oxidative effect. In the liaoleic acid autoxidation model system, RGS No 336, LK 1B-2-1-1, LK 1B-4-12-1-1, LK 1A-2-12-1-1, LK 2-7-12-1-1 and HP 883-1-1-1-B-1-1 exhibited strong antioxidative activities but Elwee, Jumlalocal-l and SC-45 showed to have oxidative effects. The rice variety of highest pigment content was Elwee and the next were RGS-No 336, IR 1544-38-2-2-1-2-2 and SC-5 with the order of higher content. The reducing power was correlated with the quantity of the pigment in the ethanolic extract of rice bran and SC-5 showed relatively high antioxidative activity in every results of antioxidative activity tests.
Background: When developing water quality improvement strategies for eutrophic lakes, questions may arise about the relative importance of point sources and nonpoint sources of phosphorus. For example, there is some skepticism regarding the effectiveness of partial reductions in phosphorus loading; because phosphorus concentrations are too high in hypertrophic lakes, in-lake phosphorus concentrations might still remain within typical range for eutrophic lakes even after the reduction of phosphorus loading. For this study, water quality and the phytoplankton and zooplankton communities were monitored in a hypertrophic reservoir (Lake Wangsong) before and after the reduction of phosphorus loading from a point source (a sewage treatment plant) by the installation of a chemical phosphorus-removal process. Results: Before phosphorus removal, Lake Wangsong was classified as hypertrophic with a median phosphorus concentration of $0.232mg\;L^{-1}$ and a median chlorophyll-a concentration of $112mg\;L^{-1}$. The dominant phytoplankton were filamentous cyanobacteria for the most of the ice-free season. Following the installation of the advanced treatment process, phosphorus concentrations were reduced to $81mg\;L^{-1}$, and the N/P atomic ratio increased from 42 to 102. Chlorophyll-a concentrations decreased to $42{\mu}g\;L^{-1}$, and the duration of cyanobacterial dominance was confined to the summer season. Cyanobacteria in spring and autumn were replaced by diatoms and cryptomonads. Filamentous cyanobacteria in summer were replaced by colony-forming unicellular Microcystis spp. It was remarkable that zooplankton biomass increased despite the decrease in phytoplankton biomass, and especially cladoceran zooplankton which increased drastically. These responses to the reduction of point source P loading to Lake Wangsong imply that reducing the point source P loading can have a big impact even when nonpoint sources account for a large fraction of the total annual phosphorus loading. Conclusions: Our results also show that the phytoplankton community can shift to decreased cyanobacterial dominance and the zooplankton community can shift to higher cladoceran dominance, even when phosphorus concentrations remain within the typical range for eutrophic lakes following the reduction of phosphorus loading.
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