• Title/Summary/Keyword: pH-dependent

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BMP-6 Attenuates Oxygen and Glucose Deprivation-Induced Apoptosis in Human Neural Stem Cells through Inhibiting p38 MAPK Signaling Pathway

  • Li Wang;Yang Chen;Lin Wei;Jing He
    • International Journal of Stem Cells
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    • v.15 no.2
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    • pp.144-154
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    • 2022
  • Background and Objectives: Neural stem cells (NSCs) remain in the mammalian brain throughout life and provide a novel therapeutic strategy for central nervous system (CNS) injury. Bone morphogenetic protein-6 (BMP-6) had shown a protective effect in different types of cells. However, the role of BMP-6 in NSCs is largely unclear. The present study was aimed to investigate whether BMP-6 could protect human NSCs (hNSCs) against the oxygen and glucose deprivation (OGD)-induced cell death. Methods and Results: Upon challenge with OGD treatment, cell viability was significantly decreased in a time-dependent manner, as indicated by the CCK-8 assay. BMP-6 could attenuate the OGD-induced cell injury in a dose-dependent manner and decrease the number of TUNEL-positive cells. Moreover, BMP-6 markedly weakened the OGD-induced alterations in the expression of procaspase-8/9/3 and reversed the expression of cleaved-caspase-3. Interestingly, noggin protein (the BMP-6 inhibitor) attenuated the neuroprotective effect of BMP-6 in cultured hNSCs. Furthermore, the p38 MAPK signaling pathway was activated by OGD treatment and BMP-6 markedly inhibited the phosphorylation of p38 in a concentration-dependent manner. Pretreatment with noggin abolished the effect of BMP-6 on p38 activation. SB239063, a selective p38 inhibitor, exerted similar effects with BMP-6 in protecting hNSCs against the OGD-induced apoptosis. These results indicated that blocking the phosphorylation of p38 might contribute to the neuroprotective effect of BMP-6 against the OGD-induced injury in hNSCs. Conclusions: These findings suggested that BMP-6 might be a therapeutic target in the OGD-induced cell death, which provides a novel therapeutic strategy for enhancing host and graft NSCs survival in hypoxic-ischemic brain injury.

Synthesis and pH-Dependent Micellization of Sulfonamide-Modified Diblock Copolymer

  • Pal Ravindra R.;Kim Min Sang;Lee Doo Sung
    • Macromolecular Research
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    • v.13 no.6
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    • pp.467-476
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    • 2005
  • The main objective of this study was to develop and characterize pH-sensitive biodegradable polymeric materials. For pH-sensitivity, we employed three kinds of moieties: 2-amino-3-(lH-imidazol-4-yl)-propionic acid (H), N-[4-( 4,6-dimethyl-pyrimidin-2ylsulfamoyl)-phenyl]succinamic acid (SM), and 2- {3-[ 4-( 4,6-dimethyl-pyrim­idin- 2-ylsulfamoyl)-phenylcarbamoyl]-propionylamino} -3-(3 H - imidazol-4-yl)-propionic acid (SH). The pH -sensitive diblock copolymers were synthesized by ring opening polymerization and coupling reaction from poly(ethylene glycol) (MPEG), $\varepsilon$-caprolactone (CL), D,L-lactide (LA) and pH-sensitive moieties. The pH-sensitive SH molecule was synthesized in a two-step reaction. The first step involved the synthesis of SHM, a methyl ester derivative of SH, by coupling reaction of SM and L-histidine methyl ester dihydrochloride, whereas the second step involved the hydrolysis of the same. The synthesized SM, SHM and SH molecules were characterized by FTIR, $^{1}H$-NMR and $^{13}C$-NMR spectroscopy, whereas diblock copolymers and pH-sensitive diblock copolymer were characterized by $^{1}H$-NMR and GPC analysis. The critical micelle concentrations were determined at various pH conditions by fluorescence technique using pyrene as a probe. The micellization and demicellization studies of pH-sensitive diblock copolymers were also done at different pH conditions. The pH-sensitivity was further established by acid-based titration and DLS analysis.

Study on Apoptosis Effect and Mechanism by Bojungikki-tang on Human Cancer Cell Line H460 (폐암세포주(肺癌細胞株) H460에 대(對)한 보중익기탕(補中益氣湯)의 세포고사효과(細胞枯死效果) 및 기전연구(機轉硏究))

  • Lee, Seung-Eon;Hong, Jae-Eui;Lee, Si-Hyeong;Shin, Jo-Young;Ro, Seung-Seok
    • The Journal of Internal Korean Medicine
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    • v.25 no.4
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    • pp.274-288
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    • 2004
  • Objectives : This study was designed to evaluate the effect on cytotoxicity of Bojungikki-tang(BIT) in human lung cancer H460 cells. Methods : BIT-induced cell death was confirmed as apoptosis characterized by chromatin condensation and increase of the $sub-G_1$, DNA content. It was tested whether the water extract of BIT affects the cell cycle regulators such as, p2l/Cipl, p27/Kipl, cyclin $B_1$. Results : The data showed that treatment of BIT decreased the viability of H460 cells in a dose-dependent manner. p2l/Cip1 is gradually decreased by the addition of the cells with BIT extract. Interestingly, p27/Kip1 is not detected for 24 hr after the addition of BIT extract, however, after 24 hr, p27/Kipl markedly increased. In addition, cyclin $B_1$, decreased in a time dependent manner after the addition of the water extract. The activation of caspase -3 protease was further confirmed by degradation of procaspase-8 protease andpoly(ADP-ribose) polymerase(P ARP) by BIT in H460 cells. Moreover, BIT induced the increase of Bak expression. Conclusion : These results suggest that the extract of BIT exerts anticancer effects to induce the death of human lung cancer H460 cells via down regulation of cell cycle regulators such as p2l/Cip1, and cyclin B1 or up regulation of cell cycle regulators such as p27/Kip1. Moerover results suggest that BIT induces an apoptosis in H460 cells via activation of intrinsic caspase cascades.

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Antioxidant Activities of Ethanol Extracts from Solidago virga-aurea var. gigantea (울릉미역취 에탄올추출물의 항산화 활성)

  • Ji, Yoon-Sun;Lee, Nam-Sun;Kil, Ki-Jung;Yoo, Ji-Hyun
    • The Korea Journal of Herbology
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    • v.34 no.1
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    • pp.109-116
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    • 2019
  • Objectives : This study aimed to analyze contents of chlorogenic acid among major ingredients and determine the optimal solvent for the antioxidant activity from Solidago virga-aurea var. gigantea(SV) aerial part. Methods : Mature aerial part of extracted SV at the first crop on June 2018 was used. SV was mixed with each at the ethanol concentrate rates of water, 10, 30, 50, 70, and 100% and extracted them for three times for eight hours at $70^{\circ}C$. The contents of chlorogenic acid and seven kinds of antioxidant activities were measured in SV extracts. Results : The highest the contents of chlorogenic acid was from 10% ethanol extracts showed. Total polyphenol and flavonoids of SV extracts were 126.16 mg/g and 105.84 mg/g, respectively. Scavenging activities of DPPH, ABTS, and hydroxyl radical significantly increased in a dose-dependent in SV extracts, while it was almost similar with control at the concentration of $500{\mu}g/mL$. $Fe^{2+}$ chelating activity significantly increase in a dose-dependent in SV extract, it was lower than control. Nitrite scavenging activity increased, dose-dependent in the sequence of pH 1.2> pH 3.0 > pH 6.0 in SV extracts, while it was almost similar with control at the concentration of $500{\mu}g/mL$, pH 1.2, and pH 3.0. Conclusions : Thus, this study found that higher contents of chlorogenic acid and excellent antioxidant activity were contained in 10% ethanol extracts in mature aerial part of SV. It is expected to be used as basic data as natural antioxidant materials.

Preformulation Study of Aspalatone, a New Antithrombotic Agent (새로운 항혈전 약물인 아스팔라톤의 전처방화 연구)

  • 곽혜선;전인구
    • Biomolecules & Therapeutics
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    • v.8 no.4
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    • pp.332-337
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    • 2000
  • Physicochemical properties of aspalatone (acetylsalicylic acid maltol ester, AM), which has been recently found to have an antithrombotic effect, were studied in terms of solubility, dissolution, partition coefficient (Pc) and stability. The solubility of AM at 37$^{\circ}C$ was about 1.2 mg/ml and the P$_{c}$ value for n-octanol/water and chloroform/water was 11.4 and 382.6, respectively. Dissolution rates of AM at pH 1.2 and 6.8 were more than 80% within 30 min. The degradation of AM followed apparent first-order kinetics, and was dependent on temperature, pH and ionic strength. From the pH-rate profile, the optimal pH was found to be at around 4.0. Half-lives at pH 1.2 and 6.8 were 33.5 and 44.4 hr, respectively. The degradation rate of AM at pH 1.2 was somewhat faster than that of aspirin, but at pH 7.0, the degradation rate of AM was slower than that of aspirin.n.

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Hydrogen Peroxide-induced Alterations in Na+-phosphate Cotransport in Renal Epithelial Cells

  • Jung, Soon-Hee
    • Korean Journal of Clinical Laboratory Science
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    • v.41 no.2
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    • pp.83-92
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    • 2009
  • This study was undertaken to examine the effect of oxidants on membrane transport function in renal epithelial cells. Hydrogen peroxide ($H_2O_2$) was used as a model oxidant and the membrane transport function was evaluated by measuring $Na^+$-dependent phosphate ($Na^+$-Pi) uptake in opossum kidney (OK) cells. $H_2O_2$ inhibited $Na^+$-Pi uptake in a dose-dependent manner. The oxidant also caused loss of cell viability in a dose-dependent fashion. However, the extent of inhibition of the uptake was larger than that in cell viability. $H_2O_2$ inhibited $Na^+$-dependent uptake without any effect on $Na^+$-independent uptake. $H_2O_2$-induced inhibition of $Na^+$-Pi uptake was prevented completely by catalase, dimethylthiourea, and deferoxamine, suggesting involvement of hydroxyl radical generated by an iron-dependent mechanism. In contrast, antioxidants Trolox, N,N'-diphenyl-p-phenylenediamine, and butylated hydroxyanisole did not affect the $H_2O_2$ inhibition. Kinetic analysis indicated that $H_2O_2$ decreased Vmax of $Na^+$-Pi uptake with no change in the Km value. Phosphonoformic acid binding assay did not show any difference between control and $H_2O_2$-treated cells. $H_2O_2$ also did not cause degradation of $Na^+$-Pi transporter protein. Reduction in $Na^+$-Pi uptake by $H_2O_2$ was associated with ATP depletion and direct inhibition of $Na^+$-$K^+$-ATPase activity. These results indicate that the effect of $H_2O_2$ on membrane transport function in OK cells is associated with reduction in functional $Na^+$-pump activity. In addition, the inhibitory effect of $H_2O_2$ was not associated with lipid peroxidation.

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Remediation of Soil Surrounding Abandoned Metal Mine By Using Low Molecular Weight Organic Acid (저분자 유기산을 이용한 폐금속광산 주변토양 정화)

  • 이동호;박옥현
    • Proceedings of the Korean Society of Soil and Groundwater Environment Conference
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    • 1998.11a
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    • pp.183-188
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    • 1998
  • The efficiency of removing cadmium, copper, and lead from a contaminated soil of abandoned metal mine was studied in a laboratory investigation where citric acid were used to extract the metal from the soil. The contamination level of Pb, Cu in the soil A were 875.5, 667.5mg/kg respectively. The mobility and bioavailability of the metals in soil were also estimated by Sequential Chemical Extractions. Citric acid were examined for its potential extractive capabilities. Concentrations of the acid examined in this study ranged from 0.025 to 0.15M. The pH of the suspensions and S/S ratio in which the extractions were performed ranged from 2.4 to 8.1, and from 2.1:1 to 20:1. Results showed that the removal of contaminant using citric acid was pH and S/S raton dependent.

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Etching and Polishing Behavior of Cu thin film according to the additive chemicals

  • Ryu, Ju-Suk;Eom, Dae-Hong;Hong, Yi-Koan;Park, Jum-Yong;Park, Jin-Goo
    • Proceedings of the International Microelectronics And Packaging Society Conference
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    • 2002.05a
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    • pp.274-278
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    • 2002
  • The purpose of this study was to characterize the reaction of Cu surface with Cu slurry and CMP performance as a function of additives in CMP slurry. The polish rate of Cu was dependent on the kind of organic acids added in slurry. It was considered that polish rate of Cu was dependent on the concentration of carboxylates and mean particle size. When the etchant and oxidant were added in slurry, the highest removal rate and lower etch rate were measured at neutral pH. The addition of etchant, oxidant and pH adjustor played key roles of CMP ability in slurry. As the pH increased, polish rate of Cu was increased by the enhanced the mechanical effects due to effective dispersion of slurry particles. Alumina abrasives was more desirable for 1st step slurry because of high removal rate of Cu and high selectivity ratio among TaN and Cu.

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Synthesis and Characterization of MPEG-b-PDPA Amphiphilic Block Copolymer via Atom Transfer Radical Polymerization and Its pH-Dependent Micellar Behavior

  • Dayananda, Kasala;Kim, Min-Sang;Kim, Bong-Sup;Lee, Doo-Sung
    • Macromolecular Research
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    • v.15 no.4
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    • pp.385-391
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    • 2007
  • Block copolymer micelles are generally formed via the self-assembly of amphiphilic block copolymers in an aqueous medium. The hydrophilic and hydrophobic blocks form shell and core micelles, respectively. The block copolymers of methoxy poly(ethylene glycol) (MPEG)-b-poly(2-diisopropylamino)ethyl methacrylate (PDPA) were synthesized via atom transfer radical polymerization, with the macro initiator synthesized by the coupling of 2-bromoisobutyryl bromide with MPEG in the presence of a triethyl amine base catalyst. The atom transfer radical polymerization of 2-diisopropylamino)ethyl methacrylate was performed in conjunction with an N,N,N',N",N"-pentamethyl-diethylenetriamine/copper bromide catalyst system, in DMF, at $70^{\circ}C$. The pH induced micellization/demicellization was studied using fluorescence, with a pyrene probe. Furthermore, the pH dependent micellization was confirmed using the microviscosity method, with a dipyme fluorescence probe. The pH dependant micelle size distribution was studied using dynamic light scattering. The characterization of the synthesized polymers was established using gel permeation chromatography and from the $^1H-nuclear$ magnetic resonance spectroscopy.

X-Ray Diffraction Studies of Uranyl Hydrolysis Precipitates Synthesized in Neutral to Alkaline Aqueous Solutions

  • 박용준;표형렬;김원호;전관식
    • Bulletin of the Korean Chemical Society
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    • v.17 no.10
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    • pp.925-929
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    • 1996
  • Uranyl hydrolysis precipitates were obtained by increasing pH value of aqueous uranyl solution in the range of neutral to alkaline pH value and their phase transformation during the solubility experiment under various conditions has been examined. The precipitates formed in the hydrolysis reaction of uranyl ion had a layered structure such as a meta-schoepite phase, a schoepite structure, or a mixed phase of meta-schoepite and schoepite. Phase transformation between them was strongly dependent on the pH value at which the precipitate was formed. The distance between the layers in meta-schoepite or schoepite phase was ∼7.35 Å, and it was increased with the pH value at which the precipitate was synthesized as well as the pH values of the aqueous solution. The phase transformation from a meta-schoepite to schoepite was fast for the precipitates formed at low pH values, however, it was not the case for the precipitates formed at high pH values. A small difference of pH value in aqueous solution gave a great change on its solubilities near pH 9.7, because a layered structure of the precipitates became amorphous above that pH value. Greater solubility for the precipitate formed at higher pH value can be explained from the fact that the precipitates formed at low pH value had a better crystallinity and also that the precipitates formed at higher pH value has a slower rate of crystallization.