Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals

Park, H.H.,Yu, H.J.,Kim, S.,Kim, G.,Choi, N.Y.,Lee, E.H.,Lee, Y.J.,Yoon, M.Y.,Lee, K.Y.,Koh, S.H. Elsevier BV 2016 NeuroToxicology Vol.55 No.-

<P>Oxidative stress is a well-known pathogenic mechanism of a diverse array of neurological diseases, and thus, numerous studies have attempted to identify antioxidants that prevent neuronal cell death. GV1001 is a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT). Considering that hTERT has a strong antioxidant effect, whether GV1001 also has an antioxidant effect is a question of interest. In the present study, we aimed to investigate the effects of GV1001 against oxidative stress in neural stem cells (NSCs). Primary culture NSCs were treated with different concentrations of GV1001 and/or hydrogen peroxide (H2O2) for various time durations. The H2O2 decreased the viability of the NSCs in a concentration-dependent manner, with 200 mu M H2O2 significantly decreasing both proliferation and migration. However, treatment with GV1001 rescued the viability, proliferation and migration of H2O2 injured NSCs. Consistently, free radical levels were increased in rat NSCs treated with H2O2, while co-treatment with GV1001 significantly reduced these levels, especially the intracellular levels. In addition, GV1001 restored the expression of survival-related proteins and reduced the expression of death associated ones in NSCs treated with H2O2. In conclusion, GV1001 has antioxidant and neuroprotective effects in NSCs following treatment with H2O2, which appear to be mediated by scavenging free radicals, increasing survival signals and decreasing death signals. (C) 2016 Elsevier B.V. All rights reserved.</P>

Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway

Park, Y-H,Kim, S-U,Kwon, T-H,Kim, J-M,Song, I-S,Shin, H-J,Lee, B-K,Bang, D-H,Lee, S-J,Lee, D-S,Chang, K-T,Kim, B-Y,Yu, D-Y Macmillan Publishers Limited 2016 Oncogene Vol.35 No.27

<P>The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently- expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.</P>

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K‐,H.,Hong, K‐,S.,Lee, B‐,C.,Oh, M‐,S.,Cho, Y‐,J.,Koo, J‐,S.,Park, J‐,M.,Bae, H‐,J.,Han, M‐,K.,Ju, Y‐,S.,Kang, D‐,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

라임병(Lyme disease : Borrelia burgdorferi) 매개진드기 (Ixodidae)에 대한 조사연구(Ⅲ)

심재철,윤영희,조양벽,이주연,신이현,양영철,박정은,이욱교,유효석,박경희 국립보건연구원 1994 국립보건원보 Vol.31 No.1

건국 우유와 유제품의 소비성향에 관한 조사연구

임종우,김종우,조광호,김영주,유제현,윤여창,장주익,권일경,안효일,이용규,이부응,박종래,이헌종 경상대학교 축산진흥연구소 1989 畜産振興硏究所報 Vol.16 No.1

Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans

Oh, J.,Chung, H.,Park, S.‐,I.,Yi, S. J.,Jang, K.,Kim, A. H.,Yoon, J.,Cho, J.‐,Y.,Yoon, S. H.,Jang, I.‐,J.,Yu, K.‐,S.,Chung, J.‐,Y. Blackwell Publishing Ltd 2016 DIABETES OBESITY AND METABOLISM Vol.18 No.1

<P>We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography‐electrospray ionization‐tandem mass spectrometry. When metformin was co‐administered with pyrimethamine, its area under the concentration–time curve from 0 to 12 h was 2.58‐fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2‐h‐post‐OGTT serum glucose concentration were −0.6 (−1, −0.2), −0.9 (−1.6, −0.3) and −0.5 (−1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal‐based pharmacology of metformin.</P>

한국산 원유의 화학적 조성에 관한 연구 : 지역별 · 계절별

이현종,강국희,고준수,김영교,김영주,김종우,김현욱,박종래,유제현,윤여창,윤영호,임종우 제주대학교 농과대학 제주도축산문제연구소 1991 畜産論叢 Vol.6 No.1

Totally 881 bulked raw milk samples were collected once a month from Oct. 1989 to Sep. 1990 at 18 districts plus 8-16 farms in the all over Korea, and general composition of raw milk were analysed for the variation and correlation in between provincial areas, districts, and collection lines of milk plant. Each components of raw milk collected in province and district were significantly differed (p<0.001), but sampling stage were not effected on the composition of milk. In the monthly variation of milk composition, all of components excepted the content of ash in raw milk were lower in July and August, and tended to increas in October to January, and significantly (0.001) greater than in July and August. The correlation coefficients for the relation between fat content and total solids or protein were 0.635, 0.135 respectively, and between protein content and total solids or SNF were 0.652, 0.742.

Improving mechanical and magnetocaloric responses of amorphous melt-extracted Gd-based microwires via nanocrystallization

Belliveau, H.F.,Yu, Y.Y.,Luo, Y.,Qin, F.X.,Wang, H.,Shen, H.X.,Sun, J.F.,Yu, S.C.,Srikanth, H.,Phan, M.H. Elsevier 2017 JOURNAL OF ALLOYS AND COMPOUNDS Vol.692 No.-

<P><B>Abstract</B></P> <P>We report on the structural, mechanical, and magnetocaloric properties of annealed melt-extracted Gd<SUB>53</SUB>Al<SUB>24</SUB>Co<SUB>20</SUB>Zr<SUB>3</SUB> amorphous microwires of ∼70 μm diameter. During heat treatment small islands of nanocrystallities are generated and isolated in the amorphous region for the wires. The size of the nanocrystallities ranges from 5 nm to 10 nm. The observed lattice distortion from the nanocrystallities causes changes in the magnetic properties of the wires. The annealing temperature of 100 °C has the largest strength (1845 MPa) as compared to wires annealed at other temperatures. This is likely to trigger nanophase transformation in the amorphous region and these nanocrystals have been preserved through the increase of annealing temperature. The formulation of the nanocrystalline islands is also verified by the selected-area electron diffraction (SAED). The microwires exhibit a large and reversible magnetocaloric effect (MCE), with the maximum isothermal magnetic entropy change (−Δ<I>S</I> <SUB>M</SUB>) and refrigerant capacity (<I>RC</I>) values of 9.5 J/kg K and 689 J/kg respectively for the microwire annealed at 100 °C. This <I>RC</I> is about 35%, 67%, and 91% larger than those of bulk Gd<SUB>53</SUB>Al<SUB>24</SUB>Co<SUB>20</SUB>Zr<SUB>3</SUB> (∼509 J/kg), Gd (∼410 J/kg), and Gd<SUB>5</SUB>Si<SUB>2</SUB>Ge<SUB>1.9</SUB>Fe<SUB>0.1</SUB> (∼360 J/kg) regardless of their ordering temperatures. These results demonstrate the ability to tune the mechanical and magnetic properties of the microwires by thermal annealing.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The impact of nanocrystallization in Gd<SUB>53</SUB>Al<SUB>24</SUB>Co<SUB>20</SUB>Zr<SUB>3</SUB> microwires. </LI> <LI> Enhanced mechanical strength. </LI> <LI> Enhanced magnetocaloric response. </LI> </UL> </P>

Lipid emulsion attenuates apoptosis induced by a toxic dose of bupivacaine in H9c2 rat cardiomyoblast cells

Ok, S-H,Yu, J,Lee, Y,Cho, H,Shin, I-W,Sohn, J-T Scientific & Medical Division,Macmillan Press 2016 Human & experimental toxicology Vol.35 No.9

<P>The goal of this in vitro study was to investigate the effect of lipid emulsion on apoptosis induced by a toxic dose of bupivacaine (BPV) in H9c2 rat cardiomyoblast cell lines. The effect of lipid emulsion on the decreased cell viability and count induced by BPV or mepivacaine (MPV) in the H9c2 cells was assessed using an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay or a cell count assay. The effect of BPV or lipid emulsion combined with BPV on cleaved caspase 3, caspase 8, and Bax in H9c2 cells was investigated using Western blotting. A terminal deoxynucleotidyl transferase dUTP2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay was performed to detect apoptosis of H9c2 cells treated with BPV alone or lipid emulsion combined with BPV. The magnitude of lipid emulsion-mediated attenuation of decreased cell viability induced by BPV was higher than that of lipid emulsion-mediated attenuation of decreased cell viability induced by MPV. Lipid emulsion attenuated the increases in cleaved caspase 3, caspase 8 and Bax induced by BPV. Lipid emulsion attenuated the increases in TUNEL-positive cells induced by BPV. These results suggest that lipid emulsion attenuates a toxic dose of BPV-induced apoptosis via inhibition of the extrinsic and intrinsic apoptotic pathways. The protective effect of lipid emulsion may be partially associated with the relatively high lipid solubility of BPV.</P>

Modeling of Brain D2 Receptor Occupancy-Plasma Concentration Relationships with a Novel Antipsychotic, YKP1358, Using Serial PET Scans in Healthy Volunteers

Lim, K S,Kwon, J S,Jang, I-J,Jeong, J M,Lee, J S,Kim, H W,Kang, W J,Kim, J-R,Cho, J-Y,Kim, E,Yoo, S Y,Shin, S-G,Yu, K-S Springer Science and Business Media LLC 2007 Clinical pharmacology and therapeutics Vol.81 No.2

<P>YKP1358 is a novel serotonin (5-HT(2A)) and dopamine (D(2)) antagonist that, in preclinical studies, fits the general profile of an atypical antipsychotic. We conducted a D(2) receptor occupancy study with YKP1358 in healthy volunteers using positron emission tomography (PET) to measure the D(2) receptor occupancy of YKP1358 and to characterize its relationship to plasma drug concentrations. A single oral dose, parallel group, dose-escalation (100, 200, and 250 mg) study was performed in 10 healthy male volunteers with the PET radiotracer [(11)C]raclopride. The D(2) receptor occupancy of striatum was measured pre-dose, and at 2, 5, and 10 h after YKP1358 administration. Serial blood samples were taken for measurement of plasma YKP1358 concentrations. D(2) receptor occupancy by YKP1358 increased to 53-83% at 2 h, and then decreased afterwards, ranging from 40-64% at 5 h to 20-51% at 10 h. The YKP1358 dose-plasma concentration relationship exhibited extensive variability, but there was a good relationship between plasma concentrations and D(2) receptor occupancy that was well predicted by a sigmoid E(max) model using nonlinear mixed effects modeling. To our knowledge, this is the first study in which the relationship between plasma concentration and the biomarker of D(2) receptor occupancy was modeled using nonlinear mixed effects modeling. It is anticipated that these results will be useful in estimating for subsequent studies the initial doses of YKP1358 required to achieve a therapeutically effective range of D(2) receptor occupancy.</P>