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      • P53 Impairs Endothelium-Dependent Vasomotor Function Through Transcriptional Upregulation of P66shc

        Kim, Cuk-Seong,Jung, Saet-Byel,Naqvi, Asma,Hoffman, Timothy A.,DeRicco, Jeremy,Yamamori, Tohru,Cole, Marsha P.,Jeon, Byeong-Hwa,Irani, Kaikobad Ovid Technologies Wolters Kluwer -American Heart A 2008 Circulation research Vol.103 No.12

        <P>The transcription factor, p53, and the adaptor protein, p66shc, both play essential roles in promoting oxidative stress in the vascular system. However, the relationship between the two in the context of endothelium-dependent vascular tone is unknown. Here, we report a novel, evolutionarily conserved, p53-mediated transcriptional mechanism that regulates p66shc expression and identify p53 as an important determinant of endothelium-dependent vasomotor function. We provide evidence of a p53 response element in the promoter of p66shc and show that angiotensin II-induced upregulation of p66shc in endothelial cells is dependent on p53. In addition, we demonstrate that downregulation of p66shc expression, as well as inhibition of p53 function in mice, mitigates angiotensin II-induced impairment of endothelium-dependent vasorelaxation, decrease in bioavailable nitric oxide, and hypertension. These findings reveal a novel p53-dependent transcriptional mechanism for the regulation of p66shc expression that is operative in the vascular endothelium and suggest that this mechanism is important in impairing endothelium-dependent vascular relaxation.</P>

      • MicroRNA signatures associated with immortalization of EBV‐transformed lymphoblastoid cell lines and their clinical traits

        Lee, J.‐,E.,Hong, E.‐,J.,Nam, H.‐,Y.,Kim, J.‐,W.,Han, B.‐,G.,Jeon, J.‐,P. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.1

        <P><B>Abstract</B></P><P><B>Objective: </B> MicroRNAs (miRNAs) are negative regulators of gene expression that play important roles in cell processes such as proliferation, development and differentiation. Recently, it has been reported that miRNAs are related to development of carcinogenesis. The aim of this study was to identify miRNAs associated with terminal immortalization of Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell line (LCL) and associated clinical traits.</P><P><B>Material and Methods: </B> Hence, we performed miRNA microarray approach with early‐ (p6) and late‐passage (p161) LCLs.</P><P><B>Results and Conclusion: </B> Microarray data showed that nine miRNAs (miR‐20b*, miR‐28‐5p, miR‐99a, miR‐125b, miR‐151‐3p, miR‐151:9.1, miR‐216a, miR‐223* and miR‐1296) were differentially expressed in most LCLs during long‐term culture. In particular, miR‐125b was up‐regulated in all the tested late‐passage LCLs. miR‐99a, miR‐125b, miR‐216a and miR‐1296 were putative negative regulators of <I>RASGRP3</I>, <I>GPR160</I>, <I>PRKCH</I> and <I>XAF1</I>, respectively, which were found to be differentially expressed in LCLs during long‐term culture in a previous study. Linear regression analysis showed that miR‐200a and miR‐296‐3p correlated with triglyceride and HbA1C levels, respectively, suggesting that miRNA signatures of LCLs could provide information on the donor’s health. In conclusion, our study suggests that expression changes of specific miRNAs may be required for terminal immortalization of LCLs. Thus, differentially expressed miRNAs would be a potential marker for completion of cell immortalization during EBV‐mediated tumorigenesis.</P>

      • Chemodosimeter functionalized diatomaceous earth particles for visual detection and removal of trace mercury ions from water

        Patil, Pravin,Madhuprasad, Pravin,Bhat, Mahesh P.,Gatti, Manasa G.,Kabiri, Shervin,Altalhi, Tariq,Jung, Ho-Young,Losic, Dusan,Kurkuri, Mahaveer Elsevier 2017 Chemical engineering journal Vol.327 No.-

        <P><B>Abstract</B></P> <P>The rhodamine based receptor, P2 has been developed for the detection of environmentally hazardous Hg<SUP>2+</SUP> ions with a limit of detection, 1.5×10<SUP>−6</SUP> M. The P2 showed a significant colour change from colourless to pink upon binding with Hg<SUP>2+</SUP> ions. As a result, a new peak at 533nm was observed in UV–vis spectroscopy which was attributed to spirolactum ring opening followed by through bond energy transfer (TBET). In addition, the presence of other competing cations did not interfere the detection of Hg<SUP>2+</SUP> ions. Further, P2 has been successfully immobilized onto the naturally available and highly porous diatomaceous earth particles (P2D) for removal of Hg<SUP>2+</SUP> ions from water. The covalently attached organic molecule in P2D forms complex with Hg<SUP>2+</SUP> ion present in the water and thus traps the Hg<SUP>2+</SUP> ions. Based on this, a proof-of-concept cartridge has been developed for water purification. The cartridge having 450mg of P2D was able to purify 30mL of water containing 1ppm Hg<SUP>2+</SUP> ions. The efficiency of cartridge could be visualized with a colour change from colourless to pink.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Detection and removal of Hg<SUP>2+</SUP> from water using chemodosimeter P2 were realized. </LI> <LI> P2 has been successfully immobilized onto naturally available diatoms (P2D). </LI> <LI> Organic receptor and hazardous Hg<SUP>2+</SUP> ions were physically contained in diatoms. </LI> <LI> Eco-friendly cartridge containing P2D was developed for the removal of Hg<SUP>2+</SUP> ions. </LI> <LI> Device efficiency (time to replace) could be realized through visual colour change. </LI> </UL> </P>

      • Unraveling the Atomistic Sodiation Mechanism of Black Phosphorus for Sodium Ion Batteries by First-Principles Calculations

        Hembram, K. P. S. S.,Jung, Hyun,Yeo, Byung Chul,Pai, Sung Jin,Kim, Seungchul,Lee, Kwang-Ryeol,Han, Sang Soo American Chemical Society 2015 The Journal of Physical Chemistry Part C Vol.119 No.27

        <P>As opposed to the standard graphite anode used for lithium (Li) ion batteries (LIBs), a standard anode material for sodium (Na) ion batteries (NIBs) has not yet been reported. Black phosphorus is potentially very attractive as an anode material for NIBs, as it has a layered structure similar to graphite but a greater interlayer distance. In this work, we propose an atomistic mechanism for the sodiation of black phosphorus, based on first-principles calculations. The layered structure of black phosphorus is maintained up to the composition of Na<SUB>0.25</SUB>P, with <I>one-dimensional</I> sodiation (an intercalation process) occurring in the interlayer spaces of the black phosphorus, resulting in sliding of the phosphorene layers because one Na atom tends to bind to four P atoms. At Na levels beyond Na<SUB>0.25</SUB>P, the intercalation process changes to an alloying process. Sodiation exceeding the critical composition leads to breaking of P–P bonds and eventual formation of an amorphous phase from the layered Na<SUB><I>x</I></SUB>P structure. After the P–P bonds in the layered Na<SUB><I>x</I></SUB>P structure are broken, in a progress in which staggered P–P bonds are preferentially broken rather than planar P–P bonds, P<SUB>2</SUB> dumbbells are generated. As sodiation proceeds further, most of the P<SUB>2</SUB> dumbbells become isolated P atoms. Thus, in the amorphous Na<SUB>3</SUB>P phase, only low-coordinate P components such as isolated atoms (primarily) and dumbbells are found. We expect that our comprehensive understanding of the sodiation mechanism in black phosphorus will provide helpful guidelines in designing new types of black phosphorus anodes to obtain better performing NIBs.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2015/jpccck.2015.119.issue-27/acs.jpcc.5b05482/production/images/medium/jp-2015-054822_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp5b05482'>ACS Electronic Supporting Info</A></P>

      • SCISCIESCOPUS

        Development of multifunctional metabolic synergists to suppress the evolution of resistance against pyrethroids in insects that blood feed on humans

        Hardstone, Melissa C,Strycharz, Joseph P,Kim, Junheon,Park, Il‐,Kwon,Yoon, Kyong Sup,Ahn, Young Joon,Harrington, Laura C,Lee, Si Hyeock,Clark, J Marshall John Wiley Sons, Ltd 2015 PEST MANAGEMENT SCIENCE Vol.71 No.6

        <P><B>Abstract</B></P><P><B>BACKGROUND</B></P><P>Pyrethroids are the insecticides of choice when exposure to humans is likely, such as occurs in vector and public‐health‐related control programs. Unfortunately, the pyrethroids share a common resistance mechanism with dichlorodiphenyltrichloroethane (DDT), knockdown resistance (<I>kdr</I>), and prior extensive use of DDT has predisposed the pyrethroids to cross‐resistance via <I>kdr</I>. Given the widespread occurrence of <I>kdr</I>, the use of synergists with pyrethroids is considered to be prudent to guard against the selection of multiply resistant insects.</P><P><B>RESULTS</B></P><P>3‐Phenoxybenzyl hexanoate (PBH) was synthesized as a multifunctional pyrethroid synergist that, besides being a surrogate substrate for sequestration/hydrolytic carboxylesterases, now also functions as a substrate for oxidative xenobiotic metabolism. The addition of PBH to permethrin‐treated females of the ISOP450 strain of <I>Culex pipiens quinquefasciatus</I> resulted in a threefold increase in synergism, as judged by the synergistic ratio. Similarly, PBH synergized the action of deltamethrin sixfold on females of the common bed bug, <I>Cimex lectularius</I>, and was 2.8‐fold more synergistic than piperonyl butoxide (PBO).</P><P><B>CONCLUSIONS</B></P><P>PBH synergized the action of both type I and type II pyrethroids in a mosquito vector (<I>Cx. p. quinquefasciatus</I>) and in a public‐health pest, <I>C. lectularius</I>, respectively, indicating a broad spectrum of action on blood‐feeding insects. PBH appears to have residual properties similar to permethrin and is itself non‐toxic, unlike PBO, and therefore should be compatible with existing pyrethroid formulations used for insecticide‐treated nets and home/residential sprays. © 2014 Society of Chemical Industry</P>

      • SCISCIESCOPUS

        Influence of flowrates to a reverse electro-dialysis (RED) stack on performance and electrochemistry of a microbial reverse electrodialysis cell (MRC)

        Kang, Heunggu,Kim, Eojin,Jung, Sokhee P. Elsevier 2017 International journal of hydrogen energy Vol.42 No.45

        <P><B>Abstract</B></P> <P>An MRC is a bioelectrochemical system combining a microbial fuel cell (MFC) with a RED stack to generate electricity from salinity gradient and organic wastewater with simultaneous treatment. Operating an MRC at an optimum flowrate to RED is important because it is closely related with energy production rate and economic feasibility. However, influence of RED flowrates on MRC electrochemistry and power production have not been investigated. For this purpose, four different flowrates of high concentration and low concentration solutions were tested. Maximum power density was highest in 10 mL/min (3.71 W/m<SUP>2</SUP>) and optimum current density was highest in 7.5 mL/min (5.36 A/m<SUP>2</SUP>). By mere increasing the flowrate to MRC, maximum power and optimum current densities increased by 17.7% and 16.2%. EIS showed that impedances of anode, cathode and full-cell were decreased by 51%, 31% and 19%, respectively. Anode CV showed that peak current density was increased by 25.7%. COD removal and CE were not affected by RED flowrate. Power generation at 7.5 mL/min and 10 mL/min were not so different, but current production was better at 7.5 mL/min. Therefore, considering energy production, the RED flowrate of 7.5 mL/min is a reasonable choice for MRC operation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> By increasing RED flowrate, P<SUB>max</SUB> increased by 17.7%. </LI> <LI> By increasing RED flowrate, I<SUB>opt</SUB> increased by 16.2%. </LI> <LI> P<SUB>max</SUB> were similar in 7.7 mL/min and 10 mL/min (∼3.7 W/m<SUP>2</SUP>). </LI> <LI> I<SUB>opt</SUB> was highest in 7.5 mL/min (∼5.4 A/m<SUP>2</SUP>). </LI> <LI> 7.5 mL/min was the best flowrate in the tested MRC. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • Balanced intake of protein and carbohydrate maximizes lifetime reproductive success in the mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae)

        Rho, M.S.,Lee, K.P. Pergamon Press 2016 Journal of insect physiology Vol.91 No.-

        <P>Recent developments in insect gerontological and nutritional research have suggested that the dietary protein:carbohydrate (P:C) balance is a critical determinant of lifespan and reproduction in many insects. However, most studies investigating this important role of dietary P:C balance have been conducted using dipteran and orthopteran species. In this study, we used the mealworm beetles, Tenebrio molitor L. (Coleoptera: Tenebrionidae), to test the effects of dietary P:C balance on lifespan and reproduction. Regardless of their reproductive status, both male and female beetles had the shortest lifespan at the protein-biased ratio of P:C 5:1. Mean lifespan was the longest at P:C 1:1 for males and at both P:C 1:1 and 1:5 for females. Mating significantly curtailed the lifespan of both males and females, indicating the survival cost of mating. Age-specific egg laying was significantly higher at P:C 1:1 than at the two imbalanced P:C ratios (1:5 or 5:1) at any given age throughout their lives, resulting in the highest lifetime reproductive success at P:C 1:1. When given a choice, beetles actively regulated their intake of protein and carbohydrate to a slightly carbohydrate-biased ratio (P:C 1:1.54-1:1.64 for males and P:C 1:1.31:1.36 for females). The self-selected P:C ratio was significantly higher for females than males, reflecting a higher protein requirement for egg production. Collectively, our results add to a growing body of evidence suggesting the key role played by dietary macronutrient balance in shaping lifespan and reproduction in insects. (C) 2016 Elsevier Ltd. All rights reserved.</P>

      • Expression phenotype changes of EBV-transformed lymphoblastoid cell lines during long-term subculture and its clinical significance

        Lee, J.-E.,Nam, H.-Y.,Shim, S.-M.,Bae, G.-R.,Han, B.-G.,Jeon, J.-P. Blackwell Publishing Ltd 2010 Cell proliferation Vol.43 No.4

        <P>Abstract</P><P>Objectives: </P><P>The EBV-transformed lymphoblastoid cell line (LCL) is a useful resource for population-based human genetic and pharmacogenetic studies. The principal objective here was to assess expression phenotype changes during long-term subculture of LCLs, and its clinical significance.</P><P>Materials and methods: </P><P>We searched for genes that were differentially expressed in 17 LCLs at late (p161) passage compared to early passage (p4) using microarray assay, then validated them by real-time RT-PCR analysis. In addition, we estimated correlations between expression phenotypes of 20 LCL strains at early passage and 23 quantitative clinical traits from blood donors of particular LCL strains.</P><P>Results: </P><P>Transcript sequences of 16 genes including nuclear factor-&kgr;B (NF-&kgr;B) pathway-related genes (such as <I>PTPN13</I>, <I>HERC5</I> and miR-146a) and carcinogenesis-related genes (such as <I>XAF1</I>, <I>TCL1A</I>, <I>PTPN13</I>, <I>CD38</I> and miR-146a) were differentially expressed (>2-fold change) in at least 15 of the 17 LCL strains. In particular, <I>TC2N</I>, <I>FCRL5</I>, <I>CD180</I>, <I>CD38</I> and miR-146a were downregulated in all 17 of the evaluated LCL strains. In addition, we identified clinical trait-associated expression phenotypes in LCLs.</P><P>Conclusion: </P><P>Our results showed that LCLs acquired expression phenotype changes involving expression of NF-&kgr;B pathway- and carcinogenesis-related genes during long-term subculture. These differentially expressed genes can be considered to be a gene signature of LCL immortalization or EBV-induced carcinogenesis. Clinical trait-associated expression phenotypes should prove useful in the discovery of new candidate genes for particular traits.</P>

      • Effect of <i>CYP3A5*3</i> genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

        Park, P.-W.,Seo, Y. H.,Ahn, J. Y.,Kim, K.-A.,Park, J.-Y. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.5

        <P>Abstract</P><P>Background and Objective: </P><P>Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the <I>CYP3A5*3</I> genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the <I>CYP3A5*3</I> genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients.</P><P>Method: </P><P>The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their <I>CYP3A5</I> genotype was determined. Fourteen patients were <I>CYP3A5</I> expressors (two for <I>CYP3A5*1/*1</I> and 12 for <I>CYP3A5*1/*3</I>) and 21 patients were <I>CYP3A5</I> non-expressors (<I>CYP3A5*3/*3</I>). Dose-normalized concentrations (mean ± SD) of CBZ were 9·9 ± 3·4 ng/mL/mg for <I>CYP3A5</I> expressors and 13·1 ± 4·5 ng/mL/mg for <I>CYP3A5</I> non-expressors (<I>P</I> = 0·032). The oral clearance of CBZ was significantly higher in <I>CYP3A5</I> non-expressors than that of <I>CYP3A5</I> expressors (0·056 ±0·017 L/h/kg vs. 0·040 ± 0·014 L/h/kg, <I>P</I> = 0·004). The <I>CYP3A5</I> genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.</P>

      • <i>In vitro</i> inhibitory effects of Wen‐pi‐tang‐Hab‐Wu‐ling‐san on human cytochrome P450 isoforms

        Lee, H. W.,Kim, D. W.,Phapale, P. B.,Lim, M. ‐,S.,Park, J.,Seo, J. J.,Park, K. M.,Park, Y. ‐,K.,Yoon, Y. ‐,R. Blackwell Publishing Ltd 2011 Journal of clinical pharmacy and therapeutics Vol.36 No.4

        <P><B>Summary</B></P><P><B>What is known and Objective: </B> Although Wen‐pi‐tang‐Hab‐Wu‐ling‐san (WHW), an oriental herbal medicine, has been prescribed for the treatment of chronic renal failure (CRF) in Korean clinics, no studies regarding WHW–drug interactions had been reported. The purpose of this study was to evaluate the possibility that WHW inhibits the catalytic activities of major cytochrome P450 (CYP) isoforms.</P><P><B>Methods: </B> The abilities of various WHW extracts to inhibit phenacetin O‐de‐ethylation (CYP1A2), tolbutamide 4‐methylhydroxylation (CYP2C9), omeprazole 4′‐hydroxylation (CYP2C19), dextromethorphan O‐demethylation (CYP2D6), chlorzoxazone 6‐hydroxylation (CYP2E1) and midazolam 1‐hydroxylation (CYP3A4) were assessed using human liver microsomes.</P><P><B>Results and Discussion: </B> WHW extract at concentrations up to 100 μ<SMALL>m</SMALL> showed negligible inhibition of the six CYP isoforms tested (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4), with apparent IC<SUB>50</SUB> values (concentration of the inhibitor causing 50% inhibition of the original enzyme activity) of 817.5, 601.6, 521.7, 310.2, 342.8 and 487.0 μg/mL, respectively.</P><P><B>What is new and Conclusion: </B> Our <I>in vitro</I> findings suggest that WHW extract at concentrations corresponding to a clinically recommended dosage range has no notable inhibitory effects on CYP isoforms. Therefore, we believe that WHW extract may be free of drug–herb interactions when co‐administered with other medicines. However, <I>in vivo</I> human studies are needed to confirm these results.</P>

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