Phytonutrients Differentially Stimulate NAD(P)H:Quinone Oxidoreductase, Inhibit Proliferation, and Trigger Mitotic Catastrophe in Hepa1c1c7 Cells

Steven J.T. Jackson,Keith W. Singletary,Laura L. Murphy,Richard C. Venema,Andrew J. Young 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.1

Phytonutrients have rapidly emerged as natural food chemicals possessing multifaceted biological actions thatmay support beneficial health outcomes. Among the vast array of phytonutrients currently being studied, sulforaphane, curcumin, quercetin, and resveratrol have been frequently reported to stimulate the expression of endogenous detoxification enzymes and may thereby facilitate the neutralization of otherwise harmful environmental agents. Some of these same phytonutrients, however, have also been implicated in disrupting normal cell proliferation and hence may possess toxic properties in and of themselves. In this study, we characterize the respective minimum threshold concentrations of the aforementioned phytonutrients in Hepa1c1c7 cells that stimulate NAD(P)H:quinone oxidoreductase (NQO1), a key enzyme in the hepatic neutralization of menadione, other biological oxidants, and some environmental carcinogens. Moreover, our findings demonstrate that relatively low concentrations of either sulforaphane or curcumin significantly (P < .05) increase NQO1 protein expression and activity without triggering G2/M cell cycle arrest or mitotic catastrophe. The minimal quercetin concentration inducing NQO1, however, was 100-fold higher than that which disrupted mitosis. Also, while resveratrol modestly stimulated NQO1, the minimally effective resveratrol concentration concomitantly induced evidence of cellular apoptosis. Taken together, these findings indicate that only particular phytonutrients are likely efficacious in upregulating NQO1 activity without also leading to hepatic cytotoxicity.

IFN-γ-indoleamine-2,3 dioxygenase acts as a major suppressive factor in 4-1BB-mediated immune suppression in vivo

Kim, Young H.,Choi, Beom K.,Kang, Woo J.,Kim, Kwang H.,Kang, Sang W.,Mellor, Andrew L.,Munn, David H.,Kwon, Byoung S. Wiley (John WileySons) 2009 Journal of leukocyte biology Vol.85 No.5

<P>It has been reported that 4-1BB triggering in vivo selectively suppressed the recall response of staphylococcal enterotoxin A (SEA)-specific CD4(+) T cells, in which CD8(+) T-derived TGF-beta was involved. Here, we have examined an alternative mechanism for the 4-1BB-mediated CD4(+) T suppression, as the neutralization of TGF-beta is only effective in rescuing the SEA-specific recall response at high cellular concentrations. We show that this selective suppression of CD4(+) T cells by 4-1BB triggering in vivo is mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO) in an IFN-gamma-dependent manner. SEA-specific CD4(+) T responses were suppressed partly by TGF-beta-expressing CD8(+) T cells, particularly CD11c(+)CD8(+) T cells, but strongly inhibited by dendritic cells (DCs) expressing IDO. IFN-gamma that increased IDO in DCs was produced primarily from CD11c(+)CD8(+) T cells, which were expanded selectively by 4-1BB stimulation. CD4(+), CD8(+), and plasmacytoid DCs exerted a similar suppressive activity toward the SEA-specific CD4(+) T cells. Neutralization of IFN-gamma or IDO activity in vivo largely reversed the 4-1BB-mediated CD4(+) T suppression. Collectively, these data indicate that 4-1BB-dependent suppression of SEA-specific CD4(+) T responses was mediated mainly by IFN-gamma-dependent IDO induction and partially by TGF-beta.</P>

Thermoset polyester droplet-based microfluidic devices for high frequency generation

Kim, Jin-young,deMello, Andrew J.,Chang, Soo-Ik,Hong, Jongin,O'Hare, Danny Royal Society of Chemistry 2011 Lab on a chip Vol.11 No.23

<P>The vast majority of droplet-based microfluidic devices are made from polydimethylsiloxane (PDMS). Unfortunately PDMS is not suitable for high frequency droplet generation at high operating pressure due to its low shear modulus. In this paper, we report the fabrication and testing of microfluidic devices using thermoset polyester (TPE). The optical characteristics of the fabricated devices were assessed and substrate resistance to pressure also investigated. TPE devices bonded using an O<SUB>2</SUB> plasma treated PET substrate at 76 °C were shown to function efficiently at pressures up to 18 MPa. TPE material retains many of the attractive features of PDMS such as ease of fabrication but significantly, has superior mechanical properties. The improved resistance of TPE to high pressures enabled investigation of high frequency droplet generation as a function of a wide range of flow-rates with three different oils as continuous phase.</P> <P>Graphic Abstract</P><P>Droplet-based microfluidic devices to withstand high pressure have been successfully fabricated using thermoset polyester (TPE) materials for high frequency generation of droplets. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1lc20603f'> </P>

The sweet potato <i>IbMYB1</i> gene as a potential visible marker for sweet potato intragenic vector system

Kim, Cha Young,Ahn, Young Ock,Kim, Sun Ha,Kim, Yun-Hee,Lee, Haeng-Soon,Catanach, Andrew S.,Jacobs, Jeanne M. E.,Conner, Anthony J.,Kwak, Sang-Soo Blackwell Publishing Ltd 2010 Physiologia plantarum Vol.139 No.3

<P>MYB transcription factors play important roles in transcriptional regulation of many secondary metabolites including anthocyanins. We cloned the R2R3-MYB type <I>IbMYB1</I> complementary DNAs from the purple-fleshed sweet potato (<I>Ipomoea batatas</I> L. cv Sinzami) and investigated the expression patterns of <I>IbMYB1</I> gene with <I>IbMYB1a</I> and <I>IbMYB1b</I> splice variants in leaf and root tissues of various sweet potato cultivars by reverse transcription-polymerase chain reaction. The transcripts of <I>IbMYB1</I> were predominantly expressed in the purple-fleshed storage roots and they were also detectable in the leaf tissues accumulating anthocyanin pigments. In addition, transcript levels of <I>IbMYB1</I> gene were up-regulated by treatment with methyl jasmonate or salicylic acid in leaf and root tissues of cv. White Star. To set up the intragenic vector system in sweet potato, we first evaluated the utilization of the <I>IbMYB1</I> gene as a visible selectable marker. The <I>IbMYB1a</I> was transiently expressed in tobacco leaves under the control of a constitutive cauliflower mosaic virus <I>35S</I> promoter, a root-specific and sucrose-inducible sporamin promoter, and an oxidative stress-inducible sweet potato anionic peroxidase2 promoter. We also showed that overexpression of <I>IbMYB1a</I> induced massive anthocyanin pigmentation in tobacco leaves and up-regulated the transcript levels of the structural genes in anthocyanin biosynthetic pathway. Furthermore, high-performance liquid chromatography analysis revealed that the expression of <I>IbMYB1a</I> led to production of cyanidin as a major core molecule of anthocyanidins in tobacco leaves. These results suggest that the <I>IbMYB1</I> gene can be applicable to a visible marker for sweet potato transformation with intragenic vectors, as well as the production of anthocyanin as important nutritive value in other plant species.</P>

Stitched α-Helical Peptides via Bis Ring-Closing Metathesis

Hilinski, Gerard J.,Kim, Young-Woo,Hong, Jooyeon,Kutchukian, Peter S.,Crenshaw, Charisse M.,Berkovitch, Shaunna S.,Chang, Andrew,Ham, Sihyun,Verdine, Gregory L. American Chemical Society 2014 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.136 No.35

<P>Conformationally stabilized α-helical peptides are capable of inhibiting disease-relevant intracellular or extracellular protein–protein interactions <I>in vivo</I>. We have previously reported that the employment of ring-closing metathesis to introduce a single all-hydrocarbon staple along one face of an α-helical peptide greatly increases α-helical content, binding affinity to a target protein, cell penetration through active transport, and resistance to proteolytic degradation. In an effort to improve upon this technology for stabilizing a peptide in a bioactive α-helical conformation, we report the discovery of an efficient and selective bis ring-closing metathesis reaction leading to peptides bearing multiple contiguous staples connected by a central spiro ring junction. Circular dichroism spectroscopy, NMR, and computational analyses have been used to investigate the conformation of these “stitched” peptides, which are shown to exhibit remarkable thermal stabilities. Likewise, trypsin proteolysis assays confirm the achievement of a structural rigidity unmatched by peptides bearing a single staple. Furthermore, fluorescence-activated cell sorting (FACS) and confocal microscopy assays demonstrate that stitched peptides display superior cell penetrating ability compared to their stapled counterparts, suggesting that this technology may be useful not only in the context of enhancing the drug-like properties of α-helical peptides but also in producing potent agents for the intracellular delivery of proteins and oligonucleotides.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-35/ja505141j/production/images/medium/ja-2014-05141j_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja505141j'>ACS Electronic Supporting Info</A></P>

Integration of monolithic porous polymer with droplet-based microfluidics on a chip for nano/picoliter volume sample analysis

Kim Jin-young,Chang Soo-Ik,deMello Andrew J,O’Hare Danny 나노기술연구협의회 2014 Nano Convergence Vol.1 No.3

In this paper, a porous polymer nanostructure has been integrated with droplet-based microfluidics in a single planar format. Monolithic porous polymer (MPP) was formed selectively within a microfluidic channel. The resulting analyte bands were sequentially comartmentalised into droplets. This device reduces band broadening and the effects of post-column dead volume by the combination of the two techniques. Moreover it offers the precise control of nano/picoliter volume samples. Background

A critical role of SHP-1 in regulation of type 2 inflammation in the lung.

Oh, Sun Young,Zheng, Tao,Kim, Yoon-Keun,Cohn, Lauren,Homer, Robert J,McKenzie, Andrew N J,Zhu, Zhou The Association 2009 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR Vol.40 No.5

<P>Asthma is a chronic inflammatory disorder of the airways. Type 2 T helper (Th) cell-dominated inflammation in the lung is a hallmark of asthma. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 is a negative regulator in the signaling pathways of many growth factor and cytokine receptors. However, a direct role of SHP-1 in the IL-4/IL-13 signaling pathway has not been established. In this study, we sought to define the function of SHP-1 in the lung by characterizing the pulmonary inflammation of viable motheaten (mev) mice, and to investigate the molecular mechanisms involved. Pulmonary histology, physiology, and cytokine expression of mev mice were analyzed to define the nature of the inflammation, and the gene-deletion approach was used to identify critical molecules involved. In mev mice, we observed spontaneous Th2-like inflammatory responses in the lung, including eosinophilia, mucus metaplasia, airway epithelial hypertrophy, pulmonary fibrosis, and increased airway resistance and airway hyperresponsiveness. The pulmonary phenotype was accompanied by up-regulation of Th2 cytokines and chemokines. Selective deletion of IL-13 or signal transducer and activator of transcription 6, key genes in the Th2 signaling pathway, significantly reduced, but did not completely eliminate, the inflammation in the lung. These findings suggest that SHP-1 plays a critical role in regulating the IL-4/IL-13 signaling pathway and in maintaining lung homeostasis.</P>

NEUROD1 Intrinsically Initiates Differentiation of Induced Pluripotent Stem Cells into Neural Progenitor Cells

Choi, Won-Young,Hwang, Ji-Hyun,Cho, Ann-Na,Lee, Andrew J.,Jung, Inkyung,Cho, Seung-Woo,Kim, Lark Kyun,Kim, Young-Joon Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.12

Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies. However, there is scarce information on which DNA regions are modified during induced pluripotent stem cell (iPSC) to neuronal progenitor cell (NPC) differentiation, the cis regulatory factors that attach to these accessible regions, or the genes that are initially expressed. In this study, we identified the DNA accessible regions of iPSCs and NPCs via the Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). We identified which chromatin regions were modified after neuronal differentiation and found that the enhancer regions had more active histone modification changes than the promoters. Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Finally, by using Hi-C data, we categorized the genes that directly interacted with the enhancers under the control of NEUROD1 during iPSC to NPC differentiation.

Terahertz-Triggered Phase Transition and Hysteresis Narrowing in a Nanoantenna Patterned Vanadium Dioxide Film

Thompson, Zachary J.,Stickel, Andrew,Jeong, Young-Gyun,Han, Sanghoon,Son, Byung Hee,Paul, Michael J.,Lee, Byounghwak,Mousavian, Ali,Seo, Giwan,Kim, Hyun-Tak,Lee, Yun-Shik,Kim, Dai-Sik American Chemical Society 2015 NANO LETTERS Vol.15 No.9

<P>We demonstrate that high-field terahertz (THz) pulses trigger transient insulator-to-metal transition in a nanoantenna patterned vanadium dioxide thin film. THz transmission of vanadium dioxide instantaneously decreases in the presence of strong THz fields. The transient THz absorption indicates that strong THz fields induce electronic insulator-to-metal transition without causing a structural transformation. The transient phase transition is activated on the subcycle time scale during which the THz pulse drives the electron distribution of vanadium dioxide far from equilibrium and disturb the electron correlation. The strong THz fields lower the activation energy in the insulating phase. The THz-triggered insulator-to-metal transition gives rise to hysteresis loop narrowing, while lowering the transition temperature both for heating and cooling sequences. THz nanoantennas enhance the field-induced phase transition by intensifying the field strength and improve the detection sensitivity via antenna resonance. The experimental results demonstrate a potential that plasmonic nanostructures incorporating vanadium dioxide can be the basis for ultrafast, energy-efficient electronic and photonic devices.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/nalefd/2015/nalefd.2015.15.issue-9/acs.nanolett.5b01970/production/images/medium/nl-2015-01970q_0007.gif'></P>

The effects of food safety education on adolescents' hand hygiene behavior: an analysis of stages of change

Eun Joo Kim,Andrew J. Pai,Nam-E Kang,Woo Kyoung Kim,Young Soon Kim,Hyun-Kyung Moon,Ae Wha Ha 한국영양학회 2012 Nutrition Research and Practice Vol.6 No.2

The hand hygiene behavior of 400 middle school students (grades 1-3) in Seoul and Gyeonggi-Do was studied to determine how stages of change were affected by food safety education, focusing on hand hygiene and general food safety. Subjects were 51.3% male and 44.3% of study subjects were first graders of middle school. Approximately 40% of subjects were at the stage of action, 42.7% were at the stage of contemplation, and 16.4% were at pre-contemplation. The most important factor that influenced proper hand washing was self efficacy (P < 0.001). Proper hand washing was also correlated significantly with positive belief (P < 0.01) and stages of change (P < 0.01). After food safety education by high-school mentors, middle-school students who were in the stages of pre-contemplation (11.1%) and contemplation (88.9%) showed significant progression toward the action stage (P < 0.001). Proper hand washing (P < 0.01) and food safety knowledge (P < 0.05) were also significantly increased after educational intervention.