Foxp3 is a key downstream regulator of p53-mediated cellular senescence

Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2

<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>

Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

Kim, J C,Ha, Y J,Roh, S A,Choi, E Y,Yoon, Y S,Kim, K P,Hong, Y S,Kim, T W,Cho, D H,Kim, S Y,Kim, Y S Nature Publishing Group 2013 The British journal of cancer Vol.108 No.9

<P><B>Background:</B></P><P>Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy.</P><P><B>Methods:</B></P><P>A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway.</P><P><B>Results:</B></P><P>For cetuximab regimens, patients homozygous for the wild-type alleles (<I>GG</I>) of <I>LIFR rs3729740</I> exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (<I>GA</I> and <I>AA</I>; <I>P</I>=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (<I>TT</I>) of <I>ANXA11 rs1049550</I> exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (<I>CC</I> and <I>CT</I>; <I>P</I>=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type <I>LIFR rs3729740</I> patients either with wild-type <I>KRAS</I> or skin toxicity (<I>P</I>=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type <I>LIFR rs3729740</I> (<I>P</I>=0.044) and in those expressing minor-type <I>ANXA11 rs1049550</I> (<I>P</I>=0.007), respectively.</P><P><B>Conclusion:</B></P><P><I>LIFR rs3729740</I> and possibly <I>ANXA11 rs1049550</I> may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.</P>

알칼리장석-일라이트가 육용오리의 생산성 및 육질에 미치는 영향

국길,김정은,정진형,김재필,선상수,김광현,정완태,정광화,안종남,이병석,정일병,양철주,양재은,Kook K.,Kim J. E.,Jeong J. H.,Kim J. P.,Sun S. S.,Kim K. H.,Jeong Y. T.,Jeong K. H.,Ahn J. N.,Lee B. S.,Jeong I. B.,Yang C. J.,Yang J. E. 한국가금학회 2005 韓國家禽學會誌 Vol.32 No.4

본 연구는 3주령의 육용오린 사료에 알칼리장석-일라이트를 0, 0+ 항생제, 0.5, 1.0 및 $1.5\%$ 첨가한 5처리구에 3반복으로 각각 12수씩 배치하여 43일간 급여하여 생산성 및 육질에 미치는 영향을 알아보고자 실행하였다. 육성오리의 일당 증체량은 알칼리장석-일라이트 1.0와 $1.5\%$ 첨가구에서 약간 증가하였다(p>0.05). 사료섭취 량은 알칼리장석-일라이트 첨가구에서 증가하는 경향이었다(p>0.05). 혈중 글루코스 농도는 알칼리장석-일라이트 $0.5\%$ 처리구에서 약간 감소한 반면에(p>0.05) 혈중 요소태 질소 함량은 알칼리장석-일라이트 $0.5\%$ 첨가구에서 유의적으로 증가하였다(p<0.05). 콜레스테롤 함량은 알칼리장석-일라이트 $0.5\%$ 첨가구에서 유의적으로 감소하였다(p<0.05). 도체중과 도체율은 알칼리장석-일라이트 첨가수준에 따라 증가하는 경향이었다(p>0.05). 알칼리 장석-일라이트 급여에 의한 육용오리 가슴육의 조지방 함량은 알칼리장석-일라이트 $1.5\%$ 첨가구에서는 유의적으로 감소하였다(p<0.05). 육색의 명도와 황색도는 알칼리장석-일라이트에서 높게 나타났으며(p>0.05), 콜레스테롤 함량은 알칼리장석-일라이트 첨가구에서 감소하였다(p>0.05). 지방산 패도는 알칼리장석-일라이트 첨가구에서 약간 감소하였다(p>0.05). 알칼리장석-일라이트 첨가에 의한 포화지방산 비율이 약간감소하는 경향인 반면에 불포화지방산 비율이 약간 증가하는 경향을 나타내었으나 유의적인 차이는 없었다(p>0.05). 알칼리장석-일라이트 첨가에 의한 육성오리 간의 중금속 함량은 납 축적량이 비교적 높게 나타났다(p>0.05). 관능 평가(appearance)에서 알칼리장석-일라이트 1.0와 $1.5\%$ 첨가구에서 외관의 유의적인 개선 효과를 나타내었다 (p<0.05). 이상의 결과를 종합해 볼 때 육성오리에 대한 알칼리장석-일라이트 급여는 증체량의 개선효과와 더불어 가슴육의 조지방 함량의 감소 그리고 관능평가에서 외관의 개선 효과가 있음을 알 수 있었다. This experiment was conducted to investigate the effect of the supplemental alkali feldspar-ilite(feldspar) on growth performance and meat quality in broiler ducks for 43 days. One hundred eighty broiler ducks were divided into 5 groups of 12ducks. Dietary levels of feldspar 0, 0+antibiotics, 0.5, 1.0 and $1.5\%$ were added to experimental diets of each of the groups. Daily weight gain was slightly increased in 1.0 and $1.5\%$ feldspar treatments. Feed intake was slightly increased at all feldspar treatments. Glucose concentration of serum profile was decreased whereas BUN concentration was significantly increased (p<0.05) at $0.5\%$ feldspar. Cholesterol concentration was decreased at all feldspar treatments, this difference was especially observed in supplemental levels of $0.5\%$ feldspar(p<0.05). Carcass weight was increased at all feldspar treatments. Moisture and crude fat contents of proximate chemical composition in duck meat were decreased at all feldspar treatment, this difference especially was observed in supplemental levels of $1.5\%$ feldspar(p<0.05) on crude fat content. Lightness and yellowness was increased at all feldspar treatment. Cholesterol contents and TBA in meat were decreased, but this parameters were not difference by feldspar treatment. The composition of saturated fatty acids(SFA) was decreased, whereas unsaturated fatty acids(USFA) was slightly increased by feldspar treatment. The Pb content of heavy metal concentrations was increased with compared control, but not difference. The appearance of sensory evaluation was improved by supplemental feldspar, especially in supplemental feldspar, 1.0 and $1.5\%$(p<0.05). The results of this study indicate that the supplemental alkali feldspar may improve the production and meat quality of broiler ducks.

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN

Hong, S-W,Moon, J-H,Kim, J-S,Shin, J-S,Jung, K-A,Lee, W-K,Jeong, S-Y,Hwang, J J,Lee, S-J,Suh, Y-A,Kim, I,Nam, K-Y,Han, S,Kim, J E,Kim, K-p,Hong, Y S,Lee, J-L,Lee, W-J,Choi, E K,Lee, J S,Jin, D-H,Kim, Macmillan Publishers Limited 2014 CELL DEATH AND DIFFERENTIATION Vol.21 No.1

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.

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>

White light emission of dysprosium doped lanthanum calcium phosphate oxide and oxyfluoride glasses

Luewarasirikul, N.,Kim, H.J.,Meejitpaisan, P.,Kaewkhao, J. Elsevier 2017 Optical materials Vol.66 No.-

<P><B>Abstract</B></P> <P>Lanthanum calcium phosphate oxide and oxyfluoride glasses doped with dysprosium oxide were prepared by melt-quenching technique with chemical composition 20La<SUB>2</SUB>O<SUB>3</SUB>:10CaO:69P<SUB>2</SUB>O<SUB>5</SUB>:1Dy<SUB>2</SUB>O<SUB>3</SUB> and 20La<SUB>2</SUB>O<SUB>3</SUB>:10CaF<SUB>2</SUB>:69P<SUB>2</SUB>O<SUB>5</SUB>:1Dy<SUB>2</SUB>O<SUB>3</SUB>. The physical, optical and luminescence properties of the glass samples were studied to evaluate their potential to using as luminescence materials for solid-state lighting applications. The density, molar volume and refractive index of the glass samples were carried out. The optical and luminescence properties were studied by investigating absorption, excitation, and emission spectra of the glass samples. The absorption spectra were investigated in the UV–Vis–NIR region from 300 to 2000 nm. The excitation spectra observed under 574 nm emission wavelength showed the highest peak centered at 349 nm (<SUP>6</SUP>H<SUB>15/2</SUB> → <SUP>6</SUP>P<SUB>7/2</SUB>). The emission spectra, excited with 349 nm excitation wavelength showed two major peaks corresponding to 482 nm blue emission (<SUP>4</SUP>F<SUB>9/2</SUB> → <SUP>6</SUP>H<SUB>15/2</SUB>) and 574 nm yellow emission (<SUP>4</SUP>F<SUB>9/2</SUB> → <SUP>6</SUP>H<SUB>13/2</SUB>). The experimental lifetime were found to be 0.539 and 0.540 for oxide and oxyfluoride glass sample, respectively. The x,y color coordinates under 349 nm excitation wavelength were (0.38, 0.43) for both glass samples, that be plotted in white region of CIE 1931 chromaticity diagram. The CCT values obtained from the glass samples are 4204 K for oxide glass and 4228 K for oxyfluoride glass corresponding to the commercial cool white light (3100–4500 K). Judd-Ofelt theory had also been employed to obtain the J-O parameters (Ω<SUB>2</SUB>, Ω<SUB>4</SUB> and Ω<SUB>6</SUB>), oscillator strength, radiative transition possibility, stimulated emission cross section and branching ratio. The Ω<SUB>2</SUB> > Ω<SUB>4</SUB> > Ω<SUB>6</SUB> trend of J-O parameters of both glass samples may indicate the good quality of a glass host for using as optical device application. Temperature dependence of emission spectra was studied from 300 K to 10 K and found that the intensity of the emission peak was found to be increased with decreasing of the temperature. The results of the investigations in this work confirmed that the present Dy-doped lanthanum calcium phosphate oxide and oxyfluoride glasses perform high potential for using as efficient luminescence materials for solid-state lighting applications, especially for white LEDs. Furthermore, the oxyfluoride glass sample provides more luminescence potential than the oxide glass sample.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Lanthanum calcium phosphate oxide and oxyfluoride glasses doped with Dy<SUP>3+</SUP> were studied. </LI> <LI> Emission spectra showed two major peaks corresponding to 482 and 574 nm. </LI> <LI> Both glasses corresponding to the commercial cool white light (3100–4500 K). </LI> <LI> Judd-Ofelt theory had also been employed to obtain the J-O parameters. </LI> <LI> Oxyfluoride glass provides more luminescence potential than the oxide glass. </LI> </UL> </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>

Beijing urban particulate matter-induced injury and inflammation in human lung epithelial cells and the protective effects of fucosterol from <i>Sargassum binderi</i> (Sonder ex J. Agardh)

Fernando, I.P. Shanura,Jayawardena, Thilina U.,Kim, Hyun-Soo,Lee, Won Woo,Vaas, A.P.J.P.,De Silva, H.I.C.,Abayaweera, G.S.,Nanayakkara, C.M.,Abeytunga, D.T.U.,Lee, Dae-Sung,Jeon, You-Jin Academic Press 2019 Environmental research Vol.172 No.-

<P><B>Abstract</B></P> <P>Particulate matter (PM) air pollution has gradually become a widespread problem in East Asia. PM may cause unfamiliar inflammatory responses, oxidative stress, and pulmonary tissue damage, and a comprehensive understanding of the underlying mechanisms is required in order to develop effective anti-inflammatory agents. In this study, fine dust collected from Beijing, China (CPM) (size < PM13 with majority < PM2.5) was evaluated for its oxidative stress- and inflammation-inducing effects, which cause cell damage, in A459 human lung epithelial cells. Oxidative stress was marked by an increase in intracellular ROS levels and the production of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1). Upon induction of oxidative stress, a marked increase was observed in the expression of key inflammatory mediators such as COX-2 and PGE<SUB>2</SUB> and the pro-inflammatory cytokines TNF-α and IL-6 via NF-kB and MAPK pathways. Cellular damage was marked by a reduction in viability, increased lactate dehydrogenase (LDH) release, formation of apoptotic and necrotic bodies, accumulation of sub-G1 phase cells, and DNA damage. Apoptosis was found to be mediated via the activation of caspases through the mitochondria-mediated pathway. Fucosterol, purified from the brown alga <I>Sargassum binderi</I> (Sonder ex J. Agardh) by bio-assay-guided fractionation and purification, exhibited potential therapeutic effects against CPM-induced detrimental effects. Further studies could focus on developing fucosterol, in forms such as steroidal inhalers, against PM-induced pulmonary tissue inflammation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Fine dust air pollution is a major reason of pulmonary complications in East Asia. </LI> <LI> Dust particles induce oxidative stress and inflammation damaging the lung epithelial cells. </LI> <LI> Fucosterol suppressed the dust induced cell damage by inhibiting oxidative stress and inflammation. </LI> <LI> Fucosterol may have beneficial effects in alleviating adverse respiratory effects of air pollution. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Toward high efficiency organic photovoltaic devices with enhanced thermal stability utilizing P3HT-b-P3PHT block copolymer additives

Zhu, M.,Kim, H.,Jang, Y.,Park, S.,Ryu, D.,Kim, K.,Tang, P.,Qiu, F.,Kim, D.,Peng, J. Royal Society of Chemistry 2016 Journal of Materials Chemistry A Vol.4 No.47

<P>Organic photovoltaics (OPVs) have drawn an extensive amount of attention due to their low cost, processibility and flexibility. However, a cell based on a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C-61-butyric acid methyl ester (PC61BM) has a limited power conversion efficiency (PCE) due to the short exciton diffusion length of similar to 10 nm. We address this issue by designing a series of all-conjugated diblock copolymers, poly(3-hexylthiophene)-b-poly(3-(6-diethylphosphonatohexyl) thiophene) (P3HT-b-P3PHT), intended for use as additives to improve the performance of P3HT:PC61BM-based photovoltaic devices. The PCE of the devices improved from 3.30% to 4.03% with the addition of P3HT-b-P3PHT (3 : 1). The thermal stability of devices with P3HT-b-P3PHT additives improved significantly relative to that of the P3HT:PC61BM reference device, where the devices including a copolymer with a higher P3PHT content exhibited a better thermal stability. It was found that the fill factor (FF) could be regulated by simply varying the block ratio of P3HT-b-P3PHT and played a crucial role in improving both the PCE and the thermal stability. The P3HT-b-P3PHT diffused at the P3HT:PC61BM interface, improved the miscibility between P3HT and PC61BM, optimized the nanoscale morphology of the photoactive layer, and reduced the active layer roughness, all of which improved the FF and thus contributed to an improvement in device performance.</P>

Isostructural metal-insulator transition in VO₂

Lee, D.,Chung, B.,Shi, Y.,Kim, G.-Y.,Campbell, N.,Xue, F.,Song, K.,Choi, S.-Y.,Podkaminer, J. P.,Kim, T. H.,Ryan, P. J.,Kim, J.-W.,Paudel, T. R.,Kang, J.-H.,Spinuzzi, J. W.,Tenne, D. A.,Tsymbal, E. Y. American Association for the Advancement of Scienc 2018 Science Vol.362 No.6418

<P><B>Separating structure and electrons in VO<SUB>2</SUB></B></P><P>Above 341 kelvin—not far from room temperature—bulk vanadium dioxide (VO<SUB>2</SUB>) is a metal. But as soon as the material is cooled below 341 kelvin, VO<SUB>2</SUB> turns into an insulator and, at the same time, changes its crystal structure from rutile to monoclinic. Lee <I>et al.</I> studied the peculiar behavior of a heterostructure consisting of a layer of VO<SUB>2</SUB> placed underneath a layer of the same material that has a bit less oxygen. In the VO<SUB>2</SUB> layer, the structural transition occurred at a higher temperature than the metal-insulator transition. In between those two temperatures, VO<SUB>2</SUB> was a metal with a monoclinic structure—a combination that does not occur in the absence of the adjoining oxygen-poor layer.</P><P><I>Science</I>, this issue p. 1037</P><P>The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.</P>