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>

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>

Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points—Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC)

Bergmeijer, Thomas O.,Reny, Jean-Luc,Pakyz, Ruth E.,Gong, Li,Lewis, Joshua P.,Kim, Eun-Young,Aradi, Daniel,Fernandez-Cadenas, Israel,Horenstein, Richard B.,Lee, Ming Ta Michael,Whaley, Ryan M.,Montane Elsevier 2018 American Heart Journal Vol.198 No.-

<P><B>Rationale</B></P> <P>The P2Y<SUB>12</SUB> receptor inhibitor clopidogrel is widely used in patients with acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke. Platelet inhibition by clopidogrel shows wide interpatient variability, and high on-treatment platelet reactivity is a risk factor for atherothrombotic events, particularly in high-risk populations. <I>CYP2C19</I> polymorphism plays an important role in this variability, but heritability estimates suggest that additional genetic variants remain unidentified. The aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify genetic determinants of clopidogrel pharmacodynamics and clinical response.</P> <P><B>Study design</B></P> <P>Based on the data published on www.clinicaltrials.gov, clopidogrel intervention studies containing genetic and platelet function data were identified for participation. Lead investigators were invited to share DNA samples, platelet function test results, patient characteristics, and cardiovascular outcomes to perform candidate gene and genome-wide studies.</P> <P><B>Results</B></P> <P>In total, 17 study sites from 13 countries participate in the ICPC, contributing individual patient data from 8,829 patients. Available adenosine diphosphate–stimulated platelet function tests included vasodilator-stimulated phosphoprotein assay, light transmittance aggregometry, and the VerifyNow P2Y<SUB>12</SUB> assay. A proof-of-principle analysis based on genotype data provided by each group showed a strong and consistent association between <I>CYP2C19</I>*2 and platelet reactivity (<I>P</I> value=5.1 × 10<SUP>−40</SUP>).</P> <P><B>Conclusion</B></P> <P>The ICPC aims to identify new loci influencing clopidogrel efficacy by using state-of-the-art genetic approaches in a large cohort of clopidogrel-treated patients to better understand the genetic basis of on-treatment response variability.</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>

Changing prevalence of upper gastrointestinal disease in 28 893 Koreans from 1995 to 2005

Kim, Jin Il,Kim, Sang Gyun,Kim, Nayoung,Kim, Jae Gyu,Shin, Sung Jae,Kim, Sang Woo,Kim, Hyun Soo,Sung, Jae Kyu,Yang, Chang Heon,Shim, Ki-Nam,Park, Seun Ja,Park, Joon Yong,Baik, Gwang Ho,Lee, Sang Woo,P Lippincott Williams Wilkins, Inc. 2009 European journal of gastroenterology & hepatology Vol.21 No.7

OBJECTIVES: Changes in the pattern of gastrointestinal diseases in a population tend to be influenced by changes in diet and lifestyle. Shifts in gastrointestinal disease from 1995 to 2005 in Korea were evaluated, retrospectively. METHODS: Seventeen nationwide medical centers participated in this study. The cross-sectional review of endoscopic findings in 28 893 patients included 8441 patients from 1995, 10 350 patients from 2000, and 10 102 patients from 2005. RESULTS: The prevalence of reflux esophagitis increased from 1.8% in 1995 to 5.9% in 2000 and 9.1% in 2005 (P<0.001, the P value was only for the comparison between 1995 and 2005, the followings were as same). The prevalence of peptic ulcer diseases was 18.0% in 1995, 19.1% in 2000, and 20.2% in 2005 (P<0.001). Although no significant differences were noted in duodenal ulcers (8.4, 8.7, and 8.2%, P=0.449), gastric ulcers showed an increasing trend (9.6, 10.5, and 12.0%, P<0.001). The prevalence of gastric cancer increased from 3.4% in 1995 to 4.5% in 2000 (P<0.001), but then decreased to 2.4% in 2005 (P<0.001). The incidence of advanced gastric cancer was 2.5, 3.2, and 1.3%, respectively (P<0.001), and that of early gastric cancer remained constant with rates of 0.8%, 1.3, and 1.1%, respectively (P=0.056). CONCLUSION: The cross-sectional review of data collected in 1995, 2000, and 2005 showed an increase in reflux esophagitis and peptic ulcer diseases. Meanwhile, the prevalence of gastric cancer increased until 2000, but decreased in 2005.

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>

Photoswitching and photocatalytic functions of Sn_xCu_1−xS nanostructures

Ilanchezhiyan, P.,Kumar, G. Mohan,Siva, C.,Venkatasubbu, G. Devanand,Kang, T.W.,Kim, D.Y. Elsevier 2019 APPLIED SURFACE SCIENCE - Vol.489 No.-

<P><B>Abstract</B></P> <P>Ultra-thin semiconducting nanostructures are garnering strategic importance in energy and environment remediation applications. In this regard, Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were processed through an eco-friendly chemical route and investigated in detail for photoswitching and photocatalytic functions. X-ray diffraction, FT-IR, Raman, UV–vis absorbance and high-resolution microscopic tools were initially used to examine the physico-chemical traits of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures. Ambiguous evidence for the substitution of Sn ions in place of Cu ions was attained through X-ray photoelectron spectroscopy. The photocatalytic performance of Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S systems was investigated through effective remediation of organic dye molecules under visible light. Scavenger based photocatalytic experiments were additionally carried out to infer the degradation mechanism. Type II <I>p-n</I> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/In<SUB>2</SUB>S<SUB>3</SUB> heterojunction diodes were also demonstrated for the first time with improved electrical conductivity and photoelectrical performances. The rectification ratio, forward current values and photo switching capabilities of these diodes were noted to improve in the Current vs. Voltage (I-V) and Current vs. Time (I-T) curves as a function of Sn composition and applied bias potential. The excellent photo switching stability augments the photo generated carriers to be effectively separated along the p-n junctions. The enhanced photoelectronic and photocatalytic functionalities in Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S has finally been reasoned to the improved charge transfer kinetics in the respective architectures, resulting from the effective Sn interaction in hexagonal host lattice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S nanostructures were fabricated by hydrothermal route. </LI> <LI> The nanostructures exhibited excellent photocatalytic activity under visible light. </LI> <LI> Sn interaction in hexagonal host lattice promoted their photocatalytic performance. </LI> <LI> p-Sn<SUB>x</SUB>Cu<SUB>1−x</SUB>S/n-In<SUB>2</SUB>S<SUB>3</SUB> diodes demonstrated improved photoswitching performance. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Crystallization Modes of Poly(3-dodecylthiophene)-Based Block Copolymers Depend on Regioregularity and Morphology

Coote, Jonathan P.,Kim, Jin-Seong,Lee, Byeongdu,Han, Junghun,Kim, Bumjoon J.,Stein, Gila E. American Chemical Society 2018 Macromolecules Vol.51 No.22

<P>Conjugated block copolymers (BCPs) can self-assemble into highly ordered nanostructures in a melt state. However, when cooled below the melting temperature, crystal growth can disrupt the self-assembled structure and produce a poorly ordered fibrillar texture. We demonstrate that crystallization modes of conjugated BCPs based on poly(3-dodecylthiophene) (P3DDT) and poly(2-vinylpyridine) (P2VP) can be tuned through P3DDT regioregularity (RR), as this attribute controls the melting temperature and crystallization rates of P3DDT. When RR is low (70-80%), crystallization is observed at temperatures near or below the glass transition of P2VP, so crystal growth is largely confined by the glassy cylindrical or lamellar BCP structure. When RR is high (94%), crystallization occurs at 40 K above the glass transition of P2VP, so there is no longer a restriction of glassy domains. Importantly, crystal growth remains confined by the rubbery P2VP lamellae, but breaks through the rubbery P2VP cylinders. This morphology-dependent behavior is attributed to geometric compatibility of P3DDT crystal growth and the self-assembled symmetry. In a lamellar phase, the P3DDT chain orientations at the P3DDT-<I>block</I>-P2VP interface are compatible with crystal growth, and both the alkyl-stacking and π-π growth directions are unrestricted within a lamellar sheet. In a cylindrical phase, the radial orientation of P3DDT chains at the P3DDT-<I>block</I>-P2VP interface is not compatible with crystal growth, and the hexagonal close-packed symmetry only allows for one direction of unrestricted crystal growth. Significantly, these studies demonstrate that tuning RR of polyalkylthiophenes can open up multiple crystallization modes with the same monomer chemistries and block lengths, thereby decoupling the parameters that govern classical BCP self-assembly and crystal growth.</P> [FIG OMISSION]</BR>

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>