Gα₁₂ gep oncogene deregulation of p53-responsive microRNAs promotes epithelial–mesenchymal transition of hepatocellular carcinoma

Yang, Y M,Lee, W H,Lee, C G,An, J,Kim, E-S,Kim, S H,Lee, S-K,Lee, C H,Dhanasekaran, D N,Moon, A,Hwang, S,Lee, S J,Park, J-W,Kim, K M,Kim, S G Macmillan Publishers Limited 2015 Oncogene Vol.34 No.22

Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα<SUB>12</SUB> gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα<SUB>12</SUB> overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα<SUB>12</SUB> expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα<SUB>12</SUB> (Gα<SUB>12</SUB>QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα<SUB>12</SUB> gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα<SUB>12</SUB>. Decreases of miR-200a/b, -192 and -215 by Gα<SUB>12</SUB> caused ZEB1 induction. The ability of Gα<SUB>12</SUB> to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα<SUB>12</SUB>QL induced ZEB1 and other epithelial–mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα<SUB>12</SUB>QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα<SUB>12</SUB> decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα<SUB>12</SUB> level, a correlation existed in the comparison of relative changes of Gα<SUB>12</SUB> and ZEB1. In conclusion, Gα<SUB>12</SUB> overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial–mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα<SUB>12</SUB> upregulation in liver tumor progression, implicating Gα<SUB>12</SUB> as an attractive therapeutic target.

Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes

Hwang, H.J.,Jung, T.W.,Ryu, J.Y.,Hong, H.C.,Choi, H.Y.,Seo, J.A.,Kim, S.G.,Kim, N.H.,Choi, K.M.,Choi, D.S.,Baik, S.H.,Yoo, H.J. North-Holland 2014 Molecular and cellular endocrinology Vol.392 No.1

The direct effects of dipeptidyl peptidase-IV (DPP-IV) inhibitors on endoplasmic reticulum (ER) stress-induced apoptosis and inflammation in cardiomyocytes have not been elucidated. H9c2 cell viability, which was reduced by tunicamycin, was increased after DPP-IV inhibitor gemigliptin treatment. Gemigliptin significantly decreased the tunicamycin-mediated increase in glucose regulated protein 78 (GRP78) expression and ER stress-mediated signaling molecules such as protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C-EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α)/c-Jun N-terminal kinase (JNK)-p38. Furthermore, gemigliptin effectively induced Akt phosphorylation in a dose-dependent manner. Using flow cytometry and Hoechst staining, we showed that treatment with Akt inhibitor significantly blocked the anti-apoptotic effects mediated by gemigliptin. The reduction in tunicamycin-induced GRP78 level and PERK/CHOP pathway activity by gemigliptin was reversed after treatment with Akt inhibitor. In conclusion, gemigliptin effectively inhibited ER stress-induced apoptosis and inflammation in cardiomyocytes via Akt/PERK/CHOP and IRE1α/JNK-p38 pathways, suggesting its direct protective role in cardiovascular diseases.

Effect of the Length of Feed Withdrawal on Weight Loss, Yield and Meat Color of Broiler

Kim, D.H.,Yoo, Y.M.,Kim, S.H.,Jang, B.G.,Park, B.Y.,Cho, S.H.,Seong, P.N.,Hah, K.H.,Lee, J.M.,Kim, Y.K.,Hwang, I.H. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.1

The current study was conducted to determine the optimum length of feed withdrawal for pre-harvest broilers. A total of three hundred broilers were sampled from an industrial population, and 30 chicks for each weight group (e.g., 1.5 and 2.5 kg) were randomly assigned to feed withdrawal treatments for 0, 3, 6, 9 and 12 h. Weight loss, yield, muscle pH, objective meat color and weights of gastro intestinal contents, crop, gizzard, provenriculus, small intestine, caecum, and rectum were determined. Live weight loss was significantly (p<0.05) increased as length of feed withdrawal extended. A significant (p<0.05) carcass yield for both 1.5 and 2.5 kg groups coincided after 9 and 6 h feed withdrawal, respectively. Net weights of intestinal contents for crop and gizzard were significantly (p<0.05) reduced by 6 h, and the reduction for proventriculus and small intestine occurred from 3 h. A noticeable effect of feed withdrawal on pH for breast muscle at 3 h postmortem occurred only when chicks were fasted for 3 h of which pH (6.05) was significantly (p<0.05) higher than that for other groups including the control (5.74). There was a linear tendency of higher lightness (Hunter L* value) numerically for chicks fasted for longer periods. The highest coefficient of determinations of regression models to estimate weight loss as a function of fasting period and body weights were achieved, when the models included both linear and quadratic terms for fasting period, and linear term for both 1.5 ($R^2=0.76$) and 2.5 kg ($R^2=0.78$) body weight groups. Given the practical aspect, approximately 1.5 kg of body weight is dominant, weight loss could be predicted by the following function; live weight $loss=26.6-0.28{\times}(fasting period)^2+12.34{\times}pasting\;period-0.012{\times}body\;weight$, $R^2=0.76$. Current data implied that the optimum fasting time for pre-slaughter chicks varied depending on slaughter weight; 6 and 9-h fasting were recommendable for 2.5 and 1.5 kg chicks, with little effect on objective meat color.

Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor

Cui, Y-H,Suh, Y,Lee, H-J,Yoo, K-C,Uddin, N,Jeong, Y-J,Lee, J-S,Hwang, S-G,Nam, S-Y,Kim, M-J,Lee, S-J Macmillan Publishers Limited 2015 Oncogene Vol.34 No.42

Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial–mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.

Preparation of [bis(amido)-phosphine] and [amido-phosphine sulfide or oxide] hafnium and zirconium complexes for olefin polymerization

Lee, C.S.,Park, J.H.,Hwang, E.Y.,Park, G.H.,Go, M.J.,Lee, J.,Lee, B.Y. Elsevier Sequoia 2014 Journal of organometallic chemistry Vol.772 No.-

New phosphine-based bidentate ligands, 2-Me-8-Ph<SUB>2</SUB>P(X)C<SUB>9</SUB>H<SUB>8</SUB>NH (3, X = O; 4, X = S) and N-R-2-Ph<SUB>2</SUB>P(X)C<SUB>6</SUB>H<SUB>4</SUB>NH (5, R = Et, X = O; 6, R = Me, X = S; 7, R = Et, X = S) were prepared via ortho-lithiation of 1,2,3,4-tetrahydroquinaldine (2-Me-C<SUB>9</SUB>H<SUB>9</SUB>NH) and aniline derivatives (N-R-C<SUB>6</SUB>H<SUB>5</SUB>NH). Reaction of the ortho-lithiated compounds with 0.5 equiv of PhP(OPh)<SUB>2</SUB> afforded the bis(amido)-phosphine ligands (2-Me-C<SUB>9</SUB>H<SUB>8</SUB>NH-8-yl)<SUB>2</SUB>PPh (8) and (N-R-C<SUB>6</SUB>H<SUB>4</SUB>NH-2-yl)<SUB>2</SUB>PPh (9, R = Me; 10, R = Et). Using these ligands, [amido-phosphine oxide]Hf(CH<SUB>2</SUB>Ph)<SUB>3</SUB>, [amido-phosphine sulfide]Hf(CH<SUB>2</SUB>Ph)<SUB>3</SUB>, [bis(amido)-phosphine]MX<SUB>2</SUB> (M = Hf, Zr; X = CH<SUB>2</SUB>Ph, Cl, Me), and [amido-phosphine-amine]MCl<SUB>3</SUB> complexes were prepared. The molecular structures of [amido-phosphine sulfide]Hf(CH<SUB>2</SUB>Ph)<SUB>3</SUB> (13) (prepared using 6), [bis(amido)-phosphine]ZrMe<SUB>2</SUB> (22) (prepared using 8), and [amido-phosphine-amine]MCl<SUB>3</SUB> (23, M = Hf; 24, M = Zr; prepared using 9) were confirmed by X-ray crystallography. Most of the prepared complexes exhibited negligible or low activity for ethylene/1-octene copolymerization. The [amido-phosphine sulfide]Hf(CH<SUB>2</SUB>Ph)<SUB>3</SUB> complex (13) exhibited relatively high copolymerization activity (19 x 10<SUP>6</SUP> g/mol-Hf h); however, this activity was unsatisfactory compared to that of the related [amido-phosphine]Hf(CH<SUB>2</SUB>Ph)<SUB>3</SUB> complexes (up to 48 x 10<SUP>6</SUP> g/mol-Hf h).

Ethanol extract of Prunus mume fruit attenuates hydrogen peroxide-induced oxidative stress and apoptosis involving Nrf2/HO-1 activation in C2C12 myoblasts

Kang, J.S.,Kim, D.J.,Kim, G.Y.,Cha, H.J.,Kim, S.,Kim, H.S.,Park, C.,Hwang, H.J.,Kim, B.W.,Kim, C.M.,Choi, Y.H. Sociedade Brasileira de Farmacognosia 2016 Revista brasileira de farmacognosia Vol.26 No.2

<P>The fruit of the Prunus mume (Siebold) Siebold & Zucc., Rosaceae (Korean name: Maesil) has long been used as a health food or valuable medicinal material in traditional herb medicine in Southeast Asian countries. In this study, we determined the potential therapeutic efficacy of the ethanol extract of P. mume fruits (EEPM) against H2O2-induced oxidative stress and apoptosis in the murine skeletal muscle myoblast cell line C2C12, and sought to understand the associated molecular mechanisms. The results indicated that exposure of C2C12 cells to H2O2 caused a reduction in cell viability by increasing the generation of intracellular reactive oxygen species and by disrupting mitochondrial membrane permeability, leading to DNA damage and apoptosis. However, pretreatment of the cells with EEPM before H2O2 exposure effectively attenuated these changes, suggesting that EEPM prevented H2O2-induced mitochondria-dependent apoptosis. Furthermore, the increased ex-pression and phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulation of heme oxygenase-1 (HO-1), a phase II antioxidant enzyme, were detected in EEPM-treated C2C12 cells. We also found that zinc protoporphyrin IX, an HO-1 inhibitor, attenuated the protective effects of EEPM against H2O2-induced reactive oxygen species accumulation and cytotoxicity. Therefore, these results indicate that the activation of the Nrf2/HO-1 pathway might be involved in the protection of EEPM against H2O2-induced cellular oxidative damage. In conclusion, these results show that EEPM contributes to the prevention of oxidative damage and could be used as a nutritional agent for oxidative stress-related diseases. (C) 2016 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. All rights reserved.</P>

HECTOMAP AND HORIZON RUN 4: DENSE STRUCTURES AND VOIDS IN THE REAL AND SIMULATED UNIVERSE

Hwang, Ho Seong,Geller, Margaret J.,Park, Changbom,Fabricant, Daniel G.,Kurtz, Michael J.,Rines, Kenneth J.,Kim, Juhan,Diaferio, Antonaldo,Zahid, H. Jabran,Berlind, Perry,Calkins, Michael,Tokarz, Susa American Astronomical Society 2016 The Astrophysical journal Vol.818 No.2

<P>HectoMAP is a dense redshift survey of red galaxies covering a 53 deg(2) strip of the northern sky. HectoMAP is 97% complete for galaxies with r < 20.5, (g-r) > 1.0, and (r -i) > 0.5. The survey enables tests of the physical properties of large-scale structure at intermediate redshift against cosmological models. We use the Horizon Run 4, one of the densest and largest cosmological simulations based on the standard. Cold Dark Matter (Lambda CDM) model, to compare the physical properties of observed large-scale structures with simulated ones in a volume-limited sample covering 8 x 10(6) h(-3) Mpc(3) in the redshift range 0.22 < z < 0.44. We apply the same criteria to the observations and simulations to identify over-and under-dense large-scale features of the galaxy distribution. The richness and size distributions of observed over-dense structures agree well with the simulated ones. Observations and simulations also agree for the volume and size distributions of under-dense structures, voids. The properties of the largest over-dense structure and the largest void in HectoMAP are well within the distributions for the largest structures drawn from 300 Horizon Run 4 mock surveys. Overall the size, richness and volume distributions of observed large-scale structures in the redshift range 0.22 < z < 0.44 are remarkably consistent with predictions of the standard Lambda CDM model.</P>

여대생의 우울, 스트레스와 문제도박과의 관계

하주희,차민주,조에스더,조세빈,홍소리,황정민,박지윤,강하영,노규상 이화여자대학교 간호과학대학 2015 이화간호학회지 Vol.- No.49

Purpose: The purpose of this study was to learn about problem-gambling level, depression and stress among female college students. Method: In this cross-sectional design study, a convenient sample of 325 female college students were recruited between September and October, 2014. Measurement used for this study were the CPGI(Canadian Problem Gambling Index), the CES-D(Center for Epidemiologic Studies Depression Scale), and the Life stress scale for college students. Data were statistically analyzed using descriptive statistics, t-test, ANOVA and chi-square test. Result: About 58.5 percent of the participants had experience of gambling; lottery was the most frequently used gambling among participants. 36 participants(11.1%) were problem gamblers. Relationship of smoking status to problem gambler group was statistically significant. There were statistically significant relationships among problem-gambling level(Non-problem, Low-risk, Moderate-risk, High-risk), depression and stress. The problem gambler group had significantly higher trait stress scores compared to the normal group. Conclusion: Problem gambling was a risk factor for both depression and stress among female college students. The proposals of this study are as follows; first, in depth-research are required with more expanded sampling as sample of this study was conveniently gathered, it is hard to generalize the result. Second, a problem gambling prevention program is recommended for low-risk problem gamblers as they have risk to become problem gambler later. Third, nursing interventions for problem gamblers should be investigated with regard to depression and stress level.

Hydrogenation of carbon monoxide to methane over mesoporous nickel-M-alumina (M=Fe, Ni, Co, Ce, and La) xerogel catalysts

Hwang, S.,Lee, J.,Hong, U.G.,Jung, J.C.,Koh, D.J.,Lim, H.,Byun, C.,Song, I.K. Korean Society of Industrial and Engineering Chemi 2012 Journal of industrial and engineering chemistry Vol.18 No.1

Mesoporous nickel(30wt%)-M(10wt%)-alumina xerogel (30Ni10MAX) catalysts with different second metal (M=Fe, Ni, Co, Ce, and La) were prepared by a single-step sol-gel method for use in the methane production from carbon monoxide and hydrogen. In the methanation reaction, yield for CH<SUB>4</SUB> decreased in the order of 30Ni10FeAX>30Ni10NiAX>30Ni10CoAX>30Ni10CeAX>30Ni10LaAX. Experimental results revealed that CO dissociation energy of the catalyst and H<SUB>2</SUB> adsorption ability of the catalyst played a key role in determining the catalytic performance of 30Ni10MAX catalyst in the methanation reaction. Optimal CO dissociation energy of the catalyst and large H<SUB>2</SUB> adsorption ability of the catalyst were favorable for methane production. Among the catalysts tested, 30Ni10FeAX catalyst with the most optimal CO dissociation energy and the largest H<SUB>2</SUB> adsorption ability exhibited the best catalytic performance in terms of conversion of CO and yield for CH<SUB>4</SUB> in the methanation reaction. The enhanced catalytic performance of 30Ni10FeAX was also due to a formation of nickel-iron alloy and a facile reduction.

The protective role of NAD(P)H:quinone oxidoreductase 1 on acetaminophen-induced liver injury is associated with prevention of adenosine triphosphate depletion and improvement of mitochondrial dysfunction

Hwang, J. H.,Kim, Y. H.,Noh, J. R.,Gang, G. T.,Kim, K. S.,Chung, H. K.,Tadi, S.,Yim, Y. H.,Shong, M.,Lee, C. H. Springer Science + Business Media 2015 Archives of toxicology Vol.89 No.11