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.

Antibiotic susceptibility and resistance of Streptococcus iniae and Streptococcus parauberis isolated from olive flounder (Paralichthys olivaceus)

Park, Y.K.,Nho, S.W.,Shin, G.W.,Park, S.B.,Jang, H.B.,Cha, I.S.,Ha, M.A.,Kim, Y.R.,Dalvi, R.S.,Kang, B.J.,Jung, T.S. Elsevier Scientific Pub. Co 2009 Veterinary microbiology Vol.136 No.1

The rates of antibiotic susceptibility and resistance were investigated in Streptococcus iniae and Streptococcus parauberis isolates obtained from diseased olive flounders (Paralichthys olivaceus) collected from fish farms in Jeju Island, Korea. Isolates of S. iniae (n=65) were susceptible to cefotaxime, erythromycin, ofloxacin, penicillin, tetracycline and vancomycin, as demonstrated by the minimum inhibitory concentration (MIC) test. Isolates of S. parauberis (n=86) were highly resistant to erythromycin (58% of the 86 isolates tested) and tetracycline (63% of the 86 isolates tested). Fifty-four isolates of tetracycline-resistant S. parauberis contained the tet(M/O/S) genes, of which 39 and 12 isolates contained the tet(M) and tet(S) genes, respectively, whereas 3 isolates contained both the tet(M) and tet(S) genes. Among the erythromycin-resistant isolates of S. parauberis (n=50) only 14 contained the erm(B) gene. These results suggest that the tet(S) and erm(B) genes of S. parauberis are involved in the acquisition of high-level resistance to erythromycin and tetracycline. Our findings reveal a high rate of antibiotic resistance among strains of S. parauberis and emphasize the need to develop an appropriate vaccine to reduce the use of antibiotics.

Characteristic polynomial of a generalized complete product of matrices

Hwang, S.G.,Park, J.W. North Holland [etc.] 2011 Linear algebra and its applications Vol.434 No.5

For a simple graph G, let G@? denote the complement of G relative to the complete graph and let P<SUB>G</SUB>(x)=det(xI-A(G)) where A(G) denotes the adjacency matrix of G. The complete product G@?H of two simple graphs G and H is the graph obtained from G and H by joining every vertex of G to every vertex of H. In [2]P<SUB>G@?H</SUB>(x) is represented in terms of P<SUB>G</SUB>, P<SUB>G@?</SUB>, P<SUB>H</SUB> and P<SUB>H@?</SUB>. In this paper we extend the notion of complete product of simple graphs to that of generalized complete product of matrices and obtain their characteristic polynomials.

Reactivities of organic isothiocyanates and thiocyanates toward dialkyl bis(phosphine) complexes of palladium(II) and platinum(II)

Lee, S.G.,Choi, K.Y.,Kim, Y.J.,Park, S.,Lee, S.W. Pergamon Press 2015 Polyhedron Vol.85 No.-

Room-temperature reactions of trans-[PdEt<SUB>2</SUB>L<SUB>2</SUB>] (L=PMe<SUB>3</SUB>, PEt<SUB>3</SUB>, PMe<SUB>2</SUB>Ph) with organic isothiocyanates [R-NCS; R=benzyl; CH(CH<SUB>3</SUB>)Ph, R-(-) and S-(+); indanyl, S-(+)] afforded the S,S-coordinated Pd(II) complexes [Pd(S<SUB>2</SUB>C?N-R)L<SUB>2</SUB>] containing a dithiocarbonimidato (S<SUB>2</SUB>C?N-R) group. Similar reactions involving allyl isothiocyanates produced the cationic η<SUP>3</SUP>-allyl Pd complex [Pd(η<SUP>3</SUP>-allyl)(PMe<SUB>3</SUB>)<SUB>2</SUB>]<SUP>+</SUP>(NCS)<SUP>-</SUP>. When [Pd(S<SUB>2</SUB>C?N-R)(PMe<SUB>3</SUB>)<SUB>2</SUB>] was treated with 1equiv of a chelating phosphine [L-L=depe (1,2-bis(diethylphosphino)ethane) and dmpe (1,2-bis(dimethylphosphino)ethane)], the corresponding complexes [Pd(S<SUB>2</SUB>C?N-R)(L-L)] were produced. Reactions of trans-[PdEt<SUB>2</SUB>L<SUB>2</SUB>] (L=PMe<SUB>3</SUB>, PMe<SUB>2</SUB>Ph) with organic thiocyanates (R-SCN; R=benzyl, Et) resulted in the formation of [Pd(CN)<SUB>2</SUB>L<SUB>2</SUB>] and an organic disulfide by S-C bond cleavage of R-SCN. However, similar reactions of the dimethyl analogs, trans-[PdMe<SUB>2</SUB>L<SUB>2</SUB>] (L=PMe<SUB>3</SUB>, PEt<SUB>3</SUB>), with benzyl thiocyanate afforded different products, [Pd(NCS)<SUB>2</SUB>L<SUB>2</SUB>] or [PdMe(NCS)L<SUB>2</SUB>]. Treating [Pt(styrene)(PMe<SUB>3</SUB>)<SUB>2</SUB>] with benzyl isothiocyanate gave the S-coordinated dithiocarbonimidato Pt(II) complex, [Pt(S<SUB>2</SUB>C?N-R)(Me<SUB>3</SUB>P)<SUB>2</SUB>] (R=benzyl). In contrast, cis-[PtEt<SUB>2</SUB>(PMe<SUB>3</SUB>)<SUB>2</SUB>] reacted with the isothiocyanate to afford the trialkyl Pt(IV) complex [PtEt<SUB>2</SUB>(SCN)(CH<SUB>2</SUB>Ph)(PMe<SUB>3</SUB>)<SUB>2</SUB>].

Two zinc-aminoclays' in-vitro cytotoxicity assessment in HeLa cells and in-vivo embryotoxicity assay in zebrafish

Chun, H.S.,Park, D.,Eun Lim, S.,Jeong, K.H.,Park, J.S.,Park, H.J.,Kang, S.,Kang, K.S.,Park, H.G.,An, H.R.,Huh, Y.S.,Lee, Y.C. Academic Press 2017 Ecotoxicology and environmental safety Vol.137 No.-

<P>Two zinc-aminoclays [ZnACs] with functionalized primary amines [(-CH2)(3)NH2] were prepared by a simple solgel reaction using cationic metal precursors of ZnCl2 and Zn(NO3)(2) with 3-aminopropyl triethoxysilane [APTES] under ambient conditions. Due to the facile interaction of heavy metals with primary amine sites and Zn-related intrinsic antimicrobial activity, toxicity assays of ZnACs nanoparticles (NPs) prior to their environmental and human-health applications are essential. However, such reports remain rare. Thus, in the present study, a cell viability assay of in-vitro HeLa cells comparing ZnCl2, Zn(NO3)(2) salts, and ZnO (similar to 50 mn average diameter) NPs was performed. Interestingly, compared with the ZnCl2, and Zn(NO3)(2) salts, and ZnO NPs (18.73/18.12/ 51.49 mu g/mL and 18.12/15.19/46.10 mu g/mL of IC50 values for 24 and 48 h), the two ZnACs NPs exhibited the highest toxicity (1050 values of 21.18/18.36 mu g/mL and 18.37/17.09 mu g/mL for 24 and 48 h, respectively), whose concentrations were calculated on Zn elemental composition. This might be due to the enhanced bioavailability and uptake into cells of ZnAC NPs themselves and their positively charged hydrophilicity by reactive oxygen species (ROS) generation, particularly as ZnACs exist in cationic NP's form, not in released Zn2+ ionic form (i.e., dissolved nanometal). However, in an in-vivo embryotoxicity assay in zebrafish, ZnACs and ZnO NPs showed toxic effects at 50-100 mu g/mL (corresponding to 37.88-75.76 of Zn wt% mu g/mL). The hatching rate (%) of zebrafish was lowest for the ZnO NPs, particularly where ZnAC-[(NO3)(2)] is slightly more toxic than ZnAC-[Cl-2]. These results are all very pertinent to the issue of ZnACs' potential applications in the environmental and biomedical fields.</P>

Full-length genomic analysis of porcine G9P[23] and G9P[7] rotavirus strains isolated from pigs with diarrhea in South Korea

Kim, H.H.,Matthijnssens, J.,Kim, H.J.,Kwon, H.J.,Park, J.G.,Son, K.Y.,Ryu, E.H.,Kim, D.S.,Lee, W.S.,Kang, M.I.,Yang, D.K.,Hyun, B.H.,Park, S.I.,Park, S.J.,Cho, K.O. Elsevier Science 2012 INFECTION GENETICS AND EVOLUTION Vol.12 No.7

Group A rotaviruses (RVAs) are agents causing severe gastroenteritis in infants and young animals. G9 RVA strains are believed to have originated from pigs. However, this genotype has emerged as the fifth major human RVA genotype worldwide. To better understand the relationship between human and porcine RVA strains, complete RVA genome data are needed. For human RVA strains, the number of complete genome data have grown exponentially. However, there is still a lack of complete genome data on porcine RVA strains. Recently, G9 RVA strains have been identified as the third most important genotype in diarrheic pigs in South Korea in combinations with P[7] and P[23]. This study is the first report on complete genome analyses of 1 G9P[7] and 3 G9P[23] porcine RVA strains, resulting in the following genotype constellation: G9-P[7]/P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. By comparisons of these genotype constellations, it was revealed that the Korean G9P[7] and G9P[23] RVA strains possessed a typical porcine RVA backbone, similar to other known porcine RVA strains. However, detailed phylogenetic analyses revealed the presence of intra-genotype reassortments among porcine RVA strains in South Korea. Thus, our data provide genetic information of G9 RVA strains increasingly detected in both humans and pigs, and will help to establish the role of pigs as a source or reservoir for novel human RVA strains.

<i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

<P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

The effects of particle size on the physicochemical properties of optimized astaxanthin-rich Xanthophyllomyces dendrorhous-loaded microparticles

Park, S.A.,Ahn, J.B.,Choi, S.H.,Lee, J.S.,Lee, H.G. Academic Press, etc 2014 FOOD SCIENCE AND TECHNOLOGY -ZURICH- Vol.55 No.2

To improve the entrapment efficiency (EE) of astaxanthin-rich Xanthophyllomyces dendrorhous (ASX)-loaded calcium alginate gel (ASX-CAG) microparticles, we used a response surface methodology to optimize preparation conditions including the ratio of ASX to total material (X<SUB>1</SUB>), alginate concentration (X<SUB>2</SUB>), and CaCl<SUB>2</SUB> concentration (X<SUB>3</SUB>). The EE and the mean size of the ASX-CAG microparticles were 76.7 g/100 g and 210.26 μm, respectively, after preparation under optimal conditions: 24 g ASX/100 g total material, 1.0 g/100 g alginate, and 200 mmol/L CaCl<SUB>2</SUB>. The effects of particle size on different characteristics were evaluated with increasing microparticle size; an increase in microparticle size significantly increased EE and the antioxidant activity of ASX, but resulted in a decrease in the release of entrapped ASX. Most importantly, the lipid peroxidation inhibitory activity of encapsulated ASX (55.1%) was significantly higher and longer-lasting than that of non-encapsulated ASX (40.5%) after 36 h of storage as determined using the thiobarbituric acid method.

Novel effects of FTY720 on perinuclear reorganization of keratin network induced by sphingosylphosphorylcholine: Involvement of protein phosphatase 2A and G-protein-coupled receptor-12

Park, M.K.,Park, S.,Kim, H.J.,Kim, E.J.,Kim, S.Y.,Kang, G.J.,Byun, H.J.,Kim, S.H.,Lee, H.,Lee, C.H. North-Holland ; Elsevier Science Ltd 2016 european journal of pharmacology Vol.775 No.-

<P>Sphingosylphosphorylcholine (SPC) evokes perinuclear reorganization of keratin 8 (K8) filaments and regulates the viscoelasticity of metastatic cancer cells leading to enhanced migration. Few studies have addressed the compounds modulating the viscoelasticity of metastatic cancer cells. We studied the effects of sphingosine (SPH), sphingosine 1-phosphate (S1P), FTY720 and FTY720-phosphate (FTY720P) on SPC-induced K8 phosphorylation and reorganization using Western blot and confocal microscopy, and also evaluated the elasticity of PANC-1 cells by atomic force microscopy. FTY720, FTY720P, SPH, and SIP concentration-dependently inhibited SPC-evoked phosphorylation and reorganization of K8, and migration of PANC-1 cells. SPC triggered reduction and narrow distribution of elastic constant K and conversely, FTY720 blocked them. A common upstream regulator of JNK and ERK, protein phosphatase 2A (PP2A) expression was reduced by SPC, but was restored by FTY720 and FTY72P. Butyryl forskolin, a PP2A activator, suppressed SPC-induced K8 phosphorylation and okadaic acid, a PP2A inhibitor, induced K8 phosphorylation. Gene silencing of PP2A also led to K8 phosphorylation, reorganization and migration. We also investigated the involvement of GPR12, a high-affinity SPC receptor, in SPC-evoked keratin phosphorylation and reorganization. GPR12 siRNA suppressed the SPC-triggered phosphorylation and reorganization of K8. GPR12 overexpression stimulated keratin phosphorylation and reorganization even without SPC. FTY720 and FTY720P suppressed the GPR12-induced phosphorylation and reorganization of K8. The collective data indicates that FTY720 and FTY720P suppress SPC-induced phosphorylation and reorganization of K8 in PANC-1 cells by restoring the expression of PP2A via GPR12. These findings might be helpful in the development of compounds that modulate the viscoelasticity of metastatic cancer cells and various SPC actions. (C) 2016 Elsevier B.V. All rights reserved.</P>

Ecotoxicological evaluation of tributyltin toxicity to the equilateral venus clam, Gomphina veneriformis (Bivalvia: Veneridae)

Park, K.,Kim, R.,Park, J.J.,Shin, H.C.,Lee, J.S.,Cho, H.S.,Lee, Y.G.,Kim, J.,Kwak, I.S. Academic Press 2012 Fish & shellfish immunology Vol.32 No.3

Tributyltin (TBT) is the most common pesticide in marine and freshwater environments. To evaluate the potential ecological risk posed by TBT, we measured biological responses such as growth rate, gonad index, sex ratio, the percentage of intersex gonads, filtration rate, and gill abnormalities in the equilateral venus clam (Gomphina veneriformis). Additionally, the biochemical and molecular responses were evaluated in G. veneriformis exposed to various concentrations of TBT. The growth of G. veneriformis was significantly delayed in a dose-dependent manner after exposure to all tested TBT concentrations. After TBT was administered to G. veneriformis, the gonad index decreased and the sex balance was altered. The percentage of intersex gonads also increased significantly in treated females, whereas no intersex gonads were detected in the solvent control group. Additionally, intersex gonads were detected in male G. veneriformis specimens exposed to relatively high TBT concentrations (20 μg L<SUP>-1</SUP>). The filtration rate was also reduced in a dose-dependent manner in TBT-exposed G. veneriformis. We also noted abnormal gill morphology in TBT-exposed G. veneriformis. Furthermore, increases in antioxidant enzyme activities were observed in TBT-exposed G. veneriformis clams, regardless of dosage. Vitellogenin gene expression also increased significantly in a dose-dependent manner in G. veneriformis exposed to TBT. These results provide valuable information regarding our understanding of the toxicology of TBT in G. veneriformis. Moreover, the responses of biological and molecular factors could be utilized as information for risk assessments and marine monitoring of TBT toxicity.