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.

Probing the impact of quercetin-7-O-glucoside on influenza virus replication influence

Gansukh, E.,Kazibwe, Z.,Pandurangan, M.,Judy, G.,Kim, D.H. G. Fischer 2016 Phytomedicine Vol.23 No.9

<P>Background: Influenza virus is still at large and seriously affects social welfare and health. Dianthus superbus is a well-known medicinal plant widely used in Mongolian and Chinese traditional medicine for anti-inflammatory purposes. Purpose: To investigate the influence of this novel herbal medicinal product over virus infection and virus-induced symptoms Method: Quercetin-7-O-glucoside was isolated by bioassay (anti-influenza)-guided fractionation. The structural elucidation was made with 1H-NMR and 13C-NMR. Influenza A/Vic/3/75 (H3N2), A/PR/8/34 (H1N1), B/Maryland/1/59 and B/Lee/40 viruses were used for the evaluation of the antiviral activity. Virus-induced reactive oxygen species and autophagy formation levels were studied. The antiviral mechanism was elucidated via time-dependent, pre-, post-incubation assay methods. The viral RNA replication inhibition of Q7G was analyzed using quantitative RT-PCR method. The blocking of polymerase basic protein subunits of influenza viral RNA polymerase by Q7G was detected by in silico molecular docking assays using AutoDock Vina program with m(7)GTP. Additionally, Q7G was tested against M-MuLV RNA polymerase. Results: Q7G was not cytotoxic (CC50 > 100 mu g/ml) in MDCK cells and it showed 3.1 mu g/ml, 6.61 mu g/ml, 8.19 mu g/ml and 5.17 mu g/ml IC50 values against influenza A/PR/8/34, A/Vic/3/75, B/Lee/40 and B/Maryland/1/59 virus strains, respectively. Treatment of Q7G highly reduced ROS and autophagy formation induced by influenza virus infection. Q7G did not reduce NA activity and did not directly interact with the virus particles. Since viral RNA synthesis was blocked by treatment of Q7G. We targeted viral RNA polymerase for further probing. Interestingly, the binding energy of Q7G on viral PB2 protein was -9.1 kcal/mol and was higher than m(7)GTP recorded as -7.5 kcal/mol. It also was observe to block M-MuLV RNA polymerase. Conclusion: Isolated compound Q7G showed strong inhibition activity against influenza A and B viruses. It also reduced virus-induced ROS and autophagy formation. Q7G does not directly bind to the virus particles and did not affect NA activity. These results indicated that Q7G inhibits viral RNA polymerase, and that it occupies the binding site of m(7)GTP on viral PB2 protein. (C) 2016 Elsevier GmbH. All rights reserved.</P>

Changes of phenolic-acids and vitamin E profiles on germinated rough rice (Oryza sativa L.) treated by high hydrostatic pressure

Kim, M.Y.,Lee, S.H.,Jang, G.Y.,Li, M.,Lee, Y.R.,Lee, J.,Jeong, H.S. Applied Science Publishers 2017 Food chemistry Vol.217 No.-

This study was performed to investigate changes in the phenolic acid and vitamin E profiles of germinated rough rice following high hydrostatic pressure treatment (HPT). Rough rice was germinated at 37<SUP>o</SUP>C for two days and subjected to 0.1, 10, 30, 50, and 100MPa pressures for 24h. The total phenolic acid content increased from 85.37μg/g at 0.1MPa to 183.52μg/g at 100MPa. The highest gallic acid (4.29μg/g), catechin (9.55μg/g), p-coumaric acid (8.36μg/g), ferulic acid (14.99μg/g), salicylic acid (14.88μg/g), naringin (6.18μg/g), trans-cinnamic acid (45.23μg/g), and kaempferol (40.95μg/g) contents occurred in the sample treated at 100MPa after germination. The maximum vitamin E content of about 2.56 (BG) and 4.34mg/100g (AG) were achieved at 30MPa. These result suggest that a combination of HPT and germination are efficient method for enhancement of functionality in rough rice, and clarify the influence of HPT conditions on the vitamin E and phenolic acid in germination rough rice.

GLOBULAR CLUSTER POPULATIONS: RESULTS INCLUDING S⁴G LATE-TYPE GALAXIES

Zaritsky, Dennis,McCabe, Kelsey,Aravena, Manuel,Athanassoula, E.,Bosma, Albert,Comeró,n, Sé,bastien,Courtois, Helene M.,Elmegreen, Bruce G.,Elmegreen, Debra M.,Erroz-Ferrer, Santiago,Gadot American Astronomical Society 2016 The Astrophysical journal Vol.818 No.1

<P>Using 3.6 and 4.5 mu m images of 73 late-type, edge-on galaxies from the S(4)G survey, we compare the richness of the globular cluster populations of these galaxies to those of early-type galaxies that we measured previously. In general, the galaxies presented here fill in the distribution for galaxies with lower stellar mass, M-*, specifically log(M-*/M-circle dot) < 10, overlap the results for early-type galaxies of similar masses, and, by doing so, strengthen the case for a dependence of the number of globular clusters per 10(9)M(circle dot) of galaxy stellar mass, T-N, on M-*. For 8.5 < log(M-*/M-circle dot) < 10.5 we find the relationship can be satisfactorily described as T-N = (M-*/10(6.7))(-0.56) M-* is expressed in solar masses. The functional form of the relationship is only weakly constrained, and extrapolation outside this range is not advised. Our late-type galaxies, in contrast to our early types, do not show the tendency for low-mass galaxies to split into two T-N families. Using these results and a galaxy stellar mass function from the literature, we calculate that, in a volume-limited, local universe sample, clusters are most likely to be found around fairly massive galaxies (M-* similar to 10(10.8)M(circle dot)) and present a fitting function for the volume number density of clusters as a function of parent-galaxy stellar mass. We find no correlation between T-N and large-scale environment, but we do find a tendency for galaxies of fixed M-* to have larger T-N if they have converted a larger proportion of their baryons into stars.</P>

Restricted growth of U‐type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity

Park, J W,Moon, C H,Harmache, A,Wargo, A R,Purcell, M K,Bremont, M,Kurath, G Blackwell Publishing Ltd 2011 Journal of fish diseases Vol.34 No.2

<P><B>Abstract</B></P><P>Previously, we demonstrated that a representative M genogroup type strain of infectious haematopoietic necrosis virus (IHNV) from rainbow trout grows well in rainbow trout‐derived RTG‐2 cells, but a U genogroup type strain from sockeye salmon has restricted growth, associated with reduced genome replication and mRNA transcription. Here, we analysed further the mechanisms for this growth restriction of U‐type IHNV in RTG‐2 cells, using strategies that assessed differences in viral genes, host immune regulation and phosphorylation. To determine whether the viral glycoprotein (G) or non‐virion (NV) protein was responsible for the growth restriction, four recombinant IHNV viruses were generated in which the G gene of an infectious IHNV clone was replaced by the G gene of U‐ or M‐type IHNV and the NV gene was replaced by NV of U‐ or M‐type IHNV. There was no significant difference in the growth of these recombinants in RTG‐2 cells, indicating that G and NV proteins are not major factors responsible for the differential growth of the U‐ and M‐type strains. Poly I:C pretreatment of RTG‐2 cells suppressed the growth of both U‐ and M‐type IHNV, although the M virus continued to replicate at a reduced level. Both viruses induced type 1 interferon (IFN1) and the IFN1 stimulated gene Mx1, but the expression levels in M‐infected cells were significantly higher than in U‐infected cells and an inhibitor of the IFN1‐inducible protein kinase PKR, 2‐aminopurine (2‐AP), did not affect the growth of U‐ or M‐type IHNV in RTG‐2 cells. These data did not indicate a role for the IFN1 system in the restricted growth of U‐type IHNV in RTG‐2 cells. Prediction of kinase‐specific phosphorylation sites in the viral phosphoprotein (P) using the NetPhosK program revealed differences between U‐ and M‐type P genes at five phosphorylation sites. Pretreatment of RTG‐2 cells with a PKC inhibitor or a p38MAPK inhibitor did not affect the growth of the U‐ and M‐type viruses. However, 100 μ<SMALL>m</SMALL> of the casein kinase II (CKII) inhibitor, 5,6‐dichloro‐1‐β‐<SMALL>d</SMALL>‐ribofuranosylbenzimidazole (DRB), reduced the titre of the U type 8.3‐fold at 24 h post‐infection. In contrast, 100 μ<SMALL>m</SMALL> of the CKII inhibitor reduced the titre of the M type only 1.3‐fold at 48 h post‐infection. Our data suggest that the different growth of U‐ and M‐type IHNV in RTG‐2 cells may be linked to a differential requirement for cellular protein kinases such as CKII for their growth.</P>

Machine-to-Machine (M2M) Communications in Vehicular Networks

( M. J. Booysen ),( J. S. Gilmore ),( S. Zeadally ),( G. J. Van Rooyen ) 한국인터넷정보학회 2012 KSII Transactions on Internet and Information Syst Vol.6 No.2

To address the need for autonomous control of remote and distributed mobile systems, Machine-to-Machine (M2M) communications are rapidly gaining attention from both academia and industry. M2M communications have recently been deployed in smart grid, home networking, health care, and vehicular networking environments. This paper focuses on M2M communications in the vehicular networking context and investigates areas where M2M principles can improve vehicular networking. Since connected vehicles are essentially a network of machines that are communicating, preferably autonomously, vehicular networks can benefit a lot from M2M communications support. The M2M paradigm enhances vehicular networking by supporting large-scale deployment of devices, cross-platform networking, autonomous monitoring and control, visualization of the system and measurements, and security. We also present some of the challenges that still need to be addressed to fully enable M2M support in the vehicular networking environment. Of these, component standardization and data security management are considered to be the most significant challenges.

HCV : PE-134 ; Hemoglobin decline during peginterferon Alfa-2B (PEG-2B)/ribavirin (RBV) treatment in real-life is associated with favorable SVR rates in difficult-to-treat patients with HCV genotype 1 (G1) infection

( G Teuber ),( S Mauss ),( D Huppe ),( E Zehnter ),( M P Manns ),( T Dahhan ),( U Meyer ),( T Witthoft ),( B Moller ),( N Dikopoulos ),( J Brack ),( B Stade ),( M Bilzer ),( Bng Hepatitis Study Group 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background and Aims: Recently, it has been shown for the overall G1 population that anemia as well as the maximal hemoglobin (Hb) decline during peginterferon/RBV treatment is associated with higher SVR rates. We here investigated whether the maximal Hb decline influences SVR rates in difficult-to-treat patients undergoing Peg2b/RBV therapy for HCV G1 infection in real-life. Methods: Data of patients treated for G1 infection within the German Peg2b/RBV observational study were retrospectively analyzed. In this real-life cohort study G1 infection was treated with Peg2b 1.5 μg/kg/wk + weight-based RBV (800-1200 mg/day) for up to 48 wks at 285 sites. Subjects who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as undetectable serum HCV-RNA 24 wks after EOT response. Only one patient received erythropoietin treatment for anemia. Results: 1851 patients had baseline and at least one Hb measurement during therapy. Overall SVR rate was 42.6% (789/1851). SVR rates were only slightly higher for subjects with an absolute Hb decline >3 g/dL (44.3%, 493/1114) compared to those with maximum Hb declines <3 g/dL (40.2%, 296/737) (p=0.08). In contrast, a significant (p=0.0004) difference in SVR rates was obtained by comparing subjects with Hb declines >2 g/dL (44.6%, 673/1510) with those who experienced Hb declines <2 g/dL (34.0%, 116/341). Similar SVR rates of 46.1% (164/356) and 44.1% (509/1154) in patients with Hb declines >2 g/dL even if they did/did not become anemic (Hb<10 g/dL) strongly support Hb decline, and not anemia, as primary beneficial mechanism improving SVR. As summarized in the table, Hb declines >2 g/dl were significantly associated with higher SVR rates in difficult-to-treat patients, such as subjects elder than 50 years or subjects with high baseline viral load >600.000 IU/ml. Interestingly no beneficial effect was observed in patients with low platelet count (<150/nL), an indicator of advanced fibrosis/cirrhosis. Patients who first developed a Hb decline >2 g/dL during weeks 0-4 were likely to achieve similar SVR (41.3%, 365/883) than those who developed a Hb decline <2 g/dL (44.9%, 386/859). In contrast, a Hb decline >2 g/dL compared to <2 g/dL during weeks 0-4 was associated with a 2-3 fold higher risk of anemia in female (16.6% vs 40.5%) and male patients (7.3% vs 19.0%) when compared with a Hb decline <2 g/dL. Conclusions: Patients with HCV genotype 1 infection and in particular the subgroup of difficult-to-treat patients elder than 50 years or with HVL, achieve up to 15% higher SVR rates when they develop a Hb decline >2 g/dL during Peg2b/RBV therapy. However, patients with low platelet count <150/nL do not achieve this beneficial virologic effect.

Effect of Genetic and Non-Genetic Factors Other Then Disease on Kid Survivability in Goat

Miah, S. G.,Husain, M. S.,Hoque, D. A.,Baik, D. H. 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.3

이 연구는 벵갈 종과 그 교잡종 산양의 번식에 있어서 생시부터 90일령 까지의 생존율에 영향을 미치는 유전적 및 비 유전적인 요인을 규명하기 위하여 수행되었다. 분석에 이용된 모델은 지역, 교배조합, 자양의 성, 출생시 산자형태(1두, 2두, 3두 및 4두), 출생계절(여름 3월∼6월; 우기 7월∼10월; 및 겨울 11월∼2월), 출생연도와 2요인 상호작용의 효과를 포함하였다. 교잡종에 비하여 순종의 생존율은 31일령과 90일령 사이에 현저히 낮은 것으로 유의성(p<0.05)을 나타냈다. 생존율에 대한 지역의 효과는 16∼60일령 기간을 제외하고는 통계적으로 유의적인 차이를 보이지 않았다. 생존율에 대한 성의 효과는 초기 0∼7일령의 기간을 제외하고는 모두 통계적 유의성이 인정되었다. 생존율은 여름에 출생한 것이 가장 높았고 겨울과 우기(rainy season)의 순서로 나타났다. 16일령부터 60일령 사이의 자양의 생존율은 어미의 비유량에 의하여 영향을 받는 것으로 (p<0.05) 나타났고, 400∼600g/day 의 비유량인 경우에 생존율이 가장 높았던 반면 비유량이 80∼200g/day인 어미의 자양이 가장 낮은 생존율을 보였다. 생시체중은 90일령 까지의 모든 성장단계에서 자양의 생존율에 영향을 미치는 주요 요인이었다. 생존율은 모양의 비유량과 그리고 자양의 생시체중과 정의 상관관계를 보였다. 성과 생산지역간 (p<0.01) 또는 성과 출생시 산자형태간(p<0.05)의 상호작용은 통계적 유의성이 있었던 반면에 성과 유전적 그룹간의 상호작용은 유의성이 없었다. This experiment was conducted to investigate the genetic and non-genetic factors affecting kid survivability in goats from birth to 90 days of age. The purebreds had lower survivability than the crossbreds, with significant (p<0.05) difference amongst themselvess for the age of 31 to 90 days. The locational effect on survivability was insignificant for all the periods except 16 to 60 days (p<0.05) of age. The sex and birth type also had significant (p<0.05) effect on survivability for all the periods except 0 to 7 days of age. The survivability was found to be significantly (p<0.05) higher for kids born in summer season followed by those born in winter and rainy season. Milk produced by the does were significantly (p<0.05) affected on the survivability of kids during the period from 16 to 60 days of age. The survivability of kids were highest and lowest having milk yield of doe found to be 400∼600 g/day and 80∼200 g/day, respectively. Birth weight had significant (p<0.05) effect on survivability for all the stages of growth up to 90 days of age. Survivability was positively correlated with does' milk yield as well as kids birth weight. Interactions of sex with location or birth type were significant (p<0.01 and p<0.05, respectively) though interaction between sex and genetic group was insignificant.

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model

Gökhan Gürkan,Özüm Atasoy,Nilsu Çini,İbrahim Halil Sever,Bahattin Özkul,Gökhan Yaprak,Cansın Şirin,Yiğit Uyanıkgil,Ceren Kızmazoğlu,Mümin Alper Erdoğan,Oytun Erbaş 대한신경외과학회 2023 Journal of Korean neurosurgical society Vol.66 No.5

Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

HCV, Alcoholic : PE-134 ; Hemoglobin decline during peginterferon Alfa-2B (PEG-2B)/ribavirin (RBV) treatment in real-Life is associated with favorable SVR rates in difficult-to-treat patients with HCV genotype 1 (G1) infection

( G Teuber ),( S Mauss ),( D Huppe ),( E Zehnter ),( M P Manns ),( T Dahhan6 ),( U Meyer ),( T Witthoft ),( B Moller9,),( N Dikopoulos ),( J Brack ),( B Stade ),( M Bilzer ),( The Bng Hepatitis Study 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background and Aims: Recently, it has been shown for the overall G1 population that anemia as well as the maximal hemoglobin (Hb) decline during peginterferon/RBV treatment is associated with higher SVR rates. We here investigated whether the maximal Hb decline influences SVR rates in difficult-to-treat patients undergoing Peg2b/RBV therapy for HCV G1 infection in real-life. Methods: Data of patients treated for G1 infection within the German Peg2b/RBV observational study were retrospectively analyzed. In this real-life cohort study G1 infection was treated with Peg2b 1.5 μg/kg/wk + weight-based RBV (800-1200 mg/day) for up to 48 wks at 285 sites. Subjects who discontinued for non-response or for any other reasons were included in the analysis. SVR was defined as undetectable serum HCV-RNA 24 wks after EOT response. Only one patient received erythropoietin treatment for anemia. Results: 1851 patients had baseline and at least one Hb measurement during therapy. Overall SVR rate was 42.6% (789/1851). SVR rates were only slightly higher for subjects with an absolute Hb decline >3 g/dL (44.3%, 493/1114) compared to those with maximum Hb declines <3 g/dL (40.2%, 296/737) (p=0.08). In contrast, a significant (p=0.0004) difference in SVR rates was obtained by comparing subjects with Hb declines >2 g/dL (44.6%, 673/1510) with those who experienced Hb declines <2 g/dL (34.0%, 116/341). Similar SVR rates of 46.1% (164/356) and 44.1% (509/1154) in patients with Hb declines >2 g/dL even if they did/did not become anemic (Hb<10 g/dL) strongly support Hb decline, and not anemia, as primary beneficial mechanism improving SVR. As summarized in the table, Hb declines >2 g/dl were significantly associated with higher SVR rates in difficult-to-treat patients, such as subjects elder than 50 years or subjects with high baseline viral load >600.000 IU/ml. Interestingly no beneficial effect was observed in patients with low platelet count (<150/nL), an indicator of advanced fibrosis/cirrhosis. Patients who first developed a Hb decline >2 g/dL during weeks 0-4 were likely to achieve similar SVR (41.3%, 365/883) than those who developed a Hb decline <2 g/dL (44.9%, 386/859). In contrast, a Hb decline >2 g/dL compared to <2 g/dL during weeks 0-4 was associated with a 2-3 fold higher risk of anemia in female (16.6% vs 40.5%) and male patients (7.3% vs 19.0%) when compared with a Hb decline <2 g/dL. Conclusions: Patients with HCV genotype 1 infection and in particular the subgroup of difficult-to-treat patients elder than 50 years or with HVL, achieve up to 15% higher SVR rates when they develop a Hb decline >2 g/dL during Peg2b/RBV therapy. However, patients with low platelet count <150/nL do not achieve this beneficial virologic effect.