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Mechanisms of regulation of PFKFB expression in pancreatic and gastric cancer cells

World Journal of Gastroenterology 2014年第38期20卷 13705-13717页

作者： oleksandr H minchenko Katsuya Tsuchihara Dmytro O minchenko Andreas Bikfalvi Hiroyasu Esumi Department of Molecular Biology Palladin Institute of Biochemistry Department of Innovative Oncology National Cancer Center Department of Pediatrics Bogomolets National Medical University INSERM U1029 Molecular Angiogenesis and Cancer Microenvironment Laboratory University Bordeaux I

Enzymes 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 and -4 (PFKFB-3 and PFKFB-4) play a significant role in the regulation of glycolysis in cancer cells as well as its proliferation and survival. The expression of these mRNAs is increased in malignant tumors and strongly induced in different cancer cell lines by hypoxia inducible factor (HIF) through active HIF binding sites in promoter region of PFKFB-4 and PFKFB-3 genes. Moreover, the expression and hypoxia responsibility of PFKFB-4 and PFKFB-3 was also shown for pancreatic (Panc1, PSN-1, and MIA PaCa-2) as well as gastric (MKN45 and NUGC3) cancer cells. At the same time, their basal expression level and hypoxia responsiveness vary in the different cells studied: the highest level of PFKFB-4 protein expression was found in NUGC3 gastric cancer cell line and lowest in Panc1 cells, with a stronger response to hypoxia in the pancreatic cancer cell line. Overexpression of different PFKFB in pancreatic and gastric cancer cells under hypoxic condition is correlated with enhanced expression of vascular endothelial growth factor (VEGF) and Glut1 mRNA as well as with increased level of HIF-1α protein. Increased expression of different PFKFB genes was also demonstrated in gastric, lung, breast, and colon cancers as compared to corresponding non-malignant tissue counterparts from the same patients, being more robust in the breast and lung tumors. Moreover, induction of PFKFB-4 mRNA expression in the breast and lung cancers is stronger than PFKFB-3 mRNA. The levels of both PFKFB-4 and PFKFB-3 proteins in non-malignant gastric and colon tissues were more pronounced than in the non-malignant breast and lung tissues. It is interesting to note that Panc1 and PSN-1 cells transfected with dominant/negative PFKFB-3 (dnPFKFB-3) showed a lower level of endogenous PFKFB-3, PFKFB-4, and VEGF mRNA expressions as well as a decreased proliferation rate of these cells. Moreover, a similar effect had dnPFKFB-4. In conclusi

关键词： 6-phosphofructo-2-kinase/fructose-2 6-bisphosphatase-3 6-phosphofructo-2-kinase/fructose-2 6-bisphosphatase-4 Hypoxia Hypoxia inducible factor Panc1 PST-1 MKN45 NUGC3 Gastric cancer Lung cancer

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The Expression of TIMP1, TIMP2, VCAN, SPARC, CLEC3Band E2F1 in Subcutaneous Adipose Tissue of Obese Males and Glucose Intolerance

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CellBio 2013年第2期2卷 45-53页

作者： Dmytro minchenko Oksana Ratushna Yulia Bashta Ruslana Herasymenko oleksandr minchenko Department of Molecular Biology Palladin Institute of Biochemistry National Academy of Sciences of Ukraine Kyiv Ukraine Department of Pediatrics National Bogomolets Medical University Kyiv Ukraine

We investigated the expression of TIMP1, TIMP2, SPARC, VCAN, and CLEC3B genes, encoded matricellular proteins with pleiotropic functions, and glucose intolerance in obese male subjects with normal and impaired glucose tolerance. The purpose of this study was to examine the association between the gene expressions and glucose intolerance in obesity. The results indicate that obesity leads to significant increase of TIMP1, TIMP2, E2F1 and CLEC3B gene expressions in subcutaneous adipose tissue, especially TIMP2 gene. However, more significant increase of the expression of TIMP1 and TIMP2 was found in adipose tissue of obese patients with glucose intolerance. No significant changes were found in the expression of VCAN and SPARC genes in adipose tissue of obese subjects with normal glucose tolerance but increased in the group of obese subjects with glucose intolerance. At the same time, the E2F1 and CLEC3B gene expressions were decreased in adipose tissue of obese patients with glucose intolerance. Results of this study provide evidence that changes in the expression of genes encoded TIMP1, TIMP2, VCAN, SPARC, E2F1 and CLEC3B in subcutaneous adipose tissue of obese individuals associate with glucose intolerance.

关键词： Obesity Glucose Intolerance Men Gene Expression TIMP1 TIMP2 VCAN SPARC CLEC3B E2F1

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Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line

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American Journal of Molecular Biology 2012年第1期2卷 21-31页

作者： Dmytro O. minchenko Leonid L. Karbovskyi Serhii V. Danilovskyi Michel Moenner oleksandr H. minchenko Department of Molecular Biology Palladin Institute of Biochemistry National Academy of Sciences of Ukraine Kyiv Ukraine Department of Molecular Biology Palladin Institute of Biochemistry National Academy of Sciences of Ukraine Kyiv Ukraine INSERM U920 Molecular Mechanisms of Angiogenesis Laboratory University Bordeaux 1 Talence France Department of Molecular Biology Palladin Institute of Biochemistry National Academy of Sciences of Ukraine Kyiv Ukraine National O.O. Bohomoletz Medical University Kyiv Ukraine INSERM U920 Molecular Mechanisms of Angiogenesis Laboratory University Bordeaux 1 Talence France INSERM U920 Molecular Mechanisms of Angiogenesis Laboratory University Bordeaux 1 Talence France

The expression of retinoblastoma and several retinoblastoma-related genes was studied in glioma cell line U87 and its subline with knockdown of ERN1 (endoplasmic reticulum—nuclei-1), the main endoplasmic reticulum stress sensing and signaling enzyme. It was shown that a blockade of the ERN1 enzyme function increases the expression levels of retinoblastoma, retinoblastoma-like 1 and most retinoblastoma related genes: EID1, JARID1B, E2F1, E2F3, RBAP48 and CTIP, does not change RNF40 and RBAP46 and decreases KDM5A. We have also demonstrated that hypoxia reduces the expression levels of retinoblastoma, EID1, and E2F1 in ERN1-deficient glioma cells only. At the same time, the expression levels of retinoblastoma-like 1, E2F3, RBAP46, RBAP48 and CTIP decrease, while JARID1B and RBBP2 increase in both types of cells in hypoxic conditions, but the expression is much stronger in cells with suppressed function of ERN1. The expression level of JARID1B and KDM-5A mRNA is also enhanced in glutamine deprivation condition in both tested cell types, moreover, this effect is amplified by the blockade of the ERN1 enzyme function. The expression levels of retinoblastoma, EID1, RBAP48, and E2F3 are decreased in glutamine deprivation condition only in ERN1-deficient glioma cells, but RBL1, CTIP, RBAP46, and E2F1—in both tested cell types with more significant effect in ERN1-deficient cells. Glucose deprivation condition leads to a decrease of expression levels of retinoblastoma, RBL1, E2F3, RBAP46, and RBAP48 in both used cell types and of EID1 and E2F1 only in glioma cells with suppressed function of signaling enzyme ERN1. Thus, expression levels of retinoblastoma and most retinoblastoma-related genes are increased under a blockade of ERN1 enzyme function and significantly changed in hypoxia, glucose or glutamine deprivation conditions both in control U87 cells and ERN1-deficient cells, but inhibition of the unfolded protein response sensor ERN1 predominantly enhances these effects. Mor

关键词： mRNA Expression Retinoblastoma RBL1 RBAP48 RBAP46 CTIP KDM5A JARID1B E2F1 E2F3 Glioma Cells ERN1 Hypoxia Glucose Deprivation Glutamine Deprivation

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Expression of casein kinase genes in glioma cell line U87: Effect of hypoxia and glucose or glutamine deprivation

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Natural Science 2012年第1期4卷 38-46页

作者： Dmytro O. minchenko Leonid L. Karbovskyi Serhii V. Danilovskyi Anastasia P. Kharkova oleksandr H. minchenko 不详

The endoplasmic reticulum-nuclei-1 (ERN1) sensing and signaling enzyme mediates a set of complex intracellular signaling events known as the unfolded protein response. We have studied the effect of hypoxia and ischemic conditions (glucose or glutamine deprivation) on the expression of several casein kinase-1 and -2 genes in glioma U87 cells and its subline with suppressed function of ERN1. It was shown that blockade of ERN1, the key endoplasmic reticulum stress sensor, leads to an increase in the expression levels of casein kinase-1G2, -1E, -2B and NUCKS1 mRNA, but suppresses casein kinase-1A1, -1D and -2A1. Moreover, the expression levels of casein kinase-1A1, -1D and 1G3 as well as casein kinase-2A1 and -2A2 mRNAs are significantly increased under glutamine dep- rivation conditions both in control and ERN1- deficient glioma cells. At the same time, casein kinase-1E, -2B and NUCKS1 mRNA expression levels are also increased under this condition, but only in cells with suppressed function of ERN1. The expression level of NUCKS1 mRNA, however, is decreased both in control glioma cells and in genetically modified cells, but casein kinase-1G2—only in control U87 cells. Cell exposure to glucose deprivation conditions enhances the expression levels of casein kinase- 1D, 1G3, -1E and -2A1 in both types of glioma cells used, but casein kinase-2B expression levels increase only in cells with suppressed function of ERN1. Hypoxia induces or suppresses the expression of most of the studied genes mainly in ERN1-knockdown cells only. Results of this study show that hypoxia as well as glutamine and glucose deprivation conditions change the expression level most of casein kinase genes and that these effects are dependent on ERN1 signaling enzyme function.

关键词： mRNA Expression Casein Kinase 1A 1D 1G2 1G3 1E 2A1 2A2 2B and NUCKS1 Glioma Cells Endoplasmic Reticulum-Nuclei-1 (ERN1 IRE-1α) Hypoxia Glucose and Glutamine Deprivation

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Effect of Hypoxia on the Expression of a Subset of Proliferation Related Genes in IRE1 Knockdown U87 Glioma Cells

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Advances in Biological Chemistry 2017年第6期7卷 195-210页

作者： Dariia O. Tsymbal Dmytro O. minchenko Oksana S. Hnatiuk Olha Y. Luzina oleksandr H. minchenko Department of Molecular Biology Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine Kyiv Ukraine

We have studied the expression of a subset of genes encoding important tumor growth related factors in U87 glioma cells with IRE1 (inositol requiring enzyme-1) knockdown as well as their hypoxic regulation. It was shown that the expression levels of activating transcription factor 6 (ATF6), clusterin (CLU), adhesion G protein-coupled receptor E5 (ADGRE5), transglutaminase?2, C polypeptide (TGM2), leukemia inhibitory factor (LIF), phosphoserine aminotransferase 1 (PSAT1), glyoxalase I (GLO1) and tetraspanin 13 (TSPAN13) are significantly down-regulated in glioma cells with the knockdown of IRE1 signaling enzyme. It was also shown that in glioma cells subjected to hypoxia, the expression levels of PSAT1, TSPAN13, EIF2AK3, and TGM2 genes were up-regulated, whereas the expression of ATF6 gene was down-regulated. At the same time, the expression levels of LIF, CLU, and ADGRE5 genes did not change in response to hypoxic treatment.?Furthermore, inhibition of IRE1, a key effector of an unfolded protein response pathway, modified the effect of hypoxia on the expression of most studied genes. Present study demonstrates that IRE1 knockdown down-regulated the expression of most studied genes and modified their hypoxic regulation and that these changes possibly contributed to the suppression of glioma growth in cells without IRE1 signaling enzyme function.

关键词： IRE1 Knockdown Hypoxia mRNA Expression EIF2AK3 ATF6 CLU PSAT1 TGM2 U87 Glioma Cells

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The vascular endothelial growth factor genes expression in glioma U87 cells is dependent from ERN1 signaling enzyme function

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Advances in Biological Chemistry 2012年第2期2卷 198-206页

作者： Dmytro O. minchenko Kateryna I. Kubaichuk Oksana O. Ratushna Serhiy V. Komisarenko oleksandr H. minchenko Department of Molecular Biology Palladin Institute of Biochemistry National Academy of Sciences of Ukraine Kiev Ukraine

The expression of different vascular endothelial growth factor (VEGF) genes was studied in glioma U87 cells with endoplasmic reticulum–nuclei-1 (ERN1) loss of function and its regulation by hypoxia and glutamine or glucose deprivation conditions as model of ischemia. The blockade of function of the ERN1 enzyme, which is a major sensor of endoplasmic reticulum stress, leads to a decrease of the VEGFA, VEGFB and VEGFC mRNA expression level. The level of VEGFA proteins also decreases at this experimental condition in the cytosolic fraction, but increases in the nuclear fraction. Hypoxia does not affect VEGFC and increases the expression level of VEGFA and VEGFB mRNA in both used cell types, however, the change was much less profound in cells with suppressed function of ERN1. The expression level of VEGFC mRNA decreases in both used cell types in glutamine deprivation condition, however, the change was more profound in control glioma cells. At the same time, the expression level of VEGFA mRNA increases and VEGFB—decreases in gluta-mine deprivation condition in control glioma cells only. Exposure of glioma cells to glucose deprivation condition increases VEGFB mRNA expression level in both used cell types;however, VEGFA—in control glioma cells only and VEGFC—in cells with ERN1 signaling enzyme loss of function only. Thus, the results of this study clearly demonstrated the down-regulation of the expression of all three VEGF genes in glioma cells with ERN1 loss of function which correlates to the suppressed angiogenesis and proliferation rate of these cells. Moreover, the effect of hy-poxia and glutamine or glucose deprivation condition on the expression level of all VEGF genes is different and mainly depends on ERN1 signaling enzyme function.

关键词： VEGF Expression ERN1 Hypoxia Ischemic Conditions Angiogenesis Glioma U87 Cells

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Realizing ultra-pure red emission with Sn-based lead-free perovskites

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Rare Metals 2020年第4期39卷 330-331页

作者： oleksandr Voznyy Department of Physical and Environmental Sciences University of Toronto ScarboroughScarboroughON MIC 1A4Canada

Light-emitting diodes(LEDs)are key for the development of next-generation displays for ultra-high-definition *** materials beyond organic LEDs are required to meet the color purity standards,while retaining low processing cost and environmental *** and colleagues report in Advanced Science that two-dimensional(2D)tin halide perovskite—efficiently stabilized by H3PO2 incorporation—has great promise for ultra-pure red LEDs.

关键词： Realizing ultra-pure red emission with Sn-based lead-free perovskites red

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Energy Engineering 2022年第1期119卷 103-121页

作者： oleksandr Kovalko Tatiana Eutukhova oleksandr Novoseltsev Naftogaz of Ukraine Kyiv01601Ukraine Interregional Academy of Personnel Management Kyiv02000Ukraine Institute of Engineering Thermophysics Kyiv03057Ukraine

The transition to low-carbon development has been recognized as one of the most important directions for the transformation of national economies in most *** we can identify two of the most common service-oriented logical models of this *** are models of Service-Dominant Logic and Product-Service Systems that are used in this study to create a service-oriented platformfor stimulating business development in the field of energy-related(ER)*** establishment of such a platform is being considered based on the conceptual provisions of the global business *** a platform has been found to be a powerful tool for systemic coordinated cooperation between actors in the ER-services market and the relevant actors in the energy sector as well as in other industrial markets,unleashing the benefits of synergies,resulting from such *** logical models of attracting energy services companies to the creation of virtual communities(centers)for large-scale implementation of measures in the field of energy efficiency and renewable energy sources are presented in *** advantages of the practical implementation of logicalmodels are confirmed by calculations performed onmathematicalmodel adapted for engineering use in the field of ER-services.

关键词： Energy services market service-oriented logic performance contracting

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Features of hardware implementation of quasi-continuous observation devices with discrete receivers

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Visual Computing for Industry,Biomedicine,and Art 2022年第1期5卷 71-77页

作者： oleksandr Maryliv Mykhailo Slonov Military-Diplomatic Academy named after Eugene Bereznyak Kyiv 04050Ukraine

This article proposes an approach to the formalization of tasks and conditions for the hardware implementation of quasi-continuous observation devices with discrete receivers in remote sensing *** devices with a matrix are used in medicine,ecology,aerospace photography,and geodesy,among other *** the discrete receivers,the sampling of an image in the matrix receiver into pixels leads to a decrease in the spatial information of the *** a greater extent,these disadvantages can be avoided by using photosensitive matrix with a regularly changing(controlled)density of elementary receivers-matrix(RCDOER-matrix).Currently,there is no substantiation of the tasks and conditions for the hardware implementation of *** algorithmic formation of a quasi-continuous image of observation devices with the RCDOER-matrix is *** algorithm used a formal pixel-by-pixel description of the signals in the *** algorithm formalizes the requirements for creating a photosensitive RCDOER-matrix of a certain size,as well as for changing the mechanism for forming and saving a frame with observation *** application of the developed method will allow multiplying the pixel size of the image relative to the pixel size of the *** algorithms for RCDOER-matrix are supplemented by formalizing the tasks that arise when creating *** addition,the conditions for hardware implementation are proposed,which ensure the completeness of registration of the observation picture,and allow avoiding excessive pixel ***,the results of the research carried out approximate the practical application of RCDOER-matrix.

关键词： Discrete receivers Formalization of tasks Conditions of hardware implementation

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Evaluation of airlift pump performance for vertical conveying of coal particles

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International Journal of Coal Science & Technology 2023年第3期10卷 155-166页

作者： Parviz Enany oleksandr Shevchenko Carsten Drebenshtedt Faculty of Mining and Special Civil Engineering Technische Universitat BergakademieGustav-Zeuner StraBe 1A09599 FreibergGermany UTF GmbH ErzstraBe 1509618 Brand-ErbisdorfGermany

One of the crucial aspects of reducing air consumption when conveying particles with an airlift pump is to know the factors that affect the process of particle motion at an initial velocity of *** determine the influence of submer-gence ratio and physical properties of particles(such as size,shape,and mass)on the onset of vertical particle motion,the airlift pump was taken as the research object,and spherical glass together with irregular shaped coal were used as experimental test *** results show that unlike the water-solid environment,the start of particle motion in the water-air mixture does not always occur at a certain value of superficial water velocity and this value also increases with increasing submergence *** the parameters considered,the role of submergence ratio is much more effective than the dimensions and the shape of the particle,because by increasing submergence from 0.3 to 0.8,it is possible to reduce air consumption by up to 8 *** on this study the corresponding theoretical model derived by Fujimoto et *** optimized,wherein the overall agreement between the modified theory and present experimental data is particularly *** to Fujimoto,the minimum superficial water velocity for lifting solids in the air-water mixture is not always smaller than water ambient which indicates on optimum submergence ratio higher than ***,a new criterion was introduced to describe the moment of onset of the particle motion as a function of the superficial fluid velocity ratio for each submergence value.

关键词： Air-water-solid flow Slurry- Coal Submergence ratio Taylor bubble Superficial velocity

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