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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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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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Dynamic stress concentration in an infinitely long cylindrical cavity due to a point spherical source embedded within a fluid-saturated poroelastic formation of infinite extent

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 139-156页

作者： h.hOSSEINI O.BALILAShAKI Department of Mechanical Engineering Faculty of EngineeringGolestan University

The effects of a harmonically exciting monopole source on an infinitely long cylindrical cavity embedded entirely within a fluid-saturated poroelastic formation of infinite extent are examined theoretically. It is assumed that the source is located outside the cavity at a specified distance from the borehole axis. The magnitudes of the hoop and radial stresses beside the pore pressures exerted on the interface and inside the porous medium surrounding the borehole are calculated and discussed. Biot's poroelastic modeling along with three types of boundary conditions for the cylindrical interface including the ideal fluid, empty borehole, and rigid inclusion with a hard boundary is employed for the analysis. Utilizing a proper translational addition theorem for expressing the incident spherical wave in terms of cylindrical wave expansions, the proposed boundary conditions at the interface are satisfied. Stresses are formulated by means of wave potential functions in a three-dimensional(3D) manner. The effects of the frequency and the radial distance between the source and borehole on the induced stresses are examined for the first cylindrical modes over frequency spectra. Two permeability conditions for the interface and three types of soils for the porous formation are considered throughout the analysis. To give an overall outline of the study, a numerical example is presented. The results clearly indicate that the distance is a key parameter and has considerable effects on the induced stress values. In addition, the interface permeability condition and soil characteristics play an important role in determining the dynamic response of the borehole. Finally,the obtained results are compared with the relevant analyses existing in the literature for some limit cases, and good agreement is achieved.

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Neuroinflammation as a therapeutic target in huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani h.Palpagama Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. huntington's disease(hD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： huntington inflammation Medicine

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Glial response in the midcingulate cortex in huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani h.Palpagama Andrea Kwakowsky Center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

huntington’s disease(hD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying hD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： huntington degeneration cortex

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Interpretable discovery of semiconductors with machine learning

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npj Computational Materials 2023年第1期9卷 1150-1160页

作者： hitarth Choubisa Petar Todorović Joao M.Pina Darshan h.Parmar Ziliang Li oleksandr Voznyy Isaac Tamblyn Edward h.Sargent Department of Electrical and Computer Engineering University of Toronto10 King’s College RoadTorontoON M5S 3G4Canada Department of Physical and Environmental Sciences University of TorontoScarboroughON M1C 1A4Canada Department of Physics University of OttawaOttawaON K1N 6N5Canada Vector Institute for Artificial Intelligence TorontoON M5G 1M1Canada

Machine learning models of material properties accelerate materials discovery,reproducing density functional theory calculated results at a fraction of the cost1–*** bridge the gap between theory and experiments,machine learning predictions need to be distilled in the form of interpretable chemical rules that can be used by *** we develop a framework to address this gap by combining evolutionary algorithm-powered search with machine-learning surrogate *** then couple the search results with supervised learning and statistical *** strategy enables the efficient search of a materials space while providing interpretable design *** demonstrate its effectiveness by developing rules for the design of direct bandgap materials,stable UV emitters,and IR perovskite ***,we conclusively show how DARWIN-generated rules are statistically more robust and applicable to a wide range of applications including the design of UV halide perovskites.

关键词： preta learning perovskite

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