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1

Adida, C., G. Ambrosini, J. Plescia, PL Crotty, J. Costa et DC Altieri. « Protease receptors in Hodgkin's disease : expression of the factor Xa receptor, effector cell protease receptor-1, in Reed-Sternberg cells ». Blood 88, no 4 (15 août 1996) : 1457–64. http://dx.doi.org/10.1182/blood.v88.4.1457.bloodjournal8841457.

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The expression of a cellular receptor for the blood-clotting protease factor Xa, designated effector cell protease receptor-1 (EPR-1), was investigated in lymphoma. Immunohistochemical analysis demonstrated prominent reactivity of monoclonal antibodies to EPR-1 with Reed- Sternberg cells in 30 of 35 cases of nodular-sclerosis, lymphocyte- depletion, and mixed-cellularity Hodgkin's disease (HD). In contrast, several non-Hodgkin's lymphomas, or the nonneoplastic cellular components of HD, did not react with anti-EPR-1 monoclonal antibodies. A single molecular species of approximately 62 kD, consistent with the size and structural organization of EPR-1, was immunoblotted by an anti- EPR-1 monoclonal antibody from tissue samples of HD, but not from normal lymph nodes. Expression of EPR-1 transcripts in Reed-Sternberg cells was demonstrated by in situ hybridization with an antisense EPR-1 riboprobe, and by amplification of reverse-transcribed HD RNA with EPR- 1-specific primers. These findings identify the factor Xa receptor, EPR- 1, as a novel marker of Reed-Sternberg cells, and suggest its potential role in the histopathogenesis of HD.
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2

Cattani, Julia, Vinod Subramaniam et Malte Drescher. « Room-temperature in-cell EPR spectroscopy : alpha-Synuclein disease variants remain intrinsically disordered in the cell ». Physical Chemistry Chemical Physics 19, no 28 (2017) : 18147–51. http://dx.doi.org/10.1039/c7cp03432f.

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Hänsel, Robert, Laura M. Luh, Ivan Corbeski, Lukáš Trantirek et Volker Dötsch. « In-Cell NMR and EPR Spectroscopy of Biomacromolecules ». Angewandte Chemie International Edition 53, no 39 (28 juillet 2014) : 10300–10314. http://dx.doi.org/10.1002/anie.201311320.

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4

Piknova, Barbora, Mark T. Gladwin, Cheryl A. Hillery et Neil Hogg. « Electron Paramagnetic Resonance Study of Cell-Free Hemoglobin in Sickle Cell Disease : Potential Antioxidant Role of Haptoglobin. » Blood 106, no 11 (16 novembre 2005) : 2345. http://dx.doi.org/10.1182/blood.v106.11.2345.2345.

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Abstract It has previously been shown that red blood cell-free oxyhemoglobin (oxyHb) can affect endothelial function in Sickle Cell Disease (SCD) by virtue of its NO scavenging properties (Reiter et al, Nat Med, 2002). This reaction may have down-stream consequence via formation of metHb which has been demonstrated to have pro-oxidant properties and can oxidize low-density lipoprotein in vitro. In this study we have examined the fate of metHb in SCD vs normal plasma by examining the characteristic single line EPR signature of metHb in the g = 6 region. We show that the EPR signature of metHb differs in SCD compared with normals and exhibits a split EPR line indicative of a more rhombic heme geometry (See Figure). Figure Figure Addition of purified metHb to SCD plasma results in a conversion of the single line EPR spectrum to the rhombic form. By addition of hemin and hemoglobin to plasma constituents we have determined that the rhombic EPR spectrum is consistent with heme bound to serum albumin. In addition, immunoprecipitation of serum albumin from SCD plasma with EPR analysis of the IP fraction revealed the presence of albumin associated metHb. Interestingly, the transfer of heme from metHb to albumin is accelereated by the presence of low-density lipoprotein and inhibited by the addition of haptoglobin suggesting that plasma components can modulate heme release from metHb and that the lack of haptoglobin in SCD plasma allowed the transfer of heme from metHb to albumin. To confirm this we added metHb to SCD plasma in the presence and absence of haptoglobin and observed that the addition of haptoglobin prevented conversion of the metHb spectrum to the albumin associated split (rhombic) species. From these studies we conclude that plasma haptoglobin not only binds hemoglobin but also limits heme release from metHb. To examine potential oxidative consequences of this effect, we incubated LDL with metHb in the presence and absence of haptoglobin. Haptoglobin inhibited LDL oxidation in a dose-dependent manner. Interestingly, the 1-1 isoform of haptoglobin was much more effective than the 2-2 isoform, in agreement with published studies on the efficacy of hemoglobin binding to the two haptoglobin varieties. Additionally, we have measured levels of 8-isoprostanes in the plasma of SCD patients as an index of lipid oxidation and show that 8-isoprostane levels are significantly elevated in SCD patients (295 209 pg/ml, mean S.D., n= 13, vs. 69 37 pg/ml, mean S.D. n= 5 for normal controls). In conclusion, these studies provide evidence that the saturation of the haptoglobin clearance mechanisms in hemolytic disorders such as SCD can not only affect the NO-axis of endothelial function due to increases in cell-free hemoglobin, but can also lead to altered heme metabolism leading to lipid oxidation and formation of pro-inflammatory lipids which have the potential to alter both endothelial and red cell function.
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5

Zaman, Guido J. R., et Edward M. Conway. « The elusive factor Xa receptor : failure to detect transcripts that correspond to the published sequence of EPR-1 ». Blood 96, no 1 (1 juillet 2000) : 145–48. http://dx.doi.org/10.1182/blood.v96.1.145.

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Abstract The coagulation protease factor Xa induces cellular responses implicated in cardiovascular and inflammatory disease. Effector-cell protease receptor 1 (EPR-1) is a functionally characterized receptor of factor Xa, and the EPR-1complementary DNA (cDNA) was published. Remarkably, the cDNA encoding an inhibitor of apoptosis, survivin, is reportedly identical to that ofEPR-1 except for a few nucleotide differences and its orientation opposite to EPR-1. To isolate the EPR-1cDNA and gene, we surveyed gene databases for expressed sequence tags (ESTs) that could be derived from EPR-1. All ESTs with strong homology to EPR-1/survivin were derived from survivinand could not encode EPR-1. By polymerase chain reaction and Southern blot hybridization, EPR-1 was not detectable in the human or murine genome, but survivin was. Our data suggest that EPR-1 is either highly cell-specific or the published EPR-1 cDNA includes sequences from clones derived from survivin messenger RNA. The means by which factor Xa mediates its cellular effects requires further evaluation.
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6

Zaman, Guido J. R., et Edward M. Conway. « The elusive factor Xa receptor : failure to detect transcripts that correspond to the published sequence of EPR-1 ». Blood 96, no 1 (1 juillet 2000) : 145–48. http://dx.doi.org/10.1182/blood.v96.1.145.013k34_145_148.

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The coagulation protease factor Xa induces cellular responses implicated in cardiovascular and inflammatory disease. Effector-cell protease receptor 1 (EPR-1) is a functionally characterized receptor of factor Xa, and the EPR-1complementary DNA (cDNA) was published. Remarkably, the cDNA encoding an inhibitor of apoptosis, survivin, is reportedly identical to that ofEPR-1 except for a few nucleotide differences and its orientation opposite to EPR-1. To isolate the EPR-1cDNA and gene, we surveyed gene databases for expressed sequence tags (ESTs) that could be derived from EPR-1. All ESTs with strong homology to EPR-1/survivin were derived from survivinand could not encode EPR-1. By polymerase chain reaction and Southern blot hybridization, EPR-1 was not detectable in the human or murine genome, but survivin was. Our data suggest that EPR-1 is either highly cell-specific or the published EPR-1 cDNA includes sequences from clones derived from survivin messenger RNA. The means by which factor Xa mediates its cellular effects requires further evaluation.
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7

Damen, J., AL Mui, P. Hughes, K. Humphries et G. Krystal. « Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin receptor-expressing lymphoid cell line ». Blood 80, no 8 (15 octobre 1992) : 1923–32. http://dx.doi.org/10.1182/blood.v80.8.1923.1923.

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Abstract Retroviral gene transfer of the murine erythropoietin receptor (EpR) cDNA into the pro-B-cell line, Ba/F3, was used to generate cells expressing high EpR levels. One of the resulting clones, Ba/F3 clone C5, contained 5 integrated copies of the gene and expressed, at the cell surface, a single affinity class of EpRs at 10 to 15 times the level present on spleen cells from phenylhydrazine-treated mice. Cross- linking studies with clone C5, using 125I-Ep, yielded the same two 105- and 88-Kd major species as that seen with typical erythroid cells. This was distinct from that obtained with EpR-transfected COS cells or L cells, which gave species of 88 and 65 Kd. This suggests that the biologically active EpR complex generated in this Ba/F3 cell line may closely resemble that present in native Ep-responsive erythroid progenitor cells. Tyrosine phosphorylation experiments showed that several proteins in clone C5 cells were rapidly phosphorylated on tyrosine residues in response to Ep, one being the EpR itself. The proportion of cell surface EpRs tyrosine phosphorylated in response to Ep was substantial, reaching a maximum of approximately 10% within 30 minutes of incubation at 37 degrees C. A comparison of Ep- and murine interleukin-3 (mIL-3)-induced tyrosine phosphorylation patterns in clone C5 cells showed that both growth factors stimulated the tyrosine phosphorylation of proteins with molecular weights of 135, 93, 70, and 55 Kd. This could suggest that the Ep and mIL-3 receptors are capable of using the same tyrosine kinase in these cells.
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8

Damen, J., AL Mui, P. Hughes, K. Humphries et G. Krystal. « Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin receptor-expressing lymphoid cell line ». Blood 80, no 8 (15 octobre 1992) : 1923–32. http://dx.doi.org/10.1182/blood.v80.8.1923.bloodjournal8081923.

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Retroviral gene transfer of the murine erythropoietin receptor (EpR) cDNA into the pro-B-cell line, Ba/F3, was used to generate cells expressing high EpR levels. One of the resulting clones, Ba/F3 clone C5, contained 5 integrated copies of the gene and expressed, at the cell surface, a single affinity class of EpRs at 10 to 15 times the level present on spleen cells from phenylhydrazine-treated mice. Cross- linking studies with clone C5, using 125I-Ep, yielded the same two 105- and 88-Kd major species as that seen with typical erythroid cells. This was distinct from that obtained with EpR-transfected COS cells or L cells, which gave species of 88 and 65 Kd. This suggests that the biologically active EpR complex generated in this Ba/F3 cell line may closely resemble that present in native Ep-responsive erythroid progenitor cells. Tyrosine phosphorylation experiments showed that several proteins in clone C5 cells were rapidly phosphorylated on tyrosine residues in response to Ep, one being the EpR itself. The proportion of cell surface EpRs tyrosine phosphorylated in response to Ep was substantial, reaching a maximum of approximately 10% within 30 minutes of incubation at 37 degrees C. A comparison of Ep- and murine interleukin-3 (mIL-3)-induced tyrosine phosphorylation patterns in clone C5 cells showed that both growth factors stimulated the tyrosine phosphorylation of proteins with molecular weights of 135, 93, 70, and 55 Kd. This could suggest that the Ep and mIL-3 receptors are capable of using the same tyrosine kinase in these cells.
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9

Ovcherenko, Sergey S., Olga A. Chinak, Anton V. Chechushkov, Sergey A. Dobrynin, Igor A. Kirilyuk, Olesya A. Krumkacheva, Vladimir A. Richter et Elena G. Bagryanskaya. « Uptake of Cell-Penetrating Peptide RL2 by Human Lung Cancer Cells : Monitoring by Electron Paramagnetic Resonance and Confocal Laser Scanning Microscopy ». Molecules 26, no 18 (7 septembre 2021) : 5442. http://dx.doi.org/10.3390/molecules26185442.

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RL2 is a recombinant analogue of a human κ-casein fragment, capable of penetrating cells and inducing apoptosis of cancer cells with no toxicity to normal cells. The exact mechanism of RL2 penetration into cells remains unknown. In this study, we investigated the mechanism of RL2 penetration into human lung cancer A549 cells by a combination of electron paramagnetic resonance (EPR) spectroscopy and confocal laser scanning microscopy. EPR spectra of A549 cells incubated with RL2 (sRL2) spin-labeled by a highly stable 3-carboxy-2,2,5,5-tetraethylpyrrolidine-1-oxyl radical were found to contain three components, with their contributions changing with time. The combined EPR and confocal-microscopy data allowed us to assign these three forms of sRL2 to the spin-labeled protein sticking to the membrane of the cell and endosomes, to the spin-labeled protein in the cell interior, and to spin labeled short peptides formed in the cell because of protein digestion. EPR spectroscopy enabled us to follow the kinetics of transformations between different forms of the spin-labeled protein at a minimal spin concentration (3–16 μM) in the cell. The prospects of applications of spin-labeled cell-penetrating peptides to EPR imaging, DNP, and magnetic resonance imaging are discussed, as is possible research on an intrinsically disordered protein in the cell by pulsed dipolar EPR spectroscopy.
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10

Bonucci, Alessio, Olivier Ouari, Bruno Guigliarelli, Valérie Belle et Elisabetta Mileo. « In‐Cell EPR : Progress towards Structural Studies Inside Cells ». ChemBioChem 21, no 4 (26 septembre 2019) : 451–60. http://dx.doi.org/10.1002/cbic.201900291.

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11

Kranenburg, Onno, Benjamin L. Emmink, Jaco Knol, Winan J. van Houdt, Inne HM Borel Rinkes et Connie R. Jimenez. « Proteomics in studying cancer stem cell biology ». Expert Review of Proteomics 9, no 3 (juin 2012) : 325–36. http://dx.doi.org/10.1586/epr.12.24.

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12

Widder, Pia, Julian Schuck, Daniel Summerer et Malte Drescher. « Combining site-directed spin labeling in vivo and in-cell EPR distance determination ». Physical Chemistry Chemical Physics 22, no 9 (2020) : 4875–79. http://dx.doi.org/10.1039/c9cp05584c.

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13

Cangiotti, Michela, Sara Salucci, Michela Battistelli, Elisabetta Falcieri, Michele Mattioli, Matteo Giordani et Maria Francesca Ottaviani. « EPR, TEM and cell viability study of asbestiform zeolite fibers in cell media ». Colloids and Surfaces B : Biointerfaces 161 (janvier 2018) : 147–55. http://dx.doi.org/10.1016/j.colsurfb.2017.10.045.

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14

Czejka, Martin, Suzan Bandak, Doris Simon, Johann Schiiller, Claudia Weiss et Eva Schernhammer. « Pharmacokinetic Interaction between 4′-Epidoxorubicin and the Multidrug Resistance Reverting Agent Quinine ». Zeitschrift für Naturforschung C 50, no 7-8 (1 août 1995) : 565–70. http://dx.doi.org/10.1515/znc-1995-7-815.

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The serum and red blood cell (RBCs) disposition of epirubicin (EPR) after intravenous bolus injection without and with coadministered quinine (QUI) was investigated in patients undergoing a cyclic chemotherapy with EPR. QUI possesses a statistical significant influence on the EPR serum concentrations and, as a consequence, on the pharmacokinetic parameters for the initial distribution phase of EPR. Within the first 15 min after administration, EPR was distributed from the central compartiment distinctly faster in compare to the control, when QUI was preadministered (t1/2 = 6 min for the control group and t1/2 = 3 min with QUI; -46% , p < 0.05). Yet, in the beta-phase when drug-elimination predominates, no statistical significant influence of QUI in regard to EPR serum and RBC concentrations could be observed. Half-life of elimination was 9.5 h for the control group and 8.6 h for the QUI group (-10% ). The mean initial serum concentration (c0) was reduced significantly by QUI from 7359 ± 506 ng/ml to 4351 ± 1682 ng/ml (-42 % . p < 0.005). Furthermore. QUI caused a reduction of the serum bioavailability of EPR (expressed as AUC0-24-values) from 3404 ± 1008 ng/ml × h to 2359 ± 1073 ng/ml × h (-3 1 % , p < 0.05). Vd and Vdß were increased at about 90% and the mean total body clearance was accelerated from 45.3 to 148.7 ml/min, but due to the large standard deviations the calculated difference for these parameters was not statistically significant. In the observed time interval of 24 h, the red blood cell coefficient of distribution kRBC of EPR was lower if QUI was coadministered (kRBC = 1.25 ± 0.12 for the control group kRBC = 1.15 ± 0.13 under QUI; p < 0.04). The results point out that QUI induces an accelerated distribution of EPR from the blood into the tissue and that QUI additionally may have influence on the red-blood cell partitioning of EPR.
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Qi, Mian, Andreas Groß, Gunnar Jeschke, Adelheid Godt et Malte Drescher. « Gd(III)-PyMTA Label Is Suitable for In-Cell EPR ». Journal of the American Chemical Society 136, no 43 (17 octobre 2014) : 15366–78. http://dx.doi.org/10.1021/ja508274d.

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Holder, Isabelle T., Malte Drescher et Jörg S. Hartig. « Structural characterization of quadruplex DNA with in-cell EPR approaches ». Bioorganic & ; Medicinal Chemistry 21, no 20 (octobre 2013) : 6156–61. http://dx.doi.org/10.1016/j.bmc.2013.04.014.

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17

Haensel, Robert, Laura M. Luh, Ivan Corbeski, Lukas Trantirek et Volker Doetsch. « ChemInform Abstract : In-Cell NMR and EPR Spectroscopy of Biomacromolecules ». ChemInform 45, no 49 (20 novembre 2014) : no. http://dx.doi.org/10.1002/chin.201449278.

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Jegdić, Bore V., et Biljana M. Bobić. « Determination of susceptibility to intergranular corrosion of stainless steels type X5CrNi18-10 in field ». Metallurgical and Materials Engineering 22, no 4 (31 décembre 2016) : 251–60. http://dx.doi.org/10.30544/236.

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In this paper, the DL EPR method (electrochemical potentiokinetic reactivation with double loop) was modified and used to study the susceptibility to intergranular corrosion and stress corrosion cracking of a stainless steel type X5CrNi18-10. The tests were performed in a special electrochemical cell, with the electrolyte in the gel form. Modified DL EPR method is characterized by simple and high accuracy measurements as well as repeatability of the test results. The indicator of susceptibility to intergranular corrosion (Qr/Qp)GBA obtained by modified DL EPR method is in a very good agreement with the same indicator obtained by standard DL EPR method. The modified DL EPR method is quantitative and highly selective method. Small differences in the susceptibility of the stainless steel type CrNi18-10 to intergranular corrosion and stress corrosion cracking can be determined. Test results can be obtained in a short time. The cost of tests performed by modified DL EPR method is much lower than the cost of tests by conventional chemical methods. Modified DL EPR method can be applied in the field on the stainless steels constructions.
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Key, Fiona B., Devina McClean et J. C. Mathers. « Tissue hypertrophy and epithelial proliferation rate in the gut of rats fed on bread and haricot beans (Phaseolus vulgaris) ». British Journal of Nutrition 76, no 2 (août 1996) : 273–86. http://dx.doi.org/10.1079/bjn19960031.

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The present study was designed to test the hypothesis that increasing short-chain fatty acid (SCFA)production in the large bowel increases gut epithelial proliferation rate (EPR). Two experiments were carried out in which rats were fed on bread (wholemeal or white)-based diets containing graded amounts of cooked haricot (Phaseofus vulgaris) beans; the latter are a rich source of fermentable carbohydrates. Consumption of beans was associated with several-fold increases in SCFA production with the greatest relative increase being for butyrate. Despite the very large increase in SCFA production, there was no evidence that this had any effect on EPR in the duodenum. Where the basal diet contained wholemeal bread (Expt 1) there was no effect of enhanced SCFA supply on EPR in either the caecum or colon, but with the white bread-based diet (Expt 2) adding beans produced increments in both SCFA supply and EPR in the caecum. Evidence that SCFA are responsible for enhanced EPR above normal levels is not convincing. In those instances where enhanced SCFA supply is associated with increased EPR, the increase may be (1) from a hypoproliferative state towards normal, (2) a transient phenomenon accompanying tissue hypertrophy or (3) a homeostatic response to increased cell loss by cell sloughing or apoptosis. It is not likely that there is any direct link with risk of colon cancer
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Brown, Kristy J., Catherine A. Formolo, Haeri Seol, Ramya L. Marathi, Stephanie Duguez, Eunkyung An, Dinesh Pillai, Javad Nazarian, Brian R. Rood et Yetrib Hathout. « Advances in the proteomic investigation of the cell secretome ». Expert Review of Proteomics 9, no 3 (juin 2012) : 337–45. http://dx.doi.org/10.1586/epr.12.21.

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Kucher, Svetlana, Sergej Korneev, Johann P. Klare, Daniel Klose et Heinz-Jürgen Steinhoff. « In cell Gd3+-based site-directed spin labeling and EPR spectroscopy of eGFP ». Physical Chemistry Chemical Physics 22, no 24 (2020) : 13358–62. http://dx.doi.org/10.1039/d0cp01930e.

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22

Krosl, J., JE Damen, G. Krystal et RK Humphries. « Erythropoietin and interleukin-3 induce distinct events in erythropoietin receptor-expressing BA/F3 cells ». Blood 85, no 1 (1 janvier 1995) : 50–56. http://dx.doi.org/10.1182/blood.v85.1.50.bloodjournal85150.

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To compare the signal transduction pathways used by erythropoietin (Ep) and interleukin-3 (IL-3), the cDNA for the murine erythropoietin receptor (EpR) was introduced into the IL-3-responsive cell lines Ba/F3 and DA-3 using retrovirally mediated gene transfer. After selection in G418 and IL-3, clones expressing comparable levels of cell surface EpR were identified using biotinylated Ep and flow cytometry. A comparison of the effects of Ep and IL-3 on these cells showed that most EpR+ Ba/F3 clones, when first exposed to Ep, dramatically increased their levels of beta-globin mRNA. The kinetics of appearance of this message after exposure to Ep varied considerably from clone to clone, with some clones showing a marked increase in beta-globin mRNA within 1 hour, while others required several days before an increase was observed. Interestingly, not only was this increase not seen with IL-3, but IL-3 prevented the Ep-induced appearance of beta-globin message. On the other hand, none of the EpR+ DA-3 cell clones tested increased their levels of beta-globin mRNA in response to Ep. While the EpR+ DA-3 clones showed identical proliferative responses to IL-3 and Ep, most EpR+ Ba/F3 clones displayed a marked, albeit transient, proliferative lag when first exposed to Ep. This was manifested as both an increased doubling time in liquid culture and a decreased colony size in methylcellulose. Plating efficiencies of EpR+ Ba/F3 cells in methylcellulose, however, were identical in response to IL-3 and Ep, suggesting that the Ep-induced lag in proliferation reflected a growth delay of the entire population of cells to Ep rather than a selection of an Ep-responsive subpopulation. Flow cytometric analysis established that this growth delay was due to a lengthening of the first G1 period after exposure to Ep. Interestingly, this Ep-induced delay in entry into the S phase was not detected in cells stimulated with both Ep and IL-3 nor in EpR+ Ba/F3 cell clones that did not show an increase in beta-globin mRNA in response to Ep. Thymidine-induced growth arrest, however, showed that delaying entry into S phase alone was not sufficient to stimulate beta-globin mRNA in the absence of Ep. Further studies established that the Ep-induced increase in beta-globin mRNA could be inhibited by the tyrosine kinase inhibitor genistein and the protein kinase C inhibitor Compound 3.(ABSTRACT TRUNCATED AT 250 WORDS)
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Damen, JE, AL Mui, L. Puil, T. Pawson et G. Krystal. « Phosphatidylinositol 3-kinase associates, via its Src homology 2 domains, with the activated erythropoietin receptor ». Blood 81, no 12 (15 juin 1993) : 3204–10. http://dx.doi.org/10.1182/blood.v81.12.3204.3204.

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Abstract The erythropoietin receptor (EpR) belongs to a family of hematopoietin receptors whose members lack tyrosine kinase activity. Nonetheless, within minutes of binding Ep, a number of cellular proteins become transiently phosphorylated on tyrosine residues. One of these proteins, as we and others have shown previously, is the EpR itself. To identify the remaining protein substrates, we have examined the antiphosphotyrosine immunoprecipitates of lysates from Ba/F3 cells expressing high levels of cell surface EpRs. We now present data showing that, in response to Ep, the 85-Kd regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase) becomes immunoprecipitable with antiphosphotyrosine antibodies. This appears to be due, in large part, to the specific association of PI 3-kinase with the tyrosine- phosphorylated EpR, either directly or through a 93- or 70-Kd tyrosine- phosphorylated intermediate. The activity of this EpR associated PI 3- kinase, assessed in anti-EpR immunoprecipitates, is maximal within 2 minutes of incubation with Ep and returns almost to baseline levels by 10 minutes. In vitro studies suggest that the interaction between PI 3- kinase and the activated EpR is mediated by the N- and C-terminal SH2 domains of p85 and tyrosine-phosphorylated motifs on the EpR.
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Damen, JE, AL Mui, L. Puil, T. Pawson et G. Krystal. « Phosphatidylinositol 3-kinase associates, via its Src homology 2 domains, with the activated erythropoietin receptor ». Blood 81, no 12 (15 juin 1993) : 3204–10. http://dx.doi.org/10.1182/blood.v81.12.3204.bloodjournal81123204.

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The erythropoietin receptor (EpR) belongs to a family of hematopoietin receptors whose members lack tyrosine kinase activity. Nonetheless, within minutes of binding Ep, a number of cellular proteins become transiently phosphorylated on tyrosine residues. One of these proteins, as we and others have shown previously, is the EpR itself. To identify the remaining protein substrates, we have examined the antiphosphotyrosine immunoprecipitates of lysates from Ba/F3 cells expressing high levels of cell surface EpRs. We now present data showing that, in response to Ep, the 85-Kd regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase) becomes immunoprecipitable with antiphosphotyrosine antibodies. This appears to be due, in large part, to the specific association of PI 3-kinase with the tyrosine- phosphorylated EpR, either directly or through a 93- or 70-Kd tyrosine- phosphorylated intermediate. The activity of this EpR associated PI 3- kinase, assessed in anti-EpR immunoprecipitates, is maximal within 2 minutes of incubation with Ep and returns almost to baseline levels by 10 minutes. In vitro studies suggest that the interaction between PI 3- kinase and the activated EpR is mediated by the N- and C-terminal SH2 domains of p85 and tyrosine-phosphorylated motifs on the EpR.
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Sang, Xiancheng, Xixiang Xu, Zeyuan Bu, Shuhao Zhai, Yiming Sun, Mingyue Ruan et Qiang Li. « Application of Electron Paramagnetic Resonance in an Electrochemical Energy Storage System ». Magnetochemistry 9, no 3 (23 février 2023) : 63. http://dx.doi.org/10.3390/magnetochemistry9030063.

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The improvement of our living standards puts forward higher requirements for energy storage systems, especially rechargeable batteries. Unfortunately, phenomena such as capacity failure, etc. have been major difficulties in the field of energy storage. Therefore, we need some advanced means to explore the reaction process and mechanisms of the cell. Electron paramagnetic resonance (EPR) has the advantages of a high sensitivity to electrons, lack of damage to samples, quantitative analysis, etc., which can make for a more in-depth exploration of most paramagnetic electrode materials and metal electrode materials. After a brief description of the principle of EPR, this review briefly summarizes the application of EPR to the characterization of transition metal oxide cathode and lithium metal anode electrode materials in recent years, such as showing how to study electrode materials by using EPR in situ and operando .
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Ando, Takahiro, et Yoshiki Yonamoto. « Cell Discrimination Using In-Situ EPR Measurement of Reactive Oxygen Species ». Free Radical Biology and Medicine 87 (octobre 2015) : S108. http://dx.doi.org/10.1016/j.freeradbiomed.2015.10.283.

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Goldfarb, Daniella. « Exploring protein conformations in vitro and in cell with EPR distance measurements ». Current Opinion in Structural Biology 75 (août 2022) : 102398. http://dx.doi.org/10.1016/j.sbi.2022.102398.

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Gowthaman, Uthaman, et Javed N. Agrewala. « In silicomethods for predicting T-cell epitopes : Dr Jekyll or Mr Hyde ? » Expert Review of Proteomics 6, no 5 (octobre 2009) : 527–37. http://dx.doi.org/10.1586/epr.09.71.

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Zhelev, Zhivko, Ekaterina Georgieva, Dessislava Lazarova, Severina Semkova, Ichio Aoki, Maya Gulubova, Tatsuya Higashi et Rumiana Bakalova. « “Redox Imaging” to Distinguish Cells with Different Proliferative Indexes : Superoxide, Hydroperoxides, and Their Ratio as Potential Biomarkers ». Oxidative Medicine and Cellular Longevity 2019 (8 avril 2019) : 1–18. http://dx.doi.org/10.1155/2019/6373685.

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The present study was directed to the development of EPR methodology for distinguishing cells with different proliferative activities, using “redox imaging.” Three nitroxide radicals were used as redox sensors: (a) mito-TEMPO—cell-penetrating and localized mainly in the mitochondria; (b) methoxy-TEMPO—cell-penetrating and randomly distributed between the cytoplasm and the intracellular organelles; and (c) carboxy-PROXYL—nonpenetrating in living cells and evenly distributed in the extracellular environment. The experiments were conducted on eleven cell lines with different proliferative activities and oxidative capacities, confirmed by conventional analytical tests. The data suggest that cancer cells and noncancer cells are characterized by a completely different redox status. This can be analyzed by EPR spectroscopy using mito-TEMPO and methoxy-TEMPO, but not carboxy-PROXYL. The correlation analysis shows that the EPR signal intensity of mito-TEMPO in cell suspensions is closely related to the superoxide level. The described methodology allows the detection of overproduction of superoxide in living cells and their identification based on the intracellular redox status. The experimental data provide evidences about the role of superoxide and hydroperoxides in cell proliferation and malignancy.
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Santucci, Roberto, Federica Sinibaldi, Antonella Patriarca, Daniele Santucci et Laura Fiorucci. « Misfolded proteins and neurodegeneration : role of non-native cytochrome c in cell death ». Expert Review of Proteomics 7, no 4 (août 2010) : 507–17. http://dx.doi.org/10.1586/epr.10.50.

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Boggio, Kristin J., Emmanuel Obasuyi, Ken Sugino, Sacha B. Nelson, Nathalie YR Agar et Jeffrey N. Agar. « Recent advances in single-cell MALDI mass spectrometry imaging and potential clinical impact ». Expert Review of Proteomics 8, no 5 (octobre 2011) : 591–604. http://dx.doi.org/10.1586/epr.11.53.

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Zapparoli, Ettore, Paola Briata, Martina Rossi, Lorenzo Brondolo, Gabriele Bucci et Roberto Gherzi. « Comprehensive multi-omics analysis uncovers a group of TGF-β-regulated genes among lncRNA EPR direct transcriptional targets ». Nucleic Acids Research 48, no 16 (5 août 2020) : 9053–66. http://dx.doi.org/10.1093/nar/gkaa628.

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Abstract Long non-coding RNAs (lncRNAs) can affect multiple layers of gene expression to control crucial cellular functions. We have previously demonstrated that the lncRNA EPR, by controlling gene expression at different levels, affects cell proliferation and migration in cultured mammary gland cells and impairs breast tumor formation in an orthotopic transplant model in mice. Here, we used ChIRP-Seq to identify EPR binding sites on chromatin of NMuMG mammary gland cells overexpressing EPR and identified its trans binding sites in the genome. Then, with the purpose of relating EPR/chromatin interactions to the reshaping of the epitranscriptome landscape, we profiled histone activation marks at promoter/enhancer regions by ChIP-Seq. Finally, we integrated data derived from ChIRP-Seq, ChIP-Seq as well as RNA-Seq in a comprehensive analysis and we selected a group of bona fide direct transcriptional targets of EPR. Among them, we identified a subset of EPR targets whose expression is controlled by TGF-β with one of them—Arrdc3—being able to modulate Epithelial to Mesenchymal Transition. This experimental framework allowed us to correlate lncRNA/chromatin interactions with the real outcome of gene expression and to start defining the gene network regulated by EPR as a component of the TGF-β pathway.
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Murray, Paul R., David Collison, Simon Daff, Nicola Austin, Ruth Edge, Brian W. Flynn, Lorna Jack et al. « An in situ electrochemical cell for Q- and W-band EPR spectroscopy ». Journal of Magnetic Resonance 213, no 1 (décembre 2011) : 206–9. http://dx.doi.org/10.1016/j.jmr.2011.09.041.

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Panchenko, A., H. Dilger, E. Möller, T. Sixt et E. Roduner. « In situ EPR investigation of polymer electrolyte membrane degradation in fuel cell applications ». Journal of Power Sources 127, no 1-2 (mars 2004) : 325–30. http://dx.doi.org/10.1016/j.jpowsour.2003.09.047.

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Boś-Liedke, Agnieszka, Magdalena Walawender, Anna Woźniak, Dorota Flak, Jacek Gapiński, Stefan Jurga, Małgorzata Kucińska et al. « EPR Oximetry Sensor—Developing a TAM Derivative for In Vivo Studies ». Cell Biochemistry and Biophysics 76, no 1-2 (4 septembre 2017) : 19–28. http://dx.doi.org/10.1007/s12013-017-0824-3.

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Abstract Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.
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Barham, R. J., et D. C. Doetschman. « Single crystal electron paramagnetic resonance study of Y2BaCuO5, a common impurity in the high temperature superconductor, YBa2Cu3O7 ». Journal of Materials Research 7, no 3 (mars 1992) : 565–71. http://dx.doi.org/10.1557/jmr.1992.0565.

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Electron paramagnetic resonance (EPR) studies of pure Y2BaCuO5 in powder and single crystal forms and of YBa2Cu3O7−δ in powder and single crystal forms provide further evidence that it is Y2BaCuO5 that is the common green impurity found in many preparations of YBa2Cu3O7−δ as a powder or in pellet forms. Y2BaCuO5 tends to be excluded in the growth of YBa2Cu3O7−δ single crystals. A method is presented for the growth of Y2BaCuO5 crystals from a flux. An apparent discrepancy between the observed single crystal EPR anisotropy and the reported crystal structure is resolved in three independent ways from the Y2BaCuO5 Powder and single crystal EPR data. These results show that the EPR spectrum is a superposition of the spectra of the two differently oriented Cu sites in the unit cell and is not a spectral average of them. The temperature independence of the EPR spectrum between 150 K and 300 K is also consistent with there being no temperature dependent exchange averaging of the EPR spectra of the two sites in this range. The orientations of the Cu crystal field axes, as indicated by the g axes, are in agreement with the crystal structure. Crystal field splittings of the Cu d-orbitals are estimated from the measured g values and indicate an appreciable covalency in the Cu–O bonds. The linewidth and its anisotropy indicate a minor degree of exchange narrowing.
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Czekański, Łukasz, Stanisław K. Hoffmann, Piotr Barczyński, Anna Gąsowska, Romualda Bregier-Jarzębowska, Alina Zalewska, Janina Goslar, Małgorzata Ratajczak-Sitarz et Andrzej Katrusiak. « Crystal structure and physical properties of 1-methyl-3-(carboxymethyl)benzimidazolium betaine·CuBr2 in crystal and water solution ». New Journal of Chemistry 40, no 12 (2016) : 10526–35. http://dx.doi.org/10.1039/c6nj03192g.

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Levasseur-Acker, Germaine, Roger Zalma, Edith Copin, Jeanine Fournier, Henri Pezerat et Roger Jankowski. « Peroxydation de l'acide linolénique en présence des fibres d'amiante ou de némalite. Résultats préliminaires avec des cellules épithéliales ». Canadian Journal of Chemistry 73, no 3 (1 mars 1995) : 453–59. http://dx.doi.org/10.1139/v95-059.

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Linolenic acid (LH) peroxidation in aqueous medium is studied in the presence of fibers of chrysotile (UICC A and B), crocidolite UICC, and némalite. Preliminary studies on the peroxydation of epithelial cell membranes were also performed. Radicals (L•, LOO•) formed from the peroxidation process are detected by EPR with a spin trapping agent, POBN. The activity of these iron(II)-containing fibers is related to the formation of activated oxygen species, particularly of some highly electrophilic species (•OH or perferryl and ferryl entities). The presence of these species is shown by EPR with a spin trapping agent, DMPO, in the presence or in the absence of certain iron(II) chelators (phosphate ions, ADP, ATP,.AMP, EDTA). The formation and the nature of activated oxygen species depend on the nature both of the inorganic material and of the chelator. It is not possible to directly extrapolate the results obtained with linolenic acid to the peroxidation of epithelial cell membranes. Keywords: asbestos, peroxidation, iron chelators, activated oxygen species, EPR.
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Kegulian, Natalie C., Ralf Langen et Janet Moradian-Oldak. « The Dynamic Interactions of a Multitargeting Domain in Ameloblastin Protein with Amelogenin and Membrane ». International Journal of Molecular Sciences 24, no 4 (9 février 2023) : 3484. http://dx.doi.org/10.3390/ijms24043484.

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The enamel matrix protein Ameloblastin (Ambn) has critical physiological functions, including regulation of mineral formation, cell differentiation, and cell–matrix adhesion. We investigated localized structural changes in Ambn during its interactions with its targets. We performed biophysical assays and used liposomes as a cell membrane model. The xAB2N and AB2 peptides were rationally designed to encompass regions of Ambn that contained self-assembly and helix-containing membrane-binding motifs. Electron paramagnetic resonance (EPR) on spin-labeled peptides showed localized structural gains in the presence of liposomes, amelogenin (Amel), and Ambn. Vesicle clearance and leakage assays indicated that peptide–membrane interactions were independent from peptide self-association. Tryptophan fluorescence and EPR showed competition between Ambn–Amel and Ambn–membrane interactions. We demonstrate localized structural changes in Ambn upon interaction with different targets via a multitargeting domain, spanning residues 57 to 90 of mouse Ambn. Structural changes of Ambn following its interaction with different targets have relevant implications for the multifunctionality of Ambn in enamel formation.
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Moreira, Rodrigo Alves, Sebastião Antonio Mendanha, Kelly Souza Fernandes, Grazzielle Guimaraes Matos, Lais Alonso, Miriam Leandro Dorta et Antonio Alonso. « Miltefosine Increases Lipid and Protein Dynamics in Leishmania amazonensis Membranes at Concentrations Similar to Those Needed for Cytotoxicity Activity ». Antimicrobial Agents and Chemotherapy 58, no 6 (10 mars 2014) : 3021–28. http://dx.doi.org/10.1128/aac.01332-13.

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ABSTRACTMiltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin label in the plasma membrane ofLeishmaniapromastigotes showed that MT causes dramatic increases in membrane dynamics. Although these alterations can be detected using a spin-labeled lipid, our experimental results indicated that MT interacts predominantly with the protein component of the membrane. Cell lysis was also detected by analyzing the supernatants of centrifuged samples for the presence of spin-labeled membrane fragments and cytoplasmic proteins. Using a method for the rapid incorporation of MT into the membrane, these effects were measured immediately after treatment under the same range of MT concentrations that cause cell growth inhibition. Cytotoxicity, estimated via microscopic counting of living and dead cells, indicated ∼70% cell death at the concentration of MT at which EPR spectroscopy detected a significant change in membrane dynamics. After this initial impact on the number of viable parasites, the processes of cell death and growth continued during the first 4 h of incubation. The EPR spectra of spin-labeled membrane-bound proteins were consistent with more expanded and solvent-exposed protein conformations, suggesting a detergent-like action. Thus, MT may form micelle-like structures around polypeptide chains, and proteins with a higher hydrophobicity may induce the penetration of hydrophilic groups of MT into the membrane, causing its rupture.
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Glatzhofer, Daniel T., et Rahul S. Kadam. « Use of Electron Paramagnetic Resonance Spectroscopy to Study Dielectric Properties of Liquids ». ISRN Analytical Chemistry 2012 (9 avril 2012) : 1–8. http://dx.doi.org/10.5402/2012/847102.

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The signal response of an EPR active species is attenuated by the medium it is in. Keeping all other parameters the same, the higher the dielectric constant of the medium, the lower the EPR signal response. This behavior is problematic in studying EPR active species in high dielectric media but can be capitalized upon to monitor changes in the dielectric constant or estimate the dielectric constant of the medium. Using a coaxial EPR cell design, the EPR signal of a stable nitroxyl radical compound (2,2,6,6-tetramethyl-piperidin-1-oxyl radical) in a low dielectric constant solvent in an inner tube is attenuated by the solvent present between the inner and outer tubes (jacket medium). The attenuation increases monotonically with an increase in the dielectric constant of the jacket medium. Calibration curves can be constructed using jacket media of known dielectric constants ranging from 2 to 80 and the dielectric constant of a sample used as the jacket medium can be estimated by interpolation. This technique is applied to estimate the dielectric constants and/or composition of mixed solvents and to monitor the rate of a reaction.
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Alfei, Silvana, et Guendalina Zuccari. « One-Step, Low-Cost, Operator-Friendly, and Scalable Procedure to Synthetize Highly Pure N-(4-ethoxyphenyl)-retinamide in Quantitative Yield without Purification Work-Up ». Molecules 27, no 11 (6 juin 2022) : 3632. http://dx.doi.org/10.3390/molecules27113632.

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It is widely reported that N-(4-hydroxyphenyl)-retinamide or fenretinide (4-HPR), which is a synthetic amide of all-trans-retinoic acid (ATRA), inhibits in vitro several types of tumors, including cancer cell lines resistant to ATRA, at 1–10 µM concentrations. Additionally, studies in rats and mice have confirmed the potent anticancer effects of 4-HPR, without evidencing hemolytic toxicity, thus demonstrating its suitability for the development of a new chemo-preventive agent. To this end, the accurate determination of 4-HPR levels in tissues is essential for its pre-clinical training, and for the correct determination of 4-HPR and its metabolites by chromatography, N-(4-ethoxyphenyl)-retinamide (4-EPR) has been suggested as an indispensable internal standard. Unfortunately, only a consultable old patent reports the synthesis of 4-EPR, starting from dangerous and high-cost reagents and using long and tedious purification procedures. To the best of our knowledge, no article existed so far describing the specific synthesis of 4-EPR. Only two vendors worldwide supply 4-ERP, and its characterization was incomplete. Here, a scalable, operator-friendly, and one-step procedure to synthetize highly pure 4-EPR without purification work-up and in quantitative yield is reported. Additionally, a complete characterization of 4-EPR using all possible analytical techniques has been provided.
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Hsiang Kong, Darren Chyi, Kenneth Yew Choy Chew, Eng Lai Tan et Suan Phaik Khoo. « Epiregulin (EPR) Reduces Epidermal Growth Factor (EGF) Receptor Expression In Oral Squamous Cell Carcinoma (OSCC) Cell Lines ». Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 119, no 3 (mars 2015) : e177. http://dx.doi.org/10.1016/j.oooo.2014.07.331.

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Godovac-Zimmermann, Jasminka. « Cancer-omics failure : warehouses, magic bullets, space/time and the Life of Brian in a cancer cell ». Expert Review of Proteomics 7, no 3 (juin 2010) : 303–6. http://dx.doi.org/10.1586/epr.10.7.

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Yang, Yin, Feng Yang, Yan-Jun Gong, Jia-Liang Chen, Daniella Goldfarb et Xun-Cheng Su. « A Reactive, Rigid GdIII Labeling Tag for In-Cell EPR Distance Measurements in Proteins ». Angewandte Chemie International Edition 56, no 11 (1 février 2017) : 2914–18. http://dx.doi.org/10.1002/anie.201611051.

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Yang, Yin, Feng Yang, Yan-Jun Gong, Jia-Liang Chen, Daniella Goldfarb et Xun-Cheng Su. « A Reactive, Rigid GdIII Labeling Tag for In-Cell EPR Distance Measurements in Proteins ». Angewandte Chemie 129, no 11 (1 février 2017) : 2960–64. http://dx.doi.org/10.1002/ange.201611051.

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Noda, Yohei, Satoshi Shimono, Masaaki Baba, Jun Yamauchi, Naohiko Ikuma et Rui Tamura. « EPR Studies on Molecular Orientation in a Surface-Stabilized Paramagnetic Liquid Crystal Cell ». Journal of Physical Chemistry B 110, no 47 (novembre 2006) : 23683–87. http://dx.doi.org/10.1021/jp063836i.

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Hartl, František, Ronald P. Groenestein et Taasje Mahabiersing. « Air-Tight Three-Electrode Design of Coaxial Electrochemical-EPR Cell for Redox Studies at Low Temperatures ». Collection of Czechoslovak Chemical Communications 66, no 1 (2001) : 52–66. http://dx.doi.org/10.1135/cccc20010052.

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The weak point of the original Allendoerfer electrochemical-EPR cell has been the reference electrode, placed outside the space-limited electrolysis cavity or not used at all in experiments at low temperatures. We present here an elegant solution to this problem, based on a modified air-tight design of an Allendoerfer cell equipped with a silver-wire pseudoreference electrode. The cell performance is demonstrated on one-electron electrochemical oxidation of heterocyclic 3,6-diphenyl-1,2-dithiine and one-electron reduction of 6-methyl-6-phenylfulvene and the pseudo-octahedral complex fac-[Re(benzyl)(CO)3(dmb)] (dmb = 4,4'-dimethyl-2,2'-bipyridine). In the latter case, the EPR spectrum of the radical anion [Re(benzyl)(CO)3(dmb)]•- points to predominant localization of the unpaired electron on the dmb ligand, in agreement with UV-VIS and IR spectroelectrochemical data.
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Vesković, Ana, Đura Nakarada, Aleksandra Pavićević, Bogomir Prokić, Milka Perović, Selma Kanazir, Ana Popović-Bijelić et Miloš Mojović. « In Vivo/Ex Vivo EPR Investigation of the Brain Redox Status and Blood-Brain Barrier Integrity in the 5xFAD Mouse Model of Alzheimer's Disease ». Current Alzheimer Research 18, no 1 (28 avril 2021) : 25–34. http://dx.doi.org/10.2174/1567205018666210324121156.

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Background: Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by cognitive decline and total brain atrophy. Despite the substantial scientific effort, the pathological mechanisms underlying neurodegeneration in AD are currently unknown. In most studies, amyloid β peptide has been considered the key pathological change in AD. However, numerous Aβ-targeting treatments have failed in clinical trials. This implies the need to shift the research focus from Aβ to other pathological features of the disease. Objective: The aim of this study was to examine the interplay between mitochondrial dysfunction, oxidative stress and blood-brain barrier (BBB) disruption in AD pathology, using a novel approach that involves the application of electron paramagnetic resonance (EPR) spectroscopy. Methods: In vivo and ex vivo EPR spectroscopy using two spin probes (aminoxyl radicals) exhibiting different cell-membrane and BBB permeability were employed to assess BBB integrity and brain tissue redox status in the 5xFAD mouse model of AD. In vivo spin probe reduction decay was analyzed using a two-compartment pharmacokinetic model. Furthermore, 15 K EPR spectroscopy was employed to investigate the brain metal content. Results: This study has revealed an altered brain redox state, BBB breakdown, as well as ROS-mediated damage to mitochondrial iron-sulfur clusters, and up-regulation of MnSOD in the 5xFAD model. Conclusion: The EPR spin probes were shown to be excellent in vivo reporters of the 5xFAD neuronal tissue redox state, as well as the BBB integrity, indicating the importance of in vivo EPR spectroscopy application in preclinical studies of neurodegenerative diseases.
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Wu, Jun. « The Enhanced Permeability and Retention (EPR) Effect : The Significance of the Concept and Methods to Enhance Its Application ». Journal of Personalized Medicine 11, no 8 (6 août 2021) : 771. http://dx.doi.org/10.3390/jpm11080771.

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Chemotherapy for human solid tumors in clinical practice is far from satisfactory. Despite the discovery and synthesis of hundreds of thousands of anticancer compounds targeting various crucial units in cancer cell proliferation and metabolism, the fundamental problem is the lack of targeting delivery of these compounds selectively into solid tumor tissue to maintain an effective concentration level for a certain length of time for drug-tumor interaction to execute anticancer activities. The enhanced permeability and retention effect (EPR effect) describes a universal pathophysiological phenomenon and mechanism in which macromolecular compounds such as albumin and other polymer-conjugated drugs beyond certain sizes (above 40 kDa) can progressively accumulate in the tumor vascularized area and thus achieve targeting delivery and retention of anticancer compounds into solid tumor tissue. Targeting therapy via the EPR effect in clinical practice is not always successful since the strength of the EPR effect varies depending on the type and location of tumors, status of blood perfusion in tumors, and the physical-chemical properties of macromolecular anticancer agents. This review highlights the significance of the concept and mechanism of the EPR effect and discusses methods for better utilizing the EPR effect in developing smarter macromolecular nanomedicine to achieve a satisfactory outcome in clinical applications.
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