Search

Your search keyword '"Medical University of Bialystok"' showing total 5,305 results
Start Over Author "Medical University of Bialystok"
5,305 results on '"Medical University of Bialystok"'

2. The HF-POL Study - Multicenter Study of Polish Patients With HF and LVEF >40% (HF-POL)

Author

Medical University of Silesia, University of Opole, Medical University of Warsaw, Wroclaw Medical University, Military Institute od Medicine National Research Institute, Jagiellonian University, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warsaw, Poland, Medical University of Bialystok, Świętokrzyskie Cardiology Center of Kielce, and Regional Specialist Hospital in Rybnik

Published
2023

6. Cardiorenal Effecs of Losartan in Kidney Transplant Recipients (CELART)

Author

Medical University of Warsaw, Pomeranian Medical University Szczecin, Jagiellonian University, Medical University of Bialystok, Nicolaus Copernicus University, Medical University of Silesia, Poznan Regional Hospital, Wroclaw Medical University, and Leszek Tylicki, Professor

Published
2022

7. Muscle Assessment Through Ultrasound in the Evaluation of Acute Sarcopenia

Author

Hospital Universitario Ramon y Cajal, Universitaire Ziekenhuizen KU Leuven, Medical University of Bialystok, Catholic University of the Sacred Heart, Universitat Autonoma de Barcelona, Jagiellonian University, Universitat Pompeu Fabra, Istanbul University, University of Oldenburg, and Stany Perkisas, Principal investigator

Published
2021

18. Nephro-oncology: clinical and biochemical aspects of kidney disease and cancer

Author

Slawomir Lizakowski, Alicja Dębska-Ślizień, Ilona Kurnatowska, Maciej Jan Zaucha, Marcin Matuszewski, Beata Naumnik, Marcin Adamczak, Jerzy Chudek, Magdalena Durlik, Carla Ferrándiz-Pulido, Bartosz Foroncewicz, Ryszard Gellert, Magdalena Krajewska, Michał Nowicki, Andrzej Więcek, Jolanta Małyszko, Institut Català de la Salut, [Lizakowski S, Dębska-Ślizień A] Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdańsk, Poland. [Kurnatowska I] Department of Internal Diseases and Transplant Nephrology, Medical University of Lodz, Łódź, Poland. [Zaucha MJ] Department of Hematology and Transplantology, Medical University of Gdansk, Gdańsk, Poland. [Matuszewski M] Department of Urology, Medical University of Gdansk, Gdańsk, Poland. [Naumnik B] 1st Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Białystok, Poland. [Ferrándiz-Pulido C] Servei de Dermatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Neoplasms [DISEASES], neoplasias [ENFERMEDADES], Insuficiència renal crònica - Factors de risc, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::insuficiencia renal crónica [ENFERMEDADES], terapéutica::tratamiento de reemplazo renal::diálisis renal [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diàlisi, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronic [DISEASES], Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Càncer - Factors de risc, Therapeutics::Renal Replacement Therapy::Renal Dialysis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], General Biochemistry, Genetics and Molecular Biology
Abstract

Kidney disease; Cancer Enfermedad renal; Cáncer Malaltia renal; Càncer Onco-nephrology is a new field of medicine which combines many aspects of kidney injury in cancer patients and cancers in patients with kidney disease. This connection takes many forms and includes drug-induced nephrotoxicity, electrolyte disorders, numerous paraneoplastic syndromes and an increased rate cancers in dialysis and transplanted patients. The appropriate laboratory assessment of the kidney function allows to optimize chemotherapy and thus minimizes the risk of complications. This article focuses on acute kidney injury (AKI), chronic kidney disease (CKD), various electrolyte and acid-base disorders, the most common cancers after kidney transplantation and the kidney disorders associated with HSCT (hematopoietic stem cell transplantation). The possibility of the application of novel cancer therapy, such as cancer immunotherapy and proton therapy in transplant recipients was also discussed.

Published
2023

19. Novel Selenoesters as a Potential Tool in Triple-Negative Breast Cancer Treatment

Author

Dominika Radomska, Robert Czarnomysy, Anna Szymanowska, Dominik Radomski, Enrique Domínguez-Álvarez, Anna Bielawska, Krzysztof Bielawski, and Medical University of Bialystok

Subjects
breast cancer, triple-negative breast cancer, anticancer drugs, selenium compounds, organoselenium compounds, selenoesters, apoptosis, cell signaling, flow cytometry, Cancer Research, Oncology
Abstract

Disturbing cancer statistics, especially for breast cancer, are becoming a rationale for the development of new anticancer therapies. For the past several years, studies have been proving a greater role of selenium in the chemoprevention of many cancers than previously considered; hence, a trend to develop compounds containing this element as potential agents with anticancer activity has been set for some time. Therefore, our study aimed to evaluate the anticancer activity of novel selenoesters (EDA-71, E-NS-4) in MCF-7 and MDA-MB-231 human breast cancer cells. The assays evaluating proliferation and cell viability, and flow cytometer analysis of apoptosis/autophagy induction, changes in mitochondrial membrane potential, disruption of cell cycle phases, and protein activity of mTOR, NF-κB, cyclin E1/A2, and caspases 3/7, 8, 9, 10 were performed. The obtained results indicate that the tested selenoesters are highly cytotoxic and exhibit antiproliferative activity at low micromolar doses (, This manuscript was supported by the Medical University of Bialystok (Grant No. SUB/2/DN/22/003/2217)

Published
2022

21. Editorial: The Role of Sphingolipid Metabolism in the Development of Type 2 Diabetes and Obesity

Author

Agnieszka Blachnio-Zabielska, Eric Hajduch, Hervé Le Stunff, Epidemiology and Metabolic Disorders Department [Medical University of Bialystok], Medical University of Białystok (MUB), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université

Subjects
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ceramides, Endocrinology, Diabetes and Metabolism, sphingosine-1-phosphate, ApoM, biomarkers, type 2 diabetes, lipotoxicity, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, RC648-665, Diseases of the endocrine glands. Clinical endocrinology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2022

22. Activity of the human immortalized endothelial progenitor cell line HEPC-CB.1 supporting in vitro angiogenesis

Author

Karol Charkiewicz, Maria Paprocka, Agnieszka Krawczenko, Aleksandra Bielawska-Pohl, Danuta Duś, Aneta Kantor, Claudine Kieda, Catherine Grillon, Hirszfeld Institute of Immunology and Experimental Therapy, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Medical University of Bialystok, GRILLON, Catherine, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Medical University of Białystok (MUB)

Subjects
Vascular Endothelial Growth Factor A, 0301 basic medicine, CD31, EPC secretome, Angiogenesis, EPC function, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 0302 clinical medicine, HLA Antigens, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cyclic AMP, Angiogenic Proteins, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cell Line, Transformed, Endothelial Progenitor Cells, Tube formation, Chemistry, Cell Differentiation, General Medicine, Fetal Blood, Cell Hypoxia, 3. Good health, Cell biology, Endothelial stem cell, 030220 oncology & carcinogenesis, Cytokines, CD146, Original Article, Cell Division, Neovascularization, Physiologic, Tretinoin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Real-Time Polymerase Chain Reaction, Endothelial progenitor cell, Colony-Forming Units Assay, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, CD, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Human Umbilical Vein Endothelial Cells, Genetics, Humans, Regeneration, RNA, Messenger, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Progenitor cell, Molecular Biology, Endothelial Cells, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, EPC, Coculture Techniques, Clone Cells, Oxygen, 030104 developmental biology, Cell culture, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

The human HEPC-CB.1 cell line with many characteristics of endothelial progenitor cells (EPC) was tested for its proangiogenic properties as a potentially therapeutic compound. HEPC-CB.1 cells’ potential to differentiate into endothelial cells was revealed after treating the cells with a mixture of ATRA, cAMP and VEGF, as shown by the reduced expression levels of CD133, CD271 and CD90 antigens, augmentation of CD146 and CD31, and a decrease in cell clonogenicity. The cooperation of HEPC-CB.1 with the endothelial cell line HSkMEC.2 resulted in the formation of a common network. Tube formation was significantly more effective when resulting from HEPC-CB.1 and HSkMEC.2 cell co-culture as compared to a monoculture of each cell line. The exocrine mechanism of HEPC-CB.1 and HSkMEC.2 cross talk by secreted factors was evidenced using the HEPC-CB.1 supernatant to increase the efficacy of HSkMEC.2 tube formation. The proangiogenic factors produced by HEPC-CB.1 were identified using cytokine antibody array. Out of 120 examined factors, the HEPC-CB.1 cell line produced 63, some with known angiogenic activity. As in vivo the angiogenic process occurs at low oxygen tension, it was observed that in hypoxia, the production of defined factors was augmented. The presented results demonstrate that HEPC-CB.1 cells are able to both cooperate and integrate in a newly formed network and produce factors that help the network formation. The results suggest that HEPC-CB.1 cells are indeed endothelial progenitors and may prove to be an effective tool in regenerative medicine. Electronic supplementary material The online version of this article (10.1007/s11033-020-05662-6) contains supplementary material, which is available to authorized users.

Published
2020

23. Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise

Author

Hingst, Janne, Kjøbsted, Rasmus, Birk, Jesper, Jørgensen, Nicolas, Larsen, Magnus, Kido, Kohei, Larsen, Jeppe, Kjeldsen, Sasha, Fentz, Joachim, Frøsig, Christian, Holm, Stephanie, Fritzen, Andreas, Dohlmann, Tine, Larsen, Steen, Foretz, Marc, Viollet, Benoit, Schjerling, Peter, Overby, Peter, Halling, Jens, Pilegaard, Henriette, Helsten, Ylva, Wojtaszewski, Jørgen, Viollet, Benoit, University of Copenhagen = Københavns Universitet (UCPH), Department of Nutrition, Exercise and Sports [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Medical University of Białystok (MUB), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Copenhagen = Københavns Universitet (KU), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Medical University of Bialystok [Bialystok, Pologne], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
AMPK, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, exercise, glycogen, muscle metabolism, fat oxidation, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, glucose uptake
Abstract

International audience; Objective: Current evidence for AMPK-mediated regulation of skeletal muscle metabolism during exercise is mainly based on transgenic mouse models with chronic (lifelong) disruption of AMPK function. Findings based on such models are potentially biased by secondary effects related to chronic lack of AMPK function. In an attempt to study the direct effect(s) of AMPK on muscle metabolism during exercise, we generated a new mouse model with inducible muscle-specific deletion of AMPKα catalytic subunits in adult mice.Methods: Tamoxifen-inducible and muscle-specific AMPKα1/α2 double KO mice (AMPKα imdKO) were generated using the Cre/loxP system with the Cre driven by the human skeletal muscle actin (HSA) promotor.Results: During treadmill running at the same relative exercise intensity, AMPKα imdKO mice showed greater depletion of muscle ATP, which was associated with accumulation of the deamination product IMP. Muscle-specific deletion of AMPKα in adult mice promptly reduced maximal running speed, muscle glycogen content and was associated with reduced expression of UGP2, a key component of the glycogen synthesis pathway. Muscle mitochondrial respiration, whole body substrate utilization as well as muscle glucose uptake and fatty acid (FA) oxidation during muscle contractile activity remained unaffected by muscle-specific deletion AMPKα subunits in adult mice.Conclusions: Inducible deletion of AMPKα subunits in adult mice reveals that AMPK is required for maintaining muscle ATP levels and nucleotide balance during exercise, but is dispensable for regulating muscle glucose uptake, FA oxidation and substrate utilization during exercise.

Published
2020

24. A 300 IR sublingual tablet is an effective, safe treatment for house dust mite-induced allergic rhinitis: An international, double-blind, placebo-controlled, randomized phase III clinical trial

Author

Krzysztof Kowal, Peter S. Creticos, Margitta Worm, Philippe Gevaert, Pascal Demoly, Frédéric de Blay, N. Nenasheva, Oliver Pfaar, Miguel Tortajada-Girbés, Carmen Vidal, Jonathan Corren, Thomas B. Casale, Giovanni Passalacqua, Peter Hellings, Martine Le Gall, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Université de Montpellier (UM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Johns Hopkins University School of Medicine [Baltimore], CHU Strasbourg, Universiteit Gent = Ghent University [Belgium] (UGENT), University Hospitals Leuven [Leuven], Medical University of Bialystok [Bialystok, Pologne], Stallergenes SA (Stallergenes), Stallergenes, Ospedale Policlinico San Martino [Genoa], University of Genoa (UNIGE), Philipps Universität Marburg, Dr Peset University Hospital, Universitat de València (UV), Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), Universidade de Santiago de Compostela [Spain] (USC ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of South Florida [Tampa] (USF), Ear, Nose and Throat, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of California (UC), Universiteit Gent = Ghent University (UGENT), Medical University of Białystok (MUB), Ministry of Health of the Russian Federation (MHRF), Università degli studi di Genova = University of Genoa (UniGe), Philipps Universität Marburg = Philipps University of Marburg, and CERRAMON, Laura

Subjects
0301 basic medicine, Allergen immunotherapy, allergic rhinitis, allergy, house-dust mite, medication score, sublingual immunotherapy, symptom score, tablet, total combined score, Male, Allergy, International Cooperation, Severity of Illness Index, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, house dust mite, biology, Pyroglyphidae, 3. Good health, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Adult, medicine.medical_specialty, Adolescent, Drug-Related Side Effects and Adverse Reactions, Immunology, Placebo, 03 medical and health sciences, Young Adult, Double-Blind Method, Internal medicine, medicine, Animals, Humans, Antigens, Dermatophagoides, Asthma, House dust mite, Sublingual Immunotherapy, business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, biology.organism_classification, Placebo Effect, Rhinitis, Allergic, Clinical trial, 030104 developmental biology, 030228 respiratory system, Quality of Life, business
Abstract

Background: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies. Objective: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged >_12) and adults with moderate to severe HDM-induced allergic rhinitis. Methods: In a phase III, international, double-blind, placebo controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300 IR tablet. The primary end point was the average total combined score during 4 weeks at the end of the treatment period. Results: A total of 1607 participants were randomized, and 1476 (including 555 [37.6%] with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean average total combined score in the 300 IR group (3.62) was significantly lower (P Superscript/Subscript Available

Published
2019

26. A new leptin-mediated mechanism for stimulating fatty acid oxidation

Author

Swati S. Jain, Iman Momken, Jan F. C. Glatz, Joost J. F. P. Luiken, Miranda Nabben, Adrian Chabowski, Ellen Dirkx, Jay T. McFarlan, Arend Bonen, RS: CARIM - R2.07 - Gene regulation, Cardiologie, Moleculaire Genetica, RS: CARIM - R2.06 - Intermediate cardiac metabolism, Unité de biologie intégrative des adaptations à l'exercice (UBIAE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, Maastricht University [Maastricht], University of Guelph, and Medical University of Białystok (MUB)

Subjects
0301 basic medicine, CD36 Antigens, Leptin, [SDV]Life Sciences [q-bio], Glucose uptake, CD36, Oleic Acids, animal cell, AMP-Activated Protein Kinases, Biochemistry, Western blotting, Mice, Sarcolemma, CD36 antigen, Myocyte, rat, animal, genetics, Myocytes, Cardiac, Phosphorylation, Beta oxidation, sulfo-N-succinimidyl oleate, fatty acid oxidation, fatty acid transport, chemistry.chemical_classification, Mice, Knockout, cardiac muscle cell, biology, Chemistry, MEMBRANE-PROTEINS, Fatty Acids, ACTIVATED PROTEIN-KINASE, hydroxymethylglutaryl coenzyme A reductase kinase, Skeletal, succinimide derivative, Protein Transport, medicine.anatomical_structure, priority journal, enzyme active site, Muscle, SKELETAL-MUSCLE, LIPID-ACCUMULATION, Cardiac, Oxidation-Reduction, Vidarabine, medicine.medical_specialty, Knockout, Succinimides, CELLULAR REDISTRIBUTION, RAT CARDIAC MYOCYTES, OB/OB MICE, Article, Fatty acid-binding protein, Cell Line, 03 medical and health sciences, male, Internal medicine, medicine, Animals, controlled study, skeletal muscle, Antigens, Muscle, Skeletal, Molecular Biology, mouse, Myocytes, Cd36 protein, nonhuman, GLUCOSE-UPTAKE, Skeletal muscle, Fatty acid, AMPK, enzyme activation, Cell Biology, TRANSPORT, protein phosphorylation, Rats, 030104 developmental biology, Endocrinology, oleic acid, drug effects, PLASMA-MEMBRANE, biology.protein, fatty acid, knockout mouse, cell membrane, metabolism, oxidation reduction reaction, energy yield
Abstract

International audience; Leptin stimulates fatty acid oxidation in muscle and heart; but, the mechanism by which these tissues provide additional intracellular fatty acids for their oxidation remains unknown. We examined, in isolated muscle and cardiac myocytes, whether leptin, via AMP-activated protein kinase (AMPK) activation, stimulated fatty acid translocase (FAT/CD36)-mediated fatty acid uptake to enhance fatty acid oxidation. In both mouse skeletal muscle and rat cardiomyocytes, leptin increased fatty acid oxidation, an effect that was blocked when AMPK phosphorylation was inhibited by adenine 9-β-D-arabinofuranoside or Compound C. In wild-type mice, leptin induced the translocation of FAT/CD36 to the plasma membrane and increased fatty acid uptake into giant sarcolemmal vesicles and into cardiomyocytes. In muscles of FAT/CD36-KO mice, and in cardiomyocytes in which cell surface FAT/CD36 action was blocked by sulfo-N-succinimidyl oleate, the leptin-stimulated influx of fatty acids was inhibited; concomitantly, the normal leptin-stimulated increase in fatty acid oxidation was also prevented, despite the normal leptin-induced increase in AMPK phosphorylation. Conversely, in muscle of AMPK kinase-dead mice, leptin failed to induce the translocation of FAT/CD36, along with a failure to stimulate fatty acid uptake and oxidation. Similarly, when siRNA was used to reduce AMPK in HL-1 cardiomyocytes, leptin failed to induce the translocation of FAT/CD36. Our studies have revealed a novel mechanism of leptin-induced fatty acid oxidation in muscle tissue; namely, this process is dependent on the activation of AMPK to induce the translocation of FAT/CD36 to the plasma membrane, thereby stimulating fatty acid uptake. Without increasing this leptin-stimulated, FAT/CD36-dependent fatty acid uptake process, leptin-stimulated AMPK phosphorylation does not enhance fatty acid oxidation. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Published
2017

27. Advantages and disadvantages of the use of the CSF Amyloid β (Aβ) 42/40 ratio in the diagnosis of Alzheimer’s Disease

Author

Markus Otto, Henrik Zetterberg, Piotr Lewczuk, Oskar Hansson, Sylvain Lehmann, Clinical Memory Research Unit [Malmö, Suède], Department of Clinical Sciences [Malmö, Suède], Lund University [Malmö, Suède]-Lund University [Malmö, Suède], Memory Clinic [Malmö, Suède], Skåne University Hospital [Malmö, Suède], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Neurology [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Clinical Neurochemistry Laboratory [Göteborg, Suède], Department of Psychiatry and Neurochemistry [Goteborg], Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg]-Institute of Neuroscience and Physiology [Göteborg]-Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Neurodegenerative Disease [Londres, Royaume-Uni], Institute of Neurology [London], University College of London [London] (UCL)-University College of London [London] (UCL), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Department of Psychiatry and Psychotherapy [Erlangen, Allemagne], Universitätsklinikum Erlangen [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Neurodegeneration Diagnostics [Bialystok, Pologne], Medical University of Bialystok [Bialystok, Pologne], Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Friedrich-Alexander Universität Erlangen-Nürnberg (FAU)-Universitätsklinikum Erlangen [Erlangen, Allemagne], Fujirebio Europe sponsored this paper, however, it had no influence on its factual content. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. OH has acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio and Euroimmun. HZ’s research is supported by the Swedish Research Council, the European Research Council, the Knut and Alice Wallenberg Foundation, the Olav Thon Foundation, the UK Dementia Research Institute at UCL and Swedish State Support for Clinical Research (ALFGBG)., Lund University [Lund]-Lund University [Lund], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Medical University of Białystok (MUB), and Bodescot, Myriam

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Neurology, Amyloid β, Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Diagnostic accuracy, Disease, Review, Aβ 42/40 ratio, Alzheimer's Disease, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Medizinische Fakultät, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ddc:610, Alzheimer’s Disease, Cognitive impairment, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biochemical markers, lcsh:Neurology. Diseases of the nervous system, Cerebrospinal Fluid, Amyloid beta-Peptides, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Peptide Fragments, 030104 developmental biology, Aβ42/40 ratio, Neurology (clinical), business, 030217 neurology & neurosurgery, Amyloidβ Peptides, Biomarkers
Abstract

International audience; The cerebrospinal fluid (CSF) biochemical markers (biomarkers) Amyloidβ 42 (Aβ42), total Tau (T-tau) and Tau phosphorylated at threonine 181 (P-tau181) have proven diagnostic accuracy for mild cognitive impairment and dementia due to Alzheimer's Disease (AD). In an effort to improve the accuracy of an AD diagnosis, it is important to be able to distinguish between AD and other types of dementia (non-AD). The concentration ratio of Aβ42 to Aβ40 (Aβ42/40 Ratio) has been suggested to be superior to the concentration of Aβ42 alone when identifying patients with AD. This article reviews the available evidence on the use of the CSF Aβ42/40 ratio in the diagnosis of AD. Based on the body of evidence presented herein, it is the conclusion of the current working group that the CSF Aβ42/40 ratio, rather than the absolute value of CSF Aβ42, should be used when analysing CSF AD biomarkers to improve the percentage of appropriately diagnosed patients.

Published
2019

28. Long-Term Measures of Dyslipidemia, Inflammation, and Oxidative Stress in Rats Fed a High-Fat/High-Fructose Diet

Author

Béatrice Bonafos, Charles Coudray, Thierry Durand, Gilles Fouret, Agnieszka Blachnio-Zabielska, Christine Feillet-Coudray, Jennifer Rieusset, Bernard Jover, Jean-François Landrier, Claire Vigor, François Casas, Sylvie Gaillet, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical University of Bialystok, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Faculté de Médecine Lyon-Sud, FACULTE DE LYON, Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre recherche en CardioVasculaire et Nutrition (C2VN), Medical University of Białystok (MUB), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MORNET, Dominique

Subjects
0301 basic medicine, Blood Glucose, Male, Hepatic steatosis, [SDV]Life Sciences [q-bio], medicine.disease_cause, Biochemistry, [CHIM] Chemical Sciences, 2. Zero hunger, chemistry.chemical_classification, biology, Chemistry, Glutathione peroxidase, Lipids, Metabolic syndrome, [SDV] Life Sciences [q-bio], High-fat diet, Liver, medicine.medical_specialty, Fructose, Diet, High-Fat, Isoprostanoids, Thiobarbituric Acid Reactive Substances, Superoxide dismutase, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, TBARS, Animals, High- fat diet, [CHIM]Chemical Sciences, Obesity, Rats, Wistar, Glucose intolerance, Dyslipidemias, Inflammation, 030109 nutrition & dietetics, Superoxide Dismutase, Organic Chemistry, Cell Biology, medicine.disease, Rats, 030104 developmental biology, Endocrinology, Oxidative stress, biology.protein, Rat, Steatohepatitis, Steatosis, Reactive Oxygen Species, Dyslipidemia
Abstract

International audience; Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.

Published
2019

29. The PDS 110 observing campaign - photometric and spectroscopic observations reveal eclipses are aperiodic

Author

M. Banfi, Simona Ciceri, C. Kotnik, S. Vanaverbeke, Matthias Mallonn, Christopher A. Watson, John Briol, H. Boussier, Joseph E. Rodriguez, P. Lewin, S. P. Littlefair, Elizabeth O. Waagen, D. W. Latham, Matthew A. Kenworthy, Alexander Scholz, F. Dubois, Edward Gomez, Richard Wilson, Gabriel Murawski, R. Papini, T. Killestein, Mike Calkins, Rafael Sfair, H. Relles, Matthew R. Burleigh, E. Dose, R. Jayawardhana, U. Quadri, G. Zhou, Peter J. Wheatley, C. Lopresti, M. Hippke, E. J. W. de Mooij, S. Kafka, Richard G. West, Jeff W. Robertson, Grant M. Kennedy, S. Dvorak, G. Myers, Liam Raynard, V. S. Dhillon, Daniel F. Evans, L. Rizzuti, P. Benni, Alessandro Marchini, J. McCormac, Maximilian N. Günther, S. N. Quinn, Timothy Butterley, K. Hills, Luigi Mancini, S. M. Brincat, Alexis M. S. Smith, L. Barbieri, R. James, Perry Berlind, I. S. Becker, Allyson Bieryla, M. Deldem, S. Ferratfiat, John Southworth, Velimir A. Popov, P. Chote, F.-J. Hambsch, E. Herrero, Othon C. Winter, S. J. Fossey, G. Bonnoli, D. Lemay, J. Hall, F. Salvaggio, Hugh P. Osborn, Gil Esquerdo, Thiam-Guan Tan, Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), UMR 7326, Leiden University, Harvard-Smithsonian Center for Astrophysics, University of Warwick, Las Cumbres Observatory, Dublin City University, Sonneberg Observatory, Universidade Estadual Paulista (Unesp), Acton Sky Portal (Private observatory), University of Siena, University of Leicester, University of Durham, Alba Nova University Center, University of Sheffield, Instituto de Astrofísica de Canarias, AstroLAB IRIS, Keele University, UCL Observatory (UCLO), University College London, Cavendish Laboratory, Vereniging Voor Sterrenkunde (VVS), Institut d'Estudis Espacials de Catalunya (IEEC), York University, American Association of Variable Star Observers, Leibniz-Institut für Astrophysik Potsdam (AIP), University of Rome Tor Vergata, Max-Planck-Institut für Astronomie Königstuhl 17, INAF - Astrophysical Observatory of Turin, Medical University of Bialystok, Shumen University, Arkansas Tech University, Astronomy, German Aerospace Center, Perth Exoplanet Survey Telescope (PEST), Queen's University Belfast, University of St Andrews. School of Physics and Astronomy, and University of St Andrews. St Andrews Centre for Exoplanet Science

Subjects
FOS: Physical sciences, Protoplanetary discs, Astrophysics, 01 natural sciences, Photometry (optics), Her-big Ae/Be, Settore FIS/05 - Astronomia e Astrofisica, 0103 physical sciences, QB Astronomy, 010303 astronomy & astrophysics, QC, Solar and Stellar Astrophysics (astro-ph.SR), QB, Physics, Earth and Planetary Astrophysics (astro-ph.EP), stars: variables: T Tauri, [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], 010308 nuclear & particles physics, protoplanetary discs, stars: individual:PDS 110, stars: variables: T Tauri, Herbig Ae/Be, Herbig Ae/Be, Astronomy and Astrophysics, 3rd-DAS, Radial velocity, QC Physics, protoplanetary discs – stars: individual:PDS 110 – stars: variables: T Tauri, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Aperiodic graph, [SDU]Sciences of the Universe [physics], variables: T Tauri [Stars], Periodic orbits, protoplanetary discs – stars: individual:PDS 110 – stars: variables: T Tauri, Herbig Ae/Be, individual:PDS 110 [Stars], variables: T Tauri, Herbig Ae/Be [Stars], Astrophysics - Earth and Planetary Astrophysics
Abstract

PDS 110 is a young disk-hosting star in the Orion OB1A association. Two dimming events of similar depth and duration were seen in 2008 (WASP) and 2011 (KELT), consistent with an object in a closed periodic orbit. In this paper we present data from a ground-based observing campaign designed to measure the star both photometrically and spectroscopically during the time of predicted eclipse in September 2017. Despite high-quality photometry, the predicted eclipse did not occur, although coherent structure is present suggesting variable amounts of stellar flux or dust obscuration. We also searched for RV oscillations caused by any hypothetical companion and can rule out close binaries to 0.1 $M_\odot$. A search of Sonneberg plate archive data also enabled us to extend the photometric baseline of this star back more than 50 years, and similarly does not re-detect any deep eclipses. Taken together, they suggest that the eclipses seen in WASP and KELT photometry were due to aperiodic events. It would seem that PDS 110 undergoes stochastic dimmings that are shallower and shorter-duration than those of UX Ori variables, but may have a similar mechanism., Comment: Accepted to MNRAS; 12 pages, 7 figures; Supplementary photometric data in zipped latex source as all_photometry.csv

Published
2019

30. Long-term follow-up of muscle lipid accumulation, mitochondrial activity and oxidative stress and their relationship with impaired glucose homeostasis in high fat high fructose diet-fed rats

Author

Bruno Baréa, Charles Coudray, Sylvie Gaillet, Yang Wang, Christine Feillet-Coudray, Gilles Fouret, Jérôme Lecomte, Cedric Moro, David Crouzier, Agnieszka Blachnio-Zabielska, Thibault Leroy, Béatrice Bonafos, College of animal sciences, Zhejiang University, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Department of Physiology, Hygiene, Epidemiology Metabolic Disorders Department, Medical University of Bialystok, UMR1048, Institute of Metabolic and Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées (IRBA), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Medical University of Białystok (MUB), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, Glucose uptake, [SDV]Life Sciences [q-bio], Clinical Biochemistry, muscle metabolism, Adipose tissue, medicine.disease_cause, Biochemistry, Santé publique, 0302 clinical medicine, Glucose homeostasis, Homeostasis, oxidative stress, S30 - Régimes alimentaires et maladies nutritionnelles, Phospholipids, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, Chemistry, Fatty Acids, [SDV] Life Sciences [q-bio], impaired glucose homeostasis, S50 - Santé humaine, muscle lipid composition, high fat/high fructose diet, Polyunsaturated fatty acid, medicine.medical_specialty, Modèle animal, Homéostasie, 030209 endocrinology & metabolism, free radicals, Fructose, Ceramides, Diet, High-Fat, 03 medical and health sciences, mitochondrial function, Internal medicine, Régime alimentaire, medicine, Animals, Rats, Wistar, Muscle, Skeletal, Molecular Biology, Surpoids, Stress oxydatif, medicine.disease, Lipid Metabolism, Mitochondria, Muscle, 030104 developmental biology, Endocrinology, Glucose, Rat, Metabolic syndrome, U30 - Méthodes de recherche, Reactive Oxygen Species, Oxidative stress, Dyslipidemia
Abstract

Metabolic syndrome components, including obesity, dyslipidemia and impaired glucose homeostasis, become a major public health issue. Muscles play a predominant role in insulin-mediated glucose uptake, and high fat diets may negatively affect muscle function and homeostasis. This work aimed to study the time-course of muscle lipid accumulation, oxidative stress and mitochondrial dysfunction and their association to impaired glucose homeostasis in rats fed an obesogenic diet. Male Wistar rats were fed with a standard or a high fat/high fructose (HFHFr) diet and sacrificed on 4, 8, 12, 16, 20 weeks. Rats fed the HFHFr diet developed mild overweight, increased liver and adipose tissue weights and glucose intolerance. The impaired glucose homeostasis increased gradually with the HFHFr diet to become significant on the 12th and 16th weeks of diet. In parallel, the muscle lipid composition showed an increase in the saturated fatty acids and the monounsaturated fatty acids with a marked decrease in the polyunsaturated fatty acids. The HFHFr diet also increased muscle contents of both diacylglycerols and Ceramides. Surprisingly, HFHFr diet did not induce major muscle mitochondrial dysfunction or oxidative stress. These results indicate that muscle lipid alterations, as well as impaired glucose homeostasis occur as early as the 8th week of HFHFr diet, increase to reach a plateau around the 12th-16th weeks of diet, and then attenuate towards the end of study. At these diet treatment durations, muscle mitochondrial activity and oxidative stress remained unchanged and do not seem to have a major role in the observed impaired glucose homeostasis.

Published
2019

31. Short Term Palmitate Supply Impairs Intestinal Insulin Signaling via Ceramide Production

Author

Armelle Leturque, Agnieszka Blachnio-Zabielska, Véronique Carrière, Sylvie Demignot, Eric Hajduch, Jean-Paul Pais de Barros, Pascal Ferré, Bárbara Graziela Postal, Agnès Ribeiro, Céline Osinski, Monique Rousset, Thi Thu Trang Tran, Centre de Recherche des Cordeliers ( CRC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Medical University of Bialystok, Physiologie de la Nutrition et Toxicologie (NUTox) (U866, Lipides et nutrition, équipe 7) (NUTox), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de santé publique et informatique médicale INSERM U872, Université Pierre et Marie Curie - Paris 6 (UPMC), Unité de génétique somatique, Institut Curie [Paris], Plateforme Lipidomique [Dijon] (LAP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Bialystok Med Univ, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies nutritionnelles et métaboliques : obésité et diabète, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Medical University of Białystok (MUB), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
0301 basic medicine, medicine.medical_specialty, Ceramide, medicine.medical_treatment, Palmitic Acid, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Palm Oil, Ceramides, Biochemistry, Palmitic acid, Mice, 03 medical and health sciences, chemistry.chemical_compound, Insulin resistance, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, medicine, Animals, Humans, Insulin, Plant Oils, Intestinal Mucosa, Phosphorylation, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, biology, Triglyceride, Cell Biology, Lipid signaling, medicine.disease, Lipids, 3. Good health, Insulin receptor, Enterocytes, 030104 developmental biology, Endocrinology, chemistry, Saturated fatty acid, biology.protein, Caco-2 Cells, Proto-Oncogene Proteins c-akt, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract

International audience; The worldwide prevalence of metabolic diseases is increasing, and there are global recommendations to limit consumption of certain nutrients, especially saturated lipids. Insulin resistance, a common trait occurring in obesity and type 2 diabetes, is associated with intestinal lipoprotein overproduction. However, the mechanisms by which the intestine develops insulin resistance in response to lipid overload remain unknown. Here, we show that insulin inhibits triglyceride secretion and intestinal microsomal triglyceride transfer protein expression in vivo in healthy mice force-fed monounsaturated fatty acid-rich olive oil but not in mice force-fed saturated fatty acid-rich palm oil. Moreover, when mouse intestine and human Caco-2/TC7 enterocytes were treated with the saturated fatty acid, palmitic acid, the insulin-signaling pathway was impaired. We show that palmitic acid or palm oil increases ceramide production in intestinal cells and that treatment with a ceramide analogue partially reproduces the effects of palmitic acid on insulin signaling. In Caco-2/TC7 enterocytes, ceramide effects on insulin-dependent AKT phosphorylation are mediated by protein kinase C but not by protein phosphatase 2A. Finally, inhibiting de novo ceramide synthesis improves the response of palmitic acid-treated Caco-2/TC7 enterocytes to insulin. These results demonstrate that a palmitic acid-ceramide pathway accounts for impaired intestinal insulin sensitivity, which occurs within several hours following initial lipid exposure.

Published
2016

32. Real-world safety and effectiveness of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C virus genotype 1- and 4-infected patients with diverse comorbidities and comedications: A pooled analysis of post-marketing observational studies from 13 countries

Author

Mariem Charafeddine, Henning Kleine, Peter Ferenci, David Back, Suzanne Norris, Dominique Larrey, Eric Crown, Robert Flisiak, Manuela Curescu, Patrick K. Dorr, Suzanne Bourgeois, Mark Bondin, Peter Buggisch, Fiona Marra, Dept of internal medicine III, Medizinische Universität Wien = Medical University of Vienna, ZNA Stuivenberg, Institute for Interdisciplinary Medicine Hamburg, Department of Hepatology, St. James's Hospital, West University of Timișoara [Roumanie] (WUT), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Liverpool, AbbVie Deutschland GmbH & Co KG, Abbott GmbH & Co KG, Abbvie Inc. [North Chicago], Medical University of Bialystok [Bialystok, Pologne], and Funding informationAbbVie

Subjects
Cyclopropanes, Male, hepatitis C virus, Internationality, Sustained Virologic Response, [SDV]Life Sciences [q-bio], Hepacivirus, chemistry.chemical_compound, 0302 clinical medicine, drug‐drug interaction, 2-Naphthylamine, Anilides, Drug Interactions, 030212 general & internal medicine, Prospective Studies, Aged, 80 and over, education.field_of_study, Sulfonamides, Dasabuvir, Valine, real‐world evidence, Middle Aged, 3. Good health, comorbidity, Infectious Diseases, Tolerability, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, Original Article, medicine.drug, Adult, medicine.medical_specialty, Macrocyclic Compounds, direct‐acting antiviral, Adolescent, Genotype, Proline, Lactams, Macrocyclic, Population, Antiviral Agents, 03 medical and health sciences, Young Adult, Virology, Internal medicine, Ribavirin, medicine, Humans, real-world evidence, education, Uracil, Aged, direct-acting antiviral, Ritonavir, Hepatology, business.industry, Original Articles, Hepatitis C, Chronic, Ombitasvir, Discontinuation, chemistry, Paritaprevir, Carbamates, business, drug-drug interaction
Abstract

International audience; Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) regimens show high efficacy and good tolerability in clinical trials for chronic hepatitis C virus (HCV) genotypes (GT) 1 or 4. To evaluate whether these results translate to clinical practice, data were pooled from observational studies across 13 countries. Treatment‐naïve or ‐experienced patients, with or without cirrhosis, received OBV/PTV/r ± DSV ± RBV according to approved local labels and clinical practice. Sustained virologic response at post‐treatment Week 12 (SVR12), adverse events (AEs) and comedication management were assessed for patients initiating treatment before 1 June 2017. The safety population included 3850 patients who received ≥1 dose of study drug. The core population (N = 3808) further excluded patients with unknown GT or cirrhosis status, or who received off‐label treatment. Patients had HCV GT1a (n = 732; 19%), GT1b (n = 2619; 69%) or GT4 (n = 457; 12%). In 3546 patients with sufficient follow‐up data at post‐treatment Week 12, the SVR12 rate was 96% (n/N = 3401/3546 [95% CI 95.2‐96.5]). In patients with or without cirrhosis, SVR12 was comparable (96%). In patients with HCV GT1a, GT1b or GT4, SVR12 rates were 93%, 97% and 94%. In GT1b‐infected patients with planned treatment for 8 weeks, SVR12 was 96%. In patients with ≥1 comorbidity (67%), SVR12 was 95%. 58% of patients received ≥1 comedication, and there was minimal impact on SVR12 rates using comedications for peptic ulcers and gastro‐esophageal reflux disease, statins, antipsychotics or antiepileptics. Most comedications were maintained during treatment although 58% of patients changed their statin medication. AEs and serious AEs occurred in 26% and 3% of patients. Post‐baseline Grade 3‐4 laboratory abnormalities were rare (

Published
2018

33. Protective role of the ELOVL2/docosahexaenoic acid axis in glucolipotoxicity-induced apoptosis in rodent beta cells and human islets

Author

Hervé Le Stunff, Kelly Meneyrol, Nadim Kassis, Mark Ibberson, Julien Véret, Christophe Magnan, Lara Bellini, Isabelle Hainault, Jessica Denom, Céline Cruciani-Guglielmacci, Véronique Lenoir, Piero Marchetti, Agnieszka Blachnio-Zabielska, Mélanie Campana, Marta Chacinska, Carina Prip-Buus, Marco Bugliani, Bernard Thorens, Claude Rouch, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical and Experimental Medicine [Pisa, Italy], University of Pisa [Italy], Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FACULTAD DE CIENCIAS Y FILOSOFIA, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Medical University of Bialystok, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), SIB Swiss Institute of Bioinformatics, and Université de Lausanne

Subjects
AMPK, 0301 basic medicine, medicine.medical_specialty, Ceramide, Docosahexaenoic Acids, Fatty Acid Elongases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Palmitates, Apoptosis, 030209 endocrinology & metabolism, Pancreatic beta cells, Islets of Langerhans, Mice, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Carnitine palmitoyltransferase 1, Downregulation and upregulation, ELOVL2, Acetyltransferases, Insulin-Secreting Cells, Internal medicine, Internal Medicine, medicine, Animals, Glucose homeostasis, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, food and beverages, Fatty acid, Type 2 diabetes, DHA, Glucolipotoxicity, Diabetes and Metabolism, Mitochondrial β-oxidation, Glucose, 030104 developmental biology, chemistry, Docosahexaenoic acid, Beta cell, Oxidation-Reduction, Etomoxir
Abstract

Dietary n-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are known to influence glucose homeostasis. We recently showed that Elovl2 expression in beta cells, which regulates synthesis of endogenous DHA, was associated with glucose tolerance and played a key role in insulin secretion. The present study aimed to examine the role of the very long chain fatty acid elongase 2 (ELOVL2)/DHA axis on the adverse effects of palmitate with high glucose, a condition defined as glucolipotoxicity, on beta cells. We detected ELOVL2 in INS-1 beta cells and mouse and human islets using quantitative PCR and western blotting. Downregulation and adenoviral overexpression of Elovl2 was carried out in beta cells. Ceramide and diacylglycerol levels were determined by radio-enzymatic assay and lipidomics. Apoptosis was quantified using caspase-3 assays and poly (ADP-ribose) polymerase cleavage. Palmitate oxidation and esterification were determined by [U-14C]palmitate labelling. We found that glucolipotoxicity decreased ELOVL2 content in rodent and human beta cells. Downregulation of ELOVL2 drastically potentiated beta cell apoptosis induced by glucolipotoxicity, whereas adenoviral Elovl2 overexpression and supplementation with DHA partially inhibited glucolipotoxicity-induced cell death in rodent and human beta cells. Inhibition of beta cell apoptosis by the ELOVL2/DHA axis was associated with a decrease in ceramide accumulation. However, the ELOVL2/DHA axis was unable to directly alter ceramide synthesis or metabolism. By contrast, DHA increased palmitate oxidation but did not affect its esterification. Pharmacological inhibition of AMP-activated protein kinase and etomoxir, an inhibitor of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme in fatty acid β-oxidation, attenuated the protective effect of the ELOVL2/DHA axis during glucolipotoxicity. Downregulation of CPT1 also counteracted the anti-apoptotic action of the ELOVL2/DHA axis. By contrast, a mutated active form of Cpt1 inhibited glucolipotoxicity-induced beta cell apoptosis when ELOVL2 was downregulated. Our results identify ELOVL2 as a critical pro-survival enzyme for preventing beta cell death and dysfunction induced by glucolipotoxicity, notably by favouring palmitate oxidation in mitochondria through a CPT1-dependent mechanism.

Published
2018

34. Ceramide Transporter CERT Is Involved in Muscle Insulin Signaling Defects Under Lipotoxic Conditions

Author

Erwann Philippe, Athanassia Sotiropoulos, Hervé Le Stunff, Agnieszka Blachnio-Zabielska, Julien Véret, Paola Giussani, Fabienne Foufelle, Cécile L Bandet, Maxime Poirier, Xavier Le Liepvre, Olivier Bourron, Pascal Ferré, Eric Hajduch, Raphaëlle Ballaire, Jan Górski, Dušan Berkeš, Rana Mahfouz, Mélanie Campana, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse cellulaire et clinique du diabète (CRC - Inserm U1138), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Nutrition, diabète et cerveau, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Bialystok Med Univ, Virologie et Immunologie Moléculaire, Faculté des Sciences Pharmaceutiques, Institut National de la Recherche Agronomique (INRA)-Université Francois Rabelais [Tours], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Slovak University of Technology in Bratislava, Department of Physiology, Medical University of Bialystok, Pathologies nutritionnelles et métaboliques : obésité et diabète, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Medical University of Białystok (MUB), Service de Diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hajduch, Eric, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Adult, Male, Ceramide, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Golgi Apparatus, Mice, Transgenic, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Protein Serine-Threonine Kinases, Ceramides, Endoplasmic Reticulum, 03 medical and health sciences, chemistry.chemical_compound, Mice, Insulin resistance, Internal Medicine, medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Myocyte, Animals, Humans, Insulin, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, biology, Muscles, Fatty Acids, medicine.disease, Sphingolipid, Cell biology, Mice, Inbred C57BL, Insulin receptor, 030104 developmental biology, chemistry, Lipotoxicity, biology.protein, Signal transduction, Insulin Resistance, Signal Transduction
Abstract

International audience; One main mechanism of insulin resistance (IR), a key feature of type 2 diabetes, is the accumulation of saturated fatty acids (FAs) in the muscles of obese patients with type 2 diabetes. Understanding the mechanism that underlies lipid-induced IR is an important challenge. Saturated FAs are metabolized into lipid derivatives called ceramides, and their accumulation plays a central role in the development of muscle IR. Ceramides are produced in the endoplasmic reticulum (ER) and transported to the Golgi apparatus through a transporter called CERT, where they are converted into various sphingolipid species. We show that CERT protein expression is reduced in all IR models studied because of a caspase-dependent cleavage. Inhibiting CERT activity in vitro potentiates the deleterious action of lipotoxicity on insulin signaling, whereas overexpression of CERT in vitro or in vivo decreases muscle ceramide content and improves insulin signaling. In addition, inhibition of caspase activity prevents ceramide-induced insulin signaling defects in C2C12 muscle cells. Altogether, these results demonstrate the importance of physiological ER-to-Golgi ceramide traffic to preserve muscle cell insulin signaling and identify CERT as a major actor in this process.

Published
2018

35. Advances in the molecular pathophysiology, genetics, and treatment of primary ovarian insufficiency

Author

Danielle Monniaux, Andres Salumets, Ilpo Huhtaniemi, Micheline Misrahi, Peter Wieacker, Outi Hovatta, Katarzyna Jarzabek, Juha S. Tapanainen, Antonio La Marca, Jenny A. Visser, Slawomir Wolczynski, Reiner A. Veitia, Luca Persani, Triin Laisk-Podar, Abdelkader Heddar, Gabriel Livera, Imperial College London, Nova Southeastern University (NSU), Karolinska Institutet [Stockholm], Università degli Studi di Modena e Reggio Emilia (UNIMORE), Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI), Istituto Auxologico Italiano, Université Paris-Sud - Paris 11 (UP11), Polish Academy of Sciences (PAN), Competence Centre on Health Technologies, Partenaires INRAE, University of Tartu, University of Helsinki, Department of Obstetrics and Gynecology, University of Oulu-Institute of Clinical Medicine, Université Paris Diderot - Paris 7 (UPD7), Erasmus University Rotterdam, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Medical University of Bialystok, and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Adult, transfer-rna synthetase, fsh receptor, chromosomal instability, DNA repair, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], perrault syndrome, Biology, Primary Ovarian Insufficiency, in-vitro, hypergonadotropic hypogonadism, of-function mutations, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Humans, genetics, [INFO]Computer Science [cs], Fertility preservation, hearing-loss, Ovarian reserve, Exome, Gene, exome, in vitro activation of dormant follicles, meiosis genes, ovary, primary ovarian insufficiency, Genetic association, Genetics, follicle-stimulating-hormone, 030219 obstetrics & reproductive medicine, Genetic heterogeneity, High-Throughput Nucleotide Sequencing, 3. Good health, Review article, Diabetes and Metabolism, 030104 developmental biology, Mutation, Female, primordial follicle, Genome-Wide Association Study
Abstract

International audience; Primary ovarian insufficiency (POI) affects similar to 1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of > 60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.

Published
2018

36. Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells

Author

Hage Hassan, Rima, Pacheco de Sousa, Ana Catarina, Mahfouz, Rana, Hainault, Isabelle, Blachnio-Zabielska, Agnieszka, Bourron, Olivier, Koskas, Fabien, Gorski, Jan, Ferré, Pascal, Foufelle, Fabienne, Hajduch, Eric, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bialystok Med Univ, Service de diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Department of Physiology, Medical University of Bialystok, Pathologies nutritionnelles et métaboliques : obésité et diabète, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université

Subjects
[SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

37. Antithrombotic properties of water-soluble carbon monoxide-releasing molecules.: Anti-thrombotic properties of CO-RMs

Author

Elżbieta Grochal, Tomasz Brzoska, Brian E. Mann, Tetsumei Urano, Wlodzimierz Buczko, Andrzej Mogielnicki, Andrzej Fedorowicz, Agnieszka Leszczynska, Roberto Motterlini, Karol Kramkowski, Stefan Chlopicki, Department of Pharmacodynamics, Medical University of Białystok (MUB), Jagiellonian Centre for Experimental Therapeutics (JCET), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Department of Experimental Pharmacology, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Medical Physiology, Hamamatsu University Medical School of Medicine, This work was supported by Polish Ministry of Science and Higher Education (grant no. NN405 260437). Supplementary funding was provided by the European Union from the resources of the European Regional Development Fund under the Innovative Economy Programme (grant coordinated by JCET-UJ, No POIG.01.01.02-00-069/09) and Grant-in-Aid for Scientific Research (C:21590230 from the Japan Society for the Promotion of Science (JSPS)., and Medical University of Bialystok

Subjects
Male, fibrin generation, Time Factors, Platelet Aggregation, Carbonates, CO-releasing molecules (CO-RMs), Blood Pressure, 030204 cardiovascular system & hematology, Mice, chemistry.chemical_compound, 0302 clinical medicine, Antithrombotic, Organic chemistry, Solubility, Boranes, Venous Thrombosis, Carbon Monoxide, 0303 health sciences, Microscopy, Confocal, plasminogen activator inhibitor-1 (PAI-1), Fibrinolysis, Injections, Intravenous, Cardiology and Cardiovascular Medicine, Blood Platelets, Green Fluorescent Proteins, chemistry.chemical_element, Arterial Occlusive Diseases, Mice, Transgenic, 03 medical and health sciences, Fibrinolytic Agents, In vivo, Plasminogen Activator Inhibitor 1, Organometallic Compounds, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, Thrombus, Blood Coagulation, 030304 developmental biology, Hemostat, Fibrin, Dose-Response Relationship, Drug, Fibrinogen, Water, Thrombosis, carbon monoxide (CO), medicine.disease, Carbon monoxide-releasing molecules, Rats, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Immunology, Prothrombin Time, Blood Gas Analysis, Carbon, Carbon monoxide
Abstract

Objective— We compared the antithrombotic effects in vivo of 2 chemically different carbon monoxide–releasing molecules (CORM-A1 and CORM-3) on arterial and venous thrombus formation and on hemostatic parameters such as platelet activation, coagulation, and fibrinolysis. The hypotensive response to CORMs and their effects on whole blood gas analysis and blood cell count were also examined. Methods and Results— CORM-A1 (10–30 µmol/kg, i.v.), in a dose-dependent fashion, significantly decreased weight of electrically induced thrombus in rats, whereas CORM-3 inhibited thrombosis only at the highest dose used (30 µmol/kg). CORM-A1 showed a direct and stronger inhibition of platelet aggregation than CORM-3 in healthy rats, both in vitro and in vivo. The antiaggregatory effect of CORM-A1, but not CORM-3, correlated positively with weight of the thrombus. Concentration of active plasminogen activator inhibitor-1 in plasma also decreased in response to CORM-A1, but not to CORM-3. Neither CORM-A1 nor CORM-3 had an effect on plasma concentration of active tissue plasminogen activator. CORM-3, but not CORM-A1, decreased the concentration of fibrinogen, fibrin generation, and prolonged prothrombin time. Similarly, laser-induced venous thrombosis observed intravitally via confocal system in green fluorescent protein mice was significantly decreased by CORMs. Although both CORM-A1 and CORM-3 (30 µmol/kg) decreased platelets accumulation in thrombus, only CORM-A1 (3–30 µmol/kg) inhibited platelet activation to phosphatidylserine on their surface. Conclusion— CORM-3 and CORM-A1 inhibited thrombosis in vivo, however CORM-A1, which slowly releases carbon monoxide, and displayed a relatively weak hypotensive effect had a more pronounced antithrombotic effect associated with a stronger inhibition of platelet aggregation associated with a decrease in active plasminogen activator inhibitor-1 concentration. In contrast, the fast CO releaser CORM-3 that displayed a more pronounced hypotensive effect inhibited thrombosis primarily through a decrease in fibrin generation, but had no direct influence on platelet aggregation and fibrynolysis.

Published
2012

38. Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE*

Author

Fabien Koskas, Eric Hajduch, Rima Hage Hassan, Fabienne Foufelle, Ana Catarina Pacheco de Sousa, Olivier Bourron, Isabelle Hainault, Pascal Ferré, Rana Mahfouz, Agnieszka Blachnio-Zabielska, Jan Górski, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Medical University of Białystok (MUB), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers ( CRC ), and Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
0301 basic medicine, Male, Ceramide, Insulin Receptor Substrate Proteins, MAP Kinase Kinase 4, Biology, Ceramides, Biochemistry, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Mice, eIF-2 Kinase, Animals, Humans, Insulin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Phosphorylation, Muscle, Skeletal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Protein kinase B, Cell Biology, Lipid signaling, IRS1, Insulin receptor, 030104 developmental biology, Metabolism, chemistry, biology.protein, Signal transduction, Insulin Resistance, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract

International audience; In vivo, ectopic accumulation of fatty acids in muscles leads to alterations in insulin signaling at both the IRS1 and Akt steps. However, in vitro treatments with saturated fatty acids or their derivative ceramide demonstrate an effect only at the Akt step. In this study, we adapted our experimental procedures to mimic the in vivo situation and show that the double-stranded RNA-dependent protein kinase (PKR) is involved in the long-term effects of saturated fatty acids on IRS1. C2C12 or human muscle cells were incubated with palmitate or directly with ceramide for short or long periods, and insulin signaling pathway activity was evaluated. PKR involvement was assessed through pharmacological and genetic studies. Short-term treatments of myotubes with palmitate, a ceramide precursor, or directly with ceramide induce an inhibition of Akt, whereas prolonged periods of treatment show an additive inhibition of insulin signaling through increased IRS1 serine 307 phosphorylation. PKR mRNA, protein, and phosphorylation are increased in insulin-resistant muscles. When PKR activity is reduced (siRNA or a pharmacological inhibitor), serine phosphorylation of IRS1 is reduced, and insulin-induced phosphorylation of Akt is improved. Finally, we show that JNK mediates ceramide-activated PKR inhibitory action on IRS1. Together, in the long term, our results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells.

Published
2015

39. CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription

Author

Oscar Junhong Luo, Jakub Wlodarczyk, Ping Wang, Emaly Piecuch, Yijun Ruan, Dariusz Plewczynski, May Penrad-Mobayed, Pawel Trzaskoma, Zhonghui Tang, Jacqueline Jufen Zhu, Przemyslaw Szalaj, Edison T. Liu, Adriana Magalska, Guoliang Li, Grzegorz M. Wilczynski, Laurent M. Sachs, Xingwang Li, Paul J. Michalski, Danjuan Wang, Blazej Ruszczycki, Xiaoan Ruan, Chia-Lin Wei, Simon Zhongyuan Tian, Meizhen Zheng, The Jackson Laboratory's research institute, National Key Laboratory of Crop Genetic Improvement, Sichuan University, College of Life Sciences-Huazhong Agricultural University, Department of Genetics and Genome Sciences, University of Connecticut (UCONN), Center for Bioinformatics and Data Analysis, Medical University of Bialystok, I-BioStat, Hasselt University, Centre of New Technologies, Medical University of Warsaw - Poland, Nencki Institute of Experimental Biology, Polska Akademia Nauk (PAN), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique/Muséum National d'Histoire Naturelle, DOE Joint Genome Institute [Walnut Creek], College of Informatics, Huazhong Agricultural University, Director Innovation Fund of Jackson Laboratory, NCI R01 CA186714, NHGRI R25HG007631, NIDDK U54DK107967 (4DN), Roux family, China '111 project' (B07041), Polish National Science Centre [UMO-2012/05/E/NZ4/02997], [2014/15/B/ST6/05082, UMO-2013/09/B/NZ2/00121], [DEC-2012/06/M/NZ3/00163], National Leading Research Centre in Bialystok, European Union under the European Social Fund, The Jackson Laboratory [Bar Harbor] (JAX), Polska Akademia Nauk = Polish Academy of Sciences (PAN), University of Turku, Evolution des régulations endocriniennes (ERE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), University of Geneva Medical School, Cancer Biology and Pharmacology, Genome Institute of Singapore (GIS), Hasselt University (UHasselt), and Physiologie moléculaire et adaptation (PhyMA)

Subjects
CCCTC-Binding Factor, Transcription, Genetic, Chromosomal Proteins, Non-Histone, RNA polymerase II, Cell Cycle Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Topology, Genome, General Biochemistry, Genetics and Molecular Biology, Chromosomes, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA Packaging, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, ChIA-PET, 030304 developmental biology, Genetics, 0303 health sciences, biology, Biochemistry, Genetics and Molecular Biology(all), Genome, Human, Salamandridae, Chromatin, Repressor Proteins, CTCF, biology.protein, Chromatin Loop, Human genome, RNA Polymerase II, 030217 neurology & neurosurgery
Abstract

International audience; Spatial genome organization and its effect on transcription remains a fundamental question. We applied an advanced chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) strategy to comprehensively map higher-order chromosome folding and specific chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) with haplotype specificity and nucleotide resolution in different human cell lineages. We find that CTCF/cohesin-mediated interaction anchors serve as structural foci for spatial organization of constitutive genes concordant with CTCF-motif orientation, whereas RNAPII interacts within these structures by selectively drawing cell-type-specific genes toward CTCF foci for coordinated transcription. Furthermore, we show that haplotype variants and allelic interactions have differential effects on chromosome configuration, influencing gene expression, and may provide mechanistic insights into functions associated with disease susceptibility. 3D genome simulation suggests a model of chromatin folding around chromosomal axes, where CTCF is involved in defining the interface between condensed and open compartments for structural regulation. Our 3D genome strategy thus provides unique insights in the topological mechanism of human variations and diseases.

Published
2015

40. Influence of Eye Diseases on the Retina Pattern Recognition

Author

Emil Saeed, Khalid Saeed, Anna Bartocha, Piotr Wachulec, Medical University of Bialystok, AGH University of Science and Technology [Krakow, PL] (AGH UST), Białystok University of Technology, Khalid Saeed, Václav Snášel, and TC 8

Subjects
Minutiae, Retina, genetic structures, Biometrics, Computer science, business.industry, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Eye disease, Pattern recognition, Retina diseases, medicine.disease, Identification of retina with anomalies, eye diseases, medicine.anatomical_structure, Pattern recognition (psychology), medicine, [INFO]Computer Science [cs], Human eye, Computer vision, sense organs, Artificial intelligence, Human identification, business
Abstract

Part 3: Biometrics and Biometrics Applications; International audience; In this paper an algorithm to extract the retina characteristic points for a human eye with diseases is presented. The background of both medical and computer science matters is given. The cataract is described and discussed as a newly considered eye disease for retina pattern recognition. The processing of the retina with this disease is introduced for comparison with previous works. The structure of the applied method is illustrated in detail with examples. The procedure of minutiae extraction from the processed sick retina is given.

Published
2014

41. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis

Author

Valeria Riccieri, László Czirják, Yannick Allanore, Jean-Luc Cracowski, Catherine Boileau, Inga Melchers, H.-Erich Wichmann, Jean-Charles Lambert, Oliver Meyer, Julien Wipff, Mohamad Saad, Jörg H W Distler, Luc Mouthon, Anne Marie Dupuy, Costanza Conti, Martina Müller, Nicolas Hunzelmann, Maria Martinez, Marco Matucci-Cerinic, Elisabeth Diot, Ulf Müller-Ladner, Paola Caramaschi, Otylia Kowal-Bielecka, André Kahan, Erika Salvi, G. Riemekasten, Arnold Munnich, Paolo Airò, Luc Letenneur, Eric Hachulla, Kiet Tiev, Barbara Ruiz, Daniele Cusi, Jérôme Avouac, Nemanja Damjanov, Philippe Dieudé, Gabriele Valentini, Philippe Amouyel, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine 3, Institute for Clinical Immunology Erlangen-Nuremberg, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Departments of Medicine, Biomedicine & Rheumatology, Università degli Studi di Firenze = University of Florence (UniFI)-Division of Rheumatology AOUC - Denothe Centre, Department of Rheumatology and Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rheumatology and Clinical Immunology, Spedali Civili, Clinical Research Unit for Rheumatology, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Service de médecine interne, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medicine, Surgery, and Dentistry, University of Milano, Genomics and Bioinformatics Platform, Fondazione Filarete, Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Institute of Epidemiology I, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Dermatology, University of Cologne, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rheumatology Unit, Università degli studi di Verona = University of Verona (UNIVR), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology and Internal Medicine, Medical University of Białystok (MUB), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Department of Immunology and Rheumatology, University of Pecs, Institute of Rheumatology, University of Belgrade [Belgrade], Kos Genetic SRL, Institute of Genetic Epidemiology, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Division of Rheumatology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This project was funded by Agence Nationale pour la Recherche (Project ANR-08-GENO-016-1) and supported by research grants from SERVIER research group, SANOFI-AVENTIS, Association des Sclérodermies de France, and Groupe Français de Recherche sur la Sclérodermie. The KORA (Cooperative health research in the Region of Augsburg) studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN). This research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. HYPERGENES (European Network for Genetic-Epidemiological Studies) is funded by EU within the FP7: HEALTH-F4-2007-201550., European Project: 201550,EC:FP7:HEALTH,FP7-HEALTH-2007-A,HYPERGENES(2008), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Division of Rheumatology AOUC - Denothe Centre-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Freiburg University Medical Center, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Verona (UNIVR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, University of Naples Federico II, German Research Center for Environmental Health, Justus-Liebig-Universität Gießen (JLU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Division of Rheumatology AOUC - Denothe Centre, Allanore, Y, Saad, M, Dieudé, P, Avouac, J, Distler, Jh, Amouyel, P, MATUCCI CERINIC, M, Riemekasten, G, Airo, P, Melchers, I, Hachulla, E, Cusi, D, Wichmann, He, Wipff, J, Lambert, Jc, Hunzelmann, N, Tiev, K, Caramaschi, P, Diot, E, KOWAL BIELECKA, O, Valentini, Gabriele, Mouthon, L, Czirják, L, Damjanov, N, Salvi, E, Conti, C, Müller, M, MÜLLER LADNER, U, Riccieri, V, Ruiz, B, Cracowski, Jl, Letenneur, L, Dupuy, Am, Meyer, O, Kahan, A, Munnich, A, Boileau, C, Martinez, M., Autard, Delphine, European Network for Genetic-Epidemiological Studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model - HYPERGENES - - EC:FP7:HEALTH2008-01-01 - 2011-12-31 - 201550 - VALID, and Service de médecine interne [CHU Saint-Antoine]

Subjects
Male, Cancer Research, Linkage disequilibrium, Epidemiology, systemic sclerosis, RHOB, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Linkage Disequilibrium, MESH: Scleroderma, Systemic, Scleroderma, Major Histocompatibility Complex, Disease Mapping, TNIP1 locus, 0302 clinical medicine, Germany, Genetics of the Immune System, HLA-DQ beta-Chains, MESH: Proteins, Connective Tissue Diseases, rhoB GTP-Binding Protein, Genetics (clinical), Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, 3. Good health, DNA-Binding Proteins, Europe, Italy, MESH: Linkage Disequilibrium, Genetic Epidemiology, Medicine, Cytokines, Female, Inflammatory and Psoriatic Arthritis, France, Research Article, Adult, lcsh:QH426-470, Medizinische Fakultät -ohne weitere Spezifikation, Rheumatoid Arthritis, Single-nucleotide polymorphism, Locus (genetics), Biology, Systemic Lupus Erythematosus, Polymorphism, Single Nucleotide, Autoimmune Diseases, 03 medical and health sciences, MESH: Major Histocompatibility Complex, Rheumatology, RhoB GTP-Binding Protein, functional polymorphism, extracellular-matrix, association, scleroderma, population, disease, susceptibility, fibrosis, receptor, stat4, Psoriasis, Humans, SNP, Genetic Predisposition to Disease, genome-wide scan, ddc:610, Molecular Biology, MESH: Germany, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, MESH: rhoB GTP-Binding Protein, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Scleroderma, Systemic, MESH: Humans, Proteins, MESH: Italy, MESH: Adult, MESH: HLA-DQ beta-Chains, MESH: Male, MESH: France, lcsh:Genetics, Immune System, Case-Control Studies, Immunology, MESH: Genome-Wide Association Study, Clinical Immunology, MESH: Europe, MESH: Female, MESH: DNA-Binding Proteins, Genome-Wide Association Study
Abstract

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P, Author Summary Systemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy, severe immunologic alterations, and massive deposits of matrix components in the connective tissue. Epidemiological investigations indicate that SSc follows a pattern of multifactorial inheritance; however, only a few loci have been replicated in multiple studies. We undertook a two-stage genome-wide association study of SSc involving over 8,800 individuals of European ancestry. Combined analyses showed independent association at the known HLA-DQB1 region and revealed associations at PSORS1C1, TNIP1, and RHOB loci, in agreement with a strong immune genetic component. Because of its biological relevance, and previous reports of genetic association at this locus with other connective tissue disorders, we investigated TNIP1 expression. We observed a markedly reduced expression of the gene and its protein product in SSc, as well as its potential implication in control of extra-cellular matrix synthesis, providing a new clue for a link between inflammation/immunity and fibrosis.

Published
2011

42. Implications of overweight in gastric cancer: a multicenter study in a Western patient population

Author

J, Kulig, M, Sierzega, P, Kolodziejczyk, J, Dadan, M, Drews, M, Fraczek, A, Jeziorski, M, Krawczyk, T, Starzynska, G, Wallner, Konrad, Wronski, 1st Department of Surgery, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Department of General and Endocrine Surgery, Medical University of Bialystok, Department of General, Department of Surgical Oncology, Medical University of Łódź (MUL), Department of Gastroenterology, Pomeranian Medical Academy, II Department of General Surgery, and Medical University of Lublin

Subjects
Male, Comorbidity, Kaplan-Meier Estimate, Overweight, Cohort Studies, 0302 clinical medicine, Medicine, Registries, 2. Zero hunger, education.field_of_study, General Medicine, 3. Good health, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, medicine.symptom, Cohort study, medicine.medical_specialty, Population, education, body mass index, lymph node dissection, Risk Assessment, Statistics, Nonparametric, 03 medical and health sciences, Gastrectomy, Stomach Neoplasms, Internal medicine, postoperative complications, Humans, overweight, Obesity, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Gynecology, business.industry, Proportional hazards model, gastric cancer, Cancer, Retrospective cohort study, medicine.disease, History, Medieval, Multivariate Analysis, Surgery, Poland, prognosis, business, Body mass index, Follow-Up Studies
Abstract

The purpose of this study was to evaluate the effects of overweight on surgical and long-term outcomes in a Western population of patients with gastric cancer (GC).An electronic database of all patients with resectable GC treated between 1986 and 1998 at seven university surgical centres cooperating in the Polish Gastric Cancer Study Group was reviewed. Overweight was defined as a body mass index (BMI) of 25 kg/m(2) or higher.Four hundred and ninety-two of 1992 (25%) patients were overweight. Postoperatively, higher BMI was associated with higher rates of cardiopulmonary complications (16% vs 12%, P = 0.001) and intra-abdominal abscess (6.9% vs 2.9%, P 0.001). However, other complications and mortality rates were unaffected. The median disease-specific survival of overweight patients was significantly higher (36.7 months, 95% confidence interval (CI) 29.0-44.4) than those with BMI25 kg/m(2) (25.7 months, 95%CI 23.2-28.1; P = 0.003). These differences were due to the lower frequencies of patients with T3 and T4 tumours, metastatic lymph nodes, distant metastases, and non-curative resections. A Cox proportional hazards model identified age, depth of infiltration, lymph node metastases, distant metastases, and residual tumour category as the independent prognostic factors.Overweight is not the independent prognostic factor for long-term survival in a Western-type population of GC.

Published
2010

43. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques

Author

Lorenzo Zaffiri, Maria Grazia Ferrari, John J. O'Shea, Monica Vaccari, Arian Laurence, R Washington Parks, Daniel C. Douek, David Venzon, Elzbieta Tryniszewska, Jean-Michel Heraud, Valentina Cecchinato, Wen-Po Tsai, Genoveffa Franchini, Christopher Trindade, Jason M. Brenchley, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Animal Models and Retroviral Vaccines Section, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Molecular Immunology and Inflammation Branch, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Advanced BioScience Laboratories Inc., Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Medical University of Bialystok, Biostatistics & Data Management Section, and This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Subjects
CD4-Positive T-Lymphocytes, MESH: Interleukin-17, Simian Acquired Immunodeficiency Syndrome, medicine.disease_cause, Virus Replication, Interleukin 21, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: Animals, Lymphocytes, Antigens, Viral, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Interleukin-17, Interleukin, MESH: CD4-Positive T-Lymphocytes, Acquired immune system, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Interleukin 12, Simian Immunodeficiency Virus, MESH: Simian Acquired Immunodeficiency Syndrome, MESH: Antigens, Viral, Immunology, MESH: Simian Immunodeficiency Virus, Biology, Virus, Article, MESH: Macaca mulatta, 03 medical and health sciences, Antigen, medicine, Animals, Humans, 030304 developmental biology, Mucous Membrane, MESH: Humans, MESH: Virus Replication, MESH: Mucous Membrane, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Simian immunodeficiency virus, Th1 Cells, Virology, Macaca mulatta, In vitro, MESH: Th1 Cells, MESH: Lymphocytes, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030215 immunology
Abstract

International audience; Loss of CD4(+) T cells in the gut is necessary but not sufficient to cause AIDS in animal models, raising the possibility that a differential loss of CD4(+) T-cell subtypes may be important. We found that CD4(+) T cells that produce interleukin (IL)-17, a recently identified lineage of effector CD4(+) T-helper cells, are infected by SIV(mac251)in vitro and in vivo, and are found at lower frequency at mucosal and systemic sites within a few weeks from infection. In highly viremic animals, Th1 cells predominates over Th17 T cells and the frequency of Th17 cells at mucosal sites is negatively correlated with plasma virus level. Because Th17 cells play a central role in innate and adaptive immune response to extracellular bacteria, our finding may explain the chronic enteropathy in human immunodeficiency virus (HIV) infection. Thus, therapeutic approaches that reconstitute an adequate balance between Th1 and Th17 may be beneficial in the treatment of HIV infection.

Published
2008

44. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment

Author

Alba Nicolas-Boluda, Javier Vaquero, Lene Vimeux, Thomas Guilbert, Sarah Barrin, Chahrazade Kantari-Mimoun, Matteo Ponzo, Gilles Renault, Piotr Deptula, Katarzyna Pogoda, Robert Bucki, Ilaria Cascone, José Courty, Laura Fouassier, Florence Gazeau, Emmanuel Donnadieu, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Laboratoire de Physique des Plasmas (LPP), Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École polytechnique (X)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Medical University of Białystok (MUB), Institute of Physics, Polish Academy of Sciences, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Courty, José, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CNRS UMR 7057 - Laboratoire Matières et Systèmes Complexes (MSC) (MSC), Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Medical University of Bialystok [Bialystok, Pologne], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
tumor, Mouse, cell migration, QH301-705.5, T-Lymphocytes, extracellular matrix, Science, Programmed Cell Death 1 Receptor, T lymphocytes, Immunoteràpia, T cells, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Physiological Phenomena, Protein-Lysine 6-Oxidase, Mice, stiffness, Cell Movement, Tumor Microenvironment, Animals, Biology (General), Càncer, Immune Checkpoint Inhibitors, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cells, Cultured, Cancer Biology, Cancer, Neoplasms, Experimental, Mice, Inbred C57BL, Cèl·lules T, Medicine, Female, Collagen, immunotherapy, Immunotherapy, Research Article
Abstract

International audience; Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy.

Full Text
View/download PDF

45. Gender, body mass index and rheumatoid arthritis disease activity: Results from the QUEST-RA study

Author

Jawaheer, D., Olsen, J., Lahiff, M., Forsberg, S., Lähteenmäki, J., Da Silveira, I. G., Rocha, F. A., Laurindo, I. M. M., Da Mota, L. M. H., Drosos, A. A., Murphy, E., Sheehy, C., Quirke, E., Cutolo, M., Rexhepi, S., Dadoniene, J., Verstappen, S. M. M., Sokka, T., Toloza, S., Aguero, S., Barrera, S. O., Retamozo, S., Alba, P., Lascano, C., Babini, A., Albiero, E., Pinheiro, G. R. C., Lazovskis, J., Hetland, M. L., Ørnbjerg, L., Hørslev-Petersen, K., Hansen, T. M., Knudsen, L. S., Hamoud, H., Sobhy, M., Fahmy, A., Magdy, M., Aly, H., Saeid, H., Nagm, A., Fathi, N. A., Abda, E., Ebraheam, Z., Müller, R., Kuuse, R., Tammaru, M., Kallikorm, R., Peets, T., Otsa, K., Laas, K., Valter, I., Mäkinen, H., Immonen, K., Luukkainen, R., Gossec, L., Dougados, M., Maillefert, J. F., Combe, B., Sibilia, J., Exarchou, S., Moutsopoulos, H. M., Tsirogianni, A., Skopouli, F. N., Mavrommati, M., Herborn, G., Rau, R., Alten, R., Pohl, C., Burmester, G. R., Marsmann, B., Géher, P., Rojkovich, B., Bresnihan, B., Minnock, P., Devlin, J., Alraqi, S., Aggarwal, A., Pandya, S., Sharma, B., Cazzato, M., Bombardieri, S., Ferraccioli, G., Morelli, A., Salaffi, F., Stancati, A., Yamanaka, H., Nakajima, A., Fukuda, W., Shono, E., Oyoo, O., Rexhepi, M., Andersone, D., Stropuviene, S., Baranauskaite, A., Najia Hajjaj-Hassouni, Benbouazza, K., Allali, F., Bahiri, R., Amine, B., Jacobs, J. W. G., Huisman, M., Hoekstra, M., Haugeberg, G., Gjelberg, H., Sierakowski, S., Majdan, M., Romanowski, W., Tlustochowicz, W., Kapolka, D., Sadkiewicz, S., Zarowny-Wierzbinska, D., Ionescu, R., Predeteanu, D., Karateev, D., Luchikhina, E., Chichasova, N., Badokin, V., Skakic, V., Dimic, A., Nedovic, J., Stankovic, A., Naranjo, A., Rodríguez-Lozano, C., Calvo-Alen, J., Belmonte, M., Baecklund, E., Henrohn, D., Oding, R., Liveborn, M., Holmqvist, A. -C, Gogus, F., Tunc, R., Celic, S., Badsha, H., Mofti, A., Taylor, P., Mcclinton, C., Woolf, A., Chorghade, G., Choy, E., Kelly, S., Pincus, T., Yazici, Y., Bergman, M., Craig-Muller, J., Kautiainen, H., Swearingen, C., University of California Los Angeles, University of California Berkeley, North Karelia Central Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Universidade Federal do Ceará, Universidade Estadual Paulista (UNESP), Hospital Universitário de Brasília, University of Ioannina Ioannina, Waterford Regional Hospital, Connolly Hospital, University of Genova, Rheumatology Department, Vilnius University, University Medical Centre Utrecht, Jyväskylä Central Hospital, Medcare Oy, Hospital Oakland Research Institute, Hospital San Juan Bautista, Hospital of Cordoba, Universidade do Estado do Rio de Janeiro (UERJ), Riverside Professional Centre, Copenhagen University Hospital at Hvidovre, King Christian the Xth Hospital, Copenhagen University Hospital at Herlev, Al-Azhar University, Assiut University Hospital, Abo Sohage University Hospital, Tartu University Hospital, East-Tallinn Central Hospital, Centre for Clinical and Basic Research, Satakunta Central Hospital, Hôpital Cochin, INSERM U887, Hôpital Lapeyronie, Hôpital Hautepierre, National University of Athens, Euroclinic Hospital, Evangelisches Fachkrankenhaus, Schlosspark-Klinik, University Medicine Berlin, Semmelweis University of Medical Sciences, Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, St. Vincent University Hospital, Our Lady's Hospice, Vedanta Institiute of Medical Sciences, Jaipur Hospital, Santa Chiara Hospital, Catholic University of Sacred Heart, University of Ancona, Tokyo Women's Medical University, Kyoto First Red Cross Hospital, Shono Rheumatism Clinic, Kenyatta Hospital, Pauls Stradina Clinical University Hospital, Kaunas University Hospital, El Ayachi Hospital Mohamed Vth Souissi University, Sint Franciscus Gasthuis Hospital, Medisch Spectrum Twente, Sørlandet Hospital, Medical University in Bialystok, Medical University of Lublin, Poznan Rheumatology Centre in Srem, Military Institute of Medicine, Silesian Hospital for Rheumatology and Rehabilitation in Ustron Slaski, Szpital Wojewodzki im. Jana Biziela, Wojewodzki Zespol Reumatologiczny im. dr Jadwigi Titz-Kosko, Spitalul Clinic Sf Maria, Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow Medical Academy, Russian Medical Academy of Postgraduate Education, Rheumatology Institut, Hospital de Gran Canaria Dr. Negrin, Hospital Sierrallana Ganzo, Hospital General de Castellón, Uppsala University Hospital, Centrallasarettet, Hudiksvall Medical Clinic, Gazi University Medical Faculty, Meram Medical Faculty, Cerrahpasa Medic Faculty, Dubai Bone and Joint Centre, American Hospital Dubai, Charing Cross Hospital, Royal Cornwall Hospital, Kings College Hospital, Vanderbilt University, NYU Hospital for Joint Diseases, Taylor Hospital, Centra Care Clinic, University of Arkansas for Medical Sciences, and New York University Hospital for Joint Diseases

Subjects
Bmi, Gender, Disease activity, Rheumatoid arthritis
Abstract

Made available in DSpace on 2022-04-28T18:56:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-12-01 Objective: To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods: Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results: A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion: BMI appears to be associated with RA disease activity in women, but not in men. © Copyright Clinical and Experimental Rheumatology 2010. University of California Los Angeles, Los Angeles, CA University of California Berkeley, Berkeley, CA North Karelia Central Hospital, Joensuu Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre Universidade Federal do Ceará, Fortaleza Universidade Estadual de São Paulo, São Paulo Hospital Universitário de Brasília, Brasilia University of Ioannina Ioannina Waterford Regional Hospital, Waterford Connolly Hospital, Dublin University of Genova, Genova Rheumatology Department, Pristine Institute of Experimental and Clinical Medicine Vilnius University, Vilnius University Medical Centre Utrecht, Utrecht Jyväskylä Central Hospital, Jyväskylä Medcare Oy, Äänekoski Hospital Oakland Research Institute, Oakland, CA Hospital San Juan Bautista, Catamarca Hospital of Cordoba, Cordoba Universidade do Estado do Rio de Janeiro, Rio de Janeiro Riverside Professional Centre, Sydney, NS Copenhagen University Hospital at Hvidovre, Hvidovre King Christian the Xth Hospital, Gråsten Copenhagen University Hospital at Herlev, Herlev Al-Azhar University, Cairo Assiut University Hospital, Assiut Abo Sohage University Hospital, Sohage Tartu University Hospital, Tartu East-Tallinn Central Hospital, Tallinn Centre for Clinical and Basic Research, Tallinn Satakunta Central Hospital, Rauma University René Descartes Hôpital Cochin, Paris Dijon University Hospital University of Burgundy INSERM U887, Dijon Hôpital Lapeyronie, Montpellier Hôpital Hautepierre, Strasbourg School of Medicine National University of Athens, Athens Euroclinic Hospital, Athens Evangelisches Fachkrankenhaus, Ratingen Schlosspark-Klinik, Berlin University Medicine Berlin, Berlin Semmelweis University of Medical Sciences, Budapest Ilona Újfalussy Polyclinic of the Hospitaller Brothers of St. John of God in Budapest, Budapest St. Vincent University Hospital, Dublin Our Lady's Hospice, Dublin Department of Immunology, Lucknow Vedanta Institiute of Medical Sciences, Ahmedabad Department of Immunology Jaipur Hospital Santa Chiara Hospital, Pisa Catholic University of Sacred Heart, Rome University of Ancona, Ancona Institute of Rheumatology Tokyo Women's Medical University, Tokyo Department of Rheumatology Kyoto First Red Cross Hospital, Kyoto Shono Rheumatism Clinic, Fukuoka Kenyatta Hospital, Nairobi Pauls Stradina Clinical University Hospital, Riga Kaunas University Hospital, Kaunas El Ayachi Hospital Mohamed Vth Souissi University, Rabat Sint Franciscus Gasthuis Hospital, Rotterdam Medisch Spectrum Twente, Enschede Sørlandet Hospital, Kristiansand Medical University in Bialystok, Bialystok Medical University of Lublin, Lublin Poznan Rheumatology Centre in Srem, Srem Military Institute of Medicine, Warsaw Silesian Hospital for Rheumatology and Rehabilitation in Ustron Slaski, Ustroñ Slaski Szpital Wojewodzki im. Jana Biziela, Bydgoszcz Wojewodzki Zespol Reumatologiczny im. dr Jadwigi Titz-Kosko, Sopot Spitalul Clinic Sf Maria, Bucharest Institute of Rheumatology of Russian Academy of Medical Sciences, Moscow Moscow Medical Academy, Moscow Russian Medical Academy of Postgraduate Education, Moscow Rheumatology Institut, Niska Banja Hospital de Gran Canaria Dr. Negrin, Las Palmas Hospital Sierrallana Ganzo, Torrelavega Hospital General de Castellón, Castellón Uppsala University Hospital, Uppsala Centrallasarettet, Västerås Hudiksvall Medical Clinic, Hudiksvall Gazi University Medical Faculty, Ankara Meram Medical Faculty, Konya Cerrahpasa Medic Faculty, Istanbul Dubai Bone and Joint Centre, Dubai American Hospital Dubai, Dubai Charing Cross Hospital, London Royal Cornwall Hospital, Truro Kings College Hospital, London Vanderbilt University, Nashville, TN NYU Hospital for Joint Diseases, New York, NY Taylor Hospital, Ridley Park, PA Centra Care Clinic, St. Cloud, MN University of Arkansas for Medical Sciences, Little Rock, AR New York University Hospital for Joint Diseases, New York, NY Universidade Estadual de São Paulo, São Paulo

46. Association between exposure to air pollution and increased ischemic stroke incidence: a retrospective population-based cohort study (EP-PARTICLES study).

Author

Święczkowski M, Lip GYH, Kurasz A, Dąbrowski EJ, Tomaszuk-Kazberuk A, Kamiński JW, Strużewska J, Dobrzycki S, and Kuźma Ł

Abstract

Aims: Short-term effects of Polish smog, particularly benzo(alpha)pyrene (B(a)P), are unclear. We aimed to examine the association between short-term exposure to air pollution and ischemic stroke (IS) incidence., Methods: We conducted a retrospective population-based cohort study including an EP-PARTICLES cohort of 8 million inhabitants in the years 2011-2020 (80 million person-years of observation). Individual clinical data on emergency hospitalizations due to IS - ICD-10: I63.X was analyzed. We used quasi-Poisson models to examine municipality-specific associations between air pollutants and IS, considering various covariates., Results: We recorded 146,262 cases of IS with a dominance of females (51.8%) and people over 65 years old (77.6%). In the overall population, exposure to PM2.5, NO2, B(a)P and SO2 increased the risk of IS onset on the day of exposure by 2.4%, 1%, 0.8%, and 0.6%, respectively. Age and sex were modifying variables for PM2.5, NO2 and B(a)P exposure with more pronounced effects in non-elderly individuals and women (all pinteraction< 0.001). Residents of regions with high tobacco and alcohol consumption were more sensitive to the effects of PM2.5 and SO2. The slopes of response-effect curves were non-linear and steeper at lower concentrations., Conclusions: Exposure to air pollution may be associated with higher IS incidence, particularly posing a higher risk to non-elderly women. Harmful lifestyle habits might exacerbate its impact. Exposure to even low levels of air pollutants had negative effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2024
Full Text
View/download PDF

47. Difficulties in ophthalmic symptom interpretation in a patient with COVID-19.

Author

Stawowski AR, Stawowski SS, Moniuszko-Malinowska A, Guziejko K, Snarska KK, Konopińska J, Groth M, and Chorąży M

Subjects
Humans, Male, Aged, SARS-CoV-2, Poland, Magnetic Resonance Imaging, Meningeal Neoplasms diagnosis, Meningeal Neoplasms diagnostic imaging, Tomography, X-Ray Computed, Vision Disorders etiology, COVID-19 diagnosis, COVID-19 complications, Meningioma diagnosis, Meningioma diagnostic imaging
Abstract

In this article, we describe the case of a 70-year-old man whose diagnosis of a brain meningioma was hindered by a SARS-CoV-2 infection. The patient, who had been vaccinated twice with the AstraZeneca COVID-19 vaccine, was admitted to Temporary Hospital No. 2, University Hospital (Białystok, Poland) with a positive PCR test result for SARS-CoV-2. The patient's general condition was good, but he reported a significant reduction in visual acuity in his left eye and headaches. A series of ophthalmological examinations were conducted, but they did not clarify the cause of the significant decrease in visual acuity. During hospitalization, an abnormal light reaction of the left pupil was observed, which led to the expansion of diagnostics to include imaging studies (CT and MRI). Computed tomography and magnetic resonance imaging revealed extensive isointense areas in the anterior cranial fossa, suggesting the presence of a meningioma. The final diagnosis and clarification of the cause of the visual impairment in the left eye resulted in the patient being transferred to the neurosurgery department for surgical treatment. COVID-19 diagnosis may mask the correct interpretation of other disease symptoms. Accidentally detected asymptomatic SARS-CoV-2 infection accelerated proper ophthalmic and neurology diagnosis. In this article, we describe the case of a 70-year-old man whose diagnosis of a brain meningioma was hindered by a SARS-CoV-2 infection. The patient, who had been vaccinated twice with the AstraZeneca COVID-19 vaccine, was admitted to Temporary Hospital No. 2, University Hospital (Białystok, Poland) with a positive PCR test result for SARS-CoV-2. The patient's general condition was good, but he reported a significant reduction in visual acuity in his left eye and headaches. A series of ophthalmological examinations were conducted, but they did not clarify the cause of the significant decrease in visual acuity. During hospitalization, an abnormal light reaction of the left pupil was observed, which led to the expansion of diagnostics to include imaging studies (CT and MRI). Computed tomography and magnetic resonance imaging revealed extensive isointense areas in the anterior cranial fossa, suggesting the presence of a meningioma. The final diagnosis and clarification of the cause of the visual impairment in the left eye resulted in the patient being transferred to the neurosurgery department for surgical treatment. COVID-19 diagnosis may mask the correct interpretation of other disease symptoms. Accidentally detected asymptomatic SARS-CoV-2 infection accelerated proper ophthalmic and neurology diagnosis.

Published
2024
Full Text
View/download PDF

48. Iron homeostasis and insulin sensitivity: unraveling the complex interactions.

Author

Sobieska K, Buczyńska A, Krętowski AJ, and Popławska-Kita A

Abstract

Diabetes has arisen as a noteworthy global health issue, marked by escalating incidence and mortality rates. Insulin, crucial for preserving euglycemia, acts as a vital energy provider for various tissues. Iron metabolism notably plays a significant role in the development of insulin resistance, a key factor in the onset of various metabolic disorders. The intricate interaction between iron and insulin signaling encompasses complex regulatory mechanisms at the molecular level, thereby impacting cellular reactions to insulin. The intricate interplay between insulin and glucagon, essential for precise regulation of hepatic glucose production and systemic glucose levels, may be influenced by certain microelements for instance zinc, copper, iron, boron, calcium, cobalt, chromium, iodine, magnesium and selenium. While significant progress has been achieved in elucidating the pathophysiological connections between iron overload and glucose metabolism, our understanding of the involvement of the Fenton reaction and oxidative stress in insulin resistance influencing many chronical conditions remains limited. Furthermore, the exploration of the multifaceted roles of insulin in the human body continues to be a subject of active investigation by numerous scientific researchers. This review comprehensively outlines the potential adverse impact of iron overload on insulin function and glucose metabolism. Additionally, we provide a synthesis of findings derived from various research domains, encompassing population studies, animal models, and clinical investigations, to scrutinize the multifaceted relationship between iron and insulin sensitivity. Moreover, we delineate instances of correlations between serum iron levels and various medical conditions, including the diabetes also gestational diabetes and obesity., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

49. Probiotic Lactobacillus plantarum 299v supplementation in patients with major depression in a double-blind, randomized, placebo-controlled trial: A metabolomics study.

Author

Godzien J, Kalaska B, Rudzki L, Barbas-Bernardos C, Swieton J, Lopez-Gonzalvez A, Ostrowska L, Szulc A, Waszkiewicz N, Ciborowski M, García A, Kretowski A, Barbas C, and Pawlak D

Abstract

Background: Understanding the multifactorial nature of major depressive disorder (MDD) is crucial for tailoring treatments. However, the complex interplay of various factors underlying the development and progression of MDD poses significant challenges. Our previous study demonstrated improvements in cognitive functions in MDD patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) supplemented with Lactobacillus plantarum 299v (LP299v)., Methods: To elucidate the biochemical mechanisms underlying cognitive functions improvements, we explored underlying metabolic changes. We employed multi-platform metabolomics, including LC-QTOF-MS and CE-TOF-MS profiling, alongside chiral LC-QqQ-MS analysis for amino acids., Results: Supplementation of SSRI treatment with LP299v intensified the reduction of long-chain acylcarnitines, potentially indicating improved mitochondrial function. LP299v supplementation reduced N-acyl taurines more than four times compared to the placebo, suggesting a substantial impact on restoring biochemical balance. The LP299v-supplemented group showed increased levels of oxidized glycerophosphocholine (oxPC). Additionally, LP299v supplementation led to higher levels of sphingomyelins, L-histidine, D-valine, and p-cresol., Limitations: This exploratory study suggests potential metabolic pathways influenced by LP299v supplementation. However, the need for further research hinders the ability to draw definitive conclusions., Conclusions: Observed metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption. Despite the subtle nature of this alterations, our research successfully detected these differences and connected them to the metabolic disruptions associated with MDD. Our findings emphasise the intricate relationship between metabolism, gut microbiota, and mental health prompting further research into the mechanisms of action of probiotics in MDD treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
Full Text
View/download PDF

50. Reduced retinol (vitamin A) and α-tocopherol (vitamin E) blood levels and increased myeloperoxidase (MPO) activity in children with high myopia.

Author

Mikoluc B, Sawicka-Powierza J, Berk K, Maciejczyk M, Powierza K, Zalewska A, Szulimowska J, MacDonald J, Koput A, Karpinska J, Sawczuk R, Hryniewicka M, and Bakunowicz-Lazarczyk A

Subjects
Humans, Male, Female, Child, Adolescent, Case-Control Studies, alpha-Tocopherol blood, Peroxidase blood, Vitamin A blood, Myopia blood, Myopia metabolism
Abstract

The study assessed selected parameters of redox status in the plasma of patients suffering from high myopia (HM). Thirty-five children with mean age 13.7 ± 2.7 years with HM and 40 healthy children were included. Plasma redox status parameters were determined using colorimetric kits. The levels of retinol, α-tocopherol and coenzyme Q10 were determined with a high-performance liquid chromatograph. Negative correlations were observed between the concentrations of retinol and the axial length of the eye (r = - 0.514 p < 0.001). Increased myeloperoxidase (MPO) activity (p < 0.018), and decreased concentrations of retinol (p < 0.001) and α-tocopherol (p < 0.023) in patients with HM and the axial length of the eye > 26 mm compared to controls were established. Significantly lower retinol and α-tocopherol concentrations were found in patients with the axial length of the eye > 26 mm compared to those with the axial length of the eye ≤ 26 mm (p < 0.001, p < 0.021, respectively). Increased MPO activity in advanced stages of HM may confirm an inflammatory process in HM patients. Reduced retinol and α-tocopherol concentrations and their link to disease progression indicate a need for monitoring their levels and supplementation in children with HM., (© 2024. The Author(s).)

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results