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GET /v1/research/project/?format=api&offset=1280&ordering=begin_effective
{ "count": 2265, "next": "https://api-test.medunigraz.at/v1/research/project/?format=api&limit=20&offset=1300&ordering=begin_effective", "previous": "https://api-test.medunigraz.at/v1/research/project/?format=api&limit=20&offset=1260&ordering=begin_effective", "results": [ { "id": 5459, "title": { "de": "Führt die Zwerchfellhernie zu Unterschieden im pulmonalen Mikrobiom und Atemgasprofil im Vergleich zu gesunden Kindern?\r\n\r\n", "en": "Does congenital diaphragmatic hernia lead to alterations in pulmonary microbiome and exhaled volatile organic compounds compared to healthy children?" }, "short": "CDH VOC Study", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-09-01T02:00:00+02:00", "end_planned": "2019-10-31T01:00:00+01:00", "end_effective": "2019-10-31T01:00:00+01:00", "assignment": "2018-08-27T14:52:47+02:00", "program": null, "subprogram": null, "organization": 14049, "category": 10, "type": 10, "partner_function": 4, "manager": null, "contact": null, "status": 2, "research": 3, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 457 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "5459-50778-12", "5459-54087-12" ] }, { "id": 5471, "title": { "de": "Klinische Anwendbarkeit ex vivo generierter Erythrozyten mit Fokus auf biomechanische Eigenschaften", "en": "Clinical translation of ex vivo cultured erythrocytes – biomechanical properties of manufactured red blood cells\r\n\r\n" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-09-01T02:00:00+02:00", "begin_effective": "2018-09-01T02:00:00+02:00", "end_planned": "2020-08-31T02:00:00+02:00", "end_effective": "2022-10-31T01:00:00+01:00", "assignment": "2018-09-11T18:08:07+02:00", "program": null, "subprogram": null, "organization": 14058, "category": 10, "type": 10, "partner_function": 4, "manager": 51164, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 12 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "5471-51164-10" ] }, { "id": 5424, "title": { "de": "Modeling subclonal heterogeneity, chemotherapy-resistance and relapse of acute myeloid leukemia in a novel refined humanized xenotransplantation model.", "en": "Ein neues humanisiertes Xenotransplantationsmodell zur Analyse von subclonaler Heterogenität, Chemotherapie-Resistenz und Relaps in der akuten myeloischen Leukämie. " }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-09-01T02:00:00+02:00", "begin_effective": "2018-09-01T02:00:00+02:00", "end_planned": "2020-08-30T02:00:00+02:00", "end_effective": "2021-12-31T01:00:00+01:00", "assignment": "2018-07-25T13:01:06+02:00", "program": null, "subprogram": null, "organization": 14082, "category": 10, "type": 10, "partner_function": 4, "manager": 50747, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 204 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "5424-50747-10" ] }, { "id": 5467, "title": { "de": "Modifikation des Mikrobioms zur Verbesserung von Metabolismus, Darmbarriere und Entzündung bei kindlichem Neuroblastom", "en": "Modification of the intestinal microbiome to improve metabolism, gut barrier function and inflammation in neuroblastoma" }, "short": "Mikrobiom-Tumor", "url": null, "abstract": { "de": "HINTERGRUND: Im Rahmen von malignen Tumorerkrankungen kann es zu einem katabolen Zustandsbild mit Verlust von Fett- und Muskelgewebe kommen. Dieses geht mit erheblicher Morbidität und Mortalität einher und wird als Kachexie bezeichnet. Obwohl die volle Ausprägung selten ist, wird bei bis zu 50% der pädiatrischen Malignome eine Unterernährung diagnostiziert. Neben dem Tumor selbst können auch Nebenwirkungen der Chemotherapie schwerwiegende Probleme bereiten. So wird in bis zu 60% dieser Kinder eine Mukositis des Gastrointestinaltraktes beobachtet, die sich klinisch durch Übelkeit, Erbrechen, Durchfall oder Obstipation, Schmerzen und – im schlimmsten Fall – lebensbedrohlichen Entzündungsreaktionen kennzeichnet. Im Alltag kann das eine Reduktion der Chemotherapie oder einen Ausfall eines Zyklus mit reduzierter Effektivität der Chemotherapie erfordern. Bisher ist die Therapie der Mukositis rein symptomatisch. Rezente Untersuchungen des Antragsstellers haben im Mikrobiom von Mäusen mit Neuroblastom (einem malignen Tumor des Kindesalters) einen signifikanten Abfall der Lactobacilli beobachtet, der mit einem pro-inflammatorischen Zustandsbild, Kachexie und gesteigerter Darmpermeabilität einherging. In diesem Modell hat auch die Chemotherapie alleine eine Dysbiose mit Abfall der Lactobacilli ausgelöst, was ursächlich mit der Entstehung einer Mukositis in Verbindung stehen könnte. Insgesamt scheint das intestinale Mikrobiom einen erheblichen Bestandteil in der Entstehung von Kachexie und chemotherapie-induzierter Mukositis zu haben.\r\nZIEL: Ziel dieses Projektes ist es zu untersuchen, ob eine Manipulation des Mikrobioms mittels Präbiotika, Probiotika oder Bakteriozinen einen positiven Einfluss auf Entzündungsreaktion, Darmwandbarriere und Metabolismus bei Neuroblastomen hat. Zusätzlich soll beurteilt werden, ob die im Tiermodell beobachten mikrobiellen Veränderungen auch bei Kindern mit Neuroblastom beobachtet werden können.\r\nMETHODEN: Im tierexperimentellen Teil wird das bereits etablierte Neuroblastommodell verwendet um bei Mäusen eine Kachexie auszulösen. Zusätzlich wird einem Teil der Mäuse eine Chemotherapie verabreicht. Danach wird im ersten Arbeitspaket der Einfluss von Omni-Logic® Apfelpektin und Omni-Biotic® AAD auf diese Mäuse untersucht. Der Hauptfokus liegt dabei auf der Beurteilung des fäkalen Mikrobioms, des bakteriellen Metabolismus, der Darmwandbarriere, Mukositis, des Entzündungssystemes und des Metabolismus. In einem weiteren Arbeitspaket werden dann speziell auf die beobachteten Veränderungen des Mikrobioms ausgerichtete Bakteriozine und antimikrobielle Metabolite hergestellt, für die in-vivo Anwendung angepasst, und im gleichen Tiermodell angewendet. Im grundlagenwissenschaftlichen humanen Teil des Projektes wird untersucht, ob zwischen Kindern mit Neuroblastom und gesunden Kontrollen ein Unterschiede im Mikrobiom und im Profil der volatilen Gase in Stuhl und Atemluft besteht. Zusätzlich wird in diesem Paket durch serielle Messungen Fokus auf mögliche Veränderungen des intestinalen Mikrobioms im Verlauf der Chemotherapie gelegt.\r\nINNOVATIONSGEHALT: Um die Forschungsschwerpunkte dieses Projektes zu beurteilen, kommen hochmoderne Verfahren zur Anwendung. Insbesondere die Untersuchung der volatilen Gase in Stuhl und Atemluft ist auf diesem Gebiet neu und gibt wichtige, nicht-invasive Einblicke in die mikrobielle Besiedelung und damit indirekt auf Metabolismus und Entzündungsreaktion der PatientInnen. Die in diesem Projekt untersuchten Prä- und Probiotika sind bereits am Markt erhältlich. Sollte sich durch ihren Einsatz eine Reduktion der Tumor- oder Chemotherapie-bedingten Störungen des Entzündungssystems, der Darmwandbarriere und des Metabolismus ergeben, könnten diese Produkte zukünftig supportiv in der Anti-Tumortherapie angewendet werden und zur Reduktion der Morbidität beitragen. Der Therapieansatz mit Bakteriozinen ist wissenschaftliches Neuland. \r\n", "en": "BACKGROUND: Malignant tumors may lead to a catabolic state with loss of muscle and adipose tissue. The full picture of catabolism is termed cachexia and is associated with significant morbidity and mortality of cancer patients. Although the full picture is rarely observed up to 50% of children with cancer suffer from significant malnourishment. Additionally to tumor-induced catabolism, side-effects of chemotherapy may be problematic for the patients. In this regard up to 60% of children suffer from gastrointestinal mucositis presenting with nausea, vomiting, diarrhea or constipation and abdominal pain. In the worst case, mucositis may lead to bacterial translocation with life-threatening inflammatory response. Clinically this may require a reduction of the dosage or the number of chemotherapy cycles resulting in reduced effectivity. Up to now the therapy of mucositis is only symptomatic. Recent research of the applicant has shown a significant reduction of Lactobacilli in mice with neuroblastoma (a malignant childhood tumor). The dysbiosis was associated with catabolism, increased gut permeability and inflammation. Astonishingly, chemotherapy alone also lead to a significant reduction of Lactobacilli compared to sham mice, which may be linked to the development of mucositis clinically. Overall, the intestinal microbiome seems to play an essential role in the development of tumor-associated catabolism and chemotherapy-induced mucositis.\r\nAIM: The aim of this project is to determine if manipulation of the intestinal microbiome with prebiotics, probiotics and bacteriocins (also referred to as lantibiotics) exerts beneficial effects on inflammation, gut permeability and metabolism in a murine model of neuroblastoma. Additionally, a human work package should determine if the changes in the intestinal microbiome observed in mice can also be seen in children with neuroblastoma.\r\nMETHODS: An established neuroblastoma model will be used to cause cachexia in mice. Additionally, a group of animals will receive chemotherapy. One work package will analyze the effect of Omni-Logic® Apfelpektin (a prebiotic containing pectin oligosaccharides) and Omni-Biotic® AAD (a probiotic) on these mice. The main focus will be on the intestinal microbiome, bacterial metabolism , gut permeability , mucositis , inflammation and metabolism. Additionally, data gained on microbial alterations by tumor and chemotherapy will be used to select specific bacteriocins and bacterial metabolites to influence the microbiome. These substances will be prepared for in vivo testing and applied to the same animal model. A basic science human work package will address the question if there are differences in the intestinal microbiome and the volatile organic compound profile between children with neuroblastoma and healthy controls. Furthermore, serial investigations in children with neuroblastoma will assess whether of not these patients show alterations of the intestinal microbiome under chemotherapy.\r\nINNOVATIONS: In this project cutting edge technology will be used to gain information about the main research topics. Especially the examination of volatile organic compounds in relation to the other tests is novel in this research field and provides non-invasive information about bacterial metabolism and indirectly on the patients’ inflammatory system and metabolism. The pre- and probiotics tested in this project are available on the market. If they lead to a reduction of tumor- or chemotherapy-induced disturbances of inflammatory system, gut barrier or metabolism in this project they may be easily used as supportive measures in the anti-cancer therapy of the future. The use of bacteriocins has presently not been tested in this context. If these substances would prove effective then this project would be a first important milestone towards human application of bacteriocins.\r\n" }, "begin_planned": "2018-08-01T02:00:00+02:00", "begin_effective": "2018-09-01T02:00:00+02:00", "end_planned": "2021-07-31T02:00:00+02:00", "end_effective": "2022-06-30T02:00:00+02:00", "assignment": "2018-09-03T17:23:35+02:00", "program": 60, "subprogram": null, "organization": 14049, "category": 10, "type": 10, "partner_function": 4, "manager": 54087, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 416 ], "funder_projectcode": "867991", "ethics_committee": null, "edudract_number": null, "persons": [ "5467-50778-12", "5467-50881-12", "5467-54087-10", "5467-73734-12", "5467-90375-12", "5467-100457-12", "5467-102412-12" ] }, { "id": 5515, "title": { "de": "COST: Krebs-Nanomedizin - vom Labor zum Patienten", "en": "COST: Cancer-Nanomedicine - from the bench to the bedside" }, "short": "NANO2CLINIC", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-09-29T02:00:00+02:00", "begin_effective": "2018-09-29T02:00:00+02:00", "end_planned": "2022-09-28T02:00:00+02:00", "end_effective": "2022-09-28T02:00:00+02:00", "assignment": "2018-10-11T11:51:19+02:00", "program": 22, "subprogram": null, "organization": 14011, "category": 10, "type": 10, "partner_function": 2, "manager": 83066, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "5515-83066-10" ] }, { "id": 5486, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Inflammatory Disorders in Pregnancy" }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:35:48+02:00", "program": 114, "subprogram": null, "organization": 14023, "category": 10, "type": 10, "partner_function": 2, "manager": 90021, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5486-90021-10", "5486-100806-12" ] }, { "id": 5370, "title": { "de": "LipoLUNG: Adipose Triglyzerid Lipase bei Lungenkrebs", "en": "LipoLUNG: Molecular and metabolic roles of Adipocyte Triglyceride Lipase in lung cancer" }, "short": "LipoLUNG", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-01-01T01:00:00+01:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2021-12-31T01:00:00+01:00", "end_effective": "2023-09-30T02:00:00+02:00", "assignment": "2018-05-23T11:31:07+02:00", "program": 72, "subprogram": null, "organization": 14020, "category": 10, "type": 10, "partner_function": 4, "manager": 51691, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "P30968", "ethics_committee": null, "edudract_number": null, "persons": [ "5370-50903-12", "5370-57409-12", "5370-51691-10" ] }, { "id": 5428, "title": { "de": "Endo/lysosomale Beweglichkeit & Funktion in Leber -Physiologie und -Pathology", "en": "Endo/lysosome motility & function in liver physiology and liver pathology" }, "short": "“Wissenschaftspreis der ÖGGH”", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2020-04-01T02:00:00+02:00", "end_effective": "2022-03-31T02:00:00+02:00", "assignment": "2018-08-03T17:24:25+02:00", "program": null, "subprogram": null, "organization": 14081, "category": 10, "type": 10, "partner_function": 4, "manager": 57596, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 203 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [ "5428-57596-10", "5428-113189-12", "5428-123430-12" ] }, { "id": 5481, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Inflammatory Disorders in Pregnancy" }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:19:32+02:00", "program": 114, "subprogram": null, "organization": 14022, "category": 10, "type": 10, "partner_function": 2, "manager": 51756, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5481-51756-10" ] }, { "id": 5449, "title": { "de": "Lysophosphatidsäure als Aktivator des MAPK Wegs in Mikroglia", "en": "Lysophospatidic acid induced signaling in microglia: the role of MAPK pathways" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2019-03-31T01:00:00+01:00", "end_effective": "2019-03-31T01:00:00+01:00", "assignment": "2018-08-20T12:02:08+02:00", "program": null, "subprogram": null, "organization": 14013, "category": 10, "type": 10, "partner_function": 4, "manager": null, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 15 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [] }, { "id": 5485, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Inflammatory Disorders in Pregnancy" }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:34:58+02:00", "program": 114, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 2, "manager": 54142, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5485-54142-10" ] }, { "id": 5479, "title": { "de": " Inflammatorische Erkrankungen in der Schwangerschaft ", "en": "Inflammatory Disorders in Pregnancy " }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:17:36+02:00", "program": 114, "subprogram": null, "organization": 14038, "category": 10, "type": 10, "partner_function": 2, "manager": null, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [] }, { "id": 5499, "title": { "de": " Promoting patient safety by a novel combination of imaging technologies for biodegradable magnesium implants", "en": " Promoting patient safety by a novel combination of imaging technologies for biodegradable magnesium implants" }, "short": "MgSafe", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-07-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-06-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-27T10:12:59+02:00", "program": 109, "subprogram": null, "organization": 14052, "category": 10, "type": 10, "partner_function": 2, "manager": 50785, "contact": null, "status": 2, "research": 2, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 10 ], "funder_projectcode": "811226", "ethics_committee": null, "edudract_number": null, "persons": [ "5499-50785-10", "5499-96335-12", "5499-98087-12", "5499-103918-12", "5499-102252-12" ] }, { "id": 5487, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Inflammatory Disorders in Pregnancy" }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:36:55+02:00", "program": 114, "subprogram": null, "organization": 14013, "category": 10, "type": 10, "partner_function": 2, "manager": 51904, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5487-51904-10" ] }, { "id": 5439, "title": { "de": "Extrazelluläre Vesikel & Kommunikation in Chordom-Zelllinien", "en": "Extracellular Vesicles & Communication in Chordoma Cell Lines" }, "short": null, "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2020-04-01T02:00:00+02:00", "end_effective": "2020-04-01T02:00:00+02:00", "assignment": "2018-08-09T12:13:32+02:00", "program": null, "subprogram": null, "organization": 27477, "category": 10, "type": 10, "partner_function": 4, "manager": null, "contact": null, "status": 2, "research": 1, "grant": 30, "event": null, "study": null, "language": null, "funders": [ 457 ], "funder_projectcode": null, "ethics_committee": null, "edudract_number": null, "persons": [] }, { "id": 5260, "title": { "de": "Entwicklung genetisch kodierter K+-Fluoreszenzsensoren", "en": "Development of genetically encoded fluorescent K+ probes" }, "short": "Shining Light on (sub)cellular K+ fluxes", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-01-01T01:00:00+01:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2020-12-31T01:00:00+01:00", "end_effective": "2022-12-31T01:00:00+01:00", "assignment": "2018-02-15T10:36:01+01:00", "program": 64, "subprogram": "I - Internationale Projekte - Joint Project - Austria/Germany", "organization": 14013, "category": 10, "type": 10, "partner_function": 4, "manager": 50810, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "3716-B27", "ethics_committee": null, "edudract_number": null, "persons": [ "5260-50810-10" ] }, { "id": 5480, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft.\r\nNuclear Rezeptor - vermittelte Regulation metabolischer und inflammatorischer Mediatoren in fetoplazentaren Endothelzellen", "en": "Inflammatory Disorders in Pregnancy.\r\nNuclear receptors regulating metabolism and inflammatory mediators in fetoplacental endothelial cells" }, "short": "DP-iDP", "url": "https://www.medunigraz.at/phd-inflammatory-disorders-in-pregnancy/", "abstract": { "de": null, "en": "Rising evidence suggests that Gestational diabetes mellitus (GDM) modulates the placental endothelium to an altered metabolic state causing vascular dysfunction and altered fetal programming. GDM is associated with oxidative stress which may contribute to endothelial dysfunction. Oxysterols, generated from cholesterol oxidation either by CYP-450 reductase or by reactive oxygen species (ROS), are endogenous activators of liver-X receptors (LXRs), nuclear transcription factors centrally involved in important biological processes, including lipid/cholesterol and glucose metabolism (1). \r\nLXRs promote high-density lipoprotein (HDL) formation by activating several target genes of reverse cholesterol transport. We earlier reported that LXR target genes (ABCA1, ABCG1 and PLTP) are centrally involved in HDL mediated cholesterol efflux from fetoplacental endothelial cells (HPEC) (2-4). \r\nA current focus of our laboratory is to define the impact of oxysterols and pharmacological activators of LXRs on cholesterol-metabolic and inflammatory functions in the GDM feto-placental vasculature. Unpublished results of our group strongly suggest that the GDM environment modulates cholesterol homeostasis by enhancing cholesterol biosynthesis and cholesterol efflux in fetoplacental endothelial cells while cellular cholesterol homeostasis is largely maintained. Thus, GDM may affect placental cholesterol metabolism via LXR activation due to increased oxysterol levels in cells and/or in the fetal circulation. \r\nWhile HDL itself exerts anti-inflammatory actions on endothelial cells, LXRs are also involved in immune regulatory functions and can reduce inflammation by sumoylation-dependent and -independent mechanisms (1). Upon activation, LXRs can be sumoylated and as a monomer can stabilize repressor complexes present on the promoter sequence of proinflammatory pathways such as activator protein 1 (AP-1) and nuclear factor kB (NF-kB), thereby preventing the expression of proinflammatory factors. In brain endothelial cells, LXR activation by oxysterols or synthetic agonist TO901317 significantly reduced expression of inflammatory genes COX-II and TNF along with modulating cellular cholesterol metabolism (5). We hypothesize that endogenous and/or pharmacologic activation of LXRs may improve fetoplacental endothelial function in conditions of GDM and other pregnancy complications related to metabolic diseases.\r\n\r\nReferences:\r\n1.\tGuillemot-Legris O, Mutemberezi V, Muccioli GG. Oxysterols in Metabolic Syndrome: From Bystander Molecules to Bioactive Lipids. Trends Mol Med. 2016; 22(7):594-614.\r\n2.\tStefulj J, Panzenboeck U1, Becker T, Hirschmugl B, Schweinzer C, Lang I, Marsche G, Sadjak A, Lang U, Desoye G, and Wadsack C. Human Endothelial Cells of the Placental Barrier Efficiently Deliver Cholesterol to the Fetal Circulation via ABCA1 and ABCG1. Circ Res. 2009; 104:600-608.\r\n4.\tScholler M, Wadsack C, Metso J, Chirackal Manavalan AP, Sreckovic I, Schweinzer C, Hiden U, Jauhiainen M, Desoye G, Panzenboeck U. Phospholipid transfer protein is differentially expressed in human arterial and venous placental endothelial cells and enhances cholesterol efflux to fetal HDL. J Clin Endocrinol Metab. 2012; 97:2466-74.\r\n5.\tScholler M, Wadsack C, Lang I, Etschmaier K, Schweinzer C, Marsche G, Dieber-Rotheneder M, Desoye G, Panzenboeck U. Phospholipid Transfer Protein in the Placental Endothelium Is Affected by Gestational Diabetes Mellitus. J Clin Endocrinol Metab. 2012; 97:437-45.\r\n7.\tSchweinzer C, Kober A, Lang I, Etschmaier K, Scholler M, Kresse A, Sattler W, Panzenboeck U. Processing of Endogenous AβPP in Blood-Brain Barrier Endothelial Cells is Modulated by Liver-X Receptor Agonists and Altered Cellular Cholesterol Homeostasis. J Alzheimers Dis. 2011; 27(2):341-360.\r\n" }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:18:44+02:00", "program": 114, "subprogram": null, "organization": 14038, "category": 10, "type": 10, "partner_function": 2, "manager": 50442, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5480-50442-10", "5480-61645-12" ] }, { "id": 5431, "title": { "de": "Koordination des Doktoratsprogramms: Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Coordination of the Doctoral Program: Inflammatory Disorders in Pregnancy " }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-01-01T01:00:00+01:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2021-12-31T01:00:00+01:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-26T15:31:56+02:00", "program": 114, "subprogram": "doc.funds", "organization": 14038, "category": 10, "type": 10, "partner_function": 3, "manager": 50442, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5431-50442-10", "5431-56938-12", "5431-59816-12", "5431-83661-12", "5431-90214-12", "5431-95608-12", "5431-100813-12", "5431-100803-12", "5431-105059-12" ] }, { "id": 5482, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Inflammatory Disorders in Pregnancy" }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:32:06+02:00", "program": 114, "subprogram": null, "organization": 14017, "category": 10, "type": 10, "partner_function": 2, "manager": 53232, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5482-53232-10" ] }, { "id": 5483, "title": { "de": "Inflammatorische Erkrankungen in der Schwangerschaft", "en": "Inflammatory Disorders in Pregnancy" }, "short": "DP-iDP", "url": null, "abstract": { "de": null, "en": null }, "begin_planned": "2018-10-01T02:00:00+02:00", "begin_effective": "2018-10-01T02:00:00+02:00", "end_planned": "2022-09-30T02:00:00+02:00", "end_effective": "2022-09-30T02:00:00+02:00", "assignment": "2018-09-19T11:32:58+02:00", "program": 114, "subprogram": null, "organization": 14022, "category": 10, "type": 10, "partner_function": 2, "manager": 53252, "contact": null, "status": 2, "research": 1, "grant": 10, "event": null, "study": null, "language": null, "funders": [ 9 ], "funder_projectcode": "Doc 31-B26", "ethics_committee": null, "edudract_number": null, "persons": [ "5483-53252-10" ] } ] }