Bibliographies thématiques / SphK-1

Littérature scientifique sur le sujet « SphK-1 »

Auteur : Grafiati
Publié le 10 mars 2023

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Articles de revues sur le sujet "SphK-1"

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Venkataraman, Krishnan, Shobha Thangada, Jason Michaud, Myat Lin Oo, Youxi Ai, Yong-Moon Lee, Mingtao Wu et al. « Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient ». Biochemical Journal 397, no 3 (13 juillet 2006) : 461–71. http://dx.doi.org/10.1042/bj20060251.

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Sphingosine 1-phosphate (S1P), produced by Sphks (sphingosine kinases), is a multifunctional lipid mediator that regulates immune cell trafficking and vascular development. Mammals maintain a large concentration gradient of S1P between vascular and extravascular compartments. Mechanisms by which S1P is released from cells and concentrated in the plasma are poorly understood. We recently demonstrated [Ancellin, Colmont, Su, Li, Mittereder, Chae, Stefansson, Liau and Hla (2002) J. Biol. Chem. 277, 6667–6675] that Sphk1 activity is constitutively secreted by vascular endothelial cells. In the present study, we show that among the five Sphk isoforms expressed in endothelial cells, the Sphk-1a isoform is selectively secreted in HEK-293 cells (human embryonic kidney cells) and human umbilical-vein endothelial cells. In sharp contrast, Sphk2 is not secreted. The exported Sphk-1a isoform is enzymatically active and produced sufficient S1P to induce S1P receptor internalization. Wild-type mouse plasma contains significant Sphk activity (179 pmol·min−1·g−1). In contrast, Sphk1−/− mouse plasma has undetectable Sphk activity and approx. 65% reduction in S1P levels. Moreover, human plasma contains enzymatically active Sphk1 (46 pmol·min−1·g−1). These results suggest that export of Sphk-1a occurs under physiological conditions and may contribute to the establishment of the vascular S1P gradient.
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Wadgaonkar, Raj, Vipul Patel, Natalia Grinkina, Carol Romano, Jing Liu, Yutong Zhao, Saad Sammani, Joe G. N. Garcia et Viswanathan Natarajan. « Differential regulation of sphingosine kinases 1 and 2 in lung injury ». American Journal of Physiology-Lung Cellular and Molecular Physiology 296, no 4 (avril 2009) : L603—L613. http://dx.doi.org/10.1152/ajplung.90357.2008.

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Two mammalian sphingosine kinase (SphK) isoforms, SphK1 and SphK2, possess identical kinase domains but have distinct kinetic properties and subcellular localizations, suggesting each has one or more specific roles in sphingosine-1-phosphate (S1P) generation. Although both kinases use sphingosine as a substrate to generate S1P, the mechanisms controlling SphK activation and subsequent S1P generation during lung injury are not fully understood. In this study, we established a murine lung injury model to investigate LPS-induced lung injury in SphK1 knockout (SphK1−/−) and wild-type (WT) mice. We found that SphK1−/− mice were much more susceptible to LPS-induced lung injury compared with their WT counterparts, quantified by multiple parameters including cytokine induction. Intriguingly, overexpression of WT SphK1 delivered by adenoviral vector to the lungs protected SphK1−/− mice from lung injury and attenuated the severity of the response to LPS. However, adenoviral overexpression of a SphK1 kinase-dead mutant (SphKKD) in SphK1−/− mouse lungs further exacerbated the response to LPS as well as the extent of lung injury. WT SphK2 adenoviral overexpression also failed to provide protection and, in fact, augmented the degree of LPS-induced lung injury. This suggested that, in vascular injury, S1P generated by SphK2 activation plays a distinctly separate role compared with SphK1-dependent S1P generation and survival signaling. Microarray and real-time RT-PCR analysis of SphK1 and SphK2 expression levels during lung injury revealed that, in WT mice, LPS treatment caused significantly enhanced SphK1 expression (∼5×) levels within 6 h, which declined back to baseline levels by 24 h posttreatment. In contrast, expression of SphK2 was gradually induced following LPS treatment and was elevated within 24 h. Collectively, our results for the first time demonstrate distinct functional roles of the two SphK isoforms in the regulation of LPS-induced lung injury.
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Serrano-Sanchez, Martin, Zahra Tanfin et Denis Leiber. « Signaling Pathways Involved in Sphingosine Kinase Activation and Sphingosine-1-Phosphate Release in Rat Myometrium in Late Pregnancy : Role in the Induction of Cyclooxygenase 2 ». Endocrinology 149, no 9 (29 mai 2008) : 4669–79. http://dx.doi.org/10.1210/en.2008-1756.

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We investigated the regulation of the sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P) axis and its role during pregnancy in the rat myometrium. SphK1 and SphK2 were coexpressed in myometrium during gestation. The levels and activity of SphK1/2 were modest at midgestation (d 12), increased at d 19 and progressively declined to low at postpartum. Similar patterns were observed for the phosphorylation of ERK and protein kinase C (PKC). Inhibition of PKC and ERK reduced SphK1/2 activity. In late pregnancy, levels of cyclooxygenase 2 (COX2) increased in parallel to SphK levels. Using a pharmacological approach, we demonstrated that in primary cultures of myometrial cells from d-19 pregnant rats, induction of COX2 was mediated by 4β-phorbol 12,13-dibutyrate and IL-1β through sequential activation of PKC, ERK1/2, and SphK1. S1P produced by SphK1 was released in the medium. Addition of S1P, IL-1β or 4β-phorbol 12,13-dibutyrate enhanced COX2 levels via Gi protein. Interestingly, S1P was also released by myometrial tissues at late gestation. This event was dependent on PKC/ERK/SphK1. By contrast, in d-12 myometrial tissues, the release of S1P was markedly reduced in association with low levels of SphK1 and COX2. However, prolonged incubation of myometrium from midgestation led to the induction of COX2. This effect was blocked by SphK inhibitors, providing evidence of the close relationship between SphK activity and COX2 induction in rat myometrium. Overall, our findings provided insight into the physiological relevance of the SphK activation and S1P release in uterine smooth muscle during gestation.
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MEACCI, Elisabetta, Francesca CENCETTI, Chiara DONATI, Francesca NUTI, Laura BECCIOLINI et Paola BRUNI. « Sphingosine kinase activity is required for sphingosine-mediated phospholipase D activation in C2C12 myoblasts ». Biochemical Journal 381, no 3 (27 juillet 2004) : 655–63. http://dx.doi.org/10.1042/bj20031636.

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Sphingosine (Sph) has been implicated as a modulator of membrane signal transduction systems and as a regulatory element of cardiac and skeletal muscle physiology, but little information is presently available on its precise mechanism of action. Recent studies have shown that sphingosine 1-phosphate (S1P), generated by the action of sphingosine kinase (SphK) on Sph, also possesses biological activity, acting as an intracellular messenger, as well as an extracellular ligand for specific membrane receptors. At present, however, it is not clear whether the biological effects elicited by Sph are attributable to its conversion into S1P. In the present study, we show that Sph significantly stimulated phospholipase D (PLD) activity in mouse C2C12 myoblasts via a previously unrecognized mechanism that requires the conversion of Sph into S1P and its subsequent action as extracellular ligand. Indeed, Sph-induced activation of PLD was inhibited by N,N-dimethyl-D-erythro-sphingosine (DMS), at concentrations capable of specifically inhibiting SphK. Moreover, the crucial role of SphK-derived S1P in the activation of PLD by Sph was confirmed by the observed potentiated effect of Sph in myoblasts where SphK1 was overexpressed, and the attenuated response in cells transfected with the dominant negative form of SphK1. Notably, the measurement of S1P formation in vivo by employing labelled ATP revealed that cell-associated SphK activity in the extracellular compartment largely contributed to the transformation of Sph into S1P, with the amount of SphK released into the medium being negligible. It will be important to establish whether the mechanism of action identified in the present study is implicated in the multiple biological effects elicited by Sph in muscle cells.
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AGEITOS, ARACELI TOBIO, GEETHANI BANDARA, ROSA MUNOZ-CANO, YUZHI YIN, AVANTI DESAI, DEAN METCALFE et ANA OLIVERA. « Sphingosine Kinase Inhibitors Effectively Inhibit Growth of Mast Cells with D816V-KIT Mutations ». Journal of Immunology 198, no 1_Supplement (1 mai 2017) : 145.13. http://dx.doi.org/10.4049/jimmunol.198.supp.145.13.

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Abstract Sphingosine-1-phosphate (S1P) is a lipid mediator that promotes cell proliferation and prevents apoptosis in a variety of cells and its increased synthesis by Sphingosine Kinase (SphK) has been associated with oncogenesis and cancer prognosis. Mastocytosis is a disorder characterized by excessive mast cell (MC) proliferation and accumulation in tissues. Treatment therapies for aggressive mastocytosis have to date been partially effective, and thus the search of new pharmacological targets is warranted. We thus investigated the involvement of SphK isoforms (SphK1 and SphK2) and generation of S1P in the regulation of abnormal MC growth. The specific SphK1 and SphK2 inhibitors, SKI-178 and ABC294640, respectively, were used in this study. The effect of SphK1 and SphK2 inhibition on human (LAD2, HMC1.1 and HMC1.2) and murine (P815) neoplastic MC proliferation and survival was evaluated. SphK2 inhibition retarded entry into the cell cycle in all MC lines with no significant effect on cell survival. However, SphK1 inhibition led to cell cycle arrest in G2/M and apoptosis predominantly in MCs carrying D816V-KIT mutation. The effect of SKI-178 was associated with an alteration in the damage response cascade. This included activation of checkpoint kinase 2 (chk2) combined with a depletion of chk1, leading respectively to p53- and caspase2-induced apoptosis and cell cycle arrest mediated by cdc25c depletion. Both SphK inhibitors reduced MC accumulation in an in vivo mouse model of aggressive mastocytosis and the number of cultured bone marrow MCs and MC progenitors from a patient with systemic mastocytosis. These results support further consideration for SphK inhibitors as a cytoreductive strategy in proliferative MC disorders.
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Magli, Elisa, Angela Corvino, Ferdinando Fiorino, Francesco Frecentese, Elisa Perissutti, Irene Saccone, Vincenzo Santagada, Giuseppe Caliendo et Beatrice Severino. « Design of Sphingosine Kinases Inhibitors : Challenges and Recent Developments ». Current Pharmaceutical Design 25, no 9 (9 juillet 2019) : 956–68. http://dx.doi.org/10.2174/1381612825666190404115424.

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Background:Sphingosine kinases (SphKs) catalyze the phosphorylation of sphingosine to form the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P). S1P is an important lipid mediator with a wide range of biological functions; it is also involved in a variety of diseases such as inflammatory diseases, Alzheimer’s disease and cancer.Methods:This review reports the recent advancement in the research of SphKs inhibitors. Our purpose is also to provide a complete overview useful for underlining the features needed to select a specific pharmacological profile.Discussion:Two distinct mammalian SphK isoforms have been identified, SphK1 and SphK2. These isoforms are encoded by different genes and exhibit distinct subcellular localizations, biochemical properties and functions. SphK1 and SphK2 inhibition can be useful in different pathological conditions.Conclusion:SphK1 and SphK2 have many common features but different and even opposite biological functions. For this reason, several research groups are interested in understanding the therapeutic usefulness of a selective or non-selective inhibitor of SphKs. Moreover, a compensatory mechanism for the two isoforms has been demonstrated, thus leading to the development of dual inhibitors.
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Lynch, Kevin R. « Building a better sphingosine kinase-1 inhibitor ». Biochemical Journal 444, no 1 (26 avril 2012) : e1-e2. http://dx.doi.org/10.1042/bj20120567.

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Sphingosine 1-phosphate (S1P) is currently one of the most intensely studied lipid mediators. Interest in S1P has been propelled by the development of fingolimod, an S1P receptor agonist prodrug, which revealed both a theretofore unsuspected role of S1P in lymphocyte trafficking and that such modulation of the immune system achieves therapeutic benefit in multiple sclerosis patients. S1P is synthesized from sphingosine by two SphKs (sphingosine kinases) (SphK1 and SphK2). Manipulation of SphK levels using molecular biology and mouse genetic tools has implicated these enzymes, particularly SphK1, in a variety of pathological processes such as fibrosis, inflammation and cancer progression. The results of such studies have spurred interest in SphK1 as a drug target. In this issue of the Biochemical Journal, Schnute et al. describe a small molecule inhibitor of SphK1 that is both potent and selective. Such chemical tools are essential to learn whether targeting S1P signalling at the level of synthesis is a viable therapeutic strategy.
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Kharel, Yugesh, Mithun Raje, Ming Gao, Amanda M. Gellett, Jose L. Tomsig, Kevin R. Lynch et Webster L. Santos. « Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphate ». Biochemical Journal 447, no 1 (12 septembre 2012) : 149–57. http://dx.doi.org/10.1042/bj20120609.

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S1P (sphingosine 1-phosphate) is a pleiotropic lipid mediator involved in numerous cellular and physiological functions. Of note among these are cell survival and migration, as well as lymphocyte trafficking. S1P, which exerts its effects via five GPCRs (G-protein-coupled receptors) (S1P1–S1P5), is formed by the action of two SphKs (sphingosine kinases). Although SphK1 is the more intensively studied isotype, SphK2 is unique in it nuclear localization and has been reported to oppose some of the actions ascribed to SphK1. Although several scaffolds of SphK1 inhibitors have been described, there is a scarcity of selective SphK2 inhibitors that are necessary to evaluate the downstream effects of inhibition of this isotype. In the present paper we report a cationic amphiphilic small molecule that is a selective SphK2 inhibitor. In the course of characterizing this compound in wild-type and SphK-null mice, we discovered that administration of the inhibitor to wild-type mice resulted in a rapid increase in blood S1P, which is in contrast with our SphK1 inhibitor that drives circulating S1P levels down. Using a cohort of F2 hybrid mice, we confirmed, compared with wild-type mice, that circulating S1P levels were higher in SphK2-null mice and lower in SphK1-null mice. Thus both SphK1 and SphK2 inhibitors recapitulate the blood S1P levels observed in the corresponding null mice. Moreover, circulating S1P levels mirror SphK2 inhibitor levels, providing a convenient biomarker of target engagement.
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Vessey, Donald A., Luyi Li, Zhu-Qiu Jin, Michael Kelley, Norman Honbo, Jianqing Zhang et Joel S. Karliner. « A Sphingosine Kinase Form 2 Knockout Sensitizes Mouse Myocardium to Ischemia/Reoxygenation Injury and Diminishes Responsiveness to Ischemic Preconditioning ». Oxidative Medicine and Cellular Longevity 2011 (2011) : 1–8. http://dx.doi.org/10.1155/2011/961059.

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Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved in ischemic preconditioning (IPC). Since the ratio of SphK1 : SphK2 changes dramatically with aging, it is important to assess the role of SphK2 in IR injury and IPC. Langendorff mouse hearts were subjected to IR (30 min equilibration, 50 min global ischemia, and 40 min reperfusion). IPC consisted of 2 min of ischemia and 2 min of reperfusion for two cycles. At baseline, there were no differences in left ventricular developed pressure (LVDP), ± dP/dtmax, and heart rate between SphK2 null (KO) and wild-type (WT) hearts. In KO hearts, SphK2 activity was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited significantly more cardiac damage (% infarct size) compared with WT (% infarct size); postischemic recovery of LVDP was lower in KO hearts. IPC exerted cardioprotection in WT hearts. The protective effect of IPC against IR was diminished in KO hearts which had much higher infarction sizes (%) compared to the IPC/IR group in control hearts (%). Western analysis revealed that KO hearts had substantial levels of phosphorylated p38 which could predispose the heart to IR injury. Thus, deletion of the SphK2 gene sensitizes the myocardium to IR injury and diminishes the protective effect of IPC.
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Jo, Hyein, Kyeonghee Shim et Dooil Jeoung. « The Crosstalk between FcεRI and Sphingosine Signaling in Allergic Inflammation ». International Journal of Molecular Sciences 23, no 22 (11 novembre 2022) : 13892. http://dx.doi.org/10.3390/ijms232213892.

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Sphingolipid molecules have recently attracted attention as signaling molecules in allergic inflammation diseases. Sphingosine-1-phosphate (S1P) is synthesized by two isoforms of sphingosine kinases (SPHK 1 and SPHK2) and is known to be involved in various cellular processes. S1P levels reportedly increase in allergic inflammatory diseases, such as asthma and anaphylaxis. FcεRI signaling is necessary for allergic inflammation as it can activate the SPHKs and increase the S1P level; once S1P is secreted, it can bind to the S1P receptors (S1PRs). The role of S1P signaling in various allergic diseases is discussed. Increased levels of S1P are positively associated with asthma and anaphylaxis. S1P can either induce or suppress allergic skin diseases in a context-dependent manner. The crosstalk between FcεRI and S1P/SPHK/S1PRs is discussed. The roles of the microRNAs that regulate the expression of the components of S1P signaling in allergic inflammatory diseases are also discussed. Various reports suggest the role of S1P in FcεRI-mediated mast cell (MC) activation. Thus, S1P/SPHK/S1PRs signaling can be the target for developing anti-allergy drugs.
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Thèses sur le sujet "SphK-1"

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Almeida, Ana Carolina de. « Expressão de SIRP'alfa' e SPH-1 na anemia hemolitica autoimune ». [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308297.

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Orientadores: Antonio Condino Neto, Sara Teresinha Olalla Saad
Tese (doutorado)- Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-13T18:06:47Z (GMT). No. of bitstreams: 1 Almeida_AnaCarolinade_D.pdf: 1227023 bytes, checksum: 25438a379e180eeb0d1972b464b909b0 (MD5) Previous issue date: 2009
Resumo: SIRP 'alfa'(Signal Regulatory Protein 'alfa') é um receptor que medeia funções inibidoras em fagócitos. Sua ativação e conseqüente fosforilação dos ITIMs ocorre pela ligação ao CD47 presente na membrana dos eritrócitos, e permite o recrutamento e a ativação de SHP-1, a qual desfosforila substratos específicos envolvidos na mediação de diversos efeitos fisiológicos. O objetivo deste trabalho foi avaliar o papel da dexametasona (dexa) e de IFN?/TNFa sobre a expressão de SIRPa e SHP-1; a consequência desta regulação sobre a eritrofagocitose; e o nível de expressão gênica de SIRPa e SHP-1 em monócitos de pacientes com anemia hemolítica autoimune (AHAI) antes e depois de corticoterapia. Monócitos de doadores sadios e células mielomonocíticas U937 foram cultivados por 48 horas com dexa (1µM) ou IFN? (100U/ml) e TNFa (1000U/ml), por 6 horas com Hemina® (30uM), ou por 72 horas com prednisolona (0,15 e 1mg/l). Monócitos foram isolados de pacientes com AHAI antes e depois da corticoterapia. A expressão gênica de SIRPa e SHP-1 foi determinada por PCR em Tempo Real, a expressão protéica de SIRPa e SHP-1 foi determinada por Western Blotting, e a capacidade de eritrofagocitose foi determinada por microscopia. IFN? e TNFa, in vitro, promoveram o aumento da expressão gênica e protéica de SIRPa e a expressão gênica de SHP-1, em paralelo com a redução da capacidade de eritrofagocitose em monócitos normais. Em contrapartida, embora tenha aumentado a expressão gênica de SIRPa e SHP-1, dexa in vitro não alterou a expressão destas proteínas, assim como não alterou a capacidade de eritrofagocitose de monócitos normais. A expressão gênica de SIRPa e SHP-1 foi maior em monócitos de pacientes com AHAI em comparação a doadores sadios. Após corticoterapia, a expressão gênica de SIRPa e SHP-1 em monócitos de pacientes com AHAI se mostrou similar a doadores sadios. Pacientes com AHAI estudados antes da corticoterapia apresentaram baixos níveis de hemoglobina e após corticoterapia esse índice de mostrou normal. A expressão gênica de SIRPa foi aumentada pela cultura de monócitos com hemina, mas a expressão de proteína permaneceu a mesma. Nossos resultados confirmam o papel fundamental da SIRPa na regulação da eritrofagocitose e sugere que a expressão de mRNA de SIRPa em monócitos de pacientes com AHAI antes de corticoterapia é aumentada pela liberação de heme, e que a redução da expressão gênica de SIRPa após corticoterapia se deve a um efeito indireto desta droga pela redução da eritrofagocitose e diminuição da disponibilidade de heme.
Abstract: SIRPa (Signal Regulatory Protein a) is an inhibitory receptor in phagocytes. Its activation and consequent phosphorylation of ITIMs occurs by the binding to CD47 on erythrocyte membrane, what allows SHP-1 recruitment, which dephosphorylates specific substrates involved in the mediation of several physiologic effects. The aim of this work was to determine the role of dexamethasone and IFN?/TNFa upon SIRPa and SHP-1 expression, and the consequence of this regulation over erythrophagocytosis; and to evaluate the regulation of SIRPa and SHP-1 in peripheral blood monocytes (PBM) of autoimmune hemolytic anemia (AIHA) patients before and after glucocorticoid (GC) therapy. PBM from healthy donors and U937 myelomonocytic cells were cultured for 48 hours with dexamethasone (1µM) or IFN? (100U/ml) and TNFa (1000U/ml), for 6 hours with Hemin (30uM), or for 72 hours with prednisolone (0.15 and 1mg/l). PBM were isolated from AIHA patients under GC therapy or not. SIRPa and SHP-1 gene expression was determined by Real Time PCR, SIRPa and SHP-1 protein level was determined by Western Blotting, and erythrophagocytosis was determined by microscopy. IFN? and TNFa increased SIRPa gene and protein expression and SHP-1 gene expression, in parallel with a decrease in erythrophagocytosis ability in PBM. On the other hand, although SIRPa and SHP-1 gene expression was significantly increased, dexamethasone did not alter SIRPa and SHP-1 protein expression, and did not alter erythrophagocytosis ability in monocytes. SIRPa and SHP-1 expression was significantly higher in PBM from AIHA patients compared to normal. After GC therapy, SIRPa and SHP-1 expression was similar in PBM of AIHA patients compared to healthy donors. AIHA patients studied before glucocorticoid therapy showed low hemoglobin and after glucocorticoid therapy the level of hemoglobin was normal. SIRPa gene expression was increased by culture with hemin, but protein expression remained the same. Our results confirm the key role of SIRPa in erythrophagocytosis regulation and suggest that SIRPa mRNA expression in AIHA patients before glucocorticoid therapy is increased by heme release, and the decrease of SIRPa gene expression after glucocorticoid therapy is due to an indirect effect of this drug by the reduction of erythophagocytosis and free heme availability.
Doutorado
Doutor em Farmacologia
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Le, Scolan Erwan Pierre Laurent. « Recherche d'altérations génétiques impliquées dans la transformation des proérythroblastes transgéniques pour spi-1 : dérégulation transcriptionnelle du gène codant pour la sphingosine kinase de type 1 ». Paris 7, 2005. http://www.theses.fr/2005PA077035.

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Zhang, Xiwen. « KNOCKOUT OF SPHINGOSINE KINASE 1 ATTENUATES RENAL INTERSTITIAL FIBROSIS IN UNILATERAL URETERAL OBSTRUCTION (UUO) MODEL ». VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/5010.

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Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite and an important signaling molecule that plays a significant role in fibrosis. S1P synthesis is catalyzed by sphingosine kinases (SphKs), which phosphorylate sphingosine into S1P. The present study tested the hypothesis that SphK1-S1P signaling pathway participates in the kidney damage in unilateral ureteral obstruction (UUO) model. Wild type and SphK1 knockout mice were subjected to UUO for 7 days or 14 days and then four groups of kidneys were collected: wild type control group (WT-C), wild type UUO group (WT-UUO), SphK1-/- control group (KO-C) and SphK1-/- UUO group (KO-UUO). The mRNA level of SphK1 in WT-UUO was increased by 6.1 folds compared to WT-C. The fibrotic markers α-smooth muscle actin (α-SMA) and collagen I were both upregulated in UUO groups, whereas the levels of these two markers were significant lower in KO-UUO than that in WT-UUO. The immunohistochemistry analyses showed that the distribution of α-SMA and collagen was located in the interstitial space and that the infiltration of immune cells was more in UUO groups than that in control groups, but there was no significant difference between KO-UUO and WT-UUO, suggesting a direct effect of SphK1 deletion on renal fibrotic markers independent of immune regulation. Further, the morphological examination showed that UUO-induced tubular injury and glomerular damage were significantly reduced in KO-UUO compared with WT-UUO. Our study suggests that SphK1-S1P signaling pathway mediates kidney damage in UUO mice. Manipulating SphK1-S1P signaling pathway may be used as a therapeutic strategy in renal interstitial fibrosis.
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Gomez-Brouchet, Anne. « Rôle de la Sphingosine Kinase 1 (SphK1) dans la régulation de la survie des cellules de neuroblastome exposées au peptide Béta-amyloïde ». Toulouse 3, 2007. http://www.theses.fr/2007TOU30251.

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La démence de type Alzheimer pose un grand problème de santé publique dans les pays industrialisés et touche en France 850 000 personnes (5 % chez les plus de 65 ans et 20 % chez les plus de 85 ans). Elles se caractérise par la présence de lésions histologiques caractéristiques : les plaques séniles (PS) et les dégénérescences neurofibrillaires (DNF). L'analyse moléculaire et spatiotemporelle de ces deux lésions élémentaires a permis de mieux préciser la cascade des dysfonctionnements moléculaires et cellulaires de la maladie au cours de ces dernières années. Des travaux récents ont impliqué la voie Sphingomyéline/Céramide dans la mort neuronale induite par le peptide Aβ et donc dans la pathogénie de la maladie d'Alzheimer. En l'espace d'une décennie, les métabolites sphingolipidiques, c'est-à-dire céramide, sphingosine et sphingosine 1-phosphate (S1P), ont émergé comme les représentants d'une nouvelle classe de seconds messagers lipidiques régulant la prolifération, la différenciation et l'apoptose. Le céramide induit des réponses antiprolifératives et proapoptotiques, alors que l'addition de S1P favorise la survie cellulaire. Les effets opposés de ces deux sphingolipides ont conduit au concept selon lequel la balance dynamique entre les taux de céramide et de S1P représente un facteur déterminant pour le devenir de la cellule. Un acteur majeur de cette balance est la sphingosine kinase-1 (SphK1), responsable de la production de S1P. Compte tenu de ces données, nous avons étudié le rôle de la sphingosine kinase (SphK1) dans la régulation des signaux de survie et de mort des cellules humaines de neuroblastome SHSY5Y sous l'action du peptide Aβ 25-35. Il ressort de nos travaux que la SphK1 régule la survie de cellules de neuroblastome exposées au peptide β-amyloïde (25-35). En effet, l'activité SphK1 est fortement inhibée en réponse au traitement par le peptide β-amyloïde (25-35) via un mécanisme redox dépendant. .
Alzheimer disease (AD) is a critical problem of public health in the industrialized countries. AD affects 24. 3 million individuals in the world. In France, the number of AD patients represents 5 % of the population over 65 years-old (20 % of people over 85 years-old). Important progress have been made during the last ten years: Mutations were characterized, as well as genetic or environmental risk factors. A better analysis of the two elementary lesions of AD in their distribution and molecular characterization has allowed a better comprehension of the disease. Thus, the description of a dysfunction of proteins APP (Amyloid Precursor Protein) and Tau in sporadic and familial AD has led to therapeutic experiments and tests on cellular or animal models with promising results. Even though the diagnosis of AD still remains related to the neuropathology, it is evoked more precociously due to the progress in neuropsychological evaluation and imaging procedures. The advances in the comprehension of the disease mechanisms should make possible the discovery of new therapeutic targets. .
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Drosos, Zacharias [Verfasser], Lars [Akademischer Betreuer] Hanker et Markus [Akademischer Betreuer] Meier. « Die prognostische Bedeutung der Expression von Acid-Ceramidase (ASAH1) und Sphingosin-Kinase 1 (SPHK1) bei Patientinnen mit Ovarialkarzinom / Zacharias Drosos ; Akademische Betreuer : Lars Hanker, Markus Meier ». Lübeck : Zentrale Hochschulbibliothek Lübeck, 2021. http://d-nb.info/1236386272/34.

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Böhm, Andreas [Verfasser], Bernhard [Akademischer Betreuer] Rauch et Joachim [Akademischer Betreuer] Ernst. « Regulation der Sphingosin-Kinase 1 (SPHK1) durch den aktivierten Gerinnungsfaktor X (FXa) und den Protease-aktivierten Rezeptor 2 (PAR-2) in glatten Gefäßmuskelzellen / Andreas Böhm. Gutachter : Bernhard Rauch ; Joachim Ernst ». Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2013. http://d-nb.info/1043802142/34.

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Stillman, Anthony D. « Targeting Sphingosine Kinase 2 as a Treatment for Cholangiocarcinoma ». VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/6067.

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Cholangiocarcinoma (CCA) has a high mortality rate and its occurrence is rising. This increase prompts the need for improved CCA treatments. Studies have suggested that CCA is highly reliant on the sphingosine-1-phosphate-receptor-2 (S1PR2) and sphingosine kinase 2 (SphK2). Recently, a competitive SphK2 inhibitor, ABC294640, has been approved for clinical trial. ABC294640 has the potential to treat CCA, which is support by a phase I clinical study that was able to temporarily treat a patient suffering from metastasized CCA with ABC294640. To determine the viability of ABC294640 as a treatment for CCA, this study focused on determining the effects of ABC294640 on rat CCA cell lines. We found that ABC294640 inhibited the growth and migration of CCA and CAFs cells. The growth and count of 3-D organotypic co-culture of CCA and CAFs, which forms the “duct-like” structures, were reduced by ABC294640. The potential of inhibiting SphK2 as a treatment for CCA is supported by our finding of increased expression of S1PR2 and SphK2 in CCA patient liver samples. In conclusion, ABC294640 represents a potential therapeutic agent for CCA.
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Gupta, Snehalata. « Molecular interactions among PAP-1, SPHs and proPO in activation of prophenoloxidase ». 2004. http://digital.library.okstate.edu/etd/umi-okstate-1040.pdf.

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Livres sur le sujet "SphK-1"

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O'Brien, Edel, et Catherine Deegan. My Wellbeing Journey 1 : For Junior Cycle SPHE. M.H. Gill & Co. U. C., 2019.

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Healthy Lifestyles 1 : SPHE Activities for First Year Students. M.H. Gill & Co. U. C., 2008.

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O'Brien, Edel, et Catherine Deegan. New Healthy Lifestyles 1 : SPHE Activities for First Year. M.H. Gill & Co. U. C., 2014.

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Paramashivam, SPH Nithyananda. Nithya Katha 1 : Stories from the Divine Discourses of the SPH Nithyananda Paramashivam. KAILASA's Nithyananda Hindu University Press, 2011.

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Chapitres de livres sur le sujet "SphK-1"

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Bart, Arnaud, Thibault Macherel, Giovanni De Cesare, Sean Mulligan et Khalid Essyad. « Vortex Siphon – From 1:1 Scale Physical Model to SPH Simulation and Prototype ». Dans Advances in Hydroinformatics, 795–807. Singapore : Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-5436-0_62.

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Actes de conférences sur le sujet "SphK-1"

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Drosos, Z., H. Gevensleben, S. Kommoss, T. Karn, U. Holtrich, M. Graeser-Mayer, M. Anglesio, A. El-Balat, A. Rody et L. Hanker. « EP833 The prognostic impact of sphingosine-kinase 1 expression (SphK1) on ovarian cancer ». Dans ESGO Annual Meeting Abstracts. BMJ Publishing Group Ltd, 2019. http://dx.doi.org/10.1136/ijgc-2019-esgo.882.

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Hanker, LC, Z. Drosos, S. Kommoss, T. Karn, U. Holtrich, M. Graeser-Mayer, M. Anglesio, A. El-Balat, A. Rody et H. Gevensleben. « Expression of Sphingosine-Kinase 1 (SPHK1) as a prognostic factor in ovarian cancer ». Dans 62. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe – DGGG'18. Georg Thieme Verlag KG, 2018. http://dx.doi.org/10.1055/s-0038-1671643.

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Beach, Jessica A., Paul-Joseph Aspuria, Dong-Joo Cheon, Maricel C. Gozo, Beth Y. Karlan et Sandra Orsulic. « Abstract B09 : Sphingosine kinase 1 (SPHK1) is a novel mediator of tumor-stroma interaction in ovarian cancer ». Dans Abstracts : AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment ; February 26 — March 1, 2014 ; San Diego, CA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.chtme14-b09.

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Rafiee, Ashkan, Sharen Cummins, Murray Rudman et Krish Thiagarajan. « The Effect of Pressure Solution in SPH Simulations of Sloshing Flow ». Dans ASME 2011 30th International Conference on Ocean, Offshore and Arctic Engineering. ASMEDC, 2011. http://dx.doi.org/10.1115/omae2011-49215.

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In modelling incompressible flows using the Smoothed Particle Hydrodynamics method (SPH), an equation of state with a large sound speed is typically used. This weakly compressible approach (WCSPH), results in a stiff set of equations with a noisy pressure field and stability issues at high Reynolds number. As a remedy, an incompressible SPH technique was introduced [1] (ISPH), which uses a pressure projection technique to model incompressibility. In this paper, the incompressible and weakly compressible forms of the SPH method are employed to study sloshing flow. Both methods are compared with experimental data. The results show the incompressible SPH method provides more accurate pressure fields and free-surface profiles when compared to experiment.
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Kawashima, Yoichi, Yuzuru Sakai et Nobuki Yamagata. « Large Deformation Analysis by Smoothed Particle Hydrodynamics ». Dans ASME 2006 Pressure Vessels and Piping/ICPVT-11 Conference. ASMEDC, 2006. http://dx.doi.org/10.1115/pvp2006-icpvt-11-93612.

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Smoothed particle hydrodynamics (SPH)[1] is extended to the elastic-plastic large deformation analysis of metals and the hyper-elastic analysis of rubbers. The elastic-plastic analysis theory and the large deformation theory used in this study are fundamentally similar to those of FEM however the theories are applied at the particle points within a smoothing radius in SPH models. In this study the volume constant condition is imposed on the plastic deformation process using a pressure equation given by the particle density condition in a unit volume. Test problems show that the large deformation analysis by SPH leads to good stability and accuracy comparing with FEM results.
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Yamagata, Nobuki, Yuzuru Sakai et Pedro Marcal. « Elastic-Plastic and Frature Analysis of Mobile Phones Using SPH ». Dans ASME 2006 Pressure Vessels and Piping/ICPVT-11 Conference. ASMEDC, 2006. http://dx.doi.org/10.1115/pvp2006-icpvt-11-93614.

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Smoothed Particle Hydrodynamics (SPH) was invented by Lucy[1], Monaghan and Gingold [2] for gas dynamics problems in astrophysics and extended to treat solid continua in this decade[3]]. The SPH technique uses no underlying grid — it is a pure Lagrangian particle method. The absence of a mesh and the calculation of interactions among particles based on their separation alone that large deformations can be computed without difficulty. It is for this reason that SPH has the potential to be a valuable computational tool. In this paper we have been using the SPH algorithm to compute the structural analysis of the mobile phones without mesh data. Using the visualization software MPAVE the particle distributions for the mobile phone could be easily produced in 3 dimensions and the elastic-plastic analysis and the fracture analysis have been performed effectively. The results show the possibility for practical use of a particle method to 3 dimensional structural analysis of the usual industrial products.
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Kruisbrink, A. Ch H., H. P. Morvan et F. R. Pearce. « Progress in Smoothed Particle Hydrodynamics to Simulate Bearing Chambers ». Dans ASME Turbo Expo 2014 : Turbine Technical Conference and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/gt2014-26403.

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In this paper some novel Smoothed Particle Hydrodynamics (SPH) concepts are presented towards a feasibility study into the use of SPH for some aero-engine applications, e.g. for internal oil or fuel applications. A first challenge is to develop a capability to model complex wall geometries, associated with two-phase flows in gear boxes and bearing chambers for example. A demonstration is made of how such complex (for SPH) geometries can be built together with an outline of some of the wall boundary condition concepts used, including moving walls. This is an important feature for the application of SPH to engineering. Other boundary conditions are needed such as inlets, outlets and pressure boundaries, and a proper treatment of the free surface. These are outlined in the context of the proposed application. From an SPH flow simulation viewpoint, one of the challenges is to reduce the non-physical density variations arising from boundary conditions (at wall, free surface and interface), which are responsible for non-physical pressure variations and particle dynamics. The flow regimes found in the engineering systems outlined above involve droplets, filaments and films. It is therefore important to be able to handle the merging of fluids, as it is to model their interaction with another phase, which calls for appropriate multi-fluid and surface tension models. This paper introduces SPH, outlines a number of concepts listed above and presents some preliminary results towards the modeling of the KIT bearing chamber, as described by Kurz et al. [1]. This work builds on a number of numerical modeling communications made by the Nottingham team to SPHERIC, the ERCOFTAC Special Interest Group (SIG) for SPH.
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Vepa, Kameswara S., Diederik Van Nuffel, Wim Van Paepegem, Joris Degroote et Jan Vierendeels. « Comparative Study of Slamming Loads on Cylindrical Structures ». Dans ASME 2011 30th International Conference on Ocean, Offshore and Arctic Engineering. ASMEDC, 2011. http://dx.doi.org/10.1115/omae2011-49408.

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Wave impact or slamming is a phenomenon characterized by large local pressures (10 bar or more) for very short durations (order of milliseconds). Slamming loads can cause severe damage to the structure [1]. Different numerical approximation methods are available for simulating the fluid structure interaction problems. Traditional mesh techniques use nodes and elements for approximating the continuum equations whereas particle methods like smoothed particle hydrodynamics (SPH) approximates the continuum equations using the kernel approximation technique and hence can be used for a wide range of fluid dynamics problems [2]. Since composite materials are finding increased application in the ship building industry because of their low weight and high strength properties, it is important to understand the effect of slamming loads on composite structures [3]. Normally, composite structures are made quasi-rigid to resist slamming loads, but inducing some deformability helps in reducing the incident pressures and at the same time reduces the overall weight of the structure and in turn the material cost. On the other side, inducing deformability effects the durability of the structure. In this paper, the effect of slamming on two-dimensional cylindrical structures is studied using three solvers i.e., 1) SPH solver, 2) Explicit solver and 3) Implicit solver. In the case of SPH solver, water is modelled using SPH particles and cylinder is modelled using finite elements (FE), in this case shell elements. A coupling between the SPH and FE solvers is made to simulate the fluid-structure interactions. Contact is modelled using the contact algorithms. In the case of the explicit solver, water is modelled using hexahedron or brick elements with one element in the thickness direction since symmetry is applicable along the thickness of the cylinder. Shell elements are used for modelling the cylinder and contact is handled using node to surface contact algorithm. In the case of the implicit solver, water is represented by pure two-dimensional elements. Quadratic elements are used to represent the continuum around the cylinder and triangular elements are used to represent the far off field and also to control the mesh movement. Line elements are used to represent the cylinder in this case. Two models are tested in all the three solvers: 1) rigid cylinder and 2) deformable cylinder. A comparative study of these three solvers shows that the implicit solver needed more calculation time compared to other solvers. The SPH method required less particles than the number of nodes in the other two methods to converge on the peak pressure. All three solvers show reduction of peak pressure in case of the deformable cylinder.
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Piwarski, Sean A., Tyler A. Allen, Dadong Zhang, Alexander B. Sibley, Patrick Healy, Brendon M. Patierno, Bonnie L. LaCroix et al. « Abstract PO-100 : Ancestry-related variation in Sphingosine Kinase Type 1-Interacting Protein (SKIP) and Sphingosine Kinase 1 (SPHK1) and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer ». Dans Abstracts : AACR Virtual Conference : Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved ; October 2-4, 2020. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7755.disp20-po-100.

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Nguyen, Nhu, Krish P. Thiagarajan et Matthew Cameron. « Validation Study of Smoothed Particle Hydrodynamics in Fluid and Structure Interaction and the Comparison to Boundary Element Method ». Dans ASME 2017 36th International Conference on Ocean, Offshore and Arctic Engineering. American Society of Mechanical Engineers, 2017. http://dx.doi.org/10.1115/omae2017-62285.

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The purpose of this research is to validate the usage of Smoothed Particle Hydrodynamics (SPH) method in solving fluid-structure interaction problems as well as study its advantages and disadvantages compared to another well-known technique Boundary Element Method (BEM). The goal is achieved by 1) evaluating the Response Amplitude Operator (RAO) and 2) analyzing the drifting motion of a 1:10 scaled 3m-discus oceanographic buoy developed by the National Oceanographic and Atmospheric Administration (NOAA), using both experimental and numerical approaches. For the experimental study, the testing was carried out in an 8-m long wave tank and the buoy motions were measured using non-intrusive techniques. For numerical analysis, the project used DualSPHysics — open source code — and ANSYS AQWA — one of the leading software widely used in the marine applications — to simulate all the experimental scenarios via SPH and BEM techniques respectively. It is observed that while BEM has clear advantages in computational time and the ability to study applicable range of frequencies, SPH, in addition to its capability to simulate drifting motion of the floating structure, has shown to outperform the RAO predictions from BEM (especially in low frequency region). In higher frequency regions, the lack of experimental data hinders the conclusion on which method might be more suitable, as both have their own limitations.
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Rapports d'organisations sur le sujet "SphK-1"

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Nelson, Jennifer, Luis Tejerina, Alexandre Bagolle, Donghyun Kang, Elisa Martinez, Pablo Orefice, Myrna Marti et al. Digital Health For All : Social Protection and Health Division Regional Policy Dialogue Report 2022. Inter-American Development Bank, novembre 2022. http://dx.doi.org/10.18235/0004575.

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The Social Protection and Health (SPH) Division of the Inter-American Development Bank (IDB) held its annual Regional Policy Dialogue (RPD) Digital Health for All: Latin America and the Caribbeans golden opportunity to improve the efficiency, quality and equity of sector on September 12-14th 2022 in Panama City, Panama. The RPD brought together over 120 participants, including leaders from over 20 countries, vice-ministers of health and directors of technology and communications, and regional and global experts in digital health. The meeting sought to provide a setting to discuss what the IDB and different countries have learned in the past four years of implementation of digital health, structural challenges to scale digital health, and the measures needed to ensure that decisions made today are both sustainable and transformational. The meetings objectives broadly included discussing three topics: 1) how to ensure that digital health adds value in terms of improved efficiency, quality, and equity;2) policy considerations for linking digital health to health outcomes; and3) the future state of our region in terms of digital transformation of the health sector.This report provides an overview of the meeting, its main findings, and the steps that lie ahead on this journey.
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