sphingosine/עששת

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Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity.

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התחבר הרשם

The sphingosine-1-phosphate (S1P) signaling pathway is an attractive drug target due to its involvement in immune cell chemotaxis and vascular integrity. The formation of S1P is catalyzed by sphingosine kinase 1 or 2 (SphK1 or SphK2) from sphingosine (Sph) and ATP. Inhibition of SphK1 and 2 to

UHPLC-MS/MS analysis of sphingosine 1-phosphate in joint cavity dialysate and hemodialysis solution of adjuvant arthritis rats: Application to geniposide pharmacodynamic study.

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התחבר הרשם

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It

Identification of novel phosphatidic acid binding domain on sphingosine kinase 1 of Arabidopsis thaliana.

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התחבר הרשם

Phosphatidic acid (PA) is an important lipid signaling molecule which interacts with Arabidopsis thaliana Sphingosine kinase1 (AtSPHK1) during several abiotic stresses particularly drought stress as a result of Abscisic acid (ABA) signaling in guard cells. PA molecules respond by generating lipid

Inhibition of the sphingosine-1-phosphate pathway promotes the resolution of neutrophilic inflammation.

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התחבר הרשם

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and

Sphingosine-1-phosphate signaling controlling osteoclasts and bone homeostasis.

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התחבר הרשם

Bone is a dynamic organ that is continuously turned over during growth, even in adults. During bone remodeling, homeostasis is regulated by the balance between bone formation by osteoblasts and bone resorption by osteoclasts. However, in pathological conditions such as osteoporosis, osteopetrosis,

Use of intravital microscopy and in vitro chemotaxis assays to study the roles of sphingosine-1-phosphate in bone homeostasis.

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התחבר הרשם

We describe a method to visualize the migration of osteoclast precursors within intact murine bone -marrow in real time using intravital multiphoton microscopy. Conventionally, cell migration has been evaluated using in vitro systems, such as transmigration assays. Although these methods are

A critical role for sphingosine kinase in anaphylatoxin-induced neutropenia, peritonitis, and cytokine production in vivo.

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התחבר הרשם

The aim of our study was to investigate the roles played by sphingosine kinase (SPHK) in the anaphylatoxin C5a-triggered responses in vivo. Our data show that i.v. administration of C5a triggers a rapid neutropenic response, but pretreating mice with the SPHK inhibitor, N,N-dimethylsphingosine

The effect of sphingosine-1-phosphate on bone metabolism in humans depends on its plasma/bone marrow gradient.

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התחבר הרשם

BACKGROUND Although recent studies provide clinical evidence that sphingosine-1-phosphate (S1P) may primarily affect bone resorption in humans, rather than bone formation or the osteoclast-osteoblast coupling phenomenon, those studies could not determine which bone resorption mechanism is more

Bacterial versus human sphingosine-1-phosphate lyase (S1PL) in the design of potential S1PL inhibitors.

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התחבר הרשם

A series of potential active-site sphingosine-1-phosphate lyase (S1PL) inhibitors have been designed from scaffolds 1 and 2, arising from virtual screening using the X-ray structures of the bacterial (StS1PL) and the human (hS1PL) enzymes. Both enzymes are very similar at the active site, as

The crystal structure of sphingosine-1-phosphate in complex with a Fab fragment reveals metal bridging of an antibody and its antigen.

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התחבר הרשם

The pleiotropic signaling lipid sphingosine-1-phosphate (S1P) plays significant roles in angiogenesis, heart disease, and cancer. LT1009 (also known as sonepcizumab) is a humanized monoclonal antibody that binds S1P with high affinity and specificity. Because the antibody is currently in clinical

The role of sphingosine 1-phosphate in migration of osteoclast precursors; an application of intravital two-photon microscopy.

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התחבר הרשם

Sphingosine-1-phosphate (S1P), a biologically active lysophospholipid that is enriched in blood, controls the trafficking of osteoclast precursors between the circulation and bone marrow cavities via G protein-coupled receptors, S1PRs. While S1PR1 mediates chemoattraction toward S1P in bone marrow,

In Silico Characterization of Structural Distinctions between Isoforms of Human and Mouse Sphingosine Kinases for Accelerating Drug Discovery.

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התחבר הרשם

Alterations in cellular signaling pathways are associated with multiple disease states including cancers and fibrosis. Current research efforts to attenuate cancers, specifically lymphatic cancer, focus on inhibition of two sphingosine kinase isoforms, sphingosine kinase 1 (SphK1) and sphingosine

Elevating Endogenous Sphingosine-1-Phosphate (S1P) Levels Improves Endothelial Function and Ameliorates Atherosclerosis in Low Density Lipoprotein Receptor-Deficient (LDL-R-/-) Mice.

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התחבר הרשם

BACKGROUND Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid and a constituent of high-density lipoprotein (HDL) exerting several atheroprotective effects in vitro. However, the few studies addressing anti-atherogenic effects of S1P in vivo have led to disparate results. We here examined

Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening.

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התחבר הרשם

Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator carried by the HDL-associated apoM protein in blood, regulating many physiological processes by activating the G protein-coupled S1P receptor in mammals. Despite the solved crystal structure of the apoM-S1P complex, the mechanism of S1P

Host sphingosine kinase 1 worsens pancreatic cancer peritoneal carcinomatosis.

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התחבר הרשם

There are no effective treatments for pancreatic cancer peritoneal carcinomatosis (PC) or cancer dissemination in abdominal cavity. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays critical roles in cancer progression. We reported

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