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Sphingosine

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https://www.readbyqxmd.com/read/27914035/mobilization-of-peripheral-blood-stem-cells-and-changes-in-the-concentration-of-plasma-factors-influencing-their-movement-in-patients-with-panic-disorder
#1
Marcin Jabłoński, Jolanta Kucharska Mazur, Maciej Tarnowski, Barbara Dołęgowska, Daniel Pędziwiatr, Ewa Kubiś, Marta Budkowska, Daria Sałata, Justyna Pełka Wysiecka, Arkadiusz Kazimierczak, Artur Reginia, Mariusz Z Ratajczak, Jerzy Samochowiec
In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin-/CD45 +/CD34 +) and HSCs (Lin-/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin-/CD45-/CD34 +) and VSELs (Lin-/CD45-/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate)...
December 2, 2016: Stem Cell Reviews
https://www.readbyqxmd.com/read/27913115/computer-design-synthesis-and-bioactivity-analyses-of-drugs-like-fingolimod-used-in-the-treatment-of-multiple-sclerosis
#2
Gurbet Çelik Turgut, Doğukan Doyduk, Yılmaz Yıldırır, Serkan Yavuz, Atilla Akdemir, Ali Dişli, Alaattin Şen
Multiple sclerosis (MS) is a very common disease of vital importance. In the MS treatment, some drugs such as fingolimod which help to protect nerves from damage are used. The main goal of the drug therapy in MS is to take control of the inflammation which leads to the destruction of myelin and axons in nerve cell and thus prevent and stop the progression of the disease. Fingolimod (FTY720) is an orally active immunomodulatory drug that has been used for the treatment of relapsing-remitting multiple sclerosis...
November 18, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27904998/alginate-chitosan-hydrogels-provide-a-sustained-gradient-of-sphingosine-1-phosphate-for-therapeutic-angiogenesis
#3
Priscilla A Williams, Kevin T Campbell, Hessam Gharaviram, Justin L Madrigal, Eduardo A Silva
Sphingosine-1-phosphate (S1P), a bioactive lipid, is a potent candidate for treatment of ischemic vascular disease. However, designing biomaterial systems for the controlled release of S1P to achieve therapeutic angiogenesis presents both biological and engineering challenges. Thus, the objective of this study was to design a hydrogel system that provides controlled and sustained release of S1P to establish local concentration gradients that promote neovascularization. Alginate hydrogels have been extensively studied and characterized for delivery of proangiogenic factors...
November 30, 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/27904661/a-novel-sphingosine-kinase-1-inhibitor-ski-5c-induces-cell-death-of-wilms-tumor-cells-in-vitro-and-in-vivo
#4
Zhi-Heng Li, Yan-Fang Tao, Li-Xiao Xu, He Zhao, Xiao-Lu Li, Fang Fang, Yi Wu, Jun Lu, Yan-Hong Li, Wei-Wei Du, Jun-Li Ren, Yi-Ping Li, Yun-Yun Xu, Xing Feng, Jian Wang, Wei-Qi He, Jian Pan
Sphingosine kinase 1 (SphK1) is over-expressed in many cancers and therefore serves as a biomarker for cancer prognosis. SKI-5C is a new SphK1 inhibitor, and until now its molecular function in Wilms' tumor cells remained unknown. Here, using CCK-8 and nude mice experiments we assessed cell growth in Wilms' tumor cell lines (SK-NEP-1 and G401) in vitro and in vivo. We demonstrated that SphK1 is highly expressed in SK-NEP-1 and G401 cells, and through annexin V/propidium iodide staining and flow cytometry analysis, we detected cell apoptosis...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27890706/the-sphingosine-1-phosphate-receptor-a-novel-therapeutic-target-for-multiple-sclerosis-and-other-autoimmune-diseases
#5
REVIEW
Yang Mao-Draayer, Jeffrey Sarazin, David Fox, Elena Schiopu
Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous system (CNS). Currently, there is no drug that provides a cure for MS. To date, all immunotherapeutic drugs target relapsing remitting MS (RR-MS); it remains a daunting medical challenge in MS to develop therapy for secondary progressive MS (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P) receptor modulator FTY720 (fingolimod [Gilenya®]). for RR-MS in 2010, there have been many emerging studies with various selective S1P receptor modulators in other autoimmune conditions...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27888572/adverse-effect-profile-of-topical-ocular-administration-of-fingolimod-for-treatment-of-dry-eye-disease
#6
Weibao Xiao, Li Sun, Nan Zhang, Wen Ye
Fingolimod is a promising prodrug in attenuating multiple sclerosis and prolonging survival of organ allograft, with many other protective effects. Its mechanism of action is related to the internalization of sphingosine 1-phosphate receptors (S1PRs). Our previous study indicated that fingolimod eyedrop was efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of Non-Obese Diabetic (NOD) mice. In the current study, we evaluated potential adverse effects of fingolimod eyedrop. Inbred 10-week-old BALB/C mice were randomly divided into four groups, fingolimod-treated groups at three different concentrations (0...
November 26, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27886183/fingolimod-therapeutic-mechanisms-and-ocular-adverse-effects
#7
REVIEW
P Mandal, A Gupta, W Fusi-Rubiano, P A Keane, Y Yang
Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur...
November 25, 2016: Eye
https://www.readbyqxmd.com/read/27883090/sphingosine-1-phosphate-lyase-ablation-disrupts-presynaptic-architecture-and-function-via-an-ubiquitin-proteasome-mediated-mechanism
#8
Daniel N Mitroi, André U Deutschmann, Maren Raucamp, Indulekha Karunakaran, Konstantine Glebov, Michael Hans, Jochen Walter, Julie Saba, Markus Gräler, Dan Ehninger, Elena Sopova, Oleg Shupliakov, Dieter Swandulla, Gerhild van Echten-Deckert
The bioactive lipid sphingosine 1-phosphate (S1P) is a degradation product of sphingolipids that are particularly abundant in neurons. We have shown previously that neuronal S1P accumulation is toxic leading to ER-stress and an increase in intracellular calcium. To clarify the neuronal function of S1P, we generated brain-specific knockout mouse models in which S1P-lyase (SPL), the enzyme responsible for irreversible S1P cleavage was inactivated. Constitutive ablation of SPL in the brain (SPL(fl/fl/Nes)) but not postnatal neuronal forebrain-restricted SPL deletion (SPL(fl/fl/CaMK)) caused marked accumulation of S1P...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879252/high-density-lipoprotein-associated-apolipoprotein-m-limits-endothelial-inflammation-by-delivering-sphingosine-1-phosphate-to-the-sphingosine-1-phosphate-receptor-1
#9
Mario Ruiz, Cecilia Frej, Andreas Holmér, Li J Guo, Sinh Tran, Björn Dahlbäck
OBJECTIVE: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27877175/thymocytes-in-lyve1-cre-s1pr1-f-f-mice-accumulate-in-the-thymus-due-to-cell-intrinsic-loss-of-sphingosine-1-phosphate-receptor-expression
#10
Akira Takeda, Mohammad Shahadat Hossain, Pia Rantakari, Szandor Simmons, Naoko Sasaki, Marko Salmi, Sirpa Jalkanen, Masayuki Miyasaka
T cell emigration from the thymus is essential for immunological homeostasis. While stromal cell-produced sphingosine-1-phosphate (S1P) has been shown to promote thymocyte egress via the S1P receptor, S1PR1, the significance of S1P/S1PR1 signaling in the thymic stromal cells that surround T cells remains unclear. To address this issue, we developed conditional knockout mice (Lyve1-CRE/S1pr1(f/f) mice) in which S1pr1 was selectively targeted in cells expressing the lymphatic endothelial cell marker, Lyve1. In these mice, T cells were significantly reduced in secondary lymphoid tissues, and CD62L(+) mature CD4 and CD8 single-positive (SP) T cells accumulated in the medulla failed to undergo thymus egress...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27875779/novel-pyrimidine-2-4-dione-1-2-3-triazole-and-furo-2-3-d-pyrimidine-2-one-1-2-3-triazole-hybrids-as-potential-anti-cancer-agents-synthesis-computational-and-x-ray-analysis-and-biological-evaluation
#11
Tomislav Gregorić, Mirela Sedić, Petra Grbčić, Andrea Tomljenović Paravić, Sandra Kraljević Pavelić, Mario Cetina, Robert Vianello, Silvana Raić-Malić
Regioselective 1,4-disubstituted 1,2,3-triazole tethered pyrimidine-2,4-dione derivatives (5-23) were successfully prepared by the copper(I)-catalyzed click chemistry. While known palladium/copper-cocatalyzed method based on Sonogashira cross-coupling followed by the intramolecular 5-endo-dig ring closure generated novel 6-alkylfuro[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids (24b-37b), a small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and described for the first time by tandem terminal alkyne dimerization and subsequent 5-endo-trig cyclization, which was additionally corroborated with computational and X-ray crystal structure analyses...
November 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27875258/sweat-lipid-mediator-profiling-a-non-invasive-approach-for-cutaneous-research
#12
Karan Agrawal, Lauren A Hassoun, Negar Foolad, Theresa L Pedersen, Raja K Sivamani, John William Newman
Recent advances in analytical and sweat collection techniques provide new opportunities to identify non-invasive biomarkers for the study of skin inflammation and repair. This study aims to characterize the lipid mediator profile including oxygenated lipids, endocannabinoids and ceramides/sphingoid bases in sweat and identify differences in these profiles between sweat collected from non-lesional sites on the unflared volar forearm of subjects with and without atopic dermatitis (AD). Adapting routine procedures developed for plasma analysis, over 100 lipid mediators were profiled using liquid chromatography-tandem mass spectrometry and 58 lipid mediators were detected in sweat...
November 8, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27872583/ablation-of-sphingosine-1-phosphate-receptor-subtype-3-impairs-hippocampal-neuron-excitability-in-vitro-and-spatial-working-memory-in-vivo
#13
Daniela Weth-Malsch, Michiel Langeslag, Dimitra Beroukas, Luca Zangrandi, Iris Kastenberger, Serena Quarta, Philipp Malsch, Theodora Kalpachidou, Christoph Schwarzer, Richard L Proia, Rainer V Haberberger, Michaela Kress
Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate (S1P) within the central nervous system has recently gained more and more attention, as it has been connected to major diseases such as multiple sclerosis and Alzheimer's disease. Even though much data about the functions of the five S1P receptors has been collected for other organ systems, we still lack a complete understanding for their specific roles, in particular within the brain. Therefore, it was the aim of this study to further elucidate the role of S1P receptor subtype 3 (S1P3) in vivo and in vitro with a special focus on the hippocampus...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27870138/promise-of-combining-antifungal-agents-in-denture-adhesives-to-fight-candida-species-infections
#14
Jorge L Garaicoa, Carol L Fischer, Amber M Bates, Julie Holloway, Gustavo Avila-Ortiz, Janet M Guthmiller, Georgia K Johnson, Clark Stanford, Kim A Brogden
PURPOSE: Several complications may arise in patients wearing complete prosthetic appliances, including denture-associated infections and mucosal stomatitis due to Candida species. This study evaluated the activity of anti-Candida agents in denture adhesive and the cytotoxicities of these preparations for primary human gingival epithelial (GE) keratinocytes. MATERIALS AND METHODS: The anti-Candida activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents against C...
November 21, 2016: Journal of Prosthodontics: Official Journal of the American College of Prosthodontists
https://www.readbyqxmd.com/read/27869314/runx1-orchestrates-sphingolipid-metabolism-and-glucocorticoid-resistance-in-lymphomagenesis
#15
A Kilbey, A Terry, S Wotton, G Borland, Q Zhang, N Mackay, A McDonald, M Bell, M J O Wakelam, E R Cameron, J C Neil
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumour suppressors and oncogenes. In mouse models the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the 'sphingolipid rheostat' from ceramide to sphingosine-1-phosphate (S1P)...
November 21, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27868302/reduced-dna-methylation-of-sphingosine-1-phosphate-receptor-5-in-alveolar-macrophages-in-copd-a-potential-link-to-failed-efferocytosis
#16
Jameel Barnawi, Hubertus Jersmann, Rainer Haberberger, Sandra Hodge, Robyn Meech
BACKGROUND AND OBJECTIVE: We previously showed that alveolar macrophages from COPD patients are defective in their ability to phagocytose apoptotic cells ('efferocytosis') and that this defect is potentially linked to the sphingosine-1 phosphate (S1P) system, in particular the sphingosine-1 phosphate receptor 5 (S1PR5). In alveolar macrophages from COPD patients, S1PR5 mRNA expression levels increased and were correlated with both lung function and efferocytosis. However, it us unknown whether these changes are under epigenetic control via DNA methylation or whether DNA methylation directly modulates macrophage function...
November 20, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27867498/bone-muscle-crosstalk-targets-muscle-regeneration-pathway-regulated-by-core-circadian-transcriptional-repressors-dec1-and-dec2
#17
REVIEW
Jeffrey P Gorski, Jeffrey L Price
Deletion of proprotein convertase Mbtps1 in bone osteocytes leads to a significant postnatal increase in skeletal muscle size and contractile function, while causing only a 25% increase in stiffness in long bones. Concerns about leakiness in skeletal muscle were discounted since Cre recombinase expression does not account for our findings, and, Mbtps1 protein and mRNA is not deleted. Interestingly, the response of normal skeletal muscle to exercise and the regenerative response of skeletal muscle to the deletion of Mbtps1 in bone share some key regulatory features including a preference for slow twitch muscle fibers...
2016: BoneKEy Reports
https://www.readbyqxmd.com/read/27864936/effect-of-sphingosine-kinase-modulators-on-interleukin-1%C3%AE-release-sphingosine-1-phosphate-receptor-1-expression-and-experimental-autoimmune-encephalomyelitis
#18
Mark Barbour, Melissa McNaughton, Stephanie D Boomkamp, Neil MacRitchie, Hui-Rong Jiang, Nigel J Pyne, Susan Pyne
BACKGROUND AND PURPOSE: The sphingosine analogue, FTY720 (Gilenya(R) ) alleviates clinical disease progression in multiple sclerosis. Here we variously assessed the effects of an azide analogue of (S)-FTY720 vinylphosphonate (compound 5; a sphingosine kinase 1 activator), (R)-FTY720 methyl ether (ROMe, a sphingosine kinase 2 inhibitor) and RB-020 (a sphingosine kinase 1 inhibitor and sphingosine kinase 2 substrate) on IL-1β formation, sphingosine 1-phosphate levels and S1P1 expression...
November 16, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27864331/role-of-sphingosine-kinase-1-and-s1p-transporter-spns2-in-hgf-mediated-lamellipodia-formation-in-lung-endothelium
#19
Panfeng Fu, David L Ebenezer, Evgeny V Berdyshev, Irina A Bronova, Mark Shaaya, Anantha Harijith, Viswanathan Natarajan
Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3k/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P1, in lamellipodia formation and perhaps motility of HLMVECs...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27861771/high-density-lipoprotein-associated-sphingosine-1-phosphate-activity-in-heterozygous-familial-hypercholesterolaemia
#20
Miguel A Frias, Aurélien Thomas, Marie-Claude Brulhart-Meynet, Oskar Kövamees, John Pernow, Mats Eriksson, Bo Angelin, Richard W James, Jonas W Brinck
BACKGROUND: Patients with heterozygous familial hypercholesterolaemia (FH) suffer from high plasma cholesterol and an environment of increased oxidative stress. We examined its potential effects on high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) content (HDL-S1P) and HDL-mediated protection against oxidative stress, both with and without statin treatment. MATERIALS AND METHODS: In a case-control study, HDL was isolated from 12 FH patients with and without statin treatment and from 12 healthy controls...
November 11, 2016: European Journal of Clinical Investigation
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