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Sphingosine

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https://www.readbyqxmd.com/read/28725183/bile-acid-mediated-sphingosine-1-phosphate-receptor-2-signaling-promotes-neuroinflammation-during-hepatic-encephalopathy-in-mice
#1
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Shamyal Khan, Juan Diocares, Anca Petrescu, Amy Wyatt, Jessica Kain, Brandi Jefferson, Sharon DeMorrow
Hepatic encephalopathy (HE) is a neuropsychiatric complication that occurs due to deteriorating hepatic function and this syndrome influences patient quality of life, clinical management strategies and survival. During acute liver failure, circulating bile acids increase due to a disruption of the enterohepatic circulation. We previously identified that bile acid-mediated signaling occurs in the brain during HE and contributes to cognitive impairment. However, the influences of bile acids and their downstream signaling pathways on HE-induced neuroinflammation have not been assessed...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28724986/core-shell-lipid-polymer-hybrid-nanoparticles-with-combined-docetaxel-and-molecular-targeted-therapy-for-the-treatment-of-metastatic-prostate-cancer
#2
Qi Wang, Heba Alshaker, Torsten Böhler, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
Many prostate cancers relapse after initial chemotherapy treatment. Combining molecular and chemotherapy together with encapsulation of drugs in nanocarriers provides effective drug delivery and toxicity reduction. We developed core shell lipid-polymer hybrid nanoparticles (CSLPHNPs) with poly (lactic-co-glycolic acid) (PLGA) core and lipid layer containing docetaxel and clinically used inhibitor of sphingosine kinase 1 (SK1) FTY720 (fingolimod). We show for the first time that FTY720 (both free and in CSLPHNPs) re-sensitizes castrate resistant prostate cancer cells and tumors to docetaxel, allowing a four-fold reduction in effective dose...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724841/sphingosine-1-phosphate-and-atherosclerosis
#3
Makoto Kurano, Yutaka Yatomi
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties...
July 20, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28716816/sphingosine-1-phosphate-receptor-1-promotes-environment-induced-and-acquired-chemoresistance
#4
Veronica Lifshitz, Saul J Priceman, Wenzhao Li, Gregory Cherryholmes, Heehyoung Lee, Adar Makovski-Silverstein, Lucia Borriello, Yves A DeClerck, Hua Yu
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28714882/vitamin-d-supplementation-enhances-c18-dihydro-ceramide-levels-in-type-2-diabetes-patients
#5
Alexander Koch, Georgios Grammatikos, Sandra Trautmann, Yannick Schreiber, Dominique Thomas, Franziska Bruns, Josef Pfeilschifter, Klaus Badenhoop, Marissa Penna-Martinez
Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D from a placebo-controlled, randomized, and double-blind study were retrospectively analyzed...
July 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28712299/evaluation-of-efficacy-and-toxicity-of-exfoliated-silicate-nanoclays-as-a-feed-additive-for-fumonisin-detoxification
#6
Chiao-Wei Yuan, Jie-Ting Huang, Ching-Chin Chen, Pin-Chi Tang, Jenn-Wen Huang, Jiang-Jen Lin, San-Yuan Huang, Shuen-Ei Chen
The efficacy of nano-silicate clay platelets (NSCP), exfoliated silicates from natural montmorillonites, as a feed additive for ameliorating fumonisin B1 (FB1) toxicosis was evaluated. Toxicological mechanisms by NSCP were examined through proteomic and biochemical analyses. Dietary supplementation with NSCP at a low level of 40 mg/kg feed improved growth performances in chickens with respect to FB1 toxicosis. Other issues of ameliorated symptoms including serum and/or hepatic AST activity, oxidative stress indicators, and sphinganine/sphingosine ratio, a hallmark of FB1 toxicosis were considered...
July 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28711498/promotion-of-hair-growth-by-newly-synthesized-ceramide-mimetic-compound
#7
Bu-Mahn Park, Soon-Sun Bak, Kyung-Oh Shin, Minhee Kim, Daehwan Kim, Sang-Hun Jung, Sekyoo Jeong, Young Kwan Sung, Hyunjong Kim
Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28711286/novel-therapeutic-targets-for-inflammatory-bowel-disease
#8
REVIEW
Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28709801/lymphatic-endothelial-cells-control-initiation-of-lymph-node-organogenesis
#9
Lucas Onder, Urs Mörbe, Natalia Pikor, Mario Novkovic, Hung-Wei Cheng, Thomas Hehlgans, Klaus Pfeffer, Burkhard Becher, Ari Waisman, Thomas Rülicke, Jennifer Gommerman, Christopher G Mueller, Shinichiro Sawa, Elke Scandella, Burkhard Ludewig
Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28709768/plasma-sphingosine-1-phosphate-concentrations-are-associated-with-systolic-heart-failure-in-patients-with-ischemic-heart-disease
#10
Amin Polzin, Kerstin Piayda, Petra Keul, Lisa Dannenberg, Annemarie Mohring, Markus Gräler, Tobias Zeus, Malte Kelm, Bodo Levkau
OBJECTIVE: Sphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. METHODS AND RESULTS: 74 patients with ischemic heart disease were investigated in this observational study...
July 12, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28706199/defective-sphingosine-1-phosphate-metabolism-is-a-druggable-target-in-huntington-s-disease
#11
Alba Di Pardo, Enrico Amico, Abdul Basit, Andrea Armirotti, Piyush Joshi, Diana M Neely, Romina Vuono, Salvatore Castaldo, Anna F Digilio, Francesco Scalabrì, Giuseppe Pepe, Francesca Elifani, Michele Madonna, Se Kyoo Jeong, Bu-Mahn Park, Maurizio D'Esposito, Aaron B Bowman, Roger A Barker, Vittorio Maglione
Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698261/adipocyte-specific-deficiency-of-de-novo-sphingolipid-biosynthesis-leads-to-lipodystrophy-and-insulin-resistance
#12
Su-Yeon Lee, Hui-Young Lee, Jae-Hwi Song, Goon-Tae Kim, Suwon Jeon, Yoo-Jeong Song, Jae Sung Lee, Jang-Ho Hur, Hyun Hee Oh, Shi-Young Park, Soon-Mi Shim, Hyun Joo Yoo, Byung Cheon Lee, Xian-Cheng Jiang, Cheol Soo Choi, Tae-Sik Park
Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes. Adipocyte-specific SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass. Fatty acids that were destined for the adipose tissue were instead shunted to liver and caused hepatosteatosis...
July 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28695300/new-fty720-docetaxel-nanoparticle-therapy-overcomes-fty720-induced-lymphopenia-and-inhibits-metastatic-breast-tumour-growth
#13
Heba Alshaker, Qi Wang, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
PURPOSE: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity...
July 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28695219/highly-efficient-chemoenzymatic-synthesis-and-facile-purification-of-%C3%AE-gal-pentasaccharyl-ceramide-gal%C3%AE-3nlc4%C3%AE-cer
#14
Abhishek Santra, Yanhong Li, Hai Yu, Teri J Slack, Peng George Wang, Xi Chen
A highly efficient chemoenzymatic method for synthesizing glycosphingolipids using α-Gal pentasaccharyl ceramide as an example is reported here. Enzymatic extension of the chemically synthesized lactosyl sphingosine using efficient sequential one-pot multienzyme (OPME) reactions allowed glycosylation to be carried out in aqueous solutions. Facile C18 cartridge-based quick (<30 minutes) purification protocols were established using minimal amounts of green solvents (CH3CN and H2O). Simple acylation in the last step led to the formation of the target glycosyl ceramide in 4 steps with an overall yield of 57%...
July 11, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28693421/lipidmatch-an-automated-workflow-for-rule-based-lipid-identification-using-untargeted-high-resolution-tandem-mass-spectrometry-data
#15
Jeremy P Koelmel, Nicholas M Kroeger, Candice Z Ulmer, John A Bowden, Rainey E Patterson, Jason A Cochran, Christopher W W Beecher, Timothy J Garrett, Richard A Yost
BACKGROUND: Lipids are ubiquitous and serve numerous biological functions; thus lipids have been shown to have great potential as candidates for elucidating biomarkers and pathway perturbations associated with disease. Methods expanding coverage of the lipidome increase the likelihood of biomarker discovery and could lead to more comprehensive understanding of disease etiology. RESULTS: We introduce LipidMatch, an R-based tool for lipid identification for liquid chromatography tandem mass spectrometry workflows...
July 10, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28693136/overexpression-of-sphingosine-kinase-1-is-predictive-of-poor-prognosis-in-human-breast-cancer
#16
Ya-Jing Zhu, Hua You, Jin-Xiang Tan, Fan Li, Zhu Qiu, Hong-Zhong Li, Hong-Yan Huang, Ke Zheng, Guo-Sheng Ren
Sphingosine kinase 1 (SPHK1) is a bioactive lipid mediator that has been identified as a biomarker in various cancers and is considered to play an important role in tumor progression. In the present study, the expression level of SPHK1 was examined in breast cancer clinical specimens, and its association with patient survival was investigated to clarify the clinical significance of SPHK1 in breast cancer. SPHK1 mRNA expression was increased in breast cancer tissues compared with that in matched adjacent breast tissues in 19 of 32 paired tissue specimens (59...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28690543/frontiers-in-drug-research-and-development-for-inflammatory-bowel-disease
#17
REVIEW
Diego Currò, Daniela Pugliese, Alessandro Armuzzi
Inflammatory bowel disease (IBD) is idiopathic, lifelong, immune-mediated diseases, for which curative therapies are not yet available. In the last 15 years, the introduction of monoclonal antibodies targeting tumor necrosis factor-α, a cytokine playing a key role in bowel inflammation, has revolutionized treatment paradigms for IBD. Despite their proven long-term efficacy, however, many patients do not respond or progressively lose response to these drugs. Major advances of knowledge in immunology and pathophysiology of intestinal inflammatory processes have made possible the identification of new molecular targets for drugs, thus opening several new potential therapeutic opportunities for IBD...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28690205/bronchoalveolar-lavage-microvesicles-protect-burn-injured-mice-from-pulmonary-infection
#18
Teresa C Rice, Amanda M Pugh, Brent T Xia, Aaron P Seitz, Brynne E Whitacre, Erich Gulbins, Charles C Caldwell
BACKGROUND: Pseudomonas aeruginosa (PA) is a major cause of morbidity and mortality among burn patients, despite antibiotic therapy. There is a need to identify innate immune defenses that prevent PA infection in injured adults in an effort to find therapeutic alternatives to antibiotics. Here, we tested our hypothesis that Microvesicles (MVs) in bronchoalveolar (BAL) fluid have a role in the immunity of the lung in response to pathogens. STUDY DESIGN: MVs were isolated from murine BAL fluid, quantified using nanoparticle tracking analysis, and injected into burn injured mice prior to PA infection...
July 6, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28687489/fas-s1p1-crosstalk-via-nf-%C3%AE%C2%BAb-activation-in-osteoclasts-controls-subchondral-bone-remodeling-in-murine-tmj-arthritis
#19
Islamy Rahma Hutami, Takashi Izawa, Akiko Mino-Oka, Takehiro Shinohara, Hiroki Mori, Akihiko Iwasa, Eiji Tanaka
Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice...
July 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28684192/involvement-of-sphingosine-kinase-sphingosine-1-phosphate-metabolic-pathway-in-spondyloarthritis
#20
Carole Bougault, Alaeddine El Jamal, Anne Briolay, Saida Mebarek, Marie-Astrid Boutet, Thomas Garraud, Benoit Le Goff, Fréderic Blanchard, David Magne, Leyre Brizuela
Spondyloarthritis (SpA) is a relatively common chronic inflammatory joint disorder, with a prevalence of about 0.2-0.5% worldwide. The primary target of the pathological process is the enthesis, where tendons and ligaments attach to underlying bone. These insertion sites are hotspots of bone formation (enthesophytes), which can lead to ankylosis. Unfortunately, the mechanisms causing the onset and progression of entheseal ossification remain largely unknown. Sphingosine 1-phosphate (S1P), a lipid generated after sphingosine phosphorylation by sphingosine kinases 1 and 2 (SK1/2), plays important roles in cell proliferation, differentiation and survival...
July 3, 2017: Bone
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