Refine
Has Fulltext
- no (102) (remove)
Year of publication
Document Type
- Article (102) (remove)
Language
- English (102)
Is part of the Bibliography
- yes (102)
Keywords
- acid sphingomyelinase (9)
- ceramide (9)
- Sphingolipids (7)
- sphingolipids (7)
- Dexamethasone (5)
- Sphingosine 1-phosphate (5)
- acid ceramidase (4)
- Drug delivery systems (3)
- Insulin resistance (3)
- Sphingosine-1-phosphate (3)
- sphingosine (3)
- sphingosine-1-phosphate (3)
- Acid sphingomyelinase (2)
- Biomarker (2)
- Ceramide (2)
- Clinical (2)
- DNA methylation (2)
- Dendritic cells (2)
- Dermal delivery (2)
- Drug delivery (2)
- FTY720 (2)
- Farber disease (2)
- Fluorescence lifetime imaging microscopy (2)
- Gestational diabetes (2)
- Global DNA methylation (2)
- Hepatocytes (2)
- LC-MS/MS (2)
- Metabolomics (2)
- Nanoparticle (2)
- Nanoparticle uptake (2)
- Nanotoxicology (2)
- Palmitate (2)
- Placenta (2)
- Pseudomonas aeruginosa (2)
- Skin nanocarrier (2)
- Skin penetration (2)
- Tandem mass spectrometry (2)
- Ulcerative colitis (2)
- amitriptyline (2)
- cystic fibrosis (2)
- liver metabolism (2)
- lysosomal storage disorders (2)
- measles virus (2)
- platelets (2)
- sphingomyelin (2)
- survival (2)
- (2E)-Hexadecenal (1)
- (2E)-hexadecenal (1)
- (2E)-hexadecenoic acid (1)
- 1-aminodecylidene bis-phosphonic acid (1)
- 1-phosphate (1)
- 3D tissue model (1)
- APOM protein (1)
- Acinetobacter baumannii (1)
- Adipocytes (1)
- Adipose tissue (1)
- Aging (1)
- Akt (1)
- Akt signaling (1)
- Alcohol dependence (1)
- Anxiety (1)
- Apoptosis (1)
- Arsenic speciation (1)
- Arsenic-containing hydrocarbons (1)
- Arsenolipids (1)
- Aryl-hydrocarbon receptor (1)
- Atherosclerosis (1)
- Atopic dermatitis (1)
- Autotaxin (1)
- B cells (1)
- Biocompatibility (1)
- Biocompatibility testing (1)
- Blood platelets (1)
- Broad-spectrum antibiotic therapy (1)
- Brown adipose tissue (1)
- CMS (1)
- CXCR2 (1)
- Caenorhabditis elegans (1)
- Cardiovascular (1)
- Case-control study (1)
- Cellular uptake (1)
- Cellulose acetate phthalate (1)
- Ceramidase inhibitors (1)
- Ceramides (1)
- Chemotherapy resistance (1)
- Citrobacter rodentium (1)
- Coating (1)
- Colitis (1)
- Colon cancer (1)
- Core-multishell nanocarriers (1)
- Cyp2b1 (1)
- DAIH (1)
- DNMT inhibitor (1)
- Delta F508 mutation (1)
- Dendritic core-multishell nanocarriers (1)
- Dengue (1)
- Depression (1)
- Derivatisation (1)
- Derivatization (1)
- Dermal drug delivery (1)
- Diagnostic (1)
- Dichlorofluorescein assay (1)
- Disease (1)
- Dolichol lipids (1)
- Dopamine (1)
- EBI3 (1)
- EDC (1)
- Electron paramagnetic resonance spectroscopy (1)
- Endocrine disruption (1)
- Endothelial cells (1)
- Endothelial nitric oxide synthase (1)
- Energy expenditure (1)
- Enteric polymer (1)
- Epigenetic (1)
- Epigenetics (1)
- Erosion kinetics (1)
- Ethyl cellulose (1)
- Eudragit (R) (1)
- Eudragit (R) RS (1)
- Eudragit L 100 (1)
- FGF21 (1)
- Factor-Xa (1)
- Fetal programming (1)
- Fingolimod (1)
- Fluorescence (1)
- Forster resonance energy transfer (FRET) (1)
- Free radicals (1)
- Gastrointestinal tract (1)
- Gene expression (1)
- Global (1)
- Glp1r(-/-) mice (1)
- Glutathione (1)
- Glycerophospholipids (1)
- HNRNPA1 (1)
- HPLC-ESI-QTOF (1)
- HPMCP (1)
- HaCaT cells (1)
- Hepatic insulin resistance (1)
- Hepatic stellate cells (1)
- High resolution microscopy (1)
- Histone deacetylase inhibitor (1)
- Human (1)
- Hyperglycaemia (1)
- Hypermethylation (1)
- IDH1 (1)
- Imiquimod (1)
- Inflammatory skin disease (1)
- Inhibitory cytokines (1)
- Insulin signaling (1)
- Insulin signalling (1)
- Interleukin-35 (1)
- Ischemia/reperfusion (1)
- Isotope-dilution (1)
- Isotope-dilution analysis (1)
- Jurkat cells (1)
- Keratinocytes (1)
- LPA(3) receptor subtype (1)
- Langerhans cells (1)
- Lipogenesis (1)
- Liquid chromatography-tandem mass spectrometry (1)
- Liver (1)
- Liver fibrosis (1)
- Liver injury (1)
- Lysophosphatidic acid (1)
- Lysophosphatidylcholines (1)
- Mass spectrometry (1)
- Metabolism (1)
- Methylation (1)
- Microbiota (1)
- Microdialysis (1)
- Multi-domain nanoparticles (1)
- Multiple sclerosis (1)
- NZO (1)
- Nanogel (1)
- Nanomaterials (1)
- Nanoparticles (1)
- Neisseria gonorrhoeae (1)
- Nitric oxide (1)
- Obesity (1)
- Ocular delivery (1)
- Oxazolone (1)
- Oxidative stress (1)
- PCaaC38:6 (1)
- PTEN (1)
- Penetration enhancement (1)
- Permeability (1)
- Phosphatidylcholine acyl-alkyl C 32:1 (1)
- Phosphatidylcholines (1)
- Phosphatidylinositols (1)
- Plasma (1)
- Plasmalogens (1)
- Plastic surfaces (1)
- Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] (1)
- Polymeric nanoparticle (1)
- Polymeric nanoparticles (1)
- Polymers (1)
- Pregnancy (1)
- Preterm birth (1)
- Proliferation (1)
- Proline (1)
- Protein restriction (1)
- Psoriasis (1)
- Retinoblastoma (1)
- S1P receptors (1)
- S1P-receptors (1)
- SAHA (1)
- SCID mice (1)
- ST-1071 (1)
- ST-1893 (1)
- ST-1894 (1)
- ST-968 (1)
- Selenium (1)
- Serotonin (1)
- Skeletal muscle cells (1)
- Skin (1)
- Skin absorption (1)
- Skin barrier disruption (1)
- Skin model (1)
- Smooth muscle cells (1)
- Smpd1 (1)
- Sphingomyelin (1)
- Sphingosine (1)
- Sphingosine 1phosphate (1)
- Sphingosine kinase (1)
- Sphingosine kinase-1 (1)
- Sphingosine-1-phosphate lyase (1)
- Srebf1 (1)
- Staphylococcus aureus (1)
- Structure-activity-relationship (1)
- T cell receptor (1)
- T(h)1 (1)
- T(h)17 (1)
- TET (1)
- TGF-beta 1 (1)
- TNF alpha (1)
- TRPC6 (1)
- Thyroid hormone (1)
- Topical treatment (1)
- Transplantation (1)
- Type 2 diabetes (1)
- UDP-glucuronosyltransferase (1)
- Ventilation (1)
- Ventilator-induced lung injury (1)
- Vitamin C (1)
- Xenobesity (1)
- YB-1 (1)
- acid ceramidase inhibitor ceranib-2 (1)
- acute lung injury (1)
- alpha-SMA (1)
- annexins (1)
- anti-inflammatory therapy (1)
- anticancer (1)
- antidepressants (1)
- anxiety-like behavior (1)
- appetite (1)
- autoimmunity (1)
- bacterial toxins (1)
- binding (1)
- birth weight (1)
- bisphosphonates (1)
- blebbing (1)
- blood banking (1)
- brain insulin signaling (1)
- burn injury (1)
- c. elegans (1)
- calcium (1)
- cancer cells (1)
- cell migration (1)
- cells (1)
- cerami-des (1)
- ceramides (1)
- cholesteryl ester (1)
- chronic kidney disease (1)
- chronic psychosocial stress (1)
- chronic subordinate colony housing (CSC) (1)
- circulation (1)
- click chemistry (1)
- colitis (1)
- collagen I (1)
- decitabine (1)
- dendritic cell (1)
- depressive-like behavior (1)
- diacylglycerol (1)
- disease (1)
- distress (1)
- drug delivery (1)
- drug design (1)
- drug metabolism (1)
- dysfunction (1)
- enzyme assays (1)
- enzymology (1)
- epigenetics (1)
- etanercept (1)
- experimental antigen-induced encephalomyelitis (1)
- extinction (1)
- fatty acid metabolism (1)
- fetal origins hypothesis (1)
- fibrosis (1)
- fingolimod (1)
- force-field (1)
- forebrain (1)
- functional inhibitors of acid sphin-gomyelinase (1)
- genes (1)
- glucocorticoid receptor (1)
- growth restriction (1)
- high density (1)
- hippocampus (1)
- human excised skin (1)
- hyperforin (1)
- immune (1)
- immunology (1)
- immunomodulator (1)
- immunonutrition (1)
- infection (1)
- inhibitory cytokines (1)
- integrins (1)
- interleukin-35 (1)
- intestine (1)
- invasion (1)
- keratinocytes (1)
- later health (1)
- life-span (1)
- linagliptin (1)
- lipid metabolism (1)
- lipid rafts (1)
- lipoproteins (1)
- liposomes (1)
- long chain base (1)
- lung cancer (1)
- lung infection (1)
- lung inflammation (1)
- lymphopenia (1)
- lyso-phospholipids (1)
- lysosomal hydrolases (1)
- lysosome (1)
- mass spectrometry (1)
- membrane fusion (1)
- membrane lipids (1)
- membrane repair (1)
- membrane-lipid therapy (1)
- menadione (1)
- microparticle (1)
- migration (1)
- mitochondria (1)
- molecular dynamics (1)
- molecular modeling (1)
- morpholino analogues of fingolimod (1)
- mortality (1)
- multiple sclerosis (1)
- n-acetyl-cysteine (1)
- nanogels (1)
- nanoparticles (1)
- nanotoxicology (1)
- neutral sphingomyelinase-2 (1)
- neutrophil chemotaxis (1)
- nutrient transport (1)
- operant behavior (1)
- oxidative stress (1)
- pH-sensitive nanoparticle (1)
- pH-sensitive nanoparticles (1)
- particle characterization (1)
- patterns (1)
- phagocytosis (1)
- plasma membrane (1)
- pneumococcal pneumonia (1)
- pregnancy (1)
- primary immunodeficiencies (1)
- proliferation (1)
- protein (1)
- proteomic analysis (1)
- refinement (1)
- repetitive elements (1)
- s-glutathionylation (1)
- serine palmitoyltransferase (1)
- skin equivalents (1)
- skin penetration (1)
- sphingolipid de novo synthesis (1)
- sphingolipid metabolism (1)
- sphingosine kinase (1)
- sphingosine kinase 1 (1)
- sphingosine kinase inhibitor SKI-II (1)
- sphingosine kinases (1)
- sphingosine-1-phosphate receptor 2 (1)
- stable-isotope labeling (1)
- storage (1)
- sulfotransferase (1)
- tacrolimus formulation (1)
- thermoresponsive-nanogel (1)
- thymosin beta 4 (1)
- topical (1)
- transfusion-related acute lung injury (1)
- transport proteins (1)
- tumor-metastasis (1)
- type 2 diabetes mellitus (1)
Institute
Aims/hypothesis Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. Methods We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Results Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure. Conclusion/interpretation Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.
Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets
(2017)
Pulmonary complications from stored blood products are the leading cause of mortality related to transfusion. Transfusion-related acute lung injury is mediated by antibodies or bioactive mediators, yet underlying mechanisms are incompletely understood. Sphingolipids such as ceramide regulate lung injury, and their composition changes as a function of time in stored blood. Here, we tested the hypothesis that aged platelets may induce lung injury via a sphingolipid-mediated mechanism. To assess this hypothesis, a two-hit mouse model was devised. Recipient mice were treated with 2 mg/kg intraperitoneal lipopolysaccharide (priming) 2 h before transfusion of 10 ml/kg stored (1-5 days) platelets treated with or without addition of acid sphingomyelinase inhibitor ARC39 or platelets from acid sphingomyelinase-deficient mice, which both reduce ceramide formation. Transfused mice were examined for signs of pulmonary neutrophil accumulation, endothelial barrier dysfunction, and histological evidence of lung injury. Sphingolipid profiles in stored platelets were analyzed by mass spectrophotometry. Transfusion of aged platelets into primed mice induced characteristic features of lung injury, which increased in severity as a function of storage time. Ceramide accumulated in platelets during storage, but this was attenuated by ARC39 or in acid sphingomyelinase-deficient platelets. Compared with wild-type platelets, transfusion of ARC39-treated or acid sphingomyelinase-deficient aged platelets alleviated lung injury. Aged platelets elicit lung injury in primed recipient mice, which can be alleviated by pharmacological inhibition or genetic deletion of acid sphingomyelinase. Interventions targeting sphingolipid formation represent a promising strategy to increase the safety and longevity of stored blood products.
Objective: We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion.
Summary Background Data: Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion.
Methods: Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units.
Results: Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice.
Conclusions: Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.
Background: Abdominal aortic aneurysm (AAA) is a deadly irreversible weakening and distension of the abdominal aortic wall. The pathogenesis of AAA remains poorly understood. Investigation into the physical and molecular characteristics of perivascular adipose tissue (PVAT) adjacent to AAA has not been done before and is the purpose of this study.
Methods and Results: Human aortae, periaortic PVAT, and fat surrounding peripheral arteries were collected from patients undergoing elective surgical repair of AAA. Control aortas were obtained from recently deceased healthy organ donors with no known arterial disease. Aorta and PVAT was found in AAA to larger extent compared with control aortas. Immunohistochemistry revealed neutrophils, macrophages, mast cells, and T-cells surrounding necrotic adipocytes. Gene expression analysis showed that neutrophils, mast cells, and T-cells were found to be increased in PVAT compared with AAA as well as cathepsin K and S. The concentration of ceramides in PVAT was determined using mass spectrometry and correlated with content of T-cells in the PVAT.
Conclusions: Our results suggest a role for abnormal necrotic, inflamed, proteolytic adipose tissue to the adjacent aneurysmal aortic wall in ongoing vascular damage.
Being born large for gestational age is associated with increased global placental DNA methylation
(2020)
Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001).
The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time-and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C-elegans
(2015)
Dopamine (DA) and serotonin (SRT) are monoamine neurotransmitters that play a key role in regulating the central and peripheral nervous system. Their impaired metabolism has been implicated in several neurological disorders, such as Parkinson's disease and depression. Consequently, it is imperative to monitor changes in levels of these low-abundant neurotransmitters and their role in mediating disease. For the first time, a rapid, specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DA and SRT in the nematode Caenorhabditis elegans (C. elegans). This model organism offers a unique approach for studying the effect of various drugs and environmental conditions on neurotransmitter levels, given by the conserved DA and SRT biology, including synaptic release, trafficking and formation. We introduce a novel sample preparation protocol incorporating the usage of sodium thiosulfate in perchloric acid as extraction medium that assures high recovery of the relatively unstable neurotransmitters monitored. Moreover, the use of both deuterated internal standards and the multiple reaction monitoring (MRM) technique allows for unequivocal quantification. Thereby, to the best of our knowledge, we achieve a detection sensitivity that clearly exceeds those of published DA and SRT quantification methods in various matrices. We are the first to show that exposure of C elegans to the monoamine oxidase B (MAOB) inhibitor selegiline or the catechol-O-methyltransferase (COMT) inhibitor tolcapone, in order to block DA and SRT degradation, resulted in accumulation of the respective neurotransmitter. Assessment of a behavioral output of the dopaminergic system (basal slowing response) corroborated the analytical LC-MS/MS data. Thus, utilization of the C elegans model system in conjunction with our analytical method is well-suited to investigate drug-mediated modulation of the DA and SRT system in order to identify compounds with neuroprotective or regenerative properties. (C) 2015 Elsevier B.V. All rights reserved.
Infection is a common and often deadly complication after burn injury. A major underlying factor is burn-induced immune dysfunction, particularly with respect to neutrophils as the primary responders to infection. Temporally after murine scald injury, we demonstrate impaired bone marrow neutrophil chemotaxis toward CXCL1 ex vivo. Additionally, we observed a reduced recruitment of neutrophils to the peritoneal after elicitation 7 days after injury. We demonstrate that neutrophil ceramide levels increase after burn injury, and this is associated with decreased expression of CXCR2 and blunted chemotaxis. A major signaling event upon CXCR2 activation is Akt phosphorylation and this was reduced when ceramide was elevated. In contrast, PTEN levels were elevated and PTEN-inhibition elevated phospho-Akt levels and mitigated the burn-induced neutrophil chemotaxis defect. Altogether, this study identifies a newly described pathway of ceramide-mediated suppression of neutrophil chemotaxis after burn injury and introduces potential targets to mitigate this defect and reduce infection-related morbidity and mortality after burn.
Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice
(2017)
The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc.