Refine
Has Fulltext
- no (102)
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
Ventilator-induced lung injury is aggravated by antibiotic mediated microbiota depletion in mice
(2018)
BackgroundAntibiotic exposure alters the microbiota, which can impact the inflammatory immune responses. Critically ill patients frequently receive antibiotic treatment and are often subjected to mechanical ventilation, which may induce local and systemic inflammatory responses and development of ventilator-induced lung injury (VILI). The aim of this study was to investigate whether disruption of the microbiota by antibiotic therapy prior to mechanical ventilation affects pulmonary inflammatory responses and thereby the development of VILI.MethodsMice underwent 6-8weeks of enteral antibiotic combination treatment until absence of cultivable bacteria in fecal samples was confirmed. Control mice were housed equally throughout this period. VILI was induced 3 days after completing the antibiotic treatment protocol, by high tidal volume (HTV) ventilation (34ml/kg; positive end-expiratory pressure=2 cmH(2)O) for 4h. Differences in lung function, oxygenation index, pulmonary vascular leakage, macroscopic assessment of lung injury, and leukocyte and lymphocyte differentiation were assessed. Control groups of mice ventilated with low tidal volume and non-ventilated mice were analyzed accordingly.ResultsAntibiotic-induced microbiota depletion prior to HTV ventilation led to aggravation of VILI, as shown by increased pulmonary permeability, increased oxygenation index, decreased pulmonary compliance, enhanced macroscopic lung injury, and increased cytokine/chemokine levels in lung homogenates.ConclusionsDepletion of the microbiota by broad-spectrum antibiotics prior to HTV ventilation renders mice more susceptible to developing VILI, which could be clinically relevant for critically ill patients frequently receiving broad-spectrum antibiotics.
Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) lead to metabolic alterations and a sustained formation of 2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite as it inhibits the activity of alpha-ketoglutarate-dependent dioxygenases such as ten-eleven translocation (TET) enzymes. Inhibitors of mutant IDH enzymes, like ML309, are currently tested in order to lower the levels of 2-HG. Vitamin C (VC) is an inducer of TET enzymes. To test a new therapeutic avenue of synergistic effects, the anti-neoplastic activity of inhibition of mutant IDH1 via ML309 in the presence of VC was investigated in the colon cancer cell line HCT116 IDH1(R132H/+) (harbouring a mutated IDH1 allele) and the parental cells HCT116 IDH1(+/+) (wild type IDH1). Measurement of the oncometabolite indicated a 56-fold higher content of 2-HG in mutated cells compared to wild type cells. A significant reduction of 2-HG was observed in mutated cells after treatment with ML 309, whereas VC produced only minimally changes of the oncometabolite. However, combinatorial treatment with both, ML309 and VC, in mutated cells induced pronounced reduction of 2-HG leading to levels comparable to those in wild type cells. The decreased level of 2-HG in mutated cells after combinatorial treatment was accompanied by an enhanced global DNA hydroxymethylation and an increased gene expression of certain tumour suppressors. Moreover, mutated cells showed an increased percentage of apoptotic cells after treatment with non-cytotoxic concentrations of ML309 and VC. These results suggest that combinatorial therapy is of interest for further investigation to rescue TET activity and treatment of IDH1/2 mutated cancers.