A5040533169- Sphingolipid Metabolism and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Barrier Structure and Function Studies
- Ovarian function and disorders
- Zebrafish Biomedical Research Applications
- Immune cells in cancer
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- CRISPR and Genetic Engineering
- Protein Tyrosine Phosphatases
- Diabetic Foot Ulcer Assessment and Management
- Virus-based gene therapy research
- Biochemical and Molecular Research
- Wnt/β-catenin signaling in development and cancer
- Sleep and Wakefulness Research
- Angiogenesis and VEGF in Cancer
- Lipid metabolism and biosynthesis
- Lipid metabolism and disorders
- Reproductive Biology and Fertility
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- Ion Transport and Channel Regulation
- Retinal Diseases and Treatments
- Fibroblast Growth Factor Research
- Neurological Disease Mechanisms and Treatments
Goethe University Frankfurt
2014-2025
University Hospital Frankfurt
2018-2020
Septic encephalopathy with confusion and agitation occurs early during sepsis contributes to the severity of disease. A decrease in sphingosine-1-phosphate (S1P) blood levels has been shown patients animal models sepsis. The lipid mediator S1P is known be involved endothelial barrier function a context-dependent manner. We utilized lipopolysaccharide (LPS)-injected mice as model for septic first performed tracer permeability assays assess blood-brain (BBB) breakdown vivo. At time points...
17-β-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a lipid droplet protein primarily expressed in the liver hepatocytes. HSD17B13 associated with clinical outcome of chronic diseases and therefore target for development drugs. Here, we demonstrate promising therapeutic effect BI-3231 as potent inhibitor based on its ability to inhibit triglyceride accumulation droplets (LDs), restore metabolism homeostasis, increase mitochondrial activity vitro.
With increasing distribution of endovascular stroke therapies, transient middle cerebral artery occlusion (tMCAO) in mice now more than ever depicts a relevant patient population with recanalized M1 occlusion. In this case, the desired therapeutic effect blood flow restauration is accompanied by breakdown blood-brain barrier (BBB) and secondary reperfusion injury. The aim study was to elucidate short intermediate-term transcriptional patterns involved pathways covering different cellular...
The precise regulation of blood-brain barrier (BBB) permeability for immune cells and blood-borne substances is essential to maintain brain homeostasis. Sphingosine-1-phosphate (S1P), a lipid signaling molecule enriched in plasma, known affect BBB permeability. Previous studies focused on endothelial S1P receptors 1 2, reporting barrier-protective effect S1P1 barrier-disruptive S1P2. Here, we present novel data characterizing the expression, localization, function receptor 4 (S1P4) primary...
Background Stroke is one of the leading causes death and long-term adult disability worldwide. neurodegeneration impairs synaptic function. Understanding role proteins associated signalling pathways in stroke pathology could offer insights into therapeutic approaches as well improving rehabilitation-related treatment regimes. Purpose The current study aims to analyse transcriptome changes acute post-stroke (1 day, 7 day timepoints), especially focusing on pre- postsynaptic genes. Methods We...
Emerging evidence suggests a complex relationship between sphingosine 1-phosphate (S1P) signaling and stroke. Here, we show the kinetics of S1P in acute phase ischemic stroke highlight accompanying changes immune cells receptors (S1PR). Using C57BL/6 mouse model middle cerebral artery occlusion (MCAO), assessed concentrations brain, plasma, spleen. We found steep gradient from spleen towards brain. Results obtained by qPCR suggested that expressing S1PR type 1 (S1P1+) were predominant...
Ischemic stroke is a highly prevalent vascular disease leading to oxygen- and glucose deprivation in the brain. In response, ischemia-induced neovascularization occurs, which supported by circulating CD34+ endothelial progenitor cells. Here, we used transient middle cerebral artery occlusion (tMCAO) mouse model characterize spatio-temporal alterations within ischemic core from acute chronic phase using multiple-epitope-ligand cartography (MELC) for sequential immunohistochemistry. We found...
Despite the efficacy of neuroprotective approaches in animal models stroke, their translation has so far failed from bench to bedside. One reason is presumed be a low quality preclinical study design, leading bias and priori power. In this study, we propose that key read-out experimental stroke studies, volume ischemic damage as commonly measured by free-handed planimetry TTC-stained brain sections, subject an unrecognized inter-rater test-retest reliability with strong implications for...
Purpose: Neovascularization is a major cause of blindness in various ocular diseases. Bioactive sphingosine 1-phosphate (S1P), synthesized by two kinases (Sphk1, Sphk2), emerged as key player multitude cellular processes, including cell survival, proliferation, inflammation, migration, and angiogenesis. We investigated the role Sphk2, S1P, S1P receptors (S1PR) during retinal neovascularization using oxygen-induced retinopathy mouse model (OIR). Methods: Sphk2 overexpressing (tgSphk2)...
An injured skin is rapidly restored in a manner of wound healing. We have previously shown that intact insulin signaling and glucose uptake are fundamental to proper closure. Consequently, under exacerbated inflammation, compromised action lead impaired However, spite the increased attention cell metabolism during tissue regeneration, metabolic mediators govern cellular physiological processes throughout repair remained largely elusive. Through assessment mRNA using real-time PCR protein...
Sphingolipids are versatile signaling molecules derived from membrane lipids of eukaryotic cells. Ceramides regulate cellular processes such as proliferation, differentiation and apoptosis involved in stress responses. Experimental evidence suggests a pivotal role sphingolipids the pathogenesis cardiovascular diseases, including ischemic stroke. A neuroprotective effect has been shown for beta-adrenergic antagonists rodent stroke models supported by observational clinical data. However,...
Sphingosine 1-phosphate (S1P) signaling influences numerous cell biological mechanisms such as differentiation, proliferation, survival, migration, and angiogenesis. Intriguingly, our current knowledge is based solely on the role of S1P with an 18-carbon long-chain base length, d18:1. Depending composition first rate-limiting enzyme sphingolipid de novo metabolism, serine palmitoyltransferase, other chain lengths have been described in vivo. While cells are also able to produce d20:1, its...
The healing of wounded skin is a highly organized process involving massive cell in- and outflux, proliferation tissue remodelling. It well accepted that metabolic constraints such as diabetes mellitus, overweight or anorexia impairs wound healing. Indeed, inflammation involves boost overall changes. As converges inflammatory processes are also common to transformation, we investigate the functional role pro-neoplastic factor pyruvate kinase (PK) M2 its active splice variant PKM1 in...
The present study aims to evaluate the effect of Sepia pharaonis ink on insulin resistance in PCOS-induced mice. Treatment with sepia dehydroepiandrosterone (DHEA)-induced PCOS mice at various doses 50 mg/kg, 100 and 200 mg/kg body weight mitigated groups decreased concentration testosterone increased concentrations estrogen progesterone compared group tested by ELISA. histopathological analysis restoration glucose showed a significant reduction treatment groups. Reduced expression genes...
Sphingosine 1‐phosphate (S1P) is a lipid mediator with numerous biological functions. The term ‘S1P’ mainly refers to the sphingolipid molecule long‐chain sphingoid base of 18 carbon atoms, d18:1 S1P. enzyme serine palmitoyltransferase catalyses first step de novo synthesis using palmitoyl‐CoA as main substrate. After further reaction steps, S1P generated. However, also stearyl‐CoA or myristoyl‐CoA can be utilised by palmitoyltransferase, which at end pathway, results in production d20:1 and...