Abstract Hypoalbuminemia is common in critically ill patients, yet albumin replacement remains controversial. Beyond volume regulation, albumin transports sphingosine 1-phosphate (S1P), a key modulator of immunity and endothelial stability. This study investigates how human albumin (HA) affects S1P distribution…
London: Macmillan Publishers Limited, part of Springer Nature, 2026-02-06
Abstract Purpose Major surgery under general anesthesia substantially alters physiologic homeostasis. Nevertheless, the intricate effects on the metabolome are poorly studied. Metabolic fingerprints may allow the identification of patients at risk for unfavourable outcomes. Methods We conducted a secondary,…
Abstract Background Ceramides are bioactive sphingolipids that have physiological effects on inflammation, apoptosis, and mitochondrial dysfunction. They may play a critical role in the harm of ischemia/reperfusion (IR). Ceramides and IR injury are not well-studied, and there is a lack of human data.…
Die Sepsis stellt aufgrund hoher Mortalität und fehlender kausaler Therapie ein großes Gesundheitsproblem dar. Tierexperimentelle Daten zeigen, dass die Aktivierung des Sphingosin-1-phosphat-Rezeptors Typ 3 (S1PR3) im manifesten Stadium das Überleben signifikant verbessert. Ziel dieser Arbeit war es,…
Glucocorticoids (GCs) stand as fundamental agents in the treatment of acute lymphoblastic leukemia (ALL). GCs are functioning through their glucocorticoid receptor (GR), a widely distributed nuclear receptor transcriptional factor, exerting regulatory control over 20% of the human genome in a cellular…
Das Sphingosin-1-phosphat (S1P) ist ein Signalmolekül, das die Endothelbarriere stabilisiert und somit den pathophysiologischen Prozessen einer Sepsis entgegenwirkt. Es ist gebunden an Serumalbumin (SA) und High Density Lipoprotein (HDL). Bei Sepsispatienten ist die Plasmakonzentration von S1P signifikant…
Typical hemolytic uremic syndrome (HUS) can occur as a severe systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli . Its pathology can be induced by Stx types, resulting in toxin-mediated damage to renal barriers, inflammation, and the development of acute kidney injury…
Influenza A virus (IAV) is an important respiratory pathogen that represents a significant burden on public health around the world. Seasonal outbreaks cause as many as 650 000 deaths per year. Similarly, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a threat to public…
Introduction Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third…
London: British Medical Journal Publishing Group, 2024-04-22
Red blood cells (RBC) are the major carriers of sphingosine-1-phosphate (S1P) in blood. Here we show that variations in RBC S1P content achieved by altering S1P synthesis and transport by genetic and pharmacological means regulate glucose uptake and metabolic flux. This is due to S1P-mediated activation…
Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate…
Insulin resistance (IR) during obesity is linked to adipose tissue macrophage (ATM)-driven inflammation of adipose tissue. Whether anti-inflammatory glucocorticoids (GCs) at physiological levels modulate IR is unclear. Here, we report that deletion of the GC receptor (GR) in myeloid cells, including…
Sphingosine kinases type 1 and 2 (SphK1/2) are required for the production of the immune modulator sphingosine 1-phosphate (S1P). SphK1 deficient mice (SphK1 −/− ) revealed 50% reduced S1P in plasma, while SphK2 −/− mice demonstrated 2–3 times increased S1P levels in plasma. Since plasma S1P is a potent…
Altered plasma sphingosine-1-phosphate (S1P) concentrations are associated with clinical manifestations of atherosclerosis. However, whether long-term elevation of endogenous S1P is pro- or anti-atherogenic remains unclear. Here, we addressed the impact of permanently high S1P levels on atherosclerosis…
Loss of active synapses and alterations in membrane lipids are crucial events in physiological aging as well as in neurodegenerative disorders. Both are related to the abnormal aggregation of amyloid-beta (Aβ) species, generally known as amyloidosis. There are two major known human Aβ species: Aβ (1–40)…
Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies,…
Doxorubicin (Dox) is a chemotherapeutic agent with cardiotoxicity associated with profibrotic effects. Dox increases ceramide levels with pro-inflammatory effects, cell death, and fibrosis. The purpose of our study was to identify the underlying ceramide signaling pathways. We aimed to characterize the…
Elevated levels of free fatty acids (FFAs) have been related to pancreatic beta-cell failure in type 2 diabetes (T2DM), though the underlying mechanisms are not yet fully understood. FFAs have been shown to dysregulate formation of bioactive sphingolipids, such as ceramides and sphingosine-1 phosphate…
Sphingosine-1-phosphate (S1P) is a lipid metabolite with multiple biological functions. The regulation of vascular permeability and control of immune cell trafficking are two elemental functions of S1P-S1P receptor (S1PR) signaling, which is related to the regulation of inflammation. The gradient of…
Das Forschungsinteresse an der Thematik Sepsis beruht auf der Tatsache, dass Sepsis sowohl national als auch international eine der häufigsten Todesursachen ist. Sphingolipide und Proteine des Sphingolipid-Stoffwechsels spielen eine zentrale Rolle bei pathophysiologischen Prozessen im Verlauf einer Sepsis.…