Investigation of nanostructured lipid carriers for fast intracellular localization screening using the Echo liquid handler.

In the field of precision medicine, therapy is optimized individually for each patient, enhancing efficacy while reducing side effects. This involves the identification of promising drug candidates through high-throughput screening on human derived cells in culture. However, screening of drugs which have poor solubility or permeability remains challenging, especially when targeting intracellular components.

On the Structure, Stability, and Cell Uptake of Nanostructured Lipid Carriers for Drug Delivery.

The efficacy of nanostructured lipid carriers (NLC) for drug delivery strongly depends on their stability and cell uptake. Both properties are governed by their compositions and internal structure. To test the effect of the lipid composition of NLC on cell uptake and stability, three kinds of liquid lipids with different degrees of unsaturation are employed.

Effects of Chronic Inflammatory Activation of Murine and Human Arterial Endothelial Cells at Normal Lipoprotein and Cholesterol Levels and .

The activation of endothelial cells is crucial for immune defense mechanisms but also plays a role in the development of atherosclerosis. We have previously shown that inflammatory stimulation of endothelial cells on top of elevated lipoprotein/cholesterol levels accelerates atherogenesis. The aim of the current study was to investigate how chronic endothelial inflammation changes the aortic transcriptome of mice at normal lipoprotein levels and to compare this to the inflammatory response of isolated endothelial cells .

R-ketorolac ameliorates cancer-associated cachexia and prolongs survival of tumour-bearing mice.

Background: Cancer-associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced life expectancy of cancer patients. CAC is characterized by unintended body weight reduction due to muscle and adipose tissue loss. A major hallmark of CAC is systemic inflammation.

Neutrophil-specific STAT4 deficiency attenuates atherosclerotic burden and improves plaque stability via reduction in neutrophil activation and recruitment into aortas of mice.

Background And Aims: Neutrophils drive atheroprogression and directly contribute to plaque instability. We recently identified signal transducer and activator of transcription 4 (STAT4) as a critical component for bacterial host defense in neutrophils. The STAT4-dependent functions of neutrophils in atherogenesis are unknown.

NF-κB in monocytes and macrophages - an inflammatory master regulator in multitalented immune cells.

Nuclear factor κB (NF-κB) is a dimeric transcription factor constituted by two of five protein family members. It plays an essential role in inflammation and immunity by regulating the expression of numerous chemokines, cytokines, transcription factors, and regulatory proteins. Since NF-κB is expressed in almost all human cells, it is important to understand its cell type-, tissue-, and stimulus-specific roles as well as its temporal dynamics and disease-specific context.

Neutrophil-specific STAT4 deficiency attenuates atherosclerotic burden and improves plaque stability via reduction in neutrophil activation and recruitment into aortas of mice.

Background And Aims: Neutrophils drive atheroprogression and directly contribute to plaque instability. We recently identified signal transducer and activator of transcription 4 (STAT4) as a critical component for bacterial host defense in neutrophils. The STAT4-dependent functions of neutrophils in atherogenesis are unknown.

Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice.

Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl) and platelet-specific Mgl-deficient (platMgl) mice.

Antagonistic Functions of Androgen Receptor and NF-κB in Prostate Cancer-Experimental and Computational Analyses.

Prostate cancer is very frequent and is, in many countries, the third-leading cause of cancer related death in men. While early diagnosis and treatment by surgical removal is often curative, metastasizing prostate cancer has a very bad prognosis. Based on the androgen-dependence of prostate epithelial cells, the standard treatment is blockade of the androgen receptor (AR).

Staphylococcus aureus extracellular adherence protein (Eap) reduces immune cell phenotype in developing but not in established atherosclerotic lesions.

Atherosclerosis is a chronic, inflammatory disease of the vessel wall where triggered immune cells bind to inflamed endothelium, extravasate and sustain local inflammation. Leukocyte adhesion and extravasation are mediated by adhesion molecules expressed by activated endothelial cells, like intercellular adhesion molecule 1 (ICAM-1). Extracellular adherence protein (Eap) from Staphylococcus aureus binds to a plethora of extracellular matrix proteins, including ICAM-1 and its ligands macrophage-1 antigen (Mac-1, αβ) and lymphocyte function-associated antigen 1 (LFA-1, αβ), thereby disrupting the interaction between leukocytes and endothelial cells.

Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia.

Phosphatidylinositol 3-kinase catalytic subunit p110β is involved in tumorigenesis and hemostasis. However, it remains unclear if p110β also regulates platelet-mediated immune responses, which could have important consequences for immune modulation during anti-cancer treatment with p110β inhibitors. Thus, we investigate how platelet p110β affects inflammation and infection.

PI3K Isoform Signalling in Platelets.

Platelets are unique anucleated blood cells that constantly patrol the vasculature to seal and prevent injuries in a process termed haemostasis. Thereby they rapidly adhere to the subendothelial matrix and recruit further platelets, resulting in platelet aggregates. Apart from their central role in haemostasis, they also kept some of their features inherited by their evolutionary ancestor-the haemocyte, which was also involved in immune defences.

Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors.

Background & Aims: Surgical resection of the cancerous tissue represents one of the few curative treatment options for neoplastic liver disease. Such partial hepatectomy (PHx) induces hepatocyte hyperplasia, which restores liver function. PHx is associated with bacterial translocation, leading to an immediate immune response involving neutrophils and macrophages, which are indispensable for the priming phase of liver regeneration.

More than Just a Monolayer: the Multifaceted Role of Endothelial Cells in the Pathophysiology of Atherosclerosis.

Purpose Of The Review: In this review, we summarize current insights into the versatile roles of endothelial cells in atherogenesis.

Recent Findings: The vascular endothelium represents the first barrier that prevents the entry of lipoproteins and leukocytes into the vessel wall, thereby controlling two key events in the pathogenesis of atherosclerosis. Disturbance of endothelial homeostasis increases vascular permeability, inflammation, and cellular trans-differentiation, which not only promotes the build-up of atherosclerotic plaques but is also involved in life-threatening thromboembolic complications such as plaque rupture and erosion.

Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo.

According to genome-wide RNA sequencing data from human and mouse platelets, adipose triglyceride lipase (ATGL), the main lipase catalyzing triglyceride (TG) hydrolysis in cytosolic lipid droplets (LD) at neutral pH, is expressed in platelets. Currently, it is elusive to whether common lipolytic enzymes are involved in the degradation of TG in platelets. Since the consequences of ATGL deficiency in platelets are unknown, we used whole-body and platelet-specific (plat)Atgl-deficient (-/-) mice to investigate the loss of ATGL on platelet function.

Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance.

Background And Aims: Lipopolysaccharide (LPS) clearance is delayed in cholestatic liver diseases. While compromised clearance by Kupffer cells (KCs) is involved, the role of LPS uptake into hepatocytes and canalicular excretion remains unclear.

Approach And Results: Wild-type (WT) and bile salt export pump (Bsep) knockout (KO) mice were challenged i.

Horizontal MicroRNA Transfer by Platelets - Evidence and Implications.

For decades, platelets have been known for their central role in hemostasis and their ability to release bioactive molecules, allowing inter-platelet communication and crosstalk with the immune system and vascular cells. However, with the detection of microRNAs in platelets and platelet-derived microvesicles (MVs), a new level of inter-cellular regulation was revealed. By shedding MVs from their plasma membrane, platelets are able to release functional microRNA complexes that are protected from plasma RNases.

Till Death Do Us Part-The Multifaceted Role of Platelets in Liver Diseases.

Platelets are tightly connected with the liver, as both their production and their clearance are mediated by the liver. Platelets, in return, participate in a variety of liver diseases, ranging from non-alcoholic fatty liver diseases, (viral) hepatitis, liver fibrosis and hepatocellular carcinoma to liver regeneration. Due to their versatile functions, which include (1) regulation of hemostasis, (2) fine-tuning of immune responses and (3) release of growth factors and cellular mediators, platelets quickly adapt to environmental changes and modulate disease development, leading to different layers of complexity.

Platelet Activation Is Not Always Associated With Platelet-Related Plasma microRNA Abundance - Results From a Randomized Controlled Trial of Periodontal Patients.

Platelets are involved in a variety of diseases, making their adequate functional assessment is essential. However, due to their easily activatable nature this has some methodological pitfalls. Therefore, the availability of stable, easily measurable surrogate markers would be beneficial.

Functional Role of B Cells in Atherosclerosis.

Atherosclerosis is a lipid-driven inflammatory disease of blood vessels, and both innate and adaptive immune responses are involved in its development. The impact of B cells on atherosclerosis has been demonstrated in numerous studies and B cells have been found in close proximity to atherosclerotic plaques in humans and mice. B cells exert both atheroprotective and pro-atherogenic functions, which have been associated with their B cell subset attribution.

Platelets mediate serological memory to neutralize viruses in vitro and in vivo.

Platelets contain virus-specific IgGs that potently diminish viral infection in vitro and in vivo. Release of platelet IgG is more efficient at virus neutralization than equal amounts of plasma IgG.

Impact of Anticoagulation and Sample Processing on the Quantification of Human Blood-Derived microRNA Signatures.

Blood-derived microRNA signatures have emerged as powerful biomarkers for predicting and diagnosing cardiovascular disease, cancer, and metabolic disorders. Platelets and platelet-derived microvesicles are a major source of microRNAs. We have previously shown that the inappropriate anticoagulation and storage of blood samples causes substantial platelet activation that is associated with the release of platelet-stored molecules into the plasma.