Accelerated maturation of ARPE-19 cells for the translational assessment of gene therapy.

The human retinal pigment epithelium (RPE) cell line ARPE-19 is widely used as an alternative to primary RPE despite losing many features of primary RPE. We aimed to determine whether a combination of RPE-specific laminin (LN) and nicotinamide (NAM) could improve ARPE-19 redifferentiation to resemble mature RPE and improve the assessment of RPE-specific gene therapy strategies. ARPE-19 cells were propagated on tissue culture plastic supplemented with NAM and human recombinant LN521-coating.

Mitigation of human iris angiogenesis through uPAR/LRP-1 interaction antagonism in an organotypic ex vivo model.

Rubeosis Iridis (RI) is characterized by an increase in neovascularization and inflammation factors in the iris. During angiogenesis, the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a pivotal role in extracellular matrix remodeling, where uPAR regulates endothelial cell migration and proliferation through assembly with transmembrane receptors. Here, in the context of hypoxia-induced angiogenesis, the uPA/uPAR system blockage was investigated by using UPARANT in a novel ex vivo human iris organotypic angiogenesis assay.

The Methyltransferase Smyd1 Mediates LPS-Triggered Up-Regulation of IL-6 in Endothelial Cells.

The lysine methyltransferase Smyd1 with its characteristic catalytic SET-domain is highly enriched in the embryonic heart and skeletal muscles, participating in cardiomyogenesis, sarcomere assembly and chromatin remodeling. Recently, significant Smyd1 levels were discovered in endothelial cells (ECs) that responded to inflammatory cytokines. Based on these biochemical properties, we hypothesized that Smyd1 is involved in inflammation-triggered signaling in ECs and therefore, investigated its role within the LPS-induced signaling cascade.

Structural Microangiopathies in Skeletal Muscle Related to Systemic Vascular Pathologies in Humans.

It is unclear how microangiopathic changes in skeletal muscle vary among systemic vascular pathologies. We therefore analyzed the capillary fine structure in skeletal muscle from patients with arterial hypertension (HYPT), diabetes mellitus type 2 (T2DM) or intermittent claudication - peripheral arterial disease (IC/PAD). Tablet-based image analysis (TBIA) was carried out to largely re-evaluate 5,000 transmission electron micrographs of capillaries from 126 vastus lateralis biopsies of 75 individuals (HYPT, T2DM or IC/PAD patients as well as healthy individuals before and after endurance exercise training) used in previous morphometric studies, but assessed using stereological counting grids of different sizes.

METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS-The METAMORPHOSIS Trial.

Extensive search for methods of overcoming morphine-related delay of the absorption and onset of action of oral P2Y inhibitors in patients presenting with acute coronary syndrome is on-going. The aim of the trial was to investigate whether metoclopramide co-administration could reduce this delay and improve the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ticagrelor and its active metabolite AR-C124900XX. Plasma concentration of both compounds and platelet reactivity were evaluated in nine pre-defined time points within 6 hours after administration of ticagrelor loading dose.

ZNF580 - a brake on Interleukin-6.

Background: Zinc finger protein 580 (ZNF580) was reported to modulate angiogenesis, endothelial homeostasis and blood pressure control. ZNF580 regulated genes include VEGF-A and IL-8. However, it is unknown if ZNF580 could play a role during inflammation.

What can patients do to facilitate shared decision making? A qualitative study of patients with depression or schizophrenia and psychiatrists.

Purpose: Patient involvement in decision making is endorsed by patients and professionals. While research has recently been conducted on how professionals can promote shared decision making (SDM), little is known about how patients can also facilitate SDM.

Methods: Seven focus groups were conducted: 3 with psychiatrists and 4 with patients with schizophrenia or depression.

The use of a novel taxane-based P-glycoprotein inhibitor to identify mutations that alter the interaction of the protein with paclitaxel.

Murine thymoma cell lines expressing mutated forms of the mdr1b P-glycoprotein were isolated using a novel taxane-based P-glycoprotein inhibitor tRA-96023 (SB-RA-31012). The selection strategy required resistance to a combination of tRA-96023 and colchicine. Five mutations were identified (N350I, I862F, L865F, L868W, and A933T) that reduce the capacity of tRA-96023 to inhibit P-glycoprotein-dependent drug resistance.