Loss of glymphatic homeostasis in heart failure.

Heart failure (HF) is associated with progressive reduction in cerebral blood flow (CBF) and neurodegenerative changes leading to cognitive decline. The glymphatic system is crucial for the brain's waste removal, and its dysfunction is linked to neurodegeneration. In this study, we used a mouse model of HF, induced by myocardial infarction (MI), to investigate the effects of HF with reduced ejection fraction on the brain's glymphatic function.

Depletion of β1,6-N-acetylglucosaminyltransferase reduces E-selectin binding capacity and migratory potential of human gastrointestinal adenocarcinoma cells.

The commonly altered glycosylation of tumor cells is a hallmark of tumor progression and metastasis formation. One prominent example is the interaction of sialylated glycans at the tumor cell surface with endothelial (E)-selectin as an early event of an adhesion cascade that enables extravasation of circulating tumor cells (CTCs) into distant tissues. In a previous study, we identified GCNT3 (mucin-type core2/ core4 β1,6-N-acetylglucosaminyltransferase) highly over-expressed in gastrointestinal adenocarcinoma cells that facilitate the canonical E-selectin ligands sialyl-Lewis A and X (sLeA/X) for E-selectin binding and endothelial adhesion.

Lyso-phosphatidylcholine as an interfacial stabilizer for parenteral monoclonal antibody formulations.

Therapeutic proteins suffer from physical and chemical instability in aqueous solution. Polysorbates and poloxamers are often added for protection against interfacial stress to prevent protein aggregation and particle formation. Previous studies have revealed that the hydrolysis and oxidation of polysorbates in parenteral formulations can lead to the formation of free fatty acid particles, insufficient long-term stabilization, and protein oxidation.

Vascular smooth muscle BK channels limit ouabain-induced vasocontraction: Dual role of the Na/K-ATPase as a hub for Src-kinase and the Na/Ca-exchanger.

Large-conductance, calcium-activated potassium channels (BK channels) and the Na/K-ATPase are expressed universally in vascular smooth muscle. The Na/K-ATPase may act via changes in the intracellular Ca concentration mediated by the Na/Ca exchanger (NCX) and via Src kinase. Both pathways are known to regulate BK channels.

Communication skills of medical students: Evaluation of a new communication curriculum at the University of Augsburg.

Objectives: Teaching communication skills plays a pivotal role in medical curricula. The aim of this article is to describe and evaluate a new communication curriculum developed at the Faculty of Medicine, University of Augsburg (KomCuA), which was conceptualized by an interdisciplinary team based on recommended quality standards (i.e.

Bitter tastants relax the mouse gallbladder smooth muscle independent of signaling through tuft cells and bitter taste receptors.

Disorders of gallbladder motility can lead to serious pathology. Bitter tastants acting upon bitter taste receptors (TAS2R family) have been proposed as a novel class of smooth muscle relaxants to combat excessive contraction in the airways and other organs. To explore whether this might also emerge as an option for gallbladder diseases, we here tested bitter tastants for relaxant properties and profiled Tas2r expression in the mouse gallbladder.

Reduction in Xenogeneic Epitopes on Porcine Endothelial Cells by Periodate Oxidation.

Background: Patterns of humoral immune responses represent a major hurdle in terms of pig-to-human xenotransplantation approaches. The best-known xenogeneic glycan antigens present in pigs are the αGal (Galili antigen) and the non-human sialic acid Neu5Gc. As there are further differences between porcine and human cellular surface glycosylation, a much broader range of glycan epitopes with xeno-reactive relevance can be anticipated.

Liver microRNA transcriptome reveals miR-182 as link between type 2 diabetes and fatty liver disease in obesity.

Background: The development of obesity-associated comorbidities such as type 2 diabetes (T2D) and hepatic steatosis has been linked to selected microRNAs in individual studies; however, an unbiased genome-wide approach to map T2D induced changes in the miRNAs landscape in human liver samples, and a subsequent robust identification and validation of target genes are still missing.

Methods: Liver biopsies from age- and gender-matched obese individuals with (n=20) or without (n=20) T2D were used for microRNA microarray analysis. The candidate microRNA and target genes were validated in 85 human liver samples, and subsequently mechanistically characterized in hepatic cells as well as by dietary interventions and hepatic overexpression in mice.

BK Channels in Tail Artery Vascular Smooth Muscle Cells of Normotensive (WKY) and Hypertensive (SHR) Rats Possess Similar Calcium Sensitivity But Different Responses to the Vasodilator Iloprost.

It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively low efficacy has been established, whereas downstream BK currents seem to be increased. Thus, the overall performance of this signaling pathway in SHR is elusive.

Phase-State-Dependent Silica Nanoparticle Uptake of Giant Unilamellar Vesicles.

We quantify endocytosis-like nanoparticle (NP) uptake of model membranes as a function of temperature and, therefore, phase state. As model membranes, we use giant unilamellar vesicles (GUV) consisting of 1,2-dipentadecanoyl-sn-glycero-3-phosphocholine (15:0 PC). Time-series micrographs of the vesicle shrinkage show uptake rates that are a highly nonlinear function of temperature.

Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body.

Background: The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive.

Transition transferases prime bacterial capsule polymerization.

Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane.

Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke.

Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples.

Macrophage- and CD4+ T cell-derived SIV differ in glycosylation, infectivity and neutralization sensitivity.

The human immunodeficiency virus (HIV) envelope protein (Env) mediates viral entry into host cells and is the primary target for the humoral immune response. Env is extensively glycosylated, and these glycans shield underlying epitopes from neutralizing antibodies. The glycosylation of Env is influenced by the type of host cell in which the virus is produced.

Microfluidic Transfection System and Temperature Strongly Influence the Efficiency of Transient Transfection.

For the process of transient transfection (TTF), DNA is often transported into the cells using polyplexes. The polyplex uptake and the subsequent transient expression of the gene of interest are of great importance for a successful transfection. In this study, we investigated a 3D-printed microfluidic system designed to facilitate direct TTF for suspension of CHO-K1 cells.

In vitro cleavage of tumor necrosis factor α (TNFα) by Signal-Peptide-Peptidase-like 2b (SPPL2b) resembles mechanistic principles observed in the cellular context.

Members of the Signal Peptide-Peptidase (SPP) and Signal Peptide-Peptidase-like (SPPL) family are intramembrane aspartyl-proteases like their well-studied homologs, the presenilins, which comprise the catalytically active subunit within the γ-secretase complex. The lack of in vitro cleavage assays for SPPL proteases limited their biochemical characterization as well as substrate identification and validation. So far, SPPL proteases have been analyzed exclusively in intact cells or membranes, restricting mechanistic analysis to co-expression of enzyme and substrate variants colocalizing in the same subcellular compartments.

Hyalocytes-guardians of the vitreoretinal interface.

Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease.

Signal peptide peptidase-like 2b modulates the amyloidogenic pathway and exhibits an Aβ-dependent expression in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disorder driven by abnormal amyloid β-peptide (Aβ) levels. In this study, we investigated the role of presenilin-like signal peptide peptidase-like 2b (SPPL2b) in AD pathophysiology and its potential as a druggable target within the Aβ cascade. Exogenous Aβ42 influenced SPPL2b expression in human cell lines and acute mouse brain slices.

Survival of infected red blood cell aggregates in elongational shear flow.

Rosetting, the formation of red blood cell aggregates, is a life-threatening condition in malaria tropica and not yet fully understood. We study rosette stability using a set of microfluidic stenotic channels, with varied narrowing angle and erythrocytes of blood groups O and A. We find reduced ability of a rosette to pass a stenosis without disruption, the longer the tapered part of the constriction and the narrower the stenosis is.

Anticarcinogenic Potency of EF24: An Overview of Its Pharmacokinetics, Efficacy, Mechanism of Action, and Nanoformulation for Drug Delivery.

EF24, a synthetic monocarbonyl analog of curcumin, shows significant potential as an anticancer agent with both chemopreventive and chemotherapeutic properties. It exhibits rapid absorption, extensive tissue distribution, and efficient metabolism, ensuring optimal bioavailability and sustained exposure of the target tissues. The ability of EF24 to penetrate biological barriers and accumulate at tumor sites makes it advantageous for effective cancer treatment.

ALDH1A1 and ALDH1A3 paralogues of aldehyde dehydrogenase 1 control myogenic differentiation of skeletal muscle satellite cells by retinoic acid-dependent and -independent mechanisms.

ALDH1A1 and ALDH1A3 paralogues of aldehyde dehydrogenase 1 (ALDH1) control myogenic differentiation of skeletal muscle satellite cells (SC) by formation of retinoic acid (RA) and subsequent cell cycle adjustments. The respective relevance of each paralogue for myogenic differentiation and the mechanistic interaction of each paralogue within RA-dependent and RA-independent pathways remain elusive.We analysed the impact of ALDH1A1 and ALDH1A3 activity on myogenesis of murine C2C12 myoblasts.

Density of Sphingosine-1-Phosphate Receptors Is Altered in Cortical Nerve-Terminals of Insulin-Resistant Goto-Kakizaki Rats and Diet-Induced Obese Mice.

Sphingosine-1-phosphate (S1P) is a phosphosphingolipid with pleiotropic biological functions. S1P acts as an intracellular second messenger, as well as extracellular ligand to five G-protein coupled receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation, apoptosis, synaptic activity and neuroglia activation.

Structure and function of SPP/SPPL proteases: insights from biochemical evidence and predictive modeling.

More than 20 years ago, signal peptide peptidase (SPP) and its homologues, the signal peptide peptidase-like (SPPL) proteases have been identified based on their sequence similarity to presenilins, a related family of intramembrane aspartyl proteases. Other than those for the presenilins, no high-resolution structures for the SPP/SPPL proteases are available. Despite this limitation, over the years bioinformatical and biochemical data have accumulated, which altogether have provided a picture of the overall structure and topology of these proteases, their localization in the cell, the process of substrate recognition, their cleavage mechanism, and their function.