From Patients to Platelets and Back Again: Pharmacological Approaches to Glycoprotein VI, a Thrilling Antithrombotic Target with Minor Bleeding Risks

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Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So fa ...

In acute ischemic stroke, the composition of the occlusive clot can be associated with the underlying pathophysiology and the response to treatment. For these reasons, it is important to characterize the clot composition from clinical scans. We examine the ...

Background:Arterial stiffening contributes to hemodynamic derangements in heart failure with preserved ejection fraction (HFpEF). We sought to investigate the impact of renal denervation on pulsatile left ventricular loading in patients with HFpEF and hype ...

The integration of technology in the medical field has greatly improved accuracy in diagnoses, thus leading to more effective treatments. Wearable and implantable medical devices offer great potential for remote patient monitoring, particularly for heart f ...

Glutathione (GSH) is the main determinant of intracellular redox potential and participates in multiple cellular signalling pathways. Achieving a detailed understanding of intracellular GSH homeostasis depends on the development of tools to map GSH compart ...

Chimeric antigen receptors (CARs) are synthetic, transmembrane proteins that trigger immune cell signaling following their engagement. They have been first utilized in T cells and later in natural killer (NK) cells to redirect their cytotoxicity toward a s ...

Native reactive electrophile species (RES) such as 4-hydroxynonenal (HNE) act as cellular signals through covalent modification of kinetically-privileged electrophile sensor proteins. Research efforts in the field focus mainly on identifying these sensor p ...

We analyse the haemodynamics of the left atrium, highlighting differences between healthy individuals and patients affected by atrial fibrillation. The computational study is based on patient-specific geometries of the left atria to simulate blood flow dyn ...

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are under active debate. However, in our opinion, it is becoming increasingly likely that electrophiles can rewi ...

De novo protein design enables the exploration of novel sequences and structures absent from the natural protein universe. De novo design also stands as a stringent test for our understanding of the underlying physical principles of protein folding and may ...

Aging is typified by a progressive decline in mitochondrial activity and stress resilience. Here, we review how mitochondrial stress pathways have pleiotropic effects on cellular and systemic homeostasis, which can comprise protective or detrimental respon ...

Despite significant advances in the treatment of cardiovascular diseases, antiplatelet therapies are still associated with a high risk of hemorrhage. In order to develop new drugs, methods to measure platelet function must be adapted for the high-throughpu ...

During wound healing, the distribution, availability, and signaling of growth factors (GFs) are orchestrated by their binding to extracellular matrix components in the wound microenvironment. Extracellular matrix proteins have been shown to modulate angiog ...

The transduction of extracellular signals through signaling pathways that culminate in a transcriptional response is central to many biological processes. However, quantitative relationships between activities of signaling pathway components and transcript ...

Atherosclerosis is a lipid driven chronic inflammatory disease that is characterized by the formation of plaques at predilection sites. These predilection sites (side branches, curved segments, and bifurcations) have often been associated with disturbed sh ...

Peptides represent a promising molecular class for drug development. They combine several strengths of small molecules (e.g. efficient tissue diffusion, low immunogenicity and access to chemical synthesis) and key properties of biologics such as monoclonal ...

Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused by severe injury, congenital defects or tumour ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and r ...

Background Venous thromboembolism (VTE) is a complex multifactorial disease influenced by genetic and environmental risk factors. An example for the latter is the regular use of combined oral contraceptives (CC), which increases the risk to develop VTE by ...

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnorma ...

Acute coronary syndrome is a life-threatening condition of utmost clinical importance, which, despite recent progress in the field, is still associated with high morbidity and mortality. Acute coronary syndrome results from a rupture or erosion of vulnerab ...

From Patients to Platelets and Back Again: Pharmacological Approaches to Glycoprotein VI, a Thrilling Antithrombotic Target with Minor Bleeding Risks

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DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance

MRI characterization of in vitro clots at 3T and 7T: A technical note

Modulation of Pulsatile Left Ventricular Afterload by Renal Denervation in Heart Failure With Preserved Ejection Fraction

Integrated Electronics for Deep Implants to Remotely Monitor Hemodynamics

A locally activatable sensor for robust quantification of organellar glutathione

Unlocking Hidden Potential: Exploring the Complexities of Signaling in Immune Cell Activation to Optimize CAR Therapy

Towards Uncovering the Mechanisms of Electrophile Sensing and Signaling

Impact of atrial fibrillation on left atrium haemodynamics: A computational fluid dynamics study

Hitting the Bullseye: Endogenous Electrophiles Show Remarkable Nuance in Signaling Regulation

A generic framework for hierarchical de novo protein design

Pleiotropic effects of mitochondria in aging

An optimized and validated 384-well plate assay to test platelet function in a high-throughput screening format

The heparin binding domain of von Willebrand factor binds to growth factors and promotes angiogenesis in wound healing

Quantitative relationships between SMAD dynamics and target gene activation kinetics in single live cells

Considerations for analysis of endothelial shear stress and strain in FSI models of atherosclerosis

Development of cyclic peptide inhibitors of coagulation factor XII and matrix metalloproteinase 2

Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle

Risk prediction of developing venous thrombosis in combined oral contraceptive users

Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs

Photodynamic therapy for the treatment of atherosclerotic plaque: Lost in translation?