Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

Age- and sex-related variations in extracellular vesicle profiling for the assessment of cardiovascular risk: the EVaging index.

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation ("inflammaging") and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups.

Matrix-assisted autologous chondrocyte transplantation is effective at mid/long-term for knee lesions: A systematic review and meta-analysis.

Purpose: This systematic review with meta-analysis evaluates the long-term efficacy of matrix-assisted autologous chondrocyte transplantation (MACT) in terms of functional scores using scaffolds made of hyaluronic acid (HA) or collagen (C).

Methods: Nineteen articles met the eligibility criteria for the analysis. Fourteen studies focused on patients treated with MACT with HA-based scaffolds, four studies with C-based scaffolds, and one study compared both scaffold types.

Endothelial-mesenchymal transition in skeletal muscle: Opportunities and challenges from 3D microphysiological systems.

Fibrosis is a pathological condition that in the muscular context is linked to primary diseases such as dystrophies, laminopathies, neuromuscular disorders, and volumetric muscle loss following traumas, accidents, and surgeries. Although some basic mechanisms regarding the role of myofibroblasts in the progression of muscle fibrosis have been discovered, our knowledge of the complex cell-cell, and cell-matrix interactions occurring in the fibrotic microenvironment is still rudimentary. Recently, vascular dysfunction has been emerging as a key hallmark of fibrosis through a process called endothelial-mesenchymal transition (EndoMT).

Spatio-temporal distribution, prediction and relationship of three major acute cardiovascular events: Out-of-hospital cardiac arrest, ST-elevation myocardial infarction and stroke.

Background: Predicting the incidence of time-sensitive cardiovascular diseases like out-of-hospital cardiac arrest (OHCA), ST-elevation myocardial infarction (STEMI), and stroke can reduce time to treatment and improve outcomes. This study analysed the spatio-temporal distribution of OHCAs, STEMIs, and strokes, their spatio-temporal correlation, and the performance of different prediction algorithms.

Methods: Adults who experienced an OHCA, STEMI, or stroke in Canton Ticino, Switzerland from 2005 to 2022 were included.

miR-24-3p secreted as extracellular vesicle cargo by cardiomyocytes inhibits fibrosis in human cardiac microtissues.

Background And Aims: Cardiac fibrosis in response to injury leads to myocardial stiffness and heart failure. At the cellular level, fibrosis is triggered by the conversion of cardiac fibroblasts (CF) into extracellular matrix-producing myofibroblasts. miR-24-3p regulates this process in animal models.

Simulation-free prediction of atrial fibrillation inducibility with the fibrotic kernel signature.

Computational models of atrial fibrillation (AF) can help improve success rates of interventions, such as ablation. However, evaluating the efficacy of different treatments requires performing multiple costly simulations by pacing at different points and checking whether AF has been induced or not, hindering the clinical application of these models. In this work, we propose a classification method that can predict AF inducibility in patient-specific cardiac models without running additional simulations.

Development of a Microfluidic Vascularized Osteochondral Model as a Drug Testing Platform for Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by changes in cartilage and subchondral bone. To date, there are no available drugs that can counteract the progression of OA, partly due to the inadequacy of current models to recapitulate the relevant cellular complexity. In this study, an osteochondral microfluidic model is developed using human primary cells to mimic an OA-like microenvironment and this study validates it as a drug testing platform.

Bayesian clustering of spatially distributed compositional data with application to the Great Barrier Reef.

The relative abundance of groups of species is often used in ecological surveys to estimate community composition, a metric that reflects patterns of commonness and rarity of biological assemblages. The focus of this paper is measurements of the abundances of four benthic groups (that live on the seafloor) at several reefs on Australia's Great Barrier Reef (GBR) gathered between 2012 and 2017. In this paper we develop a statistical model to find clusters of locations with similar composition.

A novel ionic model for matured and paced atrial-like human iPSC-CMs integrating I and I currents.

This work introduces the first atrial-specific in-silico human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) model, based on a set of phenotype-specific I,I and I membrane currents. This model is built on novel in-vitro experimental data recently published by some of the co-authors to simulate the paced action potential of matured atrial-like hiPSC-CMs. The model consists of a system of stiff ordinary differential equations depending on several parameters, which have been tuned by automatic optimization techniques to closely match selected experimental biomarkers.

Intrinsic dimension as a multi-scale summary statistics in network modeling.

Complex networks are powerful mathematical tools for modelling and understanding the behaviour of highly interconnected systems. However, existing methods for analyzing these networks focus on local properties (e.g.

High efficiency protocol for platelet derived fibrin gel loaded with mesenchymal stromal cells extracellular vesicles.

Introduction: Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) are potent stimulators of naïve cartilage and their injection is studied in clinical trials for cartilage lesions, since often cartilage repaired with conventional approaches is incomplete or less performant leading to joint degeneration. The main pitfall of these innovative approaches is the high EVs dispersion into the joint cavity and consequent low concentration at lesion site. Thus, biological scaffolds for concentration of EVs where needed might be a promising option.

ErbB2-NOTCH1 axis controls autophagy in cardiac cells.

Although the epidermal growth factor receptor 2 (ErbB2) and Notch1 signaling pathways have both significant roles in regulating cardiac biology, their interplay in the heart remains poorly investigated. Here, we present evidence of a crosstalk between ErbB2 and Notch1 in cardiac cells, with effects on autophagy and proliferation. Overexpression of ErbB2 in H9c2 cardiomyoblasts induced Notch1 activation in a post-transcriptional, p38-dependent manner, while ErbB2 inhibition with the specific inhibitor, lapatinib, reduced Notch1 activation.

Extracellular vesicles from II trimester human amniotic fluid as paracrine conveyors counteracting oxidative stress.

Background: We previously demonstrated that the human amniotic fluid (hAF) from II trimester of gestation is a feasible source of stromal progenitors (human amniotic fluid stem cells, hAFSC), with significant paracrine potential for regenerative medicine. Extracellular vesicles (EVs) separated and concentrated from hAFSC secretome can deliver pro-survival, proliferative, anti-fibrotic and cardioprotective effects in preclinical models of skeletal and cardiac muscle injury. While hAFSC-EVs isolation can be significantly influenced by in vitro cell culture, here we profiled EVs directly concentrated from hAF as an alternative option and investigated their paracrine potential against oxidative stress.

Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications.

Cardiovascular disease represents the foremost cause of mortality and morbidity worldwide, with a steadily increasing incidence due to the growth of the ageing population. Cardiac dysfunction leading to heart failure may arise from acute myocardial infarction (MI) as well as inflammatory- and cancer-related chronic cardiomyopathy. Despite pharmacological progress, effective cardiac repair represents an unmet clinical need, with heart transplantation being the only option for end-stage heart failure.

Low-density cultured cartilage cells expanded in platelet lysate present distinct features to develop an innovative clinical treatment for diffuse cartilage lesions.

Purpose: Chondrocyte-based cell therapies are effective for the treatment of chondral lesions, but remain poorly indicated for diffuse lesions in the context of early osteoarthritis (OA). The aim of this study was to develop a protocol to obtain chondroprogenitor cells suitable for the treatment of diffuse chondral lesions within early OA.

Methods: Cartilage cells were expanded at low density in human platelet lysate (hPL).

Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan-Vesicular Affinity Probes.

Extracellular vesicles (EVs), crucial mediators of cell-to-cell communication, hold significant diagnostic potential due to their ability to concentrate protein biomarkers in bodily fluids. However, challenges in isolating EVs from biological specimens hinder their widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating.

A personalized osteoarthritic joint-on-a-chip as a screening platform for biological treatments.

Osteoarthritis (OA) is a highly disabling pathology, characterized by synovial inflammation and cartilage degeneration. Orthobiologics have shown promising results in OA treatment thanks to their ability to influence articular cells and modulate the inflammatory OA environment. Considering their complex mechanism of action, the development of reliable and relevant joint models appears as crucial to select the best orthobiologics for each patient.

Extracellular vesicles selective capture by peptide-functionalized hollow fiber membranes.

Recently, membrane devices and processes have been applied for the separation and concentration of subcellular components such as extracellular vesicles (EVs), which play a diagnostic and therapeutic role in many pathological conditions. However, the separation and isolation of specific EV populations from other components found in biological fluids is still challenging. Here, we developed a peptide-functionalized hollow fiber (HF) membrane module to achieve the separation and enrichment of highly pure EVs derived from the culture media of human cardiac progenitor cells.

Transformer-based spatial-temporal detection of apoptotic cell death in live-cell imaging.

Intravital microscopy has revolutionized live-cell imaging by allowing the study of spatial-temporal cell dynamics in living animals. However, the complexity of the data generated by this technology has limited the development of effective computational tools to identify and quantify cell processes. Amongst them, apoptosis is a crucial form of regulated cell death involved in tissue homeostasis and host defense.