Diagnostic and Therapeutic Aptamers: A Promising Pathway to Improved Cardiovascular Disease Management.

Despite advances in care, cardiovascular diseases remain the leading cause of death worldwide. As a result, identifying suitable biomarkers for early diagnosis and improving therapeutic and diagnostic strategies is crucial. Because of their significant advantages over other therapeutic approaches, nucleic-based therapies, particularly aptamers, are gaining increased attention. Aptamers are innovative synthetic polymers or oligomers of single-stranded DNA (ssDNA) or RNA molecules that can form 3-dimensional structures and thus interact with their targets with high specificity and affinity. Furthermore, they outperform classical protein-based antibodies in terms of in vitro selection, production, ease of modification and conjugation, high stability, low immunogenicity, and suitability for nanoparticle functionalization for targeted drug delivery. This work aims to review the advances made in the aptamers' field in biomarker detection, diagnosis, imaging, and targeted therapy, which highlight their huge potential in the management of cardiovascular diseases.

Interaction of Bacteria, Immune Cells, and Surface Topography in Periprosthetic Joint Infections.

The incidence of periprosthetic joint infections (PJIs) is ~2% of total procedures and it is expected to rise due to an ageing population. Despite the large burden PJI has on both the individual and society, the immune response to the most commonly isolated pathogens, i.e., Staphylococcus aureus and Staphylococcus epidermidis, remains incompletely understood. In this work, we integrate the analysis of synovial fluids from patients undergoing hip and knee replacement surgery with in-vitro experimental data obtained using a newly developed platform, mimicking the environment of periprosthetic implants. We found that the presence of an implant, even in patients undergoing aseptic revisions, is sufficient to induce an immune response, which is significantly different between septic and aseptic revisions. This difference is confirmed by the presence of pro- and anti-inflammatory cytokines in synovial fluids. Moreover, we discovered that the immune response is also dependent on the type of bacteria and the topography of the implant surface. While S. epidermidis seems to be able to hide better from the attack of the immune system when cultured on rough surfaces (indicative of uncemented prostheses), S. aureus reacts differently depending on the contact surface it is exposed to. The experiments we performed in-vitro also showed a higher biofilm formation on rough surfaces compared to flat ones for both species, suggesting that the topography of the implant could influence both biofilm formation and the consequent immune response.

Harnessing the power of RNA therapeutics in treating ischemic heart failure: the TRAIN-HEART story.

Ischemic heart disease (IHD) is one of the world's foremost killers, accounting for 16% of all deaths worldwide. IHD is the main cause of heart failure (HF), as it leads to pathological changes in the heart, improper pumping function and eventual death. Therapeutic interventions usually follow a systemic general strategy for all heart failure subtypes due to the lack of a deep understanding of the disease mechanisms. Hence, HF and IHD therapeutics need groundbreaking concepts to guide the development of a new therapeutics class that tackles the disease at a molecular level. The TRAIN-HEART consortium, a Marie Sklodowska-Curie Actions Innovative Training Network (MSCA-ITN) funded by the European Commission, was established with the goal of filling that gap and developing RNA-based cardiovascular therapeutics. Created in the context of the Horizon 2020 research and innovation program, TRAIN-HEART comprises three key work packages (WPs) focusing on the pathogenesis of heart disease (WP1), the therapeutic potential of RNA therapeutics (WP2), and the development of new efficient delivery systems (WP3). Fifteen international early stage researchers (ESRs) from multiple complementary scientific disciplines were recruited to collaborate with a network of PIs from nine academic and eight non-academic partners in various disciplines to fully harness their collective potential for the betterment of HF treatment. This article provides an overview of the benefits of being part of an MSCA-ITN, with its different training and networking opportunities, maximizing ESRs' potential and broadening collaborative research possibilities. Finally, it describes what was like to do a PhD during the COVID-19 pandemic, with all the uncertainty and concern attached to it. Luckily, TRAIN-HEART stood out as a proactive network, finding new initiatives and alternatives to promote scientific and personal development. By bringing together leading academic teams, (biotech) companies, and highly motivated researchers, TRAIN-HEART is expanding scientific horizons and accelerating future development of effective RNA-based therapies to treat IHD.