The Dual Role of Neutrophils in Inflammatory Bowel Diseases

peer reviewedInflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn's disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD

The platelet ATP and ADP receptors.

peer reviewedThis review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination

TEL is a sequence-specific transcriptional repressor.

TEL is a gene frequently involved in specific chromosomal translocations in human leukemia and sarcoma that encodes a member of the ETS family of transcriptional regulators. TEL is unusual among other ETS proteins by its ability to self-associate in vivo, a property that is essential to the oncogenic activation of TEL-derived fusion proteins. We show here that TEL is a sequence-specific transcriptional repressor of ETS-binding site-driven transcription of model and natural promoters

Role of Imaging in Left Atrial Appendage Occlusion

Percutaneous left atrial appendage (LAA) occlusion is now a valid alternative to long-term oral anticoagulation in patients with non-valvular atrial fibrillation at high thrombo-embolism risk, especially for patients who are considered ineligible for anticoagulation. The most frequently used occluders worldwide include the WATCHAMN (Boston Scientific, Natick, MA, USA) and the Amplatzer Cardiac Plug or Amulet (St. Jude Medical/Abbott, St Paul, MN, USA) devices. Multimodality imaging is key in the understanding of 3D aspects of the LAA and surrounding structures anatomy. Imaging is essential for procedural planning, during each step of the procedure and for device surveillance after implantation. Multimodality imaging, including 2D/3D echocardiography, fluoroscopy, and cardiac computed tomography can increase the safety and efficacy of the procedure

Cancer and cardiovascular mortality risk: is the die cast?

peer reviewe

Atherosclerosis, an inflammatory disease.

editorial reviewedChronic inflammation is recognized as a contributing factor to the development, progression and complications of atherosclerosis. The inflammatory nature of atherosclerosis has been proven by the presence of inflammatory cells, cytokines and chemokines at all stages of the disease. There is a widely accepted association between cardiovascular events and serum inflammatory markers, such as CRP, IL-6 and IL-1? produced via the inflammasome pathway. The involvement of inflammatory processes in atherosclerosis and progress in the therapeutic strategy are detailed in the article

Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity.

peer reviewedBased on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the antibacterial activity, supporting the view that the two activities were not necessarily linked