Publications

Multiple sclerosis observed in the black population living in Martinique (M group) is characterized by frequent and severe visual problems. The visual phenotype of the FM group is quite similar to the visual phenotype of Caucasians. More than ethnic and genetic factors, the tropical area of acquisition should have an influence on the visual phenotype. For unknown reasons, the optical problems appear severe when multiple sclerosis is acquired in a low endemic area.

Abstract Over the past 2 decades, there has been a significant increase in the utilization of long-term mechanical circulatory support (MCS) for the treatment of cardiac failure. Left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed in parallel to serve as bridge-to-transplant and destination therapy solutions. Despite the distinct hemodynamic characteristics introduced by LVADs and TAHs, a comparative evaluation of these devices regarding potential complications in supported patients, has not been undertaken. Such a study could provide valuable insights into the complications associated with these devices. Although MCS has shown substantial clinical benefits, significant complications related to hemocompatibility persist, including thrombosis, recurrent bleeding, and cerebrovascular accidents. This review focuses on the current understanding of hemostasis, specifically thrombotic and bleeding complications, and explores the influence of different shear stress regimens in long-term MCS. Furthermore, the role of endothelial cells in protecting against hemocompatibility-related complications of MCS is discussed. We also compared the diverse mechanisms contributing to the occurrence of hemocompatibility-related complications in currently used LVADs and TAHs. By applying the existing knowledge, we present, for the first time, a comprehensive comparison between long-term MCS options.

The emergence of immunotherapies has revolutionized cancer treatment by leveraging the immune system to target malignancies, offering new hope where traditional therapies often fall short. Within this context, hyperthermia (HT) has re-emerged as a promising adjunctive treatment, capable of enhancing the effectiveness of radiotherapy, chemotherapy, and immunotherapy. HT influences both the innate and adaptive immune systems, enhancing the activity of immune cells such as neutrophils, NK cells, and dendritic cells, while also modulating the tumor microenvironment (TME) to promote immunogenic cell death (ICD) and reduce immunosuppressive conditions. These effects contribute to the transformation of immunologically “cold” tumors into “hot” tumors, making them more susceptible to immune-mediated destruction. Furthermore, HT can amplify the efficacy of immune checkpoint inhibitors (ICIs) by improving immune cell infiltration, inducing damage-associated molecular pattern (DAMP) release, and enhancing antigen presentation. Preclinical and clinical studies support the combination of HT with ICIs, demonstrating improved outcomes in otherwise resistant tumors. However, the full therapeutic potential of the different technologies allowing to apply HT remains to be fully understood, and further research is needed to optimize treatment protocols, explore the differential impacts of local versus whole-body hyperthermia, and identify biomarkers for patient stratification. This review underscores the multifaceted role of HT in immunity and its potential to significantly enhance the efficacy of immunotherapy.

Therapeutic neovascularization represents an alternative treatment modality for patients with advanced ischemic coronary disease or critical limb ischemia (CLI). Upregulation of HIF-1α, through specific PHDs inhibition, can be thought of as a master switch that coordinates the expression of a wide repertoire of genes involved in regulating vascular growth and remodeling. The aim of this study was to unravel the efficiency of specific prolyl-hydroxylase domain protein (PHDs) silencing in both cell and non cell-based therapeutic strategies in CLI. We first showed that PHD2 and PHD3 mRNA levels were up-regulated whereas that of HIF-1α were down-regulated in mononuclear circulating cells and in ischemic legs of diabetic and non diabetic patients with CLI. We then used short hairpin RNAs (shRNAs) to downregulate murine PHD1, PHD2 or PHD3 levels and analyzed their efficiency as a therapeutic strategy in diabetic mice with hindlimb ischemia. PHDs silencing increased post-ischemic neovascularization. This increase was associated with an up-regulation of two key pro-angiogenic factors, VEGF-A and endothelial NOS and with that of pro-arteriogenic factors including fractalkine, MCP-1, and SDF-1 leading to activation of postischemic immunoinflammatory response. In addition, concomitant silencing of PHD2 and HIF-1α abrogated the shPHD2-related effects, demonstrating that activation of HIF-1α signaling mediated the pro-angiogenic and pro-arteriogenic effects of shPHD2. Finally, we assessed the putative beneficial effects of PHDs silencing on human endothelial progenitor cells (hEPC) or bone-marrow derived mesenchymal stem cells (hMSC)-based therapies. Cells were transfected with siRNA directed against PHDs and injected in Nude mice with hind-limb ischemia. We showed that PHDs silencing enhanced human cells therapeutic effect in the ischemic leg of Nude mice compared to animals receiving untreated cells. In conclusion, our study reveals, for the first time, that silencing of PHDs by the transient and local upregulation of endogenous HIF-1α improves therapeutic angiogenesis. This study also paves the way for future strategy based on administration of siRNAs directed against PHDs to enhance the efficiency of cell-based strategy.

ABSTRACT Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We used multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and a case-control study of patients followed up after ending anticoagulant treatment for a first VTE. With replication in 5 independent studies, together totalling 1137 patients and 1272 controls, we identify Complement Factor H Related Protein (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. Using GWAS analysis of 2967 individuals we identified a genome-wide significant pQTL signal on chr1q31.3 associated with CFHR5 levels. We showed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activation in vitro . Thrombotic complications are a frequent feature of COVID-19; in hospitalised patients we found CFHR5 levels at baseline were associated with short-time prognosis of disease severity, defined as maximum level of respiratory support needed during hospital stay. Our results indicate a clinically important role for regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.