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DPP3 deficiency impacts bone quality and sensitizes to metabolic alterations

: The goal of this study was to evaluate whether the dipeptidyl peptidase 3 (DPP3), recently recognized as a key molecule in bone pathophysiology and proposed as a biomarker of bone health status, plays a role in skeletal and systemic alterations induced by common unbalanced nutritional conditions. We focused on nutrient excess, and in particular on excessive intake of calories from fat, which is known to predispose to osteoporosis, among other complications. Based on the known sex difference...

Platelets: much more than bricks in a breached wall

Platelets have various roles in vascular biology and home-ostasis. They are the first actor in primary haemostasis and play important roles in thrombosis pathogenesis, but they are also part of innate immunity, which initiates and accelerate many inflammatory conditions. In some contexts, their immune functions are protective, while in others they contribute to adverse inflammatory outcomes. Platelets express numerous receptors and contain hundreds of secretory molecules that are crucial for ...

Qualification of Hemophilia Treatment Centers to Enable Multi-Center Studies of Gene Expression Signatures in Blood Cells from Pediatric Patients

Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of functionally active coagulation factor VIII (FVIII). Most patients with the severe form of the disease require FVIII replacement therapies, which are often associated with the development of neutralizing antibodies against FVIII. Why some patients develop neutralizing antibodies while others do not is not fully understood. Previously, we could demonstrate that the analysis of FVIII-induced gene expression signatures...

Thrombin Generation Assay as a Laboratory Monitoring Tool during Bypassing Therapy in Patients with Hemophilia and Inhibitors

Hemophilia treatment relies upon replacement of the deficient factor to restore physiological levels in plasma. The development of inhibitors is the main complication of replacement therapy, which renders replacement therapy ineffective and requires the use of alternative hemostatic drugs known as bypassing agents. The hemostatic response to bypassing agents is different from patient to patient and even in the same patient during different bleeding episodes. Up to now, no routine laboratory t...

Platelet-derived sphingosine-1-phosphate and inflammation: from basic mechanisms to clinical implications

Beyond key functions in hemostasis and thrombosis, platelets are recognized as key players of inflammation, an underlying feature of a variety of diseases. In this regard, platelets act as a circulating source of several pro-and anti-inflammatory molecules, which are secreted from their intracellular stores upon activation. Among them, mounting evidence highlights a crucial role of sphingosine-1-phosphate (S1P), a multifunctional sphingoid mediator. S1P-induced pleiotropic effects include tho...

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