HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-kappaB and cGMP dependent mechanisms

BACKGROUND: Thrombotic diseases are a group of prevalent and life-threatening diseases. Selective inhibition of pathological thrombosis holds the key to treat variety of thrombotic diseases. The pathological thrombosis can be induced by either tissue necrosis and deregulated inflammation. HMGB1, as an important proinflammatory cytokine and a late mediator, also involves on thrombosis disease. However, the underlying mechanisms are not fully understood. METHODS: Immunofluorescence, ELISA assay, Platelet Aggregation, Thromboelastogram (TEG) analyzes. Flow cytometric analysis and Western blot analysis were used to investigated the role of HMGB1 in platelet aggregation and obtained following observations. RESULTS: By doing so, we obtained the following observations: i) Highly purified HMGB1 recombinant protein induces platelet aggregation and secretion in a dose-dependent manner in the presence of serum. ii) Low concentration of extracellular HMGB1 could synergistically promote subthreshold concentration of collagen or thrombin induced platelet aggregation. iii) Extracellular HMGB1 promoted platelet aggregation in a platelet-expressed GPIIb/IIIa-dependent manner. iv) We proposed that extracellular HMGB1 seems to promote the phosphorylation of GPIIb/IIIa and subsequent platelet aggregation via TLR4/NF-kappaB and cGMP pathway. CONCLUSIONS: In this study, we provide evidence for the hypothesis that HMGB1 interact with platelet might play an important role in the haemostasis and thrombotic diseases. Our research might be provide an interesting avenue for the treatment of thrombotic diseases in the future

The Unusual Superconducting State at 49 K in Electron-Doped CaFe2As2 at Ambient

We report the detection of unusual superconductivity up to 49 K in single crystalline CaFe2As2 via electron-doping by partial replacement of Ca by rare-earth. The superconducting transition observed suggests the possible existence of two phases: one starting at ~ 49 K, which has a low critical field ~ 4 Oe, and the other at ~ 21 K, with a much higher critical field > 5 T. Our observations are in strong contrast to previous reports of doping or pressurizing layered compounds AeFe2As2 (or Ae122), where Ae = Ca, Sr or Ba. In Ae122, hole-doping has been previously observed to generate superconductivity with a transition temperature (Tc) only up to 38 K and pressurization has been reported to produce superconductivity with a Tc up to 30 K. The unusual 49 K phase detected will be discussed.Comment: 11 pages, 8 figure