Toxicon : official journal of the International Society on Toxinology 20080912 7
Many snake venoms contain procoagulant toxins that activate the coagulation cascade and cause venom-induced consumptive coagulopathy (VICC). We developed a semi-mechanistic model of the clotting cascade in order to explore the effects of the procoagulant toxin from taipan venom on this system as well as the effects of antivenom. Simulations of the time course in the change of clotting factors were compared to data collected from taipan envenomed patients. The model accurately predicted the obser ...[more]
Project description:Mesenchymal stem cells (MSC) have emerged as potent therapeutic tool for a number of pathologies, including immune ones. However, unwelcome effects of MSC on the blood coagulation were revealed in some cases, which require more in-depth analysis. In this study, we explored the trombotic properties of human MSC from umbilical cord. We revealed strong procoagulant effects of umbilical cord MSC toward human and rat whole blood and platelets-free plasma using rotational thromboelastometry and thrombodynamics tests. The similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EV). In order to suggest approaches to avoid unwanted effects we studied the impact of heparin supplement on MSC/EV procoagulation properties. We found that therapeutic doses of unfractionated heparin injected in the patient's blood (administered in vivo) did not abrogate the procoagulant properties of MSC. Mass-spectrometry analysis of proteins of MSC and EV involved in coagulation-associated pathways was used to evaluate mechanisms of protrombotic effects.
Project description:Simulation results using a stochastic approach to Hockin et al. (2002) mathematical model of the blood coagulation cascade that had been previously simulated using a deterministic method.
Project description:Mathematical model of the blood coagulation cascade with new kinetic rates to simulate acidosis. Extended Hockin2002 model. Reused Mitrophanov2011 model with new parameters k: 5, 6, 7, 10, 15, 16, 17, 22, 26, 31, 32, 43 and 44.
Project description:Mathematical model of the blood coagulation cascade. Extended Hockin model with contributions from Kim2007, Naski1991, Schneider2004, Horrevoets1996, Brummel-Ziedins2012, Mitrophanov2012, Danforth2009 and Hekman1988. Model incorporates more fibrin associated species such as fibrin I and II monomers and fibrinopeptide A and B as well as factor V fragments.
Project description:Blood coagulation mathematical model derived from Chatterjee et al. (2010) and Hockin et al. (2002). Included various inhibitors: TFPI, ATIII, generic kallikrein inhibitor, C1-inhibitor, alpha1-antitrypsin and alpha2-antiplasmin.
Project description:Diabetes is a multifactorial disorder and epigenetics changes are increasingly appreciated to influence the development of diabetic complications. Chromatin remodeling and histone acetylation are implicated in activation of the inflammatory response. Recently, histone deacetylase (HDAC) inhibitors (HDACi) have proved to reduce the severity of inflammatory diseases. We have previously shown that chromatin alterations regulated by HDACi in HepG2 cells stimulated by hyperglycemia reduced hepatic glucose production. In this study, we examined gene expression patterns using next generation sequencing. We show the pharmacological HDAC inhibitor VPA attenuates hyperglycemia induced gene expression, highlighting the relevance of complement and coagulation cascade. These findings reveal a novel mechanism of VPA protection against hyperglycemia induced hepatic gene expression changes, which might improve the therapeutic approaches for diabetes. Overall design: RNA-seq was performed to understand gene expression changes in HepG2 cells in response to hyperglycemia and valproic acid. Analyses were performed in triplicate.
Project description:This study was conducted to (1) find deregulation of certain pathways in SLE at multi-omics levels; (2) evaluate the associations among blood coagulation, complement activation, inflammatory responses and SLE disease severity; (3) develop biomarkers to facilitate better the assessment of the likelihood of lupus activity.
Project description:Mathematical model of the blood coagulation cascade including meizothrombin, protein C, thrombomodulin, factor VIIIa fragments, partially proteolyzed factor Va species and inactive factor Va fragments.