Publications by authors named "Ilaria de Simone"
Background: Patients with cirrhosis develop multiple hemostatic alterations. Although fibrinolysis is also affected by liver disease, studies have produced conflicting results, highlighting the need for a reliable fibrinolysis assay. Assessing the kinetics of plasmin generation (PG) is a new method to study the fibrinolytic state of cirrhosis patients.
View Article and Find Full Text PDFBackground: Blood clot formation, triggered by vascular injury, is crucial for hemostasis and thrombosis. Blood clots are composed mainly of fibrin fibers, platelets, and red blood cells (RBCs). Recent studies show that clot surfaces also develop a fibrin film, which provides protection against wound infection and retains components such as RBCs within the clot.
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- Hypodysfibrinogenemia is a rare genetic disorder affecting fibrinogen, leading to both bleeding and thrombotic complications, and requires careful patient management beyond standard tests.
- A family case study identified a 60-year-old woman and her two daughters with the disorder, all of whom shared a specific genetic mutation causing abnormal fibrinogen function.
- Advanced testing methods showed that the daughters had a hypercoagulable state, indicating increased blood clotting risk, which was not evident in routine coagulation tests, highlighting the need for specialized evaluation in such patients.
Article Synopsis
- Agonist-induced platelet activation leads to a change in the integrin αIIbβ3, essential for fibrinogen binding and subsequent platelet aggregation, with the potential for reversibility under certain conditions.
- The study investigates how platelet signaling via collagen receptor GPVI and protease-activated receptors (PAR) affects the time-dependent activation of αIIbβ3.
- Results indicate that specific inhibitors of protein kinase C and other signaling pathways can modulate integrin activation and P-selectin expression, impacting how platelets aggregate and shape during activation.
Proteoglycans form a heterogeneous family of proteins with covalently bound sulfated glycosaminoglycans. The extracellular matrix proteoglycan perlecan has been proposed to bind to the platelet- and megakaryocyte-specific receptor G6bB, co-regulating platelet glycoprotein VI (GPVI) signaling. The derived non-sulfate proteoglycan endorepellin was previously shown to enhance platelet adhesion via the collagen receptor, integrin α2β1.
View Article and Find Full Text PDFLiquid biopsy (LB) for prostate cancer (PCa) detection could represent an alternative to biopsy. Seminal fluid (SF) is a source of PCa-specific biomarkers, as 40% of ejaculate derives from the prostate. We tested the feasibility of an SF-based LB by evaluating the yield of semen self-sampling in a cohort of >750 patients with clinically localized PCa.
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- Platelet function varies widely among individuals, and current tests typically measure only the end-point activation levels without considering how quickly platelets activate, which might overlook important details about their reactivity.
- A new real-time flow cytometry method was developed to assess the speed of platelet activation, identifying distinct rates of response to different activating agents that do not necessarily relate to maximum activation levels.
- Findings show that faster platelet responses correlate with larger and denser blood clots in arterial conditions, suggesting that the activation rate should be considered in future antiplatelet therapies to enhance effectiveness while minimizing bleeding risk.
The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney.
View Article and Find Full Text PDFBackground: Especially in disease conditions, platelets can encounter activating agents in circulation.
Objectives: To investigate the extent to which previously activated platelets can be reactivated and whether in-and reactivation applies to different aspects of platelet activation and thrombus formation.
Methods: Short-and long-term effects of glycoprotein VI (GPVI) and G protein-coupled receptor (GPCR) stimulation on platelet activation and aggregation potential were compared via flow cytometry and plate-based aggregation.
Article Synopsis
- The study looked at how a specific genetic change (T2:ERG) could be linked to imaging scores used to check for prostate cancer (PCa).
- It involved 158 men who were suspected of having PCa and who underwent biopsies to confirm the diagnosis.
- The results showed that a majority of the patients had PCa, and combining the genetic test with imaging scores improved the ability to accurately diagnose clinically significant prostate cancer.
Article Synopsis
- Platelet activation and coagulation are closely linked, where activated platelets release factors that promote coagulation, and the coagulation cascade produces signals that activate platelets.
- The study explored the effects of activated coagulation factors FXIIIa and activated protein C (APC) on platelet responses, revealing that these factors could enhance platelet activity and spread under certain conditions.
- It was found that the activation of platelets by FXIIIa was dependent on specific receptors (GPVI and PAR1), indicating that there are multiple pathways through which coagulation factors beyond thrombin can influence platelet function.
Article Synopsis
- Platelets exhibit variability in how they respond to different activating substances, influenced by bioactive molecules that can either enhance or suppress their activation.
- In patients with ischaemic heart disease, increased levels of priming substances like adenosine and succinate, along with hypercoagulability, are common phenomena.
- An advanced flow cytometric analysis identified five distinct platelet populations based on their activation state, revealing that the type of agonist used significantly affects platelet behavior, with adenosine reducing fully activated platelets while succinate increases them.
Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome-wide transcriptomes (57.
View Article and Find Full Text PDFCirculating cell-free DNA (ccfDNA), released from normal and cancerous cells, is a promising biomarker for cancer detection as in neoplastic patients it is enriched in tumor-derived DNA (ctDNA). ctDNA contains cancer-specific mutations and epigenetic modifications, which can have diagnostic/prognostic value. However, in primary tumors, and in particular in localized prostate cancer (PCa), the fraction of ctDNA is very low and conventional strategies to study ccfDNA are unsuccessful.
View Article and Find Full Text PDFAlthough an impact of processing on immunogenicity of food proteins has clearly been demonstrated, the underlying mechanisms are still unclear. We applied 3 different processing methods: wet heating (60 °C) and low- or high-temperature (50 °C or 130 °C, respectively) dry-heating in absence or presence of reducing sugars, to β-lactoglobulin (BLG), lysozyme and thyroglobulin, which represent dietary proteins with different pI or molecular weight. Uptake of the soluble fraction of the samples was tested in two types of, genetically homogeneous, antigen-presenting cells (macrophages and dendritic cells derived from THP-1 monocytes).
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- - Platelets play a crucial role in thrombosis and hemostasis, particularly in conditions like atherosclerosis-associated arterial thrombosis, where megakaryocytes in the bone marrow are considered the primary source of platelets.
- - Recent findings show that both inherited and somatic mutations in hematopoietic cells can lead to abnormal platelet production and function, resulting in complications such as essential thrombocytosis and thrombo-hemorrhagic issues.
- - The concept of clonal hematopoiesis of indeterminate potential (CHIP) highlights the importance of these mutations and their potential impact on cardiovascular disease risk, suggesting that understanding these genetic factors could improve personalized assessments for thrombotic conditions and malignancies.
Background: Guidelines indicate that a low-protein diet (LPD) delays dialysis in severe chronic kidney disease (CKD). We assessed the value of these guidelines by performing a retrospective analysis in our renal clinical practice.
Methods: The analysis was performed from 1 January 2010 to 31 March 2018 in 299 CKD Stage 4 patients followed for 70 months in collaboration with a skilled nutritionist.
Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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- Platelet interactions with collagens via von Willebrand factor trigger thrombus formation under shear stress, utilizing the GPVI receptor and integrins for signaling.
- The study investigated how various collagen peptides and types I and III collagens affected platelet activity, particularly focusing on the role of the protein tyrosine kinase Syk in this process.
- Results showed that Syk inhibition reduced platelet activation and aggregation irrespective of whether collagens contained the GPVI-activating sequence, highlighting Syk's crucial role in platelet activation during thrombus formation on collagen.
Article Synopsis
- IgA nephropathy (IgAN) shows a wide range of clinical outcomes, with baseline proteinuria being a key risk factor for progression; however, time-average proteinuria (TAp) during follow-up is identified as a stronger indicator of kidney health and treatment response.
- *In a study analyzing 325 IgAN patients from 1989 to 2005, findings reveal that lower TAp correlates with improved renal survival, with a notable 16.6% experiencing significant kidney function decline.
- *Key factors influencing lower TAp and better kidney outcomes include female gender, use of corticosteroids, lower initial protein levels, and blood pressure management, suggesting that a 6-month corticosteroid treatment is effective at improving kidney function
Peritoneal dialysis (PD) has a prevalence in Italy that does not exceed 10% of patients in substitution treatment. Among the barriers, which hinder access to DP, the lack of patient autonomy or family support has great importance. In 2012 in Lombardy, the lack of support has prevented 155 new patients to use DP and has forced 17 to stop it.
View Article and Find Full Text PDFBackground: Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function.
Objective: To evaluate the effect of glargine on the clinical course in CF patients with early glucose derangements.
Methods: CF population was screened for glucose tolerance.
Article Synopsis
- - The study investigates how diabetes influences lung health and nutrition in patients with cystic fibrosis (CF), focusing on early glucose issues.
- - Researchers compared the results of an oral glucose tolerance test (OGTT) with continuous glucose monitoring (CGMS) in 32 CF patients aged 5-20 years who had intermediate glucose levels.
- - Findings showed that OGTT and CGMS results matched in only 43.7% of patients, highlighting that using OGTT to screen for glucose problems in CF may be beneficial, and CGMS could help track these early glucose issues better in some patients.