Search results for "Blood"
showing 10 items of 5199 documents
Feedback Regulation of Syk by Protein Kinase C in Human Platelets
2019
The spleen tyrosine kinase (Syk) is essential for immunoreceptor tyrosine-based activation motif (ITAM)-dependent platelet activation, and it is stimulated by Src-family kinase (SFK)-/Syk-mediated phosphorylation of Y352 (interdomain-B) and Y525/526 (kinase domain). Additional sites for Syk phosphorylation and protein interactions are known but remain elusive. Since Syk S297 phosphorylation (interdomain-B) was detected in platelets, we hypothesized that this phosphorylation site regulates Syk activity via protein kinase C (PKC)-and cyclic adenosine monophosphate (cAMP)-dependent pathways. ADP, the GPVI-agonist convulxin, and the GPIb&alpha
Molecular Biology of Atherosclerotic Ischemic Strokes
2020
Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people w…
Tissue factor as a mediator of coagulation and signaling in cancer and chronic inflammation
2017
Thrombosis is frequently diagnosed as a first symptom in tumor patients and the clinical management of hypercoagulability in cancer patients remains challenging due to concomitant changes in risk factors for severe bleeding. It therefore remains a priority to better understand interactions of the hemostatic system with cancer biology. Specifically, further research is needed to elucidate the details and effects of new anticoagulants on extravascular coagulation and the interplay between cancer progression and chronic inflammation. In addition, it will be important to identify subgroups of cancer patients benefiting from specific modulations of the coagulation system without increasing the b…
The Impact of Small Extracellular Vesicles on Lymphoblast Trafficking across the Blood-Cerebrospinal Fluid Barrier In Vitro.
2020
Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on sub…
Screening of herbal extracts for TLR2- and TLR4-dependent anti-inflammatory effects.
2018
Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to dif…
Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity
2016
Background The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown. Methods A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels. Results Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and mul…
Modeling the Hematopoietic Landscape
2019
Some time ago, we proposed a continuum-like view of the lineages open to hematopoietic stem cells (HSCs); each HSC self-renews or chooses from the spectrum of all end-cell options and can then “merely” differentiate. Having selected a cell lineage, an individual HSC may still “step sideways” to an alternative, albeit closely related, fate: HSC and their progeny therefore remain versatile. The hematopoietic cytokines erythropoietin, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor and ligand for the fms-like tyrosine kinase 3 instruct cell lineage. Sub-populations of HSCs express each of the cytokine receptors that …
Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation.
2016
Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhi…
Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients with Nonalcoholic Fatty Liver Disea…
2016
Background The clinical determinants of fibrosis progression in nonalcoholic fatty liver disease (NAFLD) are still under definition. Aim To assess the clinical determinants of fibrosis progression rate (FPR) in NAFLD patients with baseline and follow-up histological evaluation, with a special focus on the impact of pharmacological therapy. Methods In an observational cohort of 118 Italian patients from tertiary referral centers, liver histology was evaluated according to Kleiner. Independent predictors of FPR were selected by a stepwise regression approach. Results Median follow-up was 36 months (IQR 24–77). Twenty-five patients (18%) showed some amelioration, 63 (53%) had stability, 30 (25…
Telomere length and physical performance among older people-The Helsinki Birth Cohort Study.
2019
Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses stre…