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https://www.readbyqxmd.com/read/29777136/functional-proteomic-profiling-of-secreted-serine-proteases-in-health-and-inflammatory-bowel-disease
#1
Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D Hollenberg, Nathalie Vergnolle, Céline Deraison
While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777060/protease-activated-receptor-1-inhibits-cholesterol-efflux-and-promotes-atherogenesis-via-cullin-3-mediated-degradation-of-the-abca1-transporter
#2
Somasundaram Raghavan, Nikhlesh K Singh, Arul M Mani, Gadiparthi N Rao
Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin-Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3-mediated ubiquitination and degradation of ATP-binding cassette subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29775720/diagnosing-human-blood-clotting-deficiency
#3
REVIEW
Chong Cheen Ong, Subash C B Gopinath, Leong Wei Xian Rebecca, Veeradasan Perumal, Thangavel Lakshmipriya, Mohamed Shuaib Mohamed Saheed
There are different clotting factors present in blood, carries the clotting cascade and excessive bleeding may cause a deficiency in the clotting. Diagnosis of deficiency in clotting reduces the potential fatality. For enabling a sensor to detect the clotting factors, suitable probes such as antibody and aptamer have been used to capture the clotting factors on the sensing surface. Two major clotting factors were widely studied in detail for the diagnosis of clotting deficiency, which includes factor IX and thrombin...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775297/factor-xia-inhibitors-as-new-anticoagulants
#4
Mimi L Quan, Donald J P Pinto, Joanne M Smallheer, William R Ewing, Karen A Rossi, Joseph M Luettgen, Dietmar A Seiffert, Ruth R Wexler
With the introduction of thrombin and factor Xa inhibitors to the oral anticoagulant market, significant improvements in both efficacy and safety have been achieved. Early clinical and preclinical data suggest that inhibitors of factor XIa can provide a still safer alternative, with expanded efficacy for arterial indications. This Perspective provides an overview of target rationale and details of the discovery and development of inhibitors of factor XIa as next generation antithrombotic agents.
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29774166/hemostatic-state-augmented-with-platelet-indices-among-sudanese-diabetic-septic-foot
#5
Bashir Abdrhman Bashir, Mohamed Salih Ali
Background: Diabetes mellitus is a very rampant metabolic disorder, particularly type II. It has many complications such as the septic foot. Diabetic septic foot (DSF) patients are at high risk for coagulation abnormalities as well as surgical hazards. Owing to the potential sequelae of coagulation and vascular abnormalities, this work aimed at studying the hemostatic state and platelet indices in diabetes type II patients with septic foot. Methods: A case-control study was conducted during the period from July to September 2017 at Dr...
2018: BMC Hematology
https://www.readbyqxmd.com/read/29772345/autologous-liquid-platelet-rich-fibrin-a-novel-drug-delivery-system
#6
REVIEW
Richard J Miron, Yufeng Zhang
There is currently widespread interest within the biomaterial field to locally deliver biomolecules for bone and cartilage regeneration. Substantial work to date has focused on the potential role of these biomolecules during the healing process, and the carrier system utilized is a key factor in their effectiveness. Platelet rich fibrin (PRF) is a naturally derived fibrin scaffold that is easily obtained from peripheral blood following centrifugation. Slower centrifugation speeds have led to the commercialization of a liquid formulation (liquid-PRF) resulting in an upper plasma layer composed of liquid fibrinogen/thrombin prior to clot formation that remains in its liquid phase for approximately 15 minutes until injected into bodily tissues...
May 14, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29772078/evaluating-blood-clot-progression-using-magnetic-particle-spectroscopy
#7
Hafsa Khurshid, Yipeng Shi, Brent L Berwin, John B Weaver
PURPOSE: To evaluate the thrombus maturity non-invasively providing the promise of much earlier and more accurate diagnosis of diseases ranging from stroke to myocardial infarction to deep vein thrombosis. METHODS: Magnetic spectroscopy of nanoparticle Brownian rotation (MSB), a form of magnetic particle spectroscopy sensitive to Brownian rotation of magnetic nanoparticles, was used for the detection and characterization of blood clots. The nanoparticles' relaxation time was quantified by scaling the MSB spectra in frequency to match the spectra from nanoparticles in a reference state...
May 17, 2018: Medical Physics
https://www.readbyqxmd.com/read/29769125/observational-study-of-coagulation-activation-in-early-breast-cancer-development-of-a-prognostic-model-based-on-data-from-the-real-world-setting
#8
Chiara Mandoj, Laura Pizzuti, Domenico Sergi, Isabella Sperduti, Marco Mazzotta, Luigi Di Lauro, Antonella Amodio, Silvia Carpano, Anna Di Benedetto, Claudio Botti, Francesca Ferranti, Anna Antenucci, Maria Gabriella D'Alessandro, Paolo Marchetti, Silverio Tomao, Giuseppe Sanguineti, Antonio Giordano, Marcello Maugeri-Saccà, Gennaro Ciliberto, Laura Conti, Patrizia Vici, Maddalena Barba
BACKGROUND: Cancer and coagulation activation are tightly related. The extent to which factors related to both these pathologic conditions concur to patient prognosis intensely animates the inherent research areas. The study herein presented aimed to the development of a tool for the assessment and stratification of risk of death and disease recurrence in early breast cancer. METHODS: Between 2008 and 2010, two hundreds thirty-five (N: 235) patients diagnosed with stage I-IIA breast cancer were included...
May 16, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29768939/higher-preoperative-plasma-thrombin-potential-in-patients-undergoing-surgery-for-aortic-stenosis-compared-to-surgery-for-stable-coronary-artery-disease
#9
Axel Dimberg, Ulrica Alström, Elisabeth Ståhle, Christina Christersson
Aortic stenosis (AS) and coronary artery disease (CAD) influence the coagulation system, potentially affecting hemostasis during cardiac surgery. Our aim was to evaluate 2 preoperative global hemostasis assays, plasma thrombin potential and thromboelastometry, in patients with severe aortic valve stenosis compared to patients with CAD. A secondary aim was to test whether the assays were associated with postoperative bleeding. Calibrated automated thrombogram (CAT) in platelet-poor plasma and rotational thromboelastometry (ROTEM) in whole blood were analyzed in patients scheduled for elective surgery due to severe AS (n = 103) and stable CAD (n = 68)...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29768734/in-vitro-efficacy-of-pro-and-anticoagulant-strategies-in-compensated-and-acutely-ill-patients-with-cirrhosis
#10
Ton Lisman, Simone Kleiss, Vishal C Patel, Caleb Fisher, Jelle Adelmeijer, Sarah Bos, Arjuna Singanayagam, Sidsel Hyldgaard Stoy, Debbie L Shawcross, William Bernal
BACKGROUND & AIMS: A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. METHODS: We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10)...
May 16, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29765077/homotypic-endothelial-nanotubes-induced-by-wheat-germ-agglutinin-and-thrombin
#11
Lucia Pedicini, Katarina T Miteva, Verity Hawley, Hannah J Gaunt, Hollie L Appleby, Richard M Cubbon, Katarzyna Marszalek, Mark T Kearney, David J Beech, Lynn McKeown
Endothelial barrier formation is maintained by intercellular communication through junctional proteins. The mechanisms involved in maintaining endothelial communication subsequent to barrier disruption remain unclear. It is known that low numbers of endothelial cells can be interconnected by homotypic actin-driven tunneling nanotubes (TNTs) which could be important for intercellular transfer of information in vascular physiology. Here we sought insight into the triggers for TNT formation. Wheat germ agglutinin, a C-type lectin and known label for TNTs, unexpectedly caused striking induction of TNTs...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29761851/endocytosed-factor-v-is-trafficked-to-cd42b-proplatelet-extensions-during-differentiation-of-human-umbilical-cord-blood-derived-megakaryocytes
#12
Jacqueline M Gertz, Kelley C McLean, Beth A Bouchard
Plasma- and platelet-derived factor Va are essential for thrombin generation catalyzed by the prothrombinase complex; however, several observations demonstrate that the platelet-derived cofactor, which is formed following megakaryocyte endocytosis and modification of the plasma procofactor, factor V, is more hemostatically relevant. Factor V endocytosis, as a function of megakaryocyte differentiation and proplatelet formation, was assessed by flow cytometry and microscopy in CD34+ hematopoietic progenitor cells isolated from human umbilical cord blood and cultured for 12 days in the presence of cytokines to induce ex vivo differentiation into megakaryocytes...
May 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29761540/apixaban-decreases-brain-thrombin-activity-in-a-male-mouse-model-of-acute-ischemic-stroke
#13
Doron Bushi, Joab Chapman, Anton Wohl, Efrat Shavit Stein, Ekaterina Feingold, David Tanne
Factor Xa (FXa) plays a critical role in the coagulation cascade by generation of thrombin. During focal ischemia thrombin levels increase in the brain tissue and cause neural damage. This study examined the hypothesis that administration of the FXa inhibitor, apixaban, following focal ischemic stroke may have therapeutic potential by decreasing brain thrombin activity and infarct volume. Male mice were divided into a treated groups that received different doses of apixaban (2, 20, 100 mg/kg administered I...
May 14, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29761522/thrombotic-characteristics-of-extracellular-vesicles-derived-from-prostate-cancer-cells
#14
Hassan A Al Saleh, Sandor Haas-Neill, Ali Al-Hashimi, Anil Kapoor, Bobby Shayegan, Richard C Austin, Khalid Al-Nedawi
BACKGROUND: Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor-1 PAI-1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI-1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells...
May 15, 2018: Prostate
https://www.readbyqxmd.com/read/29759183/evaluation-of-thrombin-inhibitory-activity-of-catechins-by-online-capillary-electrophoresis-based-immobilized-enzyme-microreactor-and-molecular-docking
#15
Qiao-Qiao Li, Feng-Qing Yang, Yin-Zhen Wang, Zhao-Yu Wu, Zhi-Ning Xia, Hua Chen
An online capillary electrophoresis (CE)-based thrombin (THR) immobilized enzyme microreactor (IMER) method was established to screen THR inhibitors in this study. S-2366 was used as chromogenic substrate for determination of THR activity and other kinetic constants. After continuously run for 50 times, the prepared IMER could still remain 89% of the initial immobilized enzyme activity. The Michaelis-Menten constant (Km ) of immobilized THR was measured as 0.514 mmol/L and the half-maximal inhibitory concentration (IC50 ) and inhibition constant (Ki ) of argatroban on THR were determined as 78...
August 1, 2018: Talanta
https://www.readbyqxmd.com/read/29758017/the-effects-of-dabigatran-and-rivaroxaban-on-markers-of-polymorphonuclear-leukocyte-activation
#16
Guy A Richards, Annette Theron, Gregory Tintinger, Ronald Anderson
Dabigatran is an oral direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor. Dabigatran has been implicated in the etiology of acute coronary syndromes and as these occur following inflammatory changes in the endothelium, we investigated the inflammatory potential of these agents in vitro. In order to do so, polymorphonuclear leukocytes (PMNL) were isolated from heparinized venous blood from non-smoking, healthy adults and exposed to dabigatran or rivaroxaban (0.5⁻10 µM). Generation of reactive oxygen species (ROS), elastase release, cytosolic Ca2+ fluxes, neutrophil extracellular trap (NET) formation and cell viability were measured using chemiluminescence, spectrophotometric and flow cytometric procedures respectively...
May 14, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29757761/aspirin-resistance-cardiovascular-risk-game-changer
#17
Ahmed S Yassin, Hossam Abubakar, Tushar Mishra, Ahmed Subahi, Melanie Hartman, Abdelrahman Ahmed, Walid Ibrahim, Manmohan Singh, Mohit Pahuja
BACKGROUND: Aspirin (ASA) is the most used medication on the globe. ASA is a primary pillar of the secondary prevention of cardiovascular atherothromboembolic events. However, a fraction of the population does not respond to ASA as expected in a unique phenomenon called ASA resistance. Multiple mechanisms were described and studied in the literature to explain this phenomenon. AREA OF UNCERTAINTY: ASA resistance is an interesting phenomenon that is worth studying and reviewing...
May 3, 2018: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29751949/platelet-storage-lesions-what-more-do-we-know-now
#18
REVIEW
Monica Suet Ying Ng, John-Paul Tung, John Francis Fraser
Platelet concentrate (PC) transfusions are a lifesaving adjunct to control and prevent bleeding in cancer, hematologic, surgical, and trauma patients. Platelet concentrate availability and safety are limited by the development of platelet storage lesions (PSLs) and risk of bacterial contamination. Platelet storage lesions are a series of biochemical, structural, and functional changes that occur from blood collection to transfusion. Understanding of PSLs is key for devising interventions that prolong PC shelf life to improve PC access and wastage...
April 17, 2018: Transfusion Medicine Reviews
https://www.readbyqxmd.com/read/29750159/thrombin-assessment-on-nanostructured-label-free-aptamer-based-sensors-a-mapping-investigation-via-surface-enhanced-raman-spectroscopy
#19
Elisa Scatena, Sara Pascale, Cristina Cairone, Filippo Fabbri, Costantino Del Gaudio
Aptamers, synthetic single-stranded DNA or RNA molecules, can be regarded as a valuable improvement to develop novel ad hoc sensors to diagnose several clinical pathologies. Their intrinsic potential is related to the high specificity and sensitivity to the selected target biomarkers, being capable of detecting very low concentrations and thus allowing an early diagnosis of a possible disease. This kind of probe can be usefully integrated into a number of different devices in order to provide a reliable acquisition of the analyte and properly elaborate the related signal...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29748725/non-enzymolytic-adenosine-barcode-mediated-dual-signal-amplification-strategy-for-ultrasensitive-protein-detection-using-lc-ms-ms
#20
Wen Yang, Tengfei Li, Chang Shu, Shunli Ji, Lei Wang, Yan Wang, Duo Li, Michael Mtalimanja, Luning Sun, Li Ding
A method is described for the determination of proteins with LC-MS/MS enabled by a small molecule (adenosine) barcode and based on a double-recognition sandwich structure. The coagulation protein thrombin was chosen as the model analyte. Magnetic nanoparticles were functionalized with aptamer29 (MNP/apt29) and used to capture thrombin from the samples. MNP/apt29 forms a sandwich with functionalized gold nanoparticles modified with (a) aptamer15 acting as thrombin-recognizing element and (b) a large number of adenosine as mass barcodes...
May 10, 2018: Mikrochimica Acta
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