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https://www.readbyqxmd.com/read/29679324/controlling-fibrin-network-morphology-polymerization-and-degradation-dynamics-in-fibrin-gels-for-promoting-tissue-repair
#1
Erin P Sproul, Riley T Hannan, Ashley C Brown
Fibrin is an integral part of the clotting cascade and is formed by polymerization of the soluble plasma protein fibrinogen. Following stimulation of the coagulation cascade, thrombin activates fibrinogen, which binds to adjacent fibrin(ogen) molecules resulting in the formation of an insoluble fibrin matrix. This fibrin network is the primary protein component in clots and subsequently provides a scaffold for infiltrating cells during tissue repair. Due to its role in hemostasis and tissue repair, fibrin has been used extensively as a tissue sealant...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29669778/factor-viia-induces-anti-inflammatory-signaling-via-epcr-and-par1
#2
Vijay Kondreddy, Jue Wang, Shiva Keshava, Charles T Esmon, L Vijaya Mohan Rao, Usha R Pendurthi
Recent studies show that endothelial cell protein C receptor (EPCR) interacts with diverse ligands, in addition to its known ligands protein C and activated protein C (APC). We showed in earlier studies that procoagulant clotting factor VIIa (FVIIa) binds EPCR and down-regulates EPCR-mediated anticoagulation and induces endothelial barrier protective effect. Here, we investigated the effect of FVIIa interaction with EPCR on endothelial cell inflammation and LPS-induced inflammatory responses in vivo. Treatment of endothelial cells with FVIIa suppressed TNFα- and LPS-induced expression of cellular adhesion molecules and adherence of monocytes to endothelial cells...
April 18, 2018: Blood
https://www.readbyqxmd.com/read/29665821/plasma-proteomic-analysis-reveals-altered-protein-abundances-in-cardiovascular-disease
#3
Vasiliki Lygirou, Agnieszka Latosinska, Manousos Makridakis, William Mullen, Christian Delles, Joost P Schanstra, Jerome Zoidakis, Burkert Pieske, Harald Mischak, Antonia Vlahou
BACKGROUND: Cardiovascular disease (CVD) describes the pathological conditions of the heart and blood vessels. Despite the large number of studies on CVD and its etiology, its key modulators remain largely unknown. To this end, we performed a comprehensive proteomic analysis of blood plasma, with the scope to identify disease-associated changes after placing them in the context of existing knowledge, and generate a well characterized dataset for further use in CVD multi-omics integrative analysis...
April 17, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29664014/rip-kinase-1-dependent-endothelial-necroptosis-underlies-systemic-inflammatory-response-syndrome
#4
Matija Zelic, Justine E Roderick, Joanne A O'Donnell, Jesse Lehman, Sung Eun Lim, Harish P Janardhan, Chinmay M Trivedi, Manolis Pasparakis, Michelle A Kelliher
Receptor interacting protein kinase 1 (RIPK1) has important kinase-dependent and kinase-independent scaffolding functions that activate or prevent apoptosis or necroptosis in a cell context-dependent manner. The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF-induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory "cytokine storm" has long been viewed as detrimental. Here, we demonstrate that cytokine and chemokine levels did not predict survival and, importantly, that kinase-inactive Ripk1D138N/D138N hematopoietic cells afforded little protection from TNF- or TNF/zVAD-induced shock in reconstituted mice...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29522245/thromboelastography-in-wild-florida-manatees-trichechus-manatus-latirostris
#5
Ashley Barratclough, Ruth Francis Floyd, Roger L Reep, Ray L Ball, Bobbi J Conner
BACKGROUND: Thromboelastography (TEG) provides a comprehensive evaluation of blood clot formation. This test can be used to identify abnormalities in coagulation by assessing multiple aspects of the clotting cascade, including the speed of clot initiation and formation, clot strength, and ultimately fibrinolysis. Thromboembolic disease has been hypothesized to play a role in the pathophysiology of cold stress syndrome (CSS), an important cause of mortality in the threatened Florida manatee (Trichechus manatus latirostris)...
March 9, 2018: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/29514041/recombinant-batroxobin-coated-nonwoven-chitosan-as-hemostatic-dressing-for-initial-hemorrhage-control
#6
Gyeung Mi Seon, Mi Hee Lee, Byeong-Ju Kwon, Min Sung Kim, Min-Ah Koo, Young Seomun, Jong-Tak Kim, Tae Hee Kim, Jong-Chul Park
The choice of hemostat is determined by the situation and the degree of hemorrhage. One common hemostat, the nonwoven dressing, is easy to handled and controls severe bleeding on wider wounds. In this study, chitosan-based nonwoven dressings with recombinant batroxobin (rBat) were used as efficacious hemostatic dressing agents. Hemostatic agents need to absorb blood quickly in the early stages of blood coagulation cascade to rapidly and effectively control of excessive hemorrhages. To date, most studies of hemostatic agents focused on a single material and hemostats composed of multiple materials have not been studied sufficiently...
March 4, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29508191/relative-abundance-of-proteins-in-blood-plasma-samples-from-patients-with-chronic-cerebral-ischemia
#7
Anna L Kaysheva, Artur T Kopylov, Elena A Ponomarenko, Olga I Kiseleva, Nadezhda B Teryaeva, Alexander A Potapov, Alexander А Izotov, Sergei G Morozov, Valeria Yu Kudryavtseva, Alexander I Archakov
A comparative protein profile analysis of 17 blood plasma samples from patients with ischemia and 20 samples from healthy volunteers was carried out using ultra-high resolution mass spectrometry. The analysis of measurements was performed using the proteomics search engine OMSSA. Normalized spectrum abundance factor (NSAF) in the biological samples was assessed using SearchGUI. The findings of mass spectrometry analysis of the protein composition of blood plasma samples demonstrate that the depleted samples are quite similar in protein composition and relative abundance of proteins...
March 5, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29503609/it-s-all-about-timing-the-involvement-of-kir4-1-channel-regulation-in-acute-ischemic-stroke-pathology
#8
REVIEW
Meagan Milton, Patrice D Smith
An acute ischemic stroke is characterized by the presence of a blood clot that limits blood flow to the brain resulting in subsequent neuronal loss. Acute stroke threatens neuronal survival, which relies heavily upon proper function of astrocytes. Neurons are more susceptible to cell death when an astrocyte is unable to carry out its normal functions in supporting the neuron in the area affected by the stroke (Rossi et al., 2007; Takano et al., 2009). For example, under normal conditions, astrocytes initially swell in response to changes in extracellular osmotic pressure and then reduce their regulatory volume in response to volume-activated potassium (K+ ) and chloride channels (Vella et al...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29461292/inhalation-injury-in-the-burned-patient
#9
Guillermo Foncerrada, Derek M Culnan, Karel D Capek, Sagrario González-Trejo, Janos Cambiaso-Daniel, Lee C Woodson, David N Herndon, Celeste C Finnerty, Jong O Lee
Inhalation injury causes a heterogeneous cascade of insults that increase morbidity and mortality among the burn population. Despite major advancements in burn care for the past several decades, there remains a significant burden of disease attributable to inhalation injury. For this reason, effort has been devoted to finding new therapeutic approaches to improve outcomes for patients who sustain inhalation injuries.The three major injury classes are the following: supraglottic, subglottic, and systemic. Treatment options for these three subtypes differ based on the pathophysiologic changes that each one elicits...
February 15, 2018: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29455188/laboratory-hemostasis-from-biology-to-the-bench
#10
Giuseppe Lippi, Emmanuel J Favaloro
Physiological hemostasis is an intricate biological system, where procoagulant and anticoagulant forces interplay and preserves blood fluidity when blood vessels are intact, or trigger clot formation to prevent excessive bleeding when blood vessels are injured. The modern model of hemostasis is divided into two principal phases. The first, defined as primary hemostasis, involves the platelet-vessel interplay, whilst the second, defined as secondary hemostasis, mainly involves coagulation factors, damaged cells and platelet surfaces, where the so-called coagulation cascade rapidly develops...
February 19, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29427987/advances-and-evolving-concepts-in-allergic-asthma
#11
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29399530/hemostasis-and-nanotechnology
#12
REVIEW
Patrick Hangge, Jonathan Stone, Hassan Albadawi, Yu Shrike Zhang, Ali Khademhosseini, Rahmi Oklu
Hemorrhage accounts for significant morbidity and mortality. Various techniques have been employed to augment hemostasis from simple tourniquets to self-assembling nanoparticles. A growing understanding of the natural clotting cascade has allowed agents to become more targeted for potential use in different clinical scenarios. This review discusses current and developing hemostatic techniques, including matrix agents, external agents, biologically inspired agents, and synthetic and cell-derived nanoparticles...
December 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/29394041/aminopyrimidine-class-aggregation-inhibitor-effectively-blocks-a%C3%AE-fibrinogen-interaction-and-a%C3%AE-induced-contact-system-activation
#13
Pradeep K Singh, Masanori Kawasaki, Hanna E Berk-Rauch, Goushi Nishida, Takeshi Yamasaki, Michael A Foley, Erin H Norris, Sidney Strickland, Kazuyoshi Aso, Hyung Jin Ahn
Accumulating evidence suggests that fibrinogen, a key protein in the coagulation cascade, plays an important role in circulatory dysfunction in Alzheimer's disease (AD). Previous work has shown that the interaction between fibrinogen and Β-amyloid (AΒ), a hallmark pathological protein in AD, induces plasmin-resistant abnormal blood clots, delays fibrinolysis, increases inflammation, and aggravates cognitive function in mouse models of AD. Since AΒ oligomers have a much stronger affinity for fibrinogen than AΒ monomers, we tested whether amyloid aggregation inhibitors could block the AΒ-fibrinogen interaction and found that some Aβ aggregation inhibitors showed moderate inhibitory efficacy against this interaction...
February 2, 2018: Biochemistry
https://www.readbyqxmd.com/read/29376487/surfing-the-blood-coagulation-cascade-insight-into-the-vital-factor-xa
#14
Nicolas E Nunez-Navarro, Fabian M Santana, Loreto P Parra, Flavia C Zacconi
Factor Xa (FXa) plays a key role in haemostasis, it is a central part of the blood coagulation cascade which catalyzes the production of thrombin and leads to clot formation and wound closure. Therefore, FXa is an attractive target for the development of new anticoagulant agents. In this review, we will first describe the molecular features of this fundamental protein in order to understand its mechanism of action, an essential background for the design of novel inhibitors by means of synthetic organic chemistry or using peptides obtained from recombinant methodologies...
January 25, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29314633/leucocyte-and-platelet-rich-fibrin-a-carrier-of-autologous-multipotent-cells-for-regenerative-medicine
#15
Rosa Di Liddo, Thomas Bertalot, Alessio Borean, Ivan Pirola, Alberto Argentoni, Sandra Schrenk, Carola Cenzi, Stefano Capelli, Maria Teresa Conconi, Pier Paolo Parnigotto
The wound healing is a complex process wherein inflammation, proliferation and regeneration evolve according to a spatio-temporal pattern from the activation of coagulation cascade to the formation of a plug clot including fibrin matrix, blood-borne cells and cytokines/growth factors. Creating environments conducive to tissue repair, the haemoderivatives are commonly proposed for the treatment of hard-to-heal wounds. Here, we explored in vitro the intrinsic regenerative potentialities of a leucocyte- and platelet-rich fibrin product, known as CPL-MB, defining the stemness grade of cells sprouting from the haemoderivative...
March 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29276283/bivalirudin-medication-use-evaluation-and-cost-savings-initiative
#16
Adam C Sieg, Jennifer A Gass
Bivalirudin is a parenteral anticoagulant that elicits its effect through inhibition of both free and clot bound-thrombin. Inhibition of thrombin serves as a unique mechanism for anticoagulation when compared to heparin as thrombin serves as the final common pathway for the intrinsic and extrinsic coagulation cascades. Due to unclear benefit over heparin, concerns regarding reversibility, and most importantly cost its use as a parenteral anticoagulant varies by institution. A recent drug expenditure review within our institution noted a significant increase in the contribution bivalirudin had on the overall drug budget...
September 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/29148431/comparative-efficacy-of-hemorrhage-control-of-a-novel-mesoporous-bioactive-glass-versus-two-commercial-hemostats
#17
Sara Pourshahrestani, Nahrizul Adib Bin Kadri, Ehsan Zeimaran, Nicola Gargiulo, Shani Samuel, Sangeetha Vasudevaraj Naveen, Khairunnisa Hasikin, Tunku Kamarul, Mark R Towler
Mesoporous bioactive glass containing 1% Ga2O3 (1%Ga-MBG) is attractive for hemorrhage control because of its surface chemistry which can promote blood-clotting. The present study compares this proprietary inorganic coagulation accelerator with two commercial hemostats, CeloxTM (CX) and QuikClot Advanced Clotting Sponge PlusTM (ACS+). The results indicate that the number of adherent platelets were higher on the 1%Ga-MBG and CX surfaces than ACS+ whereas a greater contact activation was seen on 1%Ga-MBG and ACS+ surfaces than CX...
November 17, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/29135251/micellar-thrombin-binding-aptamers-reversible-nanoscale-anticoagulants
#18
Alexander Roloff, Andrea S Carlini, Cassandra E Callmann, Nathan C Gianneschi
Aptamers are nucleic acid-based ligands that exhibit promising features including specific and reversible target binding and inhibition. Aptamers can function as anticoagulants if they are directed against enzymes of the coagulation cascade. However, they typically suffer from nucleolytic digestion and fast clearance from the bloodstream. We present thrombin-binding aptamer amphiphiles that self-assemble into nanoscale polymeric micelles with a densely functionalized aptamer-displaying corona. We show that these micellar aptamers retain their native secondary structure in a crowded environment and are stabilized against degradation by nucleases in human serum...
November 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29111325/inhibition-of-tissue-factor-signaling-in-breast-tumour-xenografts-induces-widespread-changes-in-the-microrna-expression-profile
#19
Esterina D'Asti, G Mark Anderson, Janusz Rak
Tissue factor (TF) is a transmembrane receptor for coagulation factor VII/VIIa and is frequently overexpressed by cancer cells. The TF/VIIa complex acts as the main initiator of the clotting cascade in blood and a trigger of intracellular signaling that changes gene expression and the cellular phenotype. However, pathways mediating these changes are still poorly characterized and especially the impact of TF signals on regulatory microRNA (miR) networks in cancer remains unknown. We show that the monoclonal antibody that selectively neutralises the signaling (but not coagulant) function of human TF (CNTO 2559) inhibits progression of MDA-MB-231 breast cancer xenografts in mice and prolongs animal survival...
December 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29053592/platelets-and-multi-organ-failure-in-sepsis
#20
REVIEW
Elisabetta Greco, Enrico Lupia, Ornella Bosco, Barbara Vizio, Giuseppe Montrucchio
Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis...
October 20, 2017: International Journal of Molecular Sciences
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