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Coagulation cascade

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https://www.readbyqxmd.com/read/28335516/marine-diterpenes-molecular-modeling-of-thrombin-inhibitors-with-potential-biotechnological-application-as-an-antithrombotic
#1
Rebeca Cristina Costa Pereira, André Luiz Lourenço, Luciana Terra, Paula Alvarez Abreu, Valéria Laneuville Teixeira, Helena Carla Castro
Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist...
March 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28321657/novel-hemostatic-agents-based-on-gelatin-microbial-transglutaminase-mix
#2
Fang Lv, Xiaonan Cong, Wenshu Tang, Yiming Han, Yu Tang, Yongrui Liu, Liqiang Su, Mingyao Liu, Mingfei Jin, Zhengfang Yi
Hemostasis is a major challenge in surgical procedures and traumas. Conventional hemostatic methods have limited efficacy and may cause additional tissue damage. In this study, we designed a novel hemostatic agent based on the in situ gel formation of gelatin cross-linked by a novel microbial transglutaminase (mTGase), in which the amino acid sequences differed from commercial mTGases. The new hemostatic agent showed the same biochemical crosslinking chemistry as the final stages of the blood coagulation cascade while using gelatin as a "structural" protein (rather than fibrin) and a calcium-independent mTGase as the crosslinking catalyst (rather than factor XIIIa)...
March 17, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28320452/compared-to-the-amniotic-membrane-wharton-s-jelly-may-be-a-more-suitable-source-of-mesenchymal-stem-cells-for-cardiovascular-tissue-engineering-and-clinical-regeneration
#3
Lei Pu, Mingyao Meng, Jian Wu, Jing Zhang, Zongliu Hou, Hui Gao, Hui Xu, Boyu Liu, Weiwei Tang, Lihong Jiang, Yaxiong Li
BACKGROUND: The success of developing cardiovascular tissue engineering (CTE) grafts greatly needs a readily available cell substitute for endothelial and interstitial cells. Perinatal annexes have been proposed as a valuable source of mesenchymal stem cells (MSCs) for tissue engineering and regenerative medicine. The objective of the present study is to evaluate the potential of human Wharton's jelly MSCs (WJ-MSCs) and amniotic membrane MSCs (AM-MSCs) as a seeding cell in CTE and cardiovascular regenerative medicine...
March 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#4
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28300869/e-selectin-inhibition-with-gmi-1271-decreases-venous-thrombosis-without-profoundly-affecting-tail-vein-bleeding-in-a-mouse-model
#5
Dorian L Culmer, Misha L Dunbar, Angela E Hawley, Suman Sood, Robert E Sigler, Peter K Henke, Thomas W Wakefield, John L Magnani, Daniel D Myers
Selectins, such as E-selectin (CD62E), function in venous thrombosis by binding and activating immune cells to initiate the coagulation cascade. GMI-1271 is a small molecule antagonist that inhibits E-selectin activity. Here we determine whether inhibition of E-selectin is sufficient to decrease acute venous thrombosis and associated inflammatory events in both prophylactic and treatment protocols without significantly affecting haemostasis. Male C57BL/6 mice underwent surgery for experimental thrombosis induction and were harvested at peak thrombus formation in our animal model, two days post induction...
March 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28288507/anticoagulation-in-cirrhosis-a-new-paradigm
#6
Filippo Leonardi, Nicola De Maria, Erica Villa
The liver plays a crucial role in coagulation cascade. Global hemostatic process is profoundly influenced by the presence of liver disease and its complications. Patients with cirrhosis have impaired synthesis of most of the factors involved in coagulation and fibrinolysis process due to a reduced liver function and altered platelet count secondary to portal hypertension. Altered routine tests and thrombocytopenia were considered in the past as associated with increased risk of bleeding. These concepts explain both the routine use of plasma and/or platelets transfusion in patients with liver cirrhosis, especially before invasive procedures, and why these patients were considered "auto-anticoagulated"...
March 14, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28287900/increased-coagulation-and-decreased-fibrinolysis-as-measured-with-overall-hemostatic-potential-are-dependent-on-bmi-and-not-associated-with-pcos
#7
Matej Rakusa, Mojca Jensterle, Mojca Božič-Mijovski, Andrej Janez
BACKGROUND: Overall hemostatic potential (OHP) captures all factors that affect coagulation and fibrinolysis cascade. It has not yet been assessed in polycystic ovary syndrome (PCOS). The aim of the study was to identify the relationship of OHP with a syndrome per se and body mass index (BMI). METHODS: In 90 women with PCOS aged 30.9 ± 8.1 years (50 obese, 13 overweight, and 27 lean) and 21 healthy age-matched controls (11 obese and 10 lean), OHP with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) was determined spectrophotometrically...
March 13, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28284660/itraq-based-quantitative-proteomics-discovering-potential-serum-biomarkers-in-locoweed-poisoned-rabbits
#8
Jifeng Jiao, Shuai Wang, Ruishi Zhang, Zhiyan Ma, Guofeng Du, Xiaolu Chen, Dayong Tao, Jinxiang Zhao
Locoism threatens the sustainable development of animal husbandry in areas around the world with intensified desertification, especially in the western United States, western China, Canada, and Mexico, among other countries. This study was conducted to discover potential serum biomarkers in locoweed-poisoned rabbits and lay a foundation for early diagnosis of locoism. We performed iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS), comparing locoweed-poisoned rabbits and healthy controls...
March 8, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28283738/anti-inflammatory-effect-of-factor-xa-inhibitors-in-japanese-patients-with-atrial-fibrillation
#9
Hiromasa Katoh, Tsuyoshi Nozue, Ichiro Michishita
Activated factor-X (FXa) plays an important role not only in the coagulation cascade, but also in pro-inflammatory responses. However, few data exist regarding the anti-inflammatory effect of FXa inhibitors in clinical practice. The aim of this study was to evaluate the anti-inflammatory and anti-atherosclerotic effects of FXa inhibitors in Japanese patients with non-valvular atrial fibrillation (NVAF). Eighty-three patients with NVAF were treated with FXa inhibitors from March 2013 to March 2015 at our institution...
March 10, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28283674/endometrial-transcriptome-in-recurrent-miscarriage-and-recurrent-implantation-failure
#10
Jin Huang, Hao Qin, Yihua Yang, Xiaoyan Chen, Jiamiao Zhang, Susan Laird, Chi Chiu Wang, Ting Fung Chan, Tin Chiu Li
The endometrium becomes receptive to the embryo only in the mid-luteal phase, but not other stages of the menstrual cycle. Endometrial factors play an important role in implantation. Women with recurrent miscarriage and recurrent implantation failure have both been reported to have altered expression of receptivity markers during the window of implantation. We aimed to compare the gene expression profiles of the endometrium in the window of implantation among women with unexplained recurrent implantation failures (RIF) and unexplained recurrent miscarriages (RM) by RNA sequencing (RNA-Seq)...
March 10, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28282887/new-insights-in-thrombin-inhibition-structure-activity-relationships-by-characterization-of-octadecasaccharides-from-low-molecular-weight-heparin
#11
Pierre A J Mourier, Olivier Y Guichard, Fréderic Herman, Philippe Sizun, Christian Viskov
Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin)...
March 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28282497/andexanet-alfa-for-the-reversal-of-anticoagulant-activity-in-patients-treated-with-direct-and-indirect-factor-xa-inhibitors
#12
Tarek Nafee, Aysha Aslam, Gerald Chi, Seyedmahdi Pahlavani, Dima Nimri, Aravind Reddy Kuchkuntla, Usama Talib, Nathan Michalak, Yazan Daaboul, Serge Korjian, Anthony Gallo, C Michael Gibson
Andexanet alfa is a recombinant factor Xa decoy molecule that inhibits direct and indirect factor Xa inhibitors to allow the normal coagulation process to resume. Its development arises in a space where novel oral anticoagulants are receiving expanded indications yet their use is limited by the lack of an effective reversal agent. Areas covered: This article reviews the biochemical properties, mechanism of action and the preclinical and clinical trials on andexanet alfa. It additionally aims to provide expert commentary and future perspectives on the efficacy, safety and challenges facing andexanet alfa as a universal antidote for direct and indirect factor Xa inhibitors...
March 22, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28278524/management-of-thrombotic-antiphospholipid-syndrome
#13
Cecilia Beatrice Chighizola, Maria Gabriella Raimondo, Pier Luigi Meroni
Persistent serum positivity for antiphospholipid antibodies (aPL) is required to diagnose antiphospholipid syndrome (APS), an autoimmune disease characterized by recurrent vascular thrombosis and/or pregnancy morbidity. The current therapeutic management of patients with thrombotic APS aims at preventing recurrences and long-term complications by attenuating the procoagulant state. There is overall consensus to reserve moderate-intensity anticoagulation to aPL-positive patients with a previous venous thrombosis; the therapeutic options for those with a history of arterial event comprise antiplatelet agents and high-intensity anticoagulation...
March 9, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28276902/comparative-proteomic-exploration-of-whey-proteins-in-human-and-bovine-colostrum-and-mature-milk-using-itraq-coupled-lc-ms-ms
#14
Mei Yang, Xueyan Cao, Rina Wu, Biao Liu, Wenhui Ye, Xiqing Yue, Junrui Wu
Whey, an essential source of dietary nutrients, is widely used in dairy foods for infants. A total of 584 whey proteins in human and bovine colostrum and mature milk were identified and quantified by the isobaric tag for relative and absolute quantification (iTRAQ) proteomic method. The 424 differentially expressed whey proteins were identified and analyzed according to gene ontology (GO) annotation, Kyoto encyclopedia of genes and genomes (KEGG) pathway, and multivariate statistical analysis. Biological processes principally involved biological regulation and response to stimulus...
February 20, 2017: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/28276481/identification-of-berberine-as-a-direct-thrombin-inhibitor-from-traditional-chinese-medicine-through-structural-functional-and-binding-studies
#15
Xing Wang, Yuxin Zhang, Ying Yang, Xia Wu, Hantian Fan, Yanjiang Qiao
Thrombin acts as a key enzyme in the blood coagulation cascade and represents a potential drug target for the treatment of several cardiovascular diseases. The aim of this study was to identify small-molecule direct thrombin inhibitors from herbs used in traditional Chinese medicine (TCM). A pharmacophore model and molecular docking were utilized to virtually screen a library of chemicals contained in compositions of traditional Chinese herbs, and these analyses were followed by in vitro bioassay validation and binding studies...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270519/plasminogen-activator-inhibitor-1-regulates-macrophage-dependent-postoperative-adhesion-by-enhancing-egf-her1-signaling-in-mice
#16
Kumpei Honjo, Shinya Munakata, Yoshihiko Tashiro, Yousef Salama, Hiroshi Shimazu, Salita Eiamboonsert, Douaa Dhahri, Atsuhiko Ichimura, Takashi Dan, Toshio Miyata, Kazuyoshi Takeda, Kazuhiro Sakamoto, Koichi Hattori, Beate Heissig
Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator-mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI-1; Serpine1) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat(-/-) and Serpine1(-/-) In addition, C57BL/6 mice were treated with the novel PAI-1 inhibitor, TM5275...
March 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28267938/applying-the-cell-based-coagulation-model-in-the-management-of-critical-bleeding
#17
K M Ho, W Pavey
The cell-based coagulation model was proposed 15 years ago, yet has not been applied commonly in the management of critical bleeding. Nevertheless, this alternative model may better explain the physiological basis of current coagulation management during critical bleeding. In this article we describe the limitations of the traditional coagulation protein cascade and standard coagulation tests, and explain the potential advantages of applying the cell-based model in current coagulation management strategies...
March 2017: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/28248073/carbon-nanotubes-activate-limulus-amebocyte-lysate-coagulation-by-interface-adsorption
#18
Man Yang, Xin Nie, Jie Meng, Jian Liu, Zhiwei Sun, Haiyan Xu
Limulus amebocyte lysate (LAL) assay is worldwide requested in the assessment of endotoxin contamination for biomaterials. As carbon nanotubes are one major nanomaterial with multiple potentials in biomedical application, here we investigate whether oxidized multiwalled carbon nanotubes (O-MWCNT) interferes the assessment by LAL assays. We showed that the endotoxin free O-MWCNT dispersing in aqueous solutions could activate both the gel-clotting and the end-point chromogenic LAL assay by converting coagulogen into coagulin through interfacial interactions between O-MWCNT and enzymes in the assays...
March 3, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28239169/cardiovascular-disease-in-haemodialysis-role-of-the-intravascular-innate-immune-system
#19
REVIEW
Kristina N Ekdahl, Inga Soveri, Jöns Hilborn, Bengt Fellström, Bo Nilsson
Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface...
February 27, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28236427/procoagulant-extracellular-vesicles-in-amniotic-fluid
#20
Lena Hell, Lukas Wisgrill, Cihan Ay, Andreas Spittler, Michael Schwameis, Bernd Jilma, Ingrid Pabinger, Peter Altevogt, Johannes Thaler
Embolization of amniotic fluid (AF) into the blood circulation leads to disseminated intravascular coagulation (DIC). Procoagulant phosphatidylserine (PS)- and tissue factor (TF)-exposing extracellular vesicles (EVs) might play an important role in AF embolism-induced DIC. It was the aim of the present study to perform analyses of the procoagulant properties of AF with a panel of functional coagulation assays and flow cytometry. We applied a prothrombinase assay (that quantifies PS exposure on EVs), an EV-associated TF activity assay, a fibrin generation assay, a thrombin generation assay, a whole blood clotting model, and flow cytometry in AF and control plasma...
February 4, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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