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https://www.readbyqxmd.com/read/29023416/neuro-coagulopathy-blood-coagulation-factors-in-central-nervous-system-diseases
#1
REVIEW
Ciro De Luca, Assunta Virtuoso, Nicola Maggio, Michele Papa
Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28993062/chronic-spontaneous-urticaria-and-the-extrinsic-coagulation-system
#2
REVIEW
Yuhki Yanase, Shunsuke Takahagi, Michihiro Hide
Chronic spontaneous urticaria (CSU) is a common skin disorder characterized by daily or almost daily recurring skin edema and flare with itch. Recently, the activation of the blood coagulation cascade has been suggested to be involved in CSU, but the trigger of the coagulation cascade remains unclear. In this article, we review recent understanding of the relationship between the pathogenesis of CSU and extrinsic coagulation reactions. In CSU, vascular endothelial cells and eosinophils may play a role as TF-expressing cells for activating the extrinsic coagulation pathway...
October 6, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28937618/novel-fxa-inhibitor-identification-through-integration-of-ligand-and-structure-based-approaches
#3
Carlos F Lagos, Gerardine F Segovia, Nicolás Nuñez-Navarro, Mario A Faúndez, Flavia C Zacconi
Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and electrostatic similarity search and protein-ligand docking to discover novel FXa-targeted scaffolds for further development of inhibitors. From an initial set of 260,000 compounds from the NCI Open database, 30 potential FXa inhibitors were identified and selected for in vitro biological evaluation...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28906455/deep-circular-rna-sequencing-provides-insights-into-the-mechanism-underlying-grass-carp-reovirus-infection
#4
Libo He, Aidi Zhang, Lv Xiong, Yongming Li, Rong Huang, Lanjie Liao, Zuoyan Zhu, And Yaping Wang
Grass carp hemorrhagic disease, caused by the grass carp reovirus (GCRV), is a major disease that hampers the development of grass carp aquaculture in China. The mechanism underlying GCRV infection is still largely unknown. Circular RNAs (circRNAs) are important regulators involved in various biological processes. In the present study, grass carp were infected with GCRV, and spleen samples were collected at 0 (control), 1, 3, 5, and 7 days post-infection (dpi). Samples were used to construct and sequence circRNA libraries, and a total of 5052 circRNAs were identified before and after GCRV infection, of which 41 exhibited differential expression compared with controls...
September 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28872471/lung-xenotransplantation
#5
Hisashi Sahara, Hironosuke Watanabe, Thomas Pomposelli, Kazuhiko Yamada
PURPOSE OF REVIEW: This review describes the most recent progress in xeno lung transplantation (XLTx) to date. It describes the potential mechanisms of early xeno lung graft loss, as well as the latest therapeutic strategies to overcome them. RECENT FINDINGS: Using ex-vivo perfusion models of porcine lungs with human blood, the use of genetically modified pig lungs along with novel pharmaceutical approaches has recently been studied. Strategies that have demonstrated improved lung survival include the knockout of known xenoantigens (GalTKO and N-glycolylneuraminic acid-KO), genes that regulate complement activation (hCD46 and hCD55), as well as the inflammation/coagulation cascade (human leukocyte antigen-E, human thrombomodulin, human endothelial protein C receptor, hCD47, hCD39, hCD73 and heme oxygenase-1)...
December 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28830606/thrombin-generation-assays-for-global-evaluation-of-the-hemostatic-system-perspectives-and-limitations
#6
Rita Carolina Figueiredo Duarte, Cláudia Natália Ferreira, Danyelle Romana Alves Rios, Helton José Dos Reis, Maria das Graças Carvalho
The existing techniques to evaluate hemostasis in clinical laboratories are not sensitive enough to detect hypercoagulable and mild hypocoagulable states. Under different experimental conditions, the thrombin generation test may meet these requirements. This technique evaluates the overall balance between procoagulant and anticoagulant forces and has provided new insights in our understanding of the coagulation cascade, as well as of the diagnosis of hypocoagulability and hypercoagulability conditions. Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample...
July 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28782177/lipid-specificity-of-the-membrane-binding-domain-of-coagulation-factor-x
#7
M P Muller, Y Wang, J H Morrissey, E Tajkhorshid
Essentials Membrane-binding GLA domains of coagulation factors are essential for proper clot formation. Factor X (FX) is specific to phosphatidylserine (PS) lipids through unknown atomic-level interactions. Molecular dynamics simulations were used to develop the first membrane-bound model of FX-GLA. PS binding modes of FX-GLA were described, and potential PS-specific binding sites identified. SUMMARY: Background Factor X (FX) binds to cell membranes in a highly phospholipid-dependent manner and, in complex with tissue factor and factor VIIa (FVIIa), initiates the clotting cascade...
October 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28750635/proteomic-analysis-of-human-follicular-fluid-associated-with-successful-in-vitro-fertilization
#8
Xiaofang Shen, Xin Liu, Peng Zhu, Yuhua Zhang, Jiahui Wang, Yanwei Wang, Wenting Wang, Juan Liu, Ning Li, Fujun Liu
BACKGROUND: Human follicular fluid (HFF) provides a key environment for follicle development and oocyte maturation, and contributes to oocyte quality and in vitro fertilization (IVF) outcome. METHODS: To better understand folliculogenesis in the ovary, a proteomic strategy based on dual reverse phase high performance liquid chromatography (RP-HPLC) coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (LC-MALDI TOF/TOF MS) was used to investigate the protein profile of HFF from women undergoing successful IVF...
July 27, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28747664/mutations-targeting-the-coagulation-pathway-are-enriched-in-brain-metastases
#9
Cristina Richichi, Lorenzo Fornasari, Giorgio E M Melloni, Paola Brescia, Monica Patanè, Massimiliano Del Bene, Dana A M Mustafa, Johan M Kros, Bianca Pollo, Giancarlo Pruneri, Angela Sciandivasci, Elisabetta Munzone, Francesco DiMeco, Pier Giuseppe Pelicci, Laura Riva, Giuliana Pelicci
Brain metastases (BMs) are the most common malignancy of the central nervous system. Recently it has been demonstrated that plasminogen activator inhibitor serpins promote brain metastatic colonization, suggesting that mutations in serpins or other members of the coagulation cascade can provide critical advantages during BM formation. We performed whole-exome sequencing on matched samples of breast cancer and BMs and found mutations in the coagulation pathway genes in 5 out of 10 BM samples. We then investigated the mutational status of 33 genes belonging to the coagulation cascade in a panel of 29 BMs and we identified 56 Single Nucleotide Variants (SNVs)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28731874/novel-targets-for-anticoagulants-lacking-bleeding-risk
#10
Julia K Bickmann, Trevor Baglin, Joost C M Meijers, Thomas Renné
PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites...
September 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28712325/pharmacodynamics-of-combined-estrogen-progestin-oral-contraceptives-2-effects-on-hemostasis
#11
REVIEW
Manuela Farris, Carlo Bastianelli, Elena Rosato, Ivo Brosens, Giuseppe Benagiano
The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel...
October 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28552561/fxii-promotes-proteolytic-processing-of-the-lrp1-ectodomain
#12
Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Peter Braubach, Gregor Warnecke, Hans-Gerd Fieguth, Armin Braun, Günter Lochnit, Philipp Markart, Liliana Schaefer, Malgorzata Wygrecka
BACKGROUND: Factor XII (FXII) is a serine protease that is involved in activation of the intrinsic blood coagulation, the kallikrein-kinin system and the complement cascade. Although the binding of FXII to the cell surface has been demonstrated, the consequence of this event for proteolytic processing of membrane-anchored proteins has never been described. METHODS: The effect of FXII on the proteolytic processing of the low-density lipoprotein receptor-related protein 1 (LRP1) ectodomain was tested in human primary lung fibroblasts (hLF), alveolar macrophages (hAM) and in human precision cut lung slices (hPCLS)...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28549866/venom-of-the-peruvian-snake-bothriopsis-oligolepis-detection-of-antibacterial-activity-and-involvement-of-proteolytic-enzymes-and-c-type-lectins-in-growth-inhibition-of-staphylococcus-aureus
#13
M A Sulca, C Remuzgo, J Cárdenas, S Kiyota, E Cheng, M P Bemquerer, M T Machini
There is a rising interest in snake venoms proteins (SVPs) because these macromolecules are related to pharmacological properties that manifest themselves during poisoning and can lead to secondary microbial infections. Interestingly, researchers have somehow neglected the antimicrobial activity of SVPs. The aims of this study were: (i) to verify whether the venom of the Peruvian snake Bothriopsis oligolepis displays such activity; (ii) to isolate and identify some of its antimicrobial constituents. Liquid growth inhibition assays revealed that the crude venom inhibited the growth of Gram-positive and Gram-negative bacteria, but not of Candida species...
May 23, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28523980/diverse-endometrial-mrna-signatures-during-the-window-of-implantation-in-patients-with-repeated-implantation-failure
#14
Cheng Shi, Hong Jing Han, Li Juan Fan, Jing Guan, Xing Bang Zheng, Xi Chen, Rong Liang, Xiao Wei Zhang, Kun Kun Sun, Qing Hua Cui, Huan Shen
High endometrial receptivity in the window of implantation (WOI) is essential for successful implantation. However, a diagnostic tool with high specificity for impaired endometrial receptivity remains to be developed. We collected endometrium specimens during the WOI from patients with RIF and women who conceived after one IVF/ICSI attempt. We conducted mRNA microarray on the samples followed by relevant comparative and functional analysis. Microarray analysis revealed 357 dysregulated mRNAs between the two groups...
May 19, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28503126/in-vitro-and-ex-vivo-measurement-of-prophylactic-dabigatran-concentrations-with-a-new-ecarin-based-thromboelastometry-test
#15
Mareike Kristina Körber, Elisabeth Langer, Martin Köhr, Klaus-Dieter Wernecke, Wolfgang Korte, Christian von Heymann
BACKGROUND: An increasing number of oral anticoagulants has been approved, including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the diluted thrombin time measured with Hemoclot® has shown reliable results. So far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM assay uses ecarin to initiate the coagulation cascade at the step of thrombin generation and measures the clotting time (CT) by thromboelastometry...
April 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28495852/high-throughput-mrna-sequencing-of-stromal-cells-from-endometriomas-and-endometrium
#16
Kadri Rekker, Merli Saare, Elo Eriste, Tõnis Tasa, Viktorija Kukuškina, Anne Mari Roost, Kristi Anderson, Külli Samuel, Helle Karro, Andres Salumets, Maire Peters
The aetiology of endometriosis is still unclear and to find mechanisms behind the disease development it is important to study each cell type from endometrium and ectopic lesions independently. The objective of this study was to uncover complete mRNA profiles in uncultured stromal cells from paired samples of endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed over 1,300 dysregulated genes in stromal cells from ectopic lesions, including several novel genes in the context of endometriosis...
May 11, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28472252/new-insights-into-the-role-of-adipose-tissue-in-thrombosis
#17
Gemma Vilahur, Soumaya Ben-Aicha, Lina Badimon
Central obesity is independently associated with an elevated risk of cardiovascular disease, particularly thrombotic complications. Increasing data supports a link between excess body weight and the risk to suffer acute myocardial infarction, stent thrombosis after percutaneous interventions, ischemic stroke and vein thrombosis. Experimental and in vitro data have provided insights as to the mechanisms currently presumed to increase the thrombotic risk in obese subjects. Obesity is characterized by a chronic low grade inflammation and systemic oxidative stress that eventually damage the endothelium losing its antithrombotic properties...
July 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28464190/amniotic-fluid-embolism-is-a-new-pregnancy-possible-case-report
#18
Ana Filipa Cabrita Caeiro, Irina Dulce Tapadinhas Matos Ramilo, Ana Paula Santos, Elizabeth Ferreira, Isabel Santos Batalha
Amniotic fluid embolism (AFE) is a rare but potentially catastrophic clinical condition, characterized by a combination of signs and symptoms that reflect respiratory distress, cardiovascular collapse and disseminated intravascular coagulation (DIC). Its pathogenesis is still unclear. More recently, the traditional view of obstruction of pulmonary capillary vessels by amniotic fluid emboli as the main explanation for the etiology has been ruled out, and immunologic factors and the activation of the inflammatory cascade took on an important role...
July 2017: Revista Brasileira de Ginecologia e Obstetrícia
https://www.readbyqxmd.com/read/28376529/role-of-direct-oral-anticoagulants-in-the-management-of-anticoagulation
#19
REVIEW
Rajiv N Thakkar, Suman W Rathbun, Scott M Wright
For decades, vitamin K antagonists (VKAs) have been the oral treatment of choice for many thromboembolic conditions. The limitations of VKAs include the need for monitoring through blood testing, drug interactions, and narrow therapeutic windows. These shortcomings have led to the development of direct oral anticoagulants. These new oral agents act on specific targets in the coagulation cascade (eg, factor Xa, thrombin) and negate some of the shortcomings of VKAs. This article reviews the roles of dabigatran, rivaroxaban, apixaban, and edoxaban in stroke prevention in nonvalvular atrial fibrillation, for prevention of venous thromboembolism after orthopedic surgery, and in the treatment of venous thromboembolism...
April 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28365976/new-anticoagulants-for-the-prevention-and-treatment-of-venous-thromboembolism
#20
REVIEW
Joo Hee Kim, Kyung-Min Lim, Hye Sun Gwak
Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions...
September 1, 2017: Biomolecules & Therapeutics
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