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https://www.readbyqxmd.com/read/29340222/direct-molecular-fishing-of-new-protein-partners-for-human-thromboxane-synthase
#1
A V Svirid, P V Ershov, E O Yablokov, L A Kaluzhskiy, Yu V Mezentsev, A V Florinskaya, T A Sushko, N V Strushkevich, A A Gilep, S A Usanov, A E Medvedev, A S Ivanov
Thromboxane synthase (TBXAS1) catalyzes the isomerization reaction of prostaglandin H2 producing thromboxane A2, the autocrine and paracrine factor in many cell types. A high activity and metastability by these arachidonic acid derivatives suggests the existence of supramolecular structures that are involved in the regulation of the biosynthesis and directed translocation of thromboxane to the receptor. The objective of this study was to identify TBXAS1 protein partners from human liver tissue lysate using a complex approach based on the direct molecular fishing technique, LC-MS/MS protein identification, and protein-protein interaction validation by surface plasmon resonance (SPR)...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29224364/new-anticoagulants-for-venous-thromboembolism-and-atrial-fibrillation-what-the-future-holds
#2
Gerasimos Dimitropoulos, S M Zubair Rahim, Alexandra Sophie Moss, Gregory Y H Lip
The field of anticoagulation has seen impressive progress over the last decade. The introduction of the Non Vitamin K Oral Anticoagulants (NOACs) has revolutionized practice surrounding thromboprophylaxis, treatment of thromboembolic disease and stroke prevention in atrial fibrillation (AF). However, the search for the 'holy grail' of anticoagulation, an agent that combines optimal efficacy with minimal bleeding diathesis, continues. Areas covered: In this paper we aim to summarize the current evidence from pre-clinical studies and early phase clinical trials, presenting the pharmacodynamic and pharmacokinetic properties as well as the safety and efficacy profiles of the most important antithrombotic agents in development...
December 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29214154/the-search-for-biomarkers-in-hereditary-angioedema
#3
REVIEW
Allen P Kaplan, Coen Maas
The unpredictable nature of attacks of tissue swelling in hereditary angioedema requires the identification of reliable biomarkers to monitor disease activity as well as response to therapy. At present, one can assess a C4 level (by ELISA) to assist in diagnosis but neither C4 nor C1 inhibitor levels reflect clinical course or prognosis. We will here review a collection of plasma proteins involved in blood coagulation, fibrinolysis, and innate immunity (Figure 1). A main focus is those proteins that are key to the formation of bradykinin (BK); namely, factor XII, plasma prekallikrein/kallikrein, high-molecular weight kininogen, and BK itself since overproduction of BK is key to the disease...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29174782/pericardial-blood-as-a-trigger-for-postoperative-atrial-fibrillation-after-cardiac-surgery
#4
REVIEW
Samuel St-Onge, Louis P Perrault, Philippe Demers, Edward M Boyle, A Marc Gillinov, James Cox, Spencer Melby
BACKGROUND: Prevention strategies have long been sought to reduce the incidence and burden of postoperative atrial fibrillation (POAF) after heart surgery. However, none has emerged as a dominant and widely applicable prophylactic measure. The purpose of this review is to consider the biological mechanisms by which shed mediastinal blood leads to oxidation and inflammation within the postoperative pericardial environment and how this might trigger POAF in susceptible persons, as well as how it could represent a new target for prevention of POAF...
November 23, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29173148/trends-and-prospects-of-plant-proteases-in-therapeutics
#5
Anastasia V Balakireva, Natalia V Kuznetsova, Anastasia I Petushkova, Lyudmila Savvateeva, Andrey A Zamyatnin
The main function of proteases in any living organism is the cleavage of proteins resulting in the degradation of damaged, misfolded and potentially harmful proteins and therefore providing the cell with amino acids essential for the synthesis of new proteins. Besides this main function, proteases may play an important role as signal molecules and participate in numerous protein cascades to maintain the vital processes of an organism. Plant proteases are no exception to this rule. Moreover, in contrast to human-encoded enzymes, many plant proteases possess exceptional features such as higher stability, unique substrate specificity and a wide pH range for enzymatic activity...
November 23, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29023416/neuro-coagulopathy-blood-coagulation-factors-in-central-nervous-system-diseases
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
REVIEW
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
#16
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
#17
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
#18
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
#19
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
#20
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
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