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https://www.readbyqxmd.com/read/28079978/targeting-coagulation-factor-receptors-protease-activated-receptors-in-idiopathic-pulmonary-fibrosis
#1
REVIEW
Cong Lin, Keren Borensztajn, C Arnold Spek
Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with a 5-year mortality rate above 50% and unknown etiology. Treatment options remain limited and, currently, only two drugs are available, nintedanib and pirfenidone. However, both of these antifibrotic agents only slow down the progression of the disease but do not remarkably prolong the survival of IPF patients. Hence, the discovery of new therapeutic targets for IPF is crucial. Studies exploring the mechanisms that are involved in IPF identified several possible targets for therapeutic interventions...
January 12, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28035007/inhibition-of-factor-xia-reduces-the-frequency-of-cerebral-microembolic-signals-derived-from-carotid-arterial-thrombosis-in-rabbits
#2
Xinkang Wang, Stan Kurowsk, Weizhen Wu, Gino A Castriota, Xueping Zhou, Lin Chu, Kenneth P Ellsworth, Scott Edmondson, Donald Chu, Amjad Ali, Patrick Andre, Dietmar Seiffert, Mark Erion, David E Gutstein, Zhu Chen
Factor XI (FXI) is an integral component of the intrinsic pathway of the coagulation cascade and plays a critical role in thrombus formation. Since its role in the pathogenesis of cerebral microembolic signals (MES) is unclear, this study utilized a potent and selective small molecule inhibitor of FXIa, Compound 1, to assess the effect of FXI blockade in our recently established preclinical model of cerebral MES induced by FeCl3 injury of the carotid artery in male New Zealand White rabbits. Ascending doses of Compound 1 were evaluated simultaneously for both carotid arterial thrombosis by a Doppler flowmeter and MES in the middle cerebral artery by a transcranial Doppler...
December 29, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28005926/the-central-role-of-kng1-gene-as-a-genetic-determinant-of-coagulation-pathway-related-traits-exploring-metaphenotypes
#3
Helena Brunel, Raimon Massanet, Angel Martinez-Perez, Andrey Ziyatdinov, Laura Martin-Fernandez, Juan Carlos Souto, Alexandre Perera, José Manuel Soria
Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i...
2016: PloS One
https://www.readbyqxmd.com/read/27928886/f376a-m388a-solulin-a-new-promising-antifibrinolytic-for-severe-haemophilia-a
#4
J Parcq, K U Petersen, A Borel-Derlon, P Gautier, M Ebel, D Vivien, Y Repessé
INTRODUCTION: Haemophilia is a major bleeding disorder due to a deficiency of procoagulant factor VIII (type A) or IX (type B). The treatment is substitutive and based on infusion of factor concentrates. Main limitations of this therapy are cost, short factor half-life and the development of inhibitors (up to 30% of severe HA patients). An important aggravating factor of haemophilia is due to a premature fibrinolysis, directing attention to the therapeutic potential of suitable antifibrinolytics...
December 8, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#5
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27876232/hypercoagulation-and-complement-connected-players-in-tumor-development-and-metastases
#6
REVIEW
Silvia Guglietta, Maria Rescigno
Hypercoagulation is a common feature of several tumors to the extent that individuals with coagulation defects often present with occult visceral cancers. Recent evidence has shown that hypercoagulation is not just a mere secondary effect due to the presence of the tumor, rather it actively contributes to tumor development and dissemination. Among the numerous mechanisms that can contribute to cancer-associated hypercoagulation, the ones involving immune-mediated processes are gaining increasing attention. In particular, complement cascade and hypercoagulation are one inducing the other in a vicious circle that involves neutrophil extracellular traps (NETs) formation...
December 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27824278/modulation-of-porcine-intestinal-epitheliocytes-immunetranscriptome-response-by-lactobacillus-jensenii-tl2937
#7
H Kobayashi, L Albarracin, N Sato, P Kanmani, A K M H Kober, W Ikeda-Ohtsubo, Y Suda, T Nochi, H Aso, S Makino, H Kano, S Ohkawara, T Saito, J Villena, H Kitazawa
In order to evaluate probiotic strains applicable for the beneficial immunomodulation of the porcine gut (immunobiotics), we previously developed a porcine intestinal epitheliocyte cell line (PIE cells). Here, transcriptomic studies using PIE cells were performed considering that this information would be valuable for understanding the mechanisms involved in the protective activity of the immunobiotic strain Lactobacillus jensenii TL2937 against intestinal inflammatory damage in pigs. In addition, those studies would provide criteria for selecting biomarkers for the screening of new immunobiotic strains...
November 30, 2016: Beneficial Microbes
https://www.readbyqxmd.com/read/27824218/coagulopathy-in-sepsis-a-new-look-at-an-old-problem
#8
Małgorzata Lipinska-Gediga
Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis...
2016: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/27782319/dangerous-liaisons-complement-coagulation-and-kallikrein-kinin-cross-talk-act-as-a-linchpin-in-the-events-leading-to-thromboinflammation
#9
REVIEW
Kristina N Ekdahl, Yuji Teramura, Osama A Hamad, Sana Asif, Claudia Duehrkop, Karin Fromell, Elisabet Gustafson, Jaan Hong, Huda Kozarcanin, Peetra U Magnusson, Markus Huber-Lang, Peter Garred, Bo Nilsson
Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27766055/platelets-and-platelet-adhesion-molecules-novel-mechanisms-of-thrombosis-and-anti-thrombotic-therapies
#10
REVIEW
Xiaohong Ruby Xu, Naadiya Carrim, Miguel Antonio Dias Neves, Thomas McKeown, Tyler W Stratton, Rodrigo Matos Pinto Coelho, Xi Lei, Pingguo Chen, Jianhua Xu, Xiangrong Dai, Benjamin Xiaoyi Li, Heyu Ni
Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that occurs prior to platelet accumulation (i...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27758696/immune-inflammatory-activation-in-acute-coronary-syndromes-a-look-into-the-heart-of-unstable-coronary-plaque
#11
Giovanni Cimmino, Francesco S Loffredo, Alberto Morello, Saverio D Elia, Raffaele De Palma, Plinio Cirillo, Paolo Golino
In the last twenty years, our comprehension of the molecular mechanisms involved in formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration...
October 13, 2016: Current Cardiology Reviews
https://www.readbyqxmd.com/read/27637304/postorthopedic-surgery-joint-replacement-surgery-venous-thromboembolism-prophylaxis
#12
REVIEW
Louis M Kwong, Jon A Kimball
Elective total hip or knee arthroplasty places patients at risk for venous thromboembolism (VTE). As our understanding of the pathophysiology of VTE after joint arthroplasty has increased, pharmacologic strategies have been developed to target different aspects of the coagulation cascade. Various approaches have been used as risk reduction strategies. In 2011 and 2014 the Food and Drug Administration approved rivaroxaban and apixaban as new oral antithrombotic agents. Although controversies remain with regard to the ideal VTE pharmacoprophylactic agent, this class of novel oral anticoagulants has been demonstrated to be safe and to be more effective than enoxaparin...
October 2016: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27574188/disulfide-hmgb1-derived-from-platelets-coordinates-venous-thrombosis-in-mice
#13
Konstantin Stark, Vanessa Philippi, Sven Stockhausen, Johanna Busse, Antonella Antonelli, Meike Miller, Irene Schubert, Parandis Hoseinpour, Sue Chandraratne, Marie-Luise von Brühl, Florian Gaertner, Michael Lorenz, Alessandra Agresti, Raffaele Coletti, Daniel J Antoine, Ralf Heermann, Kirsten Jung, Sven Reese, Iina Laitinen, Markus Schwaiger, Axel Walch, Markus Sperandio, Peter P Nawroth, Christoph Reinhardt, Sven Jäckel, Marco E Bianchi, Steffen Massberg
Deep venous thrombosis (DVT) is one of the most common cardiovascular diseases, but its pathophysiology remains incompletely understood. Although sterile inflammation has recently been shown to boost coagulation during DVT, the underlying molecular mechanisms are not fully resolved, which could potentially identify new anti-inflammatory approaches to prophylaxis and therapy of DVT. Using a mouse model of venous thrombosis induced by flow reduction in the vena cava inferior, we identified blood-derived high-mobility group box 1 protein (HMGB1), a prototypical mediator of sterile inflammation, to be a master regulator of the prothrombotic cascade involving platelets and myeloid leukocytes fostering occlusive DVT formation...
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27566655/meningiomas-and-proteomics-focus-on-new-potential-biomarkers-and-molecular-pathways
#14
REVIEW
Rosaria Viola Abbritti, Francesca Polito, Maria Cucinotta, Claudio Lo Giudice, Maria Caffo, Chiara Tomasello, Antonino Germanò, Mohammed Aguennouz
Meningiomas are one of the most common tumors affecting the central nervous system, exhibiting a great heterogeneity in grading, treatment and molecular background. This article provides an overview of the current literature regarding the molecular aspect of meningiomas. Analysis of potential biomarkers in serum, cerebrospinal fluid (CSF) and pathological tissues was reported. Applying bioinformatic methods and matching the common proteic profile, arising from different biological samples, we highlighted the role of nine proteins, particularly related to tumorigenesis and grading of meningiomas: serpin peptidase inhibitor alpha 1, ceruloplasmin, hemopexin, albumin, C3, apolipoprotein, haptoglobin, amyloid-P-component serum and alpha-1-beta-glycoprotein...
September 2016: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27513209/inhibition-of-coagulation-proteases-xa-and-iia-decreases-ischemia-reperfusion-injuries-in-a-preclinical-renal-transplantation-model
#15
Solenne Tillet, Sébastien Giraud, Thomas Kerforne, Thibaut Saint-Yves, Sandrine Joffrion, Jean-Michel Goujon, Jerôme Cau, Gérard Mauco, Maurice Petitou, Thierry Hauet
Coagulation is an important pathway in the pathophysiology of ischemia-reperfusion injuries. In particular, deceased after circulatory death (DCD) donors undergo a no-flow period, a strong activator of coagulation. Hence, therapies influencing the coagulation cascade must be developed. We evaluated the effect of a new highly specific and effective anti-Xa/IIa molecule, with an integrated innovative antidote site (EP217609), in a porcine preclinical model mimicking injuries observed in DCD donor kidney transplantation...
July 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27497655/analytical-comparison-of-a-us-generic-enoxaparin-with-the-originator-product-the-focus-on-comparative-assessment-of-antithrombin-binding-components
#16
Pierre A J Mourier, Fréderic Herman, Philippe Sizun, Christian Viskov
Enoxaparin sodium, a low-molecular-weight heparin (LMWH) prepared from porcine intestinal heparin, is widely used for the prevention and treatment of venous thromboembolism. The antithrombotic activity of heparin is mediated mainly through its activation of antithrombin (AT) and subsequent inhibition of coagulation factors. Heparin is a complex heteropolymer and the sulfation pattern of its alternating uronic acid and glucosamine sugar units is a major factor influencing its biological activity. The manufacturing process itself is associated with the introduction of exogenous microheterogeneities that may further affect its biological efficacy...
September 10, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27470592/inhibitory-serpins-new-insights-into-their-folding-polymerization-regulation-and-clearance
#17
REVIEW
Peter G W Gettins, Steven T Olson
Serpins are a widely distributed family of high molecular mass protein proteinase inhibitors that can inhibit both serine and cysteine proteinases by a remarkable mechanism-based kinetic trapping of an acyl or thioacyl enzyme intermediate that involves massive conformational transformation. The trapping is based on distortion of the proteinase in the complex, with energy derived from the unique metastability of the active serpin. Serpins are the favoured inhibitors for regulation of proteinases in complex proteolytic cascades, such as are involved in blood coagulation, fibrinolysis and complement activation, by virtue of the ability to modulate their specificity and reactivity...
August 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27456888/the-effects-of-thrombomodulin-and-activated-protein-c-on-the-pathogenesis-of-multiple-sclerosis
#18
Ece Balkuv, Asuman Orhan Varoglu, Nihal Isik, Banu Isbilen, Saadettin Duruyen, Recep Basaran, Abdulkadir Kocer
BACKGROUND: Various molecules of the coagulation cascade are thought to have varying roles in the pathophysiology of multiple sclerosis (MS). We aimed to find new information about the effects of the coagulation cascade molecules to develop new therapeutic strategies for MS. MATERIALS AND METHODS: Patients with MS were chosen from among patients who were followed up at our hospital. We examined the thrombomodulin (TM) and activated protein C (APC) serum levels in patients with MS and the healthy controls...
July 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27372899/role-of-heparin-and-non-heparin-binding-serpins-in-coagulation-and-angiogenesis-a-complex-interplay
#19
REVIEW
Teena Bhakuni, Mohammad Farhan Ali, Irshad Ahmad, Shadabi Bano, Shoyab Ansari, Mohamad Aman Jairajpuri
Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining hemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary embolism (PE). Angiogenesis is the process of sprouting of new blood vessels from pre-existing ones and plays a critical role in vascular repair, diabetic retinopathy, chronic inflammation and cancer progression...
August 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27354721/the-role-of-leukocytes-in-thrombosis
#20
REVIEW
Laura L Swystun, Patricia C Liaw
In recent years, the traditional view of the hemostatic system as being regulated by a coagulation factor cascade coupled with platelet activation has been increasingly challenged by new evidence that activation of the immune system strongly influences blood coagulation and pathological thrombus formation. Leukocytes can be induced to express tissue factor and release proinflammatory and procoagulant molecules such as granular enzymes, cytokines, and damage-associated molecular patterns. These mediators can influence all aspects of thrombus formation, including platelet activation and adhesion, and activation of the intrinsic and extrinsic coagulation pathways...
August 11, 2016: Blood
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