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https://www.readbyqxmd.com/read/29760725/the-effects-of-hyperacute-serum-on-the-elements-of-the-human-subchondral-bone-marrow-niche
#1
Melinda Simon, Bálint Major, Gabriella Vácz, Olga Kuten, István Hornyák, Adél Hinsenkamp, Dorottya Kardos, Marcell Bagó, Domonkos Cseh, Adrienn Sárközi, Denes Horvathy, Stefan Nehrer, Zsombor Lacza
Mesenchymal stem cells (MSCs) are widely used in laboratory experiments as well as in human cell therapy. Their culture requires animal sera like fetal calf serum (FCS) as essential supplementation; however, animal sera pose a risk for clinical applications. Human blood derivatives, for example, platelet-rich plasma (PRP) releasates, are potential replacements of FCS; however, it is unclear which serum variant has the best effect on the given cell or tissue type. Additionally, blood derivatives are commonly used in musculoskeletal diseases like osteoarthritis (OA) or osteonecrosis as "proliferative agents" for the topical MSC pool...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29735342/dabigatran-reduces-endothelial-permeability-through-inhibition-of-thrombin-induced-cytoskeleton-reorganization
#2
Hyun-Jung Choi, Na-Eun Kim, Jayoung Kim, Sunho An, Seung-Hee Yang, Jimin Ha, Sunghee Cho, Il Kwon, Young Dae Kim, Hyo Suk Nam, Ji Hoe Heo
Dabigatran etexilate (DE), a new oral anti-coagulant, is a direct thrombin inhibitor. Clinical trials showed the favorable benefit-to-risk profile of DE compared to warfarin for the prevention of ischemic stroke in patients with atrial fibrillation. Remarkably, patients treated with dabigatran showed reduced rates of intracerebral hemorrhage compared to warfarin. As the breakdown of endothelial barrier integrity is associated with hemorrhagic events and as thrombin increases endothelial permeability, we hypothesized that dabigatran preserves the endothelial barrier by inhibiting thrombin-induced permeability...
April 25, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29692238/advances-in-the-development-of-novel-factor-xa-inhibitors-a-patent-review
#3
Atul N Khadse, Mayank Kumar Sharma, Prashant R Murumkar, Sadhana J Rajput, Mange Ram Yadav
Development of new anticoagulants has been in constant demand throughout the world due to increasing rate of morbidity and mortality caused by thrombotic diseases. Factor Xa (FXa), one of the enzymes and validated target for anticoagulation, regulates the production of thrombin in the coagulation cascade. The importance of oral FXa inhibitors like rivaroxaban, apixaban and edoxaban in thromboembolic conditions is well supported by increasing number of patents and research publications during the recent years...
April 24, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29615702/global-proteomics-deciphered-novel-function-of-osthole-against-pulmonary-arterial-hypertension
#4
Li Yao, Yuxia Yang, Guanhong He, Chunqing Ou, Lan Wang, Kaixuan Liu
Pulmonary arterial hypertension (PAH) is a progressive cardiovascular-disease with high mortality lacking high-efficiency drug. Our efforts attempted to delineate therapeutic action of osthole produced by Angelica Pubescens Maxim, which has the capacity to treat PAH by exploiting an iTRAQ-based proteomic method. Excitingly, osthole was observed to significantly restore 98 of 315 differential proteins significantly modified by PAH progression. They were primarily annotated into 24 signaling pathways. Four mostly affected proteins (RPL15, Cathepsin S, Histone H3...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29566413/rivaroxaban-a-new-treatment-paradigm-in-the-setting-of-vascular-protection
#5
Rupert Bauersachs, Faiez Zannad
The pathophysiology of atherosclerosis involves a diseased endothelium, lipid accumulation and low-grade inflammation. In later stages of coronary artery disease (CAD) and peripheral arterial disease (PAD), plaque rupture may induce atherothrombosis caused by fibrin formation and platelet activation, leading to vessel occlusion with subsequent organ damage such as myocardial infarction, stroke or limb ischaemia. Because of the high disease burden associated with CAD and PAD, there is a need for continuous vascular protection beyond currently available treatments including antiplatelet agents...
March 22, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29556022/mobilization-of-hematopoietic-stem-cells-as-a-result-of-innate-immunity-mediated-sterile-inflammation-in-the-bone-marrow-microenvironment-the-involvement-of-extracellular-nucleotides-and-purinergic-signaling
#6
REVIEW
Mariusz Z Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes...
March 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29545340/structural-and-cellular-mechanisms-of-peptidyl-prolyl-isomerase-pin1-mediated-enhancement-of-tissue-factor-gene-expression-protein-half-life-and-pro-coagulant-activity
#7
Kondababu Kurakula, Duco S Koenis, Mark A Herzik, Yanyun Liu, John W Craft, Pieter B van Loenen, Mariska Vos, M Khang Tran, Henri H Versteeg, Marie-José T H Goumans, Wolfram Ruf, Carlie J M de Vries, Mehmet Şen
Tissue Factor is a cell-surface glycoprotein expressed in various cells of the vasculature and is the principal regulator of the blood coagulation cascade and hemostasis. Notably, aberrant expression of Tissue Factor is associated with cardiovascular pathologies such as atherosclerosis and thrombosis. Here, we sought to identify factors that regulate Tissue Factor gene expression and activity. Tissue Factor gene expression is regulated by various transcription factors, including activating protein-1 and nuclear factor-kappa B...
March 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29541874/update-on-antiphospholipid-syndrome-ten-topics-in-2017
#8
REVIEW
Ilaria Cavazzana, Laura Andreoli, Maarteen Limper, Franco Franceschini, Angela Tincani
PURPOSE OF REVIEW: This review focuses on new clinical aspects of antiphospholipid syndrome (APS) in the last 5 years. RECENT FINDINGS: The pathogenesis of APS is related to endothelial activation by mechanisms other than autoantibody-mediated massive coagulation. These include Toll-like receptors, the m-TORC pathway, and neutrophil activation, inducing an uncontrolled inflammatory cascade. Given these new pathogenetic hypotheses, the treatment of APS could be directed towards a fine balance between anticoagulation and immunomodulation...
March 15, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29468977/the-development-of-new-factor-xa-inhibitors-based-on-amide-synthesis
#9
Dmitry Tarasov, Dmitry Tovbin, Dmitry Malakhov, Arseniy Aybush, Natalia Tserkovnikova, Marina Savelyeva, Dmitry Sychev, Natalia Drozd, Alla Savchenko
BACKGROUND: Factor Xa (FXa) is known to play a central role in a blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation. OBJECTIVE: Our approach for the development of directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in this work. METHOD: Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening methods, where R1, R2, R3 are some chemical groups, (CONH) are amid bonds connecting R1, R2 and R3...
February 14, 2018: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29419408/distinct-pathogenesis-of-pancreatic-cancer-microvesicle-associated-venous-thrombosis-identifies-new-antithrombotic-targets-in-vivo
#10
Konstantin Stark, Irene Schubert, Urjita Joshi, Badr Kilani, Parandis Hoseinpour, Manovriti Thakur, Petra Grünauer, Susanne Pfeiler, Tobias Schmidergall, Sven Stockhausen, Markus Bäumer, Sue Chandraratne, Marie-Luise von Brühl, Michael Lorenz, Raffaele Coletti, Sven Reese, Iina Laitinen, Sonja Maria Wörmann, Hana Algül, Christiane J Bruns, Jerry Ware, Nigel Mackman, Bernd Engelmann, Steffen Massberg
OBJECTIVE: Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT. APPROACH AND RESULTS: Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT...
April 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29412112/novel-direct-anticoagulants-and-atherosclerosis
#11
Fabjan Andrej, Bajrovic F Fajko
Coagulation factors can affect cellular processes that include inflammatory signaling by acting on endothelial protease activated receptors, vascular smooth muscle and inflammatory cells beyond the coagulation cascade. This is important in the pathogenesis of atherosclerosis. Accordingly, experimental data points to beneficial effects of coagulation protease inhibitors on the attenuation of atherosclerosis progression in animal models. However, available clinical data do not support the use of anticoagulants as an add-on treatment of atherosclerosis...
February 5, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29410805/transcriptomic-inspection-revealed-a-possible-pathway-regulating-the-formation-of-the-high-quality-brush-hair-in-chinese-haimen-goat-capra-hircus
#12
Dejun Ji, Bo Yang, Yongjun Li, Miaoying Cai, Wei Zhang, Guohu Cheng, Haiyan Guo
The high-quality brush hair, or Type III brush hair, is coarse hair but with a tip and little medulla, which uniquely grows in the cervical carina of Chinese Haimen goat ( Capra hircus ). To unveil the mechanism of the formation of Type III brush hair in Haimen goats, transcriptomic RNAseq technology was used for screening of differentially expressed genes (DEGs) in the skin samples of the Type III and the non-Type III hair goats, and these DEGs were analysed by KEGG pathway analysis. The results showed that a total of 295 DEGs were obtained, mainly from three main functional types: cellular component, molecular function and biological process...
January 2018: Royal Society Open Science
https://www.readbyqxmd.com/read/29404650/-coagulation-factors-and-multiple-sclerosis-key-factors-in-the-pathogenesis
#13
REVIEW
K Göbel, C Kleinschnitz, S G Meuth
Environmental factors and genetic predisposition influence the individual risk to develop multiple sclerosis (MS). Preclinical results in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), prove a significant contribution of the corpuscular and plasmatic coagulation system for the severity of MS. It was recently shown that key molecules of the coagulation cascade, such as fibrinogen, thrombin and factor XII can influence neuroinflammatory disorders such as MS. The inhibition of both fibrinogen and factor XII led to a significantly improved disease course in animal models...
February 5, 2018: Der Nervenarzt
https://www.readbyqxmd.com/read/29399533/pathogenesis-of-thrombosis-cellular-and-pharmacogenetic-contributions
#14
REVIEW
Dileep D Monie, Emma P DeLoughery
Our understanding of thrombosis formation has evolved significantly ever since physician Rudolf Virchow proposed his "triad" theory in 1856. Modern science has elucidated the mechanisms of stasis, hypercoagulability, and endothelial dysfunction. Today, we have a firm understanding of the key molecular factors involved in the coagulation cascade and fibrinolytic system, as well as the underlying genetic influences. This knowledge of cellular and genetic contributors has been translated into diverse pharmaceutical interventions...
December 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/29376487/surfing-the-blood-coagulation-cascade-insight-into-the-vital-factor-xa
#15
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/29340222/direct-molecular-fishing-of-new-protein-partners-for-human-thromboxane-synthase
#16
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
#17
REVIEW
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...
January 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29214154/the-search-for-biomarkers-in-hereditary-angioedema
#18
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
#19
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...
January 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29173148/trends-and-prospects-of-plant-proteases-in-therapeutics
#20
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
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