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Chantal C Clark, Mirjam M Mebius, Steven de Maat, Aloysius G M Tielens, Philip G de Groot, Rolf T Urbanus, Rob Fijnheer, Bouke P C Hazenberg, Jaap J van Hellemond, Coen Maas
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand Factor (VWF) multimers to control their thrombogenicity. The fibrinolytic enzyme plasmin can cleave VWF in a similar manner. However, plasmin can also cleave ADAMTS13, which ultimately inactivates it. This leaves the overall role of plasmin in primary haemostasis uncertain.We investigated the combined molecular effects of plasmin on VWF and ADAMTS13. We first identified that plasmin destroys FRETS-VWF73 substrate by cleaving the ADAMTS13 binding region in a buffered system...
March 2018: Thrombosis and Haemostasis
Neelam Dubey, Prashant Singh, Suvendra Nath Bagchi
Unbranched heterocytous cyanobacteria produce a number of serine peptidases. We have characterized several peptidases in the cell-free extracts of a true-branched N2 -fixing cyanobacterium, Westiellopsis ramosa sp. nov. Upon substrate-gel zymography of intact filaments and heterocytes, five peptidase bands were resolved, whereas in vegetative cells, a single band was discernible. No band was detected in [Formula: see text]-grown cultures suggesting that the peptidases were present under diazotrophic conditions with much of them confined to heterocytes...
March 2018: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
Takashi Ishihara, Keiji Nogami, Yasufumi Takeshita, Satoshi Ochi, Midori Shima
Thrombosis and hemorrhage are serious complications in pediatric patients with solid tumors, and enhanced fibrinolysis associated with disseminated intravascular coagulation (DIC) is often observed. Fibrinolytic enzymes also play an important role in metastasis. Limited information is available, however, on the assessment of overall hemostatic function in children with malignant solid tumors. Methods We have investigated comprehensive hemostatic potential in these circumstances using simultaneous thrombin/plasmin generation assay (T/P-GA)...
March 5, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
J Caballero-Villalobos, J M Perea, E Angón, R Arias, A Garzón
Milk coagulation, especially in small ruminant species, is often hard to evaluate, as coagulation traits are normally considered individually and several factors related to udder health might distort yield calculation. Due to the lack of studies about these factors, our objective was to determine milk coagulation efficiency (CE) and its determinants using a deterministic technical efficiency approach, an ordinary least square regression model, and ANOVA. Milk from 300 Manchega ewes was collected and analyzed for composition, milk coagulation properties, and hygienic quality...
February 28, 2018: Journal of Dairy Science
Arran Hodgkinson, Mark A J Chaplain, Pia Domschke, Dumitru Trucu
Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration...
March 2, 2018: Bulletin of Mathematical Biology
Aska Sonoki, Yuri Okano, Yuichiro Yoshitake
Photoaging of the skin is marked by obvious wrinkles and mainly depends on degradation of the extracellular matrix (ECM) in the dermis. Matrix metalloproteinase (MMP)-1 is one of the most important factors involved in degradation of the ECM, however, its mechanism of activation is not fully understood. It has been thought that MMP-1 is expressed by dermal fibroblasts as an inactive precursor protein that is activated by proteinases produced by keratinocytes in the epidermis. In this study, we constructed a 3D model of the dermis using collagen-embedded fibroblasts with or without ultraviolet (UV)-A exposure to mimic photoaging in the dermis...
March 2, 2018: Experimental Dermatology
Lindsey A Miles, Nagyung Baik, Hongdong Bai, Helen P Makarenkova, William B Kiosses, Stan Krajewski, Francis J Castellino, Alex Valenzuela, Nissi M Varki, Barbara M Mueller, Robert J Parmer
BACKGROUND: Lactational competence requires plasminogen, the zymogen of the serine protease, plasmin. Plg-RKT is a unique transmembrane plasminogen receptor that promotes plasminogen activation to plasmin on cell surfaces. Plg-RKT -/- mice are viable, but no offspring of Plg-RKT -/- female mice survive to weaning. OBJECTIVES: We investigated potential lactational failure in Plg-RKT -/- mice and addressed causal mechanisms. METHODS: Fibrin accumulation, macrophage infiltration, processing of extracellular matrix components, effects of genetic deletion of fibrinogen, expression of fibrosis genes, and proliferation and apoptosis of epithelial cells were examined in lactating mammary glands of Plg-RKT -/- and Plg-RKT +/+ mice...
March 1, 2018: Journal of Thrombosis and Haemostasis: JTH
Anne-Sophie Ducloy-Bouthors, Emmanuelle Jeanpierre, Imen Saidi, Anne-Sophie Baptiste, Elodie Simon, Damien Lannoy, Alain Duhamel, Delphine Allorge, Sophie Susen, Benjamin Hennart
BACKGROUND: Evidence increases that a high or a standard dose of tranexamic acid (TA) reduces postpartum bleeding. The TRACES pharmacobiological substudy aims to establish a therapeutic strategy in hemorrhagic (H) Cesarean section (CS) with respect to the intensity of fibrinolysis by using innovative assays. METHOD/DESIGN: The TRACES trial is a multicenter, randomized, double-blind, placebo-controlled, TA dose-ranging study that measures simultaneously plasmatic and uterine and urine TA concentrations and the plasmin peak inhibition tested by a simultaneous thrombin plasmin generation assay described by Van Geffen (novel hemostasis assay [NHA])...
March 1, 2018: Trials
Anne-Sophie Bouthors, Benjamin Hennart, Emmanuelle Jeanpierre, Anne-Sophie Baptiste, Imen Saidi, Elodie Simon, Damien Lannoy, Alain Duhamel, Delphine Allorge, Sophie Susen
BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide. Tranexamic acid (TA), an antifibrinolytic drug, reduces bleeding and transfusion need in major surgery and trauma. In ongoing PPH following vaginal delivery, a high dose of TA decreases PPH volume and duration, as well as maternal morbidity, while early fibrinolysis is inhibited. In a large international trial, a TA single dose reduced mortality due to bleeding but not the hysterectomy rate. TA therapeutic dosages vary from 2...
March 1, 2018: Trials
Niaz Mahmood, Catalin Mihalcioiu, Shafaat A Rabbani
The plasminogen activator (PA) system is an extracellular proteolytic enzyme system associated with various physiological and pathophysiological processes. A large body of evidence support that among the various components of the PA system, urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) play a major role in tumor progression and metastasis. The binding of uPA with uPAR is instrumental for the activation of plasminogen to plasmin, which in turn initiates a series of proteolytic cascade to degrade the components of the extracellular matrix, and thereby, cause tumor cell migration from the primary site of origin to a distant secondary organ...
2018: Frontiers in Oncology
Rafaela S Fernandes, Luis G V Fernandes, Andre S de Godoy, Patrícia A Miyasato, Eliana Nakano, Leonardo P Farias, Ana L T O Nascimento, Luciana C C Leite
Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma which have a complex life cycle characterized by an asexual multiplication in the snail intermediate host and a sexual reproduction phase in the mammalian definitive host. The initial steps of the human host infection involve the secretion of proteins contained in the acetabular glands of cercariae that promote parasite adhesion and proteolysis of the skin layers. Herein, we performed a functional analysis of SmVAL18, identified as one of the three SCP/TAPS proteins constituent of cercarial secretions...
February 22, 2018: Molecular and Biochemical Parasitology
Michael Schuliga, Christopher Grainge, Glen Westall, Darryl Knight
Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis...
February 20, 2018: International Journal of Biochemistry & Cell Biology
Dolores A Ayón-Núñez, Gladis Fragoso, Clara Espitia, Martín García-Varela, Xavier Soberón, Gabriela Rosas, Juan P Laclette, Raúl J Bobes
The larval stage of Taenia solium (cysticerci) is the causal agent of human and swine cysticercosis. When ingested by the host, T. solium eggs are activated and hatch in the intestine, releasing oncospheres that migrate to various tissues and evolve into cysticerci. Plasminogen (Plg) receptor proteins have been reported to play a role in migration processes for several pathogens. This work is aimed to identify Plg-binding proteins in T. solium cysticerci and determine whether T. solium recombinant enolase (rTsEnoA) is capable of specifically binding and activating human Plg...
February 18, 2018: Acta Tropica
Søren D Nielsen, Robert L Beverly, David C Dallas
Previous work demonstrates that proteases present in human milk release hundreds of peptides derived from milk proteins. However, the question of whether human milk protein digestion begins within the mammary gland remains incompletely answered. The primary objective of this study was to determine whether proteolytic degradation of human milk proteins into peptides begins within the mammary gland. The secondary objectives were to determine which milk proteases participate in the proteolysis and to predict which released peptides have bioactivity...
February 20, 2018: Journal of Mammary Gland Biology and Neoplasia
Magdalena Markowicz-Piasecka, Kristiina M Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Type 2 diabetes mellitus (T2DM) is characterised not only by hyperglycaemia and insulin resistance but also an impaired balance between the processes of coagulation and fibrinolysis. The aim of this study was to examine the effects of metformin, a widely-used oral anti-diabetic drug, phenformin and eight sulfenamide and sulfonamide derivatives of metformin on several haemostasis parameters. Thrombin Time (TT) tests were performed according to the available commercial method. The activity of factor X was conducted based on deficient plasma factor X...
February 16, 2018: Chemico-biological Interactions
Ngoc T T Nguyen, Florian Röttgerding, Gayatri Devraj, Yi-Pin Lin, Arno Koenigs, Peter Kraiczy
The emerging relapsing fever spirochete Borrelia ( B .) miyamotoi is transmitted by ixodid ticks and causes the so-called hard tick-borne relapsing fever or B. miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule, CbiA exhibiting complement binding and inhibitory capacity and rendering spirochetes resistant to complement-mediated lysis. To gain deeper insight into the molecular principles of B. miyamotoi -host interaction, we examined CbiA as a plasmin(ogen) receptor that enables B...
2018: Frontiers in Cellular and Infection Microbiology
M Baithun, T Freeman-Wang, P Chowdary, R A Kadir
BACKGROUND: Congenital plasminogen deficiency is a rare autosomal recessive condition. Plasminogen deficiency is thought to result in an inability of fibrin breakdown and therefore accumulation of fibrin and formation of ligneous changes. Ligneous lesions can form on a number of mucosal membranes including the cervix and endometrium. METHODS: We report the case of a 25-year-old woman with type 1 plasminogen deficiency with ligneous cervicitis and endometritis and her treatment and clinical course over the last few years...
February 13, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Takeshi Tohgasaki, Naoko Ozawa, Takashi Yoshino, Shioji Ishiwatari, Shoko Matsukuma, Shigeru Yanagi, Hidetsugu Fukuda
OBJECTIVE: Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated and the role of high ENO1 expression in keratinocytes was characterized...
February 11, 2018: International Journal of Cosmetic Science
Jonathan R Bezenah, Yen P Kong, Andrew J Putnam
A major translational challenge in the fields of therapeutic angiogenesis and regenerative medicine is the need to create functional microvasculature. The purpose of this study was to assess whether a potentially autologous endothelial cell (EC) source derived from human induced pluripotent stem cells (iPSC-ECs) can form the same robust, stable microvasculature as previously documented for other sources of ECs. We utilized a well-established in vitro assay, in which endothelial cell-coated (iPSC-EC or HUVEC) beads were co-embedded with fibroblasts in a 3D fibrin matrix to assess their ability to form stable microvessels...
February 8, 2018: Scientific Reports
Mina Amanzadeh, Ali Mota, Nosratollah Zarghami, Sima Abedi-Azar, Sina Abroon, Naghmeh Akbarian, Aynaz Mihanfar, Mohammad Rahmati-Yamchi
INTRODUCTION: Diabetic nephropathy is pictured as matrix accumulation and thickening of glomerular basal membrane. Matrix metalloproteinases (MMPs) are major proteases involved in extracellular matrix degradation. Moreover, plasminogen activator inhibitor-1 (PAI-1) primarily regulates plasmin dependent proteolysis. It plays a role in renal fibrosis causing extracellular matrix accumulation through inhibition of plasmin-dependent extracellular matrix degradation. This study investigated PAI-1 serum level and MMP-3 activity and their correlation with glomerular filtration rate in patients with diabetes mellitus...
January 2018: Iranian Journal of Kidney Diseases
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