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https://www.readbyqxmd.com/read/28089737/browplasminin-a-condensed-tannin-with-anti-plasmin-activity-isolated-from-an-aqueous-extract-of-brownea-grandiceps-jacq-flowers
#1
Betzabeth Pereira, Josmary Brazón, Mónica Rincón, Eva Vonasek
ETHNOPHARMACOLOGICAL RELEVANCE: Following Venezuelan traditional medicine, females with heavy menstrual blood loss (menorrhagia) drink Brownea grandiceps Jacq. flowers (BG) decoctions to reduce the bleeding. In a previous study, we demonstrated that BG aqueous extract (E) possesses a potent anti-fibrinolytic activity capable of inhibiting plasmin, the main serine-protease that degrades fibrin. It is widely known that plasmin inhibitors are often used as anti-fibrinolytics to reduce bleeding during surgeries with high risk of blood loss such as cardiac, liver, vascular, tooth extraction and large orthopedic procedures, as well as for menorrhagia treatments...
January 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28081265/the-plasmin-sensitive-protein-pls-in-methicillin-resistant-staphylococcus-aureus-mrsa-is-a-glycoprotein
#2
Isabelle Bleiziffer, Julian Eikmeier, Gottfried Pohlentz, Kathryn McAulay, Guoqing Xia, Muzaffar Hussain, Andreas Peschel, Simon Foster, Georg Peters, Christine Heilmann
Most bacterial glycoproteins identified to date are virulence factors of pathogenic bacteria, i.e. adhesins and invasins. However, the impact of protein glycosylation on the major human pathogen Staphylococcus aureus remains incompletely understood. To study protein glycosylation in staphylococci, we analyzed lysostaphin lysates of methicillin-resistant Staphylococcus aureus (MRSA) strains by SDS-PAGE and subsequent periodic acid-Schiff's staining. We detected four (>300, ∼250, ∼165, and ∼120 kDa) and two (>300 and ∼175 kDa) glycosylated surface proteins with strain COL and strain 1061, respectively...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28066629/orchestration-of-the-crosstalk-between-astrocytes-and-cancer-cells-affects-the-treatment-and-prognosis-of-lung-cancer-sufferers-with-brain-metastasis
#3
COMMENT
Wangshu Dai, Hongcheng Zhu, Guangzong Chen, Hao Gu, Yihang Gu, Xinchen Sun, Xiaoning Zeng
Brain metastasis is an inauspicious consequence of lung cancer. However, the majority of cancer cells that seep into the brain died of unknown causes, only a few survived and developed into metastatic brain tumor. Communication between cancer cells and host tissue is viewed as an essential event during metastasis, but little is known about the accurate control of this processes. Within the lesion of brain metastasis, abundant activated astrocytes are observed with lung cancer cells. Previous studies have demonstrated that the astrocyte network served a protective role in the central nervous system (CNS) and most malignant cells that seep into the brain perish were rejected by astrocytes...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#4
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death due to hemorrhage remains unacceptably common and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
January 4, 2017: Blood
https://www.readbyqxmd.com/read/28052305/plasmin-ogen-at-the-nexus-of-fibrinolysis-inflammation-and-complement
#5
Jonathan H Foley
The diverse mechanisms by which the plasmin(ogen) system is involved in human physiology and pathology are constantly being delineated. For many years, the plasmin(ogen) system was chiefly known as the system responsible for vascular fibrinolysis. Although this is an important function of the plasmin(ogen) system, we now recognize that plasmin(ogen) is critically important as a mediator of inflammation and the innate immune system, which impacts upon a diverse set of mechanisms underlying the pathologies of many diseases...
January 4, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28035006/factor-xiia-as-a-novel-target-for-thrombosis-target-engagement-requirement-and-efficacy-in-a-rabbit-model-of-microembolic-signals
#6
Christopher M Barbieri, Xinkang Wang, Weizhen Wu, Xueping Zhou, Aimie M Ogawa, Kim O'Neill, Donald Chu, Gino Castriota, Dietmar A Seiffert, David E Gutstein, Zhu Chen
Coagulation Factor XII (FXII) plays a critical role in thrombosis. What is unclear is the level of enzyme occupancy of FXIIa needed for efficacy, and impact of FXIIa inhibition on cerebral embolism. A selective FXIIa inhibitor, recombinant human albumin-tagged mutant Infestin4 (rHA-Mut-inf), was generated to address these questions. rHA-Mut-inf displayed potency comparable to the original wild-type HA-Infestin4 (rHA-WT-inf) (human FXIIa KI = 0.07 and 0.12 nM, respectively), with markedly improved selectivity against FXa and plasmin...
December 29, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28028981/assessment-of-selected-rotem-parameters-kinetics-of-fibrinogen-polymerization-and-plasmin-amidolytic-activity-in-patients-with-congenital-fibrinogen-defects
#7
Jacek Treliński, Katarzyna Pachniewska, Justyna Matczak, Marta Robak, Krzysztof Chojnowski
BACKGROUND: Congenital fibrinogen disorders (CFD) are rare fibrinogen deficiencies which may be quantitative or functional. The clinical course of hypofibrinogenemia (hypoFI) or dysfibrinogenemia (dysFI) is unpredictable and cannot be determined by the application of standard hemostasis tests. OBJECTIVES: The main aim of this study was to assess ROTEM parameters in CFD patients. MATERIAL AND METHODS: Nine patients with CFD were studied. The fibrinogen concentration was measured functionally and antigenically...
November 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28028005/releasing-the-brakes-on-the-fibrinolytic-system-in-pulmonary-emboli-unique-effects-of-plasminogen-activation-and-%C3%AE-2-antiplasmin-inactivation
#8
Satish Singh, Aiilyan K Houng, Guy L Reed
BACKGROUND: -In patients with hemodynamically significant pulmonary embolism, physiologic fibrinolysis fails to dissolve thrombi acutely and recombinant tissue plasminogen activator (r-tPA) therapy may be required, despite its bleeding risk. To examine potential mechanisms, we analyzed the expression of key fibrinolytic molecules in experimental pulmonary emboli, assessed the contribution of α2-antiplasmin to fibrinolytic failure and compared the effects of plasminogen activation and α2-antiplasmin-inactivation on experimental thrombus dissolution and bleeding...
December 27, 2016: Circulation
https://www.readbyqxmd.com/read/28007568/hyaluronic-acid-decreases-the-mechanical-stability-but-increases-the-lytic-resistance-of-fibrin-matrices
#9
Erzsébet Komorowicz, Nóra Balázs, Zoltán Varga, László Szabó, Attila Bóta, Krasimir Kolev
Hyaluronic acid (HA) is a large, non-sulfated glucosaminoglycan abundantly present at sites where fibrin is also formed (during wound healing, in arterial restenotic lesions and eroded atherosclerotic plaques). The aim of the present study was to characterize the structure of composite fibrin-HA clots with scanning electron microscopy (SEM), pressure-driven permeation and small-angle X-ray scattering (SAXS) and their viscoelastic properties with an oscillation rheometer. In addition the efficiency of fibrinolysis in these clots was investigated by kinetic turbidimetric and chromogenic assays for dissolution of fibrin and plasminogen activation by tissue-type plasminogen activator (tPA)...
December 19, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27993197/tranexamic-acid-prolongs-survival-after-controlled-hemorrhage-in-rats
#10
Max Roy, Manuel Burggraf, Sven Lendemans, Herbert de Groot, Ricarda Rohrig
BACKGROUND: The plasmin/plasminogen inhibitor tranexamic acid (TXA) is mainly used in elective surgeries with a higher blood loss to avoid uncontrolled bleeding. Recently, TXA has also been shown to reduce mortality in trauma patients. It is assumed that its beneficial effects are principally caused by its antifibrinolytic properties. We hypothesize that TXA also improves survival in a modified Wigger's model of hemorrhagic shock by a mechanism other than antifibrinolysis. MATERIALS AND METHODS: Male Wistar rats were intermittently bled until the mean arterial blood pressure was dropped to 25-30 mm Hg (severe shock)...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27992087/urokinase-type-plasminogen-activator-modulates-mammalian-circadian-clock-phase-regulation-in-tissue-type-plasminogen-activator-knockout-mice
#11
Joanna M Cooper, Ashutosh Rastogi, Jessica A Krizo, Eric M Mintz, Rebecca A Prosser
Glutamate phase shifts the circadian clock in the mammalian suprachiasmatic nucleus (SCN) by activating NMDA receptors. Tissue-type plasminogen activator (tPA) gates phase shifts by activating plasmin to generate m(ature)BDNF, which binds TrkB receptors allowing clock phase shifts. Here we investigate phase shifting in tPA knockout (tPA(-/-) ; B6.129S2-Plat(tm1Mlg) /J) mice, and identify urokinase-type plasminogen activator (uPA) as an additional circadian clock regulator. Behavioral activity rhythms in tPA(-/-) mice entrain to a light-dark (LD) cycle and phase shift in response to nocturnal light pulses with no apparent loss in sensitivity...
December 19, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27989763/the-multifaceted-roles-of-leptospira-enolase
#12
Natália Salazar, Matilde Costa Lima de Souza, Amanda Gameiro Biasioli, Ludmila Bezerra da Silva, Angela Silva Barbosa
A previous study had demonstrated that Leptospira enolase is secreted extracellularly by a yet unknown mechanism and reassociates with the bacterial membrane. Surface-anchored leptospiral enolase displays plasminogen binding activity. In this work, we explored the consequences of this interaction and also assessed whether Leptospira enolase might display additional moonlighting functions by interacting with other host effector proteins. We first demonstrated that enolase-bound plasminogen is converted to its active form, plasmin...
October 28, 2016: Research in Microbiology
https://www.readbyqxmd.com/read/27986809/urokinase-type-plasminogen-activator-upa-binding-to-the-upa-receptor-upar-promotes-axonal-regeneration-in-the-central-nervous-system
#13
Paola Merino, Ariel Diaz, Valerie Jeanneret, Fang Wu, Enrique Torre, Lihong Cheng, Manuel Yepes
Axonal injury is a common cause of neurological dysfunction. Unfortunately, in contrast to axons from the peripheral nervous system, the limited capacity of regeneration of central nervous system (CNS) axons is a major obstacle for functional recovery in patients suffering neurological diseases that involve the subcortical white matter. Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to the urokinase-type plasminogen activator receptor (uPAR) catalyzes the conversion of plasminogen into plasmin on the cell surface...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27983472/characterization-of-two-new-putative-adhesins-of-leptospira-interrogans
#14
Jupciana Figueredo, Gabriela Siqueira, Gisele Souza, Marcos Heinemann, Silvio Vasconcellos, Erica Chapola, Ana Lucia T O Nascimento
We here report the characterization of two novel proteins encoded by the genes LIC11122 and LIC12287, identified in the genome sequences of Leptospira interrogans, annotated, respectively, as a putative sigma factor and hypothetical. . The coding sequences (CDSs) LIC11122 and LIC12287 have signal peptide SPII and SPI and are predicted to be located mainly at the cytoplasm membrane of the bacteria. The genes were cloned and the proteins expressed using Escherichia coli. Proteinase K digestion showed that both proteins are surface exposed...
December 15, 2016: Microbiology
https://www.readbyqxmd.com/read/27976897/potent-selective-allosteric-inhibition-of-human-plasmin-by-sulfated-non-saccharide-glycosaminoglycan-mimetics
#15
Daniel K Afosah, Rami A Al-Horani, Nehru Viji Sankaranarayanan, Umesh R Desai
Although plasmin inhibitors could be used in multiple disorders, their use has been restricted to preventing blood loss hemostatic dysregulation because of poor efficacy and adverse effects of current agents. We reasoned that a new class of direct inhibitors that offer better efficacy, selectivity and safety could be discovered by exploiting allosterism in plasmin, a protease homologous to other allosteric serine proteases. We report on the synthesis, biological activity, and mechanism of action of a group of small molecules, called non-saccharide glycosaminoglycan mimetics (NSGMs), as direct allosteric plasmin inhibitors...
December 15, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27935848/plasmin-ogen-serves-as-a-favorable-biomarker-for-prediction-of-survival-in-advanced-high-grade-serous-ovarian-cancer
#16
Shuo Zhao, Julia Dorn, Rudolf Napieralski, Axel Walch, Sandra Diersch, Matthias Kotzsch, Nancy Ahmed, John D Hooper, Marion Kiechle, Manfred Schmitt, Viktor Magdolen
In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed...
January 6, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27927771/propagation-of-thrombosis-by-neutrophils-and-extracellular-nucleosome-networks
#17
Susanne Pfeiler, Konstantin Stark, Steffen Massberg, Bernd Engelmann
Neutrophils, early mediators of innate immune defense, are recruited to developing thrombi in different types of thrombosis. They amplify intravascular coagulation by stimulating the tissue factor-dependent extrinsic pathway via inactivation of endogenous anticoagulants, enhancing factor XII activation or decreasing plasmin generation. Neutrophil-dependent prothrombotic mechanisms are supported by the externalization of decondensed nucleosomes and granule proteins that together form neutrophil extracellular traps...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27923263/microparticles-and-fibrinolysis
#18
Loris Vallier, Sylvie Cointe, Romaric Lacroix, Amandine Bonifay, Coralie Judicone, Françoise Dignat-George, Hau C Kwaan
Microparticles (MPs) are submicronic vesicles which are formed by budding of the cellular membrane of virtually any cell type in response to cell activation or apoptosis. Both circulating MPs and MPs generated within tissues harbor molecules with a large repertoire of biological activities and transfer material to target cells. Depending on their cellular origin, the stimuli triggering their formation, or their localization, they may participate in the maintenance of organ or vascular homeostasis as well as inducing dysfunction...
December 6, 2016: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/27900590/assessment-of-oxidative-nitrative-modifications-of-plasma-proteins-selected-rotem-parameters-and-kinetics-of-fibrinogen-polymerization-in-patients-with-multiple-myeloma-at-diagnosis
#19
W Nowak, J Treliński, K Chojnowski, J Matczak, M Robak, M Misiewicz, P Nowak
Patients with multiple myeloma (MM) are at increased risk of thrombosis. Growing evidence indicates that oxidative and nitrative modifications of proteins, including fibrinogen, may lead to changes in hemostasis. The study compares samples from patients with MM at diagnosis and healthy volunteers with regard to the oxidative/nitrative modifications of proteins, ROTEM and thrombin-catalyzed fibrin polymerization. The content of carbonyl groups in plasma proteins of patients with MM was significantly higher than in controls (2...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27898513/inhibition-of-plasmin-generation-in-plasma-by-heparin-low-molecular-weight-heparin-and-a-covalent-antithrombin-heparin-complex
#20
Gabriela M T Chang, Helen M Atkinson, Leslie R Berry, Anthony K C Chan
The clinical limitations of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) led to the development of an antithrombin-heparin covalent complex (ATH), which displays superior anticoagulant abilities compared with UFH. A recent study investigating its interaction with fibrinolysis showed that ATH inhibited free and fibrin bound plasmin and decreased plasmin generation on fibrin clots. These studies were conducted using purified components and did not elucidate the interaction of ATH with plasmin in the presence of its natural inhibitors α2-antiplasmin (α2-AP) and α2-macroglobulin (α2-M)...
November 24, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
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