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https://www.readbyqxmd.com/read/28035745/one-amino-acid-in-mouse-factor-viia-defines-its-endothelial-protein-c-receptor-binding-and-modulates-its%C3%A2-epcr-dependent-hemostatic-activity-in-vivo
#1
G Pavani, S M Zintner, L Ivanciu, J C Small, K A Stafford, J H Szeto, P Margaritis
BACKGROUND: Human activated Factor VII (hFVIIa), used in hemophilia treatment, binds to the endothelial Protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the Factor VIIa (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) using 3 substitutions from mouse Protein C (mPC, Leu4→Phe, Leu8→Met and Trp9→Arg)...
December 30, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28028391/vascular-genetic-variants-and-ischemic-stroke-susceptibility-in-albanians-from-the-republic-of-macedonia
#2
Bajram Kamberi, Farije Kamberi, Mirko Spiroski
BACKGROUND: Acute first-ever ischemic stroke (FIS) is a heterogeneous, polygenic disorder. The contribution of vascular genetic variants as inherited causes of ischemic stroke has remained controversial. AIM: To examine the association of genetic variants in vascular factors with the occurrence of FIS. MATERIAL AND METHODS: The current research was performed in a group of 39 patients with FIS (study group) and 102 healthy volunteers (control group)...
December 15, 2016: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28007459/endothelial-markers-are-associated-with-pancreatic-necrosis-and-overall-prognosis-in-acute-pancreatitis-a-preliminary-cohort-study
#3
Yizhe Chen, Lu Ke, Lei Meng, Qi Yang, Zhihui Tong, Yiyuan Pan, Weiqin Li, Jieshou Li
BACKGROUND: Endothelial injury is believed to play an important role in the evolution of pancreatic microcirculatory dysfunction and pancreatic necrosis (PN) in patients with acute pancreatitis (AP). The aim of this study was to investigate the role of three endothelial markers (von Willebrand factor, vWF; E-selectin; endothelial protein C receptor, EPCR) in the early phase of AP, especially the relationship between endothelial markers and PN. METHODS: From March 2015 to March 2016, 57 AP patients admitted within 72 h of symptom onset in our hospital were included for this study...
December 15, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/27995727/kinetic-analysis-and-binding-studies-of-a-new-recombinant-human-factor-viia-for-treatment-of-haemophilia
#4
J Grandoni, G Perret, C Forier
INTRODUCTION/AIM: LR769 is a new second-generation recombinant human Factor VIIa (rhFVIIa) developed for haemophilia treatment. We determined enzymatic properties of LR769 and its interaction with antithrombin, tissue factor, platelets and endothelial protein C receptor (EPCR), compared with NovoSevenRT. METHODS: Kinetic enzyme assays and active site titration were used for enzymatic studies. Surface Plasmon Resonance (SPR) was used for determination of binding constants...
December 19, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27939609/epcr-and-malaria-severity-the-center-of-a-perfect-storm
#5
REVIEW
Maria Bernabeu, Joseph D Smith
Severe malaria due to Plasmodium falciparum infection causes nearly half a million deaths per year. The different symptomatology and disease manifestations among patients have hampered understanding of severe malaria pathology and complicated efforts to develop targeted disease interventions. Infected erythrocyte sequestration in the microvasculature plays a critical role in the development of severe disease, and there is increasing evidence that cytoadherent parasites interact with host factors to enhance the damage caused by the parasite...
December 6, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/27915294/insightful-directed-evolution-of-escherichia-coli-quorum-sensing-promoter-region-of-the-lsracdbfg-operon-a-tool-for-synthetic-biology-systems-and-protein-expression
#6
Pricila Hauk, Kristina Stephens, Ryan Mckay, Chelsea Ryan Virgile, Hana Ueda, Marc Ostermeier, Kyoung-Seok Ryu, Herman O Sintim, William E Bentley
Quorum sensing (QS) regulates many natural phenotypes (e.q. virulence, biofilm formation, antibiotic resistance), and its components, when incorporated into synthetic genetic circuits, enable user-directed phenotypes. We created a library of Escherichia coli lsr operon promoters using error-prone PCR (ePCR) and selected for promoters that provided E. coli with higher tetracycline resistance over the native promoter when placed upstream of the tet(C) gene. Among the fourteen clones identified, we found several mutations in the binding sites of QS repressor, LsrR...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27909955/suppressive-effects-of-dabrafenib%C3%A2-on-endothelial-protein-c-receptor-shedding
#7
Sae-Kwang Ku, Jongdoo Kim, Sang Chan Kim, Jong-Sup Bae
Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Dabrafenib (DAB) is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. However, little is known about the effects of DAB on EPCR shedding. We investigated this issue by monitoring the effects of DAB on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1β-induced EPCR shedding in human umbilical vein endothelial cells (HUVECs), and cecal ligation and puncture (CLP)-mediated EPCR shedding in mice and underlying mechanism...
December 1, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27864015/prediction-of-overall-survival-for-patients-with-metastatic-castration-resistant-prostate-cancer-development-of-a-prognostic-model-through-a-crowdsourced-challenge-with-open-clinical-trial-data
#8
Justin Guinney, Tao Wang, Teemu D Laajala, Kimberly Kanigel Winner, J Christopher Bare, Elias Chaibub Neto, Suleiman A Khan, Gopal Peddinti, Antti Airola, Tapio Pahikkala, Tuomas Mirtti, Thomas Yu, Brian M Bot, Liji Shen, Kald Abdallah, Thea Norman, Stephen Friend, Gustavo Stolovitzky, Howard Soule, Christopher J Sweeney, Charles J Ryan, Howard I Scher, Oliver Sartor, Yang Xie, Tero Aittokallio, Fang Liz Zhou, James C Costello
BACKGROUND: Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease...
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27833109/intrapleural-adenoviral-mediated-endothelial-cell-protein-c-receptor-gene-transfer-suppresses-the-progression-of-malignant-pleural-mesothelioma-in-a-mouse-model
#9
Shiva Keshava, L Vijaya Mohan Rao, Usha R Pendurthi
Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer with a high mortality rate as it responds poorly to standard therapeutic interventions. Our recent studies showed that expression of endothelial cell protein C receptor (EPCR) in MPM cells suppresses tumorigenicity. The present study was aimed to investigate the mechanism by which EPCR suppresses MPM tumor growth and evaluate whether EPCR gene therapy could suppress the progression of MPM in a mouse model of MPM. Measurement of cytokines from the pleural lavage showed that mice implanted with MPM cells expressing EPCR had elevated levels of IFNγ and TNFα compared to mice implanted with MPM cells lacking EPCR...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27784899/plasma-ang2-and-adam17-levels-are-elevated-during-clinical-malaria-ang2-level-correlates-with-severity-and-expression-of-epcr-binding-pfemp1
#10
Jens E V Petersen, Sixbert I Mkumbaye, Anna V Vaaben, Alphaxard Manjurano, Eric Lyimo, Reginald A Kavishe, Steven B Mwakalinga, Jacklin Mosha, Daniel T R Minja, John P A Lusingu, Thor G Theander, Thomas Lavstsen, Christian W Wang
The pathogenesis of Plasmodium falciparum malaria involves a complex interplay between parasite adhesion and inflammatory response that includes release of cytokines and activation of the endothelium with accompanying release of Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloproteinase 17 (ADAM17) is a protein responsible for releasing cytokines, including Tumor Necrosis Factor α (TNFα), and shedding of adhesion proteins. In this study, we show that plasma levels of ADAM17 are increased in Tanzanian children hospitalized with a malaria infection compared with asymptomatic children but similar to children hospitalized with other infectious diseases...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27771530/thrombin-and-protein-c-pathway-in-peripheral-nerve-schwann-cells
#11
Orna Gera, Efrat Shavit-Stein, Doron Bushi, Sagi Harnof, Marina Ben Shimon, Ronen Weiss, Valery Golderman, Amir Dori, Nicola Maggio, Kate Finegold, Joab Chapman
Thrombin and activated protein C (aPC) bound to the endothelial protein C receptor (EPCR) both activate protease-activated receptor 1 (PAR1) generating either harmful or protective signaling respectively. In the present study we examined the localization of PAR-1 and EPCR and thrombin activity in Schwann glial cells of normal and crushed peripheral nerve and in Schwannoma cell lines. In the sciatic crush model nerves were excised 1h, 1, 4, and 7days after the injury. Schwannoma cell lines produced high levels of prothrombin which is converted to active thrombin and expressed both EPCR and PAR-1 which co-localized...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27671831/triggering-receptor-expressed-on-myeloid-cells-1-trem-1-and-cytokine-gene-variants-in-complicated-and-uncomplicated-malaria
#12
Selorme Adukpo, Ben A Gyan, Michael F Ofori, Daniel Dodoo, Thirumalaisamy P Velavan, Christian G Meyer
BACKGROUND: Malaria elicits inflammatory responses, which, if not well regulated, may exert detrimental effects. When activated, triggering receptor expressed on myeloid cells 1 (TREM-1) enhances inflammatory responses by increasing secretion of IL-8 and other Th1 cytokines. In contrast, TREM-like transcript 1 (TREML-1) promotes anti-inflammatory responses by binding to TREM-1 ligands and competing with TREM-1, thus antagonizing TREM-1 activation to reduce inflammation. Endothelial protein C receptor (EPCR) also mediates anti-inflammatory responses by activating endothelial protein C (PC)...
December 2016: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/27671049/-expression-and-significance-of-epcr-in-plasma-and-placenta-of-patients-with-early-onset-severe-preeclampsia
#13
J M Zhu, M He, L Huang, Y L Su, L Li, M Li
Objective: To investigate the expression of endothelial protein C receptor(EPCR)and its roles in plasma and placenta of patients with early onset severe preeclampsia. Methods: Sixty cases of severe preeclampsia women who delivered in Xuzhou Maternity and Child Health Care Hospital from March 2014 to February 2016, were recruited, which included 30 cases with early onset severe preeclampsia(early onset group, gestational week <34 weeks)and 30 patients with late onset severe preeclampsia(late onset group, gestational week ≥34 weeks)...
September 25, 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/27569971/human-endothelial-protein-c-receptor-overexpression-protects-intraportal-islet-grafts-in-mice
#14
H Gock, K F E Lee, L Murray-Segal, T B Mysore, A J F d'Apice, E J Salvaris, P J Cowan
Islet transplantation can potentially cure type 1 diabetes mellitus, but it is limited by a shortage of human donors as well as by islet graft destruction by inflammatory and thrombotic mechanisms. A possible solution to these problems is to use genetically modified pig islets. Endothelial protein C receptor (EPCR) enhances protein C activation and regulates coagulation, inflammation, and apoptosis. We hypothesized that human EPCR (hEPCR) expression on donor islets would improve graft survival and function...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27561318/occupancy-of-human-epcr-by-protein-c-induces-%C3%AE-arrestin-2-biased-par1-signaling-by-both-apc-and-thrombin
#15
Ram Vinod Roy, Abdolreza Ardeshirylajimi, Peyman Dinarvand, Likui Yang, Alireza R Rezaie
Activation of PAR1 by activated protein C (APC) and thrombin elicits paradoxical cytoprotective and cytotoxic signaling responses in vascular endothelial cells through cleavage of the receptor at Arg-46 and Arg-41 protease recognition sites, respectively. It has been reported that unlike a disruptive G-protein mediated PAR1 signaling by thrombin, APC induces a protective β-arrestin-2 biased PAR1 signaling by unknown mechanisms. We hypothesize that the occupancy of endothelial protein C receptor (EPCR) by the Gla-domain of protein C/APC is responsible for the β-arrestin-2 biased PAR1 signaling independent of the protease cleavage site...
August 25, 2016: Blood
https://www.readbyqxmd.com/read/27532815/isolation-and-assessment-of-single-long-term-reconstituting-hematopoietic-stem-cells-from-adult-mouse-bone-marrow
#16
David G Kent, Brad J Dykstra, Connie J Eaves
Hematopoietic stem cells with long-term repopulating activity can now be routinely obtained at purities of 40% to 50% from suspensions of adult mouse bone marrow. Here we describe robust protocols for both their isolation as CD45(+) EPCR(+) CD150(+) CD48(-) (ESLAM) cells using multiparameter cell sorting and for tracking their clonal growth and differentiation activity in irradiated mice transplanted with single ESLAM cells. The simplicity of these procedures makes them attractive for characterizing the molecular and biological properties of individual hematopoietic stem cells with unprecedented power and precision...
2016: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/27460991/assessment-of-the-rifle-criteria-for-the-diagnosis-of-acute-kidney-injury-a-retrospective-study-in-south-western-ghana
#17
Richard K D Ephraim, Kwame O Darkwah, Samuel A Sakyi, Mabel Ephraim, Enoch O Antoh, Prince Adoba
BACKGROUND: Acute kidney injury (AKI) affects 3-7 % of patients admitted to the hospital and approximately 25-30 % of patients in the intensive care unit. RIFLE, a newly developed international consensus classification for AKI, defines three grades of severity-class R (risk), I (injury) and F (failure). The aim of this study was to evaluate whether the RIFLE system of classification can detect the incidence of AKI using retrospective data of in-patients at the Effia-Nkwanta Regional Hospital...
2016: BMC Nephrology
https://www.readbyqxmd.com/read/27406562/interaction-between-endothelial-protein-c-receptor-and-intercellular-adhesion-molecule-1-to-mediate-binding-of-plasmodium-falciparum-infected-erythrocytes-to-endothelial-cells
#18
Marion Avril, Maria Bernabeu, Maxwell Benjamin, Andrew Jay Brazier, Joseph D Smith
UNLABELLED: Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P...
2016: MBio
https://www.readbyqxmd.com/read/27354391/plasmodium-falciparum-var-genes-expressed-in-children-with-severe-malaria-encode-cidr%C3%AE-1-domains
#19
Jakob S Jespersen, Christian W Wang, Sixbert I Mkumbaye, Daniel Tr Minja, Bent Petersen, Louise Turner, Jens Ev Petersen, John Pa Lusingu, Thor G Theander, Thomas Lavstsen
Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria...
2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27255786/the-endothelial-protein-c-receptor-rs867186-gg-genotype-is-associated-with-increased-soluble-epcr-and-could-mediate-protection-against-severe-malaria
#20
Estela Shabani, Robert O Opoka, Paul Bangirana, Gregory S Park, Gregory M Vercellotti, Weihua Guan, James S Hodges, Thomas Lavstsen, Chandy C John
The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC)...
June 3, 2016: Scientific Reports
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