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https://www.readbyqxmd.com/read/28820062/urokinase-type-plasminogen-activator-and-the-molecular-mechanisms-of-its-regulation-in-cancer
#1
Juan Francisco Santibanez
Urokinase type plasminogen activator (uPA) is a 53-kDa serine protease initially synthesized as a catalytically inactive single chain polypeptide. Inactive-uPA is subject to proteolytic cleavage which results in the two-chain active protein. uPA plays key roles in the enhancement of cell malignancy during tumor progression. uPA is finely regulated in normal cells, but dysregulated in tumor cells, which results in increased cellular invasion capacities reflecting changes in uPA activity and expression during tumor progression...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28819560/a-novel-peptide-blocking-cancer-cell-invasion-by-structure-based-drug-design
#2
Yuki Yamada, Seiji Kanayama, Fuminori Ito, Noriyuki Kurita, Hiroshi Kobayashi
The receptor for the urokinase-type plasminogen activator (uPA), uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. With computational prediction algorithms and structure-based drug design, we identified peptides containing the Gly-Lys-Gly-Glu-Gly-Glu-Gly-Lys-Gly sequence (peptide H1), which strongly interacts with uPAR. The aim of the present study was to investigate the effect of allosteric inhibition at the uPAR interface using a novel synthetic peptide and its function on ovarian cancer cell invasion...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28818858/pai-1-plasminogen-activator-inhibitor-1-expression-renders-alternatively-activated-human-macrophages-proteolytically-quiescent
#3
Philipp J Hohensinner, Johanna Baumgartner, Julia B Kral-Pointner, Pavel Uhrin, Benjamin Ebenbauer, Barbara Thaler, Konstantin Doberer, Stefan Stojkovic, Svitlana Demyanets, Michael B Fischer, Kurt Huber, Gernot Schabbauer, Walter S Speidl, Johann Wojta
OBJECTIVE: Macrophages are versatile immune cells capable of polarizing into functional subsets depending on environmental stimulation. In atherosclerotic lesions, proinflammatory polarized macrophages are associated with symptomatic plaques, whereas Th2 cytokine-polarized macrophages are inversely related with disease progression. To establish a functional cause for these observations, we analyzed extracellular matrix degradation phenotypes in polarized macrophages. APPROACH AND RESULTS: We provide evidence that proinflammatory polarized macrophages rely on membrane-bound proteases including matrix metalloproteinase 14 and the serine protease uPA (urokinase plasminogen activator) together with its receptor uPAR for extracellular matrix degradation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28804736/urokinase-type-plasminogen-activator-upa-and-its-receptor-upar-promote-neurorepair-in-the-ischemic-brain
#4
Paola Merino, Ariel Diaz, Manuel Yepes
Despite the fact that ischemic stroke has been considered a leading cause of mortality in the world, recent advances in our understanding of the pathophysiological mechanisms underlying the ischemic injury and the treatment of acute ischemic stroke patients have led to a sharp decrease in the number of stroke deaths. However, this decrease in stroke mortality has also led to an increase in the number of patients that survive the acute ischemic injury with different degrees of disability. Unfortunately, to this date we do not have an effective therapeutic strategy to promote neurological recovery in these growing population of stroke survivors...
2017: Receptors & Clinical Investigation
https://www.readbyqxmd.com/read/28803604/bone-marrow-urokinase-plasminogen-activator-receptor-levels-are-associated-with-the-progress-of-multiple-myeloma
#5
Li-Hong Shou, Dan Cao, Xiao-Hui Dong, Qiu Fang, Bao-Lian Xu, Ju-Ping Fei
Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors (uPAR) in bone marrow fluid and bone marrow tissue from multiple myeloma (MM) patients and assess association of uPAR level with prognosis of MM. Methods uPAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow (control) were examined by ELISA. Furthermore, uPAR expression in bone marrow tissue was investigated by RT-PCR and Western blot, respectively...
September 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28801387/microbubbles-and-ultrasound-accelerated-thrombolysis-must-for-peripheral-arterial-occlusions-protocol-for-a-phase-ii-single-arm-trial
#6
Harm P Ebben, Johanna H Nederhoed, Rutger J Lely, Willem Wisselink, Kakkhee Yeung
INTRODUCTION: Acute peripheral arterial occlusions can be treated with intra-arterial catheter-directed thrombolysis as an alternative to surgical thromboembolectomy. Although less invasive, this treatment is time-consuming and carries a significant risk of haemorrhagic complications. Contrast-enhanced ultrasound using microbubbles could accelerate dissolution of thrombi by thrombolytic medications due to mechanical effects caused by oscillation; this could allow for lower dosages of thrombolytics and faster thrombolysis, thereby reducing the risk of haemorrhagic complications...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28799434/metabolic-biomarkers-and-gallstone-disease-a-population-based-study
#7
Daniel Mønsted Shabanzadeh, Tea Skaaby, Lars Tue Sørensen, Jesper Eugen-Olsen, Torben Jørgensen
OBJECTIVES: The objectives for this study were to examine the associations between metabolic biomarkers of obesity including insulin resistance, vascular dysfunction, systemic inflammation, genetic susceptibility and ultrasound proven gallstone disease or cholecystectomy in a population-based cross-sectional study. MATERIAL AND METHODS: A total of 2650 participants were included, of whom 422 had gallstone disease. Associations between selected metabolic biomarkers and gallstone disease were estimated by multivariable logistic regression models and expressed as odds ratio (OR) and 95% confidence interval (CI)...
August 11, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28798909/analysis-of-urine-composition-in-type-ii-diabetic-mice-after-intervention-therapy-using-holothurian-polypeptides
#8
Yanyan Li, Jiajie Xu, Xiurong Su
Hydrolysates and peptide fractions (PF) obtained from sea cucumber with commercial enzyme were studied on the hyperglycemic and renal protective effects on db/db rats using urine metabolomics. Compared with the control group the polypeptides from the two species could significantly reduce the urine glucose and urea. We also tried to address the compositions of highly expressed urinary proteins using a proteomics approach. They were serum albumins, AMBP proteins, negative trypsin, elastase, and urinary protein, GAPDH, a receptor of urokinase-type plasminogen activator (uPAR), and Ig kappa chain C region...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28798096/activation-of-tissue-plasminogen-activator-by-metastasis-inducing-s100p-protein
#9
Christopher Clarke, Stephane R Gross, Thamir M Ismail, Philip S Rudland, Morteta Al-Medhtiy, Michael Santangeli, Roger Barraclough
S100P protein in human breast cancer cells is associated with reduced patient survival and, in a model system of metastasis, it confers a metastatic phenotype upon benign mammary tumour cells. S100P protein possesses a C-terminal lysine residue. Using a multiwell in vitro assay, S100P is now shown for the first time to exhibit a strong, C-terminal-lysine-dependent activation of tissue plasminogen activator (tPA), but not of urokinase-catalysed plasminogen activation.  The presence of 10 mM calcium ions stimulates tPA activation of plasminogen 2-fold in an S100P-dependent manner...
August 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28797406/ct-detected-growth-of-coronary-artery%C3%A2-calcification-in-asymptomatic-middle-aged-subjects-and-association-with-15-biomarkers
#10
Søren Zöga Diederichsen, Mette Hjortdal Grønhøj, Hans Mickley, Oke Gerke, Flemming Hald Steffensen, Jess Lambrechtsen, Niels Peter Rønnow Sand, Lars Melholt Rasmussen, Michael Hecht Olsen, Axel Diederichsen
OBJECTIVES: This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth. BACKGROUND: CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved. METHODS: At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score...
August 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28797008/resveratrol-attenuates-adriamycin-induced-focal-segmental-glomerulosclerosis-through-c3ar-c5ar-sphingosine-kinase-1-pathway
#11
Guoyong Liu, Qiang Wang, Yan Shi, Xiaofei Peng, Hong Liu, Youming Peng, Liyu He
BACKGROUND/AIM: Focal segmental glomerulosclerosis (FSGS) typically presents with nephrotic range proteinuria, which could eventually develop into end-stage renal disease. Resveratrol (RSV) is a natural polyphenol compound, which has been reported to suppress inflammatory response and renal interstitial fibrosis. This study is aimed at evaluating the renoprotective effect of RSV treatment on adriamycin-induced FSGS. METHODS: In Balb/c mice, adriamycin nephropathy was induced by adriamycin (10 mg/kg body weight, diluted in normal saline) via a tail vein on day 0...
August 11, 2017: Pharmacology
https://www.readbyqxmd.com/read/28794016/serine-protease-inhibitor-serpinb2-binds-and-stabilizes-p21-in-senescent-cells
#12
Hsi-Hsien Hsieh, Ying-Chieh Chen, Jing-Ru Jhan, Jing-Jer Lin
SerpinB2 is a serine protease inhibitor that is also known as plasminogen activator inhibitor type 2 (PAI-2). It has been well documented that SerpinB2 is an inhibitor of urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA). Interestingly, SerpinB2 level is increased in senescent cells and is considered a senescence biomarker. Through mimicking the elevated level of SerpinB2 in senescent cells, this study showed the proliferating human fibroblasts were induced into senescence. Senescence induced by SerpinB2 did not relate to its extracellular function as inhibition of SerpinB2 secretion, exogenous introduced SerpinB2, or a SerpinB2 mutant that failed to bind to its extracellular target uPA, did not have an effect on senescence...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28781127/evolution-of-practice-in-the-management-of-parapneumonic-effusion-and-empyema-in-children
#13
D Griffith, M Boal, T Rogers
AIM: To assess the evolution in management of children with parapneumonic effusion and empyema in a tertiary referral centre. METHOD: We conducted a retrospective case note review of paediatric patients with parapneumonic effusion, pleural effusion and pleural empyema between December 2006 and December 2015. Digital database searches were performed to identify demographic data, referring hospital, radiological and microbiological investigations. Length of stay and morbidity were analysed...
July 24, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28777401/novel-use-of-the-clarivein%C3%A2-catheter-for-pharmacomechanical-thrombolysis-of-thrombosed-hemodialysis-grafts-a-case-series
#14
Darryl Lim, Derek C Ho, Lionel Chen, Michiel A Schreve, Yih Kai Tan, Steven Kum
INTRODUCTION: The aim of this prospectively collected case series is to demonstrate a novel technique of using the ClariVein® catheter for pharmacomechanical thrombolysis of thrombosed hemodialysis grafts. METHODS: The analysis comprised 11 procedures in 9 patients from 1 July to 31 December 2016 in which the ClariVein catheter was used in combination with urokinase. Demographic data, procedural data, technical and clinical success rates, and complications were evaluated...
July 27, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28777093/expression-and-crystallographic-studies-of-the-d1d2-domains-of-c4-4a-a-homologous-protein-to-the-urokinase-receptor
#15
Shanli Chen, Lin Lin, Cai Yuan, Henrik Gårdsvoll, Mette C Kriegbaum, Michael Ploug, Mingdong Huang
C4.4A is a glycosylphosphatidylinositol-anchored membrane protein comprised of two LU domains (Ly6/uPAR-like domains) and an extensively O-glycosylated C-terminal Ser/Thr/Pro-rich region. C4.4A is a novel biomarker for squamous epithelial differentiation. Its expression is dysregulated under various pathological conditions and it is a robust biomarker for poor prognosis in various malignant conditions such as pulmonary adenocarcinoma. To facilitate crystallization, the two LU domains were excised from intact C4...
August 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28767067/sinulariolide-suppresses-cell-migration-and-invasion-by-inhibiting-matrix-metalloproteinase-2-9-and-urokinase-through-the-pi3k-akt-mtor-signaling-pathway-in-human-bladder-cancer-cells
#16
Te-Chih Cheng, Zhong-Hao Din, Jui-Hsin Su, Yu-Jen Wu, Chih-I Liu
Sinulariolide is a natural product extracted from the cultured-type soft coral Sinularia flexibilis, and possesses bioactivity against the movement of several types of cancer cells. However, the molecular pathway behind its effects on human bladder cancer remain poorly understood. Using a human bladder cancer cell line as an in vitro model, this study investigated the underlying mechanism of sinulariolide against cell migration/invasion in TSGH-8301 cells. We found that sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was concentration-dependent...
August 2, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28758975/elevated-soluble-urokinase-plasminogen-activator-receptor-and-proenkephalin-serum-levels-predict-the-development-of-acute-kidney-injury-after-cardiac-surgery
#17
Jana C Mossanen, Jessica Pracht, Tobias U Jansen, Lukas Buendgens, Christian Stoppe, Andreas Goetzenich, Joachim Struck, Rüdiger Autschbach, Gernot Marx, Frank Tacke
Acute kidney injury (AKI) develops in up to 40% of patients after cardiac surgery. The soluble urokinase plasminogen activator receptor (suPAR) has been identified as a biomarker for incident chronic kidney disease (CKD). Proenkephalin (proENK) also has been shown to be a biomarker for renal dysfunction. We hypothesized that pre-surgery suPAR and proENK levels might predict AKI in patients undergoing cardiac surgery. Consecutive patients (n = 107) undergoing elective cardiac surgery were studied prospectively...
July 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28758928/role-of-plasminogen-activator-inhibitor-type-1-in-pathologies-of-female-reproductive-diseases
#18
REVIEW
Yao Ye, Aurelia Vattai, Xi Zhang, Junyan Zhu, Christian J Thaler, Sven Mahner, Udo Jeschke, Viktoria von Schönfeldt
Normal pregnancy is a state of hypercoagulability with diminishing fibrinolytic activity, which is mainly caused by an increase of plasminogen activator inhibitor type 1 (PAI-1). PAI-1 is the main inhibitor of plasminogen activators, including tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). In human placentas, PAI-1 is expressed in extravillous interstitial trophoblasts and vascular trophoblasts. During implantation and placentation, PAI-1 is responsible for inhibiting extra cellular matrix (ECM) degradation, thereby causing an inhibition of trophoblasts invasion...
July 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28749394/serum-levels-of-soluble-urokinase-plasminogen-activator-receptor-as-a-new-inflammatory-marker-in-adolescent-obesity
#19
Ummugulsum Can, Muammer Buyukinan, Fatma Humeyra Yerlikaya
BACKGROUND & OBJECTIVES: Obesity is known for low-grade inflammatory state with enhanced production of inflammatory mediators in children and adolescents. Soluble urokinase plasminogen activator receptor (suPAR) can be generated as a pro-inflammatory marker. This study was conducted to evaluate the role of suPAR, and its association with leptin, adiponectin, interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP) and fibrinogen in adolescent obesity. METHODS: A total of 98 participants, 55 obese individuals and 43 healthy controls, aged between 10 and 17 yr, were included in the study...
March 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28737691/coagulopathy-in-the-setting-of-mild-traumatic-brain-injury-truths-and-consequences
#20
REVIEW
Joseph P Herbert, Andrew R Guillotte, Richard D Hammer, N Scott Litofsky
Mild traumatic brain injury (mTBI) is a common, although poorly-defined clinical entity. Despite its initially mild presentation, patients with mTBI can rapidly deteriorate, often due to significant expansion of intracranial hemorrhage. TBI-associated coagulopathy is the topic of significant clinical and basic science research. Unlike trauma-induced coagulopathy (TIC), TBI-associated coagulopathy does not generally follow widespread injury or global hypoperfusion, suggesting a distinct pathogenesis. Although the fundamental mechanisms of TBI-associated coagulopathy are far from clearly elucidated, several candidate molecules (tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), tissue factor (TF), and brain-derived microparticles (BDMP)) have been proposed which might explain how even minor brain injury can induce local and systemic coagulopathy...
July 22, 2017: Brain Sciences
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