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https://www.readbyqxmd.com/read/28644504/a-structural-mechanism-of-flavonoids-in-inhibiting-serine-proteases
#1
Guangpu Xue, Lihu Gong, Cai Yuan, Mingming Xu, Xu Wang, Longguang Jiang, Mingdong Huang
Quercetin is a member of the flavonoids and was previously demonstrated to inhibit trypsin-like serine proteases at micromolar potencies. Different molecular models were proposed to explain such inhibition. However, controversies remain on the molecular details of inhibition. Here, we report the X-ray crystal structure of quercetin in a complex with the urokinase-type plasminogen activator (uPA), an archetypical serine protease. The structure showed that quercetin binds to the specific substrate binding pocket (S1 pocket) of uPA mainly through its two neighboring phenolic hydroxyl groups...
June 23, 2017: Food & Function
https://www.readbyqxmd.com/read/28643938/oral-application-of-a-periodontal-pathogen-impacts-serpine1-expression-and-pancreatic-islet-architecture-in-prediabetes
#2
V Ilievski, U G Bhat, S Suleiman-Ata, B A Bauer, P T Toth, S T Olson, T G Unterman, K Watanabe
BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 β cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent...
June 23, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28643742/in-vitro-activity-of-probiotic-lactobacillus-reuteri-against-gastric-cancer-progression-by-downregulation-of-urokinase-plasminogen-activator-urokinase-plasminogen-activator-receptor-gene-expression
#3
Bahareh Sadat Rasouli, Ali Ghadimi-Darsajini, Reza Nekouian, Gholam-Reza Iragian
BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death, and most patients represent metastatic phenotype at the time of diagnosis. Urokinase plasminogen activator (uPA) system is well known for its critical roles in cancer cells invasion since uPA/uPA receptor (uPAR) overexpresses in several cancers. Subsequently, suppression of uPA/uPAR gene expression improves patients overall survival and prevents cancer progression. OBJECTIVES: The aim of the current study was to investigate possible effects of live Lactobacillus reuteri as a probiotic in inhibition of GC cells proliferation and invasion...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643198/urokinase-plasminogen-activator-protects-cardiac-myocytes-from-oxidative-damage-and-apoptosis-via-hogg1-induction
#4
Philipp J Hohensinner, Nikol Takacs, Christoph Kaun, Barbara Thaler, Konstantin A Krychtiuk, Stefan Pfaffenberger, Arezu Aliabadi, Andreas Zuckermann, Kurt Huber, Johann Wojta
The role of uPA in tissue remodeling and cell migration is already well established. In addition, uPA was reported to stabilize p53, a key cell cycle control, DNA repair and apoptosis initiation protein. We aimed to determine the role of uPA-uPAR signaling towards cell survival or apoptosis in human adult cardiac myocytes (HACM). HACM were stimulated with uPA and DNA damage was inflicted by incubating cells with 200 µM H2O2. To analyze for apoptotic cells we applied TUNEL staining. Oxidative damage foci were analyzed by staining for 8-oxoguanine base pairs...
June 22, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28632880/the-urokinase-receptor-derived-peptide-uparant-recovers-dysfunctional-electroretinogram-and-blood-retinal-barrier-leakage-in-a-rat-model-of-diabetes
#5
Maurizio Cammalleri, Filippo Locri, Stefania Marsili, Massimo Dal Monte, Claudio Pisano, Angelo Mancinelli, Liliana Lista, Dario Rusciano, Mario De Rosa, Vincenzo Pavone, Paola Bagnoli
Purpose: The activation of the urokinase-type plasminogen activator and its receptor system is associated with retinal diseases. Among peptide inhibitors of this system, UPARANT acts by preventing the onset of pathologic signs of neovascular ocular diseases. We investigated whether systemic UPARANT may act in a therapeutic regimen by suppressing the retinal damage that characterizes diabetic retinopathy using a rat model of streptozotocin-induced diabetes. Methods: In healthy rats, plasma, eye, and retina concentrations of UPARANT were evaluated by mass spectrometry...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28629718/changes-in-podocyte-trpc-channels-evoked-by-plasma-and-sera-from-patients-with-recurrent-fsgs-and-by-putative-glomerular-permeability-factors
#6
Eun Young Kim, Hila Roshanravan, Stuart E Dryer
Primary forms of focal and segmental glomeruloslerosis (FSGS) are driven by circulating factors that cause dysfunction or loss podocytes. Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca(2+)-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains. Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28627240/quercetin-has-antimetastatic-effects-on-gastric-cancer-cells-via-the-interruption-of-upa-upar-function-by-modulating-nf-%C3%AE%C2%BAb-pkc-%C3%AE-erk1-2-and-ampk%C3%AE
#7
Hai Li, Chen Chen
Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28626472/in-iga-nephropathy-glomerulosclerosis-is-associated-with-increased-urinary-cd80-excretion-and-urokinase-type-plasminogen-activator-receptor-positive-podocyturia
#8
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, José Andrews, Alejandro Iotti, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Elsa Zotta
BACKGROUND: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis...
May 2017: Nephron Extra
https://www.readbyqxmd.com/read/28624798/selection-of-optimal-molecular-targets-for-tumor-specific-imaging-in-pancreatic-ductal-adenocarcinoma
#9
Willemieke Tummers, Arantza Farina Sarasqueta, Martin Boonstra, Hendrica Prevoo, Cornelis Sier, Sven Mieog, Johannes Morreau, Casper van Eijck, Peter Kuppen, Cornelis van de Velde, Bert Bonsing, Alexander Vahrmeijer, Rutger-Jan Swijnenburg
Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases. Using immunohistochemistry (IHC), expression levels and patterns were investigated of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), Cathepsin E (Cath E), epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), thymocyte differentiation antigen 1 (Thy1), and urokinase-type plasminogen activator receptor (uPAR)...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623638/urokinase-containing-locking-solution-in-the-prevention-of-dialysis-catheter-dysfunction-a-double-blind-randomized-controlled-trial
#10
Florence Bonkain, Freya Van Hulle, Peter Janssens, Concetta Catalano, Mandelina Allamani, Jean-Claude Stolear, Dominique Vandervelde, Mark Libertalis, Serge Treille, Marie M Couttenye, Annemie Dhondt, Wim Van Biesen, Jean François Fils, Christian Tielemans, Karl M Wissing
INTRODUCTION: The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction...
June 14, 2017: Journal of Vascular Access
https://www.readbyqxmd.com/read/28618846/comparison-of-direct-iliofemoral-stenting-following-angiojet-rheolytic-thrombectomy-vs-staged-stenting-after-angiojet-rheolytic-thrombectomy-plus-catheter-directed-thrombolysis-in-patients-with-acute-deep-vein-thrombosis
#11
Guang Liu, Jinbao Qin, Chaoyi Cui, Kaichuang Ye, Huihua Shi, Xiaobing Liu, Minyi Yin, Xintian Huang, Min Lu, Mier Jiang, Weimin Li, Xinwu Lu
PURPOSE: To compare the treatment outcomes in patients with acute proximal deep vein thrombosis (DVT) and iliofemoral stenosis who underwent either direct stenting after AngioJet rheolytic thrombectomy or staged stenting after AngioJet thrombectomy plus catheter-directed thrombolysis with urokinase. METHODS: From June 2014 to February 2016, 91 DVT patients underwent 2 treatments for duplex-verified iliofemoral stenosis: direct stenting (n = 46; mean age 54.8 years; 32 men) or staged stenting (n = 45; mean age 56...
June 1, 2017: Journal of Endovascular Therapy
https://www.readbyqxmd.com/read/28614144/early-fibrinolysis-associated-with-hemorrhagic-progression-following-traumatic-brain-injury
#12
Jay Karri, Jessica C Cardenas, Nena Matijevic, Yao-Wei Wang, Sangbum Choi, Liang Zhu, Bryan A Cotton, Ryan Kitagawa, John B Holcomb, Charles E Wade
BACKGROUND: Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with worse outcomes. PHI pathophysiology remains poorly understood and difficult to predict. We performed an exploratory analysis aimed at identify markers in need of further investigation to establish their predictive value in PHI following TBI. METHODS: We performed a retrospective chart review of prospectively collected data from 424 highest-level activation trauma patients from January 2012 through December 2013...
June 13, 2017: Shock
https://www.readbyqxmd.com/read/28611361/discovery-of-a-novel-conformational-equilibrium-in-urokinase-type-plasminogen-activator
#13
Tobias Kromann-Hansen, Eva Louise Lange, Hans Peter Sørensen, Gholamreza Hassanzadeh-Ghassabeh, Mingdong Huang, Jan K Jensen, Serge Muyldermans, Paul J Declerck, Elizabeth A Komives, Peter A Andreasen
Although trypsin-like serine proteases have flexible surface-exposed loops and are known to adopt higher and lower activity conformations, structural determinants for the different conformations have remained largely obscure. The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis. We solved five X-ray crystal structures of murine uPA (muPA) in the absence and presence of allosteric molecules and/or substrate-like molecules...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610742/interventional-treatment-for-hepatic-artery-thrombosis-after-liver-transplantation
#14
Hua Zhang, Sheng Qian, Rong Liu, Wei Yuan, Jian-Hua Wang
PURPOSE: To evaluate short-term and long-term effectiveness of interventional treatment for hepatic artery thrombosis (HAT). MATERIALS AND METHODS: From March 2003 to October 2015, 34 patients (32 male and 2 female; mean age, 45 y; range 7-64 y) with HAT were identified 0-21d (mean 6.5 d ± 6.0) after liver transplantation and underwent interventional treatments. Technical success, clinical success, complications, hepatic artery patency, and survival time were assessed...
June 11, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28607341/thrombolysis-for-non-traumatic-intra-ventricular-hemorrhage-in-adults-a-critical-reappraisal
#15
Daniele Starnoni, Mauro Oddo, Rodolfo Maduri, Mahmoud Messerer, Roy T Daniel
Intra-ventricular hemorrhage (IVH) is a critical condition with high rate of morbidity and mortality due to acute hydrocephalus and secondary brain injury. Mechanisms underlining the clinical deterioration are not only related to the appearance of an acute hydrocephalus but also to blood- clot mass effect and the inflammatory effects of blood break-down products which impede local blood flow and exert a direct toxic effect on the peri-ventricular structures leading to chronic hydrocephalus. An effective treatment strategy should aim at IVH fast removal and reduction of blood-clot mass effect...
June 12, 2017: Minerva Anestesiologica
https://www.readbyqxmd.com/read/28607123/plasma-levels-of-intact-and-cleaved-urokinase-plasminogen-activator-receptor-upar-in-men-with-clinically-localised-prostate-cancer
#16
Gitte Kristensen, Kasper Drimer Berg, Solvej Lippert, Ib Jarle Christensen, Klaus Brasso, Gunilla Høyer-Hansen, Martin Andreas Røder
AIMS: Lymph node metastasis (N1) is an adverse prognostic factor for men with clinically localised prostate cancer (PCa), but the prediction of N1 disease remains difficult. Urokinase plasminogen activator receptor (uPAR) plays an important role in angiogenesis and tumorigenesis. We analysed whether plasma levels of the soluble uPAR forms uPAR(I-III), uPAR(II-III) and uPAR(I) were associated with the risk of N1 disease in men with clinically localised PCa. METHODS: The present study includes all men (n=518) who underwent radical prostatectomy (RP) for clinically localised PCa, 29 of whom had N1 disease...
June 12, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28600623/fibrin-specific-and-effective-clot-lysis-requires-both-plasminogen-activators-and-for-them-to-be-in-a-sequential-rather-than-simultaneous-combination
#17
R Pannell, S Li, V Gurewich
Thrombolysis with tissue plasminogen activator (tPA) has been a disappointment and has now been replaced by an endovascular procedure whenever possible. Nevertheless, thrombolysis remains the only means by which circulation in a thrombosed artery can be restored rapidly. In contrast to tPA monotherapy, endogenous fibrinolysis uses both tPA and urokinase plasminogen activator (uPA), whose native form is a proenzyme, prouPA. This combination is remarkably effective as evidenced by the fibrin degradation product, D-dimer, which is invariably present in plasma...
June 9, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28596971/soluble-urokinase-receptor-and-the-kidney-response-in-diabetes-mellitus
#18
REVIEW
Ranadheer R Dande, Vasil Peev, Mehmet M Altintas, Jochen Reiser
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. DN typically manifests by glomerular hyperfiltration and microalbuminuria; then, the disease progresses to impaired glomerular filtration rate, which leads to ESRD. Treatment options for DN include the strict control of blood glucose levels and pressure (e.g., intraglomerular hypertension). However, the search for novel therapeutic strategies is ongoing. These include seeking specific molecules that contribute to the development and progression of DN to potentially interfere with these "molecular targets" as well as with the cellular targets within the kidney such as podocytes, which play a major role in the pathogenesis of DN...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28595175/untreated-psoriasis-impairs-male-fertility-a-case-control-study
#19
Giacomo Caldarola, Domenico Milardi, Giuseppe Grande, Andrea Quercia, Silvia Baroni, Renato Morelli, Riccardo Marana, Alfredo Pontecorvi, Clara De Simone, Ketty Peris
BACKGROUND: Recent evidence indicates that a systemic state of inflammation may impair fertility, but data about psoriatic males are scarce. OBJECTIVES: The aim of this study was to assess gonadal function in psoriatic males implementing our knowledge about fertility in these subjects. METHODS: Male psoriatic patients, aged between 18 and 55 years, and a group of healthy subjects matched for age, BMI and geographic origin were enrolled. All subjects underwent a complete physical and andrological examination, standard semen analysis, complete microbiological analysis and ultrasound evaluation of sexual glands...
June 9, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28589505/association-between-supar-and-cardiac-diastolic-dysfunction-among-patients-with-preserved-ejection-fraction
#20
Tomohiro Fujisaka, Shu-Ichi Fujita, Daichi Maeda, Kensaku Shibata, Hideaki Takahashi, Hideaki Morita, Yoshihiro Takeda, Takahide Ito, Koichi Sohmiya, Masaaki Hoshiga, Nobukazu Ishizaka
Serum levels of the soluble urokinase-type plasminogen activator receptor (suPAR) reflect immune and inflammatory activation, and are shown to be associated with cardiovascular outcomes. We herein investigated the potential association between suPAR and left ventricular diastolic dysfunction among patients with preserved left ventricular ejection fraction (LVEF) and sinus rhythm. Among 291 patients who had sinus rhythm and an LVEF of ≥50% enrolled in the study, 26 (8.9%) were considered to have diastolic dysfunction...
June 6, 2017: Heart and Vessels
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