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Systemic urokinase

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https://www.readbyqxmd.com/read/28429105/increased-expression-of-upa-upar-and-pai-1-in-psoriatic-skin-and-in-basal-cell-carcinomas
#1
K A Rubina, V Yu Sysoeva, E I Zagorujko, Z I Tsokolaeva, M I Kurdina, Ye V Parfyonova, V A Tkachuk
There is substantial evidence implicating the urokinase system in tissue remodeling during neo-vascularization, inflammation, tumor invasion, and metastasis. Regulated degradation of the extracellular matrix at the leading edge of migrating cells, mediated by uPA and uPAR, is required for tissue remodeling, invasiveness, and angiogenesis. Psoriasis and basal cell carcinoma (BCC) are the most common skin diseases. Pathogenesis of both of them is associated with keratinocyte hyperproliferation, inflammatory cell migration, and angiogenesis-processes in which the plasminogen system (uPA, uPAR, tPA, and PAI-1) plays a crucial role...
April 20, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28416743/the-urokinase-plasminogen-activation-system-in-gastroesophageal-cancer-a-systematic-review-and-meta-analysis
#2
Daniel Brungs, Julia Chen, Morteza Aghmesheh, Kara L Vine, Therese M Becker, Martin G Carolan, Marie Ranson
BACKGROUND: The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA system expression is a clinically relevant biomarker in some solid tumours, its role in gastroesophageal cancer is uncertain. RESULTS: We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopathological features...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405670/a-long-acting-pai-1-inhibitor-reduce-thrombus-formation
#3
Shuangzhou Peng, Guangpu Xue, Lihu Gong, Chao Fang, Jingfei Chen, Cai Yuan, Zhuo Chen, Lishan Yao, Bruce Furie, Mingdong Huang
Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activators (t/uPA) and plays an important role in the fibrinolytic system. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis, indicating that PAI-1 inhibitors may be used as effective antithrombotic agents. We previously designed a PAI-1 inhibitor (PAItrap) which is a variant of inactivated urokinase protease domain. In the present study, we tried to fuse PAItrap with human serum albumin (HSA) to develop a long-acting PAI-1 inhibitor...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28385810/regulation-of-p53-mediated-changes-in-the-upa-fibrinolytic-system-and-in-lung-injury-by-loss-of-surfactant-protein-c-expression-in-alveolar-epithelial-cells
#4
Bijesh Puthusseri, Amarnath S Marudamuthu, Nivedita Tiwari, Jian Fu, Steven Idell, Sreerama Shetty
Pulmonary surfactant protein-C (SP-C) expression by type II alveolar epithelial cells (AECs) is markedly reduced in diverse types of lung injuries and is often associated with AEC apoptosis. It is unclear whether loss of SP-C contributes to the increased p53 and urokinase-type plasminogen activator (uPA) system cross talk and apoptosis of AECs. We therefore inhibited SP-C expression in human and murine AECs using lentivirus vector expressing shRNA and tested p53 and downstream changes in uPA-fibrinolytic system...
April 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28364860/regulatory-effects-of-estetrol-on-the-endothelial-plasminogen-pathway-and-endothelial-cell-migration
#5
Maria Magdalena Montt-Guevara, Giulia Palla, Stefania Spina, Guja Bernacchi, Elena Cecchi, Adrian Esteban Campelo, Jorge Eduardo Shortrede, Alessio Canu, Tommaso Simoncini
BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate...
May 2017: Maturitas
https://www.readbyqxmd.com/read/28340565/u-par-expression-in-cancer-associated-fibroblast-new-acquisitions-in-multiple-myeloma-progression
#6
S Ciavarella, A Laurenzana, S De Summa, B Pilato, A Chillà, R Lacalamita, C Minoia, F Margheri, A Iacobazzi, A Rana, F Merchionne, G Fibbi, M Del Rosso, A Guarini, S Tommasi, S Serratì
BACKGROUND: Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF...
March 24, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28298247/tissue-specific-inhibition-of-urokinase-type-plasminogen-activator-expression-in-the-testes-of-mice-by-inducible-lentiviral-rna-interference-causes-male-infertility
#7
Kai Zhao, Yan Liu, Zhe Xiong, Lian Hu, Cheng-Liang Xiong
Urokinase-type plasminogen activator (uPA) is involved in many physiological processes, including male infertility. To explore the effects of uPA in male reproduction, we constructed an inducible uPA short hairpin RNA (shRNA) system expressed by lentiviral vectors. After proving inhibition of uPA expression in the mouse Sertoli cell line TM4 by 1μgmL-1 doxycycline (Dox), two lentivirus (pLenti4-shRNA and pLenti6/TR) were co-microinjected into mouse testes to produce TetR&shuPA mice model. Though oral gavage by 0...
March 16, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28283876/purification-of-serine-protease-from-polychaeta-lumbrineris-nipponica-and-assessment-of-its-fibrinolytic-activity
#8
Seung Ju Yeon, Goo Yong Chung, Jae Sang Hong, Jin Ha Hwang, Hwa Sung Shin
Ischemic stroke and cardiovascular disease can occur from blockage of blood vessels by fibrin clots formed naturally in the body. Therapeutic drugs of anticoagulant or thrombolytic agents have been studied; however, various problems have been reported such as side effects and low efficacy. Thus, development of new candidates that are more effective and safe is necessary. The objective of this study is to evaluate fibrinolytic activity, anti-coagulation, and characterization of serine protease purified from Lumbrineris nipponica, polychaeta, for new thrombolytic agents...
March 10, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28249028/heart-rate-variability-during-hemodialysis-is-an-indicator-for-long-term-vascular-access-survival-in-uremic-patients
#9
Ya-Ting Huang, Yu-Ming Chang, I-Ling Chen, Chuan-Lan Yang, Show-Chin Leu, Hung-Li Su, Jsun-Liang Kao, Shih-Ching Tsai, Rong-Na Jhen, Woung-Ru Tang, Chih-Chung Shiao
BACKGROUND: Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes. METHODS: This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65...
2017: PloS One
https://www.readbyqxmd.com/read/28236848/the-fibrinolytic-system-a-new-target-for-treatment-of-depression-with-psychedelics
#10
R D Idell, G Florova, A A Komissarov, S Shetty, R B S Girard, S Idell
Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28210916/a-multiscale-mathematical-model-of-tumour-invasive-growth
#11
Lu Peng, Dumitru Trucu, Ping Lin, Alastair Thompson, Mark A J Chaplain
Known as one of the hallmarks of cancer (Hanahan and Weinberg in Cell 100:57-70, 2000) cancer cell invasion of human body tissue is a complicated spatio-temporal multiscale process which enables a localised solid tumour to transform into a systemic, metastatic and fatal disease. This process explores and takes advantage of the reciprocal relation that solid tumours establish with the extracellular matrix (ECM) components and other multiple distinct cell types from the surrounding microenvironment. Through the secretion of various proteolytic enzymes such as matrix metalloproteinases or the urokinase plasminogen activator (uPA), the cancer cell population alters the configuration of the surrounding ECM composition and overcomes the physical barriers to ultimately achieve local cancer spread into the surrounding tissue...
March 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28209486/vasodilator-stimulated-phosphoprotein-vasp-depletion-from-breast-cancer-mda-mb-231-cells-inhibits-tumor-spheroid-invasion-through-downregulation-of-migfilin-%C3%AE-catenin-and-urokinase-plasminogen-activator-upa
#12
Vasiliki Gkretsi, Andreas Stylianou, Triantafyllos Stylianopoulos
A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28207534/a-case-control-study-on-the-structural-equation-model-of-the-mechanism-of-coagulation-and-fibrinolysis-imbalance-in-chronic-schistosomiasis
#13
Aiping Le, Lunli Zhang, Wei Liu, Xiaopeng Li, Jianwei Ren, An Ning
A structural equation model was used for verification with chronic schistosomiasis to investigate the coagulation-anticoagulation system imbalance and to deduce the mechanism of D-dimer (D-D) level elevation in patients with advanced schistosome hepatic disease. We detected the plasma levels of tissue-type fiber plasminogen activator (tPA), urokinase type plasminogen activator (uPA), plasmin-antiplasmin complex (PAP), plasminogen (PLG), antithrombin (AT), plasminogen activator inhibitor 1 (PAI1), D-D, factor VIII: C (FVIII:C), antithrombin-III (AT-III), PLG, protein S (PS), and protein C (PC) in the healthy people as control (69), patients with chronic schistosomiasis (150) or advanced chronic schistosomiasis (90)...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28182117/fibrin-sheaths-in-central-venous-port-catheters-treatment-with-low-dose-single-injection-of-urokinase-on-an-outpatient-basis
#14
De-Hua Chang, Kamal Mammadov, Tilman Hickethier, Jan Borggrefe, Martin Hellmich, David Maintz, Christoph Kabbasch
PURPOSE: Evaluation of the efficacy of single-shot, low-dose urokinase administration for the treatment of port catheter-associated fibrin sheaths. METHODS: Forty-six patients were retrospectively evaluated for 54 episodes of port catheter dysfunction. The presence of a fibrin sheath was detected by angiographic contrast examinations. On an outpatient basis, patients subsequently received thrombolysis consisting of a single injection of urokinase (15.000 IU in 1...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28159489/atorvastatin-from-target-screening-attenuates-endothelial-cell-tube-formation-and-migration-by-regulating-urokinase-receptor-related-signaling-pathway-and-f-g-actin
#15
Li Wei, Jin-Shuen Chen, Hsin-Ting Lin, Chung-Ze Wu, Cai-Mei Zheng, Yu-Ching Chang, Li-Chien Chang, Yuh-Feng Lin
BACKGROUND: Angiogenesis and cytoskeletal transformation are common denominators of many pathological developments. The relationship between angiogenesis, urokinase plasminogen activator receptor (uPAR) signaling pathway, and cytoskeletal transformation is still unknown. In this study, a pGL3-uPAR promoter reporter system combined with Bio-Plex mRNA analysis was established for discovering uPAR modulators to analyze this interconnection. METHODS: After screening a set of clinically used drugs, atorvastatin (Ator) was found to significantly affect uPAR expression and its ideal dose, 1 μM, was determined for cell study...
January 31, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28141486/usefulness-of-humanized-cdna-upa-scid-mice-for-the-study-of-hepatitis-b-virus-and-hepatitis-c-virus-virology
#16
Takuro Uchida, Michio Imamura, Hiromi Kan, Nobuhiko Hiraga, C Nelson Hayes, Masataka Tsuge, Hiromi Abe-Chayama, Hiroshi Aikata, Grace Naswa Makokha, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama
Urokinase-type plasminogen activator-severe combined immunodeficiency (uPA/SCID) mice transplanted with human hepatocytes are permissive for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. However, one of the problems affecting uPA transgenic mice is the expansion of mouse hepatocyte colonies due to homologous recombination of the uPA gene. In this study, we attempted to infect HBV and HCV in humanized cDNA-uPA/SCID mice, a novel uPA transgenic mouse model designed to overcome this disadvantage...
January 28, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28122514/indoxyl-sulfate-the-uremic-toxin-linking-hemostatic-system-disturbances-with-the-prevalence-of-cardiovascular-disease-in-patients-with-chronic-kidney-disease
#17
Tomasz W Kamiński, Krystyna Pawlak, Małgorzata Karbowska, Michał Myśliwiec, Dariusz Pawlak
BACKGROUND: During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play. The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition. METHODS: Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study...
January 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28073983/a-novel-embryo-culture-media-supplement-that-improves-pregnancy-rates-in-mice
#18
A R Highet, T Bianco-Miotto, K G Pringle, A Peura, S Bent, J Zhang, M B Nottle, J G Thompson, C T Roberts
The preimplantation embryo in vivo is exposed to numerous growth factors in the female reproductive tract, which are not recapitulated in embryo culture media in vitro The IGF2 and plasminogen activator systems facilitate blastocyst development. We hypothesized that the addition of IGF2 in combination with urokinase plasminogen activator (uPA) and plasminogen could improve rates of blastocyst hatching and implantation in mice. B6BcF1 and CBAB6F2 mouse embryos were divided into one of four supplemented culture media treatment groups: (1) control (media only); (2) 12...
March 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28062404/endothelial-to-mesenchymal-transition-contributes-to-endothelial-dysfunction-and-dermal-fibrosis-in-systemic-sclerosis
#19
Mirko Manetti, Eloisa Romano, Irene Rosa, Serena Guiducci, Silvia Bellando-Randone, Amato De Paulis, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
OBJECTIVE: Systemic sclerosis (SSc) features multiorgan fibrosis orchestrated predominantly by activated myofibroblasts. Endothelial-to-mesenchymal transition (EndoMT) is a transdifferentiation by which endothelial cells (ECs) lose their specific morphology/markers and acquire myofibroblast-like features. Here, we determined the possible contribution of EndoMT to the pathogenesis of dermal fibrosis in SSc and two mouse models. METHODS: Skin sections were immunostained for endothelial CD31 or vascular endothelial (VE)-cadherin in combination with α-smooth muscle actin (α-SMA) myofibroblast marker...
January 6, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28060552/the-root-extract-of-gentiana-macrophylla-pall-alleviates-b19-ns1-exacerbated-liver-injuries-in-nzb-w-f1-mice
#20
Ming-Jen Sheu, Chun-Ching Chiu, Deng-Jye Yang, Tsai-Ching Hsu, Bor-Show Tzang
The nonstructural protein NS1 of human parvovirus B19 (B19) is known to exacerbate disease activity in systemic lupus erythematosus (SLE). However, no specific medicine for B19 infection is available. The roots of Gentiana macrophylla Pall. (GM), the traditional Chinese medicine "Qinjiao," have been used for centuries to treat rheumatic disease, including SLE. Herein, we aimed to investigate the effects of GM root extract (100 and 300 mg/kg body weight) on B19-NS1-exacerbated liver injury in NZB/W F1 mice; liver tissues were assessed by hematoxylin-eosin staining and immunoblotting...
January 2017: Journal of Medicinal Food
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