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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/28428025/adipokines-as-atherothrombotic-risk-factors-in-obese-subjects-associations-with-haemostatic-markers-and-common-carotid-wall%C3%A2-thickness
#2
É Csongrádi, M Káplár, B Nagy, C A Koch, A Juhász, L Bajnok, Z Varga, I Seres, Z Karányi, M T Magyar, L Oláh, A Facskó, J Kappelmayer, G Paragh
BACKGROUND AND AIMS: Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls...
March 8, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28416743/the-urokinase-plasminogen-activation-system-in-gastroesophageal-cancer-a-systematic-review-and-meta-analysis
#3
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/28408189/genetic-effects-on-the-correlation-structure-of%C3%A2-cvd-risk-factors-exome-wide-data-from-a-ghanaian-population
#4
REVIEW
Nuri Kodaman, Rafal S Sobota, Folkert W Asselbergs, Matthew T Oetjens, Jason H Moore, Nancy J Brown, Melinda C Aldrich, Scott M Williams
Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly correlated with several cardiovascular disease (CVD) risk factors. It also plays a direct role in CVD, including myocardial infarction and stroke, by impeding the dissolution of thrombi in the blood. Insofar as PAI-1 links CVD's risk factors to its endpoints, genetic variants modulating the relationship between PAI-1 and risk factors may be of particular clinical and biological interest. The high heritability of PAI-1, which has not been explained by genetic association studies, may also, in large part, be due to this relationship with CVD risk factors...
April 10, 2017: Global Heart
https://www.readbyqxmd.com/read/28405804/cytoprotective-drug-tissue-plasminogen-activator-protease-interaction-assays-screening-of-two-novel-cytoprotective-chromones
#5
Paul A Lapchak, Jacqueline M Lara, Paul D Boitano
Tissue plasminogen activator (tPA) is currently used in combination with endovascular procedures to enhance recanalization and cerebral reperfusion and is also currently administered as standard-of-care thrombolytic therapy to patients within 3-4.5 h of an ischemic stroke. Since tPA is not neuroprotective or cytoprotective, adjuvant therapy with a neuroprotective or an optimized cytoprotective compound is required to provide the best care to stroke victims to maximally promote clinical recovery. In this article, we describe the use of a sensitive standardized protease assay with CH3SO2-D-hexahydrotyrosine-Gly-Arg-p-nitroanilide•AcOH, a chromogenic protease substrate that is cleaved to 4-nitroaniline (p-nitroaniline) and measured spectrophotometrically at 405 nm (OD405 nm), and how the assay can be used as an effective screening assay to study drug-tPA interactions...
April 12, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28405670/a-long-acting-pai-1-inhibitor-reduce-thrombus-formation
#6
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/28402272/ginkgolic-acids-inhibit-migration-in-breast-cancer-cells-by-inhibition-of-nemo-sumoylation-and-nf-%C3%AE%C2%BAb-activity
#7
Sami Hamdoun, Thomas Efferth
Ginkgolic acids (GA), a group of alkyl phenols found in crude extracts of Ginkgo biloba leaves, are known to have anticancer activity, but their mode of action is not well understood. Our aim in this study was to investigate the anti-migratory activity of seven GA against breast cancer cells and to determine the molecular mechanism behind this activity. All seven GA and their mixture inhibited wound healing in MCF-7 and MDA-MB 231 breast cancer cells. None of the compounds nor the mixture showed cytotoxicity towards the two cell lines, if tested by the resazurin assay...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398634/ski-regulates-smads-and-taz-signaling-to-suppress-lung-cancer-progression
#8
Mian Xie, Xiaojun Wu, Jinjun Zhang, Jiexia Zhang, Xiangxiang Li
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro-oncogenic and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15(INK4B) ) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway...
April 11, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28397043/simvastatin-prevents-lipopolysaccharide-induced-septic-shock-in-rats
#9
Li Yu, Xing-Wen Da, Xiao-Ling Wu, Ao-di He, Ding Long
Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis. Herein, we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock. In our study, rats were divided into a saline group, an LPS group and an LPS plus simvastatin group. Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg), with variations in left ventricular pressure recorded throughout...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28395801/generation-of-human-ipscs-from-urine-derived-cells-of-patient-with-a-novel-heterozygous-pai-1-mutation
#10
Muhammad Zeeshan Afzal, Melanie Gartz, Ekaterina A Klyachko, Sadiya Sana Khan, Sanjiv J Shah, Sweta Gupta, Amy D Shapiro, Douglas E Vaughan, Jennifer L Strande
We have generated a human induced pluripotent stem cell (iPSC) line under feeder-free culture conditions using the urine derived cells (UCs) collected from subjects heterozygous for a novel Plasminogen Activator Inhibitor-1 (PAI-1) mutation. The Sendai Virus (SeV) vector encoding pluripotent Yamanaka transcription factors was used at a low multiplicity of infection to reprogram the PAI-1 UCs.
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395799/generation-of-human-ipscs-from-urine-derived-cells-of-a-non-affected-control-subject
#11
Muhammad Zeeshan Afzal, Melanie Gartz, Ekaterina A Klyachko, Sadiya Sana Khan, Sanjiv J Shah, Sweta Gupta, Amy D Shapiro, Douglas E Vaughan, Jennifer L Strande
We have generated a human induced pluripotent stem cell (iPSC) line under feeder-free culture conditions using the urine derived cells (UCs) collected from non-affected control subjects to use as a comparison group for the iPSC lines containing a Plasminogen Activator Inhibitor-1 (PAI-1 homozygous/heterozygous) mutation. The Sendai Virus (SeV) vector encoding pluripotent Yamanaka transcription factors was used at a low multiplicity of infection to reprogram the UCs.
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395596/plasminogen-activator-inhibitor-1-polymorphism-confers-a-genetic-contribution-to-the-risk-of-recurrent-spontaneous-abortion-an-updated-meta-analysis
#12
Zhan Huang, Wenqian Tang, Zhikun Liang, Qiaopei Chen, Mingyi Li, Yingfeng Li, Shaoxing Lao, Huimin Pan, Liying Huang, Min Huang, Xuehua Hu, Jiangyang Zhao
Various studies have investigated the risk of recurrent spontaneous abortion (RSA) with plasminogen activator inhibitor-1 ( PAI-1) 4G/5G polymorphism. However, the results have been somewhat contradictory. Therefore, an updated meta-analysis based on 31 studies (5617 cases and 3952 controls) was undertaken to clarify this relationship. The degree of RSA risk was estimated using the odds ratio (OR) and the 95% confidence interval (CI). Overall, the random effects OR was 1.464 (95% CI: 1.269-1.690) for 4G versus 5G, 2...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28394081/the-effect-of-low-level-laser-therapy-as-an-adjunct-to-non-surgical-periodontal-treatment-on-gingival-crevicular-fluid-levels-of-transforming-growth-factor-beta-1-tissue-plasminogen-activator-and-plasminogen-activator-inhibitor-1-in-smoking-and-non-smoking
#13
F Pamuk, M Lütfioğlu, A Aydoğdu, C Z Koyuncuoglu, E Cifcibasi, O S Badur
BACKGROUND AND OBJECTIVE: This study aimed to investigate the effects of low-level laser therapy (LLLT) as an adjunct to scaling and root planing (SRP) on smoking and non-smoking patients with chronic periodontitis. MATERIAL AND METHODS: The study was conducted using a split-mouth design with 30 patients with chronic periodontitis (15 smokers, 15 non-smokers) and 30 healthy individuals matched for age, sex and smoking status as controls. Groups were constituted as follows: Cp+SRP+Sham: non-smokers with chronic periodontitis treated with SRP; Cp+SRP+LLLT: non-smokers with chronic periodontitis treated with SRP+LLLT; SCp+SRP+Sham: smokers with chronic periodontitis treated with SRP; SCp+SRP+LLLT: smokers with chronic periodontitis treated with SRP+LLLT; C: control group comprised of periodontally healthy non-smokers; SC: control group comprised of periodontally healthy smokers...
April 10, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28386343/signaling-by-tgf-betas-in-tubule-cultures-of-adult-rat-testis
#14
Kai-Hui Chan, Sebastian P Galuska, Pradeep Kumar Kudipudi, Mohammad Assad Riaz, Kate L Loveland, Lutz Konrad
Although signal transduction of transforming growth factor-betas (TGF-βs) is well characterized in individual cell types, data about TGF-β signaling in a cellular context is still scarce. In this study, we used ex vivo tubule cultures from adult rat testis to investigate TGF-β signaling. We show for the first time in testicular tubules, that TGF-βs also signal via the BMP type I receptors, with ALK2 used by TGF-β1 and ALK3 and ALK6 by TGF-β2. This signal transduction is mediated via Smad3 as well as via Smad1...
2017: American Journal of Translational Research
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
#15
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/28382527/multiple-thrombophilia-mutations-as-a%C3%A2-possible-cause-of-premature-myocardial-infarction
#16
Gabriela Dostálová, Jan Bělohlávek, Zuzana Hlubocká, Kristýna Bayerová, Petra Bobčiková, Tomáš Kvasnička, Jan Kvasnička, Aleš Linhart, Debora Karetová
The incidence of acute myocardial infarction (AMI) increases with clustering of predisposing risk factors. In younger subjects with a positive family history of AMI occurring in relatives under the age of 60 years without obvious risk factors for atherosclerosis, there is a potential for strong inherited traits contributing to the risk of coronary disease. Among them there is increasing evidence that hereditary thrombophilia may play a major role. We present a unique case of a patient developing AMI at the age of 48 years...
April 5, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28382387/high-soluble-endoglin-levels-do-not-induce-changes-in-structural-parameters-of-mouse-heart
#17
Jana Rathouska, Petra Fikrova, Alena Mrkvicova, Katerina Blazickova, Michala Varejckova, Eva Dolezelova, Ivana Nemeckova, Barbora Vitverova, Lenka Peslova, Eunate Gallardo-Vara, Miguel Pericacho, Petr Nachtigal
A soluble form of endoglin (sEng) released into the circulation was suggested to be a direct inducer of endothelial dysfunction, inflammation and contributed to the development of hypertension by interfering with TGF-β signaling in cardiovascular pathologies. In the present study, we assessed the hypothesis that high sEng level-induced hypertension via a possible sEng interference with TGF-β signaling pathways may result in inflammatory, structural or fibrotic changes in hearts of Sol-Eng+ mice (mice with high levels of soluble endoglin) fed either chow or high-fat diet...
April 5, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28379891/relationship-between-plasma-plasminogen-activator-inhibitor-1-and-hypertension-in-american-indians-findings-from-the-strong-heart-study
#18
Hao Peng, Fawn Yeh, Giovanni de Simone, Lyle G Best, Elisa T Lee, Barbara V Howard, Jinying Zhao
OBJECTIVES: Deficient plasminogen activator inhibitor-1 (PAI-1) prevented hypertension in mice. Plasma PAI-1 was associated with hypertension in cross-sectional analyses, but the prospective association of PAI-1 with incident hypertension in large epidemiological studies is scarce. METHODS: Leveraging two longitudinal cohorts of American Indians in the Strong Heart Study (SHS, N = 1019) and the Strong Heart Family Study (SHFS, N = 1502), we examined the prospective association of plasma PAI-1 with incident hypertension by multivariate logistic regression, adjusting for age, sex, study site, smoking, drinking, dietary sodium, obesity, lipids, fasting glucose, kidney function, inflammation, and follow-up years...
April 4, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28378522/plasminogen-activator-inhibitor-1-is-associated-with-leukocyte-telomere-length-in-american-indians-findings-from-the-strong-heart-family-study
#19
Hao Peng, Fawn Yeh, Jue Lin, Lyle G Best, Shelley A Cole, Elisa T Lee, Barbara V Howard, Jinying Zhao
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) promotes cellular aging both in vitro and in vivo. Telomere length is a marker of biological aging. OBJECTIVES: To examine the cross-sectional and longitudinal associations between plasma PAI-1 and leukocyte telomere length in a large-scale epidemiological study of American Indians. METHODS: We measured leukocyte telomere length (LTL) and plasma PAI-1 in 2,560 American Indians who were free of overt CVD and participated in the Strong Heart Family Study (SHFS) clinical exam in 2001-2003...
April 5, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28378106/plasminogen-activator-inhibitor-links-obesity-and-thrombotic-cerebrovascular-diseases-the-roles-of-pai-1-and-obesity-on-stroke
#20
REVIEW
Rui Chen, Jinchuan Yan, Peijing Liu, Zhongqun Wang, Cuiping Wang
One of the global socioeconomic phenomena occurred during the last decades is the increased prevalence of obesity, with direct consequence on the risk of developing thrombotic disorders. As the physiological inhibitor of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) is well known for its role in fibrinolysis. More and more evidences have shown that PAI-1 involves in physiopathologic mechanisms of many diseases and metabolic disorder. Increased serum level of PAI-1 has been observed in obesity and it also contributes to the development of adipose tissue and then has effects on obesity...
April 4, 2017: Metabolic Brain Disease
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