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Beatriz Sarriá, Sara Martínez-López, José Luis Sierra-Cinos, Luis García-Diz, Raquel Mateos, Laura Bravo-Clemente
PURPOSE: Preventive health effects of coffee could have a widespread impact on public health. Green coffee has more phenols than roasted, and thus is healthier, although with less acceptable organoleptic properties. Therefore, the effects of regularly consuming a green/roasted coffee blend (35/65) on the main components of MetS in humans were evaluated. METHODS: A crossover, randomized, controlled study was performed in 25 normocholesterolaemic and 27 hypercholesterolaemic men and women aged 18-45 years with BMI 18-25 kg/m(2)...
October 13, 2016: European Journal of Nutrition
Asish K Ghosh, Rahul Rai, Kitae E Park, Mesut Eren, Toshio Miyata, Lisa D Wilsbacher, Douglas E Vaughan
Doxorubicin, an anthracycline antibiotic, is a commonly used anticancer drug. In spite of its widespread usage, its therapeutic effect is limited by its cardiotoxicity. On the cellular level, Doxorubicin-induced cardiotoxicity manifests as stress induced premature senescence. Previously, we demonstrated that plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of serine proteases, is an important biomarker and regulator of cellular senescence and aging. Here, we tested the hypothesis that pharmacological inhibition of cellular PAI-1 protects against stress- and aging-induced cellular senescence and delineated the molecular basis of protective action of PAI-1 inhibition...
October 6, 2016: Oncotarget
Bernardo Sousa-Pinto, Laura Gonçalves, Adriana R Rodrigues, Inês Tomada, Henrique Almeida, Delminda Neves, Alexandra M Gouveia
Transforming growth factor beta (TGF-β) plays an important role in the pathogenesis of obesity, influencing the release of inflammation mediators and promoting remodeling and collagen deposition in the adipose tissue (AT). In this context, this work aims to elucidate whether TGF-β and Smad-dependent or Smad-independent signaling pathways contribute to regional differentiation of AT in high-fat diet (HFD) and energy-restricted (ER) rat models. For this, TGF-β, TGF-β receptors I and II, PAI-1 and GLUT4 mRNA levels were quantified by real-time PCR, and western blotting assays allowed the semiquantification of TGF-β and proteins from Smad3, ERK1/2 and Akt signaling pathways in subcutaneous and visceral (epididymal, retroperitoneal and mesenteric) fat depots from control, HFD and ER-treated rats...
August 26, 2016: Journal of Nutritional Biochemistry
Nuri Kodaman, Melinda C Aldrich, Rafal Sobota, Folkert W Asselbergs, Kwabena A Poku, Nancy J Brown, Jason H Moore, Scott M Williams
Populations in sub-Saharan Africa are shifting from rural to increasingly urban. Although the burden of cardiovascular disease is expected to increase with this changing landscape, few large studies have assessed a wide range of risk factors in urban and rural populations, particularly in West Africa. We conducted a cross-sectional, population-based survey of 3317 participants from Ghana (≥18 years old), of whom 2265 (57% female) were from a mid-sized city (Sunyani, population ~250,000) and 1052 (55% female) were from surrounding villages (populations <5000)...
2016: PloS One
Mei-Chi Chang, Hsiao-Hua Chang, Po-Shuan Lin, Yu-An Huang, Chiu-Po Chan, Yi-Ling Tsai, Shen-Yang Lee, Po-Yuan Jeng, Han-Yueh Kuo, Sin-Yuet Yeung, Jiiang-Huei Jeng
Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signaling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion...
October 9, 2016: Journal of Tissue Engineering and Regenerative Medicine
Carolina Landolt-Marticorena, Stephenie D Prokopec, Stacey Morrison, Babak Noamani, Dennisse Bonilla, Heather Reich, James Scholey, Carmen Avila-Casado, Paul R Fortin, Paul C Boutros, Joan Wither
BACKGROUND: Management of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN. METHODS: Urine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels...
October 4, 2016: Arthritis Research & Therapy
Hao Wang, Ting Yang, Diandian Li, Yanqiu Wu, Xue Zhang, Caishuang Pang, Junlong Zhang, Binwu Ying, Tao Wang, Fuqiang Wen
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. METHODS: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Erik W Holy, Alexander Akhmedov, Thimoteus Speer, Giovanni G Camici, Stephen Zewinger, Nicole Bonetti, Jürg H Beer, Thomas F Lüscher, Felix C Tanner
BACKGROUND: Carbamylation alters low-density lipoprotein (LDL) structure and is thought to promote vascular inflammation and dysfunction in patients with chronic kidney disease (CKD). OBJECTIVES: This study sought to determine whether carbamylated LDL (cLDL) exerts prothrombotic effects in vascular cells and platelets and whether cLDL enhances arterial thrombus formation in vivo. METHODS: LDL was isolated from healthy subjects or patients with CKD by sequential ultracentrifugation...
October 11, 2016: Journal of the American College of Cardiology
Sisi Liu, Jianyin Long, Bo Yuan, Mingjie Zheng, Mu Xiao, Jianming Xu, Xia Lin, Xin-Hua Feng
Smad nuclear interacting protein-1 (SNIP1) is a transcription repressor for the TGF-β and NF-κB signaling pathways through disrupting the recruitment of coactivator p300. However, it is unclear how the functions of SNIP1 in the TGF-β signaling pathway are controlled. Our present studies show that SNIP1 is covalently modified by SUMO in vitro and in vivo at three lysine sites: Lys5, Lys30 and Lys108, with Lys30 being the major SUMO modification site. SUMOylation of SNIP1 is enhanced by SUMO E3 ligases PIAS proteins and inhibited by SUMO proteases SENP1/2...
October 4, 2016: Journal of Biological Chemistry
Nuri Kodaman, Melinda C Aldrich, Rafal Sobota, Folkert W Asselbergs, Nancy J Brown, Jason H Moore, Scott M Williams
BACKGROUND: Metabolic syndrome (MetS) is diagnosed by the presence of at least 3 of the following: obesity, hypertension, hyperglycemia, hypertriglyceridemia, and low high-density lipoprotein. Individuals with MetS also typically have elevated plasma levels of the antifibrinolytic factor, plasminogen activator inhibitor-1 (PAI-1), but the relationships between PAI-1 and MetS diagnostic criteria are not clear. Understanding these relationships can elucidate the relevance of MetS to cardiovascular disease risk, because PAI-1 is associated with ischemic events and directly involved in thrombosis...
October 3, 2016: Journal of the American Heart Association
Joanne L Mitchell, Ausra S Lionikiene, Georgi Georgiev, Anja Klemmer, Chelsea Brain, Paul Y Kim, Nicola J Mutch
Activated factor XII (FXIIa) has plasminogen activator capacity but its relative contribution to fibrinolysis is considered marginal compared to urokinase and tissue plasminogen activator. Polyphosphate (polyP) is released from activated platelets and mediates FXII activation. Here we investigate the contribution of polyP to the plasminogen activator function of αFXIIa. We show that both polyP70, of the chain length found in platelets (60-100-mer) and platelet-derived polyP, significantly augment the plasminogen activation capacity of αFXIIa...
September 30, 2016: Blood
Cheri L Lamb, Giovan N Cholico, Xinzhu Pu, Gerald D Hagler, Kenneth A Cornell, Kristen A Mitchell
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant and high-affinity ligand for the aryl hydrocarbon receptor (AhR). Increasing evidence indicates that AhR signaling contributes to wound healing, which involves the coordinated deposition and remodeling of the extracellular matrix. In the liver, wound healing is attributed to the activation of hepatic stellate cells (HSCs), which mediate fibrogenesis through the production of soluble mediators and collagen type I. We recently reported that TCDD treatment increases the activation of human HSCs in vitro...
September 28, 2016: Toxicology and Applied Pharmacology
Hussein M Atta, Ayman A Al-Hendy, Salama R Abdel Raheim, Hend Abdel-Ghany, Khalid A Nasif, Ahlam M Abdellah, Nagwa M Zenhom, Heba S Kamel
AIM OF THE STUDY: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. MATERIALS AND METHODS: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions...
October 3, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
John A D'Elia, George Bayliss, Ray E Gleason, Larry A Weinrauch
Since angiotensin increases the expression of plasminogen activator inhibitor (PAI), mechanisms associated with an actively functioning renin-angiotensin-aldosterone system can be expected to be associated with increased PAI-1 expression. These mechanisms are present not only in common conditions resulting in glomerulosclerosis associated with aging, diabetes or genetic mutations, but also in autoimmune disease (like scleroderma and lupus), radiation injury, cyclosporine toxicity, allograft nephropathy and ureteral obstruction...
October 2016: Clinical Kidney Journal
Yuh-Feng Lin, I-Jen Chiu, Fong-Yu Cheng, Yu-Hsuan Lee, Ying-Jan Wang, Yung-Ho Hsu, Hui-Wen Chiu
BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. RESULTS: We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation...
September 27, 2016: Particle and Fibre Toxicology
Qiang Tong, Yuxiang Zhu, Joseph W Galaske, Elizabeth A Kosmacek, Arpita Chatterjee, Bryan C Dickinson, Rebecca E Oberley-Deegan
To improve the treatment of advanced prostate cancer, the development of effective and innovative antitumor agents is needed. Our previous work demonstrated that the ROS (reactive oxygen species) scavenger, MnTE-2-PyP, inhibited human prostate cancer growth and also inhibited prostate cancer migration and invasion. We showed that MnTE-2-PyP treatment altered the affinity of the histone acetyltransferase enzyme, p300, to bind to DNA. We speculate that this may be one mechanism by which MnTE-2-PyP inhibits prostate cancer progression...
September 24, 2016: Free Radical Biology & Medicine
Hamza S Elkhidir, Jeremy B Richards, Kevin R Cromar, Cynthia S Bell, Roger E Price, Constance L Atkins, Chantal Y Spencer, Farhan Malik, Amy L Alexander, Katherine J Cockerill, Ikram U Haque, Richard A Johnston
Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h...
September 2016: Physiological Reports
Line Brøndum, Brita Singers Sørensen, Jesper Grau Eriksen, Lise Saksø Mortensen, Simon Lønbro, Jens Overgaard, Jan Alsner
OBJECTIVE: To assess the usability of archived plasma and serum by multiplex (Luminex) analysis of circulating proteins (analytes) by evaluating the day to day variation, the effect of several freeze-thaw cycles, and the influence of the media and choice of anticoagulant. METHODS: Nineteen analytes in plasma and serum from 86 head and neck cancer patients and 33 controls were evaluated: EGFR, leptin, OPN, VEGFR-1, VEGFR-2, IL-2, IL-13, PDGF-bb, TNF, PAI-1, SDF-1a, IL-4, IL-6, IL-8, eotaxin, G-CSF, VEGF, GRO-a, and HGF...
September 26, 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Giselli Scaini, Tássia Tonon, Carolina F Moura de Souza, Patricia F Schuk, Gustavo C Ferreira, Joao Seda Neto, Tatiana Amorin, Ida Vanessa D Schwartz, Emilio L Streck
Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment...
September 22, 2016: Molecular Neurobiology
M M Tomasiak-Lozowska, T Misztal, T Rusak, J Branska-Januszewska, A Bodzenta-Lukaszyk, M Tomasiak
The aim of this study was to assess whether steroid-naïve asthma modulates hemostasis. We evaluated the clot retraction rate (CRR), fibrinolysis rate (FR), clot density (CD) (by confocal microscopy), plasma levels of plasminogen activator inhibitor (PAI-1), and factor XIII (FXIII), NO in exhaled breath (FENO ), spirometry (FEV1 ) and eosinophil count (EOS) in 36 patients with allergic, steroid-naïve asthma and in 34 healthy controls. We observed significantly (P < 0.001) reduced CRR, FR, and FEV1 and increased FENO , EOS, PAI-1, FXIII, and CD in patients with asthma compared with controls...
September 23, 2016: Allergy
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