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https://www.readbyqxmd.com/read/28928169/individual-serum-saturated-fatty-acids-and-markers-of-chronic-subclinical-inflammation-the-insulin-resistance-atherosclerosis-study-iras
#1
Ingrid D Santaren, Steven M Watkins, Angela D Liese, Lynne E Wagenknecht, Marian J Rewers, Steven M Haffner, Carlos Lorenzo, Andreas Festa, Richard P Bazinet, Anthony J Hanley
Recent evidence has documented distinct effects of individual saturated fatty acids (SFA) on cardiometabolic outcomes, with potential protective effects from odd- and very long-chain (VLSFA) SFA. Cross-sectional and prospective associations of individual serum SFA (12:0, 14:0, 15:0, 16:0, 18:0, 20:0, 22:0, and total SFA) with proinflammatory biomarkers and adiponectin were investigated in 555 adults from the Insulin Resistance Atherosclerosis Study (IRAS). Principal components (PC) analysis of proinflammatory markers yielded 3 clusters: PC 1: fibrinogen, white cell count, CRP; PC 2: PAI-1, TNF-α; IL-18; PC 3: IL-6, IL-8...
September 19, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28926092/key-genes-regulating-the-liposecretion-process-of-mature-adipocytes
#2
Giulia Maurizi, Tiina Petäistö, Angela Maurizi, Lucio Della Guardia
White mature adipocytes (MAs) are plastic cells able to reversibly transdifferentiate toward fibroblast-like cells maintaining stem cell gene signatures. The main morphologic aspect of this transdifferentiation process, called liposecretion, is the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion. There is a considerable interest in the adipocyte plastic properties involving liposecretion process, but the molecular details are incompletely explored. This review analyzes the gene expression of MAs isolated from human subcutaneous fat tissue with respect to bone marrow (BM)-derived mesenchymal stem cells (MSC) focusing on gene regulatory pathways involved into cellular morphology changes, cellular proliferation and transports of molecules through the membrane, suggesting potential ways to guide liposecretion...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28924605/pai-1-is-a-critical-regulator-of-fgf23-homeostasis
#3
Mesut Eren, Aaron T Place, Paul M Thomas, Panagiotis Flevaris, Toshio Miyata, Douglas E Vaughan
Elevated levels of fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, are associated with a number of pathologic conditions including chronic kidney disease, cardiac hypertrophy, and congestive heart failure. Currently, there are no specific treatments available to lower plasma FGF23 levels. We have recently reported that genetic plasminogen activator inhibitor-1 (PAI-1) deficiency provided a significant reduction in circulating FGF23 levels while simultaneously prolonging the life span of Klotho-deficient mice...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28913669/resolving-distinct-molecular-origins-for-copper-effects-on-pai-1
#4
Joel C Bucci, Carlee S McClintock, Yuzhuo Chu, Gregory L Ware, Kayla D McConnell, Joseph P Emerson, Cynthia B Peterson
Components of the fibrinolytic system are subjected to stringent control to maintain proper hemostasis. Central to this regulation is the serpin plasminogen activator inhibitor-1 (PAI-1), which is responsible for specific and rapid inhibition of fibrinolytic proteases. Active PAI-1 is inherently unstable and readily converts to a latent, inactive form. The binding of vitronectin and other ligands influences stability of active PAI-1. Our laboratory recently observed reciprocal effects on the stability of active PAI-1 in the presence of transition metals, such as copper, depending on the whether vitronectin was also present (Thompson et al...
September 14, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28903941/increased-hazard-of-myocardial-infarction-with-insulin-provision-therapy-in-actively-smoking-patients-with-diabetes-mellitus-and-stable-ischemic-heart-disease-the-bari-2d-bypass-angioplasty-revascularization-investigation-2-diabetes-trial
#5
Asrar A Khan, Matthew J Chung, Eric Novak, David L Brown
BACKGROUND: In the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision (IP) therapy, as opposed to insulin sensitization (IS) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of IP therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction (MI)...
September 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28902433/curcumin-alleviates-il-17a-mediated-p53-pai-1-expression-in-bleomycin-induced-alveolar-basal-epithelial-cells
#6
Mahesh Manjunath Gouda, Ashwini Prabhu, Yashodhar Prabhakar Bhandary
Bleomycin mediated inflammatory pathway is known to play an important role in the up regulation of oxidative stress. IL-17A is a pro-inflammatory cytokine involved in the modulation of fibrosis. The complex underlying mechanism for the said phenomenon remains unclear. This newly defined investigation was designed to understand the changes associated with 1L-17A mediated up-regulation of p53 and PAI-1 expression and the role of curcumin in attenuating this process. A549 cells were treated with bleomycin (BLM) and IL-17A to induce the inflammatory response in vitro...
September 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28899878/endothelial-cells-promote-triple-negative-breast-cancer-cell-metastasis-via-pai-1-and-ccl5-signaling
#7
Wenwen Zhang, Jing Xu, Hehui Fang, Lin Tang, Weiwei Chen, Qian Sun, Qun Zhang, Fang Yang, Zijia Sun, Lulu Cao, Yucai Wang, Xiaoxiang Guan
Endothelial cells (ECs) in the tumor microenvironment have been reported to play a more active role in solid tumor growth and metastatic dissemination than simply providing the physical structure to form conduits for blood flow; however, the involvement of ECs in the process of triple-negative breast cancer (TNBC) metastasis has not been addressed. Here, we demonstrate that ECs-when mixed with TNBC cells-could increase TNBC cell metastatic potency. After treatment with TGF-β to induce endothelial-mesenchymal transition (EMT), TNBC cells could produce plasminogen activator inhibitor-1 (PAI-1) and stimulate the expression and secretion of the chemokine, CCL5, from ECs, which then acts in a paracrine fashion on TNBC cells to enhance their migration, invasion, and metastasis...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28893232/plasminogen-activator-inhibitor-1-deficiency-enhances-subchondral-osteopenia-after-induction-of-osteoarthritis-in-mice
#8
Akihiro Moritake, Naoyuki Kawao, Kiyotaka Okada, Kohei Tatsumi, Masayoshi Ishida, Katsumi Okumoto, Osamu Matsuo, Masao Akagi, Hiroshi Kaji
BACKGROUND: Subchondral osteopenia is important for the pathophysiology of osteoarthritis (OA). Although previous studies suggest that plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is related to bone metabolism, its role in OA remains unknown. We therefore investigated the roles of PAI-1 in the subchondral bone in OA model mice. METHODS: Wild type (WT) and PAI-1-deficient (KO) mice were ovariectomized (OVX), and then destabilization of the medial meniscus (DMM) surgery was performed...
September 11, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28888219/factor-xa-inhibition-by-rivaroxaban-in-the-trough-steady-state-can-significantly-reduce-thrombin-generation
#9
Shigeo Horinaka, Rie Sugawara, Yutaka Yonezawa, Toshihiko Ishimitsu
AIMS: The aim of the present study was to demonstrate evidence of reduced thrombin generation at the trough plasma rivaroxaban concentration. METHODS: A single-centre, prospective, non-randomised, drug intervention, self-controlled study was conducted in 51 anticoagulation therapy-naïve patients with non-valvular atrial fibrillation. Plasma rivaroxaban concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and anti-factor Xa chromogenic assay...
September 9, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28882552/prognostic-and-predictive-biomarkers-in-breast-cancer-past-present-and-future
#10
REVIEW
Andrea Nicolini, Paola Ferrari, Michael J Duffy
Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients...
September 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28877644/a-time-course-of-bevacizumab-anti-vegf-effect-on-rat-peritoneum-relations-between-antiadhesive-action-and-fibrin-regulation-enzymes
#11
Aikaterini-Eftychia Micha, Kyriakos Psarras, Odysseas Ouroumidis, Evangelia Siska, Efthymia Vlachaki, Aristotelis Lymperopoulos, Nikolaos Symeonidis, Christina Nikolaidou, Ioannis Venizelos, George Koliakos, Theodoros E Pavlidis
BACKGROUND: To investigate the early and late antiadhesive effect and any changes of fibrin matrix regulation enzymes on rat peritoneum, after local administration of bevacizumab. METHODS: Rats were subjected to cecal abrasion. Bevacizumab (5 mg/kg) against placebo was given intraperitoneally. On the 2nd, 14th, and 28th postoperative days adhesions were scored, and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), degree of fibrosis, and angiogenesis were measured in abrased cecum and in intact parietal peritoneum...
September 1, 2017: Surgical Innovation
https://www.readbyqxmd.com/read/28877230/decision-impact-and-feasibility-of-different-asco-recommended-biomarkers-in-early-breast-cancer-prospective-comparison-of-molecular-marker-endopredict-and-protein-marker-upa-pai-1
#12
Johannes Ettl, Evelyn Klein, Alexander Hapfelmeier, Kirsten Grosse Lackmann, Stefan Paepke, Christoph Petry, Katja Specht, Laura Wolff, Heinz Höfler, Marion Kiechle
BACKGROUND: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation...
2017: PloS One
https://www.readbyqxmd.com/read/28870787/conditional-plasminogen-activator-inhibitor-type-1-deletion-in-the-endothelial-compartment-has-no-beneficial-effect-on-radiation-induced-whole-lung-damage-in-mice
#13
Jérémy Lavigne, Frédéric Soysouvanh, Valérie Buard, Georges Tarlet, Olivier Guipaud, Vincent Paget, Fabien Milliat, Agnès François
PURPOSE: To investigate whether the endothelial pool of plasminogen activator inhibitor type 1 (PAI-1) plays a role in the development of radiation-induced lung damage, as previously demonstrated in the intestine. METHODS AND MATERIALS: Human lung microvascular endothelial cells were exposed to 10 Gy irradiation so as to study their ability to acquire an "activated" phenotype. Mice in which the Cre-Lox strategy was used to produce PAI-1 deletion specifically in the endothelial compartment were exposed to 17 Gy whole-thorax irradiation and followed up for 2, 13, and 23 weeks after irradiation...
July 11, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28868937/ameliorative-effect-of-nicotine-exposure-on-insulin-resistance-is-accompanied-by-decreased-cardiac-glycogen-synthase-kinase-3-and-plasminogen-activator-inhibitor-1-during-oral-oestrogen-progestin-therapy
#14
Olugbenga S Michael, Lawrence A Olatunji
CONTEXT: Cigarette smoking is considered to be a major risk factor for the development of diabetes and cardiovascular disease. Oestrogen-progestin combined oral contraceptive (COC) use has been associated with adverse cardiometabolic events. OBJECTIVE: We hypothesized that nicotine would ameliorate insulin resistance (IR) that is accompanied by decreased cardiac glycogen synthase kinase-3 (GSK-3) and plasminogen activator inhibitor-1 (PAI-1). METHODS: Female Wistar rats received (po) low-(0...
September 3, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28865249/effects-of-ultra-low-dose-versus-standard-hormone-therapy-on-fibrinolysis-and-thrombin-generation-in-postmenopausal-women
#15
Magdalena Piróg, Robert Jach, Anetta Undas
OBJECTIVE: To assess the effects of different doses of oral hormone therapy (HT) on thrombin generation and fibrinolysis. STUDY DESIGN: One hundred fifty postmenopausal women were assigned in a randomized controlled study in which the effect of standard dose (1mg 17β-estradiol/5mg dydrogesterone), ultra-low-dose HT (0.5mg 17β-estradiol/2.5mg dydrogesterone) on fibrinolysis and coagulation was compared to controls. Factors measured included plasma clot lysis time (CLT), fibrinolysis activators and inhibitors, thrombin generation (prothrombin fragments 1+2 [F1+2], endogenous thrombin potential [ETP]), normalized activated protein C sensitivity ratio (nAPCsr), and factor (F)VIII activity and were determined before and after 24 weeks of HT...
August 22, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28863189/opposing-effects-of-in-vitro-differentiated-macrophages-sub-type-on-epithelial-wound-healing
#16
Julia A Gindele, Samuel Mang, Nicolas Pairet, Ingrid Christ, Florian Gantner, Jürgen Schymeinsky, David J Lamb
Inappropriate repair responses to pulmonary epithelial injury have been linked to perturbation of epithelial barrier function and airway remodelling in a number of respiratory diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. We developed an in vitro mechanical scratch injury model in air-liquid interface differentiated primary human small airway epithelial cells that recapitulates many of the characteristics observed during epithelial wound injury in both human tissue and small animal models...
2017: PloS One
https://www.readbyqxmd.com/read/28861173/therapeutic-effect-of-rosuvastatin-and-propylthiouracil-on-ameliorating-high-cholesterol-diet-induced-fatty-liver-disease-fibrosis-and-inflammation-in-rabbit
#17
Pao-Yuan Lin, Chih-Hung Chen, Christopher Glenn Wallace, Kuan-Hung Chen, Chia-Lo Chang, Hong-Hwa Chen, Pei-Hsun Sung, Kun-Chen Lin, Sheung-Fat Ko, Cheuk-Kwan Sun, Hsueh-Wen Chang, Pei-Lin Shao, Mel S Lee, Hon-Kan Yip
This study tested the hypothesis that high-cholesterol diet (HCD)-induced fatty liver disease could be ameliorated by rosuvastatin (Ros) and propylthiouracil (PTU) therapy. Thirty-two Zealand rabbits were equally divided into group 1 (sham-control), group 2 (HCD for 8 weeks), group 3 [HCD-Ros (20 mg/kg/day administration after 4-week HFD for 4 weeks)], group 4 [HCD-PTU (0.1% PTU in drinking water) with treatment course as group 3]. Liver weight, fibrosis, collagen deposition area, and serum levels of AST/ALT were highest in group 2, lowest in group 1, and significantly higher in group 4 than group 3 (all P<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28860991/antithrombotic-potential-of-tormentil-extract-in-animal-models
#18
Natalia Marcinczyk, Dominika Jarmoc, Agnieszka Leszczynska, Agnieszka Zakrzeska, Karol Kramkowski, Jakub Strawa, Anna Gromotowicz-Poplawska, Ewa Chabielska, Michal Tomczyk
Potentilla species that have been investigated so far display pharmacological activity mainly due to the presence of polyphenols. Recently, it was shown that polyphenol-rich extract from rhizome of Potentilla erecta (tormentil extract) affects the metabolism of arachidonic acid and exerts both anti-inflammatory and anti-oxidant activities, suggesting a possible effect on thrombosis. Accordingly, the aim of the study was to evaluate the effect of tormentil extract on haemostasis in a rat model of thrombosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28860148/targeting-plasminogen-activator-inhibitor-1-in-tetracycline-induced-pleural-injury-in-rabbits
#19
Galina Florova, Ali O Azghani, Sophia Karandashova, Chris Schaefer, Serge V Yarovoi, Paul J Declerck, Douglas B Cines, Steven Idell, Andrey A Komissarov
Elevated active plasminogen activator inhibitor 1 (PAI-1) has an adverse effect on the outcomes of intrapleural fibrinolytic therapy (IPFT) in tetracycline-induced pleural injury in rabbits. In order to enhance IPFT with prourokinase (scuPA), two mechanistically distinct approaches to targeting PAI-1 were tested: slowing its reaction with urokinase (uPA) and mAb-mediated PAI-1 inactivation. Removing positively charged residues at the "PAI-1 docking site" ((179)RHRGGS(184)→(179)AAAAAA(184)) of uPA results in a 60-fold decrease in the rate of inhibition by PAI-1...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28858863/association-of-plasminogen-activator-inhibitor-1-gene-polymorphisms-and-methylene-tetrahydrofolate-reductase-polymorphisms-with-spontaneous-miscarriages
#20
Petra Bubalo, Iva Buterin, Zrinko Šalek, Vesna Ðogić, Silva Zupančić-Šalek
AIM: The objective of this study was to investigate a possible correlation between the plasminogen activator inhibitor-1 (PAI-1) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and unexplained spontaneous miscarriages (SM). MATERIALS AND METHODS: PAI-1 polymorphisms were evaluated in 150 women with pregnancy in their history. One hundred women with a history of SM formed the study group and 50 women with normal pregnancies served as the control group...
2017: Acta Haematologica
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