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Sisse R Ostrowski, Hanne H Henriksen, Jakob Stensballe, Mikkel Gybel-Brask, Jessica C Cardenas, Lisa A Baer, Bryan A Cotton, John B Holcomb, Charles E Wade, Pär I Johansson
BACKGROUND: One third of severely injured patients present with a laboratory based diagnosis of coagulopathy. This study investigated clinical and biomarker profile of patients with rapid TEG (rTEG) coagulopathy hypothesizing that sympathoadrenal activation and endothelial damage were drivers of this condition. METHODS: Prospective observational study of 404 trauma patients admitted to a Level 1 US Trauma Center. Patients with admission rTEG and plasma measurements of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial activation/damage (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin, nucleosomes) were included...
October 25, 2016: Journal of Trauma and Acute Care Surgery
Stuart A Cain, Ewa J Mularczyk, Mukti Singh, Teresa Massam-Wu, Cay M Kielty
ADAMTS10 and ADAMTS6 are homologous metalloproteinases with ill-defined roles. ADAMTS10 mutations cause Weill-Marchesani syndrome (WMS), implicating it in fibrillin microfibril biology since some fibrillin-1 mutations also cause WMS. However little is known about ADAMTS6 function. ADAMTS10 is resistant to furin cleavage, however we show that ADAMTS6 is effectively processed and active. Using siRNA, over-expression and mutagenesis, it was found ADAMTS6 inhibits and ADAMTS10 is required for focal adhesions, epithelial cell-cell junction formation, and microfibril deposition...
October 25, 2016: Scientific Reports
Cole R Drifka, Agnes G Loeffler, Kara Mathewson, Adib Keikhosravi, Jens C Eickhoff, Yuming Liu, Sharon M Weber, W John Kao, Kevin W Eliceiri
Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value...
October 20, 2016: Oncotarget
Ralph D Sanderson, Michael Elkin, Alan C Rapraeger, Neta Ilan, Israel Vlodavsky
Because of its impact on multiple biological pathways, heparanase has emerged as a major regulator of cancer, inflammation and other disease processes. Heparanase accomplishes this by degrading heparan sulfate which regulates the abundance and location of heparin-binding growth factors thereby influencing multiple signaling pathways that control gene expression, syndecan shedding and cell behavior. In addition, heparanase can act via non-enzymatic mechanisms that directly activate signaling at the cell surface...
October 18, 2016: FEBS Journal
Addolorata Pisconti, Glen B Banks, Farshad Babaeijandaghi, Nicole Dalla Betta, Fabio M V Rossi, Jeffrey S Chamberlain, Bradley B Olwin
BACKGROUND: The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. RESULTS: Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts...
2016: Skeletal Muscle
Sandeep Gopal, Hinke A B Multhaupt, Roger Pocock, John R Couchman
Cell-extracellular matrix (ECM) and cell-cell junctions that employ microfilaments are sites of tension. They are important for tissue repair, morphogenetic movements and can be emblematic of matrix contraction in fibrotic disease and the stroma of solid tumors. One cell surface receptor, syndecan-4, has been shown to regulate focal adhesions, junctions that form at the ends of microfilament bundles in response to matrix components such as fibronectin. Recently it has been shown that signaling emanating from this proteoglycan receptor includes regulation of Rho family GTPases and cytosolic calcium...
October 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Joanna Majerczak, Marcin Grandys, Krzysztof Duda, Agnieszka Zakrzewska, Aneta Balcerczyk, Leszek Kolodziejski, Dorota Szymoniak-Chochol, Ryszard T Smolenski, Grzegorz Bartosz, Stefan Chlopicki, Jerzy A Zoladz
In this study we have evaluated the effect of 20-weeks of moderate-intensity endurance training (ET) on the endothelial glycocalyx layer integrity in relation to the training-induced changes in antioxidant defence. Eleven healthy young, untrained men performed an incremental cycling exercise until exhaustion before and after 20 weeks of ET. Endurance training consisted of 40- minute sessions, mainly of moderate-intensity (∼50% of VO2max ), performed 4 times per week. Venous blood samples were taken at rest and at the end of the maximal exercise test...
October 17, 2016: Experimental Physiology
Manuela Viola, Kathrin Brüggemann, Evgenia Karousou, Ilaria Caon, Elena Caravà, Davide Vigetti, Burkhard Greve, Christian Stock, Giancarlo De Luca, Alberto Passi, Martin Götte
Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates...
October 15, 2016: Glycoconjugate Journal
Tommy A Karlsen, Gustavo Antonio de Souza, Bjørn Ødegaard, Lars Engebretsen, Jan E Brinchmann
Osteoarthritis is a serious disease of articular cartilage. The pathogenic factors contributing to this disorder are inflammation, extracellular matrix degradation and failure to rebuild the articular cartilage. Preclinical studies suggest that microRNA-140 may play a protective role in osteoarthritis development, but little is known about the mechanism by which this occurs. Here we present the results of forced expression of microRNA-140 in an in vitro model of osteoarthritis, evaluated by global proteomics analysis...
October 11, 2016: Molecular Therapy. Nucleic Acids
Per Lehnert, Pär I Johansson, Sisse R Ostrowski, Christian H Møller, Lia E Bang, Peter Skov Olsen, Jørn Carlsen
Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones)...
October 11, 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Izhar Burhan, Giulia Furini, Hugues Lortat-Jacob, Adeola G Atobatele, Alessandra Scarpellini, Nina Schroeder, John Atkinson, Mabrouka Maamra, Faith H Nutter, Philip Watson, Manlio Vinciguerra, Timothy S Johnson, Elisabetta A M Verderio
Transglutaminase-2 (TG2) is a new anti-fibrotic target for chronic kidney disease, for its role in altering the extracellular homeostatic balance leading to excessive build-up of matrix in kidney. However, there is no confirmation that TG2 is the only transglutaminase involved, neither there are strategies to control its action specifically over that of the conserved family-members. In this study, we have profiled transglutaminase isozymes in the rat subtotal nephrectomy (SNx) model of progressive renal scarring...
October 3, 2016: Scientific Reports
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor beta (TGFB) signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6, and another inhibitory SMAD (SMAD7), promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with JFH1 HCVcc; we measured HCV binding, intracellular levels of HCV RNA, and expression of target genes...
September 29, 2016: Gastroenterology
Mathias Schemmerer, Silke Apelt, Eva Trojnar, Rainer G Ulrich, Jürgen J Wenzel, Reimar Johne
Hepatitis E virus (HEV) is a human pathogen with increasing importance. The lack of efficient cell culture systems hampers systematic studies on its replication cycle, virus neutralization and inactivation. Here, several cell lines were inoculated with the HEV genotype 3c strain 47832c, previously isolated from a chronically infected transplant patient. At 14 days after inoculation the highest HEV genome copy numbers were found in A549 cells, followed by PLC/PRF/5 cells, whereas HepG2/C3A, Huh-7 Lunet BLR and MRC-5 cells only weakly supported virus replication...
2016: Viruses
Andrzej J Jaroszyński, Anna Jaroszyńska, Stanisław Przywara, Tomasz Zaborowski, Andrzej Książek, Wojciech Dąbrowski
BACKGROUND: Left ventricular hypertrophy is associated withincreased mortality in hemodialysis (HD) patients.Syndecan-4 plays a role in many processes that are involved in the heart fibrosis and hypertrophy.We designed this study to prospectively determine whether syndecan-4 was predictive of mortality in a group of HD patients. METHODS: In total, 191 HD patients were included. Clinical, biochemical and echocardiographic parameters were recorded. HD patients were followed-up for 23...
2016: PloS One
Eduardo Rodrigues Fregnani, Danyel Elias da Cruz Perez, Oslei Paes de Almeida, Felipe Paiva Fonseca, Fernando Augusto Soares, Gilberto de Castro Junior, Fábio Abreu de Alves
AIMS: The aim of this study was to investigate whether the expression of BRAF-V600E determines an aggressive clinical and molecular presentation of ameloblastoma. METHODS AND RESULTS: Ninety-three cases of solid ameloblastomas were arranged in a 1.0-mm tissue microarray block. Immunohistochemistry against a large panel of cytokeratins (CK), epidermal growth factor receptor (EGFR), parathyroid hormone-related peptide (PTHrP), syndecan-1, Ki67, p53, and BRAF-V600E were done...
September 28, 2016: Histopathology
Ildiko Kasza, Diego Hernando, Alejandro Roldán-Alzate, Caroline M Alexander, Scott B Reeder
Dermal white adipose tissue (dWAT) was recently recognized for its potential to modify whole body metabolism. Here, we show that dWAT can be quantified using a high-resolution, fat-specific magnetic resonance imaging (MRI) technique. Noninvasive MRI has been used to describe adipocyte depots for many years; the MRI technique we describe uses an advanced fat-specific method to measure the thickness of dWAT, together with the total volume of WAT and the relative activation/fat depletion of brown adipose tissues (BAT)...
2016: JCI Insight
Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi
Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression...
September 22, 2016: Cancer Letters
T K Kim, K Nam, Y J Cho, J J Min, Y J Hong, K U Park, D M Hong, Y Jeon
The infusion of fluids to patients may affect tissue microcirculation and the endothelial glycocalyx. However, the effects of hydroxyethyl starch and crystalloid on endothelial glycocalyx degradation and microvascular reactivity have not been evaluated in detail. We hypothesised that hydroxyethyl starch may cause less endothelial glycocalyx degradation and better microvascular reactivity than that caused by crystalloid. We randomly allocated 120 patients undergoing off-pump coronary artery bypass graft surgery to receive up to 20 ml...
September 26, 2016: Anaesthesia
Tania Arcondéguy, Christian Touriol, Eric Lacazette
Quantification of secreted factors is most often measured with enzyme-linked immunosorbent assay (ELISA), Western Blot, or more recently with antibody arrays. However, some of these, like low-molecular-weight fibroblast growth factor-2 (LMW FGF-2; the 18 kDa form), exemplify a set of secreted but almost non-diffusible molecular actors. It has been proposed that phosphorylated FGF-2 is secreted via a non-vesicular mechanism and that heparan sulfate proteoglycans function as extracellular reservoir but also as actors for its secretion...
2016: Methods in Molecular Biology
Jun Xie, Ran Li, Han Wu, Jianzhou Chen, Guannan Li, Qinhua Chen, Zhonghai Wei, Guixin He, Lian Wang, Albert Ferro, Biao Xu
Endothelial progenitor cells (EPCs) are a subtype of bone marrow-derived progenitor cells. Stromal cell-derived factor 1 (SDF-1)-mediated EPC mobilization from bone marrow to areas of ischemia plays an important role in angiogenesis. Previous studies have reported that advanced glycation endproducts (AGEs), which are important mediators of diabetes-related vascular pathology, may impair EPC migration and homing, but the mechanism is unclear. Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan receptor on the cell surface, involved in SDF-1-dependent cell migration...
September 24, 2016: Stem Cells
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