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Heparan sulfate

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https://www.readbyqxmd.com/read/28723112/surfen-assembled-graphene-oxide-for-fluorescence-turn-on-detection-of-sulfated-glycosaminoglycans-in-biological-matrix
#1
Yen-Ting Wang, Wei-Lung Tseng
Sulfated glycosaminoglycans (GAGs) not only serve as a biomarker for mucopolysaccharidoses disease but also participate in various biological processes, such as blood clot medication (heparin) and signal transduction (heparan sulfate). However, few fluorescent sensors, such as 1,9-dimethylmethylene blue, have been developed for the detection of sulfated GAGs in the real world. Herein, we fabricated a surfen/few-layer graphene oxide (FLGO) nanocomplex for sensing sulfated GAGs in biological fluids. Surfen molecules are self-assembled onto the surface of FLGO through electrostatic attraction, and their fluorescence was then quenched by the creation of the FLGO-surfen complex (static quenching) and partially combined with the energy transfer from surfen to FLGO (dynamic quenching)...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722668/coupling-to-a-cancer-selective-heparan-sulfate-targeted-branched-peptide-can-by-pass-breast-cancer-cell-resistance-to-methotrexate
#2
Lorenzo Depau, Jlenia Brunetti, Chiara Falciani, Silvia Scali, Giulia Riolo, Elisabetta Mandarini, Alessandro Pini, Luisa Bracci
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722655/key-steps-in-unconventional-secretion-of-fibroblast-growth-factor-2-reconstituted-with-purified-components
#3
Julia P Steringer, Sascha Lange, Sabína Čujová, Radek Šachl, Chetan Poojari, Fabio Lolicato, Oliver Beutel, Hans-Michael Müller, Sebastian Unger, Ünal Coskun, Alf Honigmann, Ilpo Vattulainen, Martin Hof, Christian Freund, Walter Nickel
FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28720149/heparanase-promotes-neuroinflammatory-response-during-subarachnoid-hemorrhage-in-rats
#4
Benjarat Changyaleket, Zhao Zhong Chong, Randal O Dull, Danop Nanegrungsunk, Haoliang Xu
BACKGROUND: Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage. METHODS: Rats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28718936/heparan-sulfate-promotes-recovery-from-acute-liver-injury-inhibition-of-progressive-cell-death-or-enhanced-regeneration
#5
EDITORIAL
Udayan Apte, Neil Kaplowitz
No abstract text is available yet for this article.
July 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28716813/inhibition-of-heparanase-in-pediatric-brain-tumor-cells-attenuates-their-proliferation-invasive-capacity-and-in-vivo-tumor-growth
#6
Argyris Spyrou, Soumi Kundu, Lulu Haseeb, Di Yu, Tommie Olofsson, Keith Dredge, Edward Hammond, Uri Barash, Israel Vlodavsky, Karin Forsberg-Nilsson
Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28713940/a-novel-method-to-identify-hub-pathways-of-rheumatoid-arthritis-based-on-differential-pathway-networks
#7
Shi-Tong Wei, Yong-Hua Sun, Shi-Hua Zong
The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713850/collagen-and-heparan-sulfate-coatings-differentially-alter-cell-proliferation-and-attachment-in-vitro-and-in-vivo
#8
Christopher M Walthers, Chase J Lyall, Alireza K Nazemi, Puneet V Rana, James C Y Dunn
Tissue engineering is an innovative field of research applied to treat intestinal diseases. Engineered smooth muscle requires dense smooth muscle tissue and robust vascularization to support contraction. The purpose of this study was to use heparan sulfate (HS) and collagen coatings to increase the attachment of smooth muscle cells (SMCs) to scaffolds and improve their survival after implantation. SMCs grown on biologically coated scaffolds were evaluated for maturity and cell numbers after 2, 4 and 6 weeks in vitro and both 2 and 6 weeks in vivo...
September 2016: Technology
https://www.readbyqxmd.com/read/28706183/modulation-of-interleukin-12-activity-in-the-presence-of-heparin
#9
Srinivas Jayanthi, Bhanu Prasanth Koppolu, Khue G Nguyen, Sean G Smith, Barbara K Felber, Thallapuranam Krishnaswamy Suresh Kumar, David A Zaharoff
Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), modulate the functions of numerous cytokines. The aims of this multidisciplinary research were to characterize heparin binding to interleukin-12 (IL-12) and determine the mechanism(s) by which heparin influences IL-12 bioactivity. Heparin and HS were found to bind human IL-12 (hIL-12) with low micromolar affinity and increase hIL-12 bioactivity by more than 6-fold. Conversely, other GAGs did not demonstrate significant binding, nor did their addition affect hIL-12 bioactivity...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700908/endothelial-glycocalyx-mediated-nitric-oxide-production-in-response-to-selective-afm-pulling
#10
Anne Marie W Bartosch, Rick Mathews, John M Tarbell
Nitric oxide (NO) is a regulatory molecule in the vascular system and its inhibition due to endothelial injury contributes to cardiovascular disease. The glycocalyx is a thin layer of glycolipids, glycoproteins, and proteoglycans on the surface of mammalian epithelial cells. Extracellular forces are transmitted through the glycocalyx to initiate intracellular signaling pathways. In endothelial cells (ECs), previous studies have shown the glycocalyx to be a significant mediator of NO production; degradation of the endothelial glycocalyx layer (EGL) drastically reduces EC production of NO in response to fluid shear stress...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28698456/combining-nmr-spectroscopy-and-chemometrics-to-monitor-structural-features-of-crude-hep-arin
#11
Lucio Mauri, Maria Marinozzi, Giulia Mazzini, Richard E Kolinski, Michael Karfunkle, David A Keire, Marco Guerrini
Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses...
July 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28697896/binding-kinetics-and-lateral-mobility-of-hsv-1-on-end-grafted-sulfated-glycosaminoglycans
#12
Nadia Peerboom, Stephan Block, Noomi Altgärde, Olov Wahlsten, Stephanie Möller, Matthias Schnabelrauch, Edward Trybala, Tomas Bergström, Marta Bally
Many viruses, including herpes simplex (HSV), are recruited to their host cells via interaction between their envelope glycoproteins and cell-surface glycosaminoglycans (GAGs). This initial attachment is of a multivalent nature, i.e., it requires the establishment of multiple bonds between amino acids of viral glycoproteins and sulfated saccharides on the GAG chain. To gain understanding of how this binding process is modulated, we performed binding kinetics and mobility studies using end-grafted GAG chains that mimic the end attachment of these chains to proteoglycans...
July 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28684085/incomplete-biomarker-response-in-mucopolysaccharidosis-type-i-after-successful-hematopoietic-cell-transplantation
#13
Gé-Ann Kuiper, Peter M van Hasselt, Jaap Jan Boelens, Frits A Wijburg, Eveline J Langereis
BACKGROUND: Residual disease, primarily involving musculoskeletal tissue, is a common problem in patients with neuronopathic mucopolysaccharidosis type I (MPS I, Hurler or severe Hurler-Scheie phenotype) after a successful hematopoietic cell transplantation (HCT). The concentration of the GAG derived biomarkers heparan sulfate (HS) and dermatan sulfate (DS), may reflect residual disease and is used for monitoring biochemical response to therapies. This study investigates the response of HS and DS in blood and urine to HCT in MPS I patients...
May 18, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28679861/enhanced-chemosensitization-of-anoikis-resistant-melanoma-cells-through-syndecan-2-upregulation-upon-anchorage-independency
#14
TingTing Tseng, WuChing Uen, JenChih Tseng, ShaoChen Lee
Syndecan family proteins are heparan sulfate proteoglycans, which involved in various cellular activities and associating with metastatic potential and chemosensitivity of tumor cells. Melanoma is one of malignant tumors with poor prognosis upon metastasis. Previously, we had shown that melanoma cells remained survived under cell detachment, which was similar to the initial steps of tumor metastasis. Downregulation of syndecan-1 and upregulation of syndecan-2 in melanoma A375 cells were observed by different suspension conditions...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28678201/characterization-of-danaparoid-complex-extractive-drug-by-an-orthogonal-analytical-approach
#15
Cristina Gardini, Elena Urso, Marco Guerrini, René van Herpen, Pauline de Wit, Annamaria Naggi
Danaparoid sodium salt, is the active component of ORGARAN, an anticoagulant and antithrombotic drug constituted of three glycosaminoglycans (GAGs) obtained from porcine intestinal mucosa extracts. Heparan sulfate is the major component, dermatan sulfate and chondroitin sulfate being the minor ones. Currently dermatan sulfate and chondroitin sulfate are quantified by UV detection of their unsaturated disaccharides obtained by enzymatic depolymerization. Due to the complexity of danaparoid biopolymers and the presence of shared components, an orthogonal approach has been applied using more advanced tools and methods...
July 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28676128/phenotype-prediction-for-mucopolysaccharidosis-type-i-by-in-silico-analysis
#16
Li Ou, Michael J Przybilla, Chester B Whitley
BACKGROUND: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease due to deficiency of α-L-iduronidase (IDUA), a lysosomal enzyme that degrades glycosaminoglycans (GAG) heparan and dermatan sulfate. To achieve optimal clinical outcomes, early and proper treatment is essential, which requires early diagnosis and phenotype severity prediction. RESULTS: To establish a genotype/phenotype correlation of MPS I disease, a combination of bioinformatics tools including SIFT, PolyPhen, I-Mutant, PROVEAN, PANTHER, SNPs&GO and PHD-SNP are utilized...
July 4, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28672878/epigenetic-regulation-of-the-biosynthesis-enzymatic-modification-of-heparan-sulfate-proteoglycans-implications-for-tumorigenesis-and-cancer-biomarkers
#17
REVIEW
Elizabeth E Hull, McKale R Montgomery, Kathryn J Leyva
Emerging evidence suggests that the enzymes in the biosynthetic pathway for the synthesis of heparan sulfate moieties of heparan sulfate proteoglycans (HSPGs) are epigenetically regulated at many levels. As the exact composition of the heparan sulfate portion of the resulting HSPG molecules is critical to the broad spectrum of biological processes involved in oncogenesis, the epigenetic regulation of heparan sulfate biosynthesis has far-reaching effects on many cellular activities related to cancer progression...
June 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28664165/clearance-of-heparan-sulfate-and-attenuation-of-cns-pathology-by-intracerebroventricular-bmn-250-in-sanfilippo-type-b-mice
#18
Mika Aoyagi-Scharber, Danielle Crippen-Harmon, Roger Lawrence, Jon Vincelette, Gouri Yogalingam, Heather Prill, Bryan K Yip, Brian Baridon, Catherine Vitelli, Amanda Lee, Olivia Gorostiza, Evan G Adintori, Wesley C Minto, Jeremy L Van Vleet, Bridget Yates, Sara Rigney, Terri M Christianson, Pascale M N Tiger, Melanie J Lo, John Holtzinger, Paul A Fitzpatrick, Jonathan H LeBowitz, Sherry Bullens, Brett E Crawford, Stuart Bunting
Sanfilippo syndrome type B (mucopolysaccharidosis IIIB), caused by inherited deficiency of α-N-acetylglucosaminidase (NAGLU), required for lysosomal degradation of heparan sulfate (HS), is a pediatric neurodegenerative disorder with no approved treatment. Intracerebroventricular (ICV) delivery of a modified recombinant NAGLU, consisting of human NAGLU fused with insulin-like growth factor 2 (IGF2) for enhanced lysosomal targeting, was previously shown to result in marked enzyme uptake and clearance of HS storage in the Naglu(-/-) mouse brain...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28661485/osteoblastic-heparan-sulfate-glycosaminoglycans-control-bone-remodeling-by-regulating-wnt-signaling-and-the-crosstalk-between-bone-surface-and-marrow-cells
#19
Rafik Mansouri, Yohann Jouan, Eric Hay, Claudine Blin-Wakkach, Monique Frain, Agnès Ostertag, Carole Le Henaff, Caroline Marty, Valérie Geoffroy, Pierre J Marie, Martine Cohen-Solal, Dominique Modrowski
Stimulating bone formation is an important challenge for bone anabolism in osteoporotic patients or to repair bone defects. The osteogenic properties of matrix glycosaminoglycans (GAGs) have been explored; however, the functions of GAGs at the surface of bone-forming cells are less documented. Syndecan-2 is a membrane heparan sulfate proteoglycan that is associated with osteoblastic differentiation. We used a transgenic mouse model with high syndecan-2 expression in osteoblasts to enrich the bone surface with cellular GAGs...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28659919/the-%C3%AE-d-endoglucuronidase-heparanase-is-a-danger-molecule-that-drives-systemic-inflammation-and-correlates-with-clinical-course-after-open-and-endovascular-thoracoabdominal-aortic-aneurysm-repair-lessons-learnt-from-mice-and-men
#20
Lukas Martin, Alexander Gombert, Jianmin Chen, Julia Liebens, Julia Verleger, Johannes Kalder, Gernot Marx, Michael Jacobs, Christoph Thiemermann, Tobias Schuerholz
Thoracoabdominal aortic aneurysm (TAAA) is a highly lethal disorder requiring open or endovascular TAAA repair, both of which are rare, but extensive and complex surgical procedures associated with a significant systemic inflammatory response and high post-operative morbidity and mortality. Heparanase is a β-d-endoglucuronidase that remodels the endothelial glycocalyx by degrading heparan sulfate in many diseases/conditions associated with systemic inflammation including sepsis, trauma, and major surgery. We hypothesized that (a) perioperative serum levels of heparanase and heparan sulfate are associated with the clinical course after open or endovascular TAAA repair and (b) induce a systemic inflammatory response and renal injury/dysfunction in mice...
2017: Frontiers in Immunology
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