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Heparan sulfate

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https://www.readbyqxmd.com/read/29785047/rationally-designed-aav2-and-aavrh8r-capsids-provide-improved-transduction-in-the-retina-and-brain
#1
Jennifer A Sullivan, Lisa M Stanek, Michael J Lukason, Jie Bu, Shayla R Osmond, Elizabeth A Barry, Catherine R O'Riordan, Lamya S Shihabuddin, Seng H Cheng, Abraham Scaria
The successful application of adeno-associated virus (AAV) gene delivery vectors as a therapeutic paradigm will require efficient gene delivery to the appropriate cells in affected organs. In this study, we utilized a rational design approach to introduce modifications to the AAV2 and AAVrh8R capsids and the resulting variants were evaluated for transduction activity in the retina and brain. The modifications disrupted either capsid/receptor binding or altered capsid surface charge. Specifically, we mutated AAV2 amino acids R585A and R588A, which are required for binding to its receptor, heparan sulfate proteoglycans, to generate a variant referred to as AAV2-HBKO...
May 22, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29779903/glycosaminoglycans-analysis-in-blood-and-urine-of-patients-with-mucopolysaccharidosis
#2
Shaukat A Khan, Robert W Mason, Roberto Giugliani, Kenji Orii, Toshiyuki Fukao, Yasuyuki Suzuki, Seiji Yamaguchi, Hironori Kobayashi, Tadao Orii, Shunji Tomatsu
To explore the correlation between glycosaminoglycan (GAG) levels and mucopolysaccharidosis (MPS) type, we have evaluated the GAG levels in blood of MPS II, III, IVA, and IVB and urine of MPS IVA, IVB, and VI by tandem mass spectrometry. Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS; mono-sulfated KS, di-sulfated KS), and the ratio of di-sulfated KS in total KS were measured. Patients with untreated MPS II had higher levels of DS and HS in blood while untreated MPS III had higher levels of HS in blood than age-matched controls...
May 17, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29775666/the-effect-of-syndecan-4-and-glypican-1-knockdown-on-the-proliferation-and-differentiation-of-turkey-satellite-cells-differing-in-age-and-growth-rates
#3
Sandra G Velleman, Daniel L Clark, Jeffrey R Tonniges
Posthatch skeletal muscle growth requires myogenic satellite cells and the dynamic expression of cell membrane-associated proteins. The membrane associated heparan sulfate proteoglycans, syndecan-4 and glypican-1, link the satellite cell niche to the intracellular environment. Sydnecan-4 and glypican-1 are differentially expressed with age in turkey satellite cells and their over-expression impacts both satellite cell proliferation and differentiation, but their effect on satellite cells from lines with different growth potentials is not known...
May 15, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29773865/perlecan-a-heparan-sulfate-proteoglycan-regulates-systemic-metabolism-with-dynamic-changes-in-adipose-tissue-and-skeletal-muscle
#4
Yuri Yamashita, Satoshi Nakada, Toshinori Yoshihara, Takeshi Nara, Norihiko Furuya, Takashi Miida, Nobutaka Hattori, Eri Arikawa-Hirasawa
Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2-/- -Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2-/- -Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29753267/the-localisation-of-the-heparin-binding-sites-of-human-and-murine-interleukin-12-within-the-carboxyterminal-domain-of-the-p40-subunit
#5
Pascale Garnier, Rosemary Mummery, Mark J Forster, Barbara Mulloy, Roslyn V Gibbs, Christopher C Rider
We have previously shown that the heterodimeric cytokine interleukin-12, and the homodimer of its larger subunit p40, both bind to heparin and heparan sulfate with relatively high affinity. In the present study we characterised these interactions using a series of chemically modified heparins as competitive inhibitors. Human interleukin-12 and p40 homodimer show indistinguishable binding profiles with a panel of heparin derivatives, but that of murine interleukin-12 is distinct. Heparin markedly protects the human and murine p40 subunits, but not the p35 subunits, from cleavage by the bacterial endoprotease LysC, further implicating the larger subunit as the location of the heparin binding site...
May 9, 2018: Cytokine
https://www.readbyqxmd.com/read/29752409/specific-glycosaminoglycan-chain-length-and-sulfation-patterns-are-required-for-cell-uptake-of-tau-vs-%C3%AE-synuclein-and-%C3%AE-amyloid-aggregates
#6
Barbara E Stopschinski, Brandon B Holmes, Gregory M Miller, Victor A Manon, Jaime Vaquer-Alicea, William L Prueitt, Linda C Hsieh-Wilson, Marc I Diamond
Transcellular propagation of protein aggregate "seeds" has been proposed to mediate the progression of neurodegenerative diseases in tauopathies and α-synucleinopathies. We previously reported that tau and α-synuclein aggregates bind heparan sulfate proteoglycans (HSPGs) on the cell surface, promoting cellular uptake and intracellular seeding. However, the specificity and binding mode of these protein aggregates to HSPGs remain unknown. Here, we measured direct binding to modified heparins to determine the size and sulfation requirements for tau, α-synuclein, and β-amyloid (Aβ) aggregate binding to glycosaminoglycans (GAGs)...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29750031/glypican-1-antibody-conjugated-gd-au-nanoclusters-for-fi-mri-dual-modal-targeted-detection-of-pancreatic-cancer
#7
Xin Huang, Chengqi Fan, Huanhuan Zhu, Wenjun Le, Shaobin Cui, Xin Chen, Wei Li, Fulei Zhang, Yong Huang, Donglu Sh, Zheng Cui, Chengwei Shao, Bingdi Chen
Introduction: Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods: In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd-Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29748549/genotype-i-of-japanese-encephalitis-virus-virus-like-particles-elicit-sterilizing-immunity-against-genotype-i-and-iii-viral-challenge-in-swine
#8
Yi-Chin Fan, Jo-Mei Chen, Jen-Wei Lin, Yi-Ying Chen, Guan-Hong Wu, Kuan-Hsuan Su, Ming-Tang Chiou, Shang-Rung Wu, Ji-Hang Yin, Jiunn-Wang Liao, Gwong-Jen J Chang, Shyan-Song Chiou
Swine are a critical amplifying host involved in human Japanese encephalitis (JE) outbreaks. Cross-genotypic immunogenicity and sterile protection are important for the current genotype III (GIII) virus-derived vaccines in swine, especially now that emerging genotype I (GI) JE virus (JEV) has replaced GIII virus as the dominant strain. Herein, we aimed to develop a system to generate GI JEV virus-like particles (VLPs) and evaluate the immunogenicity and protection of the GI vaccine candidate in mice and specific pathogen-free swine...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740281/heparan-sulfate-proteoglycans-as-drivers-of-neural-progenitors-derived-from-human-mesenchymal-stem-cells
#9
Rachel K Okolicsanyi, Lotta E Oikari, Chieh Yu, Lyn R Griffiths, Larisa M Haupt
Background: Due to their relative ease of isolation and their high ex vivo and in vitro expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation. Methods: Following the determination that hMSCs maintain neural potential throughout extended in vitro expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29740048/matrilysin-mmp-7-cleavage-of-perlecan-hspg2-complexed-with-semaphorin-3a-supports-fak-mediated-stromal-invasion-by-prostate-cancer-cells
#10
Brian J Grindel, Jerahme R Martinez, Tristen V Tellman, Daniel A Harrington, Hamim Zafar, Luay Nakhleh, Leland W Chung, Mary C Farach-Carson
Interrupting the interplay between cancer cells and extracellular matrix (ECM) is a strategy to halt tumor progression and stromal invasion. Perlecan/heparan sulfate proteoglycan 2 (HSPG2) is an extracellular proteoglycan that orchestrates tumor angiogenesis, proliferation, differentiation and invasion. Metastatic prostate cancer (PCa) cells degrade perlecan-rich tissue borders to reach bone, including the basement membrane, vasculature, reactive stromal matrix and bone marrow. Domain IV-3, perlecan's last 7 immunoglobulin repeats, mimics native proteoglycan by promoting tumoroid formation...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739251/heparan-sulfate-binding-coxsackievirus-b3-strain-pd-a-novel-avirulent-oncolytic-agent-against-human-colorectal-carcinoma
#11
Ahmet Hazini, Markian Pryshliak, Vanessa Brückner, Karin Klingel, Martina Sauter, Sandra Pinkert, Jens Kurreck, Henry Fechner
Coxsackievirus B3 (CVB3), a single-stranded RNA virus of the picornavirus family, has been described as a novel oncolytic virus. However, the used CVB3 strain induced hepatitis and myocarditis in vivo. We hypothesized that oncolytic activity and safety of CVB3 depends on the virus strain and its specific receptor tropism. We investigated different laboratory strains of CVB3 (Nancy, 31-1-93, H3) which use the coxsackievirus and adenovirus receptor (CAR) and the strain PD which uses N- and 6-O-sulfated heparin sulfate (HS) for entry into the cells, for their potential to lyse tumor cells and for their safety profile...
May 9, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29733455/the-chemokine-fragment-cxcl9-74-103-diminishes-neutrophil-recruitment-and-joint-inflammation-in-antigen-induced-arthritis
#12
Daiane Boff, Helena Crijns, Rik Janssens, Vincent Vanheule, Gustavo B Menezes, Soraia Macari, Tarcilia A Silva, Flavio A Amaral, Paul Proost
This study investigates if treatment with a peptide corresponding to the 30 C-terminal amino acids of CXCL9, CXCL9(74-103), ameliorates joint inflammation in a murine model of antigen-induced arthritis (AIA). AIA was induced in male C57BL/6J mice. Intravenous injection of CXCL9(74-103), simultaneously performed with a tibiofemoral challenge with methylated BSA (mBSA) as antigen in mice immunized with mBSA, diminished the accumulation of leukocytes, in particular neutrophils, in the synovial cavity. The levels of the chemokines CXCL1, CXCL2, and CXCL6 and of the cytokine IL-6 were decreased in inflamed periarticular tissue of mice treated with the CXCL9-derived peptide compared to non-treated AIA mice...
May 7, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29732534/epigenetic-loss-of-heparan-sulfate-3-o-sulfation-sensitizes-ovarian-carcinoma-to-oncogenic-signals-and-predicts-prognosis
#13
Rui-Lan Huang, Hsiang-Ju Chen, Lin-Yu Chen, Tai-Kuang Chao, Wei-Yu Lin, Phui-Ly Liew, Po-Hsuan Su, Yu-Chun Weng, Yu-Chi Wang, Chi-Chun Liao, Yaw-Wen Hsu, Hui- Chen Wang, Hung-Cheng Lai
Precision medicine requires markers for therapeutic guidance. The purpose of this study was to determine whether epithelial ovarian cancer (EOC) epigenetics can lead to the identification of biomarkers for precision medicine. Through integrative methylomics, we discovered and validated the epigenetic signature of NEFH and HS3ST2 as an independent prognostic factor for type II EOC in our dataset (n = 84), two independent methylomics datasets (total n = 467). Integrated transcriptomics dataset (n = 1147) and tissue microarrays (n = 54) of HS3ST2 also related to high-methylation statuses and the EOC prognosis...
May 7, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29730503/fibulin-7-a-heparin-binding-matricellular-protein-promotes-renal-tubular-calcification-in-mice
#14
Jun Tsunezumi, Hidekazu Sugiura, Lalhaba Oinam, Aktar Ali, Bui Quoc Thang, Aiko Sada, Yoshito Yamashiro, Makoto Kuro-O, Hiromi Yanagisawa
Ectopic calcification occurs during development of chronic kidney disease and has a negative impact on long-term prognosis. The precise molecular mechanism and prevention strategies, however, are not established. Fibulin-7 (Fbln7) is a matricellular protein structurally similar to elastogenic short fibulins, shown to bind dental mesenchymal cells and heparin. Here, we report that Fbln7 is highly expressed in renal tubular epithelium in the adult kidney and mediates renal calcification in mice. In vitro analysis revealed that Fbln7 bound heparin at the N-terminal coiled-coil domain...
May 3, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29729013/the-role-of-heparan-sulfates-in-protein-aggregation-and-their-potential-impact-on-neurodegeneration
#15
REVIEW
Auriane Maïza, Sandrine Chantepie, Cecilia Vera, Alexandre Fifre, Min Bao Huynh, Olivier Stettler, Mohand Ouidir Ouidja, Dulce Papy-Garcia
Neurodegenerative disorders, such as Alzheimer's, Parkinson's, and prion diseases, are directly linked to the formation and accumulation of protein aggregates in the brain. These aggregates, principally made of proteins or peptides that clamp together after acquisition of β-folded structures, also contain heparan sulfates. Several lines of evidence suggest that heparan sulfates centrally participate in the protein aggregation process. In vitro, they trigger misfolding, oligomerisation, and fibrillation of amyloidogenic proteins, such as Aβ, tau, α-synuclein, prion protein, etc...
May 4, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29726297/glioma-targeting-peptide-modified-apoferritin-nanocage
#16
Meifang Zhai, Yuli Wang, Ligang Zhang, Meng Liang, Shiyao Fu, Lin Cui, Meiyan Yang, Wei Gong, Zhiping Li, Lian Yu, Xiangyang Xie, Chunrong Yang, Yang Yang, Chunsheng Gao
Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature of drugs and the physiological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). An ideal glioma-targeted delivery system must be sufficiently potent to cross the BBB and BBTB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29721203/patient-derived-xenografts-pdx-predict-an-effective-heparanase-based-therapy-for-lung-cancer
#17
Amit Katz, Uri Barash, Ilanit Boyango, Sari Feld, Yaniv Zohar, Edward Hammond, Neta Ilan, Ran Kremer, Israel Vlodavsky
Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29718295/genetic-and-enzymatic-characterization-of-3-o-sulfotransferase-snps-associated-with-plasmodium-falciparum-parasitaemia
#18
Ngoc Thy Nguyen, Romain R Vivès, Magali Torres, Vincent Delauzun, Els Saesen, Véronique Roig-Zamboni, Hugues Lortat-Jacob, Pascal Rihet, Yves Bourne
The HS3ST3A1/B1 genes encode two homologous 3-O-sulfotransferases involved in the late modification step during heparan sulfate (HS) biosynthesis. In addition to the SNPs rs28470223 (C > T) in the promoter region of both HS3ST3A1 and rs62636623 (Gly/Arg) in the stem region of HS3ST3B1, three missense mutations (rs62056073, rs61729712 and rs9906590) located within the catalytic sulfotransferase domain of 3-OST-B1 are linked and associated to P. falciparum parasitaemia. To ascertain the functional effects of these SNP associations, we investigated the regulatory effect of rs28470223 and characterized the enzymatic activity of the missense SNP rs61729712 (Ser279Asn) localized at proximity of the substrate binding cleft...
April 28, 2018: Glycobiology
https://www.readbyqxmd.com/read/29707296/sevoflurane-did-not-show-better-protective-effect-on-endothelial-glycocalyx-layer-compared-to-propofol-during-lung-resection-surgery-with-one-lung-ventilation
#19
Hye-Jin Kim, Eunsoo Kim, Seung-Hoon Baek, Hee Young Kim, Joo-Yun Kim, Juyeon Park, Eun-Ji Choi
Background: The endothelial glycocalyx layer (EGL) coats the alveolar capillary endothelium and plays important roles in pulmonary vascular protection, modulation, and hemostasis. Ischemia-reperfusion, which occurs during lung resection surgery with one lung ventilation (OLV), can damage the EGL. Sevoflurane is known for its protective effect against ischemia-reperfusion injury. Therefore, we hypothesized that lung resection surgery produces EGL damage and sevoflurane protects the EGL better than the intravenous anesthetic propofol...
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29700203/multiple-roles-of-epithelial-heparan-sulfate-in-stomach-morphogenesis
#20
Meina Huang, Hua He, Tatyana Belenkaya, Xinhua Lin
Heparan sulfate proteoglycans (HSPGs) have been shown to regulate various developmental processes. However, the function of heparan sulfate (HS) in the development of mammalian stomach has not been characterized yet. Here we investigate the role of epithelial HS in embryonic stomach by examining glycosyltransferase gene Exostoses (multiple) 1 ( Ext1 )-deficient mice. We show that HS exhibits specific and dynamic expression pattern in mouse embryonic stomach. Depletion of the epithelial HS leads to stomach hypoplasia with phenotypic differences in the gastric mucosa between forestomach and hindstomach...
April 26, 2018: Journal of Cell Science
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