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Heparan sulfate

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https://www.readbyqxmd.com/read/28525382/sulfatase-1-overexpression-indicates-poor-prognosis-in-urothelial-carcinoma-of-the-urinary-bladder-and-upper-tract
#1
Hsiang-Ying Lee, Bi-Wen Yeh, Ti-Chun Chan, Kei-Fu Yang, Wei-Ming Li, Chun-Nung Huang, Hung-Lung Ke, Ching-Chia Li, Hsin-Chih Yeh, Peir-In Liang, Yow-Ling Shiue, Wen-Jeng Wu, Chien-Feng Li
Urothelial carcinoma (UC), arising from the urothelium of the urinary tract, can occur in the upper (UTUC) and the urinary bladder (UBUC). A representative molecular aberration for UC characteristics and prognosis remains unclear. Data mining of Gene Expression Omnibus focusing on UBUC, we identified sulfatase-1 (SULF1) upregulation is associated with UC progression. SULF1 controls the sulfation status of heparan sulfate proteoglycans and plays a role in tumor growth and metastasis, while its role is unexplored in UC...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28505124/structure-activity-relationships-of-bioengineered-heparin-heparan-sulfates-produced-in-different-bioreactors
#2
Ha Na Kim, John M Whitelock, Megan S Lord
Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains...
May 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28499870/fibronectin-on-extracellular-vesicles-from-microvascular-endothelial-cells-is-involved-in-the-vesicle-uptake-into-oligodendrocyte-precursor-cells
#3
Sho Osawa, Masashi Kurachi, Hanako Yamamoto, Yuhei Yoshimoto, Yasuki Ishizaki
We previously reported transplantation of brain microvascular endothelial cells (MVECs) into cerebral white matter infarction model improved the animal's behavioral outcome by increasing the number of oligodendrocyte precursor cells (OPCs). We also revealed extracellular vesicles (EVs) derived from MVECs promoted survival and proliferation of OPCs in vitro. In this study, we investigated the mechanism how EVs derived from MVECs contribute to OPC survival and proliferation. Protein mass spectrometry and enzyme-linked immunosorbent assay revealed fibronectin was abundant on the surface of EVs from MVECs...
May 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28499501/potential-involvement-of-chondroitin-sulfate-a-in-the-pathogenesis-of-ameloblastoma
#4
Xiangjun Li, Hiroshi Kurita, Tiepeng Xiao, Kyou Iijima, Kenji Kurashina, Jun Nakayama
Ameloblastoma is classified as a benign odontogenic tumor characterized by locally invasive behavior and high risk of recurrence. Here, we evaluate a potential role for glycosaminoglycan, a structural component of cell membranes and extracellular matrix, in ameloblstoma pathogenesis. We subjected formalin-fixed, paraffin-embedded tissue sections of 34 cases of ameloblastoma, 10 of odontogenic keratocyst, and 17 of dentigerous cyst to immunohistochemistry using monoclonal antibodies recognizing chondroitin sulfate A (CS-A), heparan sulfate (HS), and keratan sulfate (KS)...
May 9, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28490587/heparanase-upregulation-contributes-to-porcine-reproductive-and-respiratory-syndrome-virus-release
#5
Chunhe Guo, Zhenbang Zhu, Yang Guo, Xiaoying Wang, Piao Yu, Shuqi Xiao, Yaosheng Chen, Yongchang Cao, Xiaohong Liu
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Heparan sulfate (HS) is used by PRRSV for initial attachment to target cells. However, the role of HS in the late phase of PRRSV infection and the mechanism of virus release from host cells remain largely unknown. In this study, we showed that PRRSV infection caused a decrease of HS expression and upregulated heparanase, the only known enzyme capable to degrade HS. We subsequently demonstrated that the NF-κB signaling pathway and cathepsin L protease were involved in regulation of PRRSV infection-induced heparanase...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28490013/sulfatase-2-modulates-fate-change-from-motor-neurons-to-oligodendrocyte-precursor-cells-through-coordinated-regulation-of-shh-signaling-with-sulfatase-1
#6
Wen Jiang, Yugo Ishino, Hirokazu Hashimoto, Kazuko Keino-Masu, Masayuki Masu, Kenji Uchimura, Kenji Kadomatsu, Takeshi Yoshimura, Kazuhiro Ikenaka
Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2, which specifically remove sulfate from heparan sulfate proteoglycans. Although several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh) signaling during embryonic ventral spinal cord development, the detailed expression pattern and function of Sulf2 in the spinal cord remains to be determined. In this study, we found that Sulf2 also modulates the cell fate change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by regulating Shh signaling in the mouse ventral spinal cord in coordination with Sulf1...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28486399/assessment-of-heparanase-mediated-angiogenesis-using-microvascular-endothelial-cells-identification-of-%C3%AE-carrageenan-derivative-as-a-potent-anti-angiogenic-agent
#7
Nicolas Poupard, Pamela Badarou, Fabienne Fasani, Hugo Groult, Nicolas Bridiau, Frédéric Sannier, Stéphanie Bordenave-Juchereau, Claudine Kieda, Jean-Marie Piot, Catherine Grillon, Ingrid Fruitier-Arnaudin, Thierry Maugard
Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC50 of 7...
May 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28482145/a-controlled-release-system-for-simultaneous-delivery-of-three-human-perivascular-stem-cell-derived-factors-for-tissue-repair-and-regeneration
#8
Nurlan Mansurov, William C W Chen, Hassan Awada, Johnny Huard, Yadong Wang, Arman Saparov
Transplanted stem/progenitor cells improve tissue healing and regeneration anatomically and functionally mostly due to their secreted trophic factors. However, harsh conditions at the site of injury, including hypoxia, oxidative and inflammatory stress, increased fibrosis and insufficient angiogenesis, and in some cases immunological response or incompatibility, are detrimental to stem cell survival. To overcome the complexity and deficiencies of stem cell therapy, the coacervate delivery platform is deemed promising because it offers controlled and sustained release using heparin to recapitulate the binding and stabilization of extracellular proteins by heparan sulfates in native tissues...
May 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28481236/new-applications-of-heparin-and-other-glycosaminoglycans
#9
REVIEW
Marcelo Lima, Timothy Rudd, Edwin Yates
Heparin, the widely used pharmaceutical anticoagulant, has been in clinical use for well over half a century. Its introduction reduced clotting risks substantially and subsequent developments, including the introduction of low-molecular-weight heparin, made possible many major surgical interventions that today make heparin an indispensable drug. There has been a recent burgeoning of interest in heparin and related glycosaminoglycan (GAG) polysaccharides, such as chondroitin sulfates, heparan sulfate, and hyaluronate, as potential agents in various applications...
May 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28480299/the-2-8%C3%A2-%C3%A3-electron-microscopy-structure-of-adeno-associated-virus-dj-bound-by-a-heparinoid-pentasaccharide
#10
Qing Xie, John M Spear, Alex J Noble, Duncan R Sousa, Nancy L Meyer, Omar Davulcu, Fuming Zhang, Robert J Linhardt, Scott M Stagg, Michael S Chapman
Atomic structures of adeno-associated virus (AAV)-DJ, alone and in complex with fondaparinux, have been determined by cryoelectron microscopy at 3 Å resolution. The gene therapy vector, AAV-DJ, is a hybrid of natural serotypes that was previously derived by directed evolution, selecting for hepatocyte entry and resistance to neutralization by human serum. The structure of AAV-DJ differs from that of parental serotypes in two regions where neutralizing antibodies bind, so immune escape appears to have been the primary driver of AAV-DJ's directed evolution...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28478695/prevention-of-neurocognitive-deficiency-in-mucopolysaccharidosis-type-ii-mice-by-cns-directed-aav9-mediated-iduronate-sulfatase-gene-transfer
#11
Kanut Laoharawee, Kelly M Podetz-Pedersen, Tam T Nguyen, Laura B Evenstar, Kelley F Kitto, Zhenhong Nan, Carolyn A Fairbanks, Walter C Low, Karen F Kozarsky, R Scott McIvor
Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked recessive lysosomal disorder caused by defective Iduronate-2-sulfatase (IDS) resulting in accumulation of heparan sulfate and dermatan sulfate glycosaminoglycans (GAGs). Enzyme replacement is the only FDA-approved therapy available for MPS II, but it is expensive and does not improve neurologic outcomes in MPS II patients. We conducted this study to evaluate the effectiveness of adeno-associated virus (AAV) vector encoding human IDS delivered intracerebroventricularly in a murine model of MPS II...
May 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28474284/damage-associated-molecular-patterns-in-the-pathogenesis-of-osteoarthritis-potentially-novel-therapeutic-targets
#12
REVIEW
John H Rosenberg, Vikrant Rai, Matthew F Dilisio, Devendra K Agrawal
Osteoarthritis (OA) is a chronic disease that degrades the joints and is often associated with increasing age and obesity. The two most common sites of OA in adults are the knee and hip joints. Increased mechanical stress on the joint from obesity can cause the articular cartilage to degrade and release damage-associated molecular patterns (DAMPs). These DAMPs are involved in various molecular pathways that interact with nuclear factor-kappa B and result in the transcription of inflammatory cytokines and activation of matrix metalloproteinases that progressively destroy cartilage...
May 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28467516/baseline-serum-syndecan-4-predicts-prognosis-after-the-onset-of-acute-exacerbation-of-idiopathic-interstitial-pneumonia
#13
Yuki Sato, Yoshinori Tanino, Xintao Wang, Takefumi Nikaido, Suguru Sato, Kenichi Misa, Ryuichi Togawa, Charles W Frevert, Mitsuru Munakata
BACKGROUND: Patients with idiopathic interstitial pneumonia can experience acute respiratory worsening, also known as acute exacerbation, with a large deterioration on prognosis. The precise mechanism remains unclear; however, syndecan-4 may be involved. Syndecan-4, a transmembrane heparan sulfate proteoglycan expressed in a variety of cells (e.g., epithelial cells, macrophages, fibroblasts, etc.), performs various biological roles by binding to several proteins through its heparan sulfate glycosaminoglycan side chains...
2017: PloS One
https://www.readbyqxmd.com/read/28466453/hereditary-multiple-exostoses-new-insights-into-pathogenesis-clinical-complications-and-potential-treatments
#14
REVIEW
Maurizio Pacifici
PURPOSE OF REVIEW: Hereditary multiple exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal elements, including long bones, ribs, and vertebrae. Due to its intricacies and unresolved issues, HME continues to pose major challenges to both clinicians and biomedical researchers. The purpose of this review is to describe and analyze recent advances in this field and point to possible targets and strategies for future biologically based therapeutic intervention...
May 2, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28465034/heparan-sulfate-disaccharide-measurement-from-biological-samples-using-pre-column-derivatization-uplc-ms-and-single-ion-monitoring
#15
Imeobong U Antia, Darshna R Yagnik, Leonardo Pantoja Munoz, Ajit J Shah, Frank A Hills
Glycosaminoglycans are a heterogeneous family of linear polysaccharides comprised of repeating disaccharide subunits that mediate many effects at the cellular level. There is increasing evidence that the nature of these effects is determined by differences in disaccharide composition. However, the determination of GAG disaccharide composition in biological samples remains challenging and time-consuming. We have developed a method that uses derivatization and selected ion recording and RP-UPLCMS resulting in rapid separation and quantification of twelve heparin/heparin sulfate disaccharides from 5 μg GAG...
April 30, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28464847/glycosaminoglycans-are-involved-in-bacterial-adherence-to-lung-cells
#16
Olga Rajas, Luis M Quirós, Mara Ortega, Emma Vazquez-Espinosa, Jesús Merayo-Lloves, Fernando Vazquez, Beatriz García
BACKGROUND: Lower respiratory infections are among the top ten causes of death worldwide. Since pathogen to cell adhesion is a crucial step in the infection progress, blocking the interaction between eukaryotic receptors and bacterial ligands may enable the pathogenesis process to be stopped. Cell surface glycosaminoglycans (GAGs) are known to be mediators in the adhesion of diverse bacteria to different cell types, making it of interest to examine their involvement in the attachment of various pathogenic bacteria to lung cells, including epithelial cells and fibroblasts...
May 2, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28461981/antiretroviral-activity-of-a-novel-pyrimidyl-di-diazaspiroalkane-derivative
#17
E A Novoselova, O B Riabova, I A Leneva, V G Nesterenko, R N Bolgarin, V A Makarov
A novel compound, 3,3'-(5-nitropyrimidine-4,6-diyl)bis-3,12-diaza-6,9-diazoniadispiro[5.2.5.2]hexadecane tetrachloride dihydrochloride, was synthesized. The compound was found to inhibit the replication of various viral families by blocking specific heparan sulfate receptors on the host cell's surface. In experiments, the compound was found to be highly effective against several strains of HIV retroviruses.
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28458672/group-v-secreted-phospholipase-a2-induces-the-release-of-proangiogenic-and-antiangiogenic-factors-by-human-neutrophils
#18
Stefania Loffredo, Francesco Borriello, Raffaella Iannone, Anne L Ferrara, Maria R Galdiero, Vincenzo Gigantino, Pasquale Esposito, Gilda Varricchi, Gerard Lambeau, Marco A Cassatella, Francescopaolo Granata, Gianni Marone
Secreted phospholipases A2 (sPLA2s) are extracellular enzymes that catalyze the release of free fatty acids and lysophospholipids from membrane phospholipids and also bind to different receptors (e.g., PLA2R1 or integrins). To date, 12 mammalian sPLA2s have been identified, which play a critical role in pathophysiological processes including inflammation and cancer. sPLA2s activate immune cells such as human neutrophils (PMNs) by enzymatic activity- or receptor-mediated mechanisms. In addition, human PMNs synthesize and store human group V (hGV) and human group X (hGX) sPLA2s in their granules, but only the former is released upon cellular activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28457855/polysulfonate-suramin-inhibits-zika-virus-infection
#19
Chee Wah Tan, I-Ching Sam, Wei Lim Chong, Vannajan Sanghiran Lee, Yoke Fun Chan
Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition...
April 27, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28451919/a-novel-conditional-sgsh-knockout-mouse-model-recapitulates-phenotypic-and-neuropathic-deficits-of-sanfilippo-syndrome
#20
Adeline A Lau, Barbara M King, Carly L Thorsen, Sofia Hassiotis, Helen Beard, Paul J Trim, Lauren S Whyte, Sarah J Tamang, Stephen K Duplock, Marten F Snel, John J Hopwood, Kim M Hemsley
Mucopolysaccharidosis (MPS) type IIIA, or Sanfilippo syndrome, is a neurodegenerative lysosomal storage disorder caused by a deficiency of the lysosomal enzyme N-sulfoglucosamine sulfohydrolase (SGSH), involved in the catabolism of heparan sulfate. The clinical spectrum is broad and the age of symptom onset and the degree of preservation of cognitive and motor functions appears greatly influenced by genotype. To explore this further, we generated a conditional knockout (Sgsh (KO) ) mouse model with ubiquitous Sgsh deletion, and compared the clinical and pathological phenotype with that of the spontaneous Sgsh (D31N) MPS-IIIA mouse model...
April 27, 2017: Journal of Inherited Metabolic Disease
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