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Dermatan sulfate

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https://www.readbyqxmd.com/read/29674476/glycosaminoglycan-neutralization-in-coagulation-control
#1
REVIEW
Amélie I S Sobczak, Samantha J Pitt, Alan J Stewart
The glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate, and heparin are important anticoagulants that inhibit clot formation through interactions with antithrombin and heparin cofactor II. Unfractionated heparin, low-molecular-weight heparin, and heparin-derived drugs are often the main treatments used clinically to handle coagulatory disorders. A wide range of proteins have been reported to bind and neutralize these GAGs to promote clot formation. Such neutralizing proteins are involved in a variety of other physiological processes, including inflammation, transport, and signaling...
April 19, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29672913/knockout-of-hyaluronan-synthase-1-but-not-3-impairs-formation-of-the-retrocalcaneal-bursa
#2
Katie J Sikes, Kristen Renner, Jun Li, K Jane Grande-Allen, Jennifer P Connell, Valbona Cali, Ronald J Midura, John D Sandy, Anna Plaas, Vincent M Wang
Hyaluronan (HA), a high molecular weight non-sulfated glycosaminoglycan, is an integral component of the extracellular matrix of developing and mature connective tissues including tendon. There are few published reports quantifying HA content during tendon growth and maturation, or detailing its effects on the mechanical properties of the tendon extracellular matrix. Therefore, the goal of the current study was to examine the role of HA synthesis during post-natal skeletal growth and maturation, and its influence on tendon structure and biomechanical function...
April 19, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29671225/effectiveness-of-early-hematopoietic-stem-cell-transplantation-in-preventing-neurocognitive-decline-in-mucopolysaccharidosis-type-ii-a-case-series
#3
A Selvanathan, C Ellaway, C Wilson, P Owens, P J Shaw, K Bhattacharya
The early progressive form of the X-linked disorder, Hunter syndrome or mucopolysaccharidosis type II (MPS II) (OMIM #309900), is characterized by cognitive decline, and pulmonary and cardiac complications that often cause death before 20 years of age. Deficiency of the lysosomal enzyme, iduronate-2-sulfatase (EC 3.1.6.13) results in deposition of the glycosaminoglycans, dermatan, and heparan sulfate in various tissues. In recent years, enzyme replacement therapy (ERT) has become the mainstay of treatment, but is expensive and ineffective in arresting cognitive decline...
April 19, 2018: JIMD Reports
https://www.readbyqxmd.com/read/29625490/keratan-sulfate-phenotype-in-the-%C3%AE-1-3-n-acetylglucosaminyltransferase-7-null-mouse-cornea
#4
Stacy L Littlechild, Robert D Young, Bruce Caterson, Hideyuki Yoshida, Maya Yamazaki, Kenji Sakimura, Andrew J Quantock, Tomoya O Akama
Purpose: Synthesis of keratan sulfate (KS) relies on coordinated action of multiple enzymes, including the N-acetylglucosamine-transferring enzyme, β-1,3-N-acetylglucosaminyltransferase-7 (β3GnT7). A mouse model deficient in β3GnT7 was developed to explore structural changes in KS and the extracellular matrix (ECM; i.e., the corneal stroma), elucidate the KS biosynthesis mechanism, and understand its role in corneal organization. Methods: A knockout vector for the β3GnT7-encoding gene, B3gnt7, was created to develop heterozygous- (htz) and homozygous-null (null) knockouts...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29579579/deciphering-functional-glycosaminoglycan-motifs-in-development
#5
REVIEW
Robert A Townley, Hannes E Bülow
Glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate are linear glycans, which when attached to protein backbones form proteoglycans. GAGs are essential components of the extracellular space in metazoans. Extensive modifications of the glycans such as sulfation, deacetylation and epimerization create structural GAG motifs. These motifs regulate protein-protein interactions and are thereby repsonsible for many of the essential functions of GAGs. This review focusses on recent genetic approaches to characterize GAG motifs and their function in defined signaling pathways during development...
March 23, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29561836/impaired-proteoglycan-glycosylation-elevated-tgf-%C3%AE-signaling-and-abnormal-osteoblast-differentiation-as-the-basis-for-bone-fragility-in-a-mouse-model-for-gerodermia-osteodysplastica
#6
Wing Lee Chan, Magdalena Steiner, Tomasz Witkos, Johannes Egerer, Björn Busse, Shuji Mizumoto, Jan M Pestka, Haikuo Zhang, Ingrid Hausser, Layal Abo Khayal, Claus-Eric Ott, Mateusz Kolanczyk, Bettina Willie, Thorsten Schinke, Chiara Paganini, Antonio Rossi, Kazuyuki Sugahara, Michael Amling, Petra Knaus, Danny Chan, Martin Lowe, Stefan Mundlos, Uwe Kornak
Gerodermia osteodysplastica (GO) is characterized by skin laxity and early-onset osteoporosis. GORAB, the responsible disease gene, encodes a small Golgi protein of poorly characterized function. To circumvent neonatal lethality of the GorabNull full knockout, Gorab was conditionally inactivated in mesenchymal progenitor cells (Prx1-cre), pre-osteoblasts (Runx2-cre), and late osteoblasts/osteocytes (Dmp1-cre), respectively. While in all three lines a reduction in trabecular bone density was evident, only GorabPrx1 and GorabRunx2 mutants showed dramatically thinned, porous cortical bone and spontaneous fractures...
March 21, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29550275/generation-of-human-umbilical-cord-vein-cd146-perivascular-cell-origined-three-dimensional-vascular-construct
#7
Beyza Gökçinar-Yagci, Nilgün Yersal, Petek Korkusuz, Betül Çelebi-Saltik
Small-diameter vascular grafts are needed for the treatment of coronary artery diseases in the case of limited accessibility of the autologous vessels. Synthetic scaffolds have many disadvantages so in recent years vascular constructs (VCs) made from cellularized natural scaffolds was seen to be very promising but number of studies comprising this area is very limited. In our study, our aim is to generate fully natural triple-layered VC that constitutes all the layers of blood vessel with vascular cells. CD146+ perivascular cells (PCs) were isolated from human umbilical cord vein (HUCV) and differentiated into smooth muscle cells (SMCs) and fibroblasts...
March 14, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29514696/integrating-genome-wide-dna-methylation-and-mrna-expression-profiles-identified-different-molecular-features-between-kashin-beck-disease-and-primary-osteoarthritis
#8
Yan Wen, Ping Li, Jingcan Hao, Chen Duan, Jing Han, Awen He, Yanan Du, Li Liu, Xiao Liang, Feng Zhang, Xiong Guo
BACKGROUND: Kashin-Beck disease (KBD) is an endemic osteochondropathy of unknown etiology. Osteoarthritis (OA) is a form of degenerative joint disease sharing similar clinical manifestations and pathological changes to articular cartilage with KBD. METHODS: A genome-wide DNA methylation profile of articular cartilage from five KBD patients and five OA patients was first performed using the Illumina Infinium HumanMethylation450 BeadChip. Together with a previous gene expression profiling dataset comparing KBD cartilage with OA cartilage, an integrative pathway enrichment analysis of the genome-wide DNA methylation and the mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software...
March 7, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29499356/a-role-for-proteoglycans-in-vascular-disease
#9
REVIEW
Thomas N Wight
The content of proteoglycans (PGs) is low in the extracellular matrix (ECM) of vascular tissue, but increases dramatically in all phases of vascular disease. Early studies demonstrated that glycosaminoglycans (GAGs) including chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) accumulate in vascular lesions in both humans and in animal models in areas of the vasculature that are susceptible to disease initiation (such as at branch points) and are frequently coincident with lipid deposits...
February 27, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29497792/protective-effects-of-systemic-dermatan-sulfate-treatment-in-a-preclinical-model-of-radiation-induced-oral-mucositis
#10
Sylvia Gruber, Katharina Frings, Peter Kuess, Wolfgang Dörr
PURPOSE: Oral mucositis is a frequent, dose-limiting side effect of radio(chemo)therapy of head-and-neck malignancies. The epithelial radiation response is based on multiple tissue changes, which could offer targets for a biologically tailored treatment. The potential of dermatan sulfate (DS) to modulate radiation-induced oral mucositis was tested in an established preclinical mucositis model. METHODS: Irradiation was either applied alone or in combination with daily DS treatment (4 mg/kg, subcutaneously) over varying time intervals...
March 1, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/29478819/a-novel-blind-start-study-design-to-investigate-vestronidase-alfa-for-mucopolysaccharidosis-vii-an-ultra-rare-genetic-disease
#11
Paul Harmatz, Chester B Whitley, Raymond Y Wang, Mislen Bauer, Wenjie Song, Christine Haller, Emil Kakkis
BACKGROUND: Drug development for ultra-rare diseases is challenging because small sample sizes and heterogeneous study populations hamper the ability of randomized, placebo-controlled trials with a single primary endpoint to demonstrate valid treatment effects. METHODS: To overcome these challenges, a novel Blind Start design was utilized in a study of vestronidase alfa in mucopolysaccharidosis VII (Sly syndrome), an ultra-rare lysosomal disease, that demonstrates the strengths of this approach in a challenging drug-development setting...
February 12, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29472931/dendritic-cell-migration-to-skin-draining-lymph-nodes-is-controlled-by-dermatan-sulfate-and-determines-adaptive-immunity-magnitude
#12
Reza Nadafi, Jasper J Koning, Henrike Veninga, Xanthi N Stachtea, Tanja Konijn, Antonie Zwiers, Anders Malmström, Joke M M den Haan, Reina E Mebius, Marco Maccarana, Rogier M Reijmers
For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29455388/heterologous-expression-of-rtshyal-1-the-first-recombinant-hyaluronidase-of-scorpion-venom-produced-in-pichia-pastoris-system
#13
Fernanda Gobbi Amorim, Johara Boldrini-França, Karla de Castro Figueiredo Bordon, Iara Aimê Cardoso, Edwin De Pauw, Loïc Quinton, Simone Kashima, Eliane Candiani Arantes
In general, hyaluronidases have a broad potential application on medicine and esthetics fields. Hyaluronidases from animal venoms cleave hyaluronan present in the extracellular matrix, acting as spreading factors of toxins into the tissues of the victim. However, the in-depth characterization of hyaluronidase from animal venoms has been neglected due to its instability and low concentration in the venom, which hamper its isolation. Thus, heterologous expression of hyaluronidase acts as a biotechnological tool in the obtainment of enough amounts of the enzyme for structural and functional studies...
February 17, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29455055/specificity-of-glycosaminoglycan-protein-interactions
#14
REVIEW
Lena Kjellén, Ulf Lindahl
Glycosaminoglycans (GAGs) interact with a variety of proteins with important functions in development and homeostasis. Most of these proteins bind to heparin in vitro, a highly sulfated GAG species, although heparan sulfate and/or chondroitin/dermatan sulfate are more frequent physiological ligands. Binding affinity and specificity are determined by charge distribution, mainly due to sulfate and carboxylate groups and by GAG chain conformation. Interactions may be nonspecific, essentially reflecting charge density or highly specific, dependent on rare GAG-structural features...
February 1, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29370293/gene-expression-of-the-two-developmentally-regulated-dermatan-sulfate-epimerases-in-the-xenopus-embryo
#15
Nadège Gouignard, Tanja Schön, Christian Holmgren, Ina Strate, Emirhan Taşöz, Franziska Wetzel, Marco Maccarana, Edgar M Pera
Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans are abundant on the cell surface and in the extracellular matrix and have important functions in matrix structure, cell-matrix interaction and signaling. The DS epimerases 1 and 2, encoded by Dse and Dsel, respectively, convert CS to a CS/DS hybrid chain, which is structurally and conformationally richer than CS, favouring interaction with matrix proteins and growth factors. We recently showed that Xenopus Dse is essential for the migration of neural crest cells by allowing cell surface CS/DS proteoglycans to adhere to fibronectin...
2018: PloS One
https://www.readbyqxmd.com/read/29325937/histopathologic-analysis-of-tamoxifen-on-epidural-fibrosis
#16
Yasar Ozturk, Ismail Bozkurt, Mesut Emre Yaman, Yahya Guvenc, Tolga Tolunay, Pinar Bayram, Nazli Hayirli, Deniz Billur, Fatma Kubra Erbay, Salim Senturk, Gokhan Bozkurt
BACKGROUND: Epidural fibrosis is a challenging topic in spinal surgery. This phenomenon constitutes one of the main reasons behind postlaminectomy syndrome or failed back surgery syndrome, which leads to persistent back and leg pain in association with compression and/or stretching the nerve root or the dura. The exact mechanism of action in epidural fibrosis is complex and remains uncertain. Excessive deposition of collagen, fibronectin, and dermatan sulfate, known as the "extracellular matrix," and decrease of tissue cellularity results in epidural fibrosis...
March 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29245974/chondroitin-sulfatases-differentially-regulate-wnt-signaling-in-prostate-stem-cells-through-effects-on-shp2-phospho-erk1-2-and-dickkopf-wnt-signaling-pathway-inhibitor-dkk3
#17
Sumit Bhattacharyya, Leo Feferman, Joanne K Tobacman
The chondroitin sulfatases N-acetylgalactosamine-4-sulfatase (ARSB) and galactosamine-N-acetyl-6-sulfatase (GALNS) remove either the 4-sulfate group at the non-reducing end of chondroitin 4-sulfate (C4S) and dermatan sulfate, or the 6-sulfate group of chondroitin 6-sulfate, chondroitin 4,6-disulfate (chondroitin sulfate E), or keratan sulfate. In human prostate cancer tissues, the ARSB activity was reduced and the GALNS activity was increased, compared to normal prostate tissue. In human prostate stem cells, when ARSB was reduced by silencing or GALNS was increased by overexpression, activity of SHP2, the ubiquitous non-receptor tyrosine phosphatase, declined, attributable to increased binding of SHP2 with C4S...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209879/one-pot-analysis-of-sulfated-glycosaminoglycans
#18
C B Shrikanth, J Sanjana, Nandini D Chilkunda
Routine isolation, estimation, and characterization of glycosaminoglycans (GAGs) is quite challenging. This is compounded by the fact that the analysis is technique-intensive and more often there will be a limitation on the quantity of GAGs available for various structural, functional and biological studies. In such a scenario, the sample which can be made available for estimation and elucidation of disaccharide composition and species composition as well remains a challenge. In the present study, we have determined the feasibility where isolated sulfated GAGs (sGAG) that is estimated by metachromasia is recovered for further analysis...
December 5, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29206923/vascular-abnormalities-in-the-placenta-of-chst14-fetuses-implications-in-the-pathophysiology-of-perinatal-lethality-of-the-murine-model-and-vascular-lesions-in-human-chst14-d4st1-deficiency
#19
Takahiro Yoshizawa, Shuji Mizumoto, Yuki Takahashi, Shin Shimada, Kazuyuki Sugahara, Jun Nakayama, Shin'ichi Takeda, Yoshihiro Nomura, Yuko Nitahara-Kasahara, Takashi Okada, Kiyoshi Matsumoto, Shuhei Yamada, Tomoki Kosho
Collagen is one of the most important components of the extracellular matrix that is involved in the strength of tissues, cell adhesion and cell proliferation. Mutations in several collagen and post-translational modification enzyme genes cause Ehlers-Danlos syndrome (EDS) characterized by joint and skin hyperextensibility as well as fragility of various organs. Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) is a critical enzyme for biosynthesis of dermatan sulfate, a side chain of various proteoglycans including biglycan that regulates collagen fibrils through their interaction...
February 1, 2018: Glycobiology
https://www.readbyqxmd.com/read/29202552/another-novel-missense-mutation-in-arsb-gene-in-iran
#20
Samaneh Abbasi, Mehrdad Noruzinia, Oranous Bashti, Mohammad Ahmadvand, Ahmad Reza Salehi Chaleshtori, Leila Mahootipou
Mucopolysaccharidosis VI (MPS-VI) is an infrequent autosomal recessive disorder caused by mutations in ARSB gene and deficiency in lysosomal enzyyme ARSB activities subsequently. This enzyme is essential for the breaking of glycosaminoglycans (GAGs) such as dermatan sulfate and chondroitin sulfate. ARSB dysfunction results in imperfect breakdown of GAGs and their accumulation in urine. Mutations in ARSB gene are the main players in MPS-VI disease and its clinical consequences. Most reported mutations are point mutations but there are some other examples in literature...
September 2017: Acta Medica Iranica
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