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[PMID]:28453844
[Au] Autor:Suwarto S; Sasmono RT; Sinto R; Ibrahim E; Suryamin M
[Ad] Endereço:Division of Tropical and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Hospital, Jakarta, Indonesia.
[Ti] Título:Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection.
[So] Source:J Infect Dis;215(6):992-999, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. Methods: A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. Results: A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001-1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025-1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000-1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004-1.074) had an adjusted association with severe plasma leakage. Conclusions: In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.
[Mh] Termos MeSH primário: Sulfatos de Condroitina/sangue
Claudina-5/sangue
Dengue/sangue
Glicocálix/metabolismo
Sindecana-1/sangue
Junções Íntimas/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Biomarcadores/sangue
Permeabilidade Capilar
Quimiocinas/sangue
Endotélio Vascular/metabolismo
Feminino
Febre
Seres Humanos
Indonésia
Masculino
Razão de Chances
Estudos Prospectivos
Análise de Regressão
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (Chemokines); 0 (Claudin-5); 0 (Syndecan-1); 9007-28-7 (Chondroitin Sulfates)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix041


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[PMID]:27775151
[Au] Autor:Osmond M; Bernier SM; Pantcheva MB; Krebs MD
[Ad] Endereço:Department of Chemical and Biological Engineering, Colorado School of Mines, 1613 Illinois Street, 431 Alderson Hall, Golden, 80401, Colorado.
[Ti] Título:Collagen and collagen-chondroitin sulfate scaffolds with uniaxially aligned pores for the biomimetic, three dimensional culture of trabecular meshwork cells.
[So] Source:Biotechnol Bioeng;114(4):915-923, 2017 04.
[Is] ISSN:1097-0290
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glaucoma is a disease in which damage to the optic nerve leads to progressive, irreversible vision loss. The intraocular pressure (IOP) is the only modifiable risk factor for glaucoma and its lowering is considered a useful strategy for preventing or slowing down the progression of glaucomatous neuropathy. Elevated intraocular pressure associated with glaucoma is due to increased aqueous humor outflow resistance, primarily through the trabecular meshwork (TM) of the eye. Current in vitro models of the trabecular meshwork are oversimplified and do not capture the organized and complex three-dimensional nature of this tissue that consists primarily of collagen and glycoasaminoglycans. In this work, collagen and collagen-chondroitin sulfate (CS) scaffolds were fabricated via unidirectional freezing and lyophilization to induce the formation of aligned pores. Scaffolds were characterized by scanning electron microscopy, dynamic mechanical analysis, and a chondroitin sulfate quantification assay. Scaffold characterization confirmed the formation of aligned pores, and also that the CS was leaching out of the scaffolds over time. Primary porcine trabecular meshwork (TM) cells were seeded onto the surface of scaffolds and their gene expression, proliferation, viability, migration into the scaffolds, and morphology were examined. The TM cells were viable and proliferated 2 weeks after seeding. The cells migrated down into the internal scaffold structure and their morphology reflected the topography and alignment of the scaffold structure. This work is a promising step toward the development of a three dimensional in vitro model of the TM that can be used for testing of glaucoma pharmacological agents in future experimentation and to better our understanding of the trabecular meshwork and its complex physiology. Biotechnol. Bioeng. 2017;114: 915-923. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Malha Trabecular/citologia
Malha Trabecular/fisiologia
[Mh] Termos MeSH secundário: Animais
Materiais Biocompatíveis/química
Materiais Biocompatíveis/farmacologia
Materiais Biomiméticos
Técnicas de Cultura de Células
Sulfatos de Condroitina/química
Sulfatos de Condroitina/farmacologia
Colágeno/química
Colágeno/farmacologia
Glaucoma
Seres Humanos
Porosidade
Suínos
Tecidos Suporte/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biocompatible Materials); 9007-28-7 (Chondroitin Sulfates); 9007-34-5 (Collagen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171216
[Lr] Data última revisão:
171216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1002/bit.26206


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[PMID]:28450116
[Au] Autor:Shida M; Mikami T; Tamura JI; Kitagawa H
[Ad] Endereço:Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
[Ti] Título:A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus.
[So] Source:Biochem Biophys Res Commun;487(3):678-683, 2017 06 03.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide unit composed of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). CS chains are found throughout the pericellular and extracellular spaces and contribute to the formation of functional microenvironments for numerous biological events. However, their structure-function relations remain to be fully characterized. Here, a fucosylated CS (FCS) was isolated from the body wall of the sea cucumber Apostichopus japonicus. Its promotional effects on neurite outgrowth were assessed by using isolated polysaccharides and the chemically synthesized FCS trisaccharide ß-D-GalNAc(4,6-O-disulfate) (1-4)[α-l-fucose (2,4-O-disulfate) (1-3)]-ß-D-GlcA. FCS polysaccharides contained the E-type disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure and carried distinct sulfated fucose branches. Despite their relatively lower abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting activity comparable to squid cartilage-derived CS-E polysaccharides, which are characterized by their predominant E units, suggesting potential roles of the fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated fucose branches may provide new insights into understanding the structure-function relations of CS chains.
[Mh] Termos MeSH primário: Sulfatos de Condroitina/administração & dosagem
Neuritos/efeitos dos fármacos
Neuritos/fisiologia
Neurogênese/efeitos dos fármacos
Neurogênese/fisiologia
Pepinos-do-Mar/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Sulfatos de Condroitina/química
Relação Dose-Resposta a Droga
Fucose/química
Camundongos
Neuritos/ultraestrutura
Trissacarídeos/administração & dosagem
Trissacarídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Trisaccharides); 0 (fucosylated chondroitin sulfate); 28RYY2IV3F (Fucose); 9007-28-7 (Chondroitin Sulfates)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28977605
[Au] Autor:Pichette J; Fynn-Sackey N; Gagnon J
[Ad] Endereço:Laurentian University, Department of Biology, Sudbury, Ontario P3E 2C6, Canada.
[Ti] Título:Hydrogen Sulfide and Sulfate Prebiotic Stimulates the Secretion of GLP-1 and Improves Glycemia in Male Mice.
[So] Source:Endocrinology;158(10):3416-3425, 2017 Oct 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently, the gastrointestinal microbiome, and its metabolites, has emerged as a potential regulator of host metabolism. However, to date little is known on the precise mechanisms of how this regulation occurs. Hydrogen sulfide (H2S) is abundantly produced in the colon by sulfate-reducing bacteria (SRB). H2S is a bioactive gas that plays regulatory roles in many systems, including metabolic hormone regulation. This gas metabolite is produced in close proximity to the glucagonlike peptide-1 (GLP-1)-secreting cells in the gut epithelium. GLP-1 is a peptide hormone that plays pivotal roles in both glucose homeostasis and appetite regulation. We hypothesized that H2S can directly regulate GLP-1 secretion. We demonstrated that H2S donors (NaHS and GYY4137) directly stimulate GLP-1 secretion in murine L-cells (GLUTag) and that this occurs through p38 mitogen-activated protein kinase without affecting cell viability. We then increased SRB in mice by supplementing the diet with a prebiotic chondroitin sulfate for 4 weeks. Mice treated with chondroitin sulfate had elevated Desulfovibrio piger levels in the feces and increased colonic and fecal H2S concentration. These animals also had enhanced GLP-1 and insulin secretion, improved oral glucose tolerance, and reduced food consumption. These results indicate that H2S plays a stimulatory role in GLP-1 secretion and that sulfate prebiotics can enhance GLP-1 release and its downstream metabolic actions.
[Mh] Termos MeSH primário: Sulfatos de Condroitina/farmacologia
Colo/efeitos dos fármacos
Microbioma Gastrointestinal/efeitos dos fármacos
Peptídeo 1 Semelhante ao Glucagon/efeitos dos fármacos
Sulfeto de Hidrogênio/metabolismo
Mucosa Intestinal/efeitos dos fármacos
Morfolinas/farmacologia
Compostos Organotiofosforados/farmacologia
Prebióticos
Sulfetos/farmacologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Colo/metabolismo
DNA Bacteriano/análise
Desulfovibrio/efeitos dos fármacos
Ingestão de Alimentos/efeitos dos fármacos
Fezes/química
Microbioma Gastrointestinal/genética
Peptídeo 1 Semelhante ao Glucagon/secreção
Teste de Tolerância a Glucose
Insulina/secreção
Mucosa Intestinal/secreção
Masculino
Camundongos
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial); 0 (GYY 4137); 0 (Insulin); 0 (Morpholines); 0 (Organothiophosphorus Compounds); 0 (Prebiotics); 0 (Sulfides); 89750-14-1 (Glucagon-Like Peptide 1); 9007-28-7 (Chondroitin Sulfates); FWU2KQ177W (sodium bisulfide); YY9FVM7NSN (Hydrogen Sulfide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00391


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[PMID]:28867285
[Au] Autor:Woznica A; Gerdt JP; Hulett RE; Clardy J; King N
[Ad] Endereço:Howard Hughes Medical Institute, and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
[Ti] Título:Mating in the Closest Living Relatives of Animals Is Induced by a Bacterial Chondroitinase.
[So] Source:Cell;170(6):1175-1183.e11, 2017 Sep 07.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We serendipitously discovered that the marine bacterium Vibrio fischeri induces sexual reproduction in one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Although bacteria influence everything from nutrition and metabolism to cell biology and development in eukaryotes, bacterial regulation of eukaryotic mating was unexpected. Here, we show that a single V. fischeri protein, the previously uncharacterized EroS, fully recapitulates the aphrodisiac-like activity of live V. fischeri. EroS is a chondroitin lyase; although its substrate, chondroitin sulfate, was previously thought to be an animal synapomorphy, we demonstrate that S. rosetta produces chondroitin sulfate and thus extend the ancestry of this important glycosaminoglycan to the premetazoan era. Finally, we show that V. fischeri, purified EroS, and other bacterial chondroitin lyases induce S. rosetta mating at environmentally relevant concentrations, suggesting that bacteria likely regulate choanoflagellate mating in nature.
[Mh] Termos MeSH primário: Aliivibrio fischeri/enzimologia
Coanoflagelados/microbiologia
Coanoflagelados/fisiologia
Condroitinases e Condroitim Liases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Bactérias/química
Coanoflagelados/citologia
Sulfatos de Condroitina/metabolismo
Meiose
Reprodução
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 9007-28-7 (Chondroitin Sulfates); EC 4.2.2.- (Chondroitinases and Chondroitin Lyases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


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[PMID]:28859141
[Au] Autor:Maccarana M; Svensson RB; Knutsson A; Giannopoulos A; Pelkonen M; Weis M; Eyre D; Warman M; Kalamajski S
[Ad] Endereço:Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
[Ti] Título:Asporin-deficient mice have tougher skin and altered skin glycosaminoglycan content and structure.
[So] Source:PLoS One;12(8):e0184028, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The main structural component of connective tissues is fibrillar, cross-linked collagen whose fibrillogenesis can be modulated by Small Leucine-Rich Proteins/Proteoglycans (SLRPs). Not all SLRPs' effects on collagen and extracellular matrix in vivo have been elucidated; one of the less investigated SLRPs is asporin. Here we describe the successful generation of an Aspn-/- mouse model and the investigation of the Aspn-/- skin phenotype. Functionally, Aspn-/- mice had an increased skin mechanical toughness, although there were no structural changes present on histology or immunohistochemistry. Electron microscopy analyses showed 7% thinner collagen fibrils in Aspn-/- mice (not statistically significant). Several matrix genes were upregulated, including collagens (Col1a1, Col1a2, Col3a1), matrix metalloproteinases (Mmp2, Mmp3) and lysyl oxidases (Lox, Loxl2), while lysyl hydroxylase (Plod2) was downregulated. Intriguingly no differences were observed in collagen protein content or in collagen cross-linking-related lysine oxidation or hydroxylation. The glycosaminoglycan content and structure in Aspn-/- skin was profoundly altered: chondroitin/dermatan sulfate was more than doubled and had an altered composition, while heparan sulfate was halved and had a decreased sulfation. Also, decorin and biglycan were doubled in Aspn-/- skin. Overall, asporin deficiency changes skin glycosaminoglycan composition, and decorin and biglycan content, which may explain the changes in skin mechanical properties.
[Mh] Termos MeSH primário: Biglicano/genética
Decorina/genética
Proteínas da Matriz Extracelular/deficiência
Efeito Fundador
Regulação da Expressão Gênica
Pele/metabolismo
[Mh] Termos MeSH secundário: Aminoácido Oxirredutases/genética
Aminoácido Oxirredutases/metabolismo
Animais
Biglicano/metabolismo
Sulfatos de Condroitina/genética
Sulfatos de Condroitina/metabolismo
Colágeno Tipo I/genética
Colágeno Tipo I/metabolismo
Colágeno Tipo III/genética
Colágeno Tipo III/metabolismo
Decorina/metabolismo
Dermatan Sulfato/análogos & derivados
Dermatan Sulfato/genética
Dermatan Sulfato/metabolismo
Matriz Extracelular/genética
Matriz Extracelular/metabolismo
Proteínas da Matriz Extracelular/genética
Feminino
Heparitina Sulfato/genética
Heparitina Sulfato/metabolismo
Sulfato de Ceratano/genética
Sulfato de Ceratano/metabolismo
Masculino
Metaloproteinase 2 da Matriz/genética
Metaloproteinase 2 da Matriz/metabolismo
Metaloproteinase 3 da Matriz/genética
Metaloproteinase 3 da Matriz/metabolismo
Camundongos
Camundongos Knockout
Fenótipo
Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética
Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo
Pele/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aspn protein, mouse); 0 (Biglycan); 0 (COL3A1 protein, mouse); 0 (Col1a2 protein, mouse); 0 (Collagen Type I); 0 (Collagen Type III); 0 (Dcn protein, mouse); 0 (Decorin); 0 (Extracellular Matrix Proteins); 0 (collagen type I, alpha 1 chain); 0 (dermatan sulfate chondroitin sulfate); 24967-94-0 (Dermatan Sulfate); 9007-28-7 (Chondroitin Sulfates); 9050-30-0 (Heparitin Sulfate); 9056-36-4 (Keratan Sulfate); EC 1.14.11.4 (Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase); EC 1.14.11.4 (lysyl hydroxylase 2, mouse); EC 1.4.- (Amino Acid Oxidoreductases); EC 1.4.3.- (Loxl2 protein, mouse); EC 3.4.24.17 (Matrix Metalloproteinase 3); EC 3.4.24.17 (Mmp3 protein, mouse); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.24 (Mmp2 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184028


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[PMID]:28800457
[Au] Autor:Li J; Li S; Yan L; Ding T; Linhardt RJ; Yu Y; Liu X; Liu D; Ye X; Chen S
[Ad] Endereço:Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou, 310058, China. Electronic address: 18511581374@163.com.
[Ti] Título:Fucosylated chondroitin sulfate oligosaccharides exert anticoagulant activity by targeting at intrinsic tenase complex with low FXII activation: Importance of sulfation pattern and molecular size.
[So] Source:Eur J Med Chem;139:191-200, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Fucosylated chondroitin sulfates (fCSs) are structurally unusual glycosaminoglycans isolated from sea cucumbers that exhibit potent anticoagulant activity. These fCSs were isolated from sea cucumber, Isostichopus badionotus and Pearsonothuria graeffei. Fenton reaction followed by gel filtration chromatography afforded fCS oligosaccharides, with different sulfation patterns identified by mass and NMR spectroscopy, and these were used to clarify the relationship between the structures and the anticoagulant activities of fCSs. In vitro activities were measured by activated partial thromboplastin time (APTT), thrombin time (TT), thrombin and factor Xa inhibition, and activation of FXII. The results showed that free radicals preferentially acted on GlcA residues affording oligosaccharides that were purified from both fCSs. The inhibition of thrombin and factor X activities, mediated through antithrombin III and heparin cofactor II of fCSs oligosaccharides were affected by their molecular weight and fucose branches. Oligosaccharides with different sulfation patterns of the fucose branching had a similar ability to inhibit the FXa by the intrinsic factor Xase (factor IXa-VIIIa complex). Oligosaccharides with 2,4-O-sulfo fucose branches from fCS-Ib showed higher activities than ones with 3,4-O-disulfo branches obtained from fCS-Pg. Furthermore, a heptasaccharide is the minimum size oligosaccharide required for anticoagulation and FXII activation. This activity was absent for fCS oligosaccharides smaller than nonasaccharides. Molecular size and fucose branch sulfation are important for anticoagulant activity and reduction of size can reverse the activation of FXII caused by native fCSs.
[Mh] Termos MeSH primário: Anticoagulantes/farmacologia
Sulfatos de Condroitina/farmacologia
Fator XII/metabolismo
Inibidores do Fator Xa/farmacologia
Proteínas de Neoplasias/antagonistas & inibidores
Oligossacarídeos/farmacologia
[Mh] Termos MeSH secundário: Adulto
Anticoagulantes/síntese química
Anticoagulantes/química
Sulfatos de Condroitina/síntese química
Sulfatos de Condroitina/química
Cisteína Endopeptidases/metabolismo
Relação Dose-Resposta a Droga
Fator Xa/metabolismo
Inibidores do Fator Xa/síntese química
Inibidores do Fator Xa/química
Seres Humanos
Masculino
Estrutura Molecular
Proteínas de Neoplasias/metabolismo
Oligossacarídeos/síntese química
Oligossacarídeos/química
Relação Estrutura-Atividade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticoagulants); 0 (Factor Xa Inhibitors); 0 (Neoplasm Proteins); 0 (Oligosaccharides); 0 (fucosylated chondroitin sulfate); 9001-30-3 (Factor XII); 9007-28-7 (Chondroitin Sulfates); EC 3.4.21.6 (Factor Xa); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.26 (cancer procoagulant)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE


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[PMID]:28791838
[Au] Autor:Drobnik J; Pietrucha K; Piera L; Szymanski J; Szczepanowska A
[Ad] Endereço:Laboratory of Connective Tissue Metabolism, Department of Neuropeptides Research, Medical University of Lodz, Poland.
[Ti] Título:Collagenous scaffolds supplemented with hyaluronic acid and chondroitin sulfate used for wound fibroblast and embryonic nerve cell culture.
[So] Source:Adv Clin Exp Med;26(2):223-230, 2017 Mar-Apr.
[Is] ISSN:1899-5276
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Tissue engineering is a strategy aimed at improving the regeneration of injured tissues. OBJECTIVES: The aim of the present study was to determine whether a tri-copolymer composed of crosslinked collagen, chondroitin sulfate and hyaluronic acid (Col + CS + HA) provides a better environment for fibroblast and embryonic nerve cell culture than a collagenous scaffold (Col). MATERIAL AND METHODS: The porosity of each of the matrices was characterized with a scanning electron microscope. Fibroblasts were isolated from rat wound granulation tissue (polypropylene net implanted subcutaneously). Embryonic nerve cells were obtained from the brains of rat embryos. The cells were applied to scaffolds and then stained with bisbenzimide to calculate cell entrapment within the material. The metabolic activity of the cells cultured within the scaffolds was tested using the 3-(4,5-dimethythiazol2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The Col scaffolds had a homogenously porous structure with a pore diameter of 50 µm for 70% of pores. The pore diameter in the tri-copolymer (Col + HA + CS) ranged from 24 to 160 µm (95% of total pore volume). Four times more cells (fibroblasts and embryonic nerve cells) were trapped within the superficial part of the collagenous scaffold than that of the tri-copolymer. On the third day of culture the metabolic activity of the fibroblasts within the 2 tested scaffolds was significantly higher than in the control conditions (cell culture on a laminin-coated surface). Also, the embryonic nerve cells demonstrated increased metabolic activity in Col + CS + HA scaffolds than the Col scaffolds. CONCLUSIONS: Both fibroblasts and embryonic nerve cells could be seeded within the 2 tested scaffolds. Both the scaffolds provide good conditions for fibroblast culture. However, the Col + CS + HA tri-copolymer is preferable for embryonic nerve cell engineering.
[Mh] Termos MeSH primário: Sulfatos de Condroitina/metabolismo
Colágeno/metabolismo
Fibroblastos/metabolismo
Ácido Hialurônico/metabolismo
Neurônios/metabolismo
Tecidos Suporte/química
[Mh] Termos MeSH secundário: Animais
Encéfalo/citologia
Encéfalo/embriologia
Sobrevivência Celular
Células Cultivadas
Feminino
Fibroblastos/citologia
Fibroblastos/ultraestrutura
Citometria de Fluxo
Masculino
Microscopia Eletrônica
Neurônios/citologia
Porosidade
Ratos Wistar
Engenharia Tecidual/métodos
Ferimentos e Lesões/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9004-61-9 (Hyaluronic Acid); 9007-28-7 (Chondroitin Sulfates); 9007-34-5 (Collagen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.17219/acem/62835


  9 / 6542 MEDLINE  
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[PMID]:28771551
[Au] Autor:Novinec M
[Ad] Endereço:Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
[Ti] Título:Computational investigation of conformational variability and allostery in cathepsin K and other related peptidases.
[So] Source:PLoS One;12(8):e0182387, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Allosteric targeting is progressively gaining ground as a strategy in drug design. Its success, however, depends on our knowledge of the investigated system. In the case of the papain-like cysteine peptidase cathepsin K, a major obstacle in our understanding of allostery is represented by the lack of observable conformational change at the active site. This makes it difficult to understand how binding of effectors at known allosteric sites translates into modified enzyme activity. Herein, we address this issue by a computational approach based on experimental data. We analyze the conformational space of the papain-like family and the positioning of cathepsin K within it using principal component analysis and molecular dynamics simulations. We show that human cathepsin L-like endopeptidases (cathepsins L, K, S and V) adopt similar conformations which are distinct from their non-animal counterparts and other related peptidases. Molecular dynamics simulations show that the conformation of cathepsin K is influenced by known allosteric effectors, chondroitin sulfate and the small molecules NSC13345 and NSC94914. Importantly, all effectors affect the geometry of the active site around sites S1 and S2 that represent the narrowest part of the active site cleft and the major specificity determinant in papain-like endopeptidases. The effectors act by stabilizing pre-existing conformational states according to a two-state model and thereby facilitate or hinder the binding of substrate into the active site, as shown by molecular docking simulations. Comparison with other related enzymes shows that similar conformational variability and, by implication, allostery also exist in other papain-like endopeptidases.
[Mh] Termos MeSH primário: Catepsina K/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica
Sequência de Aminoácidos
Benzoatos/química
Benzoatos/metabolismo
Sítios de Ligação
Domínio Catalítico
Catepsina K/química
Sulfatos de Condroitina/química
Sulfatos de Condroitina/metabolismo
Seres Humanos
Isoenzimas/química
Isoenzimas/metabolismo
Simulação de Dinâmica Molecular
Papaína/química
Papaína/metabolismo
Análise de Componente Principal
Alinhamento de Sequência
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoates); 0 (Isoenzymes); 0 (NSC13345); 9007-28-7 (Chondroitin Sulfates); EC 3.4.22.2 (Papain); EC 3.4.22.38 (Cathepsin K)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182387


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[PMID]:28763562
[Au] Autor:Wang X; Majumdar S; Ma G; Sohn J; Yiu SC; Stark W; Al-Qarni A; Edward DP; Elisseeff JH
[Ad] Endereço:Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States 2Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, Maryland, United States.
[Ti] Título:Chondroitin Sulfate-Based Biocompatible Crosslinker Restores Corneal Mechanics and Collagen Alignment.
[So] Source:Invest Ophthalmol Vis Sci;58(10):3887-3895, 2017 Aug 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To evaluate the crosslinking effect of functionalized chondroitin sulfate (CS) in an ex vivo rabbit cornea model. Methods: Chondroitin sulfate molecules were chemically modified with the N-hydroxysuccinimide (NHS) group. Enucleated rabbit eyes were crosslinked with 2, 5, or 10 mg/mL CS-NHS solution for 30 or 60 minutes. The CS-NHS penetration, corneal swelling ratio, Young's modulus, and ultrastructure of the crosslinked corneas were characterized. In addition, rabbit corneas were further treated with a collagenase-chondroitinase solution to create an ex vivo keratoconus (KC)-like model. The KC model corneas were crosslinked with a standard riboflavin-ultraviolet (UV) method or alternatively with CS-NHS. Corneal mechanics, ultrastructure, and keratocyte gene expression were evaluated after UV and CS-NHS crosslinking. Results: CS-NHS effectively penetrated into the corneal stroma within 60 minutes of treatment initiation. CS-NHS crosslinking reduced the swelling ratio by 35%, increased Young's modulus by 20%, and increased collagen fibril diameter and density. CS-NHS crosslinking improved corneal mechanics of KC model corneas to levels comparable to those with UV crosslinking. Moreover, CS-NHS crosslinking demonstrated significant downregulation of proinflammatory gene expression of keratocytes, indicating a potential protective effect imparted by CS-NHS during crosslinking. Conclusions: Our results demonstrated that CS-NHS can reinforce normal and KC model corneal mechanics, and restore collagen density and alignment in KC model corneas without causing extensive keratocyte apoptosis and proinflammatory gene upregulation. Therefore, CS-NHS crosslinking can potentially provide an effective, safe, and biocompatible means of corneal reinforcement.
[Mh] Termos MeSH primário: Sulfatos de Condroitina/farmacologia
Colágeno/metabolismo
Córnea/efeitos dos fármacos
Reagentes para Ligações Cruzadas/farmacologia
[Mh] Termos MeSH secundário: Animais
Fenômenos Biomecânicos
Córnea/metabolismo
Córnea/fisiopatologia
Ceratócitos da Córnea/efeitos dos fármacos
Ceratócitos da Córnea/metabolismo
Modelos Animais de Doenças
Módulo de Elasticidade/efeitos dos fármacos
Fármacos Fotossensibilizantes/farmacologia
Coelhos
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cross-Linking Reagents); 0 (Photosensitizing Agents); 9007-28-7 (Chondroitin Sulfates); 9007-34-5 (Collagen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170803
[Lr] Data última revisão:
170803
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-21292



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