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1.
Adv Exp Med Biol ; 1348: 235-249, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34807422

RESUMEN

Ehlers-Danlos syndrome (EDS) is a genetically and clinically heterogeneous group of connective tissue disorders that typically present with skin hyperextensibility, joint hypermobility, and tissue fragility. The major cause of EDS appears to be impaired biosynthesis and enzymatic modification of collagen. In this chapter, we discuss two types of EDS that are associated with proteoglycan abnormalities: spondylodysplastic EDS and musculocontractural EDS. Spondylodysplastic EDS is caused by pathogenic variants in B4GALT7 or B3GALT6, both of which encode key enzymes that initiate glycosaminoglycan synthesis. Musculocontractural EDS is caused by mutations in CHST14 or DSE, both of which encode enzymes responsible for the post-translational biosynthesis of dermatan sulfate. The clinical and molecular characteristics of both types of EDS are described in this chapter.


Asunto(s)
Síndrome de Ehlers-Danlos , Colágeno , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Galactosiltransferasas/genética , Glicosaminoglicanos , Humanos , Mutación , Sulfotransferasas
2.
Pediatr Endocrinol Diabetes Metab ; 27(3): 201-208, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34743503

RESUMEN

Mucopolysaccharidoses (MPSs) are known as rare genetic diseases which are caused by mutation in the enzyme heparin sulfate, which normally leads to degradation and accumulation of glycosaminoglycans in the cells. There are 11 types of MPSs, whereby neuropathy may occur in seven of them (MPS I, II, IIIA, IIIB, IIIC, IIID and VII). Accumulation of degraded heparin sulfate in lysosomes causes cellular dysfunction and malfunction of several organs. However, the exact molecular mechanism how protein degradation and storage leads to cellular dysfunction is not understood, yet. Nonetheless, several genetic and biochemical methods for diagnosis of MPSs are available nowadays. Here we provide an overview on known molecular basis of MPS in general, including enzyme defects and symptoms of MPS; however, the main focus is on MPS type III together with potential and perspective therapy-options.


Asunto(s)
Mucopolisacaridosis , Mucopolisacaridosis III , Mucopolisacaridosis I , Glicosaminoglicanos , Humanos , Mucopolisacaridosis/tratamiento farmacológico , Mucopolisacaridosis/genética , Mutación
3.
PLoS One ; 16(10): e0250681, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34673776

RESUMEN

Induction of remission is easily achieved with dietary treatment in dogs diagnosed with Food Responsive Chronic Diarrhea (FRD). Administration of prebiotics and glycosaminoglycans (GAGs) may improve epithelial cell integrity and therefore be useful as adjunct treatment. This study evaluated whether the relapse rate of FRD dogs that are switched back to a normal diet can be influenced using supplemental treatment with prebiotics and GAGs. A randomized, controlled clinical trial (RCCT) was performed in dogs diagnosed with FRD. Dogs were diagnosed based on clinical exclusion diagnosis, endoscopic biopsies showing predominantly lymphoplasmacytic infiltration, and response to dietary treatment. Dogs were randomized to be fed a combination of prebiotics and GAGs (group 1) or placebo (group 2) in addition to a hydrolyzed diet. At week 10, a second endoscopy was performed and dogs were switched back to normal diet. Relapse rate was monitored every 2 weeks after that until week 18. Statistical analysis was performed for each outcome (Canine Chronic Enteropathy Clinical Activity Index (CCECAI), clinicopathological data, endoscopic scoring, mWSAVA histological scoring index (mWSAVA), and number of relapses following switch to normal diet) using a linear mixed effects model for group comparison. Time, group, and their interactions were included as a fixed effect, whereas each dog was treated as a random effect. Of the 35 dogs enrolled into the clinical trial, 10 in each group reached the point of second endoscopy. A total of 13 dogs (n = 8 in group 1 and n = 5 in group 2) reached the trial endpoint of 18 weeks. After switching back to normal diet, none of the dogs in either group relapsed. No significant differences were found over time or between groups for CCECAI, endoscopy scoring and histological scoring. Although there was a clinical worsening in the placebo group after switching back to the original diet, this was not statistically significant (CCECAI p = 0.58). Post-hoc power calculation revealed that 63 dogs per group would have been needed to detect statistically significant differences in CIBDAI between treatment groups. Standard dietary treatment induced rapid clinical response in all cases, however, additional supplementation with prebiotics and GAGs did not significantly improve clinical outcome within 4 months after switching back to normal diet. Since there are very few RCCT published in CE in dogs, this pilot study provides important power analyses for planning of further studies.


Asunto(s)
Enfermedades de los Perros/tratamiento farmacológico , Glicosaminoglicanos/administración & dosificación , Prebióticos/administración & dosificación , Animales , Diarrea/tratamiento farmacológico , Dieta/métodos , Perros , Femenino , Masculino , Proyectos Piloto
4.
Molecules ; 26(19)2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34641274

RESUMEN

Articular cartilage (AC) damage is quite common, but due to AC's poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-ß3 (TGF-ß3) to enhance cartilage tissue formation and ghrelin synergy TGF-ß to significantly enhance the chondrogenic differentiation. The hydrogel and microspheres were characterized in vitro, and the biocompatibility of the system was verified. Double emulsion solvent extraction technology (w/o/w) is used to encapsulate TGF-ß3 and ghrelin into microspheres, and these microspheres are encapsulated in a hydrogel to continuously release TGF-ß3 and ghrelin. According to the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) in vitro, the concentrations of the two growth factors were optimized to promote cartilage regeneration.


Asunto(s)
Cartílago Articular/citología , Ghrelina/farmacología , Células Madre Mesenquimatosas/citología , Factor de Crecimiento Transformador beta3/farmacología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Técnicas de Cultivo de Célula , Células Cultivadas , Condrogénesis/efectos de los fármacos , Medios de Cultivo/química , Glicosaminoglicanos/metabolismo , Humanos , Hidrogeles , Ensayo de Materiales , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Microesferas , Medicina Regenerativa
5.
Molecules ; 26(17)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34500644

RESUMEN

The linear anionic class of polysaccharides, glycosaminoglycans (GAGs), are critical throughout the animal kingdom for developmental processes and the maintenance of healthy tissues. They are also of interest as a means of influencing biochemical processes. One member of the GAG family, heparin, is exploited globally as a major anticoagulant pharmaceutical and there is a growing interest in the potential of other GAGs for diverse applications ranging from skin care to the treatment of neurodegenerative conditions, and from the treatment and prevention of microbial infection to biotechnology. To realize the potential of GAGs, however, it is necessary to develop effective tools that are able to exploit the chemical manipulations to which GAGs are susceptible. Here, the current knowledge concerning the chemical modification of GAGs, one of the principal approaches for the study of the structure-function relationships in these molecules, is reviewed. Some additional methods that were applied successfully to the analysis and/or processing of other carbohydrates, but which could be suitable in GAG chemistry, are also discussed.


Asunto(s)
Glicosaminoglicanos/química , Polisacáridos/química , Animales , Anticoagulantes/química , Heparina/química , Humanos , Relación Estructura-Actividad
6.
Biomacromolecules ; 22(10): 4316-4326, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34520173

RESUMEN

Glycosaminoglycans (GAGs), such as hyaluronic acid (HA) and chondroitin sulfate (CS), have seen widespread adoption as components of tissue engineering scaffolds because of their potent bioactive properties and ease of chemical modification. However, modification of the biopolymers will impair biological recognition of the GAG and reduce the bioactive properties of the material. In this work, we studied how the degree of thiolation of HA and CS, along with other key hydrogel design parameters, affected the physical and bioactive properties of the bulk hydrogel. Although properties, such as the HA molecular weight, did not have a major effect, increasing the degree of thiolation of both HA and CS decreased their biorecognition in experimental analogues for cell/matrix remodeling and binding. Furthermore, combining HA and CS into dual polymer network hydrogels also modulated the physical and bioactive properties, as seen with differences in gel stiffness, degradation rate, and encapsulated cell viability.


Asunto(s)
Glicosaminoglicanos , Hidrogeles , Sulfatos de Condroitina , Ácido Hialurónico , Polímeros , Ingeniería de Tejidos
7.
Int J Mol Sci ; 22(18)2021 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-34575990

RESUMEN

Glycosylation is an important step in post-translational protein modification. Altered glycosylation results in an abnormality that causes diseases such as malignancy and cardiovascular diseases. Recent emerging evidence highlights the importance of glycosylation in vascular calcification. Two major types of glycosylation, N-glycosylation and O-glycosylation, are involved in vascular calcification. Other glycosylation mechanisms, which polymerize the glycosaminoglycan (GAG) chain onto protein, resulting in proteoglycan (PG), also have an impact on vascular calcification. This paper discusses the role of glycosylation in vascular calcification.


Asunto(s)
Glicosaminoglicanos/metabolismo , Procesamiento Proteico-Postraduccional , Proteoglicanos/metabolismo , Calcificación Vascular/metabolismo , Animales , Glicosilación , Humanos
8.
J Phys Chem B ; 125(39): 10900-10916, 2021 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-34550710

RESUMEN

The structure and conformation of glycosaminoglycans (GAGs) are of central importance to understand the mechanisms behind their functions in biological systems. Due to the inherent chemical and structural heterogeneity of GAGs, focusing on longer, naturally existing GAG chains hinders drawing conclusions on the influence of the chemical functionalization on the basic conformational degree of freedom, that is, the dynamic shape of glycosidic linkage present in the particular disaccharide repeating unit. In the present study, we have considered the complete set of 106 GAG-related disaccharides, being potential building blocks for longer GAG chains (including hyaluronan, chondroitin, keratan, dermatan, and heparan). Both the unfunctionalized units and all possible combinations of either partially or fully sulfated derivatives contribute to this number. The unbiased and enhanced sampling molecular dynamics simulations provide a link to understand the influence of sulfation on the conformational properties of GAG glycosidic linkages. Residue-residue hydrogen bonding is not significant for either the glycosidic linkage conformation or its flexibility. It was found that in the majority of cases, the dominating conformation of the linkage is weakly affected by sulfation and the main role is played by the steric and stereoelectronic effects. However, there exist numerous cases where sulfation increases the contribution of alternative conformations to a nonnegligible extent and, in some rare cases (restricted to disaccharides building heparan), leads to the reorientation of the glycosidic linkage. The identified sulfation sites, being the most important in this context, are C6 and C3 at the GlcNAc residue. Finally, the full set of free energy maps relying on the glycosidic dihedral angle values for diverse GAG disaccharides are provided; they may be used for further studies, focused on longer GAG chains.


Asunto(s)
Disacáridos , Glicosaminoglicanos , Ácido Hialurónico , Conformación Molecular , Simulación de Dinámica Molecular
9.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34502207

RESUMEN

The complexity of skeletal pathologies makes use of in vivo models essential to elucidate the pathogenesis of the diseases; nevertheless, chondrocyte and osteoblast cell lines provide relevant information on the underlying disease mechanisms. Due to the limitations of primary chondrocytes, immortalized cells represent a unique tool to overcome this problem since they grow very easily for several passages. However, in the immortalization procedure the cells might lose the original phenotype; thus, these cell lines should be deeply characterized before their use. We immortalized primary chondrocytes from a Cant1 knock-out mouse, an animal model of Desbuquois dysplasia type 1, with a plasmid expressing the SV40 large and small T antigen. This cell line, based on morphological and biochemical parameters, showed preservation of the chondrocyte phenotype. In addition reduced proteoglycan synthesis and oversulfation of glycosaminoglycan chains were demonstrated, as already observed in primary chondrocytes from the Cant1 knock-out mouse. In conclusion, immortalized Cant1 knock-out chondrocytes maintained the disease phenotype observed in primary cells validating the in vitro model and providing an additional tool to further study the proteoglycan biosynthesis defect. The same approach might be extended to other cartilage disorders.


Asunto(s)
Ácido Anhídrido Hidrolasas/fisiología , Condrocitos/patología , Anomalías Craneofaciales/patología , Enanismo/patología , Glicosaminoglicanos/metabolismo , Inestabilidad de la Articulación/patología , Osificación Heterotópica/patología , Fenotipo , Polidactilia/patología , Animales , Línea Celular Transformada , Condrocitos/metabolismo , Anomalías Craneofaciales/etiología , Anomalías Craneofaciales/metabolismo , Enanismo/etiología , Enanismo/metabolismo , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osificación Heterotópica/etiología , Osificación Heterotópica/metabolismo , Polidactilia/etiología , Polidactilia/metabolismo
10.
Adv Exp Med Biol ; 1325: 103-116, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34495531

RESUMEN

Glycosaminoglycans (GAGs) are important constituents of human glycome. They are negatively charged unbranched polysaccharides that are usually covalently attached to proteins, forming glycan-protein conjugates, called proteoglycans. Glycosaminoglycans play critical roles in numerous biological processes throughout individual development and are also involved in the pathological processes of various diseases. Based on their remarkable bioactivities and their universal involvement in disease progression, GAGs are applied as therapeutics or are being targeted or used in treating diseases. In this chapter, we introduce the characteristics of the four classes of GAGs that constitute the glycosaminoglycan family. The pathological roles of glycosaminoglycans in major diseases including innate disease, infectious disease, and cancer are discussed. The application of GAGs and their mimetics as therapeutics is introduced, as well as those therapeutic methods developed based on GAGs' role in pathogenesis. In addition, we provide a brief and overall lookback at the history of GAG research and sort out some critical techniques that facilitated GAG and glycomics studies.


Asunto(s)
Glicómica , Glicosaminoglicanos , Biomimética , Humanos , Polisacáridos , Proteoglicanos
11.
Adv Exp Med Biol ; 1325: 189-204, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34495536

RESUMEN

Glycosaminoglycans (GAGs) are linear polysaccharides that consist of alternating disaccharides sequences of uronic acids and/or galactose hexamino sugars most of which are sulfated. GAGs are ubiquitously expressed on the cell surface, in the intracellular milieu and in the extracellular matrix of all animal cells. Thus, GAGs exhibit many essential roles in a variety of physiological and pathological processes. The targets of GAGs are GAG-binding proteins and related proteins that are of significant interest to both the academic community and in the pharmaceutical industry. In this review, the structures of GAGs, their binding proteins, and analogs are presented that further the development of GAGs and their analogs for the treatment of neurodegenerative diseases agents.


Asunto(s)
Glicosaminoglicanos , Enfermedades Neurodegenerativas , Animales , Enfermedades Neurodegenerativas/tratamiento farmacológico , Polisacáridos , Sulfatos
12.
J Am Anim Hosp Assoc ; 57(5): 205-211, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34496011

RESUMEN

Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.


Asunto(s)
Enfermedades de los Perros , Animales , Enfermedades de los Perros/tratamiento farmacológico , Perros , Glicosaminoglicanos , Inyecciones Intramusculares/veterinaria , Percepción
13.
Int J Mol Sci ; 22(17)2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34502249

RESUMEN

The replacement of damaged or degenerated articular cartilage tissue remains a challenge, as this non-vascularized tissue has a very limited self-healing capacity. Therefore, tissue engineering (TE) of cartilage is a promising treatment option. Although significant progress has been made in recent years, there is still a lack of scaffolds that ensure the formation of functional cartilage tissue while meeting the mechanical requirements for chondrogenic TE. In this article, we report the application of flock technology, a common process in the modern textile industry, to produce flock scaffolds made of chitosan (a biodegradable and biocompatible biopolymer) for chondrogenic TE. By combining an alginate hydrogel with a chitosan flock scaffold (CFS+ALG), a fiber-reinforced hydrogel with anisotropic properties was developed to support chondrogenic differentiation of embedded human chondrocytes. Pure alginate hydrogels (ALG) and pure chitosan flock scaffolds (CFS) were studied as controls. Morphology of primary human chondrocytes analyzed by cLSM and SEM showed a round, chondrogenic phenotype in CFS+ALG and ALG after 21 days of differentiation, whereas chondrocytes on CFS formed spheroids. The compressive strength of CFS+ALG was higher than the compressive strength of ALG and CFS alone. Chondrocytes embedded in CFS+ALG showed gene expression of chondrogenic markers (COL II, COMP, ACAN), the highest collagen II/I ratio, and production of the typical extracellular matrix such as sGAG and collagen II. The combination of alginate hydrogel with chitosan flock scaffolds resulted in a scaffold with anisotropic structure, good mechanical properties, elasticity, and porosity that supported chondrogenic differentiation of inserted human chondrocytes and expression of chondrogenic markers and typical extracellular matrix.


Asunto(s)
Alginatos/química , Materiales Biocompatibles/química , Quitosano/química , Hidrogeles/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Agrecanos/genética , Agrecanos/metabolismo , Anisotropía , Proteína de la Matriz Oligomérica del Cartílago/genética , Proteína de la Matriz Oligomérica del Cartílago/metabolismo , Diferenciación Celular , Proliferación Celular , Condrocitos/metabolismo , Condrogénesis , Colágeno/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Fuerza Compresiva , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Cultivo Primario de Células , Electricidad Estática
14.
Anal Methods ; 13(36): 4114-4119, 2021 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-34554158

RESUMEN

In this study, a new size exclusion chromatographic method has been developed and validated for the analysis of mucopolysaccharide polysulfate used as an anti-inflammatory and antithrombotic agent in topical formulations. Mucopolysaccharide polysulfate was analyzed in Repromer OH-4000 (10 µm, 8.0 × 300 mm) and Repromer OH-5000 (10 µm, 8.0 × 300 mm) columns using a 0.05 M sodium sulfate isocratic elution mobile phase system at 40 °C with a flow rate of 1 mL min-1 and detected by using refractive index detection. The method was validated by means of the limit of quantification, limit of detection, linearity, robustness, recovery, precision and accuracy using the Bioanalytical Method Validation Guidance. The calibration curve showed linearity in the 0.090-1.575 mg mL-1 range. The limits of detection and quantification were found to be 45.000 and 90.000 µg mL-1, respectively. Assay recovery and precision of mucopolysaccharide polysulfate from topical formulations at 0.450, 0.900 and 1.350 mg mL-1 concentrations were evaluated. Intra-day and inter-day relative standard deviation values were calculated to be less than 2.46%. The mean recovery was calculated as 96.64%. The validated method was successfully applied to the determination of mucopolysaccharide polysulfate in cream and gel formulations.


Asunto(s)
Cromatografía Líquida de Alta Presión , Glicosaminoglicanos/análisis , Calibración , Cromatografía en Gel , Reproducibilidad de los Resultados
15.
Adv Healthc Mater ; 10(22): e2101327, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34541827

RESUMEN

Poly(ethylene glycol) (PEG)-glycosaminoglycan (GAG) hydrogel networks are established as very versatile biomaterials. Herein, the synthetic gel component of the biohybrid materials is systematically varied by combining different poly(2-alkyl-2-oxazolines) (POx) with heparin applying a Michael-type addition crosslinking scheme: POx of gradated hydrophilicity and temperature-responsiveness provides polymer networks of distinctly different stiffness and swelling. Adjusting the mechanical properties and the GAG concentration of the gels to similar values allows for modulating the release of GAG-binding growth factors (VEGF165 and PDGF-BB) by the choice of the POx and its temperature-dependent conformation. Adsorption of fibronectin, growth of fibroblasts, and bacterial adhesion scale with the hydrophobicity of the gel-incorporated POx. In vitro hemocompatibility tests with freshly drawn human whole blood show advantages of POx-based gels compared to the PEG-based reference materials. Biohybrid POx hydrogels can therefore enable biomedical technologies requiring GAG-based materials with customized and switchable physicochemical characteristics.


Asunto(s)
Heparina , Hidrogeles , Materiales Biocompatibles , Glicosaminoglicanos , Humanos , Polietilenglicoles
16.
Molecules ; 26(18)2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34577086

RESUMEN

Although mucopolysaccharidoses (MPS) are caused by mutations in genes coding for enzymes responsible for degradation of glycosaminoglycans, storage of these compounds is crucial but is not the only pathomechanism of these severe, inherited metabolic diseases. Among various factors and processes influencing the course of MPS, oxidative stress appears to be a major one. Oxidative imbalance, occurring in MPS and resulting in increased levels of reactive oxidative species, causes damage of various biomolecules, leading to worsening of symptoms, especially in the central nervous system (but not restricted to this system). A few therapeutic options are available for some types of MPS, including enzyme replacement therapy and hematopoietic stem cell transplantation, however, none of them are fully effective in reducing all symptoms. A possibility that molecules with antioxidative activities might be useful accompanying drugs, administered together with other therapies, is discussed in light of the potential efficacy of MPS treatment.


Asunto(s)
Mucopolisacaridosis/terapia , Estrés Oxidativo/fisiología , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Terapia de Reemplazo Enzimático , Terapia Genética , Glicosaminoglicanos/metabolismo , Humanos , Mucopolisacaridosis/etiología , Estrés Oxidativo/efectos de los fármacos
17.
Indian J Ophthalmol ; 69(10): 2734-2739, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34571624

RESUMEN

Purpose: To compare the bleb morphology by Anterior Segment Optical Coherence Tomography (ASOCT) and clinical outcome after Phacotrabeculectomy with either mitomycin C or Ologen implant. Methods: In a prospective interventional active controlled study, 93 patients aged 18 years and above underwent phacotrabeculectomy with either mitomycin C (53 eyes) or ologen implant (40 eyes), followed up for 12 months. The primary outcome measure was to note the evolution of bleb morphology by ASOCT in the two groups over 12 months. Secondary outcome measures were mean IOP, reduction in the need for anti-glaucoma medications, and complications seen in the two groups. Results: All parameters in the two groups were comparable preoperatively (P>0.05). Best corrected visual acuity at 12 months was 0.38±0.27 in mitomycin group and 0.31±0.23 in ologen group (P=0.151). Post-operative IOP at 12 months was 14.09±3.1mmHg (95%CI 13.22-14.97) in mitomycin group, and 13.25±2.5 mmHg (95%CI 12.40-14.30) in ologen group (P=0.254). The mean number of medications was 0.36±0.68 in mitomycin group and 0.38+/-0.70 in ologen group at 12 months (P=0.91). Overall success was achieved in 98.1 % of patients in mitomycin group and 90 % of patients in ologen group at 12 months. No major sight-threatening complications were noted in any group. AS-OCT imaging at 12 months showed multiform reflectivity with multiple large cystic spaces in both groups, with good IOP control. Conclusion: Phacotrabeculectomy using Mitomycin C and Ologen implant resulted in similar morphologic and functioning blebs at one year with comparable efficacy in controlling intraocular pressure.


Asunto(s)
Mitomicina , Trabeculectomía , Vesícula , Colágeno , Estudios de Seguimiento , Glicosaminoglicanos , Humanos , Presión Intraocular , Estudios Prospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento
18.
Molecules ; 26(18)2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34576979

RESUMEN

Glycosaminoglycans are a class of linear, highly negatively charged, O-linked polysaccharides that are involved in many (patho)physiological processes. In vitro experimental investigations of such processes typically involve porcine-derived heparan sulfate (HS). Structural information about human, particularly organ-specific heparan sulfate, and how it compares with HS from other organisms, is very limited. In this study, heparan sulfate was isolated from human lung tissues derived from five donors and was characterized for their overall size distribution and disaccharide composition. The expression profiles of proteoglycans and HS-modifying enzymes was quantified in order to identify the major core proteins for HS. In addition, the binding affinities of human HS to two chemokines-CXCL8 and CCL2-were investigated, which represent important inflammatory mediators in lung pathologies. Our data revealed that syndecans are the predominant proteoglycan class in human lungs and that the disaccharide composition varies among individuals according to sex, age, and health stage (one of the donor lungs was accidentally discovered to contain a solid tumor). The compositional difference of the five human lung HS preparations affected chemokine binding affinities to various degrees, indicating selective immune cell responses depending on the relative chemokine-glycan affinities. This represents important new insights that could be translated into novel therapeutic concepts for individually treating lung immunological disorders via HS targets.


Asunto(s)
Heparitina Sulfato , Animales , Glicosaminoglicanos , Humanos , Pulmón , Porcinos
19.
Molecules ; 26(18)2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34577067

RESUMEN

Cryogels are a class of macroporous, interconnective hydrogels polymerized at sub-zero temperatures forming mechanically robust, elastic networks. In this review, latest advances of cryogels containing mainly glycosaminoglycans (GAGs) or composites of GAGs and other natural or synthetic polymers are presented. Cryogels produced in this way correspond to the native extracellular matrix (ECM) in terms of both composition and molecular structure. Due to their specific structural feature and in addition to an excellent biocompatibility, GAG-based cryogels have several advantages over traditional GAG-hydrogels. This includes macroporous, interconnective pore structure, robust, elastic, and shape-memory-like mechanical behavior, as well as injectability for many GAG-based cryogels. After addressing the cryogelation process, the fabrication of GAG-based cryogels and known principles of GAG monomer crosslinking are discussed. Finally, an overview of specific GAG-based cryogels in biomedicine, mainly as polymeric scaffold material in tissue regeneration and tissue engineering-related controlled release of bioactive molecules and cells, is provided.


Asunto(s)
Criogeles/química , Glicosaminoglicanos/química , Andamios del Tejido/química , Animales , Técnicas de Cultivo de Célula/métodos , Humanos , Ingeniería de Tejidos/métodos
20.
J Chem Inf Model ; 61(9): 4475-4485, 2021 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-34494837

RESUMEN

Docking glycosaminoglycans (GAGs) has been challenging because of the complex nature of these long periodic linear and negatively charged polysaccharides. Although standard docking tools like Autodock3 are successful when docking GAGs up to hexameric length, they experience challenges to properly dock longer GAGs. Similar limitations concern other docking approaches typically developed for docking ligands of limited size to proteins. At the same time, most of more advanced docking approaches are challenging for a user who is inexperienced with complex in silico methodologies. In this work, we evaluate the binding energies of complexes with different lengths of GAGs using all-atom molecular dynamics simulations. Based on this analysis, we propose a new docking protocol for long GAGs that consists of conventional docking of short GAGs and further elongation with the use of a coarse-grained representation of the GAG parts not being in direct contact with its protein receptor. This method automated by a simple script is straightforward to use within the Autodock3 framework but also useful in combination with other standard docking tools. We believe that this method with some minor case-specific modifications could also be used for docking other linear charged polymers.


Asunto(s)
Glicosaminoglicanos , Proteínas , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular
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