Phytoglycogen is a naturally occurring polysaccharide nanoparticle made up of extensively branched glucose monomers. It has a number of unusual and advantageous properties, such as high water retention, low viscosity, and high stability in water, which make this biomaterial a promising candidate for a wide variety of applications. In this study, we have characterized the structure and hydration of aqueous dispersions of phytoglycogen nanoparticles using neutron scattering. Small angle neutron scattering results suggest that the phytoglycogen nanoparticles behave similar to hard sphere colloids and are hydrated by a large number of water molecules (each nanoparticle contains between 250% and 285% of its mass in water). This suggests that phytoglycogen is an ideal sample in which to study the dynamics of hydration water. To this end, we used quasielastic neutron scattering (QENS) to provide an independent and consistent measure of the hydration number, and to estimate the retardation factor (or degree of water slow-down) for hydration water translational motions. These data demonstrate a length-scale dependence in the measured retardation factors that clarifies the origin of discrepancies between retardation factor values reported for hydration water using different experimental techniques. The present approach can be generalized to other systems containing nanoconfined water.
Transglutaminase-2 (TG2) is a new anti-fibrotic target for chronic kidney disease, for its role in altering the extracellular homeostatic balance leading to excessive build-up of matrix in kidney. However, there is no confirmation that TG2 is the only transglutaminase involved, neither there are strategies to control its action specifically over that of the conserved family-members. In this study, we have profiled transglutaminase isozymes in the rat subtotal nephrectomy (SNx) model of progressive renal scarring. All transglutaminases increased post-SNx peaking at loss of renal function but TG2 was the predominant enzyme. Upon SNx, extracellular TG2 deposited in the tubulointerstitium and peri-glomerulus via binding to heparan sulphate (HS) chains of proteoglycans and co-associated with syndecan-4. Extracellular TG2 was sufficient to activate transforming growth factor-β1 in tubular epithelial cells, and this process occurred in a HS-dependent way, in keeping with TG2-affinity for HS. Analysis of heparin binding of the main transglutaminases revealed that although the interaction between TG1 and HS is strong, the conformational heparin binding site of TG2 is not conserved, suggesting that TG2 has a unique interaction with HS within the family. Our data provides a rationale for a novel anti-fibrotic strategy specifically targeting the conformation-dependent TG2-epitope interacting with HS.
The worldwide prevalence of obesity has been steadily rising, reaching alarming levels. Obesity, particularly morbid obesity, carries significant health risks to the lives of affected patients, including physical, psychological, and social co-morbidities. Bariatric surgery provides the only effective and sustainable approach to treat morbid obesity and reverse its adverse effects. The reduction in well-being due to poor health in obesity may have adverse effects on health-related quality of life (HR-QOL). There are numerous studies reporting HR-QOL in bariatric patients; however, there is a paucity of studies examining the psychometric properties of the HR-QOL instruments used. The main aim of this review is to identify the instruments used in assessing HR-QOL in bariatric patients and evaluate their content validity. We believe that this is the first systematic review of its kind to look in depth at various generic- and obesity-specific HR-QOL instruments that were used in bariatric surgery, and to analyze their content validity. A systematic and structured search of Ovid databases (1980-2009) was conducted using terms synonymous with bariatric surgery, combined with terms synonymous with HR-QOL instruments. A total of 112 relevant studies were identified, detailing the use of eight generic, nine obesity-specific, and numerous other condition-specific instruments. A conceptual framework comprising 20 domains pertinent to bariatric surgery and morbid obesity was proposed, against which the identified generic- and obesity-specific instruments were assessed. The results of this assessment showed that neither the generic nor the specific instruments were adequate instruments in terms of content validity. Given the lack of adequate HR-QOL instruments in the rapidly developing field of bariatric surgery, we suggest building a new bariatric-specific instrument informed by the proposed framework, which will then enable clinicians to assess the full impact of morbid obesity and bariatric surgery on HR-QOL.
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