111 research outputs found
Supporting_Information_rev – Supplemental material for HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study
No full textSupplemental material, Supporting_Information_rev for HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study by Cristian Guarise, Carlo Barbera, Mauro Pavan, Susi Panfilo, Riccardo Beninatto and Devis Galesso in Journal of Applied Biomaterials & Functional Materials</p
Peptide engineering for the development of metalloprotease inhibitors by using yeast surface display technology
No full textL' Osteoartrite (OA) è una malattia degenerativa delle articolazioni che porta a dolore cronico e disabilità. È la forma più comune di artrite, colpisce circa il 3% della popolazione, determinando così un grave onere socioeconomico per la salute. Ad oggi, non ci sono trattamenti approvati per questa malattia. L'OA è caratterizzata dalla degenerazione della cartilagine articolare e dall'infiammazione intra-articolare. Questi processi sono causati dalle metalloproteasi, una grande famiglia di enzimi proteolitici la cui attività catalitica coinvolge un metallo. Pertanto, le metalloproteasi rappresentano importanti bersagli farmacologici per la prevenzione e il trattamento dell'OA.
Lo scopo di questa ricerca è lo sviluppo di inibitori di due cruciali metalloproteasi coinvolte nell'OA: A-disintegrina e metalloproteinasi con motivi trombospondinici-5 (ADAMTS-5) e A-disintegrina e metalloproteinasi-17 (ADAM-17 o TACE). Piuttosto che focalizzarci su queste due proteine utilizzando inibitori a base di piccole molecole e proteine, abbiamo deciso di sviluppare inibitori a base di peptidi. Analogamente agli inibitori proteici, gli inibitori peptidici sono in grado di legare il bersaglio con una superficie di interazione sufficientemente ampia da ottenere un'elevata efficienza e selettività. Come le piccole molecole, gli inibitori peptidici possono essere sintetizzati chimicamente, possedere facilità di modifica, bassa tossicità e ridotta antigenicità. La loro struttura modulare e la disponibilità commerciale di centinaia di amminoacidi, come elementi costitutivi, semplificano il rapido sviluppo di peptidi con proprietà personalizzate.
La tecnologia di espressione sulla superficie del lievito, che consente lo screening quantitativo di grandi librerie combinatoriali di sequenze peptidiche casuali, è stata applicata per lo sviluppo di inibitori a base peptidica. Sono stati esplorati due tipi di librerie di peptidi. Una libreria è stata progettata per includere esclusivamente amminoacidi canonici, mentre la seconda è stata concepita per contenere un amminoacido non canonico e consentire specifiche modifiche chimiche post-traduzionali che potrebbero modulare ulteriormente le proprietà dei peptidi espressi sulla superficie e aumentare notevolmente la loro diversità chimica
Design, sintesi e studi conformazionali di aggregati peptidici con siti di legame specifici per ioni zinco
No full textGel-like structure of a hexadecyl derivative of hyaluronic acid for the treatment of osteoarthritis
No full textHyaluronic acid is a polysaccharide with viscoelastic and mechanical properties that are crucial for the normal functioning of osteoarticular junctions. It is demonstrated that introduction of a hexadecyl side chain into HA yields an injectable polysaccharide capable of forming physical hydrogels, which are stable at very low polymer concentrations, whereas native hyaluronic acid forms viscous solutions at concentrations that are ten times higher. Characterization of this system showed that the driving force for its gel-like behavior is the occurrence of hydrophobic interactions involving aliphatic side chains, despite the low degree of substitution, as confirmed by molecular dynamics simulations of HYADD4 and HA hydrogels
Inflammatory and Non-Inflammatory Synovial Fluids Exhibit New & Distinct Tribological Endotypes
No full textInferior synovial lubrication is a hallmark of osteoarthritis (OA), and synovial fluid (SF) lubrication and composition are variable among OA patients. Hyaluronic acid (HA) viscosupplementation is a widely used therapy for improving SF viscoelasticity and lubrication, but it is unclear how the effectiveness of HA viscosupplements varies with arthritic endotype. The objective of this study was to investigate the effects of the HA viscosupplement, Hymovis®, on the lubricating properties of diseased SF from patients with non-inflammatory OA and inflammatory arthritis (IA). The composition (cytokine, HA, and lubricin concentrations) of the SF was measured as well as the mechanical properties (rheology, tribology) of the SF alone and in a 1:1 mixture with the HA viscosupplement. Using rotational rheometry, no difference in SF viscosity was detected between disease types, and the addition of HA significantly increased all fluids' viscosities. In non-inflammatory OA SF, friction coefficients followed a typical Stribeck pattern and their magnitude was decreased by the addition of HA. While some of the IA SF also showed typical Stribeck behavior, a subset showed more erratic behavior with highly variable and larger friction coefficients. Interestingly, this aberrant behavior was not eliminated by the addition of HA, and it was associated with low concentrations of lubricin. Aberrant SF exhibited significantly lower effective viscosities compared to non-inflammatory OA and IA SF with typical tribological behavior. Collectively, these results suggest that different endotypes of arthritis exist with respect to lubrication, which may impact the effectiveness of HA viscosupplements in reducing friction
The infant's miscellany [electronic resource] : or easy lessons, extracted from different authors. On a new plan. Intended to facilitate the attainment of the English language to the youngest readers, by teaching them not only to read, but likewise to understand clearly what they read.
No full textAccording the 'Advertisement' to 'Miscellaneous lessons' by Ellin Devis, that book was based on this one, with the implication that they share the same author.With an index and short questions.Below imprint: Price two shillings.Electronic reproduction.English Short Title Catalog,Reproduction of original from British Library
Distinct tribological endotypes of pathological human synovial fluid reveal characteristic biomarkers and variation in efficacy of viscosupplementation at reducing local strains in articular cartilage
No full textViscosupplementation has been used for decades to treat mild to moderate osteoarthritis, yet it is unknown if the lubricating function of different pathological synovial fluids (SF) vary, or if they respond differentially to viscosupplementation. The objectives of this study were to (i) evaluate the friction coefficients and induced shear strains in articular cartilage when lubricated with pathological SF, (ii) identify the effect of hyaluronic acid (HA) supplementation on friction coefficients and shear strains, and (iii) identify SF biomarkers that correlate with lubricating function
In Vitro Innovation of Tendon Tissue Engineering Strategies
No full textTendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process
Étude sur la puissance statistique des devis de recherche en éducation
No full textCet article propose de faire le point sur la puissance statistique moyenne des devis de recherche en éducation publiés récemment au Canada francophone. Soixante-dix-sept articles publiés entre 2004 et 2006, à l’intérieur de quatre revues scientifiques canadiennes francophones, ont été analysés avec le logiciel G*Power pour déterminer leur capacité à détecter des effets de petite, moyenne et grande taille. Les résultats montrent peu de progrès réels de la recherche en éducation au Canada français en matière de puissance statistique depuis les travaux de Cohen (1962). Des pistes concrètes pour améliorer la puissance statistique des devis sont suggérées.This article examines the mean statistical power of recent articles published in French Canadian scientific journals dedicated to research in education. 77 studies published in 4 different journals between 2004 and 2006 were analyzed with G*Power to establish their potential to detect small, medium, and large effects. Overall, results show that little progress has been made since the founding work of Cohen (1962) regarding statistical power in the field of educational research in the francophone scientific community. The author gives concrete actions for researchers to improve the statistical power of future work.El presente artículo tiene por objetivo analizar la potencia estadística promedia de los diseños de investigación en educación, publicados en los últimos años en revistas francocanadienses. Fueron analizados 77 artículos publicados entre 2004 y 2006 en cuatro revistas científicas francocanadienses con el software G*Power para determinar su capacidad para detectar efectos de tamaño pequeño, medio o grande. Los resultados muestran que la investigación francocanadiense en educación realizó pocos adelantos reales sobre el tema de la potencia estadística desde los trabajos de Cohen (1962). Se recomiendan algunas pistas concretas para mejorar la potencia estadística de los diseños de investigación
Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells
No full textHigh levels of hyaluronan (ΗΑ), a major extracellular matrix (ECM) glycosaminoglycan, have been correlated with poor clinical outcome in several malignancies, including breast cancer. The high and low molecular weight HΑ forms exert diverse biological functions. Depending on their molecular size, ΗΑ forms either promote or attenuate signaling cascades that regulate cancer progression. In order to evaluate the effects of different ΗΑ forms on breast cancer cells' behavior, ΗΑ fragments of defined molecular size were synthesized. Breast cancer cells of different estrogen receptor (ER) status – the low metastatic, ERα-positive MCF-7 epithelial cells and the highly aggressive, ERβ-positive MDA-MB-231 mesenchymal cells – were evaluated following treatment with HA fragments. Scanning electron microscopy revealed that HA fragments critically affect the morphology of breast cancer cells in a molecular-size dependent mode. Moreover, the ΗΑ fragments affect cell functional properties, the expression of major ECM mediators and epithelial-to-mesenchymal transition (ΕΜΤ) markers. Notably, treatment with 200 kDa ΗΑ increased the expression levels of the epithelial marker Ε-cadherin and reduced the expression levels of HA synthase 2 and mesenchymal markers, like fibronectin and snail2/slug. These novel data suggest that the effects of HA in breast cancer cells depend on the molecular size and the ER status. An in-depth understanding on the mechanistic basis of these effects may contribute on the development of novel therapeutic strategies for the pharmacological targeting of aggressive breast cancer
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