Mechanisms of the noxious inflammatory cycle in cystic fibrosis

Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508), accounting for this pathology, is retained in the endoplasmic reticulum (ER), induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Layer-by-layer films made from extracellular matrix macromolecules on silicone substrates

The layer-by-layer (LbL) technique has been widely used to produce nanofilms for biomedical applications. Naturally occurring polymers such as ECM macromolecules are attractive candidates for LbL film preparation. In this study, we assessed the build-up of type I collagen (Col1)/chondroitin sulfate (CS) or Col1/Heparin (HN) on polydimethylsiloxane (PDMS) substrates. The build-up was assessed by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM). Integrin-mediated cell adhesion was assessed by studying the cytoskeletal organization of mammalian primary cells (chondrocytes) seeded on different end layers and number of layers. Data generated from the QCM-D observations showed a consistent build-up of films with more adsorption in the case of Col1/HN. Col1/CS films were stable in media, whereas Col1/HN films were not. AFM analysis showed that the layers were fibrillar in structure for both systems and between 20 and 30 nm thick. The films promoted cell adhesion when compared with tissue culture plastic in serum-free media with cycloheximide. Crosslinking of the films resulted in constrained cell spreading and a ruffled morphology. Finally, beta1 integrin blocking antibodies prevented cell spreading, suggesting that cell adhesion and spreading were mediated mainly by interaction with the collagen fibrils. The ability to construct stable ECM-based films on PDMS has particular relevance in mechanobiology, microfluidics, and other biomedical applications

Characterization of the non-uniform concentration profile of binary fluids confined in mesopores by neutron scattering methods

International audienc

Petrographic and mineralogical analyses combined with sequential extractions and leaching experiments as a function of pH were performed on black clayey sediments fulfilling karsts in the Hydrogeological Experimental Site (HES) of Poitiers (France) to investigate the behavior of arsenic and selenium in a fractured limestone aquifer. Sequential extractions showed that arsenic is mainly associated with pyrite (about 35%) and secondary iron oxyhydroxides (around 13%), along with a substantial exchangeable fraction (about 13%). The soluble fraction and the fraction associated to organic matter are ∼2% and ∼5%, respectively. The distribution of selenium is mainly pyritic (around 39%) or associated with organic matter (about 18%). Its association to secondary iron oxyhydroxides minerals is low (around 2%), whereas its soluble fraction is around 5%. SEM analyses revealed the presence of arsenic “hot spots” into euhedral pyrite crystals surrounded by a halo of iron oxyhydroxides resulting from their alteration, and both are enriched with arsenic. Selenium has a similar pyritic origin but after alteration, it is predominantly associated with organic matter. Despite different distributions, the leaching experiment as a function of pH showed that the mobilization of arsenic and selenium overlapped below pH 2 and above pH 8. The main differences were observed between pH 2 and 8 with a plateau at 5% of released selenium, whereas the amount of mobilized arsenic continuously decreased. The pH-dependence of both elements is attributed to the partial dissolution of pyrite in acidic conditions combined with desorption processes at higher pH values.

International audienc

An UWB-UHF Semi-Passive RFID System for Localization and Tracking Applications

We present a novel radio-frequency identification (RFID) system with capability of localization and tracking of passive or semi-passive tags. Localization and tracking features are enabled by backscatter modulation on ultra-wide bandwidth tag's antenna. A ultra-high frequency signal allows the wake-up of the tags enabling the reduction of energy consumption and ensuring compatibility with existing RFID systems. The overall system as well as the reader and tag architectures are introduced. The localization and tracking performance evaluation is presented in some reference scenarios