326 research outputs found
A correlation between intestinal microbiota dysbiosis and osteoarthritis
© 2019 Osteoarthritis (OA) is a degenerative disease of the articular cartilage, resulting in pain and total joint disability. Recent studies focused on the role of the metabolic syndrome in inducing or worsening joint damage suggest that chronic low-grade systemic inflammation may represent a possible linking factor. This finding supports the concept of a new phenotype of OA, a metabolic OA. The gut microbiome is fundamental for human physiology and immune system development, among the other important functions. Manipulation of the gut microbiome is considered an important topic for the individual health in different medical fields such as medical biology, nutrition, sports, preventive and rehabilitative medicine. Since intestinal microbiota dysbiosis is strongly associated with the pathogenesis of several metabolic and inflammatory diseases, it is conceivable that also the pathogenesis of OA might be related to it. However, the mechanisms and the contribution of intestinal microbiota metabolites in OA pathogenesis are still not clear. The aim of this narrative review is to review recent literature concerning the possible contribution of dysbiosis to OA onset and to discuss the importance of gut microbiome homeostasis maintenance for optimal general health preservation
Ameliorative effects of PACAP against cartilage degeneration. Morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis
© 2015 by the authors; licensee MDPI, Basel, Switzerland. Osteoarthritis (OA); the most common form of degenerative joint disease, is associated with variations in pro-inflammatory growth factor levels, inflammation and hypocellularity resulting from chondrocyte apoptosis. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide endowed with a range of trophic effects in several cell types; including chondrocytes. However; its role in OA has not been studied. To address this issue, we investigated whether PACAP expression is affected in OA cartilage obtained from experimentally-induced OA rat models, and then studied the effects of PACAP in isolated chondrocytes exposed to IL-1β in vitro to mimic the inflammatory milieu of OA cartilage. OA induction was established by histomorphometric and histochemical analyses. Changes in PACAP distribution in cartilage, or its concentration in synovial fluid (SF), were assessed by immunohistochemistry and ELISA. Results showed that PACAP abundance in cartilage tissue and SF was high in healthy controls. OA induction decreased PACAP levels both in affected cartilage and SF. In vitro, PACAP prevented IL-1β-induced chondrocyte apoptosis, as determined by MTT assay; Hoechst staining and western blots of apoptotic-related proteins. These changes were also accompanied by decreased i-NOS and COX-2 levels, suggesting an anti-inflammatory effect. Altogether, these findings support a potential role for PACAP as a chondroprotective agent for the treatment of OA
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Machine learning approach for computing optical properties of a photonic crystal fiber
Photonic crystal fibers (PCFs) are the specialized optical waveguides that led to many interesting applications ranging from nonlinear optical signal processing to high-power fiber amplifiers. In this paper, machine learning techniques are used to compute various optical properties including effective index, effective mode area, dispersion and confinement loss for a solid-core PCF. These machine learning algorithms based on artificial neural networks are able to make accurate predictions of above-mentioned optical properties for usual parameter space of wavelength ranging from 0.5-1.8 µm, pitch from 0.8-2.0 µm, diameter by pitch from 0.6-0.9 and number of rings as 4 or 5 in a silica solid-core PCF. We demonstrate the use of simple and fast-training feed-forward artificial neural networks that predicts the output for unknown device parameters faster than conventional numerical simulation techniques. Computation runtimes required with neural networks (for training and testing) and Lumerical MODE solutions are also compared
Evaluation of a Cell-Free Collagen Type I-Based Scaffold for Articular Cartilage Regeneration in an Orthotopic Rat Model.
The management of chondral defects represents a big challenge because of the limited self-healing capacity of cartilage. Many approaches in this field obtained partial satisfactory results. Cartilage tissue engineering, combining innovative scaffolds and stem cells from different sources, emerges as a promising strategy for cartilage regeneration. The aim of this study was to evaluate the capability of a cell-free collagen I-based scaffold to promote cartilaginous repair after orthotopic implantation in vivo. Articular cartilage lesions (ACL) were created at the femoropatellar groove in rat knees and cell free collagen I-based scaffolds (S) were then implanted into right knee defect for the ACL-S group. No scaffold was implanted for the ACL group. At 4-, 8- and 16-weeks post-transplantation, degrees of cartilage repair were evaluated by morphological, histochemical and gene expression analyses. Histological analysis shows the formation of fibrous tissue, at 4-weeks replaced by a tissue resembling the calcified one at 16-weeks in the ACL group. In the ACL-S group, progressive replacement of the scaffold with the newly formed cartilage-like tissue is shown, as confirmed by Alcian Blue staining. Immunohistochemical and quantitative real-time PCR (qRT-PCR) analyses display the expression of typical cartilage markers, such as collagen type I and II (ColI and ColII), Aggrecan and Sox9. The results of this study display that the collagen I-based scaffold is highly biocompatible and able to recruit host cells from the surrounding joint tissues to promote cartilaginous repair of articular defects, suggesting its use as a potential approach for cartilage tissue regeneration
Antibiotic susceptibility of respiratory pathogens recently isolated in Italy: focus on ceftidoren
Current knowledge of pituitary adenylate cyclase activating polypeptide (PACAP) in articular cartilage
Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionally well conserved neuropeptide, mainly expressed by neuronal and peripheral cells. It proves to be an interesting object of study both for its trophic functions during the development of several tissues and for its protective effects against oxidative stress, hypoxia, inflammation and apoptosis in different degenerative diseases. This brief review summarises the recent findings concerning the role of PACAP in the articular cartilage. PACAP and its receptors are expressed during chondrogenesis and are shown to activate the pathways involved in regulating cartilage development. Moreover, this neuropeptide proves to be chondroprotective against those stressors that determine cartilage degeneration and contribute to the onset of osteoarthritis (OA), the most common form of degenerative joint disease. Indeed, the degenerated cartilage exhibits low levels of PACAP, suggesting that its endogenous levels in adult cartilage may play an essential role in maintaining physiological properties. Thanks to its peculiar characteristics, exogenous administration of PACAP could be suggested as a potential tool to slow down the progression of OA and for cartilage regeneration approaches
Pulmonary and systemic responses of highly pure and well-dispersed single-wall carbon nanotubes after intratracheal instillation in rats
The present study was conducted to assess the pulmonary and systemic responses in rats after intratracheal instillation of highly pure, well-dispersed, and well-characterized SWCNTs. Exposure to SWCNTs up to 2mg/kg did not produce mortality, changes in clinical signs, or body weights during the observation period. Dose-dependent changes were observed in the lung weight, BALF inflammatory cells, and biochemical parameters such as LDH value, protein content, IL-1β and IL-6 activity, and histopathology. In the 0.04 mg/kg SWCNT-exposed group, almost no changes were observed during the observation period. In the 0.2 mg/kg SWCNT-exposed group, pulmonary inflammatory responses were observed after instillation. In the 1 mg/kg and 2 mg/kg SWCNT-exposed group, acute lung inflammation and subsequent granuloma accompanied by increased lung weights were observed. Furthermore, the histopathological findings in the lungs of rats exposed to SWCNTs showed inflammatory responses related with the vital reaction to the foreign substance that was instilled intratracheally, and there were no fibrosis, atypical lesion, or tumor-related findings even at the highest dose (2 mg/kg) of SWCNT-exposed groups up to 6 months after instillation. For all groups, histopathological changes due to the instillation exposure of SWCNTs were observed only in the lungs and lung-associated lymph nodes and not in the other tissues examined (i.e. the liver, kidney, spleen, and cerebrum)
An Ultra-Compact X-Ray Free-Electron Laser
In the field of beam physics, two frontier topics have taken center stage due
to their potential to enable new approaches to discovery in a wide swath of
science. These areas are: advanced, high gradient acceleration techniques, and
x-ray free electron lasers (XFELs). Further, there is intense interest in the
marriage of these two fields, with the goal of producing a very compact XFEL.
In this context, recent advances in high gradient radio-frequency cryogenic
copper structure research have opened the door to the use of surface electric
fields between 250 and 500 MV/m. Such an approach is foreseen to enable a new
generation of photoinjectors with six-dimensional beam brightness beyond the
current state-of-the-art by well over an order of magnitude. This advance is an
essential ingredient enabling an ultra-compact XFEL (UC-XFEL). In addition, one
may accelerate these bright beams to GeV scale in less than 10 meters. Such an
injector, when combined with inverse free electron laser-based bunching
techniques can produce multi-kA beams with unprecedented beam quality,
quantified by ~50 nm-rad normalized emittances. These beams, when injected into
innovative, short-period (1-10 mm) undulators uniquely enable UC-XFELs having
footprints consistent with university-scale laboratories. We describe the
architecture and predicted performance of this novel light source, which
promises photon production per pulse of a few percent of existing XFEL sources.
We review implementation issues including collective beam effects, compact
x-ray optics systems, and other relevant technical challenges. To illustrate
the potential of such a light source to fundamentally change the current
paradigm of XFELs with their limited access, we examine possible applications
in biology, chemistry, materials, atomic physics, industry, and medicine which
may profit from this new model of performing XFEL science.Comment: 80 pages, 24 figure
Trapping virtual pores by crystal retro-engineering
Stable guest-free porous molecular crystals are uncommon. By contrast, organic molecular crystals with guest-occupied cavities are frequently observed, but these cavities tend to be unstable and collapse on removal of the guests—this feature has been referred to as ‘virtual porosity’. Here, we show how we have trapped the virtual porosity in an unstable low-density organic molecular crystal by introducing a second molecule that matches the size and shape of the unstable voids. We call this strategy ‘retro-engineering’ because it parallels organic retrosynthetic analysis, and it allows the metastable two-dimensional hexagonal pore structure in an organic solvate to be trapped in a binary cocrystal. Unlike the crystal with virtual porosity, the cocrystal material remains single crystalline and porous after removal of guests by heating
The Cyclic AMP Cascade Is Altered in the Fragile X Nervous System
Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3′, 5′-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling
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