455 research outputs found
Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts
Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc
Estrogen-receptor-positive breast cancer in postmenopausal women: The role of body composition and physical exercise
Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer-related death. To date, it is still a challenge to estimate the magnitude of the clinical impact of physical activity (PA) on those parameters producing significative changes in future BC risk and disease progression. However, studies conducted in recent years highlight the role of PA not only as a protective factor for the development of ER+ breast cancer but, more generally, as a useful tool in the management of BC treatment as an adjuvant to traditional therapies. In this review, we focused our attention on data obtained from human studies analyzing, at each level of disease prevention (i.e., primary, secondary, tertiary and quaternary), the positive impact of PA/exercise in ER+ BC, a subtype representing approximately 70% of all BC diagnoses. Moreover, given the importance of estrogen receptors and body composition (i.e., adipose tissue) in this subtype of BC, an overview of their role will also be made throughout this review
Internal alignment and position resolution of the silicon tracker of DAMPE determined with orbit data
The DArk Matter Particle Explorer (DAMPE) is a space-borne particle detector
designed to probe electrons and gamma-rays in the few GeV to 10 TeV energy
range, as well as cosmic-ray proton and nuclei components between 10 GeV and
100 TeV. The silicon-tungsten tracker-converter is a crucial component of
DAMPE. It allows the direction of incoming photons converting into
electron-positron pairs to be estimated, and the trajectory and charge (Z) of
cosmic-ray particles to be identified. It consists of 768 silicon micro-strip
sensors assembled in 6 double layers with a total active area of 6.6 m.
Silicon planes are interleaved with three layers of tungsten plates, resulting
in about one radiation length of material in the tracker. Internal alignment
parameters of the tracker have been determined on orbit, with non-showering
protons and helium nuclei. We describe the alignment procedure and present the
position resolution and alignment stability measurements
Investigating bifidobacteria and human milk oligosaccharide composition of lactating mothers
Human milk is known to carry its own microbiota, of which the precise origin remains obscure. Breastfeeding allows mother-to-baby transmission of microorganisms as well as the transfer of many other milk components, such as human milk oligosaccharides (HMOs), which act as metabolizable substrates for particular bacteria, such as bifidobacteria, residing in infant intestinal tract. In the current study, we report the HMO composition of 249 human milk samples, in 163 of which we quantified the abundance of members of the Bifidobacterium genus using a combination of metagenomic and flow cytometric approaches. Metagenomic data allowed us to identify four clusters dominated by Bifidobacterium adolescentis and Bifidobacterium pseudolongum, Bifidobacterium crudilactis or Bifidobacterium dentium, as well as a cluster represented by a heterogeneous mix of bifidobacterial species such as Bifidobacterium breve and Bifidobacterium longum. Furthermore, in vitro growth assays on HMOs coupled with in silico glycobiome analyses allowed us to elucidate that members of the Bifidobacterium bifidum and B. breve species exhibit the greatest ability to degrade and grow on HMOs. Altogether, these findings indicate that the bifidobacterial component of the human milk microbiota is not strictly correlated with their ability to metabolize HMOs
Isotopic Composition of Light Nuclei in Cosmic Rays: Results from AMS-01
The variety of isotopes in cosmic rays allows us to study different aspects
of the processes that cosmic rays undergo between the time they are produced
and the time of their arrival in the heliosphere. In this paper we present
measurements of the isotopic ratios 2H/4He, 3He/4He, 6Li/7Li, 7Be/(9Be+10Be)
and 10B/11B in the range 0.2-1.4 GeV of kinetic energy per nucleon. The
measurements are based on the data collected by the Alpha Magnetic
Spectrometer, AMS-01, during the STS-91 flight in 1998 June.Comment: To appear in ApJ. 12 pages, 11 figures, 6 table
The DArk Matter Particle Explorer mission
The DArk Matter Particle Explorer (DAMPE), one of the four scientific space
science missions within the framework of the Strategic Pioneer Program on Space
Science of the Chinese Academy of Sciences, is a general purpose high energy
cosmic-ray and gamma-ray observatory, which was successfully launched on
December 17th, 2015 from the Jiuquan Satellite Launch Center. The DAMPE
scientific objectives include the study of galactic cosmic rays up to
TeV and hundreds of TeV for electrons/gammas and nuclei respectively, and the
search for dark matter signatures in their spectra. In this paper we illustrate
the layout of the DAMPE instrument, and discuss the results of beam tests and
calibrations performed on ground. Finally we present the expected performance
in space and give an overview of the mission key scientific goals.Comment: 45 pages, including 29 figures and 6 tables. Published in Astropart.
Phy
DNA Aptamers against the Lup an 1 Food Allergen
Using in vitro selection, high affinity DNA aptamers to the food allergen Lup an 1, ß-conglutin, were selected from a pool of DNA, 93 bases in length, containing a randomised sequence of 49 bases. ß-conglutin was purified from lupin flour and chemically crosslinked to carboxylated magnetic beads. Peptide mass fingerprinting was used to confirm the presence of the ß-conglutin. Single stranded DNA was generated from the randomised pool using T7 Gene 6 Exonuclease and was subsequently incubated with the magnetic beads and the captured DNA was released and amplified prior to a further round of Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Evolution was monitored using enzyme linked oligonucleotide assay and surface plasmon resonance. Once a plateau in evolution was reached, the isolated DNA sequences were cloned and sequenced. The consensus motif was identified via alignment of the sequences and the affinities of these sequences for immobilised ß-conglutin were determined using surface plasmon resonance. The selected aptamer was demonstrated to be highly specific, showing no cross-reactivity with other flour ingredients or with other conglutin fractions of lupin. The secondary structures of the selected aptamers were predicted using m-fold. Finally, the functionality of the selected aptamers was demonstrated using a competitive assay for the quantitative detection of ß-conglutin. . Future work will focus on structure elucidation and truncation of the selected sequences to generate a smaller aptamer for application to the analysis of the Lup an 1 allergen in foodstuffs
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