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MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and after renal transplantation
No full textAbstractChronic kidney disease (CKD) is associated with a multifactorial dysregulation of bone and vascular calcification and closely linked to increased cardiovascular mortality and concomitant bone disease. We aimed to investigate specific microRNA (miRNA) signatures in CKD patients to find indicators for vascular calcification and/or bone mineralization changes during CKD and after kidney transplantation (KT).A miRNA array was used to investigate serum miRNA profiles in CKD patients, then selected miRNAs were quantified in a validation cohort comprising 73 patients in CKD stages 3 to 5, 67 CKD patients after KT, and 36 healthy controls. A spectrum of biochemical parameters including markers for kidney function, inflammation, glucose, and mineral metabolism was determined.The relative expression of miR-223-3p and miR-93-5p was down-regulated in patients with CKD stage 4 and 5 compared to healthy controls. This down-regulation disappeared after kidney transplantation even when lower glomerular filtration rates (eGFR) persisted. MiR-223-3p and miR-93-5p were associated with interleukin-6 (IL-6) and eGFR levels, and by trend with interleukin-8 (IL-8), C-peptide, hematocrit, and parathyroid hormone (PTH).This study contributes new knowledge of serum miRNA expression profiles in CKD, potentially reflecting pathophysiological changes of bone and calcification pathways associated with inflammation, vascular calcification, mineral and glucose metabolism. Identified miRNA signatures can contribute to future risk markers or future therapeutic targets in bone and kidney disease
Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach
No full textAbstractAlzheimer's disease (AD) represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID) drugs, and genome wide association studies (GWAS) show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive.In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database) simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin). Gene expression signatures were derived for disease from both blood (n=344) and post-mortem brain (n=690), and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level.These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness
Search for heavy resonances decaying to a Z boson and a photon in pp collisions at s=13 TeV with the ATLAS detector
No full textAbstractThis Letter presents a search for new resonances with mass larger than 250 GeV, decaying to a Z boson and a photon. The dataset consists of an integrated luminosity of 3.2 fb−1 of pp collisions collected at s=13 TeV with the ATLAS detector at the Large Hadron Collider. The Z bosons are identified through their decays either to charged, light, lepton pairs (e+e−, μ+μ−) or to hadrons. The data are found to be consistent with the expected background in the whole mass range investigated and upper limits are set on the production cross section times decay branching ratio to Zγ of a narrow scalar boson with mass between 250 GeV and 2.75 TeV
Intrinsic character of Stokes matrices
No full textAbstractTwo germs of linear analytic differential systems xk+1Y′=A(x)Y with a non-resonant irregular singularity are analytically equivalent if and only if they have the same eigenvalues and equivalent collections of Stokes matrices. The Stokes matrices are the transition matrices between sectors on which the system is analytically equivalent to its formal normal form. Each sector contains exactly one separating ray for each pair of eigenvalues. A rotation in S allows supposing that R+ lies in the intersection of two sectors. Reordering of the coordinates of Y allows ordering the real parts of the eigenvalues, thus yielding triangular Stokes matrices. However, the choice of the rotation in x is not canonical. In this paper we establish how the collection of Stokes matrices depends on this rotation, and hence on a chosen order of the projection of the eigenvalues on a line through the origin
Accelerated expansion of the Universe without an inflaton and resolution of the initial singularity from Group Field Theory condensates
No full textAbstractWe study the expansion of the Universe using an effective Friedmann equation obtained from the dynamics of GFT (Group Field Theory) isotropic condensates. The evolution equations are classical, with quantum correction terms to the Friedmann equation given in the form of effective fluids coupled to the emergent classical background. The occurrence of a bounce, which resolves the initial spacetime singularity, is shown to be a general property of the model. A promising feature of this model is the occurrence of an era of accelerated expansion, without the need to introduce an inflaton field with an appropriately chosen potential. We discuss possible viability issues of this scenario as an alternative to inflation
Pulmonary vein isolation in absence and presence of mild to moderate mitral valve regurgitation in patients with paroxysmal AF: A sub group analysis
No full textIL-1β–Induced Protection of Keratinocytes against Staphylococcus aureus-Secreted Proteases Is Mediated by Human β-Defensin 2
No full textAtopic dermatitis (AD) is a common chronic inflammatory skin disease that results in significant morbidity. A hallmark of AD is disruption of the critical barrier function of upper epidermal layers, causatively linked to environmental stimuli, genetics, and infection, and a critical current target for the development of new therapeutic and prophylactic interventions. Staphylococcus aureus is an AD-associated pathogen producing virulence factors that induce skin barrier disruption in vivo and contribute to AD pathogenesis. We show, using immortalized and primary keratinocytes, that S. aureus protease SspA/V8 is the dominant secreted factor (in laboratory and AD clinical strains of S. aureus) inducing barrier integrity impairment and tight junction damage. V8-induced integrity damage was inhibited by an IL-1β–mediated mechanism, independent of effects on claudin-1. Induction of keratinocyte expression of the antimicrobial/host defense peptide human β-defensin 2 (hBD2) was found to be the mechanism underpinning this protective effect. Endogenous hBD2 expression was required and sufficient for protection against V8 protease-mediated integrity damage, and exogenous application of hBD2 was protective. This modulatory property of hBD2, unrelated to antibacterial effects, gives new significance to the defective induction of hBD2 in the barrier-defective skin lesions of AD and indicates therapeutic potential
Tissue factor pathway inhibitor-2 induced hepatocellular carcinoma cell differentiation
No full textAbstractTo investigate the effect of over-expression of tissue factor pathway inhibitor-2 (TFPI-2) on the differentiation of hepatocellular carcinoma (HCC) cells (Hep3B and HepG2). The TFPI-2 recombinant adenovirus (pAd-TFPI-2) was constructed using the pAdeasy-1 vector system. Transfected by pAd-TFPI-2, the cell proliferation of HCC cells was evaluated by CCK-8 assay, flow cytometry was used to detect cell apoptosis and CD133 expression. Real-time PCR and Western blot were used to detect the expression levels of markers of hepatocellular cancer stem cells (CSC) and hepatocytes. The over-expression of TFPI-2 significantly suppressed cell proliferation, induced apoptosis, and dramatically decreased the percentage of CD133 cells, which was considered as CSC in HCC. Real-time PCR and Western blot showed that the expression of markers of CSC in Hep3BcellsandHepG2 cells infected with pAd-TFPI-2 was markedly lower than those of the control group (P<0.05), while the expression of markers of hepatocytes was significantly increased (P<0.05). Hence, TFPI-2 could induce the differentiation of hepatocellular carcinoma cells into hepatocytes, and is expected to serve as a novel way for the treatment of HCC
Biomineralization of a calcifying ureolytic bacterium Microbacterium sp. GM-1
No full textAbstractBackgroundBiomineralization is a significant process performed by living organisms in which minerals are produced through the hardening of biological tissues. Herein, we focus on calcium carbonate precipitation, as part of biomineralization, to be used in applications for environmental protection, material technology, and other fields. A strain GM-1, Microbacterium sp. GM-1, isolated from active sludge, was investigated for its ability to produce urease and induce calcium carbonate precipitation in a metabolic process.ResultsIt was discovered that Microbacterium sp. GM-1 resisted high concentrations of urea up to 60g/L. In order to optimize the calcification process of Microbacterium sp. GM-1, the concentrations of Ni2+ and urea, pH value, and culture time were analyzed through orthogonal tests. The favored calcite precipitation culture conditions were as follows: the concentration of Ni2+ and urea were 50μM and 60g/L, respectively, pH of 10, and culture time of 96h. Using X-ray diffraction analysis, the calcium carbonate polymorphs produced by Microbacterium sp. GM-1 were proven to be mainly calcite.ConclusionsThe results of this research provide evidence that Microbacterium sp. GM-1 can biologically induce calcification and suggest that strain GM-1 may play a potential role in the synthesis of new biominerals and in bioremediation or biorecovery