Divergent effects of quercetin conjugates on angiogenesis

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3′-sulphate (Q3′S) and quercetin-3-glucuronide (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3′S per se promoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3′S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G andQ3′S are the two major conjugates in plasma, but their ratio is dependenton several factors, so thatinhibition or activation of angiogenesis could be subtly shifted as a result of metabolismin viv

The Gaia-ESO survey: 3D NLTE abundances in the open cluster NGC 2420 suggest atomic diffusion and turbulent mixing at the origin of chemical abundance variations

Atomic diffusion and mixing processes in stellar interiors influence the structure and the surface composition of stars. Some of these processes cannot yet be modelled from the first principles. This limits their applicability in stellar models used for studies of stellar populations and Galactic evolution. Our main goal is to put constrains on the stellar structure and evolution models using new refined measurements of chemical composition in stars of Galactic open cluster. We use medium-resolution, 19 200 <= R <= 21 500, optical spectra of the stars in the open cluster NGC 2420 obtained within the Gaia-ESO survey. The sample covers all evolutionary stages from the main-sequence to red giant branch. Stellar parameters are derived using a combined Bayesian analysis of spectra, 2MASS photometry, and astrometric data from Gaia DR2. The abundances of Mg, Ca, Fe, and Li are determined from non-local thermodynamic equilibrium (NLTE) synthetic spectra, computed using one-dimensional (1D) and averaged three-dimensional (3D) model atmospheres. We compare our results with a grid of Code d'Evolution Stellaire Adaptatif et Modulaire (CESTAM) stellar evolution models, which include atomic diffusion, turbulent and rotational mixing. We find prominent evolutionary trends in the abundances of Fe, Ca, Mg, and Li with the mass of the stars in the cluster. Fe, Mg, and Ca show a depletion at the cluster turn-off, but the abundances gradually increase and flatten near the base of the RGB. The abundance trend for Li displays a signature of rotational mixing on the main-sequence and abrupt depletion on the subgiant branch, which is caused by advection of Li-poor material to the surface. The analysis of abundances combined with the CESTAM model predictions allows us to place limits on the parameter space of the models and to constrain the zone in the stellar interior where turbulent mixing takes place.Comment: accepted for publication in A&

Anti-Inflammatory Effect of the Natural H2S-Donor Erucin in Vascular Endothelium

Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling need. In this study, we tested erucin, the natural isothiocyanate H2S-donor derived from Eruca sativa Mill. (Brassicaceae), in an in vivo mouse model of lipopolysaccharide (LPS)-induced peritonitis, where it significantly reduced the amount of emigrated CD11b positive neutrophils. We then evaluated the anti-inflammatory effects of erucin in LPS-challenged human umbilical vein endothelial cells (HUVECs). The pre-incubation of erucin, before LPS treatment (1, 6, 24 h), significantly preserved cell viability and prevented the increase of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-alpha) levels. Moreover, erucin downregulated endothelial hyperpermeability and reduced the loss of vascular endothelial (VE)-Cadherin levels. In addition, erucin decreased vascular cell adhesion molecule 1 (VCAM-1), cyclooxygenase-2 (COX-2) and microsomal prostaglandin E-synthase 1 (mPGES-1) expression. Of note, erucin induced eNOS phosphorylation and counteracted LPS-mediated NF-kappa B nuclear translocation, an effect that was partially abolished in the presence of the eNOS inhibitor L-NAME. Therefore, erucin can control endothelial function through biochemical and genomic positive effects against VI

Gaia-ESO Survey: INTRIGOSS - A New Library of High-resolution Synthetic Spectra

We present a high resolution synthetic spectral library, INTRIGOSS, designed for studying FGK stars. The library is based on atmosphere models computed with specified individual element abundances via ATLAS12 code. Normalized SPectra (NSP) and surface Flux SPectra (FSP), in the 4830-5400 A, wavelength range, were computed with the SPECTRUM code. INTRIGOSS uses the solar composition by Grevesse et al. 2007 and four [alpha/Fe] abundance ratios and consists of 15,232 spectra. The synthetic spectra are computed with astrophysical gf-values derived by comparing synthetic predictions with a very high SNR solar spectrum and the UVES-U580 spectra of five cool giants. The validity of the NSPs is assessed by using the UVES-U580 spectra of 2212 stars observed in the framework of the Gaia-ESO Survey and characterized by homogeneous and accurate atmospheric parameter values and by detailed chemical compositions. The greater accuracy of NSPs with respect to spectra from the AMBRE, GES_Grid, PHOENIX, C14, and B17 synthetic spectral libraries is demonstrated by evaluating the consistency of the predictions of the different libraries for the UVES-U580 sample stars. The validity of the FSPs is checked by comparing their prediction with both observed spectral energy distribution and spectral indices. The comparison of FSPs with SEDs derived from ELODIE, INDO--U.S., and MILES libraries indicates that the former reproduce the observed flux distributions within a few percent and without any systematic trend. The good agreement between observational and synthetic Lick/SDSS indices shows that the predicted blanketing of FSPs well reproduces the observed one, thus confirming the reliability of INTRIGOSS FSPs

VizieR Online Data Catalog: GES: pre-main-sequence clusters [Fe/H] (Spina+, 2017)

Stellar parameters, equivalent widths of the lithium line at 6707.8Å and gamma indexes of the cluster members. Values from the Gaia-ESO Survey iDR4 catalogue

VizieR Online Data Catalog: Complete line list and solar values (Baratella+, 2020)

Line list used in this study (table2.dat), complete of the atomic data, references of the log(gf) values adopted and with equivalent width and abundances measured in the Sun. (1 data file)

Influence of Circulating Endothelin-1 and Asymmetric Dimethylarginine on Whole Brain Circulation Time in Multiple Sclerosis

Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay. Lesion load (LL) and brain volume (BV) were obtained by magnetic resonance imaging. Cerebral circulation time was correlated to ET1, ADMA, LL, BV, disease duration (DD), and Expanded Disability Status Scale (EDSS). In MS, both ET1 and ADMA were significantly higher than C (P < .0001); CCT was approximately 2 times lower than C (P < .0001) and significantly slower in SP than in RR-MS (P = .0215). Cerebral circulation time significantly correlated with ET1 in SP-MS (r = 0.38), whereas in RR-MS CCT significantly correlated with DD (r = 0.75). The LL, BV, and EDSS did not correlate with CCT. Endothelin-1 significantly influences CCT delay in SP-MS. Diversely, CCT in RR-MS is independent of ET1 and correlates significantly with DD. We conclude that in RR-MS, DD responds to neurovascular damage accumulation. It is supposed that high ET1 and ADMA levels stem from a protective response to early insults, aimed at opposing nitric oxide overproduction, whereas persistent pathological ET1 and ADMA levels translate into detrimental long-term effects, due to increased brain micro-vessel resistance

Divergent effects of quercetin conjugates on angiogenesis.

The present study reports the activities of quercetin and its main circulating conjugates in man (quercetin-3'-sulphate (Q3'S) and quercetin-3-glucuronide (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor (VEGF) and examines the effects of these molecules on cultured endothelial cells. We found opposing effects of quercetin and its metabolites on angiogenesis. While quercetin and Q3G inhibited VEGF-induced endothelial cell functions and angiogenesis, Q3'S per se promoted endothelial cell proliferation and angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by VEGF. The activation of endothelial cells by Q3'S was associated to stimulation of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol-3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for ERK1/2 phosphorylation. These data indicate that the effects of circulating quercetin conjugates on angiogenesis are different depending on the nature of the conjugate. Q3G and Q3'S are the two major conjugates in plasma, but their ratio is dependent on several factors, so that inhibition or activation of angiogenesis could be subtly shifted as a result of metabolism in vivo