Microsomal prostaglandin E(2) synthase (mPGES)-1 catalyzes the transformation of PGH(2) to PGE(2) that is involved in several pathologies like fever, pain, and inflammatory disorders. To identify novel mPGES-1 inhibitors, we used in silico screening to rapidly direct the synthesis, based on the copper-catalyzed 3 + 2 Huisgen's reaction (click chemistry), of potential inhibitors. We designed 26 new triazole-based compounds in accordance with the pocket binding requirements of human mPGES-1. Docking results, in agreement with ligand efficiency values, suggested the synthesis of 15 compounds that at least in theory were shown to be more efficient in inhibiting mPGES-1. Biological evaluation of these selected compounds has disclosed three new potential anti-inflammatory drugs: (I) compound 4 displaying selectivity for mPGES-1 with an IC(50) value of 3.2 μM, (II) compound 20 that dually inhibits 5-lipoxygenase and mPGES-1, and (III) compound 7 apparently acting as 5-lipoxygenase-activating protein inhibitor (IC(50) = 0.4 μM).
Objective: The aim of the study is to evaluate the effect of moderate Sicilian red wine consumption on cardiovascular risk factors and, in particular, on some inflammatory biomarkers. Methods: A total of 48 subjects of both sexes who were nondrinkers or rare drinkers of moderate red wine were selected and randomly subdivided into two groups assigned to receive with a crossover design a Sicilian red wine (Nero d'Avola or Etna Torrepalino) during meals: Group A (n ¼ 24), in whom the diet was supplemented for 4 weeks with 250 ml/day of red wine, followed by 4 weeks when they returned to their usual wine intake; and Group B (n ¼ 24), in whom the usual wine intake was maintained for 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml/day of red wine. The following were values measured in all tests: blood glucose, total and HDL-cholesterol and triglycerides, LDL-cholesterol, LDL/HDL ratio, apolipoproteins A1 and B, Lp(a), plasma C-reactive protein, TGFb1, D-Dimer, Factor VII , PAI Ag, t-PA Ag, fibrinogen, oxidized LDL Ab, total plasma antioxidant capacity. Results: At the end of the red wine intake period, LDL/HDL, fibrinogen, factor VII, plasma C-reactive protein and oxidized LDL Ab were significantly decreased, while HDL-C, Apo A1,TGFb1, t-PA, PAI and total plasma antioxidant capacity were significantly increased. Conclusions: Our results show a positive effect of two Sicilian red wines on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet.
We present results of three wide-band directed searches for continuous gravitational waves from 15 young supernova remnants in the first half of the third Advanced LIGO and Virgo observing run. We use three search pipelines with distinct signal models and methods of identifying noise artifacts. Without ephemerides of these sources, the searches are conducted over a fRequency band spanning from 10 to 2 kHz. We find no evidence of continuous gravitational radiation from these sources. We set upper limits on the intrinsic signal strain at 95% confidence level in sample subbands, estimate the sensitivity in the full band, and derive the corresponding constraints on the fiducial neutron star ellipticity and r-mode amplitude. The best 95% confidence constraints placed on the signal strain are 7.7 × 10 −26 and 7.8 × 10 −26 near 200 Hz for the supernova remnants G39.2-0.3 and G65.7+1.2, respectively. The most stringent constraints on the ellipticity and r-mode amplitude reach 10 −7 and 10 −5 , respectively, at frequencies above ∼400 Hz for the closest supernova remnant G266.2-1.2/Vela Jr.
We search for signatures of gravitational lensing in the gravitational-wave signals from compact binary coalescences detected by Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) and Advanced Virgo during O3a, the first half of their third observing run. We study: (1) the expected rate of lensing at current detector sensitivity and the implications of a non-observation of strong lensing or a stochastic gravitational-wave background on the merger-rate density at high redshift; (2) how the interpretation of individual high-mass events would change if they were found to be lensed; (3) the possibility of multiple images due to strong lensing by galaxies or galaxy clusters; and (4) possible wave-optics effects due to point-mass microlenses. Several pairs of signals in the multiple-image analysis show similar parameters and, in this sense, are nominally consistent with the strong lensing hypothesis. However, taking into account population priors, selection effects, and the prior odds against lensing, these events do not provide sufficient evidence for lensing. Overall, we find no compelling evidence for lensing in the observed gravitational-wave signals from any of these analyses.
The three advanced Virgo and LIGO gravitational wave detectors participated to the third observing run (O3) between 1 April 2019 15:00 UTC and 27 March 2020 17:00 UTC, leading to several gravitational wave detections per month. This paper describes the advanced Virgo detector calibration and the reconstruction of the detector strain h(t) during O3, as well as the estimation of the associated uncertainties. For the first time, the photon calibration technique as been used as reference for Virgo calibration, which allowed to cross-calibrate the strain amplitude of the Virgo and LIGO detectors. The previous reference, so-called free swinging Michelson technique, has still been used but as an independent cross-check. h(t) reconstruction and noise subtraction were processed online, with good enough quality to prevent the need for offline reprocessing, except for the two last weeks of September 2019. The uncertainties for the reconstructed h(t) strain, estimated in this paper in a 20–2000 Hz frequency band, are frequency independent: 5% in amplitude, 35 mrad in phase and 10 μs in timing, with the exception of larger uncertainties around 50 Hz.
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