Nutraceutical Value of Citrus Flavanones and Their Implications in Cardiovascular Disease

Background- Cardiovascular diseases, including myocardial infarction, dyslipidaemia and coronary artery pathology, are a major cause of illness and death in Western countries. Therefore, identifying effective therapeutic approaches and their cellular signalling pathways is a challenging goal for medicine. In this regard, several epidemiological studies demonstrate a relationship between the intake of flavonoid-rich foods and the reduction of cardiovascular risk factors and mortality. In particular, flavonoids present in citrus fruits, such as oranges, bergamots, lemons and grapefruit (95% from flavanones), are emerging for their considerable nutraceutical value. Methods- In this review an examination of literature was performed while considering both epidemiological, clinical and pre-clinical evidence supporting the beneficial role of the flavanone class. We evaluated studies in which citrus fruit juices or single flavanone administration and cardiovascular risk factors were analysed; to identify these studies, an electronic search was conducted in PUBMED for papers fulfilling these criteria and written in English. Results- In addition to epidemiological evidence and clinical studies demonstrating that fruits in the Citrus genus significantly reduce the incidence of cardiovascular disease risk, pre-clinical investigations highlight cellular and subcellular targets that are responsible for these beneficial effects. There has been special attention on evaluating intracellular pathways involved in direct cardiovascular and cardiometabolic effects mediated by naringenin, hesperetin and eriodictyol or their glycosylated derivatives. Conclusions- Although some mechanisms of action remain unclear and bioavailability problems remain to be solved, the current evidence supports the use of a nutraceutical approach with citrus fruits to prevent and cure several aspects of cardiovascular disease

There is a short gamma-ray burst prompt phase at the beginning of each long one

We compare the prompt intrinsic spectral properties of a sample of short Gamma--ray Burst (GRB) with the first 0.3 seconds (rest frame) of long GRBs observed by Fermi/GBM. We find that short GRBs and the first part of long GRBs lie on the same E_p--E_iso correlation, that is parallel to the relation for the time averaged spectra of long GRBs. Moreover, they are indistinguishable in the E_p--L_iso plane. This suggests that the emission mechanism is the same for short and for the beginning of long events, and both short and long GRBs are very similar phenomena, occurring on different timescales. If the central engine of a long GRB would stop after ~0.3 * (1+z) seconds the resulting event would be spectrally indistinguishable from a short GRB.Comment: 14 pages, 6 figures, MNRAS accepte

A structure-based proposal for the catalytic mechanism of the bacterial acid phosphatase AphA belonging to the DDDD superfamily of phosphohydrolases

The Escherichia coli gene aphA codes for a periplasmic acid phosphatase called AphA, belonging to class B bacterial phosphatases, which is part of the DDDD superfamily of phosphohydrolases. After our first report about its crystal structure, we have started a series of crystallographic studies aimed at understanding of the catalytic mechanism of the enzyme. Here, we report three crystal structures of the AphA enzyme in complex with the hydrolysis products of nucleoside monophosphate substrates and a fourth with a proposed intermediate analogue that appears to be covalently bound to the enzyme. Comparison with the native enzyme structure and with the available X-ray structures of different phosphatases provides clues about the enzyme chemistry and allows us to propose a catalytic mechanism for AphA, and to discuss it with respect to the mechanism of other bacterial and human phosphatases. (c) 2005 Elsevier Ltd. All rights reserved

SARS-CoV-2 Mproinhibition by a zinc ion: structural features and hints for drug design

The first structure of the SARS-CoV-2 main protease in complex with an isolated zinc ion provides solid ground for the design of potent and selective metal-conjugated inhibitors

DBATE: database of alternative transcripts expression

The use of high-throughput RNA sequencing technology (RNA-seq) allows whole transcriptome analysis, providing an unbiased and unabridged view of alternative transcript expression. Coupling splicing variant-specific expression with its functional inference is still an open and difficult issue for which we created the DataBase of Alternative Transcripts Expression (DBATE), a web-based repository storing expression values and functional annotation of alternative splicing variants. We processed 13 large RNA-seq panels from human healthy tissues and in disease conditions, reporting expression levels and functional annotations gathered and integrated from different sources for each splicing variant, using a variant-specific annotation transfer pipeline. The possibility to perform complex queries by cross-referencing different functional annotations permits the retrieval of desired subsets of splicing variant expression values that can be visualized in several ways, from simple to more informative. DBATE is intended as a novel tool to help appreciate how, and possibly why, the transcriptome expression is shaped. DATABASE URL: http://bioinformatica.uniroma2.it/DBATE/

Changes in eggshell ultrastructure of Falco naumanni and Tyto alba exposed to pesticides and polychlorinated biphenyls (PCBs)

Changes in the quality of eggs of birds exposed to environmental contaminants have been described, but few reports concern eggshell ultrastructure. In this study, infertile or addled Lesser Kestrels (Falco naumanni) and Barn owls (Tyto alba) eggs were collected from the polluted area of Gela plain (Sicily) during 2007, and compared in terms of organophosphate and organochlorine pesticides, and PCBs levels, and eggshell ultrastructure as determined by scanning electron microscopy. Pesticide and PCB residues in eggs were determined by Gas chromatography/ mass spectrometry (GC/MS) [GC Agilent 7890A/MS Agilent 5975C (Agilent technologies) using a DB-5 capillary column in the selected ion monitoring mode]. The GC/MS analysis revealed that eggs contained measurable amounts of some pesticides and PCBs. There was a low detection of organophosphate pesticides while the most abundant organochlorine residues detected were p,p’ DDT, p,p’ DDE, and Hexachlorobenzene. While, the most abundant PCBs detected congeners were PCB 138, 153, 170, 180, and 187. Although the general structure of the eggshell layers was maintained, the results showed ultrastructural differences in mammillary and palisade eggshell layers between high level and low level contaminated eggs in Tyto alba. Furthermore, mammillary cores of the eggshell had an increased distance between themselves with respect to well organized structures present in uncontaminated egg. In this paper we verify the presence of environmental contaminants in the eggs and document structural changes in bird of prey eggshells. The data could suggest that some contaminants can contribute to reduced reproductive performance (infertile or addled egg) by structural changes in the eggshell. The alteration in morphological disposition of mammillary cores could also suggest an impairment of gas exchange

Direct Expression of Fluorinated Proteins in Human Cells for 19F In-Cell NMR Spectroscopy

: In-cell NMR spectroscopy is a powerful approach to study protein structure and function in the native cellular environment. It provides precious insights into the folding, maturation, interactions, and ligand binding of important pharmacological targets directly in human cells. However, its widespread application is hampered by the fact that soluble globular proteins often interact with large cellular components, causing severe line broadening in conventional heteronuclear NMR experiments. 19F NMR can overcome this issue, as fluorine atoms incorporated in proteins can be detected by simple background-free 1D NMR spectra. Here, we show that fluorinated amino acids can be easily incorporated in proteins expressed in human cells by employing a medium switch strategy. This straightforward approach allows the incorporation of different fluorinated amino acids in the protein of interest, reaching fluorination efficiencies up to 60%, as confirmed by mass spectrometry and X-ray crystallography. The versatility of the approach is shown by performing 19F in-cell NMR on several proteins, including those that would otherwise be invisible by 1H-15N in-cell NMR. We apply the approach to observe the interaction between an intracellular target, carbonic anhydrase 2, and its inhibitors, and to investigate how the formation of a complex between superoxide dismutase 1 and its chaperone CCS modulates the interaction of the chaperone subunit with the cellular environment