Comparison of 24-h volume and creatinine-corrected total urinary polyphenol as a biomarker of total dietary polyphenols in the Invecchiare InCHIANTI study

Polyphenols have beneficial effects on several chronic diseases but assessing polyphenols intake from self-reported dietary questionnaires tends to be inaccurate and not very reliable. A promising alternative is to use urinary excretion of polyphenols as a proxy measure of intake. The best method to assess urinary excretion is to collect 24-h urine. However, since collecting 24-h urine method is expensive, time consuming and may be difficult to implement in large population-based studies, measures obtained from spot urine normalized by creatinine are commonly used. The purpose of the study was to evaluate the correlation between polyphenols dietary intake and total urinary polyphenol excretion (TPE), expressed by both 24-h volume and urinary creatinine normalization in 928 participants from the InCHIANTI study. Dietary intake data were collected using a validated food frequency questionnaire. Urinary TPE was analyzed by Folin-Ciocalteau assay. Both urinary TPE expression models were statistically correlated (r=0.580), and the partial correlation coefficient improved (pr=0.722) after adjusting for the variables that modify the urinary creatinine excretion (i.e. gender, age, BMI, physical activity and renal function). In crude models, polyphenol intake was associated with TPE corrected by 24-h volume (r=0.211; P<0.001), but not with creatinine normalization (r=0.014; P=0.692). However, urinary TPE expressed by creatinine correction was significantly correlated with dietary polyphenols after adjusting for covariates (pr=0.113; P=0.002). We conclude that urinary TPE expressed by 24-h volume is a better biomarker of polyphenol dietary intake than by urinary creatinine normalization. After covariate adjustment, both can be used for studying the relationships between polyphenol intake and health in large-scale epidemiological studies.     

Multivalent calixarene-based C-fucosyl derivative: a new Pseudomonas aeruginosa biofilm inhibitor

The first example of multivalent conjugate in which four α-l-C-fucosyl units are clustered by means of a calix[4]arene platform was designed as a new potential Pseudomonas aeruginosa biofilm inhibitor. The anti-biofilm activity of the synthesized compound (6) against PAO1 strain was assayed and it was found to be dose-dependent. The presence of the fucose cluster improves the biofilm inhibitor efficiency as proven by the lower inhibitor activity of the analogous glycyl-calix[4]arene derivative (3) lacking in the fucose moieties.     

Vibrational density of states of hydration water at biomolecular sites: hydrophobicity promotes low density amorphous ice behavior

Inelastic neutron scattering experiments and molecular dynamics simulations have been used to investigate the low frequency modes, in the region between 0 and 100 meV, of hydration water in selected hydrophilic and hydrophobic biomolecules. The results show changes in the plasticity of the hydrogen-bond network of hydration water molecules depending on the biomolecular site. At 200 K, the measured low frequency density of states of hydration water molecules of hydrophilic peptides is remarkably similar to that of high density amorphous ice, whereas, for hydrophobic biomolecules, it is comparable to that of low density amorphous ice behavior. In both hydrophilic and hydrophobic biomolecules, the high frequency modes show a blue shift of the libration mode as compared to the room temperature data. These results can be related to the density of water molecules around the biological interface, suggesting that the apparent local density of water is larger in a hydrophilic environment.     

Effects of lipoic acid, caffeic acid and a synthesized lipoyl-caffeic conjugate on human hepatoma cell lines

Hepatocellular carcinoma (HCC) is among the most aggressive and fatal cancers. Its treatment with conventional chemotherapeutic agents is inefficient, due to several side effects linked to impaired organ function typical of liver diseases. Consequently, there exists a decisive requirement to explore possible alternative chemopreventive and therapeutic strategies. The use of dietary antioxidants and micronutrients has been proposed for HCC successful management. The aim of this work was to test in vitro the effects of lipoic acid, caffeic acid and a new synthesized lipoyl-caffeic conjugate on human hepatoma cell lines in order to assess their effect on tumor cell growth. The results of cytotoxicity assays at different times showed that the cell viability was directly proportional to the molecule concentrations and incubation times. Moreover, to evaluate the pro- or anti-inflammatory effects of these molecules, the cytokine concentrations were evaluated in treated and untreated cellular supernatants. The obtained cytokine pattern showed that, at the increasing of three molecules concentrations, three pro-inflammatory cytokines such as IL-1β, IL-8 and TNF-α decreased whereas the anti-inflammatory cytokine such as IL-10 increased.     

On the Stability of a SEIR Reaction Diffusion Model for Infections Under Neumann Boundary Conditions

This paper deals with a reaction-diffusion SEIR model for infections under homogeneous Neumann boundary conditions. The longtime behaviour of the solutions is analyzed and, in particular, absorbing sets in the phase space are determined. By using a peculiar Lyapunov function, the nonlinear asymptotic stability of endemic equilibrium is investigated.     

New Open‐Chain and Cyclic Tetrapeptides,Consisting of α‐, β2‐, and β3‐Amino‐Acid Residues,as Somatostatin Mimics – A Survey

Cyclo‐β‐tetrapeptides are known to adopt a conformation with an intramolecular transannular hydrogen bond in solution. Analysis of this structure reveals that incorporation of a β²‐amino‐acid residue should lead to mimics of ‘α‐peptidic β‐turns’ (cf. A, B, C ). It is also known that short‐chain mixed β/α‐peptides with appropriate side chains can be used to mimic interactions between α‐peptidic hairpin turns and G protein‐coupled receptors. Based on these facts, we have now prepared a number of cyclic and open‐chain tetrapeptides, 7 – 20 , consisting of α‐, β²‐, and β³‐amino‐acid residues, which bear the side chains of Trp and Lys, and possess backbone configurations such that they should be capable of mimicking somatostatin in its affinity for the human SRIF receptors (hsst_1–5). All peptides were prepared by solid‐phase coupling by the Fmoc strategy. For the cyclic peptides, the three‐dimensional orthogonal methodology (Scheme 3) was employed with best success. The new compounds were characterized by high‐resolution mass spectrometry, NMR and CD spectroscopy, and, in five cases, by a full NMR‐solution‐structure determination (in MeOH or H₂O; Fig. 4). The affinities of the new compounds for the receptors hsst_1–5 were determined by competition with [¹²⁵I]LTT‐SRIF₂₈ or [¹²⁵I] [Tyr¹⁰]‐CST₁₄. In Table 1, the data are listed, together with corresponding values of all β‐ and γ‐peptidic somatostatin/Sandostatin^® mimics measured previously by our groups. Submicromolar affinities have been achieved for most of the human SRIF receptors hsst_1–5. Especially high, specific binding affinities for receptor hsst₄ (which is highly expressed in lung and brain tissue, although still of unknown function!) was observed with some of the β‐peptidic mimics. In view of the fact that numerous peptide‐activated G protein‐coupled receptors (GPCRs) recognize ligands with turn structure (Table 2), the results reported herein are relevant far beyond the realm of somatostatin: many other peptide GPCRs should be ‘reached’ with β‐ and γ‐peptidic mimics as well, and these compounds are proteolytically and metabolically stable, and do not need to be cell‐penetrating for this purpose (Fig. 5).     

Autonomous Non-Equilibrium Self-Assembly and Molecular Movements Powered by Electrical Energy**

The ability to exploit energy autonomously is one of the hallmarks of life. Mastering such processes in artificial nanosystems can open technological opportunities. In the last decades, light- and chemically driven autonomous systems have been developed in relation to conformational motion and self-assembly, mostly in relation to molecular motors. In contrast, despite electrical energy being an attractive energy source to power nanosystems, its autonomous harnessing has received little attention. Herein we consider an operation mode that allows the autonomous exploitation of electrical energy by a self-assembling system. Threading and dethreading motions of a pseudorotaxane take place autonomously in solution, powered by the current flowing between the electrodes of a scanning electrochemical microscope. The underlying autonomous energy ratchet mechanism drives the self-assembly steps away from equilibrium with a higher energy efficiency compared to other autonomous systems. The strategy is general and might be extended to other redox-driven systems.     

Isolation and Characterization of Monomeric Human RAD51: A Novel Tool for Investigating Homologous Recombination in Cancer

DNA repair protein RAD51 is a key player in the homologous recombination pathway. Upon DNA damage, RAD51 is transported into the nucleus by BRCA2, where it can repair DNA double-strand breaks. Due to the structural complexity and dynamics, researchers have not yet clarified the mechanistic details of every step of RAD51 recruitment and DNA repair. RAD51 possesses an intrinsic tendency to form oligomeric structures, which make it challenging to conduct biochemical and biophysical investigations. Here, for the first time, we report on the isolation and characterization of a human monomeric RAD51 recombinant form, obtained through a double mutation, which preserves the protein's integrity and functionality. We investigated different buffers to identify the most suitable condition needed to definitively stabilize the monomer. The monomer of human RAD51 provides the community with a unique biological tool for investigating RAD51-mediated homologous recombination, and paves the way for more reliable structural, mechanistic, and drug discovery studies.