Phloridzin derivatives inhibiting pro-inflammatory cytokine expression in human cystic fibrosis IB3-1 cells.

Cystic Fibrosis (CF) is the most diffuse autosomal recessive genetic disease affecting Caucasians. A persistent recruitment of neutrophils in the bronchi of CF patients contributes to exacerbate the airway tissue damage, suggesting that modulation of chemokine expression may be an important target for the patient's well being thus the identification of innovative anti-inflammatory drugs is considered a longterm goal to prevent progressive tissue deterioration. Phloridzin, isolated from Malus domestica by a selective molecular imprinting extraction, and its structural analogues, Phloridzin heptapropionate (F1) and Phloridzin tetrapropionate (F2), were initially investigated because of their ability to reduce IL-6 and IL-8 expression in human CF bronchial epithelial cells (IB3-1) stimulated with TNF-α. Release of these cytokines by CF cells was shown to be controlled by the Transcription Factor (TF) NF-kB. The results of the present investigation show that of all the derivatives tested, Phloridzin tetrapropionate (F2) is the most interesting and has greatest potential as it demonstrates inhibitory effects on the expression and production of different cytokines involved in CF inflammation processes, including RANTES, VEGF, GM-CSF, IL-12, G-CSF, MIP-1b, IL-17, IL-10 and IP-10, without any correlated anti-proliferative and pro-apoptotic effects.

Molecular dynamics simulation of the antimicrobial salivary peptide histatin-5 in water and in trifluoroethanol: a microscopic description of the water destructuring effect.

The results of 520 ps molecular dynamics simulation of histatin-5, a small peptide present in human saliva and possessing antimicrobial activity, dissolved in water and in 2,2,2-trifluoroethanol, are reported. The simulations indicate that histatin-5 is destabilized in water and begins to unfold after 250 ps, while in organic solvent it maintains a regular secondary structure throughout the trajectory. Analysis of the peptide-solvent hydrogen bonds indicates that 2,2,2-trifluoroethanol is a poorer proton acceptor than water. The fluorine atom of the alcohol is almost never engaged in a hydrogen bond and the organic solvent interacts mainly with the peptide through its hydroxyl group. For some residues analysis of the solvent residence time indicated longer values for 2,2,2-trifluoroethanol than for water. The most striking difference is related to the number of times the solvent enters and leaves the first coordination shell of the peptide. This value was more than one order of magnitude higher for water than for the alcohol, suggesting that this may be the main cause of alpha-helix destabilization perpetrated by water.

Self-perception of fitness and personality traits.

Our aim was to analyze how subjects perceive their own physical fitness. In Study 1 the 247 subjects assessed their own fitness, endurance, strength, flexibility, and body composition according to specific category scales. Analyses showed that self-perceived physical fitness was mainly related to perceived cardiovascular endurance. According to sex and age, strength, flexibility, and body composition could have a significant influence. The scores obtained on the five scales were highly correlated, suggesting they were overdetermined by a more general factor assimilated to physical self-worth. In Study 2 the 91 subjects completed the same five scales, the Spielberger State-Trait Anxiety Inventory, the Coopersmith Self-esteem Inventory, and the Bem Sex-role Inventory. Results confirmed the hierarchical model of Fox and Corbin (1989) and showed that physical self-worth is related to self-esteem, anxiety, and masculinity.