Dual Effect of Prussian Blue Nanoparticles on Aß40 Aggregation: ß-Sheet Fibril Reduction and Copper Dyshomeostasis Regulation.

Alzheimer's disease (AD), affecting almost 50 million individuals worldwide, is currently the first cause of dementia. Despite the tremendous research efforts in the last decade, only four supportive or palliative drugs, namely, acetylcholinesterase (AChE) inhibitors donepezil, galantamine, and rivastigmine and the glutamate NMDA receptor antagonist memantine, are currently available. New therapeutic strategies are becoming prominent, such as the direct inhibition of amyloid formation or the regulation of metal homeostasis. In the present report, the potential use of Prussian blue (PB), a drug that is in the World Health Organization Model List of Essential Medicines, in AD treatment is demonstrated. Both in vitro and in cellulo studies indeed suggest that PB nanoparticles (PBNPs) are capable of reducing the formation of typical amyloid-ß fibers (detected by thioflavin T fluorescence) and restoring the usual amyloid fibrillation pathway via chelation/sequestration of copper, which is found in high concentrations in senile plaques.

Dual Behavior of Long-Chain Fatty Acids and Their Cyclooxygenase/Lipoxygenase Metabolites on Human Intestinal Caco-2 Cell Growth.

Etiology of colorectal cancer (CRC) is related, at least in part, with nutritional profile and epidemiological data indicating a key role of dietary fat on CRC pathogenesis. Moreover, inflammation and eicosanoids produced from arachidonic acid might have a pivotal role in CRC development. However, the effect of specific fatty acids (FAs) on intestinal epithelial cell growth is not completely studied now. By this reason, the aim of this work is to unravel the effect of different saturated and unsaturated long-chain fatty acids (LCFA) and some LCFA metabolites on CRC cell line growth and their possible mechanisms of action. Our results demonstrated that oleic acid is a potent mitogenic factor to Caco-2 cells, at least in part, through 10-hydroxy-8-octadecenoic synthesized by lipoxigenase pathway, whereas polyunsaturated FAs such as eicosapentaenoic (EPA) acid has a dual behavior effect depending on its concentration. A high concentration, EPA induced apoptosis through intrinsic pathway, whereas at low concentration induced cell proliferation that could be related to the synthesis of eicosanoids such as prostaglandin E3 and 12-hydroxyeicosapentaenoic acid and the subsequent induction of mitogenic cell signaling pathways (ERK 1/2, CREB, p38α). Thus, this study contributes to understand the complicated relationship between fat ingest and CRC.

Combined in Vitro Cell-Based/in Silico Screening of Naturally Occurring Flavonoids and Phenolic Compounds as Potential Anti-Alzheimer Drugs.

Alzheimer's disease (AD) is the main cause of dementia in people over 65 years. One of the major culprits in AD is the self-aggregation of amyloid-ß peptide (Aß), which has stimulated the search for small molecules able to inhibit Aß aggregation. In this context, we recently reported a simple, but effective in vitro cell-based assay to evaluate the potential antiaggregation activity of putative Aß aggregation inhibitors. In this work this assay was used together with docking and molecular dynamics simulations to analyze the anti-Aß aggregation activity of several naturally occurring flavonoids and phenolic compounds. The results showed that rosmarinic acid, melatonin, and o-vanillin displayed zero or low inhibitory capacity, curcumin was found to have an intermediate inhibitory potency, and apigenin and quercetin showed potent antiaggregation activity. Finally, the suitability of the combined in vitro cell-based/in silico approach to distinguish between active and inactive compounds was further assessed for an additional set of flavonols and dihydroflavonols.

Effects of overlapping GB virus C/hepatitis G virus synthetic peptides on biomembrane models.

The present study was undertaken to examine the physicochemical properties of three overlapping peptides belonging to the E2 envelope protein of Hepatitis G virus (GBV-C/HGV) and its interaction with phospholipid biomembrane models using biophysical techniques. We describe our findings concerning the surface activity and the interaction of the peptides with monolayers and liposomes composed of the zwitterionic phospholipids dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine (DMPC) and a mixture of DMPC with the anionic phospholipid dimyristoylphosphatidylglycerol. The results inform about the effect of the chain length on their interaction with biomembrane models. The longest chain peptide interacts in a higher extent with all the phospholipid studied as a result of a combination of hydrophobic and electrostatic forces.

Interaction of E2 and NS3 synthetic peptides of GB virus C/hepatitis G virus with model lipid membranes.

The membrane-interacting properties of two potential epitopes of the GB virus C/Hepatitis G virus, located respectively at the regions (99-118) of the E2 structural protein and (440-460) of the NS3 non-structural protein were studied. Changes in the intrinsic fluorescence of Trp and Tyr residues after the addition of DPPC-LUV revealed that the peptide-membrane interaction was optimal above the gel-liquid crystalline transition temperature of the lipid. Differential scanning calorimetry studies showed that the E2 peptide incorporated into lipid bilayers perturbs the packing of lipids and affects their thermotropic properties. Moreover, the 20-mer structural peptide induced a slow leakage of vesicular contents at 55 degrees C.