A potent integrin antagonist from a small library of cyclic RGD pentapeptide mimics including benzyl-substituted azabicycloalkane amino acids

A small library of cyclic RGD pentapeptide mimics, including benzyl-substituted azabicycloalkane amino acids, was synthesized with the aim of developing active and selective integrin antagonists. In vitro binding assays established one particular compound with affinity for both the alpha(v)beta(3) and the alpha(v)beta(5) integrins. The synthesis in solution and the in vitro screening of these RGD derivatives, as well as the determination of the conformational properties of the integrin ligands by spectroscopic and computational methods are described.     

Synthesis of novel DC-SIGN ligands with an alpha-fucosylamide anchor

The dendritic cell-specific intercellular adhesion molecule (ICAM) 3-grabbing nonintegrin (DC-SIGN) is a C-type lectin that appears to perform several different functions. Besides mediating adhesion between dendritic cells and T lymphocytes, DC-SIGN recognizes several pathogens some of which, including HIV, appear to exploit it to invade host organisms. The intriguing diversity of the roles attributed to DC-SIGN and their therapeutic implications have stimulated the search for new ligands that could be used as biological probes and possibly as lead compounds for drug development. The natural ligands of DC-SIGN consist of mannose oligosaccharides or fucose-containing Lewis-type determinants. Using the known 3D structure of the Lewis-x trisaccharide, we have identified some monovalent alpha-fucosylamides that bind to DC-SIGN with inhibitory constants 0.4-0.5 mM, as determined by SPR, and have characterized their interaction with the protein by STD NMR spectroscopy. This work establishes for the first time alpha-fucosylamides as functional mimics of chemically and enzymatically unstable alpha-fucosides and describes interesting candidates for the preparation of multivalent systems able to block the receptor DC-SIGN with high affinity and with potential biomedical applications.     

Generation of entangled photon pairs using small-coherence-time continuous wave pump lasers

We address the generation of entangled photon pairs by parametric downconversion from solid state cw lasers with small coherence time. We consider a compact and low-cost setup based on a two-crystal scheme with type-I phase matching. We reconstruct the full density matrix by quantum tomography and analyze in detail the entanglement properties of the generated state as a function of the crystal's length and the coherence time of the pump. We verify the possibility to improve the visibility using a purification protocol based on a compensation crystal.     

Polyphenol compounds in artichoke plant tissues and varieties

Polyphenol compounds, particularly caffeoylquinic acids and flavonoids, were measured in different tissues and developmental stages of 6 artichoke varietal types diffused in the Mediterranean region. Flower heads were subdivided into external, intermediate, internal bracts, and receptacle, while leaves were collected at the vegetative and productive stages. The main polyphenols detected were chlorogenic acid, cynarin, luteolin 7-O-rutinoside, and luteolin 7-O-glucoside. "Violet de Provence" artichoke proved to retain the highest content of total phenols. Single polyphenols accumulated preferentially in specific parts of capitula. In leaves, most polyphenols were detected in the productive stage of the plant. Altogether, results provide useful indications for the promotion of artichoke as nutraceutical food and for the extraction of health-promoting substances in particular tissues/stages of the artichoke plant. PRACTICAL APPLICATION: We describe the content of phenolic compounds in various artichoke tissues, developmental stages, and varieties. Results indicate that artichoke leaves represent an important source of these health-promoting compounds, also useful for phytopharmaceutical applications. A wider utilization of specific artichoke types should be strongly encouraged not only as a food for the fresh market, as they are now used, but also for the pharmaceutical industry, since the content of phenolic compounds is abundant both in the heads and in the leaves.     

DRP1 Inhibition Rescues Mitochondrial Integrity and Excessive Apoptosis in CS-A Disease Cell Models

Cockayne syndrome group A (CS-A) is a rare recessive progeroid disorder characterized by sun sensitivity and neurodevelopmental abnormalities. Cells derived from CS-A patients present as pathological hallmarks excessive oxidative stress, mitochondrial fragmentation and apoptosis associated with hyperactivation of the mitochondrial fission dynamin related protein 1 (DRP1). In this study, by using human cell models we further investigated the interplay between DRP1 and CSA and we determined whether pharmacological or genetic inhibition of DRP1 affects disease progression. Both reactive oxygen and nitrogen species are in excess in CS-A cells and when the mitochondrial translocation of DRP1 is inhibited a reduction of these species is observed together with a recovery of mitochondrial integrity and a significant decrease of apoptosis. This study indicates that the CSA-driven modulation of DRP1 pathway is key to control mitochondrial homeostasis and apoptosis and suggests DRP1 as a potential target in the treatment of CS patients.     

Parameters for the evaluation of the thermal damage and nutraceutical potential of lupin-based ingredients and food products

Foods based on sweet lupin proteins are gaining attention from industry and consumers because of their possible role in the prevention of cardiovascular disease. When promoting lupin-based foods for inclusion in a daily diet, the thermal damage suffered during processing is of relevance to the bioactive and nutritional quality of the food product. N-(2-furoylmethyl)-L-lysine (furosine) quantification demonstrates that currently available sweet lupin protein isolates have a thermal damage comparable to or lower than other traditional food ingredients, and are a good source of lysine in non-dairy products. In lupin-based foods claiming to have cholesterol-lowering potential, shotgun proteomics offers itself as a fast and effective screening method for assessing the biological availability of active peptides. Such a method is readily applicable to other legume-enriched food products.     

Food packaging based on polymer nanomaterials

Since its starting in the 19th century, modern food packaging has made great advances as results of global trends and consumer preferences. These advances are oriented to obtain improved food quality and safety. Moreover, with the move toward globalization, food packaging requires also longer shelf life, along with the monitoring of safety and quality based upon international standards. Nanotechnology can address all these requirements and extend and implement the principal packaging functions - containment, protection and preservation, marketing and communications. Applications of polymer nanotechnology in fact can provide new food packaging materials with improved mechanical, barrier and antimicrobial properties, together with nano-sensors for tracing and monitoring the condition of food during transport and storage.The latest innovations in food packaging, using improved, active and smart nanotechnology will be analyzed. It will be also discuss the limits to the development of the new polymer nanomaterials that have the potential to completely transform the food packaging industry.     

The Efficacy of the Quorum Sensing Inhibitor FS8 and Tigecycline in Preventing Prosthesis Biofilm in an Animal Model of Staphylococcal Infection

We investigated the efficacy of tigecycline and FS8, alone or combined, in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2 × 10⁷ colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis, and three contaminated groups that received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii) tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L) four-fold lower with respect to tigecycline alone in in vitro studies. The rat groups treated with tigecycline showed the lowest bacterial numbers (4.4 × 10⁴ ± 1.2 × 10⁴ CFU/mL). The FS8-treated group showed a good activity and significant differences compared to control group with bacterial numbers of 6.8 × 10⁴ ± 2.0 × 10⁴ CFU/mL. A stronger inhibition of bacterial growth was observed in rats treated with a combined FS8 and tigecycline therapy than in those that were singly treated with bacterial numbers of 10¹ CFU/mL graft. In conclusion, the ability to affect biofilm formation as well, its property to be an antibiotic enhancer suggests FS8 as alternative or additional agent to use in conjunction with conventional antimicrobial for prevention of staphylococcal biofilm related infection.