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Hyaluronic acid (HA)-based prodrugs bearing double-responsive (acid pH or oxidation) boronates of catechol-containing drugs were used to treat xenografted human prostate tumours (LNCaP) in SCID mice. The HA prodrugs accumulated significantly only in tumours (impressively, up to 40% of the injected dose after 24 h) and in liver, with negligible – actually anti-inflammatory - consequences in the latter. A quercetin-HA prodrug significantly slowed down tumour growth, in a dose-dependent fashion and with a much higher efficacy (up to 4 times) than equivalent doses of free quercetin. In short, boronated HA appears to be a very promising platform for targeted chemotherapy.

Background: Surgical site infection (SSI) is a common complication of surgical procedures.Aim: Our study aimed at investigating a new method based on assessment of suture thread colonization to identify patients developing an SSI.Materials and Methods: We prospectively enrolled 119 patients undergoing elective surgery. For each patient, a synthetic absorbable thread in Lactomer 9-1 (Polisorb Gauge 2) inserted in the surgical site at the end of surgery was sent to the microbiology laboratory after 48 h to assess colonization of its inner tract.Results: Forty (33.6% of cases) patients had a colonized thread. Antibiotic prophylaxis was administered to 66 of 79 patients who did not display a colonized thread and to 20 of the 40 patients with a colonized thread (83.5% versus 50%, respectively, P = 0.0002). An SSI was observed only in patients with a colonized thread (10% versus 0, P = 0.02). The microorganisms identified in colonized threads were the same identified in SSIs.Conclusions: Since an SSI was found only in patients with colonized threads, the method described here may be valuable for identifying patients developing an SSI. Moreover, the method can also be useful for targeting efficient antibiotic therapy to the culprit microorganisms. (C) 2017 Elsevier Inc. All rights reserved.

The structural and stability properties of a novel zinc-dependent alcohol dehydrogenase from the hyperthermophilic archaeon Pyrobaculum aerophilum (PyAeADHII) were investigated by Fourier transformed infrared spectroscopy (FTIR). This enzyme is a thermostable homo-tetramer belonging to the GroES-fold motif proteins characterized by an irregular β-barrel conformation. Our results revealed a protein with a secondary structure rich in β-sheet (32% of the total secondary elements) and it showed a three-step thermal unfolding pathway. The complete enzyme denaturation was preceded by the formation of a relaxed tertiary/quaternary structure and previously by an excited native-like conformation. Two-dimensional correlation spectroscopy analysis (2D-COS) and differential scanning calorimetry (DSC) experiments supported these data and allowed us to determine the protein melting temperature at 96.9 °C as well as to suggest the sequence of the events that occurred during the protein denaturation process.

The gene encoding a novel alcohol dehydrogenase (ADH) that belongs to the medium chain dehydrogenase/reductase (MDR) superfamily was identified in the hyperthermophilic archaeon, Pyrobaculum aerophilum . The P. aerophilum ADH gene ( Pae2687 ) was over-expressed in Escherichia coli , and the protein (PyAeADHII) was purified to homogeneity and characterized. The PyAeADHII belongs to a medium chain class because its monomer size is 330 residues and even if it is structurally similar to other enzymes belonging to MDR superfamily, it lacks key residues involved in the coordination of the catalytic Zn ion and in the binding of alcoholic substrates typical of other ADHs. Consistently, PyAeADHII does not show activity on a large number of alcohols, aldheydes or ketones. It is active only when α-tetralone is used as a substrate. The enzyme has a strict requirement for NADP(H) as the coenzyme and has remarkable thermophilicity, displaying activity at temperatures up to 95 °C. The study of the metabolic pathways of P. aerophilum can provide information on the evolution of genes and enzymes and may be crucial for understanding the evolution of eukaryotic cells.

Copolymerisation of charged and neutral monomers is a well-tested strategy to introduce charged moieties in a polymeric chain and obtain polyelectrolyte polymers. We have synthesized new cationic and anionic polyelectrolytes by bulk radical copolymerisation of 2-hydroxyethyl methacrylate with [2-methacryloyloxyethyltrimethyl ammonium chloride (METAC)] or [2-acrylamido-2-methylpropane-sulphonic acid (AMPS)] monomers. The chemical structure of the synthesized copolymers was confirmed by FT-IR spectroscopy. Swelling studies on synthesized copolymers showed a high water content in the swollen state and a “smart behaviour” upon changes in external stimuli (pH and ionic strength). Cytotoxicity and cytocompatibility studies demonstrated that synthesized materials were not toxic. Moreover, the cationic copolymer showed good cell adhesion, whereas the anionic copolymer showed poor cell adhesion on its surface. X-ray photoelectron spectroscopy (XPS) showed that the disparate behaviour was due to the chemical nature of charged groups on the copolymer surfaces.

Polyelectrolite hydrogels were submitted to the biomimetic method. The experimental results clearly show that the method has coated them with HA globular crystals of similar to 500 nm in diameter. Moreover, the method strongly influences the swelling of the hydrogels. The results strongly suggest that a biologically active HA layer forms also on the surface of the internal pores. Therefore, it is a powerful method for producing micro- and nano-patterned structures of biologically active apatite on the surface of hydrogels and of their pores. (C) 2002 Elsevier Science B.V. All rights reserved.