Protection of normal cells from irradiation bystander effects by silica-flufenamic acid nanoparticles

The development of a myriad of nanoparticles types has opened new possibilities for the diagnostics and treatment of many diseases, especially for cancer. However, most of the researches done so far do not focus on the protection of normal cells surrounding a tumor from irradiation bystander effects that might lead to cancer recurrence. Gap-junctions are known to be involved in this process, which leads to genomic instability of neighboring normal cells, and flufenamic acid (FFA) is included in a new group of gap-junction blockers recently discovered. The present work explores the use of mesoporous silica nanoparticles MCM-41 functionalized with 3-Aminopropyltriethoxysilane (APTES) for anchoring the flufenamic acid for its prolonged and controlled release and protection from radiation bystander effects. MCM-41 and functionalized samples were structurally and chemically characterized with multiple techniques. The biocompatibility of all samples was tested in a live/dead assay performed in cultured MRC-5 and HeLa cells. HeLa cells cultured were exposed to 50?Gy of gamma-rays and the media transferred to fibroblast cells cultured separately. Our results show that MCM-41 and functionalized samples have high biocompatibility with MCR-5 and HeLa cells, and most importantly, the FFA delivered by these NPs was able to halt apoptosis, one of main bystander effects.     

A methacrylic hyaluronic acid derivative for potential application in oral treatment of celiac disease

Objective: Aim of this work was the synthesis of a methacrylic hyaluronic acid (HA) derivative and the production, via photocrosslinking, of related hydrogels loaded with an endopeptidase intended for a potential oral treatment of celiac disease.

Methods: The methacrylic derivative of HA was prepared through a one-pot procedure involving the reaction with ethylenediamine (EDA) and methacrylic anhydride (MA). The obtained derivative, named HA-EDA-MA, was used to prepare photocrosslinked hydrogels loaded with a prolyl endopeptidase derived from Flavobacterium meningosepticum (PEP FM) able to detoxify gliadin. Obtained hydrogels were recovered as gels or freeze-dried powders.

Results: Hydrogels obtained as freeze-dried powders, are able to protect loaded enzyme from degradation due to freeze-drying process and from alteration during storage, overall in the presence of a cryoprotectant. All photocrosslinked HA-EDA-MA hydrogels (gels and powders) release PEP FM in simulated intestinal fluid in sustained manner and in active form. HA-EDA-MA hydrogels are nontoxic as demonstrated through in vitro studies on BALB 3T3 cells.

Conclusions: Prepared hydrogels show a potential application for oral treatment of celiac disease thanks to the possibility to release enzymes able to detoxify the gliadin peptide that induces the immunogenic response.     

Remotely Light‐Powered Soft Fluidic Actuators Based on Plasmonic‐Driven Phase Transitions in Elastic Constraint

Materials capable of actuation through remote stimuli are crucial for untethering soft robotic systems from hardware for powering and control. Fluidic actuation is one of the most applied and versatile actuation strategies in soft robotics. Here, the first macroscale soft fluidic actuator is derived that operates remotely powered and controlled by light through a plasmonically induced phase transition in an elastomeric constraint. A multiphase assembly of a liquid layer of concentrated gold nanoparticles in a silicone or styrene–ethylene–butylene–styrene elastic pocket forms the actuator. Upon laser excitation, the nanoparticles convert light of specific wavelength into heat and initiate a liquid‐to‐gas phase transition. The related pressure increase inflates the elastomers in response to laser wavelength, intensity, direction, and on–off pulses. During laser‐off periods, heating halts and condensation of the gas phase renders the actuation reversible. The versatile multiphase materials actuate—like soft “steam engines”—a variety of soft robotic structures (soft valve, pnue‐net structure, crawling robot, pump) and are capable of operating in different environments (air, water, biological tissue) in a single configuration. Tailored toward the near‐infrared window of biological tissue, the structures actuate also through animal tissue for potential medical soft robotic applications.     

Correlating Nanocrystalline Structure with Electronic Properties in 2D Platinum Diselenide

Platinum diselenide (PtSe₂) is a 2D material with outstanding electronic and piezoresistive properties. The material can be grown at low temperatures in a scalable manner, which makes it extremely appealing for many potential electronics, photonics, and sensing applications. Here, the nanocrystalline structure of different PtSe₂ thin films grown by thermally assisted conversion (TAC) is investigated and is correlated with their electronic and piezoresistive properties. Scanning transmission electron microscopy for structural analysis, X-ray photoelectron spectroscopy (XPS) for chemical analysis, and Raman spectroscopy for phase identification are used. Electronic devices are fabricated using transferred PtSe₂ films for electrical characterization and piezoresistive gauge factor measurements. The variations of crystallite size and their orientations are found to have a strong correlation with the electronic and piezoresistive properties of the films, especially the sheet resistivity and the effective charge carrier mobility. The findings may pave the way for tuning and optimizing the properties of TAC-grown PtSe₂ toward numerous applications.     

Minimizing conservativity violations in ontology alignments: algorithms and evaluation

In order to enable interoperability between ontology-based systems, ontology matching techniques have been proposed. However, when the generated mappings lead to undesired logical consequences, their usefulness may be diminished. In this paper, we present an approach to detect and minimize the violations of the so-called conservativity principle where novel subsumption entailments between named concepts in one of the input ontologies are considered as unwanted. The practical applicability of the proposed approach is experimentally demonstrated on the datasets from the Ontology Alignment Evaluation Initiative.     

Mixing processes in the cavity transfer mixer: A thorough study

In many industrial applications, the quality of mixing between different materials is fundamental to guarantee the desired properties of products. However, properly modeling and understanding polymer mixing presents noticeable difficulties, because of the variety and complexity of the phenomena involved. This is also the case with the Cavity Transfer Mixer (CTM), an add‐on to be mounted downstream of existing extruders, to improve distributive mixing. The present work proposes a fully three‐dimensional model of the CTM: a finite element solver provides the transient velocity field, which is used in the mapping method implementation to compute the concentration field evolution and quantify mixing. Several simulations are run assessing the impact on mixing of geometrical and functioning parameters. In general, the number of cavities per row should be limited and the cavity size rather big to guarantee good mixing quality. © 2017 American Institute of Chemical Engineers AIChE J, 64: 1034–1048, 2018     

Enterococcus populations in Pecorino Abruzzese cheese: biodiversity and safety aspects

The presence of enterococci in Pecorino Abruzzese cheese during ripening was evaluated. Counts were high, especially in fully ripened summer batches. Seventy strains were isolated and identified based on phenotypical and genotypical features as Enterococcus faecium (48.5%), Enterococcus faecalis (40%), and Enterococcus durans (11.5%), with the first species predominant in spring batches and the second predominant in summer batches. High biodiversity was revealed by random amplification of polymorphic DNA and a PCR assay, suggesting the presence of autochthonous strains. E. faecium isolates were the most resistant to the tested antibiotics, especially to erythromycin, chloramphenicol, and penicillin, but all strains were susceptible to vancomycin, as confirmed by the absence of vanA and vanB genes. The presence of some virulence determinants was investigated, revealing the diffusion of aggregation substance (asal) and gelatinase (gelE) genes in 37.5% of E. faecalis strains. However, none of the isolates produced gelatinase in vitro, suggesting the presence of silent genes. The virulence genes were absent in E. durans. Among E. faecium strains, only Lab 41/1 possessed gelE and asal, whose presence previously has been reported only in E. faecalis. Decarboxylating activity was revealed for phenylalanine (27% of the strains) and tyrosine (96%) but not histidine. The presence of a tyrosine decarboxylase-encoding gene was observed for all strains. A comparison of these results with those of previous studies of clinical and food isolates indicates that enterococci from Pecorino Abruzzese cheese have low pathogenic potential.     

Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems

melatonin (MT) is a hormone produced by the pineal gland at night, involved in the regulation of circadian rhythms. For clinical purposes, exogenous MT administration should mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favourable due to short half-life of elimination. Aim of this study is to examine pharmacokinetics of MT incorporated in solid lipid nanoparticles (SLN), administered by oral and transdermal route. SLN peculiarity consists in the possibility of acting as a reservoir, permitting a constant and prolonged release of the drugs included. In 7 healthy subjects SLN incorporating MT 3 mg (MT-SLN-O) were orally administered at 8.30 a.m. MT 3 mg in standard formulation (MT-S) was then administered to the same subjects after one week at 8.30 a.m. as controls. In 10 healthy subjects SLN incorporating MT were administered transdermally (MT-SLN-TD) by the application of a patch at 8.30 a.m. for 24 hours. Compared to MT-S, Tmax after MT-SLN-O administration resulted delayed of about 20 minutes, while mean AUC and mean half life of elimination was significantly higher (respectively 169944.7 +/- 64954.4 pg/ml x hour vs. 85148.4 +/- 50642.6 pg/ml x hour, p = 0.018 and 93.1 +/- 37.1 min vs. 48.2 +/- 8.9 min, p = 0.009). MT absorption and elimination after MT-SLN-TD demonstrated to be slow (mean half life of absorption: 5.3 +/- 1.3 hours; mean half life of elimination: 24.6 +/- 12.0 hours), so MT plasma levels above 50 pg/ml were maintained for at least 24 hours. This study demonstrates a significant absorption of MT incorporated in SLN, with detectable plasma level achieved for several hours in particular after transdermal administration. As dosages and concentrations of drugs included in SLN can be varied, different plasma level profile could be obtained, so disclosing new possibilities for sustained delivery systems.     

Comparison of static and step-pulsed ultra-high pressure on the microbial stability of fresh cut pineapple

Fresh cut pineapple cubes inoculated with 10^4–5 CFU g⁻¹ Saccharomyces cerevisiae were packed in heat-sealed polyethylene pouches and subjected at ambient temperature to static and step-pulsed ultra-high pressure (UHP) treatments. Static treatments included 100 and 9000 s at 270 MPa and 9000 s at 340 MPa. Step-pulsed pressure treatments included 100, 300 and 600 s at 0–270 MPa using 0·5-s and 10-s pulses. Inoculated treated and untreated samples were held at 4°C for 60 days. Bacteria and yeast counts were determined using plate count agar and yeast extract peptone dextrose agar, respectively. Static treatment at 270 and 340 MPa for 9000 s resulted in <240 CFU g⁻¹ yeast and bacteria counts for up to 60 days. Step-pulsed pressure treatments for 100 s at 0–270 MPa using 0·5-s (200 pulses) and 10-s pulses (10 pulses) were more effective than a 100-s static 270-MPa treatment. Step-pulsed pressure treatments (300 and 600 s) using 0·5-s pulses (600 and 1200 pulses) and 10-s pulses (30 and 60 pulses) were as effective as 9000-s static pressure treatments at 270 and 340 MPa. This storage study confirmed the superiority of step-pulsed over static pressure treatments. © 1998 SCI.     

Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/w_PLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft’s antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts.