Electrospun Membranes Designed for Burst Release of New Gold-Complexes Inducing Apoptosis of Melanoma Cells

Two non-commercial metallic Au-based complexes were tested against one of the most aggressive malignant melanomas of the skin (MeWo cells), through cell viability and time-lapse live-cell imaging system assays. The tests with the complexes were carried out both in the form of free metallic complexes, directly in contact with the MeWo cell line culture, and embedded in fibers of Polycaprolactone (PCL) membranes produced by the electrospinning technique. Membranes functionalized with complexes were prepared to evaluate the efficiency of the membranes against the melanoma cells and therefore their feasibility in the application as an antitumoral patch for topical use. Both series of tests highlighted a very effective antitumoral activity, manifesting a very relevant cell viability inhibition after both 24 h and 48 h. In the case of the AuM1 complex at the concentration of 20 mM, melanoma cells completely died in this short period of time. A mortality of around 70% was detected from the tests performed using the membranes functionalized with AuM1 complex at a very low concentration (3 wt.%), even after 24 h of the contact period. The synthesized complexes also manifest high selectivity with respect to the MeWo cells. The peculiar structural and morphological organization of the nanofibers constituting the membranes allows for a very effective antitumoral activity in the first 3 h of treatment. Experimental points of the release profiles were perfectly fitted with theoretical curves, which easily allow interpretation of the kinetic phenomena occurring in the release of the synthesized complexes in the chosen medium.     

Characterization of Tribological and Mechanical Properties of the Si3N4 Coating Fabricated by Duplex Surface Treatment of Pack Siliconizing and Plasma Nitriding on AISI D2 Tool Steel

Silicon nitride (Si₃N₄) coating was deposited on AISI D2 tool steel through employing duplex surface treatments—pack siliconizing followed by plasma nitriding. Pack cementation was performed at 650 °C, 800 °C, and 950 °C for 2 and 3 hours by using various mixtures to realize the silicon coating. X-ray diffraction analyses and scanning electron microscopy observations were employed for demonstrating the optimal process conditions leading to high coating adhesion, uniform thickness, and composition. The optimized conditions belonging to siliconizing were employed to produce samples to be further processed via plasma nitriding. This treatment was performed with a gas mixture of 75 pct H₂-25 pct N₂, at the temperature of 550 °C for 7 hours. The results showed that different nitride phases such as Si₃N₄-β, Si₃N₄-γ, Fe₄N, and Fe₃N can be recognized as coatings reinforcements. It was demonstrated that the described composite coating procedure allowed to obtain a remarkable increase in hardness (80 pct higher with respect to the substrate) and wear resistance (30 pct decrease of weight loss) of the tool steel.

     

Captopril plus losartan in early post-infarction. Neurohormonal effects: a pilot study

BACKGROUND: Suppression of the formation of angiotensin II (A II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-inhibitor) therapy. However, during ACE-inhibitor treatment, A II plasma levels may also recover through tissue chymase. This study has attempted to verify the feasibility, safety and tolerability of a combined treatment using captopril (75 mg/day) and losartan (25 mg/day), and to ascertain its ability to reduce the formation and action of A II in the early post-infarction phase of reperfused anterior myocardial infarction (AMI). METHOD: Forty-four patients hospitalized for suspected AMI within 4 hours of the onset of symptoms, who were suitable for thrombolysis (first episode), in Killip class I-II, reperfused, treated with 75 mg/day of captopril within 3 days of admission and with a blood pressure level of more than 120 mmHg, were randomized (single-blind) into two groups that were similar with regard to age, sex, blood pressure, CK peak, ejection fraction, end-systolic volume and risk factors. Group A (22 subjects: 6 women/16 men) received captopril (75 mg/day) and placebo, while group B (22 subjects: 5 women/17 men) was given captopril (75 mg/day) plus losartan, initially at 12.5 mg and then at 25 mg/day thereafter (BP > 110 mmHg). Norepinephrine (NE) and A II plasma levels were measured on the third and tenth day after admission. RESULTS: Ten days after admission, group B (captopril plus losartan) showed a significant decrease in blood pressure (BP) on an intragroup level (p < 0.001) as well as in comparison with group A (p < 0.001), with values of 108 + 6.4 and 118 + 11 mmHg respectively. At the same time interval, NE and A II values did not show significant differences within or between groups. CONCLUSIONS. For the first time, our data suggest that a combined captopril-losartan treatment is feasible and that it has no particular side effects. In addition, it shows no significant increase of A II that would be produced by losartan alone.     

Biochemical Hazards during Three Phases of Assisted Reproductive Technology: Repercussions Associated with Epigenesis and Imprinting

Medically assisted reproduction, now considered a routine, successful treatment for infertility worldwide, has produced at least 8 million live births. However, a growing body of evidence is pointing toward an increased incidence of epigenetic/imprinting disorders in the offspring, raising concern that the techniques involved may have an impact on crucial stages of early embryo and fetal development highly vulnerable to epigenetic influence. In this paper, the key role of methylation processes in epigenesis, namely the essential biochemical/metabolic pathways involving folates and one-carbon cycles necessary for correct DNA/histone methylation, is discussed. Furthermore, potential contributors to epigenetics dysregulation during the three phases of assisted reproduction: preparation for and controlled ovarian hyperstimulation (COH); methylation processes during the preimplantation embryo culture stages; the effects of unmetabolized folic acid (UMFA) during embryogenesis on imprinting methyl “tags”, are described. Advances in technology have opened a window into developmental processes that were previously inaccessible to research: it is now clear that ART procedures have the potential to influence DNA methylation in embryonic and fetal life, with an impact on health and disease risk in future generations. Critical re-evaluation of protocols and procedures is now an urgent priority, with a focus on interventions targeted toward improving ART procedures, with special attention to in vitro culture protocols and the effects of excessive folic acid intake.     

Analysis of Residual Stresses and Dislocation Density of AA6082 Butt Welds Produced by Friction Sir Welding

Metallurgical and Materials Transactions A - The Friction Stir Welding (FSW) method was employed to join AA6082 sheets. The welds were produced with different tool traverse speed (200 and...     

Some considerations concerning lubrication in high‐performance internal combustion engines

The increasing rotational speeds and the weight reduction of high‐performance internal combustion engines are accompanied by problems of lubrication, heat transfer, and vibration that are mostly negligible in medium‐ and low‐performance engines. To deal with such phenomena under demanding operating conditions necessitates a specific design. The dynamics of the power system between crankshaft and related sub‐components, e. g., bending and torsional vibrations of the connecting rod, ovalisation of the head and eye of the connecting rod, and vibrations of thin cylinder liners, are critical for the lubrication system in general, and for oil film pressure fields in particular. In some cases, no information on these features has existed until now, so no quantification of the variables involved has been possible. Over the last few years a systematic investigation has been performed to take into account the critical points and their fundamental importance in the design of such engines. The present paper considers some of the phenomena related to lubrication in high‐performance engines. The need is highlighted for further investigations using computational and experimental methodologies.     

Milling performance and bread-making aptitude of the new soft kernel durum wheat variety Faridur

Faridur is the first ‘soft kernel’ durum wheat variety released in Italy. This variety has not yet been evaluated for its end-use quality. In the present study, the milling performance (using two different mills) and bread-making ability of Faridur were compared with Svevo. An effect of the mill type on flour properties was observed, with the Chopin CD1 mill leading to finer particle size, higher starch damage and water absorption than Bühler MLU 202. Protein and gluten content was significantly higher in Faridur, but gluten quality was lower, as indicated by alveograph and farinograph analyses. The softer nature of Faridur facilitated milling, reducing energy consumption and starch damage. The baking test led to a compact product, with low specific volume, needing adjustments in processing and formulation. As energy saving has become a key competitive factor in the milling sector, Faridur has potential for expanding the use of durum wheat.     

Hydrogen-Based Direct Reduction of Iron Oxides Pellets Modeling

The present study deals with the analyses of the direct reduction kinetics during the hydrogen reduction of industrial iron oxide pellets. Various types of pellets with different percentage of total iron content and metal oxides are examined. They are reduced at different temperatures and pressure (700–1100 °C and 1–6 bar) in hydrogen atmosphere. The reduction behavior is described in terms of time to reduction, rate of reduction, and kinetics constant. All the obtained results are analyzed through the employment of a commercial multiobjective optimization tool to precisely define the weight that each single parameter has on the reduction behavior. It is shown that from the point of view of the processing conditions, temperature is the main factor influencing the time to total reduction. From the point of view of the pellets properties, it is mainly influenced by the total iron percentage and then by porosity and basicity index. Also, the kinetics behavior is largely influenced by the reduction temperature even if it is mainly governed by the porosity and pores size from the point of view of the reduced pellets. The reduction rate is also mainly influenced by temperature and then by iron percentage, gas pressure, basicity index, and porosity.     

Evaluating the Efficiency of Chitosan-Graphene Oxide Hybrid Hydrogels as Drug Delivery Systems

With the objective of creating an electro-responsive and antimicrobial device suitable as delivery system for Rose Bengal (RB) to the skin, a hybrid hydrogel combining Chitosan (CS) and Graphene Oxide (GO) are designed, serving as functional polymer support and active filling element, respectively. The hybrid system, synthesized using tripolyphosphate as a crosslinker via ionic gelation, shows a uniform and homogeneous surface, as verified by SEM investigations, high biocompatibility when tested on human fibroblast lung cells MRC-5 cells, and biodegradability in phosphate buffered medium at physiological pH. Drug loading and release experiments, extensively analyzed using suitable mathematical modeling, shows the enhancement of the binding efficiency conferred by GO (534 and 979 mg g⁻¹ for blank and hybrid hydrogels, respectively) and an electro-responsive behavior (maximum BR release of 36 and 23% at 0 and 12 V, respectively). Additionally, hybrid hydrogel is found to prevent the adhesion of methicillin-resistant Staphylococcus aureus and to kill the bacterial cells by taking advantage of the sustained release of the antimicrobial RB.     

Conformationally Constrained Sialyl Analogues as New Potential Binders of h-CD22

Here, two conformationally constrained sialyl analogues were synthesized and characterized in their interaction with the inhibitory Siglec, human CD22 (h-CD22). An orthogonal approach, including biophysical assays (SPR and fluorescence), ligand-based NMR techniques, and molecular modelling, was employed to disentangle the interaction mechanisms at a molecular level. The results showed that the Sialyl-TnThr antigen analogue represents a promising scaffold for the design of novel h-CD22 inhibitors. Our findings also suggest that the introduction of a biphenyl moiety at position 9 of the sialic acid hampers canonical accommodation of the ligand in the protein binding pocket, even though the affinity with respect to the natural ligand is increased. Our results address the search for novel modifications of the Neu5Ac-α(2-6)-Gal epitope, outline new insights for the design and synthesis of high-affinity h-CD22 ligands, and offer novel prospects for therapeutic intervention to prevent autoimmune diseases and B-cell malignancies.