S-Adenosyl-l-Methionine Overcomes uL3-Mediated Drug Resistance in p53 Deleted Colon Cancer Cells

Purpose: In order to study novel therapeutic approaches taking advantage of natural compounds showing anticancer and anti-proliferative effects, we focused our interest on S-adenosyl-l-methionine, a naturally occurring sulfur-containing nucleoside synthesized from adenosine triphosphate and methionine by methionine adenosyltransferase, and its potential in overcoming drug resistance in colon cancer cells devoid of p53. Results: In the present study, we demonstrated that S-adenosyl-l-methionine overcomes uL3-mediated drug resistance in p53 deleted colon cancer cells. In particular, we demonstrated that S-adenosyl-l-methionine causes cell cycle arrest at the S phase; inhibits autophagy; augments reactive oxygen species; and induces apoptosis in these cancer cells. Conclusions: Results reported in this paper led us to propose S-adenosyl-l-methionine as a potential promising agent for cancer therapy by examining p53 and uL3 profiles in tumors to yield a better clinical outcomes.     

Production of chitosan PVA PCL hydrogels to bind heparin and induce angiogenesis

New blood vessel formation is an essential part of wound healing to provide cells with the nutrients and oxygen for their survival. Many nonhealing ulcers fail to heal because of poor blood supply and skin grafts will also fail to take on poorly vascularized wound beds. There is a real need for proangiogenic biomaterials to assist wound healing. In vivo heparin binds proangiogenic growth factors and helps regulate new blood vessel formation, hence heparin containing biomaterials are attractive. To achieve a hydrogel with high heparin binding capacity a composite of chitosan, poly(vinyl alcohol) (PVA) and polycaprolactone (PCL) was produced. Chitosan is a biodegradable natural polymer with great potential for biomedical applications due to its biocompatibility, high charge density and nontoxicity. PVA is biocompatible and nontoxic with good chemical stability, film-forming ability, and high hydrophilicity. PCL has physicochemical and mechanical properties comparable to those of the biological tissues and due its hydrophilic nature helps in the sustained release of drugs. Accordingly in this study we explored a range of PCL concentrations from 4% to 16% added to hydrogels composed of chitosan and PVA. Heparin was blended into the polymer mixture and the nanoporous structure was created by freeze-drying the PCL hydrogel. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR) and XPS confirmed the presence of sulfur on the surface of the hydrogels. Their porous morphology was investigated by scanning electron microscope (SEM). The Chick Chorionic Allantoic Membrane (CAM) assay was used to study the angiogenic potential of these materials and histology (H&E and Goldner trochome) was used to confirm the presence of new blood vessels inside the hydrogels. We report that the addition of 8% PCL to the hydrogels gave porous structures containing heparin, which significantly increased new blood vessel formation into the hydrogels. These hydrogels offer a new approach to biomaterials, which could be added to wounds to improve vascularization.     

Carboxymethylinulin–Chitosan Nanoparticles for the Delivery of Antineoplastic Mitoxantrone

Mitoxantrone (MTX) is an antineoplastic agent whose use is limited by serious side effects on non‐neoplastic cells. The aim of this study was the development of a new drug release system using an ionotropic gelation technique for microencapsulation of MTX in chitosan–carboxymethylinulin nanoparticles (CCInp), followed by evaluation of their cytotoxic effects on neoplastic MDA‐MB‐231 and non‐neoplastic NIH3T3 cell lines. The CCInp were prepared through a new reliable method for easy functionalization of both inulin and chitosan. Both unloaded and drug‐loaded nanoparticles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) and showed a spherical morphology with an average hydrodynamic diameter between 40 and 80 nm. Both nanoparticles were stable and easily degraded by lysozyme. MTX‐loaded nanoparticles led to a greater mortality of MDA‐MB‐231 relative to free drug due to the ability of the nanoparticles to accumulate preferentially in neoplastic cells. The developed drug release system retains the ability to kill MDA‐MB‐231 cells in vitro, improving the survival of NIH3T3 cells.     

Properties of epitaxial, (001)- and (110)-oriented (PbMg1/3Nb2/3O3)2/3-(PbTiO3)1/3 films on silicon described by polarization rotation

Epitaxial (PbMg_1/3Nb_2/3O₃)_2/3-(PbTiO₃)_1/3 (PMN-PT) films with different out-of-plane orientations were prepared using a CeO₂/yttria stabilized ZrO₂ bilayer buffer and symmetric SrRuO₃ electrodes on silicon substrates by pulsed laser deposition. The orientation of the SrRuO₃ bottom electrode, either (110) or (001), was controlled by the deposition conditions and the subsequent PMN-PT layer followed the orientation of the bottom electrode. The ferroelectric, dielectric and piezoelectric properties of the (SrRuO₃/PMN-PT/SrRuO₃) ferroelectric capacitors exhibit orientation dependence. The properties of the films are explained in terms of a model based on polarization rotation. At low applied fields domain switching dominates the polarization change. The model indicates that polarization rotation is easier in the (110) film, which is ascribed to a smaller effect of the clamping on the shearing of the pseudo-cubic unit cell compared to the (001) case.     

Revealing Photoluminescence Modulation from Layered Halide Perovskite Microcrystals upon Cyclic Compression

Halide perovskites show promise for high‐efficiency solar energy conversion and light‐emitting diode devices owing to their bandgap, which falls within the visible optical range. However, due to their rigidity, GPa pressures are necessary to control the complex interplay between their electronic and crystallographic structure. Layered perovskites are likely to be controlled using much lower pressures by exploiting the optical anisotropy of the embedded organic molecules in the structure. This work introduces layered perovskite microplatelets and demonstrates the extreme sensitivity of their emission to cyclic mechanical loading in the range of tens of MPa. A drastic change in their emission is observed in situ, from near‐white to an enhanced blue color. This process is reversible, as is evident from a hysteresis loop in the photoluminescence (PL) intensity of the microplatelets. A combination of experimental analysis and computational modelling shows that such behavior cannot be attributed to changes in the crystallographic structure of the flakes. Instead, it suggests that, thanks to their structural anisotropy, microplate alignment and reorientation are responsible for the observed PL modulation. The possibility to tune the optical emission of layered perovskite crystals via low pressures makes them highly interesting as active materials in applications where stress sensing or light modulation is desired.     

欧洲电网的发展及其与全球能源互联网的兼容性

全球能源互联网(Global Energy Interconnection,GEI)旨在通过建立洲际输电走廊来实现可再生能源发电在全球范围内的自由调度。研究表明,GEI愿景可有效促进全球去碳化。然而,各地区电网的现有发展计划分别以独立的愿景为基础框架,其与GEI的兼容性尚不清晰。文章旨在讨论由欧洲输电网运行商联盟(European Network of Transmission System Operators for Electricity, ENTSO-E)提出的欧洲电网发展十年计划(Ten Years Network Development Plan, TYNDP)与GEI愿景的兼容性,提出一种结合电力系统技术经济分析模型和社会经济决策支持工具的多准则优化方法。通过该方法,在充分考虑环境、社会和政治因素的影响下,对GEI跨洲互联通道在欧洲电网本地的落脚点进行优化配置,并计算了2030年和2050年GEI情景下欧洲电网规划模型内部的最优潮流。结果显示,在GEI情景所预测的高负荷水平下,斯堪的纳维亚地区和欧洲大陆之间将出现分布广泛的阻塞,从而限制来自北极地区风电向欧洲大陆的调度。研究认为,GEI的发展与实施需要各地区电网间的密切配合。     

Heat Pipe Finned Heat Exchanger for Heat Recovery: Experimental Results and Modeling

This paper presents an experimental and theoretical analysis of a 6-row horizontal microfin Heat Pipe Finned Heat Exchanger (HPFHE) used for energy recovery purposes inside an air conditioning unit. The experimental campaign investigated both the summer and the winter conditions for European countries by varying the operating conditions at the inlet of the HPFHE. New experimental tests are presented for the identification of low – global warming potential refrigerants, environmental friendly substitutes of the more traditional HFC134a. The results showed the interesting heat transfer capabilities of HFC152a as an alternative HPFHE working fluid. A simulation model previously developed by present authors was validated against the new experimental data collected and then used to simulate the thermal performance of the HPFHE under different operating test conditions, in order to assess the potentiality of seasonal energy savings with HFC152a.     

Olive Oil Phenolics Prevent Oxysterol‐Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells,Through Modulation of p38 and JNK Pathways

1 Scope

The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells.

2 Methods and results

Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin‐1β, regulated on activation, normal T‐cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation.

3 Conclusions

These results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes.