5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer

Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated in vitro the antiproliferative activity of some 5-(carbamoylmethylene)-oxazolidin-2-ones on MCF-7 and HeLa cells. The tested compounds displayed a wide range of cytotoxicity on these cancer cell lines, measured by MTT assay, exhibiting no cytotoxicity on non-tumorigenic MCF-10A cells. Among the nine tested derivatives, four displayed a good anticancer potential. Remarkably, OI compound showed IC50 values of 17.66 and 31.10 µM for MCF-7 and HeLa cancer cells, respectively. Furthermore, we assessed OI effect on the cell cycle by FACS analysis, highlighting a G1 phase arrest after 72 h, supported by a low expression level of Cyclin D1 protein. Moreover, mitochondrial membrane potential was reduced after OI treatment driven by high levels of ROS. These findings demonstrate that OI treatment can inhibit MCF-7 and HeLa cell proliferation and induce apoptosis by caspase-9 activation and cytochrome c release in the cytosol. Hence, 5-(carbamoylmethylene)-oxazolidin-2-ones have a promising anticancer activity, in particular, OI derivative could represent a good candidate for in vivo further studies and potential clinical use

Dielectric spectroscopy of PP/MWCNT nanocomposites: Relationship with crystalline structure and injection molding condition

In this paper, we study the correlation between the dielectric behavior of polypropylene/multi-walled carbon nanotube (PP/MWCNT) nanocomposites and the morphology with regard to the crystalline structure, nanofiller dispersion and injection molding conditions. As a result, in the range of the percolation threshold the dielectric behavior shifts to a more frequency-independent behavior, as the mold temperature increases. Moreover, the position further from the gate appears as the most conductive. This effect has been associated to a modification of the morphology of the MWCNT clusters induced by both the flow of the molten polymer during the processing phase and the variation of the crystalline structure, which is increasingly constituted by γ-phase as the mold temperature increases. The obtained results allow one to understand the effect of tuning the processing condition in the frequency-dependent electrical behavior of PP/MWCNT injection-molded nanocomposites, which can be successfully exploited for an advanced process/product design

Diabetic retinopathy, oxidative stress and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegenerative and metabolic diseases. In DR, sirtuins 1,3,5 and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g. antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focuse on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR

Analysis of ischaemic crisis using the informational causal entropy-complexity plane

In the present work, an ischaemic process, mainly focused on the reperfusion stage, is studied using the informational causal entropy-complexity plane. Ischaemic wall behavior under this condition was analyzed through wall thickness and ventricular pressure variations, acquired during an obstructive flow maneuver performed on left coronary arteries of surgically instrumented animals. Basically, the induction of ischaemia depends on the temporary occlusion of left circumflex coronary artery (which supplies blood to the posterior left ventricular wall) that lasts for a few seconds. Normal perfusion of the wall was then reestablished while the anterior ventricular wall remained adequately perfused during the entire maneuver. The obtained results showed that system dynamics could be effectively described by entropy-complexity loops, in both abnormally and well perfused walls. These results could contribute to making an objective indicator of the recovery heart tissues after an ischaemic process, in a way to quantify the restoration of myocardial behavior after the supply of oxygen to the ventricular wall was suppressed for a brief period.Fil: Legnani, Walter. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Universidad Nacional de Lanús; ArgentinaFil: Traversaro Varela, Francisco. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Redelico, Francisco Oscar. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Cymberknop, Leandro Javier. Instituto Tecnologico de Buenos Aires. Departamento de Bioingenieria; Argentina. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; ArgentinaFil: Armentano, Ricardo Luis. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; Argentina. Instituto Tecnologico de Buenos Aires. Departamento de Bioingenieria; ArgentinaFil: Rosso, Osvaldo Aníbal. Universidad de los Andes; Chile. Universidade Federal de Alagoas; Brasil. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Polynomial Eigenvalue Problem is Well Conditioned for Random Inputs

We compute the exact expected value of the squared condition number for the polynomial eigenvalue problem, when the input matrices have entries coming from the standard complex Gaussian distribution, showing that in general this problem is quite well conditioned.The first author's work was partially supported by Agencia Nacional de Investigación e Innovación (ANII), Uruguay, and by CSIC group 618, Universidad de La República, Uruguay. The second author's work was partially supported by MTM2017-83816-P and MTM2017-90682-REDT from Spanish Ministry of Science MICINN and by 21.SI01.64658 from Universidad de Cantabria and Banco de Santander

A New Constructive Heuristic for the Fm|block|ST

This paper deals with the blocking flow shop problem and proposes new constructive procedures for the total tardiness minimization of jobs. The heuristic has three-phases to build the sequence; the first phase selects the first job to be scheduled, the second phase arranges the remaining jobs and the third phase uses the insertion procedure of NEH to improve the sequence. The proposed procedures evaluate the tardiness associated to the sequence obtained before and after the third phase in order to keep the best of both because the insertion phase can worsen the result. The computational evaluation of these procedures against the benchmark constructive procedures from the literature reveals their good performance.Postprint (published version