Search results for " MEC"

Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment

2020

Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients&rsquo

Human Dental Pulp Stem Cells Exhibit Different Biological Behaviours in Response to Commercial Bleaching Products

2018

The purpose of this study was to evaluate the diffusion capacity and the biological effects of different bleaching products on human dental pulp stem cells (hDPSCs). The bleaching gel was applied for 90, 30 or 15 min to enamel/dentine discs that adapted in an artificial chamber. The diffusion of hydrogen peroxide (HP) was analysed by fluorometry and the diffusion products were applied to hDPSCs. Cell viability, cell migration and cell morphology assays were performed using the eluates of diffusion products. Finally, cell apoptosis and the expression of mesenchymal stem cell markers were analysed by flow cytometry. Statistical analysis was performed using analysis of variance and Kruskal&nda…

A Dehydrogenase Dual Hydrogen Abstraction Mechanism Promotes Estrogen Biosynthesis: Can We Expand the Functional Annotation of the Aromatase Enzyme?

2018

Cytochrome P450 (CYP450) enzymes are involved in the metabolism of exogenous compounds and in the synthesis of signaling molecules. Among the latter, human aromatase (HA) promotes estrogen biosynthesis, which is a key pharmacological target against breast cancers. After decades of debate, interest in gaining a comprehensive picture of HA catalysis has been renewed by the recent discovery that compound I (Cpd I) is the reactive species of the peculiar aromatization step. Herein, for the first time, a complete atomic-level picture of all controversial steps of estrogen biosynthesis is presented. By performing cumulative quantum-classical molecular dynamics and metadynamics simulations of abou…

Molecular Mechanism Involved in the Pathogenesis of Early-Onset Epileptic Encephalopathy

2019

Recent studies have shown that neurologic inflammation may both precipitate and sustain seizures, suggesting that inflammation may be involved not only in epileptogenesis but also in determining the drug-resistant profile. Extensive literature data during these last years have identified a number of inflammatory markers involved in these processes of “neuroimmunoinflammation” in epilepsy, with key roles for pro-inflammatory cytokines such as: IL-6, IL-17 and IL-17 Receptor (IL-17R) axis, Tumor-Necrosis-Factor Alpha (TNF-α) and Transforming-Growth-Factor Beta (TGF-β), all responsible for the induction of processes of blood-brain barrier (BBB) disruption and inflammation of the Central Nervou…

2019

The DNA-binding of the natural benzophenanthridine alkaloid chelerythrine (CHE) has been assessed by combining molecular modeling and optical absorption spectroscopy. Specifically, both double-helical (B-DNA) and G-quadruplex sequences—representative of different topologies and possessing biological relevance, such as telomeric or regulatory sequences—have been considered. An original multiscale protocol, making use of molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, allowed us to compare the theoretical and experimental circular dichroism spectra of the different DNA topologies, readily providing atomic-level details of the CHE–DNA binding…

Collective behavior of quorum-sensing run-and-tumble particles in confinement

2016

We study a generic model for quorum-sensing bacteria in circular confinement. Every bacterium produces signaling molecules, the local concentration of which triggers a response when a certain threshold is reached. If this response lowers the motility then an aggregation of bacteria occurs, which differs fundamentally from standard motility-induced phase separation due to the long-ranged nature of the concentration of signal molecules. We analyze this phenomenon analytically and by numerical simulations employing two different protocols leading to stationary cluster and ring morphologies, respectively.

Cohesive Model for the Simulation of Crack Initiation and Propagation in Mixed-Mode I/II in Composite Materials

2019

A cohesive element able to connect and simulate crack growth between independently modeled finite element subdomains with non-matching meshes is proposed and validated. The approach is based on penalty constraints and has several advantages over conventional FE techniques in disconnecting two regions of a model during crack growth. The most important is the ability to release portion of the interface that are smaller than the local finite element length. Thus, the growth of delamination is not limited to advancing by releasing nodes of the FE model, which is a limitation common to the methods found in the literature. Furthermore, it is possible to vary the penalty parameter within the cohes…

Topographic Independent Component Analysis reveals random scrambling of orientation in visual space

2017

Neurons at primary visual cortex (V1) in humans and other species are edge filters organized in orientation maps. In these maps, neurons with similar orientation preference are clustered together in iso-orientation domains. These maps have two fundamental properties: (1) retinotopy, i.e. correspondence between displacements at the image space and displacements at the cortical surface, and (2) a trade-off between good coverage of the visual field with all orientations and continuity of iso-orientation domains in the cortical space. There is an active debate on the origin of these locally continuous maps. While most of the existing descriptions take purely geometric/mechanistic approaches whi…

Economic assessment based on scenario analysis for the production of a new functional pasta

2018

Abstract Nowadays functional foods are becoming more popular due to their capacity to prevent and/or reduce the risk of certain diseases. Functional foods improve health and give physiological benefits providing nutrients beyond the simple nutritional value. The market for functional foods is growing rapidly and the consumers are willing to pay a premium price for these products. In this context, the production of pasta comprising Opuntia may represent an opportunity to combine the widespread consumption of pasta in the traditional Mediterranean Diet and the beneficial characteristics of the Opuntia, including anti-inflammatory, antioxidant, hypoglycemic, antimicrobial and neuroprotective p…

Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury

2017

Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…