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A bioinformatic approach was applied to evaluate the effect of treatment with Bevacizumab on the gene expression profile of colorectal adenocarcinoma cells. The transcriptomic profile of Bevacizumab-adapted HCT-116 (Bev/A) colorectal adenocarcinoma cells was determined and compared with that of the corresponding control cell line by Agilent microarray analysis. Raw data were preprocessed, normalized, filtered, and subjected to a differential expression analysis using standard R/Bioconductor packages (i.e., limma, RankProd). As consequence of Bevacizumab adaptation, 166 differentially expressed genes (DEGs) emerged, most of them (123) resulted downregulated and 43 overexpressed. The list of statistically significant dysregulated genes was used as an input for functional overrepresentation analysis using ToppFun web tool. Such analysis pointed at cell adhesion, cell migration, extracellular matrix organization and angiogenesis as the main dysregulated biological process involved in Bevacizumab-adaptation of HCT116 cells. In addition, gene set enrichment analysis was performed using GSEA, searching for enriched terms within the Hallmarks (H), Canonical Pathways (CP), and Gene Ontology (GO) gene sets. GO terms that showed significant enrichment included: transportome, vascularization, cell adhesion and cytoskeleton, extra cellular matrix (ECM), differentiation and epithelial–mesenchymal transition (EMT), inflammation and immune response. Raw and normalized microarray data were deposited in the Gene Expression Omnibus (GEO) public repository with accession number GSE221948.

Titanium and titanium alloys are the prevailing dental implant materials owing to their favorable mechanical properties and biocompatibility, but how roughness dictates the biological response is still a matter of debate. In this study, laser texturing was used to generate eight paradigmatic roughened surfaces, with the aim of studying the early biological response elicited on MC3T3-E1 pre-osteoblasts. Prior to cell tests, the samples underwent SEM analysis, optical profilometry, protein adsorption assay, and optical contact angle measurement with water and diiodomethane to determine surface free energy. While all the specimens proved to be biocompatible, supporting similar cell viability at 1, 2, and 3 days, surface roughness could impact significantly on cell adhesion. Factorial analysis and linear regression showed, in a robust and unprecedented way, that an isotropic distribution of deep and closely spaced valleys provides the best condition for cell adhesion, to which both protein adsorption and surface free energy were highly correlated. Overall, here the authors provide, for the first time, a thorough investigation of the relationship between roughness parameters and osteoblast adhesion that may be applied to design and produce new tailored interfaces for implant materials. [ABSTRACT FROM AUTHOR]

Living organisms are multiscale complex systems that have evolved high degrees of multifunctionality and redundancy in the structure–function relationship. A number of factors, only in part determined genetically, affect the jobs of proteins. The overall structural organization confers unique molecular properties that provide the potential to perform a pattern of activities, some of which are co‐opted by specific environments. The variety of multifunctional proteins is expanding, but most cases are handled individually and according to the still dominant 'one structure–one function' approach, which relies on the attribution of canonical names typically referring to the first task identified for a given protein. The present topical review focuses on the multifunctionality of ion channels as a paradigmatic example. Mounting evidence reports the ability of many ion channels (including members of voltage‐dependent, ligand‐gated and transient receptor potential families) to exert biological effects independently of their ion conductivity. 'Functionally based' nomenclature (the practice of naming a protein or family of proteins based on a single purpose) is a conceptual bias for three main reasons: (i) it increases the amount of ambiguity, deceiving our understanding of the multiple contributions of biomolecules that is the heart of the complexity; (ii) it is in stark contrast to protein evolution dynamics, largely based on multidomain arrangement; and (iii) it overlooks the crucial role played by the microenvironment in adjusting the actions of cell structures and in tuning protein isoform diversity to accomplish adaptational requirements. Biological information in protein physiology is distributed among different entwined layers working as the primary 'locus' of natural selection and of evolutionary constraints. [ABSTRACT FROM AUTHOR]

The mechanical and biological behaviors of PMMA/Al2O3 composites incorporating 30 wt.%, 40 wt.%, and 50 wt.% of Al2O3 were thoroughly characterized as regards to their possible application in implant-supported prostheses. The Al2O3 particles accounted for an increase in the flexural modulus of PMMA. The highest value was recorded for the composite containing 40 wt.% Al2O3 (4.50 GPa), which was about 18% higher than that of its unfilled counterpart (3.86 GPa). The Al2O3 particles caused a decrease in the flexural strength of the composites, due to the presence of filler aggregates and voids, though it was still satisfactory for the intended application. The roughness (Ra) and water contact angle had the same trend, ranging from 1.94 µm and 77.2° for unfilled PMMA to 2.45 µm and 105.8° for the composite containing the highest alumina loading, respectively, hence influencing both the protein adsorption and cell adhesion. No cytotoxic effects were found, confirming that all the specimens are biocompatible and capable of sustaining cell growth and proliferation, without remarkable differences at 24 and 48 h. Finally, Al2O3 was able to cause strong cell responses (cell orientation), thus guiding the tissue formation in contact with the composite itself and not enhancing its osteoconductive properties, supporting the PMMA composite's usage in the envisaged application. [ABSTRACT FROM AUTHOR]

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in--or are close to--clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity. [ABSTRACT FROM AUTHOR]

Magnetic Nanoparticles (MNPs) are of great interest in biomedicine, due to their wide range of applications. During recent years, one of the most challenging goals is the development of new strategies to finely tune the unique properties of MNPs, in order to improve their effectiveness in the biomedical field. This review provides an up-to-date overview of the methods of synthesis and functionalization of MNPs focusing on Iron Oxide Nanoparticles (IONPs). Firstly, synthesis strategies for fabricating IONPs of different composition, sizes, shapes, and structures are outlined. We describe the close link between physicochemical properties and magnetic characterization, essential to developing innovative and powerful magnetic-driven nanocarriers. In conclusion, we provide a complete background of IONPs functionalization, safety, and applications for the treatment of Central Nervous System disorders. [ABSTRACT FROM AUTHOR]

Aim: To clarify the mechanisms of interaction between SiO 2 nanoparticles (NPs) and the plasma membrane of GT1-7 neuroendocrine cells, with focus on the activation of calcium-permeable channels, responsible for the long lasting calcium influx and modulation of the electrical activity in these cells., Materials & Methods: Nontoxic doses of SiO 2 NPs were administered to the cells. Calcium imaging and patch clamp techniques were combined with a pharmacological approach., Results: TRPV4, Cx and Panx-like channels are the major components of the NP-induced inward currents. Preincubation with the antioxidant N-acetyl-L-cysteine strongly reduced the [Ca 2+ ] i increase., Conclusion: These findings suggest that SiO 2 NPs directly activate a complex set of calcium-permeable channels, possibly by catalyzing free radical production.

One of the most challenging goals in pharmacological research is overcoming the Blood Brain Barrier (BBB) to deliver drugs to the Central Nervous System (CNS). The use of physical means, such as steady and alternating magnetic fields to drive nanocarriers with proper magnetic characteristics may prove to be a useful strategy. The present review aims at providing an up-to-date picture of the applications of magnetic-driven nanotheranostics agents to the CNS. Although well consolidated on physical ground, some of the techniques described herein are still under investigation on in vitro or in silico models, while others have already entered in-or are close to-clinical validation. The review provides a concise overview of the physical principles underlying the behavior of magnetic nanoparticles (MNPs) interacting with an external magnetic field. Thereafter we describe the physiological pathways by which a substance can reach the brain from the bloodstream and then we focus on those MNP applications that aim at a nondestructive crossing of the BBB such as static magnetic fields to facilitate the passage of drugs and alternating magnetic fields to increment BBB permeability by magnetic heating. In conclusion, we briefly cite the most notable biomedical applications of MNPs and some relevant remarks about their safety and potential toxicity., Competing Interests: The authors declare no conflict of interest.