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1.
Front Bioeng Biotechnol ; 11: 1289299, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38356932

RESUMO

The currently available treatments for inner ear disorders often involve systemic drug administration, leading to suboptimal drug concentrations and side effects. Cochlear implants offer a potential solution by providing localized and sustained drug delivery to the cochlea. While the mechanical characterization of both the implants and their constituent material is crucial to ensure functional performance and structural integrity during implantation, this aspect has been mostly overlooked. This study proposes a novel methodology for the mechanical characterization of our recently developed cochlear implant design, namely, rectangular and cylindrical, fabricated using two-photon polymerization (2 PP) with a novel photosensitive resin (IP-Q™). We used in silico computational models and ex silico experiments to study the mechanics of our newly designed implants when subjected to torsion mimicking the foreseeable implantation procedure. Torsion testing on the actual-sized implants was not feasible due to their small size (0.6 × 0.6 × 2.4 mm³). Therefore, scaled-up rectangular cochlear implants (5 × 5 × 20 mm³, 10 × 10 × 40 mm³, and 20 × 20 × 80 mm³) were fabricated using stereolithography and subjected to torsion testing. Finite element analysis (FEA) accurately represented the linear behavior observed in the torsion experiments. We then used the validated Finite element analysis models to study the mechanical behavior of real-sized implants fabricated from the IP-Q resin. Mechanical characterization of both implant designs, with different inner porous structures (pore size: 20 µm and 60 µm) and a hollow version, revealed that the cylindrical implants exhibited approximately three times higher stiffness and mechanical strength as compared to the rectangular ones. The influence of the pore sizes on the mechanical behavior of these implant designs was found to be small. Based on these findings, the cylindrical design, regardless of the pore size, is recommended for further research and development efforts.

2.
Adv Med Sci ; 57(2): 183-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23183765

RESUMO

FoxO transcription factors act at the interconnections between metabolic pathways inducible by many important signal transducers and mediators, such as p53, Ikk-ß, NFKB, Akt, sirtuins, PTEN, and others. This may account for a crucial significance of disruptions in FoxO functions both in many kinds of diseases (including cancer, chronic inflammatory diseases, degenerative diseases, obesity, polymetabolic syndrome) and in some disease-like conditions (such as inflammaging, cachexia related to chronic inflammation, cancer-promotion by some chronic inflammatory responses, and the aging process itself). This paper reviews complex interactions between FoxOs and other signal transducers, trying to pinpoint how exactly disruptions of FoxO functions may occur, and how they may contribute to occurrence, development or complications of the conditions mentioned above.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Envelhecimento/metabolismo , Animais , Homeostase , Humanos , Inflamação/metabolismo , Transdução de Sinais , Estresse Fisiológico
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