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1.
Sci Rep ; 10(1): 20954, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262378

RESUMO

Amyloid-ß (Aß), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aß species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of Aß. Fibrillar (Aß40, Aß42) and oligomeric (Aß42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various Aß assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of Aß species. Oligomeric Aß42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar Aß42, whereas no retinal compromise was recorded in response to Aß40 fibrils. The toxic effect of Aß42 architectures was further reflected by retinal glial response. Fluorescence labelling of Aß42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular Aß species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological Aß aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Fenômenos Biofísicos , Multimerização Proteica , Retina/fisiopatologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Eletrorretinografia , Proteína Glial Fibrilar Ácida/metabolismo , Injeções Intravítreas , Multimerização Proteica/efeitos dos fármacos , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/patologia
2.
Int J Mol Sci ; 21(19)2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33036210

RESUMO

Bacterial biofilm formation on wet surfaces represents a significant problem in medicine and environmental sciences. One of the strategies to prevent or eliminate surface adhesion of organisms is surface modification and coating. However, the current coating technologies possess several drawbacks, including limited durability, low biocompatibility and high cost. Here, we present a simple antibacterial modification of titanium, mica and glass surfaces using self-assembling nano-structures. We have designed two different nano-structure coatings composed of fluorinated phenylalanine via the drop-cast coating technique. We investigated and characterized the modified surfaces by scanning electron microscopy, X-ray diffraction and wettability analyses. Exploiting the antimicrobial property of the nano-structures, we successfully hindered the viability of Streptococcus mutans and Enterococcus faecalis on the coated surfaces in both aerobic and anaerobic conditions. Notably, we found lower bacteria adherence to the coated surfaces and a reduction of 86-99% in the total metabolic activity of the bacteria. Our results emphasize the interplay between self-assembly and antimicrobial activity of small self-assembling molecules, thus highlighting a new approach of biofilm control for implementation in biomedicine and other fields.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Aderência Bacteriana , Fenômenos Fisiológicos Bacterianos , Biofilmes/efeitos dos fármacos , Nanoestruturas/química , Aerobiose , Anaerobiose , Bactérias/metabolismo , Materiais Revestidos Biocompatíveis/química , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/metabolismo , Enterococcus faecalis/fisiologia , Fenilalanina/análogos & derivados , Fenilalanina/química , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/metabolismo , Streptococcus mutans/fisiologia , Propriedades de Superfície
3.
ACS Appl Mater Interfaces ; 11(24): 21334-21342, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31134790

RESUMO

The rapid advancement of peptide- and amino-acid-based nanotechnology offers new approaches for the development of biomedical materials. The utilization of fluorenylmethyloxycarbonyl (Fmoc)-decorated self-assembling building blocks for antibacterial and anti-inflammatory purposes represents promising advancements in this field. Here, we present the antibacterial capabilities of the nanoassemblies formed by Fmoc-pentafluoro-l-phenylalanine-OH, their substantial effect on bacterial morphology, as well as new methods developed for the functional incorporation of these nanoassemblies within resin-based composites. These amalgamated materials inhibit and hinder bacterial growth and viability and are not cytotoxic toward mammalian cell lines. Importantly, due to the low dosage required to confer antibacterial activity, the integration of the nanoassemblies does not affect their mechanical and optical properties. This approach expands on the growing number of accounts on the intrinsic antibacterial capabilities of self-assembling building blocks and serves as a basis for further design and development of enhanced composite materials for biomedical applications.


Assuntos
Antibacterianos/química , Materiais Biocompatíveis/química , Nanoestruturas/química , Nanotecnologia/métodos , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Resinas Compostas/química , Materiais Dentários/química , Materiais Dentários/farmacologia
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