RESUMEN
The periosteum, a vascularized tissue membrane, is essential in bone regeneration following fractures and bone loss due to some other reasons, yet there exist several research gaps concerning its regeneration. These gaps encompass reduced cellular proliferation and bioactivity, potential toxicity, heightened stiffness of scaffold materials, unfavorable porosity, expensive materials and procedures, and suboptimal survivability or inappropriate degradation rates of the implanted materials. This research used an interdisciplinary approach by forming a new material fabricated through electrospinning for the proposed application as a layer-by-layer tissue-engineered periosteum (TEP). TEP comprises poly(ε-caprolactone) (PCL), PCL/gelatin/magnesium-doped zinc oxide (vascular layer), and gelatin/bioactive glass/COD liver oil (osteoconductive layer). These materials were selected for their diverse properties, when integrated into the scaffold formation, successfully mimic the characteristics of native periosteum. Scanning electron microscopy (SEM) was employed to confirm the trilayer structure of the scaffold and determine the average fiber diameter. In-vitro degradation and swelling studies demonstrated a uniform degradation rate that matches the typical recovery time of periosteum. The scaffold exhibited excellent mechanical properties comparable to natural periosteum. Furthermore, the sustained release kinetics of COD liver oil were observed in the trilayer scaffold. Cell culture results indicated that the three-dimensional topography of the scaffold promoted cell growth, proliferation, and attachment, confirming its non-toxicity, biocompatibility, and bioactivity. This study suggests that the fabricated scaffold holds promise as a potential artificial periosteum for treating periostitis and bone fractures.
Asunto(s)
Gelatina , Andamios del Tejido , Andamios del Tejido/química , Gelatina/química , Periostio , Biomimética , Aceite de Hígado de Bacalao , Poliésteres/química , Ingeniería de Tejidos/métodosRESUMEN
A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC50 values ranging from 11.73±0.49 to 27.36±0.29â µM for AChE and 21.83±0.39 to 39.43±0.44â µM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The drug-likeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.
Asunto(s)
Enfermedad de Alzheimer , Butirilcolinesterasa , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Oxadiazoles , Relación Estructura-Actividad , Compuestos de SulfhidriloRESUMEN
Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides into the corresponding 5'-monophosphate deoxyribonucleosides to supply the cell with nucleic acid precursors. In mitochondrial fractions of the model plant Arabidopsis thaliana, we detected deoxyadenosine and thymidine kinase activities, while the cytosol fraction contained six-fold lower activity and chloroplasts contained no measurable activities. In addition, a mitochondrial fraction isolated from the potato Solanum tuberosum contained thymidine kinase and deoxyadenosine kinase activities. We conclude that an active salvage of deoxyribonucleosides in plants takes place in their mitochondria. In general, the observed localization of the plant dNK activities in the mitochondrion suggests that plants have a different organization of the deoxyribonucleoside salvage compared to mammals.