Impaired wound healing in diabetics usually leads to life-threatening complications. To develop a system for fastening skin wound healing efficiently and safely in diabetics, thermos-sensitive hydrogel containing the nanodrug, loaded in the form of gelatin microspheres (GMs), was designed to deliver curcumin (Cur) as a therapeutic drug. Cur is a naturally existing polyphenolic compound with a broad range of biological functions useful for potential therapies. Because Cur molecule has weakness in both bioavailability and in vivo stability, delivery of Cur requires assistance from other molecules to act as carrier vehicles in a sustained manner for therapeutic use. At first, self-assembly of Cur nanoparticles (CNPs) was done to improve bioavailability. The CNPs were further enclosed into GMs for responding to the matrix metalloproteinases (MMPs) that usually overexpress at diabetic nonhealing wound sites. The GMs containing CNPs were loaded into the thermos-sensitive hydrogel and were finally proved for the capacity of specially induced drug release at the wound bed, which promoted the efficacy in healing the standardized skin wounds in streptozotocin-induced diabetic mice. Our results indicated that the successfully developed CNP delivery system had the capacity to significantly promote skin wound healing, which suggested that it could have the potential to become a wound dressing with the properties of antioxidants and promotions of cell migration.
Unfavorable genetic correlations between growth and wood quality traits are one of the biggest challenges in advanced conifer breeding programs. To examine and deal with such correlation, increment cores were sampled at breast height from 5,618 trees in 524 open-pollinated families in two 21-year-old Norway spruce progeny trials in southern Sweden, and age trends of genetic variation, genetic correlation, and efficiency of selection were investigated. Wood quality traits were measured on 12-mm increment cores using SilviScan. Heritability was moderate (~0.4-0.5) for wood density and modulus of elasticity (MOE) but low (~0.2) for microfibril angle (MFA). Different age trends were observed for wood density, MFA, and MOE, and the lower heritability of MFA relative to wood density and MOE in Norway spruce contrasted with general trends of the three wood quality traits in pine. Genetic correlations among growth, wood density, MFA, and MOE increased to a considerably high value from pith to bark with unfavorable genetic correlations (−0.6 between growth and wood density, −0.74 between growth and MOE). Age-age genetic correlations reached 0.9 after ring 4 for diameter at breast height (DBH), wood density, MFA, and MOE traits. Early selections at ring 10 for diameter and at ring 6 or 7 for wood quality traits had similar effectiveness as selection conducted at reference ring 15. Selection based on diameter alone produced 19.0 % genetic gain in diameter but resulted in 4.8 % decrease in wood density, 9.4 % decrease in MOE, and 8.0 % increase in MFA. Index selection with a restriction of no change in wood density, MOE, and MFA, respectively, produced relatively lower genetic gains in diameter (16.4, 12.2, and 14.1 %, respectively), indicating such index selection could be implemented to maintain current wood density. Index selection using economic weights is, however, recommended for maximum economic efficiency.
Rapid progress in understanding the molecular mechanisms associated with cochlear and auditory nerve degenerative processes offers hope for the development of gene-transfer and molecular approaches to treat these diseases in patients. For therapies based on these discoveries to become clinically useful, it will be necessary to develop safe and reliable mechanisms for the delivery of drugs into the inner ear, bypassing the blood-labyrinthine barrier. Toward the goal of developing an inner ear perfusion device for human use, a reciprocating microfluidic system that allows perfusion of drugs into the cochlear perilymph through a single inlet hole in scala tympani of the basal turn was developed. The performance of a prototype, extracorporeal reciprocating perfusion system in guinea pigs is described. Analysis of the cochlear distribution of compounds after perfusion took advantage of the place-dependent generation of responses to tones along the length of the cochlea. Perfusion with a control artificial perilymph solution had no effect. Two drugs with wellcharacterized effects on cochlear physiology, salicylate (5 mM) and DNQX (6,7-Dinitroquinoxaline-2,3-dione; 100 and 300 μM), reversibly altered responses. The magnitude of drug effect decreased with distance from the perfusion pipette for up to 10 mm, and increased with dose and length of application.
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