Human corneal substitute Dotaz Zobrazit nápovědu
Cannabidiol (CBD) is the non-psychoactive component of the plant Cannabis sativa (L.) that has great anti-inflammatory benefits and wound healing effects. However, its high lipophilicity, chemical instability, and extensive metabolism impair its bioavailability and clinical use. Here, we report on the preparation of a human cornea substitute in vitro and validate this substitute for the evaluation of drug penetration. CBD nanoemulsion was developed and evaluated for stability and biological activity. The physicochemical properties of CBD nanoemulsion were maintained during storage for 90 days under room conditions. In the scratch assay, nanoformulation showed significantly ameliorated wound closure rates compared to the control and pure CBD. Due to the lower cytotoxicity of nanoformulated CBD, a higher anti-inflammatory activity was demonstrated. Neither nanoemulsion nor pure CBD can penetrate the cornea after the four-hour apical treatment. For nanoemulsion, 94 % of the initial amount of CBD remained in the apical compartment while only 54 % of the original amount of pure CBD was detected in the apical medium, and 7 % in the cornea, the rest was most likely metabolized. In summary, the nanoemulsion developed in this study enhanced the stability and biological activity of CBD.
- Klíčová slova
- Anti-inflammatory, Bioavailability, Cannabidiol, Human corneal substitute, Nanoemulsion, Wound healing,
- MeSH
- antiflogistika farmakologie MeSH
- biologická dostupnost MeSH
- hojení ran MeSH
- kanabidiol * chemie MeSH
- lidé MeSH
- rohovka MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- kanabidiol * MeSH
The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.
- MeSH
- abnormality očí enzymologie genetika MeSH
- alely MeSH
- dítě MeSH
- fenotyp MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- katarakta genetika MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- oči embryologie růst a vývoj MeSH
- rodokmen MeSH
- vývojové poruchy u dětí genetika MeSH
- zákal rohovky genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- forkhead transkripční faktory MeSH
- FOXE3 protein, human MeSH Prohlížeč
A Czech family with three individuals carrying a novel mutation, 290 A-->T (Glu97Val), in the myelin protein zero gene (P0) is reported. The two eldest carriers developed progressive sensorineural hearing loss and abnormal pupillary reaction at age 18. These preceded the onset of the classic signs of Charcot-Marie-Tooth disease (CMT) by more than a decade. Sural nerve biopsy and nerve conduction studies were compatible with the axonal type of CMT. The authors show that progressive hearing loss can be the first symptom in P0 mutation carriers.
- MeSH
- abnormální reflex genetika MeSH
- biopsie MeSH
- bodová mutace * MeSH
- Charcotova-Marieova-Toothova nemoc epidemiologie genetika MeSH
- dospělí MeSH
- exony genetika MeSH
- falešně negativní reakce MeSH
- fenotyp MeSH
- lidé MeSH
- missense mutace * MeSH
- myelinový P0 protein nedostatek genetika MeSH
- nervové vedení MeSH
- nervus suralis patologie MeSH
- percepční nedoslýchavost genetika MeSH
- progrese nemoci MeSH
- reflex pupilární genetika MeSH
- rodokmen MeSH
- senioři MeSH
- substituce aminokyselin MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Československo MeSH
- Názvy látek
- myelinový P0 protein MeSH