The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.
Purpose. To evaluate the relationships between C-reactive protein (CRP) and retinal and choroidal thickness by swept-source optical coherence tomography (SS-OCT). Methods. The participants included in the prospective cross-sectional study underwent a comprehensive ophthalmic examination. Based on the CRP values, the subjects were divided into the CRP (+) group (
CRP
≥
8.2
mg/L) and the CRP (−) group (
CRP
<
8.2
mg/L). The retinal and choroidal thickness was compared between the two groups. Results. This study enrolled 43 right eyes of 43 subjects from the CRP (+) group and 86 right eyes of 86 gender- and age-match subjects from the CRP (−) group. The choroidal thickness in the CRP (+) group was thinner than that in the CRP (−) group except for the outer nasal sector of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. However, the retinal thickness only in the inner temporal sector showed a significant difference. According to Pearson’s correlation analysis, the CRP was significantly negatively correlated with the choroidal thickness in all sectors and the retinal thickness only in the inner temporal and outer nasal sectors of the ETDRS grid. Conclusion. CRP levels are associated with retinal and choroidal thickness. The data related to the retinal and choroidal thickness changes may help understand the pathogenesis of specific ocular abnormalities in patients with systemic inflammation.
N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.
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