Search

Context: Fungal keratitis, a corneal fungal infection of the eye caused mainly byCandidaspecies, has become the leading cause of blindness resulting from corneal disease in China. Present limitations in the management of ophthalmic fungal infections include the inability to provide long-term extraocular drug delivery without compromising intraocular structures and/or systemic drug exposure. Objective: The aim of this study was to construct amphotericin B (AmB) loaded, chitosan-modified, nanostructured lipid carriers (AmB-CH-NLC) for prolonged ocular application and for the improvement of the targeted delivery of AmB to the ocular mucosa. Materials and methods: The AmB-CH-NLC was produced by the method of emulsion evaporation-solidification at low temperature. The particle size, zeta potential, and encapsulation efficiency, drug-release behavior, and corneal penetration ability were performedin vitroandin vivo. Results and discussion: The prepared AmB-CH-NLC nanoparticles exhibited a measured size of 185.4 nm, a zeta potential of 27.1 mV, and an entrapment efficiency of 90.9%. Sustained drug release behavior was observedin vitro. Thein vivoocular pharmacokinetic study indicated improved bioavailability of AmB-CH-NLC. The corneal penetration study showed that the AmB-CH-NLC could successfully penetrate into the cornea with no obvious irritation to the rabbits’ eyes. Conclusion: The results support that this novel nanomedicine could be a promising system for effective ocular delivery of amphotericin B for fungal keratitis-targeted therapy. [ABSTRACT FROM AUTHOR]

Autophagy is a cellular process that executes the turnover of dysfunctional organelles and misfolded or abnormally aggregated proteins. Microtubule-associated protein MAP1S interacts with autophagy marker LC3 and positively regulates autophagy flux. LC3 binds with fibronectin mRNA and facilitates its translation. The synthesized fibronectin protein is exported to cell surface to initiate the assembly of fibronectin extracellular matrix. Fibronectin is degraded in lysosomes after it is engulfed into cytosol via endocytosis. Here, we show that defects in MAP1S-mediated autophagy trigger oxidative stress, sinusoidal dilation, and lifespan reduction. Overexpression of LC3 in wild-type mice increases the levels of fibronectin and γ-H2 AX, a marker of DNA double-strand breakage. LC3-induced fibronectin is efficiently degraded in lysosomes to maintain a balance of fibronectin levels in wild-type mice so that the mice live a normal term of lifespan. In the LC3 transgenic mice with MAP1S deleted, LC3 enhances the synthesis of fibronectin but the MAP1S depletion causes an impairment of the lysosomal degradation of fibronectin. The accumulation of fibronectin protein promotes liver fibrosis, induces an accumulation of cell population at the G0/G1 stage, and further intensifies oxidative stress and sinusoidal dilatation. The LC3-induced overexpression of fibronectin imposes stresses on MAP1S-deficient mice and dramatically reduces their lifespans. Therefore, MAP1S-mediated autophagy plays an important role in maintaining mouse lifespan especially in the presence of extra amount of fibronectin. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the burden of type 2 diabetes (T2D) among adolescents (15-24 years old) from 1990 to 2019., Methods: The age-standardized incidence rate (ASIR) and disability-adjusted life years (DALYs) rate of adolescents were analyzed according to age, sex, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) was estimated to quantify the trends., Results: From 1990 to 2019, the ASIR (EAPC = 1.07) and age-standardized DALY rate (EAPC = 2.01) of T2D in adolescents showed an increasing trend. The ASIR was higher in males than in females. The burden was greater in the 20-24-year age group. Of the five SDI regions, the highest ASIR and age-standardized DALY rate were found in low-middle-SDI regions, while the greatest increase in these rates was observed in high-SDI regions (EAPC = 3.28 and 3.55, respectively). Of the 21 regions analyzed, the highest ASIR and age-standardized DALY rate were found in Oceania. Of the 204 countries analyzed, the Marshall Islands (651.16) and Kiribati (277.42) had the highest ASIR and DALYs, respectively. The regions with the greatest increase in the ASIR from 1990 to 2019 were Western Europe (EAPC = 4.15), high-income North America (EAPC = 4.72)., Conclusions: The global burden of T2D in adolescents showed an overall upward trend from 1990 to 2019. It is necessary to strengthen prevention measures related to risk factors for T2D among young people, especially in areas with a low-to-medium SDI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Hou, Yi, Li and Zhao.)

Aim: This study was aimed to detect the correlation of nitric oxide synthase 3 (NOS3) gene polymorphisms (T-786C and G894T) and retinopathy of prematurity (ROP) susceptibility. Interaction between NOS3 gene polymorphisms and the duration of oxygen therapy was also explored in ROP babies., Methods: Genotypes of NOS3 gene polymorphisms were genotyped by MassArray method. Hardy-Weinberg equilibrium (HWE) was used to calculate the representativeness of the cases and controls. Crossover analysis was utilized to explore the gene environment interactions. Relative risk of ROP was presented by odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs)., Results: Among the subject features, oxygen therapy had obvious difference between case and control groups (P<0.05). There existed significant association between-786C allele and ROP susceptibility (P=0.049, OR=0.669, 95% CI=0.447-0.999). Genotypes of T-786C polymorphism and genotypes and alleles of G894T polymorphism did not related to the susceptibility of ROP. Interactions were existed between NOS3 gene polymorphisms and oxygen therapy duration. When the duration of oxygen therapy was less than 17 days, both -786CC genotype and 894GT genotype were correlated with ROP susceptibility (P=0.020, OR=0.115, 95% CI=0.014-0.960; P=0.011, OR=0.294, 95% CI=0.100-0.784)., Conclusion: -786C allele might have a protective effect for ROP. Interactions of -786CC and 894GT genotype with oxygen therapy duration (less than 17 days) were both protection factors of ROP.

Diabetic Retinopathy (DR) is one of the most common complications of the late phase diabetes, and also a common cause of blindness. High mobility group box 1 (HMGB-1) is considered to be an inflammatory mediator in the late phase that promotes inflammation and neovascularization in diabetes. Therefore, this paper discussed the role of HMGB-1 in diabetic retinopathy inflammation and neovascularization. 96 adult SD rats were randomly divided into control and diabetes group. The diabetic rat model was established by intraperitoneal injection of streptomycin (0.1 mol/L). Western blot was applied to determine HMGB-1 and its receptor RAGE and TLR2 protein expression in the serum. TUNEL was used to detect retinal apoptosis. Immunofluorescence was performed to test HMGB1 protein expression in retina. HBGM-1 and RAGE expression in diabetic rat retina was significantly higher than the control (P < 0.05), while TLR2 expression was lower (P < 0.05). TUNEL detection showed that diabetic rat retinal cells presented obviously higher apoptosis rate (P < 0.05). Immunofluorescence test revealed that HMGB1 largely expressed in the diabetic rat retinal cells (P < 0.05). HMGB1 may involve in the pathogenesis of diabetic retinopathy by binding with RAGE receptor to accelerate rat retinal cells apoptosis.

Glaucoma is a complex class of degenerative optic neuropathy. Multiple mechanisms were involved in glaucomatous optic nerve damage. In recent years, research progression has been made in the relationship between axonal degeneration and glaucoma with more attention and effort dedicated to explicate the pathogenesis of progressive optic nerve injury. Series of studies indicate that the interplay between distal axonal degeneration and axon neuron damage may play an important role in the progression of the disease. Distal axonal lesions may contribute to glaucoma, the pathological basis may be the retrograde degeneration of the optic nerve in visual pathways. In this article, we review the latest findings in the distal axonal degeneration and glaucomatous optic neuropathy.

Objective: To evaluate the effect of basic fibroblast growth factor (bFGF) treated collagen composite sponge on vascularization of HA orbital implants., Methods: New Zealand rabbits received three different orbital implants:naked implants, implants wrapped with collagen composite sponge and implants wrapped with bFGF treated collagen composite sponge.Implants were harvested 2, 4, 6, 8 and 12 weeks after surgery. The vascularization of implants was then assessed by light and electron microscopy., Results: At post-surgery weeks of 2, 4 and 6, bFGF treated collagen composite sponge induced the highest degree of vascularization of orbital implants. Collagen composite sponge alone resulted in higher extent of vascularization than naked implants. Complete vascularization of implants was observed at post-surgery 6 weeks by bFGF treated collagen composite sponge, which was not observed in the other two groups until post-surgery 8 weeks. There were significant differences in the average length of fibrovasculature and in the degree of vascularization among each group at post-surgery 2, 4 and 6 weeks (P<0.05), while no statistical difference was observed at post-surgery 8 and 12 weeks (P>0.05)., Conclusions: bFGF treated collagen composite sponge facilitates fibrovascularization of orbital implants, and shortens the time required for complete vascularization. Collagen composite sponge alone promotes early-stage fibrovascularization, but fails to facilitate complete vascularization of orbital implants.