Endothelia inflammation damage is vital to the development and progression of chronic venous disease. In the present study, we explored the protective effect of melatonin on endothelia apoptosis induced by LPS, particularly focusing on the mitochondrial fission. We demonstrated that human umbilical vein endothelial cells (HUVEC) subjected to LPS for 12 h exhibited a higher apoptotic rate. However, melatonin (1-20 μM) treatment 12 h before LPS had the ability to protect HUVEC cell against LPS-mediated apoptosis in a dose-dependent manner. Furthermore, LPS induced the cytoplasmic calcium overload which was responsible for the upregulation of calcium-dependent xanthine oxidase (XO). Higher XO expression was associated with reactive oxygen species (ROS) overproduction, leading to the Drp1 phosphorylation at the Ser616 site and migration on the surface of mitochondria. Furthermore, phosphorylated Drp1 initiated the mitochondrial fission contributing to the caspase9-dependent mitochondrial apoptosis as evidenced by lower membrane potential, more cyt-c leakage into the nuclear, and higher expression of proapoptotic proteins. However, melatonin treatment could trigger the AMPK pathway, which was followed by the increased SERCA2a expression. Activation of AMPK/SERCA2a by melatonin inhibited the calcium overload, XO-mediated ROS outburst, Drp1-required mitochondrial fission, and final mitochondrial apoptosis. In summary, this study confirmed that LPS induced HUVEC apoptosis through Ca-XO-ROS-Drp1-mitochondrial fission axis and that melatonin reduced the apoptosis of HUVEC through activation of the AMPK/SERCA2a pathway.
Epidemiological data about the prevalence of amblyopia around the world vary widely among regions and periods. This meta-analysis aimed to determine the global prevalence of amblyopia in children. PubMed, Embase, and the Cochrane Library were searched for prevalence studies published up to 5 November 2021. The outcome was the prevalence of amblyopia, analyzed as pooled estimates with 95% confidence intervals (CI). A total of 97 studies were included, including 4,645,274 children and 7,706 patients with amblyopia. The overall worldwide pooled prevalence of amblyopia was 1.36% (95%CI: 1.27–1.46%). The prevalence of amblyopia was higher in males (1.40%, 95%CI: 1.10–1.70%) than in females (1.24%, 95%CI: 0.94–1.54%) (OR = 0.885, 95%CI: 0.795–0.985, P = 0.025). The results of the meta-regression analysis showed that there were no significant associations between the prevalence of amblyopia and geographical area, publication year, age, sample size, and whether it was carried out in a developed or developing country (all P > 0.05). Begg’s test (P = 0.065) and Egger’s test (P < 0.001) showed that there was a significant publication bias in the prevalence of amblyopia. In conclusion, amblyopia is a significant vision problem worldwide, and public health strategies of early screening, treatment, and management are important.
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