Objective This study evaluates the epidemiological characteristics, ophthalmological manifestations, and different therapeutic options available for patients with multiple sclerosis (MS) in China, Spain, and Cuba. Methods A self-designed questionnaire was used to conduct a comparable descriptive cross-sectional study on patients with MS. The survey included patients' demographic data, ocular manifestations related to MS, and treatment methodology followed in the three countries. The online survey was designed using the Wenjuanxing survey platform, and a survey link was circulated through WhatsApp, WeChat, and emails. Quantitative data were expressed as mean and standard deviation, the Kruskal-Wallis test was used for non-parametric variables. Qualitative data were expressed as numerical and percentage. The chi-square test (χ2) was used to compare the group's response categories. The statistical difference was considered significant when p < 0.05. Results The female-to-male ratio in all the three countries was 2-3:1, and relapsing-remitting MS (RRMS) was the most frequent in all three countries. Vision loss was slow and progressive in half of the patients from the three countries, with no significant differences ( p = 0.524). A higher percentage of steroid treatment was observed in Chinese patients in comparison with the patients from other two countries ( p < 0.001), and a similar trend was seen in the use of traditional medicines. Almost one-third of patients who did not receive any treatment recovered spontaneously in all the three countries ( p = 0.097). Conclusions MS occurs more frequently in the relapsing-remitting clinical form and there is a clear female predominance. The first ocular crisis or clinical debut of MS is characterized by slow and progressive visual impairment, increasing and adding to other ocular manifestations during its evolutionary course. Spontaneous recovery of vision after an attack of optic neuritis in the course of MS is possible.
Background Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Thus, there is an urgent need to solve this problem. Results Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. In our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, silencing GPX4 and DHODH might be a new and effective strategy to overcome sorafenib resistance. Here, a new ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nanodelivery system (ExoSP94−lamp2b−RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance, which might open a new avenue for clinically overcoming sorafenib resistance. Conclusions We designed HCC-targeted exosomes (ExoSP94−Lamp2b−RRM) that can deliver a new ferroptosis inducer. Our data show that ExoSP94−lamp2b−RRM-multi-siRNA could enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib. This is the first study to describe the use of engineered exosomes to overcome acquired sorafenib resistance with respect to ferroptosis.
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