Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), some defects prevent its clinical application, such as severe side effects and loss of anticancer activity due to lack of selectivity to cancer cells and hydrolysis of ring E, respectively. To address the issue, herein a multifunctional SN38 derivative (compound 9) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound 9 exhibited superior cytotoxicity as irinotecan against human cervical cancer HeLa cells, albeit inferior to SN38. More significantly, compound 9 significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound 9 had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that compared with irinotecan, compound 9 induced similar apoptosis of cancer cells. Consequently, compound 9 can not only improve its tumor-targeting ability mediated by biotin but also exert the potent anticancer activity through the synergism of SN38 and valproic acid, indicating that the design concept is an effective strategy for structural modification of SN38.

Abstract Objective: Endometriosis is a chronic disease characterized by the growth of endometrial cells outside the uterine cavity. The dysfunction of the immune system is strongly associated with the progression of endometriosis, and is also correlated to the diversity of microbiota in the genital tract. According to previous studies, the microbiota significantly contributes to multi-systemic function, but the evidence of endometriosis and adenomyosis remains insufficient. Thus, the present study attempted to identify the characteristics of microbiota in endometriosis patients, and the connection between microbiota and immunological dysfunction. Methods: In order to compare and explore the potential microbiota correlated to endometriosis and adenomyosis in the genital tract, 134 samples obtained from the cervical canal, posterior fornix and uterine cavity were analyzed by 16s-rRNA sequencing. The raw data was filtered, analyzed and visualized, and bio-information methods were used to identify the different and distinctive characteristics of microbiota. Results: Two different locations near the cervix, cervical canal and posterior fornix, exhibited no differences in alpha diversity. Among the different disease groups, five microbiota were distinctive in the genus level, and Atopobium presented with the greatest significance in adenomyoisis-endometriosis patients. The LEfSe analysis failed to identify the special biomarkers, while several characteristic functions were identified through PICRUSt. Conclusion: Lactobacillus is dominant in the female lower genital tract, and Atopobium is distinctively higher in patients with endometriosis combined with adenomyosis. Several different functions of microbiota were explored, and these are found to be associated with endometriosis and adenomyosis. These findings may provide a new concept of microbiota/immune system/endometriosis system. There is an urgent need to investigate the potential microbial biomarkers of endometriosis in the future.

In recent years, green and healthy foods have attracted much attention. Plant-based foods have become a new trend to replace animal-derived foods. In this study, we used walnut and purple rice as the primary raw materials to produce yogurt. The process included boiling, mixing, grinding, inoculation, fermentation, and sterilization. We then analyzed the similarities and differences between the resulting walnut purple rice yogurt and unfermented walnut purple rice milk, as well as dairy-based yogurt, in terms of physical chemistry, flavor, and sensory characteristics. We also examined the similarities and differences between fermented walnut purple rice milk and conventional warm yogurt. The study results revealed that walnut purple rice yogurt exhibited greater viscosity than walnut purple rice milk and conventional dairy-based yogurt. Additionally, the former displayed enhanced stability and recovery ability. Notably, distinguishable differences were observed between the three types of yogurts in terms of the presence of unknown volatiles and the umami signal as indicated by electronic nose/tongue and GC-IMS analyses. The umami flavour of walnut purple rice yogurt surpasses that of traditional dairy-based yogurt, whilst its salty taste is lower than that of walnut purple rice milk. Despite possessing a weaker aroma than dairy-based yogurt, it is more potent than walnut purple rice milk. Additionally, its relative abundance of olefins, ketones, and alcohols enhances its unique flavour profile, surpassing both other options. Based on sensory analysis, it can be deduced that walnut purple rice yogurt has the highest overall acceptance rate.