Orange-derived extracellular vesicles nanodrugs for efficient treatment of ovarian cancer assisted by transcytosis effect

Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.

Dissemination of insertion sequences IS605, IS606 among clinical isolates of Helicobacter pylori in China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the distribution of IS605, IS606 among clinical isolates of Helicobacter pylori in China.</p><p><b>METHODS</b>A total of 104 H.pylori strains isolated from 5 different geographic regions in China were analyzed by PCR and dot-blot.</p><p><b>RESULTS</b>Forty-two strains out of the 104 isolates from 5 regions in China were found containing IS605 with 19 containing IS606. The frequency (66%) of IS605 positive strains from Yunnan province was higher than that from other areas. The different distribution of IS606 was neither associated with geographical regions nor with the presence of IS605 but IS606 were associated with the different clinical outcomes. However, the two reading frames ORFA and ORFB of IS605 were constantly coexisting.</p><p><b>CONCLUSION</b>In China, IS605 and IS606 of H. pylori were widely existing but the presence of IS605 in H. pylori might be associated with geographic origin.</p>