{"title":"纳米颗粒介导的递送系统通过激活TRPV5减轻感染结石的形成。","authors":"Hui Xiao, Gang Qin, Bo Fang","doi":"10.4149/gpb_2022028","DOIUrl":null,"url":null,"abstract":"<p><p>Infection stones constitute a small but intractable group of diseases of urinary system. In this study, we explored the potential therapeutic effect of a small activation RNA, ds-320, encapsulated in chitosan (320-chitosan). Western blot analysis verified the downregulation of TRPV5 in patients and rat model of infection stones, as well as the stimulation of ds-320 on TRPV5 expression. MTT assay showed that chitosan-mediated delivery was less cytotoxic to ds-320 compared with liposome delivery. Further a modified invasion assay revealed an inhibitory effect of 320-chitosan on bacterial invasion into normal rat kidney epithelial NRK-52E cells. The establishment of infection stone model was performed by intravesical injection of 1×108 CFU of Proteus mirabilis. In animal experiments, no visible stones were obtained. The number of live bacteria and white blood cells in urine showed no difference among all infected rats at the time of sacrifice. However, we observed a decline in urine calcium and pH, suggesting the effect of acidification. Overall, our study provides evidence for the protective effect of 320-chitosan, for its ability to down-regulate urinary calcium, acidify urine, and inhibit bacteria from invading renal epithelial cells. Thus, it can be served as an important complementary therapy for infection stones.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nanoparticle-mediated delivery system alleviates the formation of infection stones by activating TRPV5.\",\"authors\":\"Hui Xiao, Gang Qin, Bo Fang\",\"doi\":\"10.4149/gpb_2022028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Infection stones constitute a small but intractable group of diseases of urinary system. In this study, we explored the potential therapeutic effect of a small activation RNA, ds-320, encapsulated in chitosan (320-chitosan). Western blot analysis verified the downregulation of TRPV5 in patients and rat model of infection stones, as well as the stimulation of ds-320 on TRPV5 expression. MTT assay showed that chitosan-mediated delivery was less cytotoxic to ds-320 compared with liposome delivery. Further a modified invasion assay revealed an inhibitory effect of 320-chitosan on bacterial invasion into normal rat kidney epithelial NRK-52E cells. The establishment of infection stone model was performed by intravesical injection of 1×108 CFU of Proteus mirabilis. In animal experiments, no visible stones were obtained. The number of live bacteria and white blood cells in urine showed no difference among all infected rats at the time of sacrifice. However, we observed a decline in urine calcium and pH, suggesting the effect of acidification. Overall, our study provides evidence for the protective effect of 320-chitosan, for its ability to down-regulate urinary calcium, acidify urine, and inhibit bacteria from invading renal epithelial cells. Thus, it can be served as an important complementary therapy for infection stones.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2022-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.4149/gpb_2022028\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.4149/gpb_2022028","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Nanoparticle-mediated delivery system alleviates the formation of infection stones by activating TRPV5.
Infection stones constitute a small but intractable group of diseases of urinary system. In this study, we explored the potential therapeutic effect of a small activation RNA, ds-320, encapsulated in chitosan (320-chitosan). Western blot analysis verified the downregulation of TRPV5 in patients and rat model of infection stones, as well as the stimulation of ds-320 on TRPV5 expression. MTT assay showed that chitosan-mediated delivery was less cytotoxic to ds-320 compared with liposome delivery. Further a modified invasion assay revealed an inhibitory effect of 320-chitosan on bacterial invasion into normal rat kidney epithelial NRK-52E cells. The establishment of infection stone model was performed by intravesical injection of 1×108 CFU of Proteus mirabilis. In animal experiments, no visible stones were obtained. The number of live bacteria and white blood cells in urine showed no difference among all infected rats at the time of sacrifice. However, we observed a decline in urine calcium and pH, suggesting the effect of acidification. Overall, our study provides evidence for the protective effect of 320-chitosan, for its ability to down-regulate urinary calcium, acidify urine, and inhibit bacteria from invading renal epithelial cells. Thus, it can be served as an important complementary therapy for infection stones.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.