Background
This study was aimed to prepare a novel magnetic thermosensitive cationic liposome drug carrier for the codelivery of Oxaliplatin (OXA) and antisense lncRNA of MDC1 (MDC1-AS) to Cervical cancer cells and evaluate the efficiency of this drug carrier and its antitumor effects on Cervical cancer.
Methods
Thermosensitive magnetic cationic liposomes were prepared using thin-film hydration method. The OXA and MDC1-AS vectors were loaded into the codelivery system, and the in vitro OXA thermosensitive release activity, efficiency of MDC1-AS regulating MDC1, in vitro cytotoxicity, and in vivo antitumor activity were determined.
Results
The codelivery system had desirable targeted delivery efficacy, OXA thermosensitive release, and MDC1-AS regulating MDC1. Codelivery of OXA and MDC1-AS enhanced the inhibition of cervical cancer cell growth in vitro and in vivo, compared with single drug delivery.
Conclusion
The novel codelivery of OXA and MDC1-AS magnetic thermosensitive cationic liposome drug carrier can be applied in the combined chemotherapy and gene therapy for cervical cancer.
Neural crest-derived ecto-mesenchymal stem cells (EMSCs), as the progenitor cells of odontogenic stem cells, may be the suitable seed cell for regenerative dentistry. p75NTR, as the neural crest stem cell marker, plays a crucial role during the teeth development of EMSCs. Nevertheless, the interaction networks p75NTR connecting with odonto/osteogenic differentiation and mineralization are still poorly studied. Circular RNAs (circRNAs) regulate life processes mainly by performing as a competitive endogenous RNA (ceRNA) to prevent the process that microRNAs (miRNAs) bind with their target mRNAs. But the roles of p75NTR-related circRNAs in EMSCs are largely unknown. We used circRNA-seq to examine the differentially expressed circRNAs between WT and p75NTR (-/-) EMSCs and three of them were selected for qRT-PCR verification. GO, KEGG and Reactome enrichment analyses showed that differentially expressed circRNAs interact with cell proliferation, locomotory behavior, cell differentiation and are mainly involved in Wnt, JAK/STAT, Hippo and TGF-β signaling pathways. Then, CCK8, transwell assay and ALP staining assay were performed to verify the result of enrichment analyses. Then, the circRNA-miRNA interaction networks were constructed by using bioinformatics analysis. A new circRNA, mmu_circ_0001380 and mmu_circ_0013536 were selected to predict potential target miRNAs. Besides, with TargetScan, we noticed that these three circRNAs may influence the expression of DSPP and RUNX2 and qRT-PCR was performed for verification. Therefore, these three circRNAs are inclined to be vital in developing EMSCs and be novel core molecules for the further understanding of odontogenesis related to p75NTR.
Background: Thymocyte antigen-1 (THY-1) is a potential therapeutic target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate rheumatoid arthritis development. In this study, we screened a full human antibody targeting THY-1 and exploring its anti-RA activity and mechanism.
Methods: We screened antibody targeting THY-1 (i.e. THY-1 Ab), an antagonistic antibody from human ScFv phage antibody library, by using THY-1 as a target. After proving its binding ability with surface plasmon resonance (SPR), we explored its effect on RA based on FLS transcriptomic analysis and bioinformatics analysis tips treated with THY-1 Ab. Both in vivo and in vitro experiments have proved its effectiveness in the treatment of rheumatoid arthritis. What’s up, we clarified the mechanism of action of the scFv antibody.
Results:THY-1 Ab could not only bind to human THY-1 extracellular domains, but also combine to Murine THY-1. In addition, THY-1 Ab restrained the proliferation and secretion of the proinflammatory factors. THY-1 Ab restrained angiogenesis by inhibiting VEGF expression in RA FLS, and the THY-1 Ab and RA FLS combination can effectively inhibit the differentiation of osteoclasts, which down-regulated the expression of JUNB via hsa_circ_0094342—miRNA-155-5P—SPI1 axis, thus regulating AP-1 to suppress angiogenesis and osteoclast differentiation. In Collagen induced arthritis (CIA), disease progression was effectively alleviated by THY-1 Ab.
Conclusions: These findings support that THY-1 Ab is a potential drug for the rheumatoid arthritis treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.