Project description:As one of the widely-used broad-spectrum anti-cancer drug, ototoxicity occurrence limited the usage of Cisplatin in clinical practice. At the same time, Eleutheroside E are found with kindny and never protection. However, the mechanism of the protection is remained unclear. In this study, 27 C57BL/6J mice were used and divided into Ctrl group with normal Saline injected, Cis and Cis + EE group with injection of Cis and Cis + EE peritoneally for Cisplatin-reduced ototoxicity modelling and intervention, then cochlears were dissected for proteomics. Network pharmacology to predict the target and biological mechanism of Eleutheroside E against cisplatin ototoxicity and Eleutheroside E might play an antagonistic role through the regulation of MAPK and pyrogenic signaling pathway. Compare with Cis group, Cis+EE group mice have a lower threshold value in ABR result and the group shows less cell pyroptosis than Cis group. Morphology results also indicated that Cis+EE group reduced space of spiral ganglion and the vascular structure was relatively clear than the Cis group. In addition, compared with Cis group, mRNA expression of NLRP3, GSDMD, ASC, Caspase-1, IL-1β and IL-18 genes in Cis+EE group decreased. The expression of p-JNK, p-ERK, P-P38, NF-κB P65, Cleaved Caspase-1, GSDMD was decreased, and the expression of IκB was increased. This study demonstrated that Eleutheroside E exerts an antagonistic effect on Cisplatin ototoxicity by down-regulating the activity of MAPK/NF-κB/NLRP3 signaling pathway, reducing the expression level of pyroptosis related proteins and inflammatory factors after cisplatin administration, and then inhibiting pyroptosis.
Project description:cis-antisense RNAs (cis-asRNAs) in prokaryotes are more pervasive than originally thought. However, little is known about their expression patterns and functions. Here we determined transcriptomes and proteomes of E. coli at multiple time points in five culture conditions using directional RNA-seq and tandem mass spectrometry. We found that a highly varying portion (27.2%~90.8%) of transcribed genes had cis-asRNAs dependent on growth phases and culture conditions, and that almost all transcribed genes changed their cis-asRNA levels relative to the mRNA level at different growth phases and culture conditions. Intriguingly, the correlation between the protein and mRNA levels of genes is abolished the increasing cis-asRNA levels relative to the mRNA levels, suggesting that cis-asRNAs might directly or indirectly inhibit translation by forming duplexes with mRNAs. All data sets are available for data mining from a unified resource to support further biological discoveries and insights into cis-asRNA-mediated gene expressional regulation.