Benzoylaconitine Inhibits Production of IL-6 and IL-8 via MAPK, Akt, NF-κB Signaling in IL-1ß-Induced Human Synovial Cells.

Benzoylaconitine (BAC), the main hydrolysate of aconitine, is a lower toxic monoester type alkaloid considered as the pharmacodynamic constituent in Aconitum species. In this study, the effects and mechanisms of BAC on production of inflammatory cytokines interleukin (IL)-6 and IL-8 were investigated in IL-1ß-stimulated human synovial SW982 cells. The SW982 cells were incubated with BAC (0, 5 and 10 µM) before stimulating with IL-1ß (10 ng/mL). The results revealed that BAC suppressed gene and protein expression of IL-6 and IL-8 induced by IL-1ß. BAC decreased activation of mitogen-activated protein kinase (MAPK) and phosphorylation of Akt. BAC also inhibited degradation of inhibitor of kappaB (IκB)-α, phosphorylation and nuclear transposition of p65 protein. The results demonstrate that BAC exerts an anti-inflammatory effect dependent on MAPK, Akt and nuclear factor-κB (NF-κB) pathways in human synovial cells stimulated with IL-1ß, suggesting that BAC may be exploited as a potential therapeutic agent for rheumatoid arthritis (RA) treatment.

Potential and application of abortive transcripts as a novel molecular marker of cancers.

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

Generation of a competing endogenous RNA network and validation of BNIP1 expression in the lung of irradiated mice.

BACKGROUND: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy, and it is mediated by long non-coding RNAs (lncRNAs). STUDY DESIGN AND METHODS: Mouse lung tissues were examined using RNA-Seq and RNA-Seq libraries 72 h after the administration of 6 Gy of X-ray irradiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and target miRNA-based mRNAs were predicted after irradiation to establish the lncRNA-miRNA-mRNA ceRNA axis. RESULTS: The analyses showed that relative to unirradiated controls, 323 mRNAs, 114 miRNAs, and 472 lncRNAs were significantly up-regulated following irradiation, whereas 1907 mRNAs, 77 miRNAs, and 1572 lncRNAs were significantly down-regulated following irradiation. Voltage-gated ion channels, trans-membrane receptor protein tyrosine kinases, and vascular endothelial growth factor have all been associated with dysregulated miRNA-mRNA relationships. KEGG pathway analysis of the dysregulated miRNA-mRNA targets revealed involvement in pathways associated with the hedgehog signaling pathway-fly, ErbB signaling, VEGF signaling, axon guidance, and focal adhesion. KEGG analysis of differentially expressed showed enrichment of mRNAs in primary immunodeficiency, the intestinal immune axis for IgA production, hematopoietic cell lineages, systemic lupus erythematosus, and Th1 and Th2 cell differentiation. Finally, the ceRNA network revealed that BNIP1 was a critical mRNA modulated by the most significant upregulation of lncRNA E230013L22Rik. CONCLUSION: In summary, the lncRNA-miRNA-mRNA ceRNA axis of RILI was constructed following irradiation in a mouse model. RNA dysregulation in the early stage of RILI may lead to severe complications at a later stage, with BNIP1 contributing to radiation-induced cellular apoptosis in RILI.