CircEpc1 Promotes Ricin Toxin-Induced Inflammation via Activation of NF-κB and MAPK Signaling Pathways by Sponging miR-5114.

Increasing studies have concentrated on investigating circular RNAs (circRNAs) as pivotal regulators in the progression of numerous diseases and biological processes and abundant evidence shows that circRNAs are participated in the regulation of innate immune responses. Several studies showed that Ricin Toxin (RT) could induce inflammatory injury. There was no research on the particular functions and underlying mechanisms of circRNAs in RT-induced inflammation. In this study, RNA sequencing performed on RT-treated and normal RAW264.7 macrophage cells was used to investigated the differentially expressed circRNAs. Based on the dataset, the expression of circEpc1 (mmu_circ_0,000,842) was identified higher in RT-treated cells. Moreover, gain-and-loss function assays showed that circEpc1 function as a promoter in RT-induced inflammation in vivo and in vitro. Mechanistically, circEpc1 acted as a miR-5114 sponge to relieve the suppressive effect of miR-5114 on its target NOD2 and thereby activating NF-κB and MAPK signaling pathways. Our results illuminated a link between RT-induced inflammation and the circEpc1 regulatory loop and provided novel insight into the functions of circRNA in innate immune, which may emerge as a potential target in immunotherapy to control the RT-induced inflammatory injury.

Critical role of toll-like receptor 4 (TLR4) in ricin toxin-induced inflammatory responses in macrophages.

Ricin toxin (RT) is a natural plant-derived protein toxin from the seed of castor beans that belongs to a family of type II ribosome-inactivating proteins (RIPs). In addition to its main toxic mechanism of inhibiting the synthesis of cellular proteins, RT can induce the production of inflammatory cytokines and cause inflammatory injury. Macrophages play a crucial role in innate immunity and the adaptive immune response as the first line of host defense against bacterial infections and various types of invading pathogens. Upon activation, macrophages release types of cytokines to remove pathogens. However, the effect of RT on the immune response and its mechanism are not well characterized. In the current study, we investigated the activation of the TLR4-mediated signaling pathway by low-dose RT treatment and its interaction with signaling molecules in the transduction pathway. We found that low-dose RT can activate MyD88- and TRIF-dependent signaling pathways, revealing a possible mechanism by which low-dose RT-activates TLR4-mediated signaling pathways. We also confirmed that the TLR4-induced activation of the inflammatory signaling pathways was produced via its binding to RT. This study may help to identify the most important target molecules and clarify the mechanism of inflammatory injury of ricin.

Optimized Axillary Vein Technique versus Subclavian Vein Technique in Cardiovascular Implantable Electronic Device Implantation: A Randomized Controlled Study.

BACKGROUND: The conventional venous access for cardiovascular implantable electronic device (CIED) is the subclavian vein, which is often accompanied by high complication rate. The aim of this study was to assess the efficacy and safety of optimized axillary vein technique. METHODS: A total of 247 patients undergoing CIED implantation were included and assigned to the axillary vein group or the subclavian vein group randomly. Success rate of puncture and complications in the perioperative period and follow-ups were recorded. RESULTS: The overall success rate (95.7% vs. 96.0%) and one-time success rate (68.4% vs. 66.1%) of punctures were similar between the two groups. In the subclavian vein group, pneumothorax occurred in three patients. The subclavian gaps of three patients were too tight to allow operation of the electrode lead. In contrast, there were no puncture-associated complications in the axillary vein group. In the patient follow-ups, two patients in the subclavian vein group had subclavian crush syndrome and both of them received lead replacement. The incidence of complications during the perioperative period and follow-ups of the axillary vein group and the subclavian vein group was 1.6% (2/125) and 8.2% (10/122), respectively (χ2 = 5.813, P = 0.016). CONCLUSION: Optimized axillary vein technique may be superior to the conventional subclavian vein technique for CIED lead placement. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02358551; https://clinicaltrials.gov/ct2/show/NCT02358551?term=NCT02358551& rank=1.