Astragalus polysaccharides (APS), which is widely used as a remedy to promote immunity of breast cancer patients, can enhance immune responses and exert anti-tumor effects. In this study, we investigated the effects and mechanisms of APS on macrophage RAW 264.7 and EAC tumor-bearing mice. Griess reaction and ELISA assays revealed that the concentrations of nitric oxide, TNF-α, IL-1β and IL-6 were increased by APS. However, this effect was diminished in the presence of TAK-242 (TLR4 inhibitor) or ST-2825(MyD88 inhibitor). In C57BL/10J (TLR4+/+wild-type) and C57BL/6J (MyD88+/+wild-type) tumor-bearing mice, the tumor apoptosis rate, immune organ indexes and the levels of TNF-α, IL-1β and IL-6 in blood increased and the tumor weight decreased by oral administration of APS for 25 days. APS had no obvious effects on IL-12p70. However, these effects were not significant in C57BL/10ScNJ (TLR4-deficient) and C57BL/B6.129P2(SJL)-Myd88m1.1Defr/J (MyD88-deficient) tumor-bearing mice. qRT-PCR and Western blot indicated that APS stimulated the key nodes in the TLR4-MyD88 dependent signaling pathway, including TLR4, MyD88, TRAF-6, NF-κB and AP-1, both in vitro and in vivo. However, TRAM was an exception. Moreover, TRAF-6 and NF-κB were not triggered by APS in gene-deficient tumor-bearing mice. Therefore, APS may modulate immunity of host organism through activation of TLR4-mediated MyD88-dependent signaling pathway.

Ferroptosis is a specific iron-dependent cell death form that can induce the production of lipid peroxide, but the roles of circular RNAs (circRNAs) in ferroptosis are completely unaware. Circ-interleukin-4 receptor (circIL4R) was reported to express highly in hepatocellular carcinoma (HCC). This study focused on the function of circIL4R dysregulation in tumor progression and ferroptosis of HCC, as well as its molecular mechanism. The quantitative real-time polymerase chain reaction was implemented for measuring RNA expression. Cell proliferation and survival were evaluated using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide. Apoptotic cells were detected via flow cytometry. The quantification of protein expression was executed through western blotting analysis. The target binding was assessed via the dual-luciferase reporter, RNA immunoprecipitation, and RNA pulldown assays. The experiment in vivo was performed using a xenograft model. Cir-cIL4R was abnormally overexpressed in HCC tissues and cells. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells. CircIL4R could directly sponge microRNA-541-3p (miR-541-3p) and miR-541-3p inhibition mitigated the effects of circIL4R knockdown on HCC cells. CircIL4R acted as a miR-541-3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR-541-3p-induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in HCC via the miR-541-3p/GPX4 axis in vivo. Our data suggested that circIL4R served for a tumor promoter and ferroptosis inhibitor in HCC by the miR-541-3p/GPX4 network.

The present evidences indicated that the motion-preservation procedures had an advantage on reducing the prevalence of ASDeg, ASDis and the reoperation rate due to the adjacent segment degeneration compared with the lumbar fusion. And the clinical outcomes of the two procedures are similar.

Study Design. Retrospective comparative study. Objective. To compare the efficacy and safety of one-stage posterior multiple-level asymmetrical Ponte osteotomies (MAPOs) and single-level posterior vertebral column resection (VCR) for severe and rigid adult idiopathic scoliosis (ADIS). Summary of Background Data. The surgical treatment of severe and rigid ADIS is a demanding and difficult challenge due to its complicated characteristics. Spine surgeons have often pursued advanced correction techniques such as VCR for such patients, which reported to present excellent correction outcomes. But this attractive procedure brought the greatest risk to both surgeons and patients. Methods. A total of 48 patients who underwent MAPO or VCR and fusion surgery with minimum 2-year follow-up between February 2009 and November 2015 were enrolled. Twenty-six patients were included in MAPO group and 12 patients in VCR group with an average age of 26.65 ± 8.40 and 27.92 ± 7.50 years, respectively. The average follow-up was 30.24 ± 10.55 months. The surgical details and complications were recorded. The radiological parameters and clinical outcome including Oswestry Disability Index and Scoliosis Research Society-22 questionnaire scores were collected and analyzed. Results. The main curve in MAPO and VCR group were corrected from an average of 98.52° ± 16.50° to 44.11° ± 17.72° and 108.91° ± 16.56° to 56.49° ± 18.82° with no significant difference. The postoperative coronal and sagittal parameters of the two groups were all improved and it showed no significant differences between the two groups. The mean operative time and blood loss of VCR group were significantly greater than those of MAPO group. All the clinical scores were significantly improved at final follow-up, with no significant difference. The incidence of complications in MAPO group was 3.85%, which was significantly lower than that of VCR group. Conclusion. The surgical procedure of multiple asymmetrical Ponte osteotomy is a safe, easy-to-operate, and effective technique that can correct scoliosis and restore the sagittal alignment. It can gain similar correction outcome to VCR, offering the advantages of reduced operation time, blood loss, and greatly reduced the complication. Level of Evidence: 3