Exosome-transmitted circular RNA circ-LMO7 facilitates the progression of osteosarcoma by regulating miR-21-5p/ARHGAP24 axis.

The potential function and mechanism of circRNAs in regulating malignant performances of Osteosarcoma (OS) cells have not been well investigated. The expression level of CircLMO7, miR-21-5p and ARHGAP24 were detected by RT-qPCR. The relationship between miR-21-5p and circ-LMO7, as well as between miR-21-5p and ARHGAP24, was predicted and examined through bioinformatics analysis and luciferase reporter gene experiments. Moreover, OS cell growth, invasion, migration, and apoptosis were detected using the cell counting kit-8 (CCK-8), transwell and flow cytometry assays, respectively. ARHGAP24 protein level was measured using western blotting. In present study, we choose to investigate the role and mechanism of circ-LOM7 on OS cell proliferation, migration and invasion. circ-LOM7 was found to be down-regulated in OS tissues and cell lines. Enforced expression of circ-LOM7 suppressed the growth, invasion, and migration of OS cells. In contrast, decreasing circ-LMO7 expression had opposite effects. Furthermore, miR-21-5p was predicted to be sponged by circ-LMO7, and had an opposite role of circ-LMO7 in OS. Moreover, ARHGAP24 served as miR-21-5p's downstream target. Mechanistically, circ-LMO7 was packed in exosomes and acted as a cancer-suppresser on OS by sponging miR-21-5p and upregulating the expression of ARHGAP24. The exosomal circ-LMO7 expression was significantly decreased in OS cell exosomes, and co-culture experiments showed that exosomal circ-LMO7 suppressed the proliferation ability of OS cells. Circ-LMO7 exerts as a tumor suppressor in OS, and the circ-LMO7/miR-21-5P/ARHGAP24 axis is involved in OS progression.

The Use of Spiral Cement Injector for Percutaneous Vertebroplasty to Treat Kümmell Disease: A Retrospective Study.

BACKGROUND: Percutaneous vertebroplasty (PVP) is a common method used to treat Kümmell disease. In patients without neurologic symptoms, we sought to evaluate whether using the new spiral injectors instead of the traditional push-rod injectors in PVP can result in improved clinical efficacy for the treatment of Kümmell disease. METHODS: A clinical retrospective study was conducted between August 2018 and December 2020. The study included patients diagnosed with single-level thoracolumbar Kümmell disease who underwent PVP surgery. The patients were divided into 2 groups: an observation group consisting of 53 patients treated with spiral injectors and a control group consisting of 68 patients treated with push-rod injectors. RESULTS: A 2-year follow-up period was adopted. The bone cement injection volume and occurrence of bone cement leakage were significantly greater in the observation group compared with the control group (P < 0.05). The observation group had significantly shorter operation time and intraoperative fluoroscopy times compared with the control group (P < 0.05). The scores for the visual analog scale and Oswestry Disability Index in both groups were significantly lower at 3 days or 3 months and 2 years after surgery compared with before surgery, with the scores at 2 years after surgery being significantly lower than those at 3 days or 3 months for both groups (P < 0.05). The relative anterior ledge height and Cobb angle showed significant improvement at 3 days and 2 years after surgery compared with before surgery in both groups (P < 0.05), but patients in the observation group experienced substantial improvement at 3 days and 2 years after surgery compared with those in the control group (P < 0.05). In both groups, the relative anterior ledge height was noticeably lower 2 years after surgery compared with 3 days after surgery (P < 0.05). Concurrently, there was a significant increase in the local Cobb angle over time in both groups (P < 0.05). CONCLUSIONS: The implementation of both spiral injectors and traditional push-rod injectors in PVP surgery yields effective pain relief, improved function, partially restored vertebral height, and corrected kyphosis in treating Kümmell disease. Compared with the push-rod injector, the spiral injector is highly efficient in restoring vertebral height, correcting kyphosis, and minimizing fluoroscopy use and operation time, but it carries a greater risk of bone cement leakage.

KLF5-induced miR-487a augments the progression of osteosarcoma cells by targeting NKX3-1 in vitro.

MicroRNAs (miRNAs or miRs) are involved in the development and progression of numerous types of cancer however their role in osteosarcoma has not been fully clarified. The present study aimed to use high-throughput bioinformatics analysis as well as in vitro experiments to investigate the potential role of transcription factors, miRNAs and their targets in the progression of osteosarcoma. miRNA data and clinical information of osteosarcoma were obtained from Gene Expression Omnibus database to investigate differentially expressed miRNAs. The expression of miRNAs/mRNAs in osteosarcoma cell lines was detected via reverse transcription-quantitative (RT-qPCR). MTT and colony formation assay were used to determine cell proliferation ability and transwell assay was used to observe cell invasion and migration ability. A total of four prediction algorithms for miRNA-mRNA interactions were used to determine potential target genes of miR-487a. Predicted target genes were used to intersect with overlapped differentially expressed genes (DEGs) from GSE12865 and The Cancer Genome Atlas osteosarcoma datasets. Expression of NK3 homeobox 1 (NKX3-1) was analyzed by western blotting and RT-qPCR assay. Dual luciferase assay was conducted to verify whether NKX3-1 was a direct target of miR-487a. The regulatory association between Kruppel-like factor 5 (KLF5) and miR-487a was detected using chromatin immunoprecipitation assay. miR-487a was upregulated in osteosarcoma tissue (GSE65071 and GSE28423) and cell lines (HOS and MG63). miR-487a mimic promoted proliferation, migration and invasion of osteosarcoma cells. NKX3-1 was a direct target of miR-487a and transfection of NKX3-1 plasmid reversed the effect of miR-487a on proliferation, migration and invasion of osteosarcoma cells. KLF5 enhanced miR-487a expression by directly binding to its promoter region and miR-487a inhibitor reversed the effect of KLF5 on proliferation, migration and invasion of osteosarcoma cells. The present results indicated that KLF5/miR-487a signaling promoted invasion and metastasis of osteosarcoma cells via targeting NKX3-1.

N-acetylcysteine reduces oxidative stress, nuclear factor­κB activity and cardiomyocyte apoptosis in heart failure.

The roles of oxidative stress on nuclear factor (NF)­κB activity and cardiomyocyte apoptosis during heart failure were examined using the antioxidant N­acetylcysteine (NAC). Heart failure was established in Japanese white rabbits with intravenous injections of doxorubicin, with ten rabbits serving as a control group. Of the rabbits with heart failure, 12 were not treated (HF group) and 13 received NAC (NAC group). Cardiac function was assessed using echocardiography and hemodynamic analysis. Myocardial cell apoptosis, apoptosis­related protein expression, NF­κBp65 expression and activity, total anti­oxidative capacity (tAOC), 8­iso­prostaglandin F2α (8­iso­PGF2α) expression and glutathione (GSH) expression levels were determined. In the HF group, reduced tAOC, GSH levels and Bcl­2/Bax ratios as well as increased 8­iso­PGF2α levels and apoptosis were observed (all P<0.05), which were effects that were attenuated by the treatment with NAC. NF­κBp65 and iNOS levels were significantly higher and the P­IκB­α levels were significantly lower in the HF group; expression of all three proteins returned to pre­HF levels following treatment with NAC. Myocardial cell apoptosis was positively correlated with left ventricular end-diastolic pressure (LVEDP), NF­κBp65 expression and 8­iso­PGF2α levels, but negatively correlated with the maximal and minimal rates of increase in left ventricular pressure (+dp/dtmax and ­dp/dtmin, respectively) and the Bcl­2/Bax ratio (all P<0.001). The 8­iso­PGF2α levels were positively correlated with LVEDP and negatively correlated with +dp/dtmax and ­dp/dtmin (all P<0.001). The present study demonstrated that NAC increased the antioxidant capacity, decreased the NF­κB activation and reduced myocardial cell apoptosis in an in vivo heart failure model.