Targeted delivery of cancer drug paclitaxel to chordomas tumor cells via an RNA nanoparticle harboring an EGFR aptamer.

Paclitaxel has been extensively used in clinics for cancer treatment. However, its limited solubility in aqueous solution and high occurrence of side effects have also been widely reported. In this study, we constructed a biocompatible RNA nanoparticle delivery system (3WJ-EGFRapt) that includes 3WJ (3-way junction) nanoparticle with a size of 4.85 ± 0.59 nm as a backbone and an EGFR (epidermal growth factor receptor) aptamer for specific targeting to chordomas cells, which owns the encapsulation ability of drug paclitaxel (PTX) for cancer therapy. Confocal microscopy and flow cytometry results confirmed 3WJ-EGFRapt nanoparticle exhibited excellent specific targeting to chordomas cell U-CH2 which is an EGFR(+) cell line; while the 3WJ nanoparticle lose the targeted ability. Both of the two nanoparticles own no sensitivity to lung cancer cell H520 which is an EGFR(-) cell line. Moreover, the 3WJ-EGFRapt nanoparticle encapsulated drug PTX could enhance the inhibition efficiency of chordomas tumor cells U-CH2 as compared to free PTX alone. This work demonstrates that RNA-3WJ constructed with a targeting aptamer provides a compromising targeted drug delivery ability on chordomas cells for therapeutics.

A minimum 8-year follow-up comparative study of decompression and coflex stabilization with decompression and fusion.

The current study aimed to compare the outcomes of decompression and interlaminar stabilisation with those of decompression and fusion for the treatment of lumbar degenerative disease (LDD) at a minimum 8-year follow-up. The current study also aimed to analyse the risk factors of radiographic adjacent segment degeneration (ASD). A total of 82 consecutive patients with LDD who underwent surgery between June 2007 and February 2011 were retrospectively reviewed. Of these patients, 39 underwent decompression and Coflex interspinous stabilisation (Coflex group) and 43 underwent decompression and posterior lumbar interbody fusion (PLIF) (PLIF group). All patients had a minimum of 8-years of follow-up data. Radiographic and clinical outcomes were compared between the groups, and the risk factors of developing radiographic ASD were also evaluated. The Oswestry disability index and visual analogue scale leg and back pain scores of both groups significantly improved compared with the baseline (all P<0.05), and no difference were indicated between the two groups at each follow-up time point (P>0.05). The Coflex group exhibited preserved mobility (P<0.001), which was associated with a decreased amount of blood loss (P<0.001), shorter duration of surgery (P=0.001), shorter duration of hospital stay and a lower incidence of ASD (12.8 vs. 32.56%; P=0.040) compared with the fusion group. The current study indicated that coflex and fusion technologies are safe and effective for the treatment of LDD, based on long-term follow-up data. However, Coflex interspinous stabilisation was revealed to reduce ASD incidence. Under strict indications, Coflex interspinous stabilisation is an effective and safe treatment method.

Circular RNA YAP1 attenuates osteoporosis through up-regulation of YAP1 and activation of Wnt/ß-catenin pathway.

BACKGROUND: Osteoporosis is a systemic bone disease resulting from decreased bone mass and bone microstructure degeneration. Yes-associated protein 1 (YAP1) belongs to YAP family and plays a significant part in controlling bone quality. AIM OF THE STUDY: Present study aimed to study the function and up-stream mechanism of YAP1 in the differentiation of BMSCs (bone marrow stromal cells) and MC3T3-E1. METHODS: ALP staining, alizarin red staining and western blot analysis of osteogenic biomarkers determined osteogenic differentiation in BMSCs and MC3T3-E1. Mechanistic assays including luciferase reporter assay, RIP assay and RNA pull down assay disclosed the interplays between RNAs. RESULTS: YAP1 promoted osteogenic differentiation of BMSCs and MC3T3-E1. Circ_0024097 originated from YAP1 sponged miR-376b-3p to elevate YAP1 expression in BMSCs and MC3T3-E1. Further, YAP1 mediated circ_0024097- promoted effects on osteogenic differentiation. Moreover, circ_0024097 activated Wnt/ß-catenin pathway to facilitate osteogenic differentiation. CONCLUSION: It was firstly uncovered in present study that circ_0024097 attenuated osteoporosis through promoting osteogenic differentiation via miR-376b-3p/YAP1 axis and Wnt/ß-catenin pathway.

Therapeutic effect of percutaneous kyphoplasty combined with anti-osteoporosis drug on postmenopausal women with osteoporotic vertebral compression fracture and analysis of postoperative bone cement leakage risk factors: a retrospective cohort study.

BACKGROUND: The purpose of this study is to explore the therapeutic effect of percutaneous kyphoplasty (PKP) combined with anti-osteoporosis drug, zoledronic acid, on postmenopausal women with osteoporotic vertebral compression fracture (OVCF) and to perform an analysis of postoperative bone cement leakage risk factors. METHODS: A total of 112 OVCF patients, according to therapeutic regimens, were divided into control group (n = 52, treated with PKP) and observation group (n = 60, treated with PKP and zoledronic acid injection). RESULTS: Postoperative tumor necrosis factor-α and interleukin-6 levels were significantly decreased in the two groups, compared with those before treatment (both P < 0.05); bone mineral density (BMD), serum bone gla protein (BGP), and vertebral height ratio of injured vertebrae were significantly increased, and procollagen type I N-terminal propeptide (PINP), Cobb angle, visual analogue scale/score (VAS), and Oswestry disability index (ODI) were significantly decreased compared with those before treatment (all P < 0.05). There were significantly higher changes in difference value of BMD, PINP, BGP, vertebral height ratio of injured vertebrae, Cobb angle, VAS, and ODI levels and significantly better therapeutic effect in the observation group than those in the control group (all P < 0.05). Multivariate logistic regression analysis showed that the use of zoledronic acid, vertebral height ratio of injured vertebrae, and ODI were independent factors affecting the therapeutic effect, and that the dosage of bone cement, and peripheral vertebrae wall damage were independent risk factors causing postoperative bone cement leakage. There were no significant differences in postoperative bone cement leakage rate between the two groups. CONCLUSIONS: Peripheral vertebrae wall damage and the dosage of bone cement are independent risk factors causing bone cement leakage in OVCF patients treated with PKP. PKP combined with zoledronic acid has an improvement effect on the condition of postmenopausal women with OVCF and reduces the inflammation and pain in patients, which is beneficial to clinical treatment.

LncRNA SNHG1 was down-regulated after menopause and participates in postmenopausal osteoporosis.

The functions of long (>200 nt) non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) have only been investigated in cancer biology. We found that plasma LncRNA SNHG1 was down-regulated in postmenopausal than in premenopausal females. Among postmenopausal females, the ones with postmenopausal osteoporosis showed much lower expression levels of plasma lncRNA SNHG1. A 6-year follow-up study on postmenopausal females revealed that plasma lncRNA SNHG1 decreased in females with postmenopausal osteoporosis but not in healthy postmenopausal females. Levels of plasma lncRNA SNHG1 at 12 months before diagnosis is sufficient to distinguish postmenopausal osteoporosis patients from healthy controls. After treatment, plasma lncRNA SNHG1 were significantly up-regulated. Therefore, lncRNA SNHG1 was down-regulated after menopause and plasma level of lncRNA SNHG1 may serve as a biomarker for the diagnosis and treatment of postmenopausal osteoporosis.

Downregulation of long noncoding RNA Sox2ot protects PC-12 cells from hydrogen peroxide-induced injury in spinal cord injury via regulating the miR-211-myeloid cell leukemia-1 isoform2 axis.

This study aimed to investigate the effects and possible mechanisms of long noncoding RNA (lncRNA) Sox2 overlapping transcript (Sox2ot) on hydrogen peroxide (H2 O2 )-induced injury in pheochromocytoma (PC-12) cells. PC-12 cells were treated with H2 O2 to cell injury. The cells were transfected with short-hairpin RNA directed against Sox2ot (sh-Sox2ot), small interfering RNA directed against myeloid cell leukemia-1 (MCL-1) isoform2 (si-MCL-1), a miR-211 mimic, a miR-211 inhibitor, and their negative controls. Under different transfected treatments, cell viability, migration, invasion, and apoptosis as well as the expressions of apoptosis- and autophagy-related proteins were investigated. Besides, the regulatory relationships between Sox2ot and miR-211, miR-211 and MCL-1, as well as between MCL-1 and the protein kinase B (Akt)/mammalian target of the rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway were explored. Suppression of Sox2ot inhibited H2 O2 -induced PC-12 cell injury by increasing cell viability, migration, invasion, and decreasing apoptosis and autophagy. Moreover, suppression of Sox2ot increased miR-211 expression and alleviated H2 O2 -induced injury in PC-12 cells possibly via upregulation of miR-211. Furthermore, MCL-1 isoform2 was identified as a direct target of miR-211 and could be negatively regulated by miR-211. Suppression of miR-211 aggravated H2 O2 -induced cell injury by regulation of MCL-1 isoform2. Besides, inhibition of miR-211 suppressed the activation of the Akt/mTOR/p70S6K signaling pathway in H2 O2 -treated PC-12 cells, which was reversed after knockdown of MCL-1 isoform2 at the same time. Our findings indicate that downregulation of Sox2ot may protect PC-12 cells from H2 O2 -induced injury in SCI via targeting the miR-211/MCL-1 isoform2 axis. MCL-1 isoform2 may further regulate the activation of the Akt/mTOR/p70S6K pathway to mediate H2 O2 -induced injury. The Sox2ot-miR-211-MCL-1 isoform2 axis may be a promising therapeutic strategy for SCI.