Lycorine inhibits tumor growth of human osteosarcoma cells by blocking Wnt/ß-catenin, ERK1/2/MAPK and PI3K/AKT signaling pathway.

Osteosarcoma (OS) is the most common type of primary bone cancer. Even with advances in early diagnosis and aggressive treatment, the overall prognosis for OS remains to be further elevated. Lycorine was an isoquinoline alkaloid mainly existed in the bulb of lyco salvia miltiorrhiza and was shown to inhibit several types of cancer. In the present study, we investigated the anti-OS activity of lycorine and the possible underlying mechanism. We found that lycorine inhibited cell proliferation of human OS cells while had lower cytotoxcity against normal cells, and triggered cell cycle arrest at the G1/S transition. Moreover, we validated that lycorine promoted apoptosis via death receptor pathway and mitochondrial pathway, suppressed migration and invasion by reversing epithelial mesenchymal transition (EMT) and suppressing the degradation of extracellular matrix (ECM) in vitro. In addition, orthotopic implantation model of 143B OS cells further confirmed that lycorine suppressed OS growth and lung metastasis in vivo. Mechanically, lycorine reduced the protein level of ß-catenin and its' downstream molecule c-Myc. Furthermore, lycorine also decreased the phosphorylation of ERK1/2 and AKT. Together, our results reveal that lycorine may inhibit tumor growth of OS cells possibly through suppressing Wnt/ß-catenin, ERK1/2 and PI3K/AKT signaling pathway.

Implant complications after one-level or two-level cervical disc arthroplasty: A retrospective single-centre study of 105 patients.

The aim of study was to investigate the complications of cervical disc arthroplasty (CDA) and to discuss the factors affecting the mobility of the prosthesis and the measures to prevent these complications. Hundred and five patients who underwent CDA between 2009 and 2016 were enrolled. The clinical and radiographic outcomes were used to assess and the complications were recorded as well.All the patients were followed-up with an average of 41.30 ±â€Š16.90 months with an average age of 47.90 ±â€Š9.22 years. The visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopaedic Association (JOA) scores improved significantly at the final follow-up (FU) compared with the preoperative values. At the final FU, the overall incidence of heterotopic ossification (HO) was 51.42%. The distribution of different grades of HO was low-level HO (53.7%) and high-level HO (46.3%). No significant differences were found in the NDI, VAS, or JOA scores between patients with HO and those without HO (P > .05). In the high-level HO patients, the range of mobility (ROM) was significantly reduced compared with the low-level HO patients and those without HO (P < .05). The anterior displacement, subsidence, and instability were observed in 1 patient respectively and the segmental kyphosis, adjacent segment degeneration in 3 patients respectively. The patient of CDA instability also suffered severe neck pain and the revision surgery was performed.Postoperative complications in CDA such as HO, segmental kyphosis, and prosthesis displacement are prone to occur, affecting prosthesis mobility. Surgical indications should be strictly controlled, and intraoperative and postoperative treatments should be given great attention in order to reduce prosthesis-related complications.

One-stage posterior debridement with transverse process strut as bone graft in the surgical treatment of single-segment thoracic tuberculosis: A retrospective single-center study.

This retrospective study investigated the effect of the novel bone graft transverse process strut (TPS) in single segmental thoracic spinal tuberculosis (TB) with the one-stage posterior approach of debridement, fusion, and internal instrumentation. Thirty patients treated in our department from March 2014 to October 2016 were retrospectively analyzed. Surgical time, blood loss, hospitalization time, drainage volume, and follow-up (FU) duration were recorded. The visual analog scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, segmental angle, and bone fusion were compared between preoperative and final FU. All the patients were followed for a mean 50.10 ±â€Š25.10 months; the mean age, surgical time in minutes, blood loss, hospitalization time, and drainage volume were 46.23 ±â€Š17.20 years, 195.08 ±â€Š24.0 minutes, 280.77 ±â€Š189.90 mL, 17.31 ±â€Š4.23 days, 436.92 ±â€Š193.81 mL, respectively. VAS and ODI scores were significantly improved at the final FU. The ESR and CRP returned to normal. All patients achieved bony fusion with a mean time of 5.85 ±â€Š1.82 months and a mean segmental angle of 18.77 ±â€Š2.49° preoperatively, which significantly decreased to 9.31 ±â€Š1.54° at the final FU (P < .05). No complications, such as bone graft failure, pleural effusion, fistula, or wound infection were recorded except for cerebrospinal fluid leakage (one case), water electrolyte imbalance (5 cases), superficial infection (1 case), and mild intestinal obstruction (1 case). TPS as a bone graft is reliable, safe, and effective for segmental stability reconstruction for surgical management of single-segment thoracic spinal TB.

Does Concomitant Degenerative Spondylolisthesis Influence the Outcome of Decompression Alone in Degenerative Lumbar Spinal Stenosis? A Meta-Analysis of Comparative Studies.

OBJECTIVE: To investigate whether the preoperative presence of degenerative spondylolisthesis (DS) worsens the outcome of patients undergoing decompression alone for degenerative lumbar stenosis. METHODS: We conducted a comprehensive search in the PubMed, Embase, and Cochrane Library databases. All comparative studies were included in this meta-analysis. The literature search, data extraction, and quality assessment were conducted by 2 independent reviewers. The functional outcomes were clinical scores and reoperation rate. The radiologic outcomes were slippage rate and postoperative instability rate. RESULTS: A total of 11 studies with 1081 cases, including 469 cases of degenerative lumbar stenosis with DS (DS group) and 612 degenerative lumbar stenosis without spondylolisthesis (noDS group), were enrolled in our meta-analysis. There were no significant differences between the 2 groups for functional outcomes in terms of Japanese Orthopedic Association score, Japanese Orthopedic Association recovery rate, Oswestry Disability Index score, visual analog scale back/leg, and reoperation rate after decompression alone. For the radiologic outcomes, slippage rate was found not changed significantly before and after minimally invasive decompression alone in the DS group and the postoperative instability rate did not differ significantly between the 2 groups after decompression alone by a minimally invasive method. CONCLUSIONS: Our meta-analysis revealed that concomitant DS (Meyerding grade I-II) does not influence the outcome of decompression alone in degenerative lumbar spinal stenosis, especially when a minimally invasive procedure was performed and patients did not have predominant symptoms of mechanical back pain. The presence of DS should not be an indication for fusion surgery in degenerative lumbar spinal stenosis.

Notch signaling negatively regulates BMP9-induced osteogenic differentiation of mesenchymal progenitor cells by inhibiting JunB expression.

Although interaction between BMP and Notch signaling has been demonstrated to be crucial for osteogenic differentiation of mesenchymal stem cells (MSCs), the precise molecular mechanism remains unknown. Here, we show that Notch intracellular domain (NICD) overexpression inhibits BMP9-induced C3H10T1/2 cell osteogenesis in vivo and in vitro. Our results show that activated Notch signaling results in down-regulation of Runx2 and early osteogenesis differentiation factors, without affecting p-Smad1/5/8 expression, and that blocking Notch signaling with DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) significantly increases p-Smad1/5/8 expression. Interestingly, Notch signaling also regulates the cell cycle by increasing PCNA (proliferation cell nuclear antigen) and CyclinD1 expression. Furthermore, similar results were obtained by ectopic bone formation and histological analyses, indicating that Notch signaling activation significantly inhibits BMP9-induced MSC osteogenic, cartilage and adipogenic differentiation. Moreover, we are the first to show that Notch regulates by suppressing JunB synthesis and that the negative effect of Notch is partially reversed by treatment with the JunB activator TPA (12-O-tetradeca-noylphorbol-13-acetate). Our findings demonstrate that Notch signaling significantly enhances cell proliferation but inhibits MSC osteogenic differentiation induced by BMP9 via JunB protein suppression rather than by BMP/Smad signaling regulation.

Prevalence of axial symptoms after posterior cervical decompression: a meta-analysis.

PURPOSE: To investigate the prevalence of axial symptoms (AS) in patients following posterior cervical decompression. METHODS: We searched the PubMed, Embase, and Cochrane databases for relevant studies that reported the incidence of AS after posterior cervical decompression, and manually screened reference lists for additional studies. Relevant prevalence estimates were calculated. Subgroup analysis, sensitivity analysis and publication bias assessment were also performed. RESULTS: Our meta-analysis included 44 studies, with 893 AS cases in 2984 patients. The pooled AS prevalence was 28 % (95 % CI 24-32). The prevalence of AS was higher after expansive open-door laminoplasty (39 %) than after modified open-door laminoplasty (MOLP, 23 %) and laminectomy instrumented fusion (29 %). AS prevalence was also higher in those that wore a neck collar for 2-3 months (34 %) compared with 2 weeks (21 %). The lowest AS prevalence (9 %) was found in patients who underwent MOLP with C3 laminectomy and C7 spinous processes conserved. There was an intermediate AS prevalence after MOLP with C7 spinous processes conserved (16 %), MOLP with preservation of the unilateral posterior muscular-ligament complex (19 %), MOLP with C3 laminectomy (22 %), and MOLP with plate fixation (23 %). Prevalence of AS might be higher in patients <60 years and increased in populations with a higher proportion of females. CONCLUSIONS: Posterior cervical surgery carries a high risk of postoperative AS. Postoperative AS may be reduced through preserving posterior muscles and structures, stabilizing cervical vertebrae, and reducing external cervical immobilization time.

MicroRNA-212 inhibits osteosarcoma cells proliferation and invasion by down-regulation of Sox4.

BACKGROUND: Multiple MicroRNAs (miRNAs) have been identified in the development and progression of osteosarcoma. However, the expression and roles of miR-212 in osteosarcoma remain largely undefined. METHODS: Real-time PCR assays were used to detect the expression of miR-212 in human osteosarcoma tissues. MiR-212 mimics were introduced into MG63 and U2OS cells. Bioinformatic prediction was used to identify the potential targets of miR-212. Protein expression analysis, luciferase assays and rescue assays were used to confirm the substrate of miR-212. RESULTS: miR-212 was significantly down-regulated in human osteosarcoma tissues, compared with adjacent normal tissues. Introduction of miR-212 mimics into MG63 and U2OS cells inhibited cell proliferation and invasion. Besides, miR-212 overexpression could also inhibit tumor growth in the nude mice. Additionally, bioinformatic prediction suggested that the sex-determining region Y-box 4 (Sox4) is a target gene of miR-212. Sox4 inhibition phenocopied the roles of miR-212, while restored expression of Sox4 dampened miR-212-mediated suppression of tumor progression. CONCLUSION: The miR-212/Sox4 interaction plays an important role of in the osteosarcoma progression.

Lipopolysaccharide preconditioning attenuates neuroapoptosis and improves functional recovery through activation of Nrf2 in traumatic spinal cord injury rats.

The previous studies suggested that low-dose lipopolysaccharide (LPS) provides neuroprotection against subsequent challenge with ischemic/reperfusion injury in the brain. But there were few reports about the neuroprotective effects of low-dose LPS against spinal cord injury (SCI). In this study, we evaluated the effect of low-dose LPS preconditioning on neuroapoptosis status after traumatic SCI (TSCI), using a standardized contusion model (NYU, New York University, impactor). SCI-induced rats were randomly divided into three groups: sham operation, control (receiving only normal saline) and LPS preconditioning (0.2 mg/kg, ip; 72 hours before injury). Neurologic function was assessed by the Basso, Beattie and Bresnahan (BBB) score at 6, 12, 24, 48 and 72 hours after TSCI. Rats were sacrificed at 72 hours postinjury. Histological changes were studied using Nissl staining. Apoptotic neural cells were assessed using the TdT-mediated dUTP Nick End Labeling (TUNEL) assay. Nuclear factor erythroid 2-related factor 2 (Nrf2) and caspase-3 were detected with immunohistochemistry and Western blot. LPS preconditioning reduced neuron apoptosis, improved neurologic outcome and actived Nrf2 expression. Moreover, Histological changes and the number of apoptotic cells were correlated with Nrf2 expression after the rats suffered the SCI. Our results suggest that LPS preconditioning exerted a neuroprotective effect against TSCI in rats, and activation of Nrf2 was believed to be one of the contributing mechanisms.

The effects of NSAIDs on types I, II, and III collagen metabolism in a rat osteoarthritis model.

The effects of long-term use of celecoxib, ibuprofen, and indomethacin on types I, II, and III collagen metabolism were evaluated in rat osteoarthritis (OA) model. One hundred and thirty wistar rats were randomly divided into 4 groups: the celecoxib group, the ibuprofen group, the indomethacin group, and the normal saline group. The osteoarthritis was induced by the excision of the left Achilles tendon. In the 3rd, 6th, and 9th month of treatment after surgically induced osteoarthritis, the articular cartilage was observed with microscope using HE staining. The expression of proteoglycans was semiquantified using toluidine blue staining. And, the expressions of types I, II, and III collagen in chondrocytes were examined using immunohistochemistry. The results suggested that celecoxib had no remarkable effects on the expression of types I, II, and III collagen. Ibuprofen upgraded the expression of types I, II, and III collagen and increased the synthesis of collagen. Indomethacin suppressed the expression of type II collagen and enhanced the expression of types I and III collagen. Therefore, during the long-term use of NSAIDs in osteoarthritis, celecoxib may have no remarkable influences on collagen metabolism of the articular cartilage and may be the ideal choice in the treatment of chronic destructive joint disease when anti-inflammatory drugs need to be used for a prolonged period. Ibuprofen may be unfavorable, and indomethacin may be harmful to collagen metabolism in OA treatment.

Therapeutic efficacy and bone marrow protection of the mdr1 gene and over-dose chemotherapy with doxorubicin for rabbits with VX2 hepatocarcinoma.

BACKGROUND: Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efficacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits. METHODS: The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efficacy of over-dose chemotherapy were observed. RESULTS: The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efficiency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26 +/- 1.03) x 10(4)/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00 +/- 46.75 d) of the rabbits was extended (P<0.05) and the healing rate of the tumor was increased (P<0.05). CONCLUSIONS: The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be prescribed for the treatment of malignant tumors.