Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress.

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured. Aroclor 1254 reduced cell viability and induced overproduction of intracellular reactive oxygen species in a dose-dependent manner. Activity of superoxide dismutase was decreased, and malondialdehyde content was promoted after exposure. Moreover, inhibitory effects of Aroclor 1254 on calcium metabolism and mineralization of osteoblasts were observed, as indicated by reduction of the intracellular calcium concentration, osteocalcin content, and modules formation rate. The decreased expression of osteocalcin, alkaline phosphatase, bone sialoprotein, and transient receptor potential vanilloid 6 further confirmed the impairment of Aroclor 1254 on calcium homeostasis and osteoblast differentiation. Addition of the antioxidant N-acetyl-L-cysteine partially restored the inhibitory effects on calcium metabolism and mineralization. In general, Aroclor 1254 exposure reduces calcium homeostasis, osteoblast differentiation and bone formation, and oxidative stress plays a vital role in the underlying molecular mechanism of osteotoxicity.

Posterior cervical full-endoscopic technique for the treatment of cervical spondylotic radiculopathy with foraminal bony stenosis: A retrospective study.

Objective: In the treatment of cervical spondylotic radiculopathy (CSR), spinal endoscopy has been developed vigorously in the past 30 years. However, its effectiveness and subsequent problem of cervical spine stability have always been the controversial hotspots. This study aims to conduct a retrospective study using posterior cervical full-endoscopic technique for the treatment of CSR with foraminal bony stenosis, and evaluate its clinical effect and application value. Methods: All 22 patients treated for CSR with foraminal bony stenosis using posterior cervical full-endoscopic technique were analyzed since Dec 1, 2016, to Apr 30, 2020. The data collection included operation time, length of stay, wound healing, surgical complications, visual analog scale (VAS), Japanese Orthopaedic Association (JOA) scores, intervertebral foramen diameter, intervertebral foramen area and cervical instability. The relevant indicators were observed on admission, at postoperative 1 week and 3 months, and at the last follow-up. Results: The operation time was 141.6 ± 13.7 min. The length of stay was 6.0 ± 2.5 days. VAS and JOA at different time points after operation were decreased compared with before operation (p < 0.05). There were no statistical differences between VAS or JOA at different postoperative time points (p > 0.05). The height, anteroposterior diameter and area of intervertebral foramen after operation were significantly increased compared with before operation (p < 0.05). Conclusion: Posterior cervical full-endoscopic technique shows the advantages of smaller invasion, faster recovery, significant effectiveness and fewer complications in our study. Meanwhile, it has little influence on the ROM and stability of the cervical spine. Therefore, it is a minimally invasive, safe and effective surgical method for the treatment of CSR with foraminal bony stenosis.

[Comparison of the predictive value of tip-apex distance and calcar referenced tip-apex distance in treatment of femoral intertrochanteric fractures with Asian type proximal femoral nail fixation].

OBJECTIVE: To compare the predictive value of the two concepts for complications by comparing the incidences of surgical complications associated with different tip-apex distance (TAD) and calcar referenced tip-apex distance (Cal-TAD) in the treatment of femoral intertrochanteric fractures with Asian type proximal femoral nail (APFN) fixation. METHODS: A total of 188 cases of femoral intertrochanteric fractures treated with APFN fixation between January 2014 and December 2018 were collected according to inclusion criteria. TAD and Cal-TAD were measured on the X-ray film at immediate after operation; the patients were divided into two groups according to the measurement results: <25 mm and ≥25 mm. Gender, age, and fracture side and AO type were recorded. The patients in each group were reviewed whether there was delayed fracture union or nonunion, whether the screw blade moved axially, whether the femoral neck collapsed or even screw blade cut out, whether the internal fixator became loose or broken within 12 months after operation. Then statistical analysis was performed. RESULTS: There were 119 patients with TAD<25 mm and 69 patients with TAD≥25 mm, and 142 patients with Cal-TAD<25 mm and 46 patients with Cal-TAD≥25 mm. There was no significant difference in gender, age, or fracture side and AO type between groups ( P>0.05). During the follow-up, 6 patients (5.04%) with TAD<25 mm, 10 patients (14.49%) with TAD≥25 mm had complications, and 1 patient (0.70%) with Cal-TAD<25 mm and 15 patients (32.61%) with Cal-TAD≥25 mm had complications. There were significant differences in the incidence of complication between the patients with different TAD, between the patients with different Cal-TAD, and between patients with TAD<25 mm and Cal-TAD<25 mm ( P<0.05). CONCLUSION: In the operation of femoral intertrochanteric fracture with APFN fixation, surgical complications can be significantly reduced when TAD or Cal-TAD was controlled within 25 mm, Cal-TAD is more significant in the prediction of postoperative complications.

Identification of Key Gene Signatures Associated With Bone Metastasis in Castration-Resistant Prostate Cancer Using Co-Expression Analysis.

About 80-90% of castration-resistant prostate cancer (CRPC) patients would develop bone metastasis. However, the molecular mechanisms of bone metastasis are still not clear. This study aimed to detect the differences between the tumor and normal samples in bone after metastatic colonization. Four transcriptional datasets (GSE32269, GSE101607, GSE29650, and GSE74685) were obtained from the GEO database. 1983 differentially expressed genes (DEGs) were first identified between tumor and normal marrow samples in GSE32269. Most of the top 10 up-regulated DEGs are related with prostate cancer, and the top 10 down-regulated DEGs are mainly related with bone development. Seven co-expression modules were then detected based on the 1469 DEGs shared by the four datasets. Three of them were found highly preserved among the four datasets. Enrichment analysis showed that the three modules were respectively enriched in Cell adhesion molecules (CAMs), Leukocyte transendothelial migration and cell cycle, which might play significantly important roles in the tumor development in bone marrow. Ten, 17, and 99 hub genes for each module were then identified. And four genes (C3AR1, IL10RA, LY86, and MS4A6A) were detect to be tightly related to progression of bone metastatic CRPC. ROC curve was plotted and AUC was calculated to distinguish tumor and normal bone marrow samples as well as bone and non-bone metastatic CRPCs. The present study identified key genes and modules involved in bone metastatic CRPCs, which may provide new insights and biomarkers for understanding of the molecular mechanisms of bone metastatic CRPC.

Suppression of Development of Ankylosing Spondylitis Through Soluble Flt-1.

BACKGROUND/AIMS: Circulating monocytes/macrophages are origins of osteoclasts that mediate the development of ankylosing spondylitis (AS). Moreover, infiltrated macrophages facilitate the AS progression through production and secretion of pro-inflammatory cytokines. Thus, suppression of the recruitment of circulating monocytes/macrophages may be an effective AS treatment, which is, however, not available so far in clinic. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor for vascular endothelial growth factor (VEGF) to compete with VEGF receptor (VEGFR2) for VEGF binding in endothelial cells, while its application in treating AS and effects on the recruitment of circulating monocytes/macrophages has not been reported before. METHODS: We used a proteoglycan-induced arthritis (PGIA) mouse model for human AS. We injected sFlt-1 into the articular cavity and evaluated its effects on PGIA by incidence of arthritis, and clinical and pathological arthritis severity. We isolated and analyzed macrophages and endothelial cells in the articular cavity before and after treatment. RESULTS: Injection of sFlt-1 significantly decreased the incidence and severity of PGIA in mice, and significantly reduced the number of infiltrated macrophages, possibly through reduction of vessel permeability, in a VEGFR2-dependent manner. CONCLUSION: Our data suggest that sFlt-1 may have a therapeutic effect on AS, resulting from suppression of VEGF signaling-mediated recruitment of circulating monocytes/macrophages.

Overexpression of miR-506 inhibits growth of osteosarcoma through Snail2.

Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis accounts for the majority of OS-related death. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Thus, elucidation of the involvement of specific miRNAs in the metastasis of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-506 were significantly decreased and the levels of Snail2 were significantly increased, compared to the paired normal bone tissue. MiR-506 and Snail2 inversely correlated in patients' specimen. Bioinformatics analyses predicted that miR-506 may target the 3'-UTR of Snail2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Moreover, miR-506 overexpression inhibited Snail2-mediated cell invasiveness, while miR-506 depletion increased Snail2-mediated cell invasiveness in OS cells. Together, our data suggest that miR-506 suppression in OS cells may promote Snail2-mediated cancer metastasis.

Knockdown of galectin-1 suppresses the growth and invasion of osteosarcoma cells through inhibition of the MAPK/ERK pathway.

Galectin-1 (GAL1), a widely expressed ß­galacto-side-binding protein, exerts pleiotropic biological functions. GAL1 has been found to be upregulated in many malignancies; yet the role of GAL1 in the pathophysiology of human osteosarcoma (OS) remains uncertain. The present study was carried out to investigate the expression of GAL1 in human OS tissues and to explore its effects on the growth and invasion of OS cells. OS and corresponding adjacent non-cancerous tissues (ANCT) were collected from 30 consecutive cases. The expression of GAL1 was detected by immunohistochemical assay through tissue microarray procedure. Using small hairpin RNA (shRNA)-mediated GAL1 knockdown (Lv-shGAL1) in OS (MG-63 and U-2 OS) cells, we observed the changes in the malignant phenotype in OS cells in vitro and in vivo. As a consequence, the positive expression of GAL1 was significantly higher in OS tissues than that in the ANCT (63.3 vs. 36.7%, P=0.029), and was positively correlated with distant metastasis in the OS patients (P=0.022). Knockdown of GAL1 suppressed cell proliferative activities and invasive potential and induced apoptosis in OS cells with decreased expression of p38MAPK, p-ERK, Ki-67 and matrix metallopeptidase-9 (MMP-9) and increased expression of caspase-3. In addition, the tumor volume in the MG-63 subcutaneous tumor models treated with Lv-shGAL1 was significantly smaller than that in the negative control (NC) group (P<0.01). Altogether, our findings indicate that high expression of GAL1 is associated with distant metastasis of OS patients, and knockdown of GAL1 inhibits growth and invasion of OS cells possibly through inhibition of the MAPK/ERK pathway, suggesting that GAL1 may represent a potential target for the treatment of cancer.

Clinical efficacy of semi-laminectomy and posterior stabilization for treatment of thoracolumbar burst fracture.

OBJECTIVE: The purpose of the present study was to investigate the efficacy of posterior semi-laminectomy, restoration of bony fragments and short-segment pedicle screw fixation for treatment of thoracolumbar burst fractures. METHODS: From January 2008 to April 2011, 21 patients (19 males and 2 females) who suffered single-level thoracolumbar burst fractures were enrolled in this study. Fractures at T11, T12, L1, L2 and L3 level occurred in 3, 5, 8, 4 cases and 1 case, respectively. The patients enrolled were presented with 30%-50% encroachment of spinal canal, partial neurological function deficits and intact pedicles, and underwent semi-laminectomy on the fractured thoracolumbar spine, restoration of the fractured bony fragments with special bone punch beneath dural sac, as well as pedicle screw fixation of the fractured thoracolumbar spine and the two vertical neighboring segments. RESULTS: All patients were followed up for 12-48 months, with a mean of 17 months. The mean kyphotic deformity was reduced from (17.3 ± 5.3)° preoperatively to (9.2 ± 4.1)° at follow-up within 12 months. The mean spinal canal diameter increased from (9.7 ± 2.7) mm before surgery to (13.3 ± 1.4) mm at follow-up. Neurological improvement occurred in all subjects after average 2.5 months (range, 1-7 months). Only postoperative wound dehiscence was observed in 1 case, which was caused by implant reaction of calcium phosphate and healed after debridement. CONCLUSION: Semi-laminectomy and restoration of bony fragments is a safe and effective therapeutic measure for thoracolumbar burst fractures with spinal canal encroachment of less than 50%.

Effect of a single high loading dose of rosuvastatin on percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVES: A high loading dose of atorvastatin has been confirmed to reduce postprocedural events in patients undergoing percutaneous coronary intervention (PCI). In this study, we sought to investigate the protective effects of rosuvastatin in patients with acute coronary syndromes (ACS) undergoing PCI and to determine the effect of rosuvastatin pretreatment on the postprocedural levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). METHODS: A total of 125 patients with non-ST-segment elevation ACS were randomized to pretreatment with rosuvastatin (20 mg 2-4 hours before PCI [n = 62]) or placebo (n = 63). All the patients received subsequent long-term rosuvastatin treatment (10 mg/d). The main end point of the trial was the 30-day incidence of major adverse cardiac events (death, myocardial infarction, or unplanned revascularization). Plasma levels of hs-CRP, IL-6, and MCP-1 were detected before PCI and 6 hours, 24 hours, and 3 days after PCI. RESULTS: The primary end point occurred in 8.1% of the patients in the rosuvastatin arm and 22.2% in the placebo arm (P < .01); this difference was entirely attributed to a reduced incidence of myocardial infarction (8.1% vs 22.2%; P < .01). The postprocedural elevation in creatine kinase-MB and troponin I was also significantly lower in the rosuvastatin group at 6 hours, 24 hours, and 3 days. Plasma levels of hs-CRP, IL-6, and MCP-1 increased significantly after PCI in both the rosuvastatin and control groups; however, the postprocedural elevations in hs-CRP and IL-6 levels were significantly lower in the rosuvastatin group than the control group. CONCLUSIONS: A single, high dose (20 mg) of rosuvastatin prior to PCI reduces postprocedural myocardial injury in patients with ACS, with a concomitant attenuation of the postprocedural increase in hs-CRP and IL-6 levels.