miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1ß.

Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor γ coactivator 1ß as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor γ coactivator 1ß-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.

Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1ß expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

Posterior reduction and instrumentation with rod-screw construct for atlanto-axial dislocation: a single institutional study with 21 consecutive cases.

OBJECTIVE: Atlanto-axial dislocation is one of the leading causes for occipito-cervical instability. This study aimed for investigating the clinical outcome of rod-screw construct rather than traditional posterior wiring for atlanto-axial dislocation. METHODS: Twenty one consecutive atlanto-axial dislocation patients undergoing surgery in our institution from April 2008 to May 2011 were retrospectively reviewed. Posterior reduction and instrumentation between occipital/C1 lateral mass and C2 pedicle, and concomitant occipital-atlanto-axial fusion were achieved with polyaxial-screw and rod construct. Clinical outcomes and complications were analyzed postoperatively at 3, 6, and 12 months. RESULTS: The satisfactory repositioning and internal fixation of the atlanto-axial joint, rigid screw placement and successful atlanto-axial fusion were confirmed in the 20 cases during follow-up. One patient died of a secondary ischemic injury to the brainstem 12 days after operation. The exception was a pediatric patient with loosened screws at 3 months follow-up postoperatively. Importantly, clinical symptoms and neurological function were significantly improved in all 20 cases during each follow-up as compared to preoperative scenarios. In addition, we noted that ischemic injury and screw detachment may be the main surgical risks. CONCLUSIONS: This surgical procedure provided satisfactory reduction of the atlanto-axial joint with significant neurological improvement. Moreover, we successfully avoided complications of posterior wiring.

One-stage apertura thoracis superior approach for four-vessel occlusion in rats.

OBJECTIVE: There are a great number of modified models based on the four-vessel occlusion (4VO) model of Pulsinelli and Brierley which has been used worldwide for brain ischemia research. However, up to now the problems of collateral circulations of 4VO and the difficulty in arranging a surgery to occlude the basilar artery in other models are not satisfactorily solved yet. In this study, an improved 4-vessel occlusion (I4VO) rat model which is easy to handle and able to decrease the effect of collateral circulation is reported. METHODS: The common carotid arteries and the beginning of the subclavical arteries of rats were occluded for different time by one-stage apertura thoracis superior approach. Neurological deficit scores defined by the modified Garcia scoring system and histopathological method were used to evaluate the effects of this model up to 7 days after reperfusion. RESULTS: The neurological scores in the 15-min and 25-min groups decreased significantly at 24, 48 and 72 hours after reperfusion (P less than 0.05), and the histopathologic study showed that there were stable, symmetrical changes of lesions in bilateral hippocampus in all the ischemia samples from two ischemia groups compared with sham operated group (P less than 0.05). CONCLUSION: This modified model is safe, easy, reliable, stable, mini-invasive as well as time-saving in making bilateral hemispheric ischemia, which can effectively decrease collateral circulations and meanwhile lead to stable lesions in hippocampus and cortex.

Modified approach to construct a vascularized coral bone in rabbit using an arteriovenous loop.

The most important factor for the survival of thick three-dimensional tissues is the degree of vascularization. In this study, a modified arteriovenous loop (AVL) model was developed to prefabricate an axial vascularized tissue-engineered coral bone. In group A (n = 28), an arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. The AVL was placed in a coral block (6 x 8 x 10 mm (3)) as a vascular carrier. The complex was wrapped with polytetrafluoroethylene membrane and implanted subcutaneously. In group B (n = 20), there was no vascular carrier, and the same dimensional coral was directly implanted beneath inguinal skin. After 2, 4, 6, and 8 weeks, the rabbits were perfused with heparinized saline (for scanning electron microscopy), India ink (for histological examination), and ethylene perchloride (for vascular casts) via the abdominal aorta. In group A, histology showed that newly formed vasculature extended over the surfaces and invaded the entire coral blocks. The vascular density was significantly superior to that in group B. Vascular casts showed that new blood vessels robustly sprouted from the AVL. Scanning electron microscopy demonstrated that there were minute sprouting cavities in the vascular endangium. In this model, an axial vascularized coral bone could be effectively constructed.

[Exogenous nitric oxide inhibits the proliferation of mouse neural progenitor cells].

OBJECTIVE: To explore the inhibitive effect of exogenous nitric oxide (NO) on the proliferation of mouse neural progenitor cells (NPCs). METHODS: NPCs were cultured in medium containing EGF, and SNP was added as a donor of NO in vitro. The concentration of NO was measured by the Griess assay; The amount of living cells was measured by MTT assay. The NPCs were induced to differentiate in medium supplemented with serum. RESULT: The NO(-)2 concentrations in the supernatants of the experimental groups 1, 2, and 3 were 64.701 +/- 0.606, 82.659 +/- 0.394 and 93.648 +/- 0.394 micro mol/L respectively, 3.099 +/- 0.420 micro mol/L in th control group. After culture with SNP for 24 hours, MTT assay showed the A values of 0.546 +/- 0.016, 0.484 +/- 0.007, and 0.357 +/- 0.007 in the experimental groups 1, 2, and 3 respectively, 0.642 +/- 0.021 in th control group (all P < 0.01). After further culture in the medium without SNP for 24 hours, MTT assay showed the A values of 1.243 +/- 0.036, 1.064 +/- 0.097, and 0.834 +/- 0.031 in the experimental groups 1, 2, and 3 respectively, 1.581 +/- 0.072 in the control group (all P < 0.01). The differences between the A values of the supernatants in the same wells filled with the medium with and without SNP were all significant (P < 0.01). In the medium with serum the NPCs still proliferated actively and differentiated into neuron and glial cell after SNP was removed. CONCLUSION: Exogenous nitric oxide inhibits the proliferation of mice NPC in vitro.