miR-202 modulates the progression of neuropathic pain through targeting RAP1A.

Neuropathic pain is a somatosensory disorder which is caused by disease or nerve injury that affects the nervous system. microRNAs (miRNAs) are proved to play crucial roles in the development of neuropathic pain. However, the role of miR-202 in neuropathic pain is still unknown. Sprague-Dawley rats were used for constructing the neuropathic pain model. The expression of miR-202 was determined by quantitative real-time polymerase chain reaction. Potential target gene for miR-202 was measured using bioinformatics methods and Western blot analysis. In this study, we used rats to establish a neuropathic pain model and measured the effect of miR-202 in neuropathic pain. We demonstrated that miR-202 expression was downregulated in the spinal dorsal horn of bilateral sciatic nerve chronic constriction injury (bCCI) rat. However, miR-202 expression was not changed in the dorsal root ganglion, hippocampus, and anterior cingulated cortex of bCCI rat. We identified that RAP1A was a direct target gene of miR-202 in the PC12 cell. RAP1A expression was upregulated in the spinal dorsal horn of bCCI rat. Overexpression of miR-202 could improve the pain threshold for bCCI rats in both hindpaws, indicating that miR-202 overexpression could lighten the pain threshold for model rats. Moreover, RAP1A overexpression increased the pain threshold effect of miR-202 overexpression treated bCCI rats, indicating that miR-202 could lighten the pain threshold through inhibiting RAP1A expression. These data suggested that miR-202 acted pivotal roles in the development of neuropathic pain partly through targeting RAP1A gene.

MicroRNA miR-1249 downregulates adenomatous polyposis coli 2 expression and promotes glioma cells proliferation.

Continuous activation of the Wnt/ß-Catenin signaling has been reported to play important roles in multiple process of tumor progression, leading to uncontrolled cancer cell proliferation, growth, and survival. However, the mechanism underlying the regulation of the Wnt/ß-Catenin pathway remains largely unknown. Determining the molecular mechanism of the Wnt/ß-Catenin pathway's aberrant activation in glioma carcinogenesis might improve therapeutic strategies for patients with glioma. In this study, we showed that the expression of microRNA miR-1249 was markedly upregulated in glioma cell lines and tissues. Upregulation of miR-1249 enhanced, whereas downregulation inhibited, the proliferation of glioma cells both in vitro and in vivo. Furthermore, bioinformatic and experimental approaches showed that miR-1249 targets and suppresses APC2 expression, an important Wnt/ß-Catenin pathway-regulated factor. These data suggested that miR-1249 could be a novel therapeutic target of microRNA-mediated cell proliferation in glioma.

The efficacy of dexmedetomidine-remifentanil versus dexmedetomidine-propofol in children undergoing flexible bronchoscopy: A retrospective trial.

Flexible bronchoscopy has been more and more used for diagnosis and management diseases of respiratory system in pediatrics. Previous studies have reported that remifentanil (RF) and propofol are safe and effective for flexible bronchoscopy in adults, however, there have no trials evaluate the efficacy of DEX-RF versus dexmedetomidine-propofol in children undergoing flexible bronchoscopy.We divided 123 children undergoing flexible bronchoscopy with DEX-RF or dexmedetomidine-propofol into 2 groups: Group DR (n = 63, DEX infusion at 1.0 µg kg for 10 minutes, then adjusted to 0.5-0.7 µg kg h; RF infusion at 1.0 µg kg for 5 minutes, then adjusted to 0.05-0.2 µg kg min), Group DP (n = 60, DEX infusion at 1.0 µg kg for 10 minutes, then adjusted to 0.5-0.7 µg kg h; propofol infusion at 10 µg kg for 5 minutes, then adjusted to 0.05-0.1 µg kg min). Ramsay sedation scale of the 2 groups was maintained at 3. Anesthesia onset time; total number of intraoperative patient movements; hemodynamics; total cumulative dose of DEX; amount of and time to first-dose rescue midazolam and lidocaine; postoperative recovery time; adverse events; and bronchoscopist satisfaction score were recorded.Anesthesia onset time was significantly shorter in DP (8.22 ±â€Š2.48 vs 12.25 ±â€Š6.43 minutes, respectively, for DP, DR, P = 0.015). The perioperative hemodynamic profile was more stable in DR than DP group. More children moved during flexible bronchoscopy in DP group (P = 0.009). Total dose of rescue midazolam and lidocaine was significantly higher in DR than in DP (P < 0.001). Similarly, the time to first dose of rescue midazolam and lidocaine was significantly longer in DP than in DR (P < 0.001). Total cumulative dose of DEX was more in DR than DP group (P < 0.001). The time to recovery for discharge from the postanesthesia care unit (PACU) was significantly shorter in DP than in DR group (P < 0.001). The bronchoscopist-satisfaction scores were higher for DR than DP (P = 0.036). There were significant differences between the 2 groups in terms of the overall incidence of hypertension, tachycardia, and hypoxemia (P < 0.05).Although underwent longer recovery time and more incidence of rescue scheme, DEX-RF resulted in more stable hemodynamic profiles and bronchoscopist-satisfaction scores, lesser patient movements, and can hence be more effectively used in children undergoing flexible bronchoscopy than dexmedetomidine-propofol.

Expression and clinical significance of nestin in astrocytic tumors.

PURPOSE: This study aimed to investigate the expression and clinical significance of nestin in human astrocytic tumors. METHODS: Indirect immunofluorescent staining and flow cytometry were used to quantitatively detect the nestin content in 35 specimens, including 3 normal brain tissues, 29 astrocytic tumor (AT) tissues, and 3 peritumoral tissues. RESULTS: In normal brain tissues, nestin expression was extremely low. Nestin expression was significantly positively correlated with the histological grade of astrocytic tumors (p<0.05, rs=0.83). Nestin content in the peritumoral tissues was between the levels of nestin in tumor tissue and in normal brain tissue (p<0.01). Nestin expression was unrelated to the patient's gender, age, tumor location, size, etc. (p>0.05). CONCLUSION: The application of flow cytometry in the determination of nestin content could improve the accuracy of early cancer diagnosis. This method would be helpful for developing a reference range that is closely related to the pathological grading of ATs through routine assessments of nestin in many patients. Additionally, through examining nestin levels in peritumoral tissues, the invasiveness of ATs can be clarified.

MiR-454 inhibited cell proliferation of human glioblastoma cells by suppressing PDK1 expression.

It has been well documented that aberrant expression of microRNAs is associated with carcinogenesis of glioblastoma (GBM), however the underlying mechanisms are not clear. In this present study, we aimed to clarify the biological function of miR-454 in GBM. MiR-454 was identified to be significantly down-regulated in GBM primary tumors and cell lines. Overexpression of miR-454 in GBM cells resulted in arresting cells at G0/G1 phase and thus inhibiting cell proliferation. Bioinformatic analysis predicted 3-phosphoinositide-dependent protein kinase-1 (PDK1) as a target of miR-454 which acted as a tumor promoter gene. Increased miR-454 significantly repressed PDK1 expression, and then regulating cell proliferation and cell cycle regulators, down-regulation of Cyclin D1 and p-pRb and p21 was up-regulated. Taken together, our study has revealed miR-454 as a tumor suppressor in GBM.