GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis.

Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell-autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2). The SQSTM1-ERK1/2 signaling cascade was essential for GBP3-promoted cell growth because depletion of SQSTM1 markedly reduced the phosphorylated ERK1/2 levels and GBP3-mediated cell growth, and inhibition of mitogen-activated protein kinase/ERK kinase abolished GBP3-induced glioma cell proliferation. Consistently, GBP3 overexpression significantly promoted glioma tumor growth in vivo and its expression was inversely correlated with the survival rate of glioma patients. Taken together, these results for the first time suggest that GBP3 contributes to the proliferation of glioma cells via regulating SQSTM1-ERK1/2 pathway, and GBP3 might represent as a new potential therapeutic target against glioma.

Systematic review and meta-analysis of traditional Chinese medicine in the treatment of constipation-predominant irritable bowel syndrome.

AIM: This meta-analysis analyzed the efficacy and safety of traditional Chinese medicine (TCM) for the treatment of irritable bowel syndrome with constipation (IBS-C). METHODS: We searched seven electronic databases for randomized controlled trials investigating the efficacy of TCM in the treatment of IBS-C. The search period was from inception to June 1, 2017. Eligible RCTs compared TCM with cisapride and mosapride. Article quality was evaluated with the Cochrane Risk Bias Tool in the Cochrane Handbook by two independent reviewers. Begg's test was performed to evaluate publication bias. Review Manager 5.3 and Stata 12.0 were used for analyses. RESULTS: Eleven eligible studies comprising a total of 906 participants were identified. In the primary outcome, TCM showed significant improvement in overall clinical efficacy compared with cisapride and mosapride (odds ratio [OR] = 4.00; 95% confidence interval [CI]: 2.74,5.84; P < 0.00001). In terms of secondary outcomes, TCM significantly alleviated abdominal pain (OR = 5.69; 95% CI: 2.35, 13.78; P = 0.0001), defecation frequency (OR = 4.38; 95% CI: 1.93, 9.93. P = 0.0004), and stool form (OR = 4.96; 95% CI: 2.11, 11.65; P = 0.0002) in the treatment group as compared to the control group. A lower recurrence rate was associated with TCM as compared to cisapride and mosapride (OR = 0.15; 95% CI: 0.08, 0.27; P < 0.00001). No adverse effects were observed during TCM treatment. CONCLUSIONS: TCM showed greater improvement in terms of clinical efficacy in the treatment of IBS-C than cisapride and mosapride, although it was not possible to draw a definitive conclusion due to the small sample size, high risk, and low quality of the studies. Large multi-center and long-term high-quality randomized control trials are needed.

Calycosin inhibits migration and invasion through modulation of transforming growth factor beta-mediated mesenchymal properties in U87 and U251 cells.

In this study, we investigated the potential anticancer effects of calycosin against human glioblastoma cells, including the impacts on cell proliferation, apoptosis, and cell cycle distribution. We further studied its inhibitory activity on migration and invasion in U87 and U251 cells. Furthermore, transforming growth factor beta-mediated reductions of mesenchymal-associated genes/activators, matrix metalloproteinases-2, and -9 were detected in this process. Administration of calycosin in a glioblastoma xenograft model showed that calycosin could not only reduce tumor volume but also suppress transforming growth factor beta as well as its downstream molecules. These results revealed calycosin as a potential antitumor agent in human glioblastoma.

Paeoniflorin inhibits human glioma cells via STAT3 degradation by the ubiquitin-proteasome pathway.

We investigated the underlying mechanism for the potent proapoptotic effect of paeoniflorin (PF) on human glioma cells in vitro, focusing on signal transducer and activator of transcription 3 (STAT3) signaling. Significant time- and dose-dependent apoptosis and inhibition of proliferation were observed in PF-treated U87 and U251 glioma cells. Expression of STAT3, its active form phosphorylated STAT3 (p-STAT3), and several downstream molecules, including HIAP, Bcl-2, cyclin D1, and Survivin, were significantly downregulated upon PF treatment. Overexpression of STAT3 induced resistance to PF, suggesting that STAT3 was a critical target of PF. Interestingly, rapid downregulation of STAT3 was consistent with its accelerated degradation, but not with its dephosphorylation or transcriptional modulation. Using specific inhibitors, we demonstrated that the prodegradation effect of PF on STAT3 was mainly through the ubiquitin-proteasome pathway rather than via lysosomal degradation. These findings indicated that PF-induced growth suppression and apoptosis in human glioma cells through the proteasome-dependent degradation of STAT3.

[Treatment of thoracolumbar deformity with transpedicular eggshell technique].

OBJECTIVE: To evaluate the clinical effects of transpedicular eggshell technique in treating thoracolumbar deformity. METHODS: From December 2008 to December 2011,36 patients with thoracolumbar deformity were treated with transpedicular eggshell technique. There were 20 males and 16 females with an average age of 45 years old (ranged from 20 to 58). Among them, 5 cases were congenital hemivertebrae deformity, 12 cases were secondary to tuberculotic deformity, 14 cases were post-traumatic deformity with pain, 5 cases were ankylosing spondylitis. Low back pain, living ability, scoliotic Cobb angle were analyzed according to VAS scoring, Oswestry Disability Index (ODI), radiological examination. RESULTS: Average operative time was 245 min and average bleeding was 1 900 ml in 36 patients. All patients were followed up more than 1 year and obtained bone fusion at 1 year after operation. Preoperative,postoperative at 1 week and 1 year, VAS scoring was 7.2 +/- 1.4, 2.5 +/- 1.0, 1.8 +/- 0.5, respectively; ODI was (72.50 +/- 10.80)%, (42.50 +/- 11.10)%, (22.50 +/- 7.90)%, respectively; kyphosis Cobb angle was (76.31 +/- 2.52) degrees, (23.66 +/- 1.16) degrees, (23.67 +/- 1.16) degrees, respectively; lumbar scoliosis Cobb angle was (71.86 +/- 4.02) degrees, (30.81 +/- 2.33) degrees, (30.82 +/- 2.32) degrees, respectively. Postoperative at 1 week and 1 year,above data had obviously improved than that of preoperative (P < 0.05); and there was no significant difference in Cobb angle between postoperative at 1 week and postoperative at 1 year (P > 0.05). CONCLUSION: Treatment of thoracolumbar deformity with transpedicular eggshell technique could obtain effective correcting and clinical results.

[One-stage radical eradication and wedged vertebral osteotomy through a purely posterior procedure in treating thoracic and lumbar spine tuberculosis associated with kyphosis or scoliokyphosis demormity].

OBJECTIVE: To investigate the feasibility, clinical indications and significance of one-stage radical eradication, wedged vertebral osteotomy and instrumentation in the treatment of tuberculosis of thoracic and lumbar spine associated with kyphosis or scoliokyphosis through a purely posterior procedure. METHODS: Sixteen cases with tuberculosis of thoracic and lumbar spine associated with kyphosis or scoliokyphosis were treated by one-stage radical eradication, wedged vertebral osteotomy and instrumentation fixation through posterior procedure. All patients included 12 males and 4 females, and the average age was 37.1 years (from 17 to 53 years). The preoperative average Cobb angle of kyphosis was 78.3 degrees (range from 54 degrees to 138 degrees ). There were 2 cases associated with scoliosis (the Cobb angle of scoliosis was 31 degrees and 24 degrees), and 1 case with lateral transition. Spinal cord compression were found in 7 cases. According to the Frankel's classification, 2 cases belonged to C degree, and 5 cases to D degree. There were 2 cases with caudal equina or nerve root lesions. RESULTS: The average blood loss during the operation was 1100 ml (range from 450 to 2200 ml), and the average operation time was 265 min (range from 215 to 325 min). The postoperative results were satisfactory, 14 cases were excellent and 2 cases were good. Obvious improvement was obtained in 9 cases with neurological dysfunction. The postoperative average Cobb' angle was 28.5 degrees (range from 0 degrees to 67 degrees), and the corrective rate was 63.6%. The followed-up was ranged from 14 to 52 months with an average of 26.3 months. There were no major complications related to the fixations, loss of correction and the fusion were achieved in all patients. CONCLUSIONS: One-stage radical eradication, wedged vertebral osteotomy and instrumentation is a feasible and an effective procedure in the treatment of spinal tuberculosis associated with kyphosis or scoliokyphosis. Compared with combined anterior and posterior procedure, the surgical technique may decrease injuries and has better result.

[Inhibition of magnesium lithospermate B on the c-Jun N-terminal kinase 3 mRNA expression in cardiomyocytes encountered ischemia/reperfusion injury].

AIM: To study the function of c-Jun N-terminal kinase 3 (JNK3) in the process of ischemic/reperfused heart injury and the mechanism underlying the protective action of magnesium lithospermate B (MTB), a bioactive compound isolated from Danshen. METHODS: By in situ hybridization, JNK3 mRNA was detected in the ventricular preparations of the Langendorff ischemic/reperfused rat heart. The inhibitory effect of MTB on the expression of JNK3 mRNA was also investigated. RESULTS: The purple and blue hybridization signals were located in the cytoplasm of the cardiomyocytes, which were weaker in the non-perfused hearts and stronger in the hearts encountered 30 min of ischemia and 30 min of reperfusion. Image analysis showed that the expression of JNK3 mRNA in the cardiomyocytes increased after 30 min of ischemia and 30 min of reperfusion, which showed significant difference compared with that in the cardiomyocytes of the non-perfused heart and the control heart (P < 0.05). Treatment with of 0.1, 1 and 10 mumol.L-1 MTB abolished the elevation of JNK3 mRNA expression in the ischemic/reperfused heart (P < 0.05). CONCLUSION: JNK3 may be another component in the signal transduction pathway of ischemia/reperfusion induced cardiomyocyte apoptosis. MTB may protect the heart from ischemia/reperfusion injury by reducing apoptosis through inhibition of the JNK3 activity.