Circ_ORC2 enhances the regulatory effect of miR-19a on its target gene PTEN to affect osteosarcoma cell growth.

Osteosarcoma is a highly malignant and aggressive bone tumor. Its occurrence and development involve many factors and multiple signaling pathways. Some studies have shown that circular RNAs (circRNAs) play important roles in the development of various tumors. This research showed that circ_ORC2 was generally up-regulated in various osteosarcoma cell lines, and mainly distributed in the cytoplasm. Circ_ORC2 had the binding site of miR-19a, and its expression was positively correlated with miR-19a expression. RIP experiments showed that circ_ORC2 could bind to Ago2 protein. RNA pull-down using biotinylated circ_ORC2 or miR-19a showed that circ_ORC2 could directly interact with miR-19a, and dual luciferase reporter gene assay also confirmed that miR-19a could bind to circ_ORC2. After circ_ORC2 knockdown, miR-19a expression was down-regulated, but the downstream target gene PTEN expression was up-regulated, and the phosphorylation level of Akt was reduced, which indicated that circ_ORC2 enhanced the inhibition of miR-19a on PTEN expression by combining miR-19a. Further functional experiments showed that after circ_ORC2 knockdown, cell proliferation and invasion decreased, while the apoptosis level increased. When co-transfected with circ_ORC2 siRNA and miR-19a mimics or PTEN siRNA, the above cell biological behaviors did not change significantly. Therefore, circ_ORC2 binds with miR-19a and enhances its expression, thereby inhibiting downstream PTEN expression and activating Akt pathway to promote osteosarcoma cell growth and invasion. These findings enrich the circRNA molecular regulation mechanism, and provide more reference ideas for the research and application of circRNAs in tumors and other diseases.

Increased histone deacetylase 6 expression serves as a favorable prognostic factor for diffuse large B-cell lymphoma.

OBJECTIVE: This study aims to investigate ectopic expression of histone deacetylase 6 (HDAC6) in diffuse large B-cell lymphoma (DLBCL). METHODS: This study analyzed patients with DLBCL (n=132) and reactive lymph node hyperplasia (n=32) diagnosed in our hospital from December 2007 to May 2016. Correlation between HDAC6 expression and clinical pathologic features was analyzed by χ2 test. The significant differences between the 5-year overall survival (OS) or progression-free survival (PFS) and high HDAC6 expression as well as DLBCL clinic-pathological features including age, International Prognostic Index (IPI) score, Eastern Cooperative Oncology Group score, lactate dehydrogenase (LDH), and germinal center B-cell-like were assessed by univariate and multivariate analyses. RESULTS: HDAC6 high-expression percentage in DLBCL was significantly higher than that in the control group. The proportion of IPI score of 0-2, 5-year OS, and PFS in the high-expression group, which had lower percentage of patients with increased LDH and ß2-microglobulin, were significantly higher than those in the low-expression group. Moreover, HDAC6 mRNA expression in HDAC6 protein low expression was markedly lower than that in protein high expression. The multivariate analysis demonstrated that HDAC6 high expression was an independent prognostic factor for patients with DLBCL. CONCLUSION: HDAC6 high expression might be a prognostic factor for DLBCL.

More vulnerability of left than right hippocampal damage in right-handed patients with post-traumatic stress disorder.

Previous studies have shown hippocampal abnormalities in people with post-traumatic stress disorder (PTSD), but findings of diminished volume in shortages in the hippocampus have been inconsistent. In this study, we investigated changes in hippocampal volume and neuronal metabolites in right-handed PTSD patients to determine their possible relationship(s) with PTSD severity. We performed a case-control study of 11 right-handed PTSD patients and 11 healthy controls using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS). Hippocampal volume and metabolite ratios of N-acetylaspartate (NAA) to creatine (Cr) (NAA/Cr) and choline compounds (Cho) to Cr (Cho/Cr) were calculated. The severity of PTSD was evaluated by the Clinician-Administered PTSD Scale (CAPS). Significantly decreased left and total normalized hippocampal volumes were found in PTSD patients compared with controls (6.6% for the left hippocampus, 5.5% for total hippocampus). Also, the bilateral hippocampal NAA/Cr ratio of PTSD patients was significantly reduced compared with controls. The volume of the left hippocampus was negatively correlated to the CAPS total and CPAS-C scores. The left hippocampal NAA/Cr ratio was negatively correlated to the CAPS-total, CAPS-B, CAPS-C, and CAPS-D scores. The CAPS total and the CAPS-B scores were positively correlated to the Cho/Cr ratio of the right hippocampus. Our results indicate that hippocampal dysfunction is asymmetric in right-handed PTSD patients, with the left side affected more than the right.

Tianeptine reverses stress-induced asymmetrical hippocampal volume and N-acetylaspartate loss in rats: an in vivo study.

Stress-induced hippocampal volume loss and decrease in N-acetylaspartate (NAA) level have been reported to be associated with impaired neural plasticity and neuronal damage in adults. Accordingly, reversing structural and metabolite damage in the hippocampus may be a desirable goal for antidepressant therapy. The present study investigated the effects of tianeptine on chronic stress-induced hippocampal volume loss and metabolite alterations in vivo in 24 Sprague-Dawley rats. Rats were subjected to a consecutive 28-day forced swimming test stress. Tianeptine (50mg/kg) or saline was administered intragastrically 4h after swimming each day. Spontaneous behaviors, serum corticosterone concentration, hippocampal volume and NAA level were evaluated after stress. Chronic tianeptine treatment counteracted the chronic stress-induced suppression of spontaneous behaviors, elevated serum corticosterone concentration, reduced hippocampal volume and decreased NAA level. Moreover, we found asymmetrical right-left hippocampal volume loss in stressed rats, with the left hippocampus more sensitive to chronic stress than the right hippocampus. In addition, stressed rats showed a decreased level of hippocampal metabolites, without significant loss of hippocampal volume. These findings provide experimental evidence for impaired structural plasticity of the brain being an important feature of depressive illness and suggest that prophylactic tianeptine treatments could reverse structural changes in brain. The structural and neurochemical alterations in the hippocampus may be valuable indexes for evaluating the prophylactic and curative effect of antidepressant treatments in depressive and stress-related disorders.

[Imaging evaluation of the contribution of the deep circumflex iliac arterial vascularized iliac bone grafting to the reconstruction of blood supply of the femoral head].

OBJECTIVE: To evaluate the contribution of the deep circumflex iliac arterial vascularized iliac bone grafting to the reconstruction of the blood supply of the femoral head through the digital subtraction angiography (DSA) or computied tomographic scanning angiography (CTA) of the both deep circumflex iliac artery and ECT, MRI judgement. METHODS: Forty-five patients with the intracapsular fracture of femoral neck included 30 males and 15 females with an average age of 36.5 years ranging from 16 to 50. The course was from 6 to 25 days(means 10.2 days). There were 20 cases of sub-headfractures, 10 cases of head-neck, 15 cases of trans-neck. All patients were treated by 3 titanium alloy cannulated screws and deep circumflex iliac arterial vascularized iliac bone grafting. A follow-up for an average of 3 years and 6 months was performed. The engorging of the artery and reconstruction of the blood supply of the femoral head was viewed dynamicly,using digital subtraction angiography (DSA) or computied tomographic scanning angiography (CTA) of the both deep circumflex iliac artery and ECT, MRI judgement of the femoral head. RESULTS: Three weeks after operation, 38 transferred arteries were engorging via DSA, 2 of 7 not via CTA, but engorging via DSA. One year later after operation, all arteries were engorging via DSA or CTA. ECT examination in 3, 6, 12 months after operation displayed nuclide enriching in the femoral head and distributing uniformity. The region of interest (ROI) ratios of the fractured head of femur to contralateral counterpart (D/N) in all cases > 1.0. The average D/N after 3 months was (2.12 +/- 0.21), (2.04 +/- 0.14) after 6 months, (l1.71 +/- 0.11) after 12 months. There was statistical differation between D/N after 12 months and 3 or 6 months (P < 0.05), but not between 3 and 6 months (P > 0.05), and MRI examination in all cases no founded decreasing of the density and changing of the form of the femoral head. CONCLUSION: DSA, CTA, ECT, MRI confirmed that the deep circumflex iliac arterial vascularized iliac bone can provide effective blood supply and is profit to the reconstruction of the blood supply of the femoral head after the fracture of the femoral neck.