Expression profile of circular RNAs in IDH-wild type glioblastoma tissues.

OBJECTIVE: The aim of the present study is to investigate the expression profiles of circular RNAs (circRNAs) in IDH-wild type (IDH-wt) glioblastoma and explore the differences in circRNAs expression between IDH-wt glioblastoma and adjacent normal brain. PATIENTS AND METHODS: circRNA expression profiles were detected by circRNA microarray in three matched pairs of IDH-wt glioblastoma and adjacent normal brain. qRT-PCR was used to verify the differential expression of circRNAs from microarray analysis. Bioinformatics analysis was used to analyze potential functions of the differentially expressed circRNAs in IDH-wt glioblastoma. RESULTS: Compared with the adjacent normal brain tissues, 254 circRNAs were upregulated and 361 circRNAs were downregulated in IDH-wt glioblastoma with a ≥1.5-fold change. A total of 12 differentially expressed circRNAs were randomly selected and validated a good correlation of results from circRNA-seq with qRT-PCR. Gene Ontology (GO) analysis revealed the differentially expressed circRNAs possibly involved in cell division, DNA damage repair, cytoskeleton, and protein ubiquitination. 46 and 50 miRNAs were predicted to be adsorbed by the top 10 upregulated circRNAs and top 10 downregulated circRNAs, respectively. CONCLUSION: Differential expression of circRNAs may be associated with IDH-wt glioblastoma development and progression, and these circRNAs can be identified as biomarkers for prognosis prediction and targets for treatment.

CPEB4 regulates glioblastoma cell proliferation and predicts poor outcome of patients.

OBJECTIVE: Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene expression at transcriptional level and has been reported to be associated with biological malignancy in cancers. However, little was known about the correlation between CPEB4 and glioblastoma cell proliferation and the prognostic significance in patients. Our aim was to investigate the functional role and prognostic value of CPEB4 in glioblastoma. PATIENTS AND METHODS: We determined the expression of CPEB4 protein using immunohistochemistry in tissue microarrays containing 278 glioma patients (including 98 primary glioblastomas) and evaluated its association with pathological grades and clinical outcome by univariate and multivariate analyses. And then, lentiviral-mediated RNAi targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell proliferation. RESULTS: In our cohort, CPEB4 expression was positively related to glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01). High expression of CPEB4 was associated with significantly poor prognosis, and could be identified as an independent risk factor for overall survival (OS) and progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) = 1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies further showed that downregulation of CPEB4 significantly reduced the growth rate of T98G and U251 cells comparing with the controls. CONCLUSION: Our study indicated that increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients and suppression of CPEB4 inhibit tumor cell proliferation, suggesting a potential therapeutic target for glioblastoma.

Overexpression of G-protein-coupled receptors 65 in glioblastoma predicts poor patient prognosis.

OBJECTIVE: G-protein-coupled receptors 65 (GPR65), identified as an acid-sensing receptor, is overexpressed in several malignancies and promote tumor development. Our aim was to investigate the expression and prognostic value of GPR65 in glioblastoma. MATERIALS AND METHODS: We determined the expression of GPR65 protein using immunohistochemistry in tissue microarrays containing 11 Grade I, 107 Grade II, 47 Grade III, and 102 Grade IV gliomas and 16 normal brains. Then we evaluated its association with pathological grades, prognosis, and recurrence. The Cancer Genome Atlas (TCGA) group (N=528) was further employed to examine transcriptional level of GPR65 in glioblastoma and the correlation between GPR65 expression and clinical outcome. RESULTS: In our cohort, GPR65 expression was positively related to glioma pathological grade (p<0.01) and elevated in glioblastoma (p<0.01). High expression of GPR65 was associated with significantly short overall survival (OS) (p=0.013) and progression-free survival (PFS) (p=0.029), and could be identified as an independent risk factor for OS of glioblastoma patients (Hazard Ratio [HR]=1.596, p=0.037). As an aiding evidence, increased GPR65 mRNA expression was also found in TCGA glioblastoma group (p<0.001) and its high level predicted a poor clinical outcome (OS, p=0.003; PFS, p=0.001). CONCLUSION: Our findings suggest that GPR65 is overexpressed in glioblastoma and its high expression predicts unfavorable clinical outcome for patients. Targeting GPR65 may serve as a potential therapy for treating glioblastoma.

[Anti-inflammatory activity and healing-promoting effects of topical application of emu oil on wound in scalded rats].

OBJECTIVE: To investigate the effects of topical application of emu oil on wound healing in scalded rats. METHODS: In 144 male Wistar rats with 10%; total body surface superficial II degree scald treated on a random basis with physiological saline, povidone iodine and emu oil, respectively, the changes of the wound were observed and the wound tissue and blood samples harvested at different times after injury for evaluation of histopathological changes, total tissue water content (measured by wet:dry weight ratios), and tumor necrosis factor (TNF)-alpha levels in the wound tissue and plasma by enzyme-linked immunosorbent assay (ELISA). The general condition of the wound healing was also observed. RESULTS: After application of emu oil, the swelling and effusion of the burn wound were alleviated and evidences of wound infection or adverse effects were not observed. Pathological examination showed that emu oil could alleviate topical inflammation, which was particularly obvious on days 1 and 3 after injury as compared with the other two groups. On day 3 after injury, water content and TNF-alpha level in the tissues was markedly decreased with the application of emu oil (P<0.05), with a significant correlation between their changes (P<0.001) and shortened wound healing time (P<0.05). Pathological examination showed that emu oil could promote epithelialization and differentiation of various epidermal layers. CONCLUSION: Emu oil has topical anti-inflammatory activity in rats with superficial II degree scald, possibly in association with decreased levels of the proinflammatory cytokines in the tissues and can promote wound healing by inhibiting local secondary inflammation.

[Reconstruction [correction to Reconstrction] of mandibular bone defects by using the techniques [correction to teachniques] of the reverse engineering and rapid prototyping].

OBJECTIVE: To evaluate the feasibility of designing and fabricating customized titanium bone substitutes to restore mandibular bone defects using reverse engineering (RE) and rapid prototyping (RP) techniques. METHODS: Titanium tray for mandibular defects were designed and fabricated through multi-step procedures of reverse engineering and rapid prototyping, then in operation it was filled with cancellous bone and fixed. RESULTS: The bone substitutes fabricated by this method had been successfully put into clinical use for maxillofacial surgery in 2 patients and got a satisfactory result. CONCLUSIONS: Reverse engineering combining with rapid prototyping could accomplish the design and manufacture of implant for the restoration of mandibular bone defects.

Effect of recombinant human basic fibroblast growth factor on angiogenesis during mandible fracture healing in rabbits.

OBJECTIVE: To investigate the effect of recombinant human basic fibroblast growth factor (rhbFGF) on angiogenesis during mandible fracture healing in rabbit. METHODS: Fifty adult white rabbits were used for animal model and randomly divided into a control group (25 rabbits) and an experimental group (25 rabbits). The membranous complex of rhbFGF and bovine type I collagen was prepared and implanted into the rabbit mandible fracture site under periosteum. The animals were sacrificed on 7, 14, 28, 56 and 84 days respectively after operation and the whole mandibles were harvested. The expression of factor VIII related antigen (F8-RA) in callus was examined with immunohistochemical staining. RESULTS: The amounts of microvascular formation in calluses in the rhbFGF-treating group on days 7, 14, 28 and 56 were more than those of the control group (P<0.01). CONCLUSIONS: The results indicated that rhbFGF could stimulate microvascular formation during mandible fracture healing in rabbits.