hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real-time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa-miR-933 overexpression. hsa_circRNA_100533 binds to hsa-miR-933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533-miR-933-GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.

Comparative Outcomes of Block and Cancellous Iliac Bone Grafting in Older Unilateral Alveolar Cleft Patients.

OBJECTIVE: To compare osseous outcomes of block and cancellous iliac bone grafting in older unilateral alveolar cleft patients. DESIGN: Retrospective and observational follow-up study. SETTING: Cleft Lip and Palate Centre, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. PATIENTS: Forty-five nonsyndromic patients with unilateral complete alveolar cleft were enrolled in this study (25 patients in block bone graft group and 20 patients in cancellous bone graft group). INTERVENTIONS: In cancellous bone graft group, the alveolar cleft was filled with iliac cancellous bone particulate. In group of block bone graft, the harvested bone block was trimmed and fixed in alveolar defect. MAIN OUTCOME MEASURES: A novel method was proposed to investigate the volume and density of residual bone graft at 1-week, 3- and 6-month, 1- and 2-year postoperatively based on cone beam computed tomography scans. RESULTS: No difference in bone graft volume was found between 2 groups at 1-week and 3-month postoperatively; however, the residual volume of block bone graft group was significantly larger than that of cancellous bone graft group at 6-month, 1- and 2-year postoperatively. The bone density of block bone graft group was lower at 1-week and 3-month postoperatively but was comparable at 6-month, 1- and 2-year postoperatively. Our method was reliable and accurate to identify the range of residual bone graft when the boundary of grafted bone could not be identified clearly. CONCLUSION: Block bone graft could achieve comparable bone density and retain a greater amount of residual bone comparing to cancellous bone graft.

Fraxinellone alleviates inflammation and promotes osteogenic differentiation in lipopolysaccharide-stimulated periodontal ligament stem cells by regulating the bone morphogenetic protein 2/Smad pathway.

OBJECTIVE: The aim of the present study was to investigate the role of fraxinellone in periodontitis and identify its potential mechanisms. DESIGN: Lipopolysaccharide-induced periodontal ligament stem cells (PDLSCs) was employed to simulate the periodontitis in vitro. The levels of inflammatory factors were evaluated. After treatment with fraxinellone, alkaline phosphatase activity was determined. Additionally, calcium nodules staining was evaluated by alizarin red staining and the expression of osteogenesis differentiation-associated proteins was detected using western blot analysis. Moreover, the levels of proteins in bone morphogenetic protein 2 (BMP2)/Smad pathway were measured. Subsequently, BMP2 was silenced by transfection with small hairpin RNA to explore the underlying mechanisms of fraxinellone in lipopolysaccharide-induced PDLSCs. RESULTS: Lipopolysaccharide stimulation significantly upregulated the levels of inflammatory factors, which were inhibited by fraxinellone intervention. Moreover, fraxinellone notably promoted osteogenic differentiation and calcification shown by increasing levels of alkaline phosphatase, calcification and osteogenic marker proteins. Furthermore, the expression of BMP2, phosphorylated Smad1 and phosphorylated Smad5 was remarkably upregulated when fraxinellone exposure in lipopolysaccharide-induced PDLSCs. What's more, BMP2 silencing dramatically restored the effects of fraxinellone on inflammation and osteogenic differentiation of PDLSCs stimulated by lipopolysaccharide. CONCLUSION: These data demonstrated that fraxinellone alleviates inflammation and promotes osteogenic differentiation in lipopolysaccharide-stimulated PDLSCs by regulating the BMP2/Smad pathway, providing experimental supports for the clinical application of fraxinellone in the treatment of periodontitis.

Block iliac bone grafting enhances osseous healing of alveolar reconstruction in older cleft patients: A radiological and histological evaluation

Background: Older alveolar cleft patients (>12 years old) often have wide bone defect as well as teeth loss, resulting in poor osseous healing with conventional alveolar bone grafting (ABG). In this study, we investigated a surgical technique of block iliac bone grafting for the alveolar cleft reconstruction and evaluated the clinical and radiological outcomes of these cleft patients. Material and Methods: Fifteen patients were included in this study. All cases received preoperative cone bean computed tomography (CBCT) scans for the alveolar cleft evaluation. Osseous outcomes of block iliac bone grafting were assessed at 1 week, 3- and 6-month postoperatively. Volume changes and bone resorption rates were calculated using the measurement modules of Simplant software. Bone samples from one patient undergoing dental implantation were assessed by micro-CT and histological examination. The morbidities of donor-site were analyzed by clinical examination and questionnaire survey. Results: The average age of the case series was 18.53±2.50 years. The intraoral incision of thirteen cases healed well. However, two cases had oronasal fistula and graft exposure at 1-week postoperatively. The results of follow-up CBCT scans showed significant resistance to radiation on both sides of the bone graft, suggesting a good osseous healing and new bone formation. The mean residual bone volume was 1.68±0.26 cm3 , 1.29±0.23 cm3 and 1.15±0.23 cm3 at 1-week, 3- and 6-month postoperatively. Correspondingly, the mean bone resorption rates in 3- and 6-month postoperative were 21.78±6.88% and 30.66±8.97%, respectively. From micro-CT and HE examinations, the block bone samples exhibited a cancellous structure in which mature bone trabecula and functional blood vessels appeared. The average scores of donor-site morbidities were drastically decreased at 3- and 6-month postoperatively compared with those at 1-week postoperatively. Conclusions: Our results demonstrated that block iliac bone grafting could achieve satisfying osseous outcomes in older alveolar cleft patients, and this technique provided favorable bony condition for further treatments, especially dental implantation (AU)

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