MiR-101-3p inhibits EMT to attenuate proliferation and metastasis in glioblastoma by targeting TRIM44.

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor originating in the brain parenchyma. The invasive and infiltrative properties of glioblastoma result in poor clinical prognosis to conventional therapies. Emerging reports on microRNAs as important regulators during the process of EMT provide new insights into treating glioblastoma through new targets. However, underlying molecular mechanism of the regulation of miR-101-3p in glioblastoma remains unclear. METHODS: Level of miR-101-3p was determined in GBM cell lines by qRT-PCR. MTT, colony formation and transwell assays were utilized to evaluate functions of overexpression of miR-101-3p/knock down of TRIM44 on proliferation, migration and invasion in GBM cells. Direct interaction between miR-101-3p and TRIM44 was validated using dual luciferase reporter system and impacts of overexpression of miR-101-3p/knock down of TRIM44 on regulation of EMT markers were assessed by Western blotting. RESULTS: MiR-101-3p was validated to be repressed expressed in glioblastoma cancer cell lines. Both overexpression of miR-101-3p and knock down of TRIM44 attenuated proliferation, migration and invasion of glioblastoma cell lines in vitro. TRIM44 was shown to promote EMT in GBM progress and reverse inhibitory function of miR-101-3p. MiR-101-3p was found to suppress the expression of TRIM44 via directly targeting its 3'UTR. CONCLUSIONS: Our findings suggested miR-101-3p regulated proliferation and migration of glioblastoma cells through attenuating TRIM44 induced EMT via direct targeting 3'UTR of TRIM44, which provided preliminary study of potential therapeutic target in future GBM treatment.

Effect of cyclic uniaxial compressive stress on human dental pulp cells in vitro.

PURPOSE: Teeth are exposed to various forces during functional and parafunctional movements. These processes inevitably affect the dental pulp, and the mechanism of these influences has been the subject of many previous studies using different apparatuses and obtaining different results. In this study, we aimed to investigate the effects of compressive stress on the proliferation and differentiation of human dental pulp cells (hDPCs). MATERIALS AND METHODS: A four-point bending strain system was adopted to apply low-density cyclic uniaxial compressive stress (2000 microstrain, 0.5 Hz) to hDPCs for 1.5, 3, 6, 12, and 24 h. The cell cycle progression and mRNA expression of differentiation-related genes (BMP2, ALP, DMP1, DSPP, COL I) were then examined to investigate the proliferation and differentiation of hDPCs. RESULTS: The results showed that cyclic compressive stress changed the morphology of hDPCs after 12 and 24 h of mechanical loading; cell cycle progression was promoted, especially in the 24-h group (p < 0.05). The expression of BMP2 was significantly upregulated after 3 and 6 h of mechanical loading but declined in the 12- and 24-h groups, whereas the expression levels of DMP1 and DSPP were significantly upregulated in the 12- and 24-h loading groups (p < 0.05). CONCLUSIONS: Dental pulp cells were sensitive to compressive stress, especially after 12 and 24 h of applied force. Proliferation and odontogenic differentiation were significantly promoted in this in vitro model.

Effects of combined exogenous dextranase and sodium fluoride on Streptococcus mutans 25175 monospecies biofilms.

PURPOSE: To investigate the effects of exogenous dextranase and sodium fluoride on a S. mutans monospecies biofilm. METHODS: S. mutans 25175 was grown in tryptone soya broth medium, and biofilm was formed on glass slides with 1.0% sucrose. Exogenous dextranase and sodium fluoride were added alone or together. The biofilm morphology was analyzed by confocal laser scanning microscopy. The effects of the drug on the adhesion and exopolysaccharide production by the biofilms were evaluated by scintillation counting and the anthrone method, respectively. RESULTS: In this study, we found that the structure of initial biofilm and mature biofilm were partly altered by dextranase and high concentrations of sodium fluoride separately. However, dextranase combined with a low concentration of sodium fluoride could clearly destroy the typical tree-like structure of the biofilm, and led to less bacterial adhesion than when the dextranase or fluoride were used alone (P < 0.05). The amounts of soluble and insoluble exopolysaccharide were significantly reduced by combining dextranase with a low concentration of sodium fluoride, much more than when they were used alone (P < 0.05). These data indicate that dextranase and a low concentration of sodium fluoride may have synergistic effects against S. mutans biofilm and suggest the application of a low concentration of sodium fluoride in anticaries treatment.

The effects of light on bleaching and tooth sensitivity during in-office vital bleaching: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the influence of light on bleaching efficacy and tooth sensitivity during in-office vital bleaching. DATA SOURCES: We performed a literature search using Medline, EMBASE and Cochrane Central up to September 2011. STUDY SELECTION: All randomised controlled trials (RCTs) or quasi-RCTs comparing the light-activated bleaching system with non-activation bleaching system were included. Reports without clinical data concerning bleaching efficacy or tooth sensitivity were excluded. RESULTS: Eleven studies were included in the meta-analysis. A light-activated system produced better immediate bleaching effects than a non-light system when lower concentrations of hydrogen peroxide (15-20% HP) were used (mean difference [MD], -1.78; 95% confidence interval [CI]: [-2.30, -1.26]; P<0.00001). When high concentrations of HP (25-35%) were employed, there was no difference in the immediate bleaching effect (MD, -0.39; 95% CI: [-1.15, 0.37]; P=0.32) or short-term bleaching effect (MD, 0.25; 95% CI: [-0.47, 0.96]; P=0.50) between the light-activated system and the non-light system. However, the light-activated system produced a higher percentage of tooth sensitivity (odds ratio [OR], 3.53; 95% CI: [1.37, 9.10]; P=0.009) than the non-light system during in-office bleaching. CONCLUSIONS: Light increases the risk of tooth sensitivity during in-office bleaching, and light may not improve the bleaching effect when high concentrations of HP (25-35%) are employed. Therefore, dentists should use the light-activated system with great caution or avoid its use altogether. Further rigorous studies are, however, needed to explore the advantages of this light-activated system when lower concentrations of HP (15-20%) are used.

ß-Catenin and Rho GTPases as downstream targets of TGF-ß1 during pulp repair.

TGF-ß1 (transforming growth factor-ß1) plays a central role in regulating proliferation, migration and differentiation of dental pulp cells during the repair process after tooth injury. Our previous study showed that p38 mitogen-activated protein kinase may act downstream of TGF-ß1 signalling to effect the differentiation of dental pulp cells. However, the molecular mechanisms that trigger and regulate the process remain to be elucidated. TGF-ß1 interacts with signalling pathways such as Wnt/ß-catenin and Rho to induce diverse biological effects. TGF-ß1 activates ß-catenin signalling, increases ß-catenin nuclear translocation and interacts with LEF/TCF to regulate gene expression. Morphologic changes in response to TGF-ß1 are associated with activation of Rho GTPases, but are abrogated by inhibitors of Rho-associated kinase, a major downstream target of Rho. These results suggest that the Wnt/ß-catenin and Rho pathways may mediate the downstream events of TGF-ß1 signalling.

The presence of open dentinal tubules affects the biological properties of dental pulp cells ex vivo.

To investigate the effects of open dentinal tubules on the morphological and functional characteristics of dental pulp cells. Morphological changes in human dental pulp cells that were seeded onto dentin discs with open dentinal tubules were investigated on days 1, 2, 4, and 10 of culture using scanning electron microscopy and fluorescence microscopy. Samples collected on days 1, 3, 6, 8, and 10 of culture were evaluated for cell proliferation rate and alkaline phosphatase activity. Cultured human dental pulp cells developed a columnar or polygonal morphology and monopolar cytoplasmic processes that extended into the dentinal tubules. The cells formed a multilayer and secreted an extracellular matrix onto the cell surface. Scanning electron microscopy and fluorescence microscopy revealed polarized organization of odontoblasts. Cells seeded onto dentin discs proliferated minimally but showed high levels of ALP activity. Dental pulp cells seeded onto treated dentin discs develop an odontoblastlike phenotype, which may be a potential alternative for use in experimental research on dentinogenesis.

Roles of lysophosphatidic acid and the Rho-associated kinase pathway in the migration of dental pulp cells.

During the dental pulp repair process, dental pulp cells (DPCs) migrate to the site of injury and differentiate into odontoblasts or odontoblast-like cells. Although migration of DPCs is an important reparative process, the underlying mechanism remains unknown. The objective of this study was to determine the roles of lysophosphatidic acid (LPA) and the Rho-associated kinase (ROCK) pathway in the migration and morphology of dental pulp cells and alpha smooth muscle actin expression in vitro. We demonstrated that both LPA and ROCK inhibition enhanced cell motility and that their combined effects significantly increased migration rate. LPA induced fine cytoskeleton assembly and increased the level of alpha smooth muscle actin (alpha-SMA). ROCK inhibition by Y-27632 and ROCK-(1+2) small interfering RNA (siRNA) resulted in less actin cytoskeleton formation, a lower alpha-SMA level, a star-like cellular morphology and membrane ruffling. LPA and ROCK inhibition induced activation of another Rho GTPase, Rac, which may explain how LPA and ROCK inhibition increases cellmigration and lamellipodium formation.

Interleukin-6 polymorphisms modify the risk of periodontitis: a systematic review and meta-analysis.

OBJECTIVE: To clarify the association of IL-6 polymorphisms and periodontitis, a meta-analysis of case-control studies and a systemic review were conducted. MATERIAL AND METHODS: We performed a literature search using PubMed and Medline database to May 2009, with no restrictions. We also reviewed references from all retrieved articles. Six case-control studies involving 1 093 periodontitis cases and 574 controls were selected for meta-analysis to assess the purported associations between IL-6 polymorphisms and the risk of periodontitis. IL-6 -174 G/C and -572 C/G polymorphisms were included in the present meta-analysis, and the association between IL-6 -6331 T/C polymorphism and the risk of periodontitis was adequately reviewed as well. RESULTS AND CONCLUSION: The present meta-analysis indicates that the IL-6 -174 G allele could not modify the risk of chronic periodontitis, but increased the risk of aggressive periodontitis. And -572 C/G polymorphism is associated with the pathogenesis of periodontitis, including chronic periodontitis or aggressive periodontitis.

Dental erosion and severe tooth decay related to soft drinks: a case report and literature review.

Soft drinks have many potential health problems. The inherent acids and sugars have both acidogenic and cariogenic potential, resulting in dental caries and potential enamel erosion. In this report we present a 25-year-old man complaining with the severe worn-out of the front teeth during the past 3 years. He had a history of drinking cola for more than 7 years and had a poor oral hygiene. Severe decays were present in the incisors and the canines, while less severe lesions were noted on the premolars and the molars. The review is to show the relationship between dental erosion and caries and soft drinks. Some efforts have been taken to reduce the harmful effect of soft drinks.