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Staphylococcus arlettae is a rarely reported coagulase-negative staphylococcus (CoNS) isolated from infected humans and livestock. Observing phage-bacteria interaction could improve the understanding of bacterial pathogenetic mechanisms, providing foundational evidence for phage therapy or phage detection. Herein, we aimed to characterise and annotate a novel bacteriophage, vB_SarS_BM31 (BM31), specific to S. arlettae. This bacteriophage was isolated from a milk sample associated with bovine mastitis and collected in the Sichuan Province, China.The BM31 genome comprised a linear double-stranded DNA of 42,271 base pair in length with a G + C content of 34.59%. A total of 65 open reading frames (ORFs) were assembled from phage DNA, of which 29 were functionally annotated. These functional genes were divided into four modules: the structural, DNA packing and replication, lysis, and lysogeny modules. Holin (ORF25), lysin (ORF26), and integrase (ORF28) were located closely in the entire BM31 genome and were important for lyse or lysogeny cycle of BM31. The phage was identified as a temperate phage according to whole genome analysis and life cycle assay, with basic biological characteristics such as small burst size, short latency period, and narrow host range, consistent with the characteristics of the family Siphoviridae, subcluster B14 of the Staphylococcus bacteriophage.The present isolation and characterisation of BM31 contributes to the Staphylococcus bacteriophage database and provides a theoretical foundation for its potential applications. To the best of our knowledge, BM31 is the only shared and completely reported phage against S. arlettae in the entire public database.

Two of the challenges for clinical implementation of nano-therapeutic strategies are optimization of tumor targeting and clearance of the nanoagents in vivo. Herein, a cell-mediated therapy by transporting 2D Bi2Se3 nanosheets within macrophage vehicles is described. The Bi2Se3 nanosheets with excellent near-infrared photothermal performance exhibit high macrophage uptake and negligible cytotoxicity thus facilitating the fabrication of Bi2Se3-laden-macrophages. Compared with bare Bi2Se3, the Bi2Se3-laden-macrophages after intravenous injection show prolonged blood circulation and can overcome the hypoxia-associated drug delivery barrier to target the tumor efficiently and dramatically enhance the efficiency of photothermal cancer therapy. The Bi2Se3-laden-macrophages possess good biocompatibility as demonstrated by the biochemical and histological analyses and furthermore, most of the materials are excreted from the body within 25 days. Our findings reveal a desirable system for highly efficient near-infrared photothermal cancer therapy.

As a new kind of two-dimensional (2D) material, black phosphorus (BP) has attracted explosive interest in biomedical applications. It is well-recognized that the biomedical performances of nanoparticles depend not only on their properties, but also on their structures and dimensions. Here in this study, we successfully prepared three kinds of BP nanosheets with different sizes, then systematically investigated their cytocompatibility and photothermal effects to ablate cancer cells. It is evident from various assays that all the three BP samples have excellent cytocompatibility, and the BP nanosheets with a large size have better photothermal efficiency for cancer cell ablation. Our findings may provide a new insight into the fundamental cyto-performances of BP.

During the orthodontic tooth movement, cells in periodontal ligament could differentiate into osteoblasts to synthesize alveolar bone as well as affect the proliferation, migration and differentiation of mesenchymal stem cells, which also contribute to bone remodeling. However, the mechanism is still largely elusive. Here, we evaluated the expression of CREB at the tension site of mouse periodontal ligament under orthodontic mechanical strain and in the cyclic tension strain treated human periodontal ligament cells. Then, through gain and loss of function analysis, we revealed that CREB in PDLCs promotes SDF-1 and FGF2 secretion, which enhance the migration and osteoblastic differentiation of BMSCs. We further discovered that CREB transcriptionally activates FGF2 and SDF-1 expressions by binding to the promoter regions.In conclusion, this study confirms that CREB is an upregulated gene in periodontal ligament under orthodontic tension strain stimulation and plays an important role in regulating BMSCs' physiological activity in orthodontic tension strain-induced bone formation.

Orthodontic tooth movement (OTM) is associated with bone remodeling mediated by orthodontic mechanical loading. Increasing studies reported that Wnt signaling played crucial roles in mechanical stimuli induced bone remodeling. However, little is known about the involvement of Wnt signaling in orthodontic force-induced bone formation during OTM. In virtue of the OTM mice model as we previously reported, where new bone formation was determined by micro-CT and immunoreactivity of osteocalcin and osterix, we explored the activation of Wnt signaling pathway during OTM. Our results proved the nuclei translocation of β-catenin, suggesting the activation of canonical Wnt signaling pathway in the periodontal ligament cells (PDLCs) near the alveolar bone at the tension site (TS). Moreover, the immunoreactivity of Wnt5a, but not Wnt3a in PDLCs indicated the activation of canonical Wnt pathway might be mediated by Wnt5a, but not Wnt3a as in most cases. The co-location of Wnt5a and β-catenin that was evidenced by double labeling immunofluorescence staining further supported the hypothesis. In addition, the high expression of FZD4 and LRP5 in PDLCs at TS of periodontium suggested that the activation of Wnt signaling pathway was mediated by these receptors. The negligible expression of ROR2 also indicated that canonical but not non-canonical Wnt signaling pathway was activated by Wnt5a, since previous studies demonstrated that the activation of canonical/non-canonical Wnt signaling pathway was largely dependent on the receptors. In summary, we here reported that Wnt5a mediated activation of canonical Wnt signaling pathway might contribute to the orthodontic force induced bone remodeling.

Periodontal remodeling and alveolar bone resorption and formation play essential roles during orthodontic tooth movement (OTM). In the process, human periodontal ligament cells (HPDLCs) sense and respond to orthodontic forces, contributing to the alveolar bone formation. However, the underlying mechanism in this process is not fully elucidated. In the present study, cyclic stress stimulus was applied on HPDLCs to mimic the orthodontic forces during OTM. Our results demonstrated that cyclic stretch promoted the osteogenic differentiation of HPDLCs. Moreover, our data suggested that yes-associated protein (YAP), the Hippo pathway effector, which also involved in mechanical signaling transduction, was activated as we found that the nuclear translocation of YAP was significantly increased in the cyclic stress treated HPDLCs. The mRNA expression of CTGF and CYR61, the target genes of YAP, was also remarkably increased. Furthermore, knockdown of YAP suppressed the cyclic stretch induced osteogenesis in HPDLCs, while overexpression of YAP in HPDLCs enhanced osteogenesis. We also noticed that YAP activities could be suppressed by the ROCK and nonmuscle myosin II inhibitors, Y-27632 and Blebbistatin. The inhibitors also significantly inhibited the cyclic stretch induced osteogenesis in HPDLCs. Finally, in the murine OTM model, our results revealed that YAP was upregulated and nuclearly translocated in the PDLCs at the tension side. In summary, our present study demonstrated that cytoskeleton remodeling induced activation of YAP signaling pathway was crucial for the cyclic stretch-induced osteogenesis of HPDLCs, which might play important roles during OTM.

A boy, aged 12 years 3 months, sought treatment for a complete unilateral Brodie bite. His maxillary dental arch was asymmetric, and his dentition was 10 mm wider than normal values for his age. The transverse discrepancy was his chief complaint because it caused a chewing dysfunction. We used a special slow maxillary contraction appliance, which contains a screw, connectors, and retainers, to contract the maxillary transverse asymmetric dental arch. This was followed by preadjusted fixed appliances to level the teeth and adjust the occlusion. A symmetric and functional Class I occlusion was achieved.

Osteogenic differentiation and bone formation are tightly regulated by several factors, including microRNAs (miRNAs). However, miRNA expression patterns and function during mechanical loading-induced osteogenic differentiation of human periodontal ligament cells (PDLCs) remain unclear. Here, we investigated the differential expression of miRNA-195-5p in the periodontal tissues of mice under orthodontic mechanical loading and in primary human PDLCs exposed to a simulated tension strain. The miR-195-5p was observed to be down-regulated and negatively correlated with osteogenic differentiation. Overexpression of miR-195-5p significantly inhibited PDLC differentiation under cyclic tension strain (CTS), whereas the functional inhibition of miR-195-5p yielded an opposite effect. Further experiments confirmed that WNT family member 3A (WNT3A), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein receptor-1A (BMPR1A), proteins important for osteogenic activity and stability, were direct targets of miR-195-5p. Mechanical loading increased the WNT3A, FGF2, and BMPR1A protein levels, while miR-195-5p inhibited WNT3A, FGF2, and BMPR1A protein expression. WNT, FGF, and BMP signaling were involved in osteogenic differentiation of PDLCs under CTS. Further study confirmed that reintroduction of WNT3A and BMPR1A can rescue the inhibition of miR-195-5p on osteogenic differentiation of PDLCs. Our findings are the first to demonstrate that miR-195-5p is a mechanosensitive gene that plays an important role in mechanical loading-induced osteogenic differentiation and bone formation.

OBJECTIVE: To develop a model of gradually induced backward movement of the mandible under normal masticatory action and to examine morphological changes in the mandible and condylar cartilage in rats. MATERIALS AND METHODS: The newly developed Twin Inclined Plane Device (TIPD) was composed of upper and lower posterior metal crowns with a long inclined plane on both sides separately and was applied in experimental groups of 6-week-old male Wister rats. After 3, 14, 30, and 60 days, the rats were euthanatized and samples were collected. Various measurements and hematoxylin-and-eosin stains were performed. RESULTS: From day 30 on, the length of the condylar process was shorter in the TIPD groups than in the control groups (P < .05). The angulation of the condylar process axis to the mandibular plane was greater in the TIPD groups (P < .01). The thickness of the condylar cartilage in the posterior part of the posterior region was thinner in the TIPD groups (P < .05) on day 30 and even thinner (P < .01) on day 60; from day 30 on, the thickness in the anterior part of the posterior region was thicker in the TIPD groups (P < .01). CONCLUSION: TIPD can successfully induce backward movement of the mandible under normal masticatory action. TIPD can cause region-specific changes in condylar cartilage and leads to a continuous remodeling.

In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process, and loaded with the plasmid vector encoding human bone morphogenetic protein-7 (BMP-7) gene. To investigate the feasibility and efficacy of this gene-activated scaffold on dental tissue engineering, human dental pulp stem cells (DPSCs) were seeded in this scaffold for in vitro and in vivo study. In vitro results indicated that cells can be transfected successfully by loaded plasmid and secrete BMP-7 until day 24. Evaluation of DNA content, ALP activity, calcium content, SEM, and real-time PCR revealed that cells on gene-activated scaffold showed better proliferation properties and odontoblastic differentiation behaviors than cells on pure scaffolds. Then, these cell-scaffold complexes were implanted subcutaneously and retrieved after 4 weeks for histology evaluation. In vivo results that gene-activated scaffold group could still trace the existence of tranfected cells at week 4 and showed the upregulated expression of DSPP compared to pure scaffold groups. On the basis of our results, chitosan/collagen-loaded BMP-7 DNA appears to be an effective substrate candidate for gene delivery and indeed enhanced DPSCs differentiation toward an odontoblast-like phenotype in vitro and in vivo. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Tension force-induced bone formation is a complex biological process altered by various factors, for example miRNAs and gene regulatory network. However, we know little about critical gene regulators and their functional consequences on this complex process. The aim of this study was to determine the integrated relation between microRNA and mRNA expression in tension force-induced bone formation in periodontal ligament cells by a system biological approach. We identified 818 mRNAs and 32 miRNAs differentially expressed between cyclic tension force-stimulated human periodontal ligament cells and control cells by microarrays. By using miRNA/mRNA network analysis, protein-protein interactions network analysis, and hub analysis, we found that miR-195-5p, miR-424-5p, miR-1297, miR-3607-5p, miR-145-5p, miR-4328, and miR-224-5p were core microRNAs of tension force-induced bone formation. WDR33, HSPH1, ERBB3, RIF1, IKBKB, CREB1, FGF2, and PAG1 were identified as hubs of the PPI network, suggesting the biological significance in this process. The miRNA expression was further examined in human PDLC and animal samples by using quantitative real-time PCR. Thus, we proposed a model of tension force-induced bone formation which is co-regulated through integration of the miRNA and mRNA. This study illustrated the benefits of system biological approaches in the analysis of tension force-induced bone formation as a complex biological process. We used public information and our experimental data to do comprehensive analysis and revealed the coordination transcriptional control of miRNAs of tension force-induced bone formation.

The ideal denture adhesive demonstrates a neutral or slightly basic pH, satisfactory bonding load, and minimal toxicity to the oral mucosa. The purpose of this study was to evaluate the properties of a new denture adhesive (Comfort-DA, developed by the authors).Comfort-DA was evaluated in the laboratory to determine the clinical effect of pH, bonding strength, and cytotoxicity. Firstly, the material was diluted at 1.0, 2.0, 3.3, 5.0, and 10% concentrations. Then the pH values were measured at 1-, 2-, 3-, 4-, 5-, 6-, and 8-hour intervals. Secondly, bonding load test was performed between acrylic resin samples on a universal testing machine. An existing product, Fittydent, was used as a control. Finally, the cytotoxicity of several dilutions of Comfort-DA was recorded with a MTT assay on human oral fibroblast cells. Cell viability was recorded by optical density after culturing in an atmosphere of 5% CO2 and 95% air at 37 degrees C for 2, 3 and 4 days, respectively. Wells containing fresh medium alone served as controls. All the results were compared with ANOVA or Tukey intervals (alpha = 0.05).Comfort-DA remained above the critical pH for hydroxyapatite (pH 6.5) in all dilutions throughout the study. Results of bonding strength test indicated that Comfort-DA was significantly stronger than Fittydent (p0.05). The statistical analysis of results for cytotoxicity showed that Comfort-DA only displayed slight cytotoxicity.The generally favorable laboratory performance of Comfort-DA formulations indicates that this product may be an efficacious denture adhesive.

The aim of this investigation was to compare root resorption in the same individual after application of continuous intrusive and extrusive forces. In nine patients (mean age 15.3 years), the maxillary first premolars were randomly intruded or extruded with a continuous force of 100 cN for eight weeks. Eleven maxillary first premolars from six randomly selected orthodontic patients served as controls. Root resorption was determined using scanning electron microscopy. Quantitative assessment of the percentage of resorbed area of the total root surface was performed on composite micrographs. The severity of root resorption was also assessed by visual scoring of the roots. Root resorption mainly occurred at the apical part of the roots in both experimental groups. A significant difference in root resorption was found between the intruded and the control teeth (P = .006) but not between the extruded and the control teeth. However, the mesial and distal root surfaces showed resorption on 5.78 +/- 3.86% of the root surface of the intruded teeth and 1.28 +/- 1.24% of the root surface of the extruded teeth, and this difference was significant (P = .004). In addition, a large individual variation was found. From this study, it can be concluded that intrusion of teeth causes about four times more root resorption than extrusion. Because the amount of root resorption due to intrusion or extrusion in the same patient is correlated, every clinician should be aware that the extrusion of teeth might also cause root resorption in susceptible patients.

A hexagonal onplant of 7.7 mm diameter was placed on the palatal bone of the maxilla in an 1-year five-month-old female patient with a Class III malocclusion and midface deficiency. Elastic traction (400 g per side) was applied from a facemask to the onplant at 30 degrees to the occlusal plane 12 hours per day for 12 months. The maxilla was found to have displaced forward and downward by 2.9 mm. The mandible was rotated downward and backward. There was a 3 degrees increase in mandibular plane angle and an increase in the lower face height. Clinically, there was a significant improvement in midface esthetics, noted by an increase in fullness of the infraorbital region and correction of the skeletal discrepancy between the maxillary and mandibular jaw relationship. Contrary to the reports that use teeth rather than onplants as anchorage, there was no forward movement of the maxillary molars and minimal extrusion of the maxillary molars. These results suggest that onplants can be used as an extremely stable anchorage for maxillary orthopedic facemask treatment.