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The ubiquitin-proteasome system is regulated by deubiquitinating enzymes (DUBs), which include the complex Ubiquitin-specific protease 1 (USP1) and WD40 repeat-containing protein 48 (WDR48). In normal conditions, these proteins contribute to genome integrity by regulating the DNA repair pathways. However, studies have associated abnormalities in this complex with the pathogenesis of cancer. Simultaneously, Tumor Suppressor Protein p53 is also regulated by ubiquitin-dependent degradation and its overexpression suggests that several DUBs are interacting and deubiquitinating this protein. Objective: To evaluate the immunoexpression of p53, USP1, and WDR48 in Oral Squamous Cell Carcinoma (OSCC). Material and methods: Thirty cases of OSCC and 40 non-neoplastic oral epithelium (NNOE, control group) were selected for immunohistochemical investigation. The histopathological classification was performed using H&E-stained sections. Values were statistically analyzed using the non-parametric test Kruskal Wallis. Results: Higher positivity of the markers was found in OSCC (p53:65%; USP1:96.4%; WDR48: 68.9%) than in NNOE (p53:35.1%; USP1:85%; WDR48: 65.2%). Poorly-differentiated cases of OSCC exhibited higher nuclear immunostaining of all proteins when compared with well-differentiated samples. Conclusion: This is a pioneer study and suggests that p53 and deubiquitinating enzymes (USP1 and WDR48) can affect the biological behavior of OSCC as they are related to the tumor development and histological malignancy grading.

Background Salivary gland tumors are a rare and morphologically diverse group of lesions and their frequency is still unknown in several parts of the world. The knowledge of its population characteristics contributes to a better understanding of its etiopathogenesis. Objectives: This study investigated the frequency of salivary gland tumors in a region of southern Brazil and compared these data in a literature review. Material and Methods A retrospective study was conducted of salivary gland tumors diagnosed at two pathology centers from 1995 to 2016. Patient age and gender, tumor site and frequency, histopathological diagnosis, and symptomatology were evaluated. Chi-squared tests were used to assess the associations between variables. To compare our data, we also conducted a literature review of publications in the PubMed and LILACS databases of retrospective studies of salivary gland tumors. Results A total of 124 salivary gland tumor cases was identified, 81 (65.3%) of which were classified as benign and 43 (34.6%) as malignant. Most tumors occurred in the parotid gland (57.2%). Pleomorphic adenoma was the most common tumor (59.6%), followed by adenocarcinoma not otherwise specified (8.8%). The tumors occurred more often in women (54.8%) than in men (45.2%). Malignant tumors were associated with pain in 31.4% of cases (p

The aim of this study was to synthesize, characterize, and evaluate degradation and biocompatibility of poly(lactic-co-glycolic acid) + hydroxyapatite/β-tricalcium phosphate (PLGA+HA/βTCP) scaffolds incorporating simvastatin (SIM) to verify if this biomaterial might be promising for bone tissue engineering. Samples were obtained by the solvent evaporation technique. Biphasic ceramic particles (70% HA, 30% βTCP) were added to PLGA in a ratio of 1:1. Samples with SIM received 1% (m/m) of this medication. Scaffolds were synthesized in a cylindric shape and sterilized by ethylene oxide. For degradation analysis, samples were immersed in phosphate-buffered saline at 37°C under constant stirring for 7, 14, 21, and 28 days. Nondegraded samples were taken as reference. Mass variation, scanning electron microscopy, porosity analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetry were performed to evaluate physico-chemical properties. Wettability and cytotoxicity tests were conducted to evaluate the biocompatibility. Microscopic images revealed the presence of macro-, meso-, and micropores in the polymer structure with HA/βTCP particles homogeneously dispersed. Chemical and thermal analyses presented similar results for both PLGA+HA/βTCP and PLGA+HA/βTCP+SIM. The incorporation of simvastatin improved the hydrophilicity of scaffolds. Additionally, PLGA+HA/βTCP and PLGA+HA/βTCP+SIM scaffolds were biocompatible for osteoblasts and mesenchymal stem cells. In summary, PLGA+HA/βTCP scaffolds incorporating simvastatin presented adequate structural, chemical, thermal, and biological properties for bone tissue engineering.

To determine the efficacy of a single session protocol (SSP) in the reduction of septic content of primary teeth root canals and identify the persistence of bacterial species associated with unsuccessful treatment. Primary teeth root canals (16) with pulp necrosis and peri-radicular lesions were treated. Samples were collected at baseline (T1), and after chemo-mechanical preparation, before filling (T2). Identification of the microorganisms was determined using checkerboard DNA–DNA hybridisation. Statistical analysis: Wilcoxon test was applied for comparison of mean number of species, proportion and mean count of each species between the evaluation times. Significant reductions were found in the mean number of bacteria species between T1 and T2 (p 0.05). There was a reduction (6.0–4.6) of the mean number of species associated with failure, without statistical significance. The SSP was capable of significantly reducing the septic content, even though, many of the bacteria associated with failure persisted at the time of root canal filling.

Objective: To investigate the perceptions of dental students on the learning process regarding the dentist-pediatric patient relationship. Material and Methods: A qualitative study with an exploratory approach was conducted involving semi-structured interviews with sixteen dental undergraduate students randomly selected from the thirty-two students in the last semester of the dentistry course. The transcribed interviews were submitted to content analysis. Results: The sample was composed of nine female (56.3%) and seven male (43.7%) students (median age: 23 years). The factors perceived as most influential with regard to learning the dentist-pediatric patient relationship were observations of professors, other dentists or colleagues and the regular practice of dental procedures. While half of the participants considered lectures on the subject satisfactory, the other half reported a need for more instruction on how to deal with specific clinical situations. Most of the participants would like to have learned more about the dentist-pediatric patient relationship. Conclusion: The majority of students recognized that the teaching and learning process regarding the dentist-pediatric patient relationship is not easy. They reported having little counseling on the how to develop this relationship. The students suggested that the dentist-patient relationship should be addressed more during the course through the inclusion of lectures or classes on this issue as well as the demonstration of specific clinical situations.

Objective: Failures in endodontic treatment may occur by several reasons. Endodontic retreatment is an interesting alternative to manage this clinical problem. However, it is not possible to completely remove the root canal filling by any current retreatment technique. The aim of this study was to evaluate the presence of residual root canal filling materials after endodontic re-instrumentation. Material and Methods: Sixty extracted anterior human teeth were prepared by step-back technique with Flexofiles, K-files and Gates-Glidden (GG) burs. Between the use of each file or bur, root canals were irrigated with sodium hypochlorite (NaOCl). Smear layer was removed by irrigation with ethylenediaminetetraacetic acid and NaOCl. After drying with paper points the root canals were randomly divided into 5 groups (n = 12), according to filling material: Resilon cones/Real Seal sealer or gutta-percha cones and Endofill, Sealapex, AH Plus or MTA Fillapex sealers. After one week, root canal fillings were removed using Eucaliptol and K-files. Root canals were re-instrumented with K-files and GG burs sized larger than the first ones. The removal of root canal filling material was analyzed by radiography and scanning electron microscopy (SEM). Statistical analysis was performed using Binary Logistic Regression test (P < 0.05). Results: Radiographic and SEM analysis showed that material from the MTA Fillapex group was better removed than that from Endofill, Sealapex, AH Plus and Real Seal groups. Conclusion: After re-instrumentation, MTA Fillapex group showed less remnants into the root canals than Endofill, Sealapex, AH Plus and Real Seal groups. Residual material was most often found in the apical third.Keywords Dental radiography; Endodontic retreatment; Root canal filling materials; Scanning electron microscopy.

Stem cells (SCs) enabled great advances in differenthealth fields, including Dentistry. Objective: To investigate theknowledge of last year Dentistry undergraduate students regardingSCs and its applications. Material and methods: A questionnairewith open-ended questions was applied to the students, followedby qualitative-quantitative analysis involving the clustering of theanswers. Results: The majority of students (70%) defined SCsadequately, only half of the interviewees (48.8%) were unable toclassify SCs and just 26.2% classified it correctly. On the questionabout SCs from dental tissues, 77.5% reported it was possibleand 70.9% knew which tissues could be used. The main sourceof knowledge was the media (36.4%), followed by the University(26.6%); 88.5% stated that the topic was only addressed in the firstyear of the course. Consequently, only 7.5% reported being capableof answering questions about it. Conclusion: The students are notreceiving enough information about the topic.

The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic-co-glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico-chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate-buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two-dimensional and three-dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X-ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal-shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152-2164, 2019.

Malignant neoplasms may be composed of several cell groups, including cancer stem cells (CSC). These cells have been related with the capacity of metastasis, relapse and resistance to multiple drugs during chemotherapy. This study aims to identify CSC biomarkers and their expression pattern in human head and neck carcinomas. This study was conducted following the PRISMA checklist. The search for articles was carried out in five databases (PubMed, Scopus, Web of Science, Lilacs and Scielo). The articles found were selected in two phases: 1) reading the titles and / or abstract and 2) reading the full text. At the end, the selected articles were evaluated by QUADAS-2. Most studies evaluated oral neoplastic tissues and, as a control, samples of normal local mucosa. All studies performed immunohistochemistry as a method of immunolocalization and some also applied immunofluorescence. The most commonly used biomarker was CD44. However, other such as Sox2, Oct4, Nestin, Nanog, BMI1, ALDH1, CD133 and CD166 were also found. Several biomarkers were (ALDH1, Sox2, Oct4, ABCB5, AGR2 and TAZ) correlated with clinical characteristics of the tumor, such as staging, tumor size and lymph node metastasis. These data reinforce the CSC theory and favor the use of these biomarkers as possible determinants of prognosis.

Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in melanoma, central nervous system tumours, osteosarcoma, neuroblastoma, myeloproliferative neoplasms, breast, lung, prostate, ovarian, colorectal, pancreatic, and hepatocellular carcinoma have been showed. Moreover, advantages as clinical use approved by the Food and Drug Administration (FDA), high clinical safety, low side effects, and reasonable price have stimulated the treatment with Pimozide instead of other agents. The action mechanism remains unclear, but three vias associated to cancer stem cell (CSC) hypothesis show that Pimozide: (a) blocks CSC features, as epithelial-to-mesenchymal transition (EMT), through inhibition of Wnt-β/catenin signalling; (b) acts as an inhibitor of signal transducer and activator of transcription (STAT-3 and 5), pathway which is activated and up-regulated in CSCs; (c) inhibits ubiquitine specific protease (USP1) and WD repeat-containing protein 48 (WDR48), that are proteins responsible to inhibit the differentiation and to maintain the cell in an undifferentiated state. Based on this perspective, the aim of this manuscript is to review the antineoplastic role of Pimozide during tumorigenesis and its potential to revert the process of undifferentiation and proliferation of CSC through different vias.

PURPOSE This study evaluated the tissue and inflammatory responses to the use of simvastatin and poly(lactic-co-glycolic acid) + hydroxyapatite + β-tricalcium phosphate (PLGA+HA+βTCP) scaffold for bone repair. MATERIALS AND METHODS Two defects of 5 mm in diameter were made in the calvaria of rats, which were shared into the following 6 groups: naive, sham, vehicle, PLGA+HA+βTCP scaffold, simvastatin (4 mg/mL), and simvastatin with the scaffold. Tissue samples were collected at 1, 7, 15, 30, and 60 days after surgery. Inflammation was evaluated by interleukin-1 beta and tumor necrosis factor alpha quantification and by a hemogram, whereas bone repair was evaluated using densitometry and scanning electron microscopy. Data were statistically analyzed using ANOVA followed by post hoc tests (P < 0.05). RESULTS There was an increased cytokine expression in the scaffold and simvastatin groups (P < 0.001 and P < 0.05, respectively) 1 day after surgery but no alterations on the hemogram were observed. It was found on bone tissue samples that 60 days after surgery all groups presented similar densitometry values and morphology characteristics, despite the occurrence of bone formation delay in the simvastatin group (P < 0.01). CONCLUSION The use of simvastatin and PLGA+HA+βTCP scaffold, associated or not, did not lead to improvement in bone repair.

Regenerative endodontic procedure (REP) has been proposed as a new approach to treat immature permanent teeth. However, materials used in REP for root canal disinfection or cervical sealing may induce tooth discoloration. Objectives To assess tooth crown’s color after intracanal treatment with triple antibiotic paste (TAP) or calcium hydroxide (CH); cervical sealing with glass ionomer cement (GIC) or mineral trioxide aggregate (MTA); and bleaching with carbamide peroxide. Material and Methods After pulp removal and color spectrophotometer measurement, 50 bovine incisors were divided into 4 experimental groups and one control (untreated). Experiments were performed in phases (Ph). Ph1: TAP (ciprofloxacin, metronidazole, minocycline), TAPM (ciprofloxacin, metronidazole, amoxicillin), DAP (ciprofloxacin, metronidazole), or CH treatment groups. After 1 and 3 days (d); 1, 2, 3 weeks (w); and 1, 2, 3 and 4 months (m), color was measured and medications were removed. Ph2: GIC or MTA cervical sealing, each using half of the specimens from each group. Color was assessed after 1d, 3d; 1w, 2w, 3w; 1m and 2m. Ph3: Two bleaching sessions, each followed by color measurement. Data were analyzed with ANOVA and post-hoc Holm-Sidak method. Results Ph1: Specimens of TAP group presented higher color alteration (ΔE) mean than those of TAPM group. No significant difference was found among TAP or TAPM and CH, DAP or Control groups. Ph2: cervical sealing materials showed no influence on color alteration. Ph3: Different ΔE means (from different groups), prior to bleaching, became equivalent after one bleaching session. Conclusions TAP induces higher color alteration than TAPM; color alteration increases over time; cervical sealing material has no influence on color alteration; and, dental bleaching was able to recover, at least partially, the tooth crown’s color.

Objective: To estimate the prevalence of unintentional injuries among children attending public preschools of Florianopolis (Santa Catarina, Brazil) and describe their epidemiological characteristics. Materials and Methods: This is a descriptive cross-sectional study conducted with 398 children in 2009 and data were collected through a questionnaire, filled by parents. Statistical analysis was performed, considering a confidence interval of 95%. Results: Among the 398 children included, 275 (69.1% - 95%: 66.8 to 71.4%) suffered unintentional injuries, making a total of 573 cases. The sample comprised 55.5% male children between 13 and 36 months (61.6% - 95% CI: 59.3 to 63.9%) that were affected. Child home was the place where 352 (61.4% - 95% CI: 59.0 to 63.8%) injuries occurred, 372 (64.9% - IC95%: from 59.1 to 73.7%), which were caused by falls, and 342 (59.7% - 95%:57.3 to 62.1%) were considered mild. In 223 (38.9% - 95%: 36.5% -41.3%) cases, the mother accompanied the child at the time of injury. Conclusion: The prevalence of unintentional injuries was high. In the context of prevention, combined actions among health professionals, government and civil society should be proposed based on local research on the topic. In the era of family health care performed by multidisciplinary teams, it is critical that these injuries receive adequate importance by health professionals and attention in public health policies.

Ramos-Jorge ML, Vieira-Andrade RG, Martins-Junior PA, Cordeiro MMR, Ramos-Jorge J, Paiva SM, Marques LS. Level of agreement between self-administered and interviewer-administered CPQ8–10 and CPQ11–14. Community Dent Oral Epidemiol 2011. © 2011 John Wiley & Sons A/S Abstract – Objectives: The aim of the present study was to assess the psychometric properties and level of agreement between the self-administered and interviewer-administered Child Perceptions Questionnaire (CPQ) for children between 8 and 10 years of age (CPQ8–10) and between 11 and 14 (CPQ11–14) years of age. Methods: A randomized cross-over study was carried out, involving 180 children (Group 1 – 90 children between 8 and 10; Group 2 – 90 children between 11 and 14 years of age) in the state of Minas Gerais, Brazil. All children completed both administration modes of the CPQ; half of each group received interviewer-administered mode first [Subgroup A (CPQ8–10n = 45) and Subgroup C (CPQ11–14n = 45)], and the other half performed the self-administered mode first [Subgroup B (CPQ8–10n = 45) and Subgroup D (CPQ11–14n = 45)]. Test–retest reliability of each mode of administration was tested on 60 children (30 for CPQ8–10; 30 for CPQ11–14), who were not included in the other analyses. The level of agreement between scores on the self-administered and interviewer-administered versions of the CPQ8–10 and CPQ11–14 was established using the intraclass correlation coefficient (ICC). The order of presentation of both instruments was tested considering the four subgroups (A, B, C and D). The calculation of effect size proposed by Cohen (1992) was used to test the clinical significance of the findings. Results: Both the self-administered and interviewer-administered versions of CPQ8–10 and CPQ11–14 demonstrated acceptable psychometric properties. Agreement between the administration modes for the CPQ8–10 and CPQ11–14 was 0.90 and 0.88 (ICC), respectively. With the exception of the functional limitation subscale, the scores of the subscales and overall score on the CPQ8–10 were significantly higher in the group of children who responded to the interviewer-administered measure first. With the CPQ11–14, statistically significant differences were found only for the emotional well-being subscale. Conclusions: Both administration modes of the CPQ8–10 and CPQ11–14 demonstrated satisfactory psychometric properties and a high level of agreement. Although statistically significant differences were observed for oral symptoms, emotional well-being and social well-being, with the first administration of the interviewer-administered version, the effect of the order of administration had small to medium effects on the CPQ scores.

Background Physiological root resorption differentiates primary from permanent teeth. The understanding of what protects and regulates root resorption might help to develop therapies to its control. Aim To verify the presence and distribution of ECRM and the expression of CK14, OPG, TRAP and COX-2 in the periodontal ligament (PDL) of human primary and permanent teeth. Design. Eight primary teeth undergoing physiological or pathological root resorption and 4 permanent teeth were immunohistochemically processed for CK14, TRAP, COX-2 and OPG expression. Results PDL from primary and permanent teeth showed similar morphological features; however, fewer ECRM clusters and higher immunoreactivity to CK14 were found in primary PDL. In permanent teeth, ECRM were distributed along the entire PDL tissue. Howship's lacunae were found only in primary teeth, associated with the presence of TRAP-positive cells and increase in COX-2 expression. OPG expression in primary PDL was detected in nonresorptive cervical areas and in lacunae showing reparative tissue. It was observed higher expression of OPG in all permanent teeth when compared to primary specimens. Conclusions It may be concluded that PDL from primary teeth shows less ECRM clusters and lower expression of OPG. These features may be associated with lower protection against root resorption in primary teeth.

Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer's disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. This characteristic facilitates ex vivo expansion and enhances the translational potential of these cells. Notably, the dental pulp is arguably the most accessible source of postnatal stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

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Objective: To evaluate the parent's esthetic acceptance of the use of the cariostatic agent diamine silver fluoride in children aged 0 to 3 years treated at ...

Aim The aim of this paper is to present a review and discussion of the current status of stem cell research with regard to tooth generation. Background Stem cells have been isolated from the pulp tissue of both deciduous and permanent teeth as well as from the periodontal ligament. Dental pulp stem cells demonstrate the capacity to form a dentin pulp-like complex in immunocompromised mice. A tooth-like structure was successfully formed, using a heterogeneous mixture of dental enamel epithelium, pulp mesenchymal cells, and scaffolds. Conclusion The scientific community understands the need for more investigations to completely understand the conditions that would best favor the creation of a tooth substitute. Recent gains in the understanding of the molecular regulation of tooth morphogenesis, stem cell biology, and biotechnology offers the opportunity to realize this goal. Clinical Significance These findings, combined with the recent progress in stem cell research and tissue engineering, might allow the development of alternatives for current materials and therapies used to treat tooth tissue loss (e.g., enamel, dentin, pulp), reconstruct dentoalveolar and craniofacial bone defects, and eventually replace an entire tooth. Citation Nedel F, André DA, Oliveira IO, Cordeiro MM, Casagrande L, Tarquinio SBC, Nor JE, Demarco FF. Stem Cells: Therapeutic Potential in Dentistry. J Contemp Dent Pract 2009 July; (10)4:090-096.

Stem cells from human exfoliated deciduous teeth (SHED) have been isolated and characterized as multipotent cells. However, it is not known whether SHED can generate a dental pulp-like tissue in vivo. The purpose of this study was to evaluate morphologic characteristics of the tissue formed when SHED seeded in biodegradable scaffolds prepared within human tooth slices are transplanted into immunodeficient mice. We observed that the resulting tissue presented architecture and cellularity that closely resemble those of a physiologic dental pulp. Ultrastructural analysis with transmission electron microscopy and immunohistochemistry for dentin sialoprotein suggested that SHED differentiated into odontoblast-like cells in vivo. Notably, SHED also differentiated into endothelial-like cells, as demonstrated by B-galactosidase staining of cells lining the walls of blood-containing vessels in tissues engineered with SHED stably transduced with LacZ. This work suggests that exfoliated deciduous teeth constitute a viable source of stem cells for dental pulp tissue engineering.

Field cancerization involves the lateral spread of premalignant or malignant disease and contributes to the recurrence of head and neck tumors. The overall hypothesis underlying this work is that endothelial cells actively participate in tumor cell invasion by secreting chemokines and creating a chemotactic gradient for tumor cells. Here we demonstrate that conditioned medium from head and neck tumor cells enhance Bcl-2 expression in neovascular endothelial cells. Oral squamous cell carcinoma-3 (OSCC3) and Kaposi's sarcoma (SLK) show enhanced invasiveness when cocultured with pools of human dermal microvascular endothelial cells stably expressing Bcl-2 (HDMEC-Bcl-2), compared to cocultures with empty vector controls (HDMEC-LXSN). Xenografted OSCC3 tumors vascularized with HDMEC-Bcl-2 presented higher local invasion than OSCC3 tumors vascularized with control HDMEC-LXSN. CXCL1 and CXCL8 were upregulated in primary endothelial cells exposed to vascular endothelial growth factor (VEGF), as well as in HDMEC-Bcl-2. Notably, blockade of CXCR2 signaling, but not CXCR1, inhibited OSCC3 and SLK invasion toward endothelial cells. These data demonstrate that CXC chemokines secreted by endothelial cells induce tumor cell invasion and suggest that the process of lateral spread of tumor cells observed in field cancerization is guided by chemotactic signals that originated from endothelial cells.

Background Ameloblastoma (AM) is a benign odontogenic neoplasm characterized by local invasiveness and recurrence. We compared the immunohistochemical expression of matrix metalloproteinases in different clinical types of AM as well as in normal odontogenic tissue. Methods Thirteen cases of solid AMs, five cases of unicystic AM and eight pericoronal follicles (PF) were selected and subjected to immunohistochemical investigation for matrix metalloproteinase-1, matrix metalloproteinase-2 and matrix metalloproteinase-9 expressions. Results The expressions of MMP-1 and MMP-2 were very high in the cytoplasm of cells throughout the entire epithelium and in fibroblasts from the adjacent connective tissue. MMP-9 expression was observed in the same location although with weaker staining. The Kruskal–Wallis test showed statistically significant differences in the epithelial expressions of MMP-1 and MMP-2; there was lower expression among solid AMs when compared with unicystic AM and PF. Compared to both types of AM, higher stromal expression of MMP-9 was found in PF. Conclusion MMP-1, MMP-2 and MMP-9 seem to be associated with AM tumour behaviour as well as physiological tissue remodelling within PF.

BACKGROUND Recently, some studies identified the Basic-Helix-Loop-Helix (bHLH) transcription factor as a significant regulator for the evolution of neoplasms. The binding between bHLH proteins and DNA is restricted by heterodimerization with Inhibitors of DNA binding (ID). IDs prevent cellular differentiation, promote growth and sustain tumor development. The wide presence of stem cells in cancers suggests that genes ID are essential to cancer stem cells (CSC) progress. The enzyme Ubiquitin-specific protease 1 (USP1) is reported to deubiquitinate and stabilize IDs. Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics. USP1 has its activity potentiated when bound to protein WD repeat-containing protein (WDR48). OBJECTIVE To identify the influence of the complex USP1/WDR48 during the CSC tumorigenesis process, and whether this complex is a possible therapeutic target. METHODS A literature search regarding the role of the complex USP1/WDR48 in inhibiting differentiation and increasing proliferation of CSC was performed, and possible selective molecule inhibitors of these deubiquitinase proteins were investigated. RESULTS There is evidence that USP1/WDR48 complex promotes stem cell conservation and regulation of DNA damage repair. For this reason, inhibitors as Pimozide, GW7647, C527, SJB2-043, ML323 have been studied to inhibit USPs in cases of treatment intervention. CONCLUSION It is consolidated in the literature the role of USP1/WDR48 during tumorigenesis. However, these studies are not enough to completely clarify the process; but certainly, the researchers are converging towards a promising direction to provide a new treatment option for cancer.

There is an association between persistent, prolonged inflammation of a primary tooth and the development of an inflammatory dentigerous cyst involving the succedaneous tooth. The purpose of this case report is to describe the management of an inflammatory dentigerous cyst of the permanent maxillary left central incisor in a nine-year-old boy caused by a long-term inflammation/infection of its predecessor. The treatment consisted of conservative decompression, which allowed for rapid healing and the eruption of the permanent tooth. The patient was followed up with periodic clinical and radiographic evaluations for several years.

The purpose of this study was to assess the microbial content of root canals of human primary teeth with pulp necrosis and periradicular lesion.Microbial samples were collected from 24 canals of children treated at a pediatric dentistry clinic. Microbiological identification was performed using checker-board DNA-DNA hybridization for 40 different bacteria. Data were analyzed per canal based on the mean count and frequency of each bacterial species.Detectable levels of bacterial species were observed for 35 probes (88%). The most frequent bacteria were Fusobacterium nucleatum sp. nucleatum, Fusobacterium periodonticum, Prevotella melaninogenica, Prevotella nigrescens, and Prevotella intermedia. Facultative species were identified in 20 root canals (83%), anaerobic species were identified in 24 root canals (100%), and aerobic species in 18 root canals (75%). Black-pigmented bacilli were found in 23 samples (96%). The number of different bacterial species detected per canal ranged from five to 33.Endodontic infection in primary teeth with pulp necrosis and periradicular lesion is multimicrobial, including aerobic, facultative, and anaerobic micro-organisms.

Literature showed that the interaction of Mineral Trioxide Aggregate (MTA) with dentin in phosphate-buffered saline (PBS) promotes a biomineralization process that leads to the formation of an interfacial layer with mineralized structures at the cement-dentin interface. Thus, we investigated the in vivo biomineralization process promoted by MTA and Ca(OH)² with dentin. Human dentin tubes filled with ProRoot MTA, Ca(OH)² or kept empty were implanted in subcutaneous tissues in the back of mice. After 12h, 1, 3, 7, 15, 30 and 60 days, the dentin tubes were processed for Scanning Electron Microscope (SEM) observations. SEM examination showed the presence of apatite-like clusters on collagen fibrils over the surface of tubes containing the biomaterials. This mineral deposition was more extensive and compact through time. At day 7, a compact layer of apatite was formed. The MTA/Ca(OH)² -dentin interface showed intratubular mineralization as early as 12h post-implantation. MTA and Ca(OH)² in an in vivo environment promoted a biomineralization process with dentin, simultaneously to the acute inflammatory response. MTA triggered an earlier and denser interfacial layer.

Multipotency is a defining characteristic of post-natal stem cells. The human dental pulp contains a small subpopulation of stem cells that exhibit multipotency, as demonstrated by their ability to differentiate into odontoblasts, neural cells, and vascular endothelial cells. These discoveries highlight the fundamental role of stem cells in the biology of the dental pulp and suggest that these cells are uniquely suited for dental pulp tissue-engineering purposes. The availability of experimental approaches specifically designed for studies of the differentiation potential of dental pulp stem cells has played an important role in these discoveries. The objective of this review is to describe the development and characterization of the Tooth Slice/Scaffold Model of Dental Pulp Tissue Engineering. In addition, we discuss the multipotency of dental pulp stem cells, focusing on the differentiation of these cells into functional odontoblasts and into vascular endothelial cells.

The aim of the present study was to evaluate the pattern of fluoride-containing dentifrice use and associated factors in Brazilian preschoolers.A structured questionnaire was answered by parents of 432 children, who were aged 2 to 6 years, from 12 public preschools in Ijuí, South Brazil. Primary outcomes were age of starting fluoride-containing dentifrice use and amount of dentifrice applied to the toothbrush. Poisson regression with robust variance was used to determine the factors associated with the main outcomes.About 75% of the participants were introduced to fluoride-containing dentifrice before the age of 2 years. The current predominant amount of dentifrice used was obtained by transversal (57.7%), followed by longitudinal deposition on the toothbrush (33.6%), corresponding to 0.3 and 0.9 g of dentifrice, respectively. Previous dental visits and maternal education greater than 4 years were associated with the introduction of fluoride-containing dentifrice before 2 years of age. The probability of using dentifrice in amounts higher than the recommendations doubled in children aged 5 and 6 years.Oral health interventions should reinforce the importance of early introduction of fluoride-containing dentifrice, especially in less-educated mothers. Furthermore, the amount of dentifrice should be reduced to maximise the caries-preventive effect while minimising dental fluorosis.

Introduction Mineral trioxide aggregate (MTA) and calcium hydroxide [Ca(OH) 2 ] are promising biomaterials for stimulating dentinogenesis and cementogenesis. This research was undertaken to understand how MTA and CA(OH) 2 participate in the inflammatory, healing, and biomineralization processes. In this part of the study, we evaluated inflammatory signaling molecules promoted by in vivo host interaction with MTA and Ca(OH) 2 . Methods Human dentin tubes were filled with ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), Ca(OH) 2 , or kept empty. After 12 hours and 1, 3, 7, 15, 30, and 60 days of implantation in subcutaneous tissues in the backs of mice, the tubes and surrounding tissues were retrieved for cytokine level quantification and histological and immunohistochemical analysis. Results MTA and Ca(OH) 2 induced proinflammatory cytokine up-regulation for up to 3 days. Moreover, interleukin-10 overexpression was noted on the tissue in contact with the biomaterials during the acute phase of the inflammatory reaction. Immunohistochemical analyses showed an increased expression of myeloperoxidase, nuclear factor kappa B (NF-κB), cyclooxygenase-2, inducible nitric oxide synthase enzymes, and vascular endothelial growth factor on day 1 for all groups. Conclusions MTA and Ca(OH) 2 increased the activation of the NF-κB signaling system on day 1 for all groups. This finding can be associated with a proinflammatory and pro–wound healing environment, which was promoted earlier by MTA.

Introduction: The biological processes underlying the ability of mineral trioxide aggregate (MTA) to promote hard-tissue deposition and wound healing remain unclear. To further study these processes, specific signaling molecules related to the inflammatory response and the biomineralization process were analyzed to assess host-MTA interactions in vivo. Methods: For cytokine level quantification and immunohistochemical analysis, human dentin tubes were filled with ProRoot MTA (Dentsply, Tulsa Dental, OK) or kept empty and were implanted in subcutaneous tissues in the backs of mice. Dentin tubes were retrieved and subsequently observed using a scanning electron microscope. Results: MTA induced a time-dependent proinflammatory cytokine up-regulation up to 3 days. Immunohistochemical analyses showed an upregulated expression of myeloperoxidase, nuclear factor-kappa B, activating protein-1, cyclooxygenase-2, inducible nitric oxide synthase, and vascular endothelial growth factor on day 1. Scanning electron microscopic examination revealed the presence of apatite-like clusters on collagen fibrils over the surface of tubes containing MTA. With the increase in time after implantation, a more extensive mineralization showing a compact layer of apatite was observed. Conclusion: MTA induced a proinflammatory and pro–wound healing environment. The biomineralization process occurred simultaneously at the biomaterial-dentin-tissue interface, with the acute inflammatory response. This promoted the integration of the biomaterial into the environment. (J Endod 2010;36:1347–1353)

Transformation of small avascular masses of tumor cells into rapidly progressive cancers is triggered by the angiogenic switch, a process that involves vascular endothelial growth factor (VEGF) signaling. We have shown that VEGF enhances the survival and angiogenic potential of endothelial cells by activating the Bcl-2-CXCL8 signaling axis. The purpose of this study was to evaluate the effect of a small-molecule inhibitor of VEGF receptors (PTK/ZK) on the initial stages of head and neck tumor angiogenesis. In vitro, PTK/ZK blocked head and neck tumor cell (OSCC3 or UM-SCC-17B)-induced Bcl-2 and CXCL8 expression in endothelial cells. Oral administration of PTK/ZK decreased xenograft head and neck tumor microvessel density, and inhibited Bcl-2 and CXCL8 expression in tumor-associated endothelial cells. Analysis of these data demonstrates that PTK/ZK blocks downstream targets of VEGF signaling in endothelial cells, and suggests that PTK/ZK may inhibit the angiogenic switch in head and neck tumors. Abbreviations: HDMEC, human dermal microvascular endothelial cells; VEGF, vascular endothelial growth factor; CXCL8, CXC ligand-8; PTK/ZK, PTK787/ZK222584.

This study aimed to evaluate, ex vivo, time and dentin removal by manual and rotary instrumentation in human primary teeth.Eighty primary teeth were divided into 2 groups, embedded in resin, and sectioned for evaluation before and after instrumentation. For manual technique, teeth were prepared using K-type files and rotary preparation was performed with Hero 642. All root canals were prepared up to size 40, and the instrumentation time was recorded. Dentin removal was calculated using digital image software. Data was statistically analyzed using chi-squared, Mann-Whitney, and t tests.Manual instrumentation removed more dentin in all groups compared with rotary instrumentation (P.05). In some specimens, root perforations were observed in areas coinciding with largest root resorption. Rotary technique showed the shortest instrumentation time (P.05).Deciduous teeth, without significant root resorption, have enough root structure for instrumentation up to size 40. Rotary technique required less time and generated less dentin removal.

Primary teeth and the permanent successors must be understood as interdependent units, where each one of them interacts with and depends on each other. Pulpal inflammation/infection of a primary tooth and the spread of this condition over the periradicular tissues can lead to alterations in the dental germ of the permanent successor and to the surrounding structures if no therapy is done, i.e. endodontics or extraction. This work will present cases of permanent teeth that showed alteration in eruption and / or in development, as a consequence of inflammation / infection of the preceding primary teeth, such as: hypoplasia, morphological alteration on the dental crown or total arrest of radicular formation. The teeth analysed in this study belong to patients who attended the Universidade Federal de Santa Catarina Children's Dentistry Clinic. The earlier these lesions are diagnosed, the less were the destructive effects and the consequences on the primary tooth / permanent germ unit.