RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation. RG108 increases NANOG and OCT4 through epigenetic activation.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) are important for tissue regeneration but their epigenetic regulation is not well understood. Here we investigate the ability of a non-nucleoside DNA methylation inhibitor, RG108 to induce epigenetic changes at both global and gene-specific levels in order to enhance mesenchymal cell markers, in hBMSCs. hBMSCs were treated with complete culture medium, 50 μM RG108 and DMSO for three days and subjected to viability and apoptosis assays, global and gene-specific methylation/hydroxymethylation, transcript levels' analysis of epigenetic machinery enzymes and multipotency markers, protein activities of DNMTs and TETs, immunofluorescence staining and western blot analysis for NANOG and OCT4 and flow cytometry for CD105. The RG108, when used at 50 μM, did not affect the viability, apoptosis and proliferation rates of hBMSCs or hydroxymethylation global levels while leading to 75% decrease in DNMTs activity and 42% loss of global DNA methylation levels. In addition, DNMT1 was significantly downregulated while TET1 was upregulated, potentially contributing to the substantial loss of methylation observed. Most importantly, the mesenchymal cell markers CD105, NANOG and OCT4 were upregulated being NANOG and OCT4 epigenetically modulated by RG108, at their gene promoters. We propose that RG108 could be used for epigenetic modulation, promoting epigenetic activation of NANOG and OCT4, without affecting the viability of hBMSCs. DMSO can be considered a modulator of epigenetic machinery enzymes, although with milder effect compared to RG108

Nachrichten aus der Bruder-Gemeine, 1842, no. 02

The Moravian Church's monthly journal of its worldwide activities, including in Labrador, published from 1819-94

Evidence that metyrapone in the presence of inflammation modulates cytokine mRNA expression

Objective: Metyrapone (MT) has been used clinically to decrease glucocorticoid levels in human and animal studies. However, the potential effects of MT in the presence of inflammation are poorly understood. Thus, the aim of this study was to evaluate the effects of the administration of MT on the mRNA levels of pro-inflammatory cytokines in the presence of inflammation induced by the well-established model of ligature-induced periodontitis in rats.Material and methods: Sixty animals were randomly assigned into three experimental groups of 20 rats each: G1-control; G2-periodontal disease (PD) induced by cotton ligature; G3-PD associated with 3 daily doses of MT (50 mg/kg/3 x 3 h). After 30 days, all animals were killed by decapitation. Blood samples were taken and the concentrations of corticosterone and catecholamines measured. Marginal tissues around ligated and non-ligated teeth were harvested and gene expression was assessed by quantitative polymerase chain reaction technique (qPCR). Moreover, the area of interradicular bone loss (ABL) was histometrically determined.Results: Data analysis showed that: (i) ligature placement resulted in a significant ABL, as compared to non-ligated sites of G1 group; (ii) mRNA levels of all the pro-inflammatory factors assessed (INF-gamma, TNF-alpha, IL-1 beta and IL-6) were increased in the PD group (G2) (p < 0.05) when compared to G1; (iii) there were no significant differences in corticosterone and catecholamine plasmatic levels between the three groups; (iv) MT administration, in the presence of inflammation, induces an increased ABL and significantly increased mRNA levels of all pro-inflammatory cytokines analyzed (p < 0.05).Conclusion: Within the limits of this study, it can be concluded that MT in the presence of inflammation may modulate expression of pro-inflammatory cytokines, regardless of its effect on plasma corticosterone levels. (C) 2010 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estadual Campinas, UNICAMP, Fac Odontol Piracicaba, Div Periodont,Sch Dent Piracicaba, BR-13414903 Piracicaba, SP, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilFAPESP: 04/14361-6FAPESP: 04/14363-9Web of Scienc

Coronally Positioned Flap With Or Without Enamel Matrix Protein Derivative For The Treatment Of Gingival Recessions.

To evaluate, histometrically, the healing of gingival recessions treated by coronally positioned flaps associated with enamel matrix protein derivative (EMD-Group) and to compare it to that obtained with coronally positioned flaps alone (CPF-Group). Five mongrel dogs were used. Gingival recessions were surgically created on the buccal aspect of the upper cuspids. The defects (5 x 7 mm) were exposed to plaque accumulation for 3 months. After a preparation period, the contralateral defects were randomly assigned to each group. After 3 months of healing, the dogs were sacrificed and the blocks were processed. The histometric parameters evaluated included: gingival recession, length of epithelium, new connective tissue attachment and new bone. The gingival recession was -0.1 +/- 0.2 mm for the EMD-Group and -0.8 +/- 1.3 mm for the CPF-Group (P = 0.17). The extension of the epithelium was 1.2 +/- 1.0 mm for the EMD-Group and 1.3 +/- 0.7 mm for the CPF-Group (P = 0.89). The new connective tissue attachment was 4.8 +/- 0.7 in the EMD-Group and 4.0 +/- 1.4 in the CPF-Group (P = 0.22). The new bone was 0.1 +/- 1.8 mm and -0.5 +/- 1.4 mm in the EMD-Group and CPF-Group, respectively (P = 0.50). Histologically, the defect coverage observed was 98.2% for the EMD-Group and 85.8% for the CPF-Group.16287-9

Neuropilin controls endothelial differentiation by mesenchymal stem cells from the periodontal ligament

Background: Periodontal ligament (PDL) has been reported to be a source of mesenchymal stem cells (MSCs). New vascular networks from undifferentiated cells are essential for repair/regeneration of specialized tissues, including PDL. The current study aims to determine potential of CD105(+)-enriched cell subsets of periodontal ligament cells (PDLSCs) to differentiate into endothelial cell (EC)-like cells and to give insights into the mechanism involved. Methods: CD105(+)-enriched PDLSCs were induced to EC differentiation by endothelial growth medium 2 (EGM-2) for 3, 7, 14, and 21 days, with mRNA/protein levels and functional activity assessed by: 1) real-time polymerase chain reaction; 2) Western blotting; 3) fluorescence-activated cell sorting; 4) immunohistochemistry; 5) immunofluorescence; 6) matrigel; and 7) small interfering RNA assays. Results: Data analyses demonstrated that EGM-2 treated PDLSCs presented increased expression of EC markers, including: 1) CD105; 2) kinase domain-containing receptor; and 3) Ulex europaeus agglutinin 1, and were able to form cord/tube-like structures. Gene and protein expression analysis showed that neuropilin 2 (NRP2), a key factor for vascular development, was significantly downregulated during EC differentiation. NRP2 was constitutively expressed in mouse PDL tissues by immunohistochemistry analysis, and NRP2 knockdown in CD105(+)-enriched PDLSCs resulted in increased cord/tube-like structures in a matrigel assay. Conclusion: These findings demonstrated the potential of CD105(+)-enriched PDLSCs to support angiogenesis, and NRP2 as a pivotal factor regulating this process.877E138E147COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES02426/09-

Enamel Matrix Protein Derivative And/or Synthetic Bone Substitute For The Treatment Of Mandibular Class Ii Buccal Furcation Defects. A 12-month Randomized Clinical Trial.

This study aims to clinically evaluate the treatment of mandibular class II furcation defects with enamel matrix derivative (EMD) and/or a bone substitute graft made of β-tricalcium phosphate/hydroxyapatite (βTCP/HA). Forty-one patients, presenting a mandibular class II buccal furcation defect, probing pocket depth (PPD) ≥4 mm and bleeding on probing, were included. They were randomly assigned to the groups: 1-EMD (n = 13); 2-βTCP/HA (n = 14); 3-EMD + βTCP/HA (n = 14). Plaque index (PI), gingival index (GI), relative gingival margin position (RGMP), relative vertical and horizontal attachment level (RVCAL and RHCAL), and PPD were evaluated at baseline and 6 and 12 months. The mean horizontal clinical attachment level gain was considered the primary outcome variable. No significant intragroup differences were observed for RGMP, but significant changes were observed for RVCAL, RHCAL, and PPD for all groups (p < 0.05). After 12 months, the mean horizontal clinical attachment level gain was 2.77 ± 0.93 mm for EMD, 2.64 ± 0.93 mm for βTCP/HA, and 2.93 ± 0.83 mm for EMD + βTCP/HA, with no significant differences among the groups. At the end of the study, 85.3 % of the sites were partially closed; however, no complete closure was observed. EMD + βTCP/HA does not provide a significant advantage when compared to the isolated approaches. All three tested treatments promote significant improvements and partial closure of class II buccal furcation defects. Based on its potential to induce periodontal regeneration, EMD may be considered an attractive option for this type of defect, but complete closure remains an unrealistic goal. The partial closure of buccal furcation defects can be achieved after the three tested approaches. However, the combined treatment does not provide a significant benefit when compared to the isolated approaches

Coronally Positioned Flap With Or Without Acellular Dermal Matrix Graft In Gingival Recessions: A Histometric Study.

To evaluate, histometrically, the healing of gingival recession treated by coronally positioned flaps (CPF) with or without acellular dermal matrix (ADM) as a subepithelial graft. Gingival recessions were created on the upper cuspids of six dogs and were randomly assigned to: CPF+ADM (ADM group) or CPF alone (CPF group). After 4 months, the dogs were sacrificed, and the histometric measurements were performed. The epithelial length was 2.28 + 0.92 mm and 2.10 + 0.46 mm for the ADM and CPF groups, respectively (P=0.74). The connective tissue adaptation was 0.05 + 0.08 mm for the ADM group and 0.06 + 0.08 mm for the CPF group (P=0.36). The new cementum was 2.35 + 1.55 mm and 2.90 + 0.96 mm in the ADM and CPF groups, respectively (P=0.53). The new bone was 0.60 + 1.36 mm for the ADM group and 0.35 + 0.82 mm for the CPF group (P=0.53). The gingival recession was -0.88 + 1.33 mm in the ADM group and -0.21 + 0.22 mm in the CPF group (P=0.21). The gingival thickness was 1.63 + 0.28 mm in the ADM group and 1.16 + 0.20 mm in the CPF group (P=0.002).19128-3

The Combination of Amoxicillin and Metronidazole Improves Clinical and Microbiologic Results of One-Stage, Full-Mouth, Ultrasonic Debridement in Aggressive Periodontitis Treatment

Background: The aim of the present study is to assess clinical, microbiologic, and immunologic benefits of amoxicillin/metronidazole (AM) when performing full-mouth ultrasonic debridement (FMUD) in generalized aggressive periodontitis (GAgP) treatment.Methods: Twenty-four GAgP patients were divided into two groups: the FMUD group (n = 12), which received FMUD plus placebo, and the FMUD+AM group (n = 12), which received FMUD and 375 mg amoxicillin plus 250 mg metronidazole for 7 days. The following clinical outcomes were tested: plague and bleeding on probing indices, pocket probing depth (PD), relative gingival margin position (GMP), and relative clinical attachment level (CAL). Total amount of Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythia (Tf), and gingival crevicular fluid (GCF) concentration of interleukin (IL)-10 and IL-1 beta were also determined. All clinical, microbiologic, and immunologic parameters were assessed at baseline and at 3 and 6 months post-therapy. The ANOVA/Tukey test was used for statistical analysis (alpha = 5%).Results: Amoxicillin/metronidazole used as an adjunct to the FMUD protocol added clinical and microbiologic benefits to GAgP treatment (P0.05).Conclusion: It may be concluded that amoxicillin/metronidazole improves clinical and microbiologic results of FMUD in GAgP treatment. J Periodontol 2012;83:988-998.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of aggressive periodontitis: a split-mouth randomized controlled trial

The management of aggressive periodontitis (AgP) represents a challenge for clinicians because there are no standardized protocols for an efficient control of the disease. This randomized controlled clinical trial evaluated the effects of repeated applications of antimicrobial photodynamic therapy (aPDT) adjunctive to scaling and root planing (SRP) in patients with AgP. Using a split-mouth design, 20 patients with generalized AgP were treated with aPDT + SRP (test group) or SRP only (control group). aPDT was applied at four periods. All patients were monitored for 90 days. Clinical, microbiologic, and immunologic parameters were statistically analyzed. In deep periodontal pocket analysis (probing depth [PD] >= 7 mm at baseline), the test group presented a decrease in PD and a clinical attachment gain significantly higher than the control group at 90 days (P <0.05). The test group also demonstrated significantly less periodontal pathogens of red and orange complexes and a lower interleukin-1 beta/interleukin-10 ratio than the control group (P <0.05). The application of four sessions of aPDT, adjunctive to SRP, promotes additional clinical, microbiologic, and immunologic benefits in the treatment of deep periodontal pockets in single-rooted teeth in patients with AgP86337638

GTR in class III furcation defects with resorbable polylactic acid membranes. A histomorphometric study in dogs

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