The flow behavior and sealing ability of calcium silicate root canal cement containing dimethyl sulfoxide: An in vitro study.

INTRODUCTION: To develop a calcium silicate (CaSi)-based cement containing dimethyl sulfoxide (DMSO) and cement deliver device for new root canal filling technique, and to assess the flow behavior, leakage, and root canal filling quality of CaSi containing DMSO. METHODS: CaSi containing DMSO (CSC-DMSO) and CaSi containing PEG (CSC-PEG) were prepared, and the flow characteristics of both cements were compared in gypsum and resin channels using a high-speed camera. Eight root canals were obturated by CSC-DMSO or CSC-PEG using a cement delivery device, and root canal filling quality was assessed in terms of filling length using periapical radiographs. The filling length was evaluated by 'apico-coronal extension,' measuring length in reference to apical constriction. Microleakage was measured for thirty human molars that were randomly filled with CSC-DMSO, CSC-PEG, or gutta-percha and AH plus. Preliminary obturation of CSC-DMSO with cement delivery device in human teeth was analyzed in terms of filling length and void, using periapical radiographs. Statistical analysis was performed with the Kruskal Wallis test for simulated root canal fillings and one-way ANOVA for leakage test. RESULTS: The flow speed of CSC-DMSO reduced in gypsum channels compared to resin channels, but CSC-PEG did not exhibit significant differences in the channels. The median absolute value of apico-coronal extension was significantly lower in CSC-DMSO compared to CSC-PEG (p < 0.05). Microleakage did not statistically differ between the groups (p > 0.05). In the preliminary obturation, the mean apico-coronal extension of CSC-DMSO was -0.297 ± 0.724 mm, while CSC-PEG was not feasible due to excess apical extrusions. CONCLUSIONS: CSC-DMSO could be considered as an alternative filling material for root canal obturation.

Cpne7 deficiency induces cellular senescence and premature aging of dental pulp.

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.

Physiologic dentin regeneration: its past, present, and future perspectives.

Regenerative dentistry has rapidly progressed since the advancement of stem cell biology and material science. However, more emphasis has been placed on the success of tissue formation than on how well the newly generated tissue retains the original structure and function. Once dentin is lost, tertiary dentinogenesis can be induced by new odontoblastic differentiation or re-activation of existing odontoblasts. The characteristic morphology of odontoblasts generates the tubular nature of dentin, which is a reservoir of fluid, ions, and a number of growth factors, and protects the inner pulp tissue. Therefore, understanding the dynamic but delicate process of new dentin formation by odontoblasts, or odontoblast-like cells, following dentinal defects is crucial. In this regard, various efforts have been conducted to identify novel molecules and materials that can promote the regeneration of dentin with strength and longevity. In this review, we focus on recent progress in dentin regeneration research with biological molecules identified, and discuss its potential in future clinical applications.

Comprehensive assessment of the estrogenic activity of resin composites.

Resin-based dental composites have been developed to restore decayed teeth or modify tooth color due to their excellent physical and chemical properties. Such composites may have intrinsic toxicity due to components released into the mouth during the early stage of polymerization, and afterward as a result of erosion or material decomposition. In addition, resin-based dental composites have potential environmental pollutant by elution of monomers and degradation. Since certain monomers of resin matrices are synthesized from bisphenol A (BPA), which acts as an estrogenic endocrine disruptor, these resin matrices may have estrogenic activity. Therefore, the estrogenic endocrine-disrupting activity of various dental composites should be evaluated. In this study, we evaluated the estrogenic endocrine-disrupting activity of 10 resin composites by using a BRET-based estrogen receptor (ER)α and ERß dimerization assays and ER transactivation assay. BPA, BisDMA, BisGMA, BisEMA, TEGDMA, HMBP, and DMPA mediated ERα dimerization, and BPA, BisDMA, and DMPA also mediated ERß dimerization. Except for UDMA and CQ, all the compounds were identified as estrogen agonists or antagonists. In-depth information for the safe use of dental composites was acquired, and it was confirmed how the component of dental composites acts in the ER signaling pathway. Further studies on the low-dose and long-term release of these compounds are needed to ensure the safe use of these resin-based dental composites.

Development of a new universal adhesive containing CPNE7-derived peptide and its potential role in reducing postoperative sensitivity.

Post-operative sensitivity (POS) is the most common clinical dental complaint after tooth preparation and resin-based composite restoration. In our previous study, copine 7 (CPNE7) and CPNE7-derived peptide (CPNE7-DP) induced in vitro odontoblast differentiation and in vivo dentin formation. Here, we incorporated CPNE7-DP into All-Bond Universal (ABU) adhesive, developing ABU/CPNE7-DP. This study aimed to investigate the possibility of reducing POS using ABU/CPNE7-DP. We first determined the stability of CPNE7-DP under low pH. Furthermore, we evaluated its dentinal tubule penetration, in vitro odontogenic differentiation potential, in vivo tertiary dentin formation and its effects on bonding performance. CPNE7-DP was stable at pH 1.2, even lower than ABU's pH of 3.2. ABU/CPNE7-DP can penetrate dentinal tubules, stimulate odontoblast differentiation in vitro and generate tertiary dentin with tubular structure in vivo without interfering with bonding performance. Therefore, ABU/CPNE7-DP may serve as a novel bioactive adhesive for reducing POS.

Efficacy of a novel remotely-generated ultrasonic root canal irrigation system for removing biofilm-mimicking hydrogel from a simulated isthmus model.

AIM: To evaluate the efficacy of a novel ultrasonic irrigation device, remotely-generated irrigation with a non-invasive sound field enhancement (RINSE) system, in removing biofilm-mimicking hydrogel from a simulated isthmus model and compare it with sonically- and ultrasonically-activated irrigation systems. METHODOLOGY: A polycarbonate root canal model containing two standardized root canals (apical diameter of 0.20 mm, 4% taper, 18 mm long with a coronal reservoir) connected by three isthmuses (0.40 mm deep, 2 mm high, 4 mm long) was used as the test model. The isthmuses were filled with a hydroxyapatite powder-containing hydrogel. The canals were filled with irrigant, and the models were randomly assigned to the following activation groups (n = 15): EndoActivator (EA), ultrasonically activated irrigation (UAI), and RINSE system (RS). Syringe irrigation (SI) with a 30G needle served as the control. Standardized images of the isthmuses were taken before and after irrigation, and the amount of hydrogel removed was determined using image analysis software and compared across groups using anova (p < .05). RESULTS: Hydrogel removal was significantly higher with the RS (83.7%) than with UAI, EA, or SI (p ≤ .01). UAI (69.2%) removed significantly more hydrogel than SI and EA (p < .05), while there was no significant difference between SI (24.3%) and EA (25.7%) (p = .978). CONCLUSIONS: RINSE system resulted in the most hydrogel removal, performing better than UAI or EA. The effect of RS was also not reliant on the insert or tip entering the pulp chamber or root canal, making it particularly useful in conservative endodontics.

Root canal irrigation system using remotely generated high-power ultrasound.

Root canal treatment is performed to remove the bacteria proliferating in the root canals of a tooth. Many conventional root canal irrigation methods use an instrument inserted into the root canals. However, bacteria removal is often incomplete in the apical region of the root canal, and the treatment carries clinical risks, such as instrument fracture and extrusion of irrigation liquid through the canal apex. We here suggest a novel, remotely generated high-intensity ultrasound irrigation system that exhibits better irrigation performance and a reduced clinical risk. Our device employs powerful ultrasonic waves generated by a transducer placed outside a target tooth. The generated ultrasonic waves are guided to travel into the root canals. In the root canals of the target tooth, acoustic cavitation occurs, and vapor bubbles are created. The dynamic motions of vapor bubbles create remarkable cleaning effects. Using root canal models, we tested the cleaning performance of the proposed system and compared it with other conventional irrigation methods. The results revealed that biofilm in the apical region of the root canal models can be removed exclusively using the proposed system, thus demonstrating an improvement in cleaning performance. We also measured pressure at the apex of the root canals of an extracted tooth while operating the proposed system. Our system exhibited a smaller pressure compared to the syringe irrigation method, thus suggesting a reduced risk of apical extrusion of the irrigation liquid. Since the proposed system operates without inserting instruments into the root canal, it can clean multiple root canals in a tooth simultaneously with a single treatment. The proposed device would be a breakthrough in root canal treatment in terms of irrigation performance, clinical safety, and ease of treatment.

Novel strategy for dental caries by physiologic dentin regeneration with CPNE7 peptide.

OBJECTIVE: CPNE7-derived functional peptide (CPNE7-DP) has been introduced as a bioactive therapeutics for dentin diseases. CPNE7-DP regenerates tubular dentin on the pulpal side and occlude dentinal tubules. CPNE7-DP was capable to treat dentin hypersensitivity typically associated with dentinal wear at the neck of the tooth. However, the role of CPNE7-DP in another common dentin disease, dental caries, remains uninvestigated. In this study, we evaluated the potential application of CPNE7-DP in dentin caries using an experimental dentin caries model in rats. DESIGN: The stability of CPNE7-DP in caries-like environments including pathologic bacteria of caries or low pH was tested. We established a nutrition-time/hyposalivation-based dental caries rat model by inoculating caries-inducing bacteria and diet for sufficient time. Glycopyrrolate has been treated to induce reversible hyposalivation for accelerating caries progression. Then the tubular dentin regeneration was investigated with histologic methods. Also, modulation of inflammation or autophagy by CPNE7-DP was investigated with marker gene expression in human dental pulp cells (hDPCs) and immunohistochemistry. RESULTS: CPNE7-DP was stable with caries-inducing bacteria and low pH. Establishment of dentin caries was confirmed with radiographic and histologic evaluation. CPNE7-DP regenerated a substantial amount of tubular tertiary dentin and alleviated the pulp inflammation of dentin caries. Under inflammatory conditions, CPNE7-DP reduced the expression of inflammatory cytokines. These phenomena could be the consequence of the modulation of autophagy by CPNE7-DP, which reactivates inflamed odontoblasts. CONCLUSIONS: Overall, CPNE7-DP, which repairs caries through physiological dentin regeneration, might help overcoming the limitations of current restorative caries treatments.

Biocompatibility and osteogenic potential of mineral trioxide aggregate mixed with hydrophilic synthetic polymer: An in vitro and in vivo study.

This study aimed to investigate in vitro biologic properties of mineral trioxide aggregate (MTA) mixed with 3% PVA (MTA-3% PVA) and in vivo dental pulp responses to direct capping in comparison with MTA mixed with distilled water (MTA-DW). Cell proliferation and osteogenic differentiation in culture of human dental pulp cells (hDPCs), and pH changes were evaluated. Pulps in 24 mandibular premolars of four 9-month-old beagle dogs were mechanically exposed and direct pulp capping was performed. Histological specimens were scored according to the degree of mineralization. MTA-3% PVA showed similar cell proliferation and similar or superior osteogenic differentiation of hDPCs compared with MTA-DW. All specimens were associated with calcified bridge formation and there were no significant differences in mineralization scores between the groups (p>0.05). The results suggested that MTA-3% PVA exhibited favorable biocompatibility and osteogenic differentiation in vitro compared with MTA-DW. Furthermore, both groups demonstrated similar results when used as pulp-capping agents in vivo.

Comparing cleaning effects of gas and vapor bubbles in ultrasonic fields.

The dynamic actions of cavitation bubbles in ultrasonic fields can clean surfaces. Gas and vapor cavitation bubbles exhibit different dynamic behaviors in ultrasonic fields, yet little attention has been given to the distinctive cleaning effects of gas and vapor bubbles. We present an experimental investigation of surface cleaning by gas and vapor bubbles in an ultrasonic field. Using high-speed videography, we found that the primary motions of gas and vapor bubbles responsible for surface cleaning differ. Our cleaning tests under different contamination conditions in terms of contaminant adhesion strength and surface wettability reveal that vapor and gas bubbles are more effective at removing contaminants with strong and weak adhesion, respectively, and furthermore that hydrophobic substrates are better cleaned by vapor bubbles. Our study not only provides a better physical understanding of the ultrasonic cleaning process, but also proposes novel techniques to improve ultrasonic cleaning by selectively employing gas and vapor bubbles depending on the characteristics of the surface to be cleaned.

Effect of mineral trioxide aggregate plug location on root development in regenerative endodontic procedure.

This retrospective study investigated the effect of mineral trioxide aggregate (MTA) plug location on treatment outcome and root maturation after regenerative endodontic procedures (REP) in immature permanent teeth. Thirty-three roots (n = 33) in cohort that underwent REP consistently according to AAE guideline were included to trace radiographic changes for the root and canal dimensions. Based on intraoral radiographs, roots were divided into two groups depending on the location of MTA plug within whole root length: coronal group (n = 14), within the upper half; apical group (n = 19), within the lower half. Periapical radiographs were standardized to assess treatment outcomes and root maturation including root development stages and digital measurements on the change ratios of root length, apex width, radiographic root area (RRA), modified RRA (mRRA), and periapical rarefaction area. The data were statistically analysed using the Mann-Whitney test. The patients' average age was 11 years and 10 months, with no significant between-group difference in sex. Premolars were the most prevalent tooth type (62.1%), followed by incisiors and molars. Pre-existing symptoms and signs subsided within 6 months in all cases. The teeth showed similar radiographic root development in both groups (P > 0.05). However, mRRA increase ratio was significantly higher in apical group than that in coronal group at early (< 6 months) and late (< 24 months) periods of follow-up (P < 0.05). Significant changes of root development stage were observed at early period for apical group and at late period for coronal group (P < 0.05). All the observed cases showed continuing root development after REP. Significant changes in root developments occurred at different follow-up periods according to the location of MTA plugs.

Comparative Analysis of Root Canal Filling Debris and Smear Layer Removal Efficacy Using Various Root Canal Activation Systems during Endodontic Retreatment.

The complete removal of obturation material can be a challenge in nonsurgical root canal retreatment. The insufficient removal of obturation material is a reason for root canal retreatment failure. The purpose of this study was to assess the efficacy of different final root canal irrigation activation methods in removing debris and smear layers in the apical and middle portions of root canals during retreatment. Sixty-six distal roots of freshly extracted molars were randomly divided into six groups: (1) primary root canal treatment with no obturation (negative control); (2) retreatment with only conventional instrumentation and irrigation (positive control); (3) retreatment with additional ultrasonic irrigation using the Piezon Master 700; (4) ultrasonic irrigation with the ENDOSONIC Blue; (5) sonic irrigation with the EDDY; and (6) multisonic irrigation with the GentleWave system. Roots were split and prepared for scanning electron microscopic (SEM) evaluation. Acquired images were assessed to quantify the amount of debris and smear remaining. Among the treatment groups, Group 6 had a significantly lower debris score than Group 2 (positive control) in both the middle and apical regions (p = 0.004, p = 0.012). All treatment groups showed significantly lower smear scores than Group 2 in the middle and apical regions (p < 0.05). The GentleWave multisonic System showed a more optimal cleaning efficacy of the root canal debris but did not differ significantly with the tested passive ultrasonic or sonic irrigation method.

Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide.

We aim to examine the effects of a newly developed peptide derived from CPNE7 (Cpne7-DP) in tertiary dentin formation and peritubular space occlusion, and comprehensively evaluate its potential as a bioactive therapeutic agent. Human dental pulp cells (HDPCs) and a mouse pre-odontoblast cell line, MDPC-23, were chosen for in vitro studies to characterize lineage-specific cell responses after Cpne7-DP treatment. Whether Cpne7-DP reproduces the dentin regenerative potential of CPNE7 was tested using a beagle dog model by generating dentinal defects of various degrees in vivo. Peritubular space occlusion was further examined by scanning electron microscopy and microleakage test, while overall mineralization capacity of Cpne7-DP was tested ex vivo. CPNE7 promotes tubular dentin formation under both shallow and deep dentinal defects, and the functional peptide Cpne7-DP induces odontoblast-like differentiation in vitro, mineralization ex vivo, and tubular dentin formation in in vivo beagle dog dentin exposure and pulp exposure models. Moreover, Cpne7-DP leads to peritubular space occlusion and maintains stability under different conditions. We show that CPNE7 and its derivative functional peptide Cpne7-DP promotes dentin regeneration in dentinal defects of various degrees and that the regenerated hard tissue demonstrates the characteristics of true dentin. Limitations of the current dental materials including post-operative hypersensitivity make biological repair of dentin a field of growing interest. Here, we suggest that the dual functions of Cpne7-DP in tubular dentin formation and peritubular space occlusion are promising for the treatment of dentinal loss and sensitivity.

Effects of Caries Activity on Compositions of Mutans Streptococci in Saliva-Induced Biofilm Formed on Bracket Materials.

This study aimed to investigate effects of caries activity on composition of mutans streptococci in saliva-induced biofilms formed on bracket materials. Three bracket materials were used as specimens: ceramic, metal, and plastic. After saliva was collected using a spitting method from caries-active (CA, decayed, missing, filled teeth (DMFT) score ≥ 10) and caries-free (CF, DMFT score = 0) subjects, saliva was mixed with growth media in a proportion of 1:10. The saliva solution was then incubated with each bracket material. After a saliva-induced biofilm was developed on the surface of the bracket material, the amounts of total bacteria and mutans streptococci were determined using real-time polymerase chain reaction. The results showed that biofilms from CA saliva contained more mutans streptococci but less total bacteria than biofilms from CF saliva, regardless of material type. Adhesion of total bacteria to ceramic was higher than to plastic, regardless of caries activity. Mutans streptococci adhered more to ceramic than to metal and plastic in both biofilms from CA and CF saliva, but there was a difference in adhesion between Streptococcus mutans and Streptococcus sobrinus. The amount of S. mutans was higher than that of S. sobrinus in biofilms from CA saliva despite similar amounts of the two strains in biofilms from CF saliva. The stronger adhesion of S. mutans to ceramic than to metal and plastic was more evident in biofilms from CA saliva than in biofilms from CF saliva. This study suggests that caries activity and material type significantly influenced composition of mutans streptococci in biofilms formed on bracket materials.

Combined Effect of Melittin and DNase on Enterococcus faecalis Biofilms and Its Susceptibility to Sodium Hypochlorite.

Biofilm communities are tolerant to antimicrobials and difficult to eradicate. This study aimed to investigate the effect of melittin, an antimicrobial peptide, either alone or in combination with deoxyribonuclease (DNase), an inhibitor of extracellular deoxyribonucleic acid (eDNA), against Enterococcus faecalis (E. faecalis) biofilms, and biofilm susceptibility to sodium hypochlorite (NaOCl). Biofilms of E. faecalis were developed in root canals of bovine teeth. The biofilms were treated with distilled water (control), melittin, DNase, or DNase+melittin. The antibiofilm effects of the treatments were analyzed using colony forming unit (CFU) assay, crystal violet staining, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscope (FE-SEM). The susceptibility of DNase+melittin-treated biofilms to NaOCl (0%, 2.5% and 5%) was investigated by the CFU assay. The data were statistically analyzed using one-way analysis of variance, followed by Tukey's test. A p-value of <0.05 was considered significant. Specimens treated with DNase+melittin showed a more significant decrease in the CFUs, eDNA level, and biofilm formation rate than those treated only with melittin or DNase (p < 0.05). CLSM analysis showed DNase+melittin treatment significantly reduced the volume of biofilms and extracellular polymeric substance compared to either treatment alone (p < 0.05). FE-SEM images showed a high degree of biofilm disruption in specimens that received DNase+melittin. 2.5% NaOCl in specimens pretreated with DNase+melittin showed higher antibacterial activity than those treated only with 5% NaOCl (p < 0.05). This study highlighted that DNase improved the antibiofilm effects of melittin. Moreover, DNase+melittin treatment increased the susceptibility of biofilms to NaOCl. Thus, the complex could be a clinical strategy for safer use of NaOCl by reducing the concentration.

Morphological measurements of two separate mesiobuccal canals in maxillary first molars using micro-computed tomography.

OBJECTIVES: To obtain radicular measurements of two separate mesiobuccal (MB) root canals in maxillary first molars using micro-computed tomography (µCT) with customized software. MATERIALS AND METHODS: Human maxillary first molar MB roots (N = 36) with two separate canals (MB1, MB2) and apical foramina were scanned by µCT and analyzed with Kappa2 software to reconstruct three-dimensional (3D) surface models of roots and canals. These models were sectioned at 0.1 mm intervals perpendicular to the central axis of each canal. Canal widths, 3D curvatures, and surrounding dentine thicknesses were measured concurrently on each section. Dentine thicknesses were analyzed statistically for differences between each direction and the different levels of both canals. RESULTS: Dentine walls around MB1 were thicker than MB2 (p < 0.05). Thinnest dentine was most often located at disto-inside direction in both canals. Canal widths were significantly smaller in MB2 than MB1 (p < 0.01). Apical constrictions were smaller (p < 0.05) and further (p < 0.05) from the apex in MB2 than MB1. Canal curvatures were greatest in the apical third of both canals (p < 0.001), and they were greater in MB2 than MB1 (p < 0.05). CONCLUSIONS: MB2 canals had shorter lengths, smaller widths, and more severe curvatures and were surrounded by thinner dentine walls. In MB2, apical constrictions were between 1 and 2 mm from the apex, compared to about 1 mm for MB1. CLINICAL RELEVANCE: These detailed measurements and in-depth 3D analyses of maxillary first molar MB roots with two separate canals and apical foramina provide morphologic references for root canal therapy.

A telomerase-derived peptide vaccine inhibits laser-induced choroidal neovascularization in a rat model.

GV1001, a novel peptide derived from human telomerase reverse transcriptase, reportedly has anticancer and anti-inflammatory effects. Choroidal neovascularization (CNV) is a complex pathogenic process that involves angiogenesis, inflammation, cellular immunity, and other factors. This study was aimed at investigating the effect of GV1001 on laser-induced CNV in a rat model. Brown Norway rats were subcutaneously administered GV1001 (0.1 nM, 1 nM, and 10 nM) daily, beginning 3 days prior, and ending 14 days after laser photocoagulation. Optical coherence tomography, fluorescein angiography, choroidal flat mount, and histologic analysis were performed to analyze CNV. The protein level of IκB-α and nuclear translocation of nuclear factor κB (NF-κB) was analyzed via immunohistochemistry of p65. Multiplex immunoassay was performed to evaluate the interleukin (IL)-1ß, IL-6, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1, and tumor necrosis factor-α levels. The GV1001-treated group had significantly lower CNV thickness, smaller CNV area, and lower proportion of CNV lesions with clinically significant fluorescein leakage than vehicle-treated group. GV1001 treatment inhibited IκB-α degradation and NF-κB p65 nuclear translocation. At 1 nM concentration, GV1001 had highest inhibitory effect on CNV and NF-κB signaling activation; moreover, it suppressed the levels of IL-1ß, IL-6, and VEGF significantly. The present study demonstrates that GV1001 treatment led to significant suppression of laser-induced CNV, alongside inhibition of inflammatory processes including NF-κB activation and subsequent upregulation of proinflammatory cytokines. Therefore, this provides molecular evidence of potential validity of GV1001 treatment as a therapeutic strategy for neovascular age-related macular degeneration.

Comparative Analysis of Biofilm Removal Efficacy by Multisonic Ultracleaning System and Passive Ultrasonic Activation.

The purpose of this study was to compare disinfection and the biofilm removal efficacy of the GentleWave System (Sonendo, Inc., Laguna Hills, CA, USA) with passive ultrasonic activation method. Forty-seven freshly extracted human molars were inoculated with Enterococcus faecalis and cultured for five weeks to establish biofilm. Eight molars were tested for confirmation of infection. Four of the eight teeth were not inoculated in order to provide a negative control. The remaining 39 inoculated molars were randomly separated into three treatment groups (n = 13 per group): Group 1-no treatment, Group 2-conventional rotary instrumentation and passive ultrasonic activation, and Group 3-minimal instrumentation and the GentleWave System treatment. Roots were subsequently prepared per standard histological tissue processing procedures. Modified Brown and Brenn stained sections and Hematoxylin and Eosin stained sections were visualized at 4× and 13.5× magnification using a stereomicroscope. The sections were scored and blindly analyzed by two independent evaluators, including a histopathologist, to evaluate the presence of biofilm on canal wall. A significant difference was found between Group 2 and Group 3 in both apical and middle regions (p = 0.001) of the mesial roots of mandibular molars and mesiobuccal roots of maxillary molars. Group 3 revealed significantly less biofilm than the controls (p = 0.003). The GentleWave System demonstrated significantly greater reduction in biofilm within the mesial roots of mandibular molars and mesiobuccal roots of maxillary molars than those treated with conventional rotary instrumentation and passive ultrasonic activation protocol.

Novel Calcium Zirconate Silicate Cement Biomineralize and Seal Root Canals.

This study evaluated the sealing ability of gutta-percha (GP) with a calcium silicate-based sealer and a novel calcium zirconate containing calcium silicate cement (ZC). The root canals of the extracted premolars were prepared, which were then randomly allocated to three experimental groups (12 root canals per group) for obturation by continuous wave of condensation with the GP and AH 26 sealer (CW); obturation using a single GP with a calcium silicate-based EndoSequence BC sealer (SC); or obturation with ZC. The roots were inserted into sterile Eppendorf tubes, which were inoculated coronally with Porphyromonas gingivalis. The amount of endotoxin leakage into the apical reservoirs were measured using the Limulus Amebocyte Lysate (LAL) assay over 21 days, with comparisons made using one-way ANOVA and Scheffe's tests (α = 0.05). After 21 days, 75% of the canals that had been obturated by SC, 50% of those obturated by CW and 42% of those obturated by ZC showed endotoxin leakage. The amount of leakage was higher in the SC canals than in the CW (p = 0.031) or ZC (p = 0.03) canals, although there was no significant difference in the amount of leakage for CW and ZC (p > 0.05). X-ray diffraction revealed the presence of tricalcium silicate (Ca3SiO5) and calcium zirconate (CaZrO3) in the synthesized ZC. Scanning electron microscopy revealed mineralized precipitates on the dentin of canals obturated by ZC. The novel calcium zirconate silicate cement appears to promote biomineralization and seal root canals at least as effectively as the conventional sealer.

hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF­ß signaling.

GV1001 is a 16­amino acid peptide derived from the human telomerase reverse transcriptase (hTERT) protein (616­626; EARPALLTSRLRFIPK), which lies within the reverse transcriptase domain. Originally developed as an anticancer vaccine, GV1001 demonstrates diverse cellular effects, including anti­inflammatory, tumor suppressive and antiviral effects. In the present study, the radioprotective and antifibrotic effects of GV1001 were demonstrated through suppressing transforming growth factor­ß (TGF­ß) signaling. Proliferating human keratinocytes underwent premature senescence upon exposure to ionizing radiation (IR), however, treatment of cells with GV1001 allowed the cells to proliferate and showed a reduction in senescent phenotype. GV1001 treatment notably increased the levels of Grainyhead­like 2 and phosphorylated (p­)Akt (Ser473), and reduced the activation of p53 and the level of p21/WAF1 in irradiated keratinocytes. It also markedly suppressed the level of TGF­ß signaling molecules, including p­small mothers against decapentaplegic (Smad)2/3 and Smad4, and TGF­ß target genes, including zinc finger E­box binding homeobox 1, fibronectin, N­cadharin and Snail, in irradiated keratinocytes. Furthermore, GV1001 suppressed TGF­ß signaling in primary human fibroblasts and inhibited myofibroblast differentiation. Chromatin immunoprecipitation revealed that GV1001 suppressed the binding of Smad2 on the promoter regions of collagen type III α1 chain (Col3a1) and Col1a1. In a dermal fibrosis model in vivo, GV1001 treatment notably reduced the thickness of fibrotic lesions and the synthesis of Col3a1. These data indicated that GV1001 ameliorated the IR­induced senescence phenotype and tissue fibrosis by inhibiting TGF­ß signaling and may have therapeutic effects on radiation­induced tissue damage.