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.

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.

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.

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.

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.

Revascularization-associated Intracanal Calcification: Assessment of Prevalence and Contributing Factors.

INTRODUCTION: Intracanal calcifications have been reported in endodontic cases after revascularization. The purpose of the current study was to determine the incidence of intracanal calcification and potential contributing factors in retrospective revascularization cases. METHODS: Among 37 patients who had undergone revascularization between 2010 and 2014, 29 cases were assessed with average follow-up period of 24.9 months. Clinical and radiographic examinations were performed to evaluate the treatment outcomes, eg, resolution of apical periodontitis (AP), root development, and occurrence of intracanal calcification. Radiographic assessment revealed varied calcification patterns, which were classified into calcific barrier or canal obliteration, collectively referred to as revascularization-associated intracanal calcification (RAIC). RESULTS: All 29 cases demonstrated resolution of AP, whereas continued root development with apical closure occurred in 23 of 29 cases (79.3%). RAIC was noted in 18 of 29 cases (62.1%), among which 5 of 18 cases (27.8%) were classified as calcific barrier and 13 of 18 cases as canal obliteration (72.2%). Higher frequency of RAIC was noted in the cases with induced bleeding (16 of 23 cases, 69.6%), whereas the 6 cases without induced bleeding showed RAIC at 33.4%. Also, RAIC occurred more frequently in cases medicated with Ca(OH)2 (10 of 13 cases, 76.9%) than in those medicated with antibiotic pastes (6 of 13 cases, 46.2%). CONCLUSIONS: This study indicated that RAIC is common (62.1%) among cases treated with revascularization. Multiple contributing factors may include the type of medicaments and induction of intracanal bleeding. Although RAIC does not interfere with resolution of AP, some cases may progress to complete obliteration of root canals and would impede normal function of dental pulp tissues.

Saving an Integrating Implant Involved with Endodontic Implant Pathology Using Surgical Treatment.

Endodontic implant pathology (EIP) refers to cases in which endodontic infections cause infections in adjacent implants, and vice versa. This case report demonstrates the successful resolution of two types of EIPs, implant endodontitis and endodontic implantitis, by endodontic intervention with surgical treatment. In case 1, the patient complained of tooth discomfort after implant placement in the adjacent tooth. The tooth was sensitive to percussion and showed slight mobility with a negative reaction to an electric pulp test. The symptoms persisted despite conventional root canal treatment, and surgical treatment of the symptomatic tooth and implant lesion was performed. In case 2, the patient suffered from repeated infection around a newly installed implant. The adjacent devitalized tooth exhibited a periapical lesion that was contiguous with the implant. Conventional root canal treatment and retreatment did not successfully resolve the symptoms. Surgical root canal therapy was then performed with regenerative biomaterials as needed. Neither case showed radiographic or clinical evidence of failure after 4 and 5 years of follow-up, respectively, after the surgery and the adjacent implants were successfully osseointegrated. Endodontic intervention combined with surgical treatment resolved both types of EIPs and led to tooth preservation and successful osseointegration of adjacent implants.

Preameloblast-Derived Factors Mediate Osteoblast Differentiation of Human Bone Marrow Mesenchymal Stem Cells by Runx2-Osterix-BSP Signaling.

Epithelial-mesenchymal interaction occurs during development of various tissues, including teeth and bone. Recently, a preameloblast-conditioned medium (PA-CM) from mouse apical bud cells (ABCs), a type of dental epithelial cell, was found to induce odontogenic differentiation of dental pulp stem cells and promote dentin formation. The aims of the present study were to investigate the effects of PA-CM on human bone marrow mesenchymal stem cells (hBMSCs) in vitro, and to investigate the bone regenerative capacity in vivo through epithelial-mesenchymal interactions of developmental osteogenesis. Coculturing with ABCs and PA-CM treatment upregulated osteoblast differentiation markers of hBMSCs compared to cells cultured alone. PA-CM accelerated mineralized nodule formation and also increased bone sialoprotein promoter activity in hBMSCs. PA-CM facilitated the migration of hBMSCs, but did not significantly influence proliferation. PA-CM promoted bone formation of hBMSCs in vivo. Radiographic and histologic findings showed that PA-CM induced the bony regeneration at calvarial defects in rat. Taken together, these data show that PA-CM enhances the migration and osteogenic differentiation of hBMSCs in vitro and induces bone formation in vivo.

The Anti-Inflammatory Effect of Human Telomerase-Derived Peptide on P. gingivalis Lipopolysaccharide-Induced Inflammatory Cytokine Production and Its Mechanism in Human Dental Pulp Cells.

Porphyromonas gingivalis is considered with inducing pulpal inflammation and has lipopolysaccharide (LPS) as an inflammatory stimulator. GV1001 peptide has anticancer and anti-inflammation activity due to inhibiting activation of signaling molecules after penetration into the various types of cells. Therefore, this study examined inhibitory effect of GV1001 on dental pulp cells (hDPCs) stimulated by P. gingivalis LPS. The intracellular distribution of GV1001 was analyzed by confocal microscopy. Real-time RT-PCR was performed to determine the expression levels of TNF-α and IL-6 cytokines. The role of signaling by MAP kinases (ERK and p38) was explored using Western blot analysis. The effect of GV1001 peptide on hDPCs viability was measured by MTT assay. GV1001 was predominantly located in hDPC cytoplasm. The peptide inhibited P. gingivalis LPS-induced TNF-α and IL-6 production in hDPCs without significant cytotoxicity. Furthermore, GV1001 treatment markedly inhibited the phosphorylation of MAP kinases (ERK and p38) in LPS-stimulated hDPCs. GV1001 may prevent P. gingivalis LPS-induced inflammation of apical tissue. Also, these findings provide mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability.

The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.

GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation.

Effect of conditioned medium from preameloblasts on regenerative cellular differentiation of the immature teeth with necrotic pulp and apical periodontitis.

INTRODUCTION: The purpose of this study was to investigate the effect of conditioned medium (CM) from murine preameloblasts on the cellular differentiation of mesenchymal stem cells (MSCs) in immature teeth with necrotic pulp and apical periodontitis. METHODS: Pulp necrosis and apical periodontitis were induced in 30 immature permanent double-rooted premolars of 3 beagles and were randomly assigned to the following treatment groups: group CM (n = 10), revascularization treatment was performed using CM from preameloblasts of C57BL/6 mice apical bud cells; group CR (n = 10), conventional revascularization treatment was performed; positive control group (n = 5), left infected; and negative control group (n = 5), untreated. The dogs were followed up for 12 weeks and assessed for treatment outcomes with radiographic and histologic analyses. The effect of the CM on sequential Runx2 and osterix messenger RNA gene expression during the differentiation of MG63 osteoblastlike cells was analyzed with real-time polymerase chain reaction. RESULTS: The overall treatment outcomes were not significantly different between the 2 treatment groups. However, the teeth in the CM group showed significantly more mature apices and a higher degree of hard tissue formation with projections intercalating into the pre-existing root dentin (P < .05). In CM-treated teeth, regenerated pulplike tissue was more frequently observed (P < .05). During differentiation, the CM induced early peak expression of Runx2 followed by sustained osterix overexpression. CONCLUSIONS: CM from preameloblasts rendered a favorable effect in providing a physiologic microenvironment for the differentiation of MSCs after revascularization treatment.

Shaping ability of the conventional nickel-titanium and reciprocating nickel-titanium file systems: a comparative study using micro-computed tomography.

INTRODUCTION: This study used micro-computed tomographic imaging to compare the shaping ability of Mtwo (VDW, Munich, Germany), a conventional nickel-titanium file system, and Reciproc (VDW), a reciprocating file system morphologically similar to Mtwo. METHODS: Root canal shaping was performed on the mesiobuccal and distobuccal canals of extracted maxillary molars. In the RR group (n = 15), Reciproc was used in a reciprocating motion (150° counterclockwise/30° clockwise, 300 rpm); in the MR group, Mtwo was used in a reciprocating motion (150° clockwise/30° counterclockwise, 300 rpm); and in the MC group, Mtwo was used in a continuous rotating motion (300 rpm). Micro-computed tomographic images taken before and after canal shaping were used to analyze canal volume change and the degree of transportation at the cervical, middle, and apical levels. The time required for canal shaping was recorded. Afterward, each file was analyzed using scanning electron microscopy. RESULTS: No statistically significant differences were found among the 3 groups in the time for canal shaping or canal volume change (P > .05). Transportation values of the RR and MR groups were not significantly different at any level. However, the transportation value of the MC group was significantly higher than both the RR and MR groups at the cervical and apical levels (P < .05). In the scanning electron microscopic analysis, file deformation was observed for 1 file in group RR (1/15), 3 files in group MR (3/15), and 5 files in group MC (5/15). CONCLUSIONS: In terms of shaping ability, Mtwo used in a reciprocating motion was not significantly different from the Reciproc system.

Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1α-VEGF signaling axis.

A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Previously, we have shown that GV1001 interacts with heat shock proteins (HSPs) and penetrates cell membranes to be localized in the cytoplasm. In this study, we have found that GV1001 lowered the level of intracellular and surface HSPs of various cancer cells. In hypoxic conditions, GV1001 treatment of cancer cells resulted in decreases of HSP90, HSP70, and HIF-1α. Subsequently, proliferation of cancer cells and synthesis of VEGF were significantly reduced by treatment using GV1001 in hypoxic conditions. In an experiment using a nude mouse xenograft model, GV1001 exerted a similar tumor suppressive effect, further confirming its anti-tumor efficacy. Higher apoptotic cell death, reduced proliferation of cells, and fewer blood vessels were observed in GV1001-treated tumors compared to control. In addition, significant reduction of Tie2+ CD11b+ monocytes, which were recruited by VEGF from tumor cells and play a critical role in angiogenesis, was observed in GV1001-treated tumors. Collectively, the results suggest that GV1001 possesses potential therapeutic efficacy in addition to its ability to induce anti-cancer immune responses by suppressing both HSP70 and HSP90.

Clinical efficiency and reusability of the reciprocating nickel-titanium instruments according to the root canal anatomy.

The application of the single-file technique using the reciprocating motion is gaining concern in root canal preparation. The purpose of this research is to compare the efficiency of the reciprocating motion-employing files (RECIPROC and WaveOne) by measuring the working time for complete canal shaping, and to evaluate their reusability under scanning examinations. One hundred curved root canals of the extracted molars were used. The working length was determined and the glide path was confirmed using a #15 K-file. Canals shaping was completed to the length either with RECIPROC R25 file (n = 50), or with WaveOne Primary file (n = 50). The time taken for the file to reach the working length was also measured. Each file was repeatedly used in a maximum of 10 canals for comparing the change of the efficiency (shaping time) according to the working length, canal curvature, and number of file re-use. The deformations or surface defects of the files after the in vitro use were observed using a scanning electron microscope (SEM). There was no difference under the SEM between the 2 file groups with no initiation of micro-cracks until they were re-used up to 5 canals. WaveOne Primary file showed significantly shorter working time than RECIPROC R25 (p < 0.05). There was a statistically significant correlation between the working time and three variables. As the working length and the curvature of the canal increased, the shaping time was increased in both file systems. Reusability of these reciprocating instruments might be maximum 5 canals with minimal surface deformations.

Effect of 1440-nanometer neodymium:yttrium-aluminum-garnet laser irradiation on pain and neuropeptide reduction: a randomized prospective clinical trial.

INTRODUCTION: The purpose of this study was to investigate the efficacy of a 1440-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser on relieving pain in relation to the levels of inflammatory cytokine and neuropeptides in the root canal exudates of teeth with persistent symptomatic apical periodontitis. METHODS: Forty teeth with persistent symptomatic apical periodontitis were randomly assigned to treatment groups: group L, intracanal irradiation of 1440-nm Nd:YAG laser with a 300-µm-diameter fiberoptic tip in addition to conventional root canal retreatment, and group C, conventional root canal re-treatment. The degrees of both spontaneous pain and the pain on percussion before and after treatment were recorded, and root canal exudate samples were collected to quantify the associated levels of substance P, calcitonin gene-related peptide (CGRP), and matrix metalloproteinase (MMP)-8 by immunoassay. RESULTS: All of the measured parameters were significantly reduced in group L (P < .05), whereas the level of pain on percussion, CGRP, and MMP-8 were significantly reduced in group C (P < .05). The 1440-nm Nd:YAG laser had significantly better effect on the relief of pain on percussion and the reduction of substance P, CGRP, and MMP-8 levels. The visual analog scale scores of perceived pain correlated with pain-related neuropeptides and inflammatory cytokine levels in root canal exudates. CONCLUSIONS: The 1440-nm Nd:YAG laser irradiation via fiberoptic tip to the teeth with persistent apical periodontitis provided promising consequences of pain and inflammation modulation.

Heat shock protein-mediated cell penetration and cytosolic delivery of macromolecules by a telomerase-derived peptide vaccine.

A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. Here, we report an unexpected function of GV1001 as a cell-penetrating peptide (CPP). GV1001 was delivered into a variety of cells including various cancer cell lines and primary blood cells. Moreover, the delivered GV1001 was predominantly located in the cytoplasm of the cells, while a significantly higher proportion of TAT peptide was localized in the nucleus. Macromolecules such as proteins, DNA and siRNA, which were linked to GV1001 by direct covalent conjugation or non-covalent complexation through poly-lysine, were successfully delivered into cells, indicating that GV1001 can be used as a carrier for macromolecules. Expression of the delivered DNA, and lowered expression of the target gene by the delivered siRNA, suggest the potential therapeutic use of GV1001. Pull-down analysis identified Heat Shock Protein 90 (HSP90) and 70 (HSP70) as GV1001 interacting proteins. Treatment of Anti-HSP90 and HSP70 antibodies lowered the internalization of GV1001, indicating that the interaction is critical for the efficient internalization of GV1001. Collectively, the results of this study suggest the pharmaceutical potential of GV1001, already proven safe in clinical trials, as a carrier for the delivery of macromolecular therapeutics into cells, in addition to its own anti-cancer activity.

Autotransplantion of a displaced mandibular second premolar to its normal position.

The patient was a 13-year-old Korean girl who had a displaced mandibular second premolar. She was reluctant to undergo a lengthy orthodontic treatment and opted instead for transplantation of the premolar to its usual site. On the basis of computed tomography, a replica tooth model was manufactured to shorten the extraoral time, and a root canal treatment was performed because root formation was complete. No negative signs or symptoms were found during a 3-year follow up. Autotransplantation for this patient obviated the need for orthodontic traction and prosthetic therapy.

Effects of calcium phosphate endodontic sealers on the behavior of human periodontal ligament fibroblasts and MG63 osteoblast-like cells.

In regard to biological properties of endodontic sealers, there are many characteristics that should be considered. The aim of this study was to examine the biological effects of new calcium phosphate-based root canal sealers, CAPSEAL I and CAPSEAL II (CPS), on human periodontal fibroblast cells by examining the expression levels of inflammatory mediators and to compare the effects of CPS on the viability and osteogenic potential of human osteoblast MG63 cells compared to those of other commercially available calcium phosphate sealers [Apatite Root Sealer type I (ARS I) and Apatite Root Sealer III (ARS III); Sankin Kogyo, Tokyo, Japan] and a zinc oxide eugenol-based sealer (Pulp Canal Sealer EWT [PCS EWT]; Kerr, Detroit, MI). The levels of IL-6 in the new CPS group (CAPSEAL I, II) were higher than those in the control and all experimental groups at all time points after 2 h. TGF-ß1 and FGF-1 levels decreased at 72 h compared to the levels in the control, in cells treated with every sealers except ARS I. The new CPS sealers showed low cytotoxicity. Reverse transcription polymerase chain reaction showed that CAPSEAL I, II, and Apatite Root Sealer type III induced expression of early stage markers of differentiation (alkaline phosphatase and osteopontin) at 7 days. Also, new CPS showed higher mineralized nodule formation at 28 days. These results suggest that CAPSEAL I and II facilitate the periapical dentoalveolar and alveolar healing by controlling cellular mediators from PDL cells and osteoblast differentiation of precursor cells.