1,720,978 research outputs found

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

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    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-1 alpha. 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. (C) 2013 Elsevier Ltd. All rights reserved.N

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

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    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.N

    Oxygen saturation and perfusion index from pulse oximetry in adult volunteers with viable incisors

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    Objective: Evaluation of pulp vitality is an important diagnostic procedure in dentistry. Conventional techniques for measurement of pulp vitality, including thermal stimulation, electrical stimulation, or direct dentin stimulation, are frequently associated with false positive or false negative results. Recently, oxygen saturation from pulse oximetry has been utilized in the evaluation of pulp vitality. Perfusion index (PI) data calculated from photoplethysmography have been widely used to evaluate peripheral perfusion. The combination of oxygen saturation and PI may aid in the accurate measurement of pulp vitality. We aimed to investigate the baseline values of oxygen saturation and PI using pulse oximetry in adult volunteers. Material and methods: Fifteen adult volunteers with viable incisors were tested. To measure PI, a fabricated oxygen sensor was applied to an incisor without a pulp lesion while oxygen saturation was simultaneously measured in the finger. Oxygen saturation and PI were continuously measured with customized software. The normal reference values of oxygen saturation and PI were obtained by analyzing the recorded data. Results: Pulse oximetry showed relatively stable, objective, and accurate oxygen saturation results. The tooth oxygen saturation ranged from 97% to 100%. The PI ranged from 0.3% to 0.5%, and PI and oxygen saturation showed relatively consistent values across subjects. Conclusions: Although there are some limitations to our study, these results may prove useful for detecting teeth with impaired vitality and non-invasively differentiating between necrotic and vital pulp.N

    Tubular Dentin Regeneration Using a CPNE7-Derived Functional Peptide

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    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

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

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    Objectives To obtain radicular measurements of two separate mesiobuccal (MB) root canals in maxillary first molars using micro-computed tomography (mu CT) 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 mu CT 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.N

    Dynamic intratubular biomineralization following root canal obturation with pozzolan‐based mineral trioxide aggregate sealer cement

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    The application of mineral trioxide aggregates (MTA) cement during the root canal obturation is gaining concern due to its bioactive characteristic to form an apatite in dentinal tubules. In this regard, this study was to assess the biomineralization of dentinal tubules following root canal obturation by using pozzolan-based (Pz-) MTA sealer cement (EndoSeal MTA, Maruchi). Sixty curved roots (mesiobuccal, distobuccal) from human maxillary molars were instrumented and prepared for root canal obturation. The canals were obturated with gutta-percha (GP) and Pz-MTA sealer by using continuous wave of condensation technique. Canals obturated solely with ProRoot MTA (Dentsply Tulsa Dental) or Pz-MTA sealer were used for comparison. In order to evaluate the biomineralization ability under different conditions, the PBS pretreatment before the root canal obturation was performed in each additional samples. At dentin-material interfaces, the extension of intratubular biomineralization was analyzed using scanning electron microscopy (SEM) and energy dispersive spectroscopy. When the root canal was obturated with GP and Pz-MTA sealer, enhanced biomineralization of the dentinal tubules beyond the penetrated sealer tag was confirmed under the SEM observation (p<0.05). Mineralized apatite structures (calcium/phosphorous ratio, 1.45-1.89) connecting its way through the dentinal tubules were detected at 350-400m from the tubule orifice, and the pre-crystallization seeds were also observed along the intra- and/or inter-tubular collagen fiber. Intratubular biomineralization depth was significantly enhanced in all PBS pretreated canals (p<0.05). Pz-MTA cement can be used as a promising bioactive root canal sealer to enhance biomineralization of dentinal tubules under controlled environment. SCANNING 38:50-56, 2016. (c) 2015 The Authors. Scanning Published by Wiley Periodicals, Inc.OAIID:RECH_ACHV_DSTSH_NO:T201608221RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A076889CITE_RATE:1.345FILENAME:Yoo_et_al-2016-Scanning.pdfDEPT_NM:치의학과EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/3527ef8d-fb12-44a7-9e41-b674281bd59e/linkY

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

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    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.OAIID:RECH_ACHV_DSTSH_NO:T201607758RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A076889CITE_RATE:1.113DEPT_NM:치의학과EMAIL:[email protected]_YN:YN

    Novel Calcium Zirconate Silicate Cement Biomineralize and Seal Root Canals

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    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

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

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    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.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000006653/8SEQ:8PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000006653ADJUST_YN:YEMP_ID:A077651DEPT_CD:806CITE_RATE:7.604FILENAME:heat shock protein-mediated cell penetration and cytosolic delivery.pdfDEPT_NM:의과학과EMAIL:[email protected]_YN:YCONFIRM:

    Effect of acidic solutions on the microhardness of dentin and set OrthoMTA and their cytotoxicity on murine macrophage

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    Objectives To evaluate the effects of three acids on the microhardness of set mineral trioxide aggregate (MTA) and root dentin, and cytotoxicity on murine macrophage. Materials and Methods OrthoMTA (BioMTA) was mixed and packed into the human root dentin blocks of 1.5 mm diameter and 5 mm height. Four groups, each of ten roots, were exposed to 10% citric acid (CA), 5% glycolic acid (GA), 17% ethylenediaminetetraacetic acid (EDTA), and saline for five minutes after setting of the OrthoMTA. Vickers surface microhardness of set MTA and dentin was measured before and after exposure to solutions, and compared between groups using one-way ANOVA with Tukey test. The microhardness value of each group was analyzed using student t test. Acid-treated OrthoMTA and dentin was examined by scanning electron microscope (SEM). Cell viability of tested solutions was assessed using WST-8 assay and murine macrophage. Results Three test solutions reduced microhardness of dentin. 17% EDTA demonstrated severe dentinal erosion, significantly reduced the dentinal microhardness compared to 10% CA (p = 0.034) or 5% GA (p = 0.006). 10% CA or 5% GA significantly reduced the surface microhardness of set MTA compared to 17% EDTA and saline (p < 0.001). Acid-treated OrthoMTA demonstrated microporous structure with destruction of globular crystal. EDTA exhibited significantly more cellular toxicity than the other acidic solutions at diluted concentrations (0.2, 0.5, 1.0%). Conclusions Tested acidic solutions reduced microhardness of root dentin. Five minute's application of 10% CA and 5% GA significantly reduced the microhardness of set OrthoMTA with lower cellular cytotoxicity compared to 17% EDTA
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