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Min Y.,Wuhan UniversityWuhanChina | Ma J.-Z.,Huazhong University of Science and Technology | Cheung G.S.-P.,Comprehensive Dental CareUniversity of Hong KongHong KongChina | Gao Y.,State Key Laboratory of Oral Diseases
Scanning | Year: 2016

The aim of this study was to investigate the clinical negotiation of various apical anatomic features of the mandibular first molars in a Chinese population using micro-computed tomography (micro-CT). A total of 152 mandibular first molars were scanned with micro-CT at 30μm resolution. The apical 5mm of root canal (ARC) was reconstructed three dimensionally and classified. Subsequently, the access cavity was prepared with the ARC anatomy blinded to the operator. The ARC was negotiated with a size 10K file with or without precurve. Information on the ability to obtain a reproducible glide path was recorded. The anatomical classification of ARC was Type I with 68.45% in mandibular first molars. The negotiation result of ARC with Category i was 387 canals (74.00%). With a bent negotiating file, 96 canals were negotiated, including 88 reproducible glide paths (Category ii) and 8 irregular glide paths (Category iii). About 7.65% canals could not be negotiated with patency successfully (Category iv). The statistical analyze shown the anatomic feature of ARC had effect on the negotiation of ARC (p<0.05). In conclusion, ARC anatomic variations had a strong potential impact on the negotiation. The category of negotiation in ARC would be helpful in the using of NiTi rotary instruments. Negotiation of ARC to the working length with patency should be careful and skillful because of the complexities of ARC. © Wiley Periodicals, Inc.

Meng W.,State Key Laboratory of Oral Diseases | Meng W.,Southern Medical University | Wu Y.,State Key Laboratory of Oral Diseases | Wu Y.,Chongqing Medical University | And 12 more authors.
Cancer Research | Year: 2014

The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-β receptor III (TβRIII) is found as an epithelial-mesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TβRIII in the oral cancerous epithelial cells and their adjacent carcinoma-Associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TβRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies. © 2014 American Association for Cancer Research.

Yu J.-H.,University of Cooperative Education | Zhu L.-W.,University of Cooperative Education | Xia S.-T.,University of Cooperative Education | Li H.-M.,University of Cooperative Education | And 3 more authors.
Biotechnology and Bioengineering | Year: 2016

To balance the flux of an engineered metabolic pathway to achieve high yield of target product is a major challenge in metabolic engineering. In previous work, the collaborative regulation of CO2 transport and fixation was investigated with co-overexpressing exogenous genes regulating both CO2 transport (sbtA and bicA) and PEP carboxylation (phosphoenolpyruvate (PEP) carboxylase (ppc) and carboxykinase (pck)) under trc promoter in Escherichia coli for succinate biosynthesis. For balancing metabolic flux to maximize succinate titer, a combinatorial optimization strategy to fine-tuning CO2 transport and fixation process was implemented by promoter engineering in this study. Firstly, based on the energy matrix a synthetic promoter library containing 20 rationally designed promoters with strengths ranging from 0.8% to 100% compared with the widely used trc promoter was generated. Evaluations of rfp and cat reporter genes provided evidence that the synthetic promoters were stably and had certain applicability. Secondly, four designed promoters with different strengths were used for combinatorial assembly of single CO2 transport gene (sbtA or bicA) and single CO2 fixation gene (ppc or pck) expression. Three combinations, such as Tang1519 (P4-bicA+pP19-pck), Tang1522 (P4-sbtA+P4-ppc), Tang1523 (P4-sbtA+P17-ppc) with a more than 10% increase in succinate production were screened in bioreactor. Finally, based on the above results, co-expression of the four transport and fixation genes were further investigated. Co-expression of sbtA, bicA, and ppc with weak promoter P4 and pck with strong promoter P19 (AFP111/pT-P4-bicA-P4-sbtA+pACYC-P19-pck-P4-ppc) provided the best succinate production among all the combinations. The highest succinate production of 89.4g/L was 37.5% higher than that obtained with empty vector control. This work significantly enhanced succinate production through combinatorial optimization of CO2 transport and fixation. The promoter engineering and combinatorial optimization strategies used herein represents a powerful approach to tailor-making metabolic pathways for the production of other industrially important chemicals. © 2016 Wiley Periodicals, Inc.

Wu H.,State Key Laboratory of Oral Diseases | Wu H.,University of Sichuan | Lin J.,Beijing Chaoyang Hospital | Zhou L.,State Key Laboratory of Oral Diseases | And 3 more authors.
Journal of Craniofacial Surgery | Year: 2010

Classification of gummy smile was tried first according to gingival exposure site during posed smile, then several items were measured on cephalometric radiograph to analyze the morphologic features in both sexes and further divided into subgroups. Two hundred twenty-eight adolescents with gingival display of more than 2 mm during smile were clustered according to gingival exposure site. Measurements of 18 pertinent items with great clinical concern or controversy in previous study in each groups were compared with corresponding references. Four distinctive types of gummy smile could be distinguished, and they exposed a continuous band, posterior parts, and one side or anterior part of upper gingiva, respectively. The type exposing a continuous band of upper gingiva took up the majority (200 cases, 88%) of all subjects and were chosen for further cephalometric analysis. Among the characteristic features of gummy smile, adolescents have skeletal class II relationship, vertical growth pattern, retrusive mandible, excessive anterior maxillary height, labially inclined upper incisors and upper lip, great overjet and overbite, and relatively short lip compared with anterior maxillary height. Skeletal class III relationship and horizontal growth pattern were absolutely absent. As a result, treatment planning should be adjusted according to the exposure site and craniofacial feature of each individual patient to obtain the best result. Copyright © 2010 by Mutaz B. Habal, MD.

Chen W.,State Key Laboratory of Oral Diseases | Tang Y.,State Key Laboratory of Oral Diseases | Zheng M.,State Key Laboratory of Oral Diseases | Jiang J.,State Key Laboratory of Oral Diseases | And 4 more authors.
Molecular Medicine Reports | Year: 2013

To investigate the mechanism of cartilage degradation induced by overloading in the temporomandibular joint (TMJ), the effect of cyclic mechanical compressive stress on the activity of plasminogen activator (PA) and the expression of the predominant components of the PA system were analyzed in cultured mandibular condylar chondrocytes (MCCs) in rats. MCCs were exposed to cyclic mechanical compressive stress (2000, 4000 and 6000 ? strain) at 0.5 Hz by a four-point bending system. The activity of PA was determined by hydrolysis of the chromogenic substrate H-D-Val-Leu-Lys-pNA (S-2251). The mRNA and protein expression levels of urokinase-type PA (uPA), tissue-type PA (tPA), uPA receptor (uPAR) and PA inhibitor 1 (PAI-1) were detected by qPCR and western blot analysis, respectively. Cyclic mechanical stress at 4000 and 6000 ? strain induced the expression of uPA, tPA and uPAR, and increased the activity of PA. Furthermore, cyclic mechanical stress at 6000 ? strain also inhibited the expression of PAI-1. Analysis of pericellular proteolytic activity demonstrated that PA functioned as the active enzyme in excessive mechanical stress responsiveness (e.g., 4000 and 6000 ? strain) largely via uPAR, not PAI-1. Cyclic mechanical stress at 2000 ? strain induced the expression of tPA and PAI-1; however, it did not change the activity of PA. These results suggested that the mechanical induction of uPA, tPA and uPAR upregulated PA activity, which may provide a proteolytic environment of extracellular matrix components and subsequently contribute to the cartilage degradation in TMJ osteoarthritis.

Tan Y.-Y.,Chongqing Medical University | Bai S.,Chongqing Medical University | Liao Y.-M.,State Key Laboratory of Oral Diseases
Chinese Journal of Tissue Engineering Research | Year: 2014

Background: With the development of tissue engineering, porous bioceramics are more and more used to repair bone defects. Current research focuses on the biological synthesis of this bioceramics and its performance evaluation. Objective: To discuss the preparation of a new kind of bone cement and to determine its physicochemical properties and biocompatibility with osteoblasts. Methods: Biphasic tricalcium phosphate powders were prepared using co-precipitation method. The powder was turned into granular stuff by arabic gum. After sintering, porous hydroxyapatite/tricalcium phosphate bioceramics were harvested, and then mixed with alpha-hemihydrate to prepare the bone cement. Results and Conclusion: X-ray diffraction confirmed that the synthetic substance was a kind of biphasic calcium phosphate ceramic having a porous structure. The bone cement could be in the plastic state within 3 minutes. The curing time was 15 minutes, and the curing temperature was 36.5 °C. The maximum compression strength was 5.82 MPa, and the MTT toxicity was level 0. Osteoblasts could grew well on the material surface.

Jiang Y.,University of Sichuan | Long H.,University of Sichuan | Long H.,State Key Laboratory of Oral Diseases | Li T.,University of Sichuan | And 3 more authors.
Journal of Parasitology | Year: 2012

To investigate whether schistosomiasis can contribute to appendiceal goblet cell carcinoid, appendix samples were obtained from 3 patients with combined appendiceal schistosomiasis and goblet cell carcinoid (CSG), 6 patients with goblet cell carcinoid only (GCC), 12 patients with appendiceal schistosomiasis only (ASO), and 12 cases with normal appendix (NA), all of similar gender ratio and age distributions. Hematoxylin and eosin-(H&E) stained sections were studied in 3 CSGs and 12 ASOs to diagnose schistosomiasis by detecting schistosome eggs. H&E and alcian blue/PAS-stained sections and immunohistochemistry of CgA and CEA were employed to establish the diagnosis of GCC in the 3 CSGs and 6 GCCs. Then, to determine whether schistosomiasis can contribute to GCC, immunostaining patterns of CgA and Ki67 in mucosal crypt epithelia were investigated and compared among all 33 cases. Our results revealed typical histological and immunohistochemical phenotypes of GCC in the 3 CSGs and 6 GCCs and schistosome egg deposits in 3 CSGs and 12 ASOs. We found that the expression levels of both CgA and Ki67 in mucosal crypt epithelia were significantly higher in CSG than in GCC (P < 0.05 0.013 and P 0.004, respectively). Moreover, high expression levels of both CgA and Ki67 in mucosal crypt epithelia favor ASO as compared to NA (P < 0.001 3.4 × 10 -6 and 3.1 × 10-5, respectively). Our findings suggest that appendiceal schistosomiasis was associated with increased proliferation and neuroendocrine differentiation of mucosal pluripotent crypt cells and that it may contribute to GCC, which is documented to originate from mucosal pluripotent crypt cells in mucosal crypt epithelia. © 2012 American Society of Parasitologists.

PubMed | State Key Laboratory of Oral Diseases
Type: Journal Article | Journal: International endodontic journal | Year: 2015

To investigate the effects of mammalian homologue of Drosophila diaphanous-1(mDia1) and Rho-associated coiled-coil-containing protein kinase (ROCK) on the migration and adhesion of dental pulp cells (DPCs).Lysophosphatidic acid (LPA) was used to activate Rho signalling. mDia1 and ROCK were inhibited by short interfering RNA and the specific inhibitor, Y-27632, respectively. The migration of DPCs was assessed using the transwell migration assay and scratch test. Formation of cytoskeleton and focal adhesions(FAs) was observed by confocal laser scanning microscopy. Cell adhesion and spreading assays were performed. Phosphorylation of focal adhesion kinase (FAK) and paxillin was detected by Western blotting, and the bands were analysed using Adobe Photoshop CS5 software. All experiments were performed at least three times, and data were analysed with one-way anova and a post hoc test.LPA-triggered activation of Rho and inhibition of ROCK significantly increased the cell migration rate. Cell migration was inhibited by silencing mDia1. mDia1 silencing and ROCK inhibition suppressed the LPA-induced formation of the cytoskeleton, FA and phosphorylation of FAK and paxillin. Inhibition of ROCK or mDia1 facilitated early cell adhesion and spreading; by contrast, the combined inhibition of ROCK and mDia1 neutralized these effects.mDia1 promoted RhoA-induced migration of DPCs, but ROCK had an opposite effect. Both mDia1 and ROCK participated in cytoskeleton formation and adhesion of DPCs. The interactions between mDia1 and ROCK might influence dental pulp repair by determining the migration and adhesion of DPCs.

PubMed | State Key Laboratory of Oral diseases, University of Sichuan, University of Bonn, University College West and Chongqing Medical University
Type: | Journal: Archives of oral biology | Year: 2016

The aim of this study was to analyze and compare the expression patterns of human -defensin-4 (hBD-4) with those of hBD-1, hBD-2, and hBD-3 in healthy and chronically inflamed gingival tissues.A total of 96 gingival samples were collected, comprising 46 biopsies from chronic periodontitis (CP) patients and 50 from individuals with healthy tissue. Of these, 21CP and 21 healthy samples were used to examine the protein expression of the hBDs by immunohistochemistry. The remaining 25CP and 29 healthy tissue samples were subjected to real-time reverse transcription polymerase chain reaction to quantify the mRNA expression of the hBDs.All four types of -defensin peptides were confined to the gingival epithelia. The percentage of samples positive for hBD-4 mRNA was significantly lower than the percentages for the other three -defensins, both in healthy (p=0.003) and in inflamed (p=0.030) gingiva. However, in the case of the relative mRNA expression levels, that of hBD-4 was significantly higher than the levels for hBD-2 (healthy group: p<0.01; CP group: p<0.01) and hBD-3 (healthy group: p=0.004; CP group: p<0.01).Our study demonstrates differential expression of hBD-1, hBD-2, hBD-3, and hBD-4 in healthy and CP gingiva.

PubMed | State Key Laboratory of Oral Diseases
Type: Journal Article | Journal: Medical hypotheses | Year: 2011

The clinical use of dental implants has a high success rate, but overload-induced bone loss around implant is not uncommon in patients with implant-supported denture especially those with long cantilever designs and greatly harmful to the long-term implant success. The mechanism underlying the bone loss is thought to be the imbalance of bone remodeling involving a detrimental positive feedback activated by overloading. While surgical regenerative treatments may be useful in promoting bone regeneration, extra suffering and risk of infection have to be fully recognized. To date, no optimal method is available to solve this problem. We hereby propose a novel therapy that may potentially improve this condition. Many studies have shown that parathyroid hormone (PTH), an anabolic agent targeting bone, is effective in reversing bone loss caused by osteoporosis with negative bone remodeling in clinical studies. Moreover, PTH has the potential to accelerate the bone healing in patients with fracture and fracture nonunion and improve osseointegration of implant inserted in pre-existed bone defect via its anabolic effect to increase bone formation in animal model studies. Specifically for alveolar bone, PTH is associated with effective bone regeneration in patients with severe periodontitis. What is more, PTH and mechanical loading has a synergistic effect on bone formation, which is in favor of bone healing under physiological loading. The mechanisms underlying its anabolic effect may involve increased osteoblasts activity, prolonged osteoblasts life-span and recruitment of new osteoblasts from marrow stromal cells. Furthermore, PTH could activate resting lining cells to initial de novo bone formation. Considering these actions of PTH, we hypothesize that PTH may be a potential treatment for overload-induced bone loss around implant.

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