41 research outputs found
Use of multifunctional phosphorylated PAMAM dendrimers for dentin biomimetic remineralization and dentinal tubule occlusion
No full textThe disequilibrium between demineralization and remineralization of teeth, especially of dentin, may lead to serious consequences like dental caries that are considered to affect people's quality of life. The employment of biomimetic analogs of proteins to duplicate biomineralization, which is a well-regulated process mediated by extracellular matrix proteins, may provide new insights to solve these problems. Here we report the use of a modified multifunctional dendrimer, synthesized by the introduction of phosphate groups via a Mannich-type reaction onto poly(amidoamine) (PAMAM) dendrimers, to biomimetically remineralize dentin. The phosphorylated PAMAM dendrimers were demonstrated to act, along with an amorphous calcium phosphate stabilizing agent, polyacrylic acid (PAA), as biomimetic analogs of noncollagenous proteins to induce the remineralization of demineralized dentin. Phosphorylated PAMAM dendrimers treated demineralized dentin discs were immersed in a remineralizing solution containing PAA for up to 7 days. The success of this remineralization was examined using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and electron microscopy. These results showed that demineralized dentinal collagen fibrils were successfully phosphorylated by the treatment of phosphorylated PAMAM dendrimers and embedded with calcium-deficient hydroxyapatite after remineralization. The surfaces of demineralized dentin discs were covered with newly induced crystals and the patent dentinal tubules were occluded. A good biocompatibility was also determined. Thus, phosphorylated PAMAM dendrimers could be applied as a minimally invasive method of management of dentin caries, employed to improve the resin-dentin bonding stability and also be used in the treatment of dentin hypersensitivity.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348986900037&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Chemistry, MultidisciplinarySCI(E)[email protected]
Use of poly (amidoamine) dendrimer for dentinal tubule occlusion: a preliminary study.
No full textThe occlusion of dentinal tubules is an effective method to alleviate the symptoms caused by dentin hypersensitivity, a significant health problem in dentistry and daily life. The in situ mineralization within dentinal tubules is a promising treatment for dentin hypersensitivity as it induces the formation of mineral on the sensitive regions and occludes the dentinal tubules. This study was carried out to evaluate the in vitro effect of a whole generation poly(amidoamine) (PAMAM) dendrimer (G3.0) on dentinal tubule occlusion by inducing mineralization within dentinal tubules. Dentin discs were treated with PAMAM dendrimers using two methods, followed by the in vitro characterization using Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM) and Energy-Dispersive X-ray Spectroscopy (EDS). These results showed that G3.0 PAMAM dendrimers coated on dentin surface and infiltrated in dentinal tubules could induce hydroxyapatite formation and resulted in effective dentinal tubule occlusion. Moreover, crosslinked PAMAM dendrimers could induce the remineralization of demineralized dentin and thus had the potential in dentinal tubule occlusion. In this in vitro study, dentinal tubules occlusion could be achieved by using PAMAM dendrimers. This could lead to the development of a new therapeutic technique for the treatment of dentin hypersensitivity
Transcriptional activation of the senescence regulator Lsh by E2F1
No full textLsh, a protein related to the SNF2 family of chromatin-remodeling ATPases, is a major epigenetic regulator that is essential for DNA methylation and histone acetylation at repetitive elements. Lsh represses endogenous p16(INK4a) expression by recruiting HDAC to the p(16IN4Ka) promoter, which in turn delays cell senescence. However, the molecular mechanisms that govern loss of Lsh expression during cellular senescence have yet to be elucidated. Here we investigate the transcriptional regulation of the human Lsh promoter. We find that the minimal Lsh promoter is located between positions -216 and -119 relative to the transcription start site, and contains two putative E2F binding sites. Ectopic E2F1 increases expression of Lsh at both transcriptional and translational levels. E2F1 physically interacts with the Lsh promoter by binding to each of the two putative binding sites and transactivates the Lsh promoter. E2F1 also induces Lsh protein expression and transactivates the Lsh promoter in 2BS cells. At the same time, E2F1-induced Lsh promoter activity is reduced in senescent cells compared to young cells. These results indicate that E2F1 plays a crucial role in transcriptional control of the human Lsh gene and the decrease of Lsh expression in senescent cells is related to the repression of E2F1. Published by Elsevier Ireland Ltd.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000291628000006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cell BiologyGeriatrics & GerontologySCI(E)PubMed2ARTICLE4180-18613
Tcf4 Controls Neuronal Migration of the Cerebral Cortex through Regulation of Bmp7
No full textAbstractBackground: Transcription factor 4 (TCF4) is found to be associated with schizophrenia. TCF4 mutations also cause Pitt-Hopkins Syndrome, a neurodevelopmental disorder associated with severe mental retardation. However, the function of TCF4 during brain development remains unclear. Results: Here, we report that Tcf4 is expressed in the developing cerebral cortex. In utero suppression of Tcf4 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. Knockdown of Tcf4 impaired leading process formation. Furthermore, Bone Morphogenetic Protein 7 (Bmp7) is upregulated in Tcf4-deficient neurons. In vivo gain of function and rescue experiments demonstrated that Bmp7 is the major downstream effector of Tcf4 required for neuronal migration. Conclusion: Thus, we have uncovered a new Tcf4/Bmp7-dependent mechanism underlying neuronal migration, and provide insights into the pathogenesis of neurodevelopmental disorders
Shared and divergent contribution of vitamin A and oxytocin to the aetiology of autism spectrum disorder
No full textRare genetic variations contribute to the heterogeneity of autism spectrum disorder (ASD) and the responses to various interventions for ASD probands. However, the associated molecular underpinnings remain unclear. Herein, we estimated the association between rare genetic variations in 410 vitamin A (VA)-related genes (VARGs) and ASD aetiology using publicly available de novo mutations (DNMs), rare inherited variants, and copy number variations (CNVs) from about 50,000 ASD probands and 20,000 normal controls (discovery and validation cohorts). Additionally, given the functional relevance of VA and oxytocin, we systematically compared the similarities and differences between VA and oxytocin with respect to ASD aetiology and evaluated their potential for clinical applications. Functional DNMs and pathogenic CNVs in VARGs contributed to ASD pathogenesis in the discovery and validation cohorts. Additionally, 324 potential VA-related biomarkers were identified, 243 of which were shared with previously identified oxytocin-related biomarkers, while 81 were unique VA biomarkers. Moreover, multivariable logistic regression analysis revealed that both VA- and oxytocin-related biomarkers were able to predict ASD aetiology for individuals carrying functional DNM in corresponding biomarkers with an average precision of 0.94. As well as, convergent and divergent functions were also identified between VA- and oxytocin-related biomarkers. The findings of this study provide a basis for future studies aimed at understanding the pathophysiological mechanisms underlying ASD while also defining a set of potential molecular biomarkers for adjuvant diagnosis and intervention in ASD
An in vitro study evaluating the effect of ferrule design on the fracture resistance of endodontically treated mandibular premolars after simulated crown lengthening or forced eruption methods
No full textAbstract Background The purpose of this study was to evaluate the effect of ferrule design on the fracture resistance of endodontically treated mandibular first premolars after simulated crown lengthening and orthodontic forced eruption methods restored with a fiber post-and-core system. Methods Forty extracted and endodontically treated mandibular first premolars were decoronated to create lingual-to-buccal oblique residual root models, with a 2.0 mm height of the lingual dentine wall coronal to the cemento-enamel junction, and the height of buccal surface at the cemento-enamel junction. The roots were divided randomly into five equal groups. The control group had undergone incomplete ferrule preparation in the cervical root, with 0.0 mm buccal and 2.0 mm lingual ferrule lengths (Group F0). Simulated surgical crown lengthening method provided ferrule preparation of 1.0 mm (Group CL/F1) and 2.0 mm (Group CL/F2) on the buccal surface, with ferrule lengths of 3.0 mm and 4.0 mm on the lingual surface, respectively. Simulated orthodontic forced eruption method provided ferrule preparation of 1.0 mm (Group OE/F1) and 2.0 mm (Group OE/F2) on the buccal surface and ferrule lengths of 3.0 mm and 4.0 mm on the lingual surface, respectively. After restoration with a glass fiber post-and-core system and a cast Co-Cr alloy crown, each specimen was embedded in an acrylic resin block to a height on the root 2.0 mm from the apical surface of the crown margin and loaded to fracture at a 135° angle to its long axis in a universal testing machine. Data were analyzed statistically using two-way ANOVA with Tukey HSD tests and Fisher’s test, with α = 0.05. Results Mean fracture loads (kN) for groups F0, CL/F1, CL/F2, OE/F1 and OE/F2 were as follows: 1.01 (S.D. = 0.26), 0.91 (0.29), 0.73 (0.19), 0.96 (0.25) and 0.76 (0.20), respectively. Two-way ANOVA revealed significant differences for the effect of ferrule lengths (P = 0.012) but no differences for the effect of cervical treatment methods (P = 0.699). The teeth with no buccal ferrule preparation in control group F0 had the highest fracture resistance. In contrast, the mean fracture loads for group CL/F2 with a 2.0-mm buccal and 4.0-mm lingual ferrule created by simulated crown lengthening method were lowest (P = 0.036). Conclusions Increased apically complete ferrule preparation resulted in decreased fracture resistance of endodontically treated mandibular first premolars, regardless of whether surgical crown lengthening or orthodontic forced eruption methods been used
An in vitro study evaluating the effect of ferrule design on the fracture resistance of endodontically treated mandibular premolars after simulated crown lengthening or forced eruption methods
No full textComposition of Simulated Body Fluid (SBF).
No full text<p>Composition of Simulated Body Fluid (SBF).</p
Mechanism of glutaraldehyde crosslinking.
No full text<p>(A) Chemical reaction equation. (B) Schema chart that reveals the process of PAMAM dendrimers crosslinked to demineralized dentinal collagen by using glutaraldehyde.</p
SEM images of the remineralization of demineralized dentin discs.
No full text<p>(A, B) Dentin discs demineralized with neutral EDTA solution for 72h. (C, D) EDTA demineralized dentin discs crosslinked with G3.0 PAMAM dendrimers using 0.25% glutaraldehyde for 24h, exhibiting a “corn-on-the-cob” appearance. (E, F) Flake-like crystals were induced on the surface and covered the wall of dentinal tubules after PAMAM crosslinked dentin discs were treated with SBF for 1w, with dentinal tubules still left patent. (Insert of (E)) EDS showed the Ca/P molar ratio of the mineral crystals was 1.59±0.05. (G, H) No significant mineral crystals formed on the demineralized dentin discs after they were immersed in SBF for 1w, without treated with PAMAM dendrimers.</p
