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Purpose: Wogonin, a plant flavonoid, has antitumor activity in various cancers. Dysregulation of GSK-3β has been implicated in tumorigenesis and cancer progression. In this study, we investigated the antitumor activity and the mechanistic action of wogonin in human nasopharyngeal carcinoma (NPC) cells. Methods: The effects of wogonin on the cell survival and apoptosis in NPC cells were investigated by MTS assay, flow cytometry, and PARP cleavage assays. Pharmacological inhibitors (BIO, LiCl, and OA), or small interfering RNA (siRNA) were used to address the expression status of GSK-3β and the anticancer effect of ΔNp63 in NPC cells. Results: Wogonin was shown to induce dose-dependent cell apoptosis due to the induction of sub-G1-phase cells, PARP cleavage, and downregulation of ΔNp63, a survival factor in NPC cells. Strikingly, the apoptotic effect of wogonin involved GSK-3β inactivation via prominent inhibition of phosphorylation at Tyr216 and slightly increment of phosphorylation at Ser9, while there is no change in total GSK-3β proteins. Dysregulation of GSK-3β caused cell apoptosis was confirmed by pharmacological inhibitors (lithium chloroid, LiCl, and 6-bro-moindirubin-3-oxime, BIO). Administration of okadaic acid (OA, a protein phosphatase inhibitor) that significantly inactivated GSK-3β also induced ΔNp63 downregulation and apoptosis. Targeted silencing of ΔNp63 repressed the phosphorylation of GSK-3β at Tyr216 and sensitized NPC cells to wogonin-induced apoptosis. Furthermore, GSK-3β or PP2A inhibitors enhanced wogonin-induced apoptosis via activation of caspase 3/7. Conclusion: These results indicate that GSK-3β, as well as ΔNp63, are novel targets for wogonin action and suggest that wogonin might provide a potential therapeutic option in NPC. Further in vitro and in vivo studies will help to clarify the therapeutic role of wogonin in NPC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate a near-infrared-to-blue luminescence upconversion curing method for polymerizing resin cements under zirconia discs., Methods: Lava zirconia discs of different thicknesses (0.5-2.0 mm) were manufactured. First, the transmittances of the NIR and two blue lights (BLs) (LED and halogen lights) through these discs were measured. Second, NaYF 4 :Yb 3+ /Tm 3+ upconversion phosphor (UP) powder was milled into 0.5-μm particle sizes. A light-curable resin cement VariolinkII base was chosen as the control (UP0), and an experimental cement (UP5) was prepared by adding 5 % UPs. These two cements were examined using multiphoton excitation microscopy for particle distribution. UP5 and UP0 were polymerized with or without zirconia shielding then subjected to a microhardness test. A multifold analysis was performed to examine the effects of zirconia thickness, curing protocols (pure BL or combined BL and NIR curing), and cement type., Results: The transmittance of NIR was superior to that of BL through zirconia discs of all thicknesses. UP particles were homogeneously distributed in UP5 and emitted blue luminescence under 980-nm NIR excitation. UP5 showed higher microhardness values than UP0 under any curing protocol or zirconia shielding condition. The combination of 20-s BL and 40-s NIR curing yielded the highest microhardness in uncovered UP5. However, combining 40-s BL and 20-s NIR curing surpassed the other groups when the zirconia discs were thicker than 0.5 mm., Significance: NIR exhibits higher transmission through zirconia than BL. UP particles work as strengthen fillers and photosensitizers in cements. NIR upconversion curing could be a new strategy for polymerizing resin cements under thick zirconia restorations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To examine the polymerization shrinkage of different resin-based composite (RBC) restorations using optical coherence tomography (OCT) image-based digital image correlation (DIC) analysis., Methods: The refractive index (RI) of three RBCs, Filtek Z350XT (Z350), Z350Flowable (Z350F), and BulkFill Posterior (Bulkfill), was measured before and after polymerization to calibrate their axial dimensions under OCT. Class I cavities were prepared in bovine incisors and individually filled with these RBCs under nonbonded and bonded conditions. A series of OCT images of these restorations were captured during 20-s light polymerization and then input into DIC software to analyze their shrinkage behaviors. The interfacial adaptation was also examined using these OCT images., Results: The RI of the three composites ranged from 1.52 to 1.53, and photopolymerization caused neglectable increases in the RI values. For nonbonded restorations, Z350F showed maximal vertical displacements on the top surfaces (-16.75 µm), followed by Bulkfill (-8.81 µm) and Z350 (-5.97 µm). In their bonded conditions, all showed increased displacements. High variations were observed in displacement measurements on the bottom surfaces. In the temporal analysis, the shrinkage of nonbonded Z350F and Bulkfill decelerated after 6-10 s. However, Z350 showed a rebounding upward displacement after 8.2 s. Significant interfacial gaps were found in nonbonded Z350 and Z350F restorations., Significance: The novel OCT image-based DIC analysis provided a comprehensive examination of the shrinkage behaviors and debonding of the composite restorations throughout the polymerization process. The flowable composite showed the highest shrinkage displacements. Changes in the shrinkage direction may occur in nonbonded conventional composite restorations., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the feasibility of optical coherence tomography (OCT)-based digital image correlation (DIC) analysis and to identify the experimental parameters for measurements of polymerization shrinkage., Methods: Class I cavities were prepared on bovine incisors and filled with Filtek Z350XT Flowable (Z350F). One OCT image of the polymerized restoration was processed to generate virtually displaced images. In addition, the tooth specimen was physically moved under OCT scanning. A DIC software analyzed these virtual and physical transformation sets and assessed the effects of subset sizes on accuracy. The refractive index of unpolymerized and polymerized Z350F was measured via OCT images. Finally, different particles (70-80 µm glass beads, 150-212 µm glass beads, and 75-150 µm zirconia powder) were added to Z350F to inspect the analyzing quality., Results: The analyses revealed a high correlation (>99.99%) for virtual movements within 131 pixels (639 µm) and low errors (<5.21%) within a 10-µm physical movement. A subset size of 51 × 51 pixels demonstrated the convergence of correlation coefficients and calculation time. The refractive index of Z350F did not change significantly after polymerization. Adding glass beads or zirconia particles caused light reflection or shielding in OCT images, whereas blank Z350F produced the best DIC analysis results., Significance: The OCT-based DIC analysis with the experimental conditions is feasible in measuring polymerization shrinkage of RBC restorations. The subset size in the DIC analysis should be identified to optimize the analysis conditions and results. Uses of hyper- or hypo-reflective particles is not recommended in this method., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/purpose: Nowadays, zirconia-based framework has been used for longspan or full-arch fixed dental prostheses (FDPs). This study aimed to evaluate the effect of pontic distribution on marginal and internal gaps of five-unit anterior zirconiabased DPs., Materials and Methods: Right maxillary central incisor and second premolar were selected as terminal abutments and three different edentulous conditions with one nonterminal abutment were simulated. Marginal and internal gaps in each zirconia-based samples(n = 10) were examined by computer-aided replica technique. Five regions, including marginal gaps at mesial or distal finishing line, internal gaps at the mesial or distal axial wall, and occlusal surface, were statistically analyzed (α = .05)., Results: Most of marginal gaps and internal gaps at axial wall were clinically acceptable, but larger at occlusal surface. For the three experimental groups, clinically accepted percentage with qualified gaps were less than 30%.There were statistical differences at axial wall over pontic side and marginal gaps over non-pontic side between groups ( P <0.05). For sum of gaps of all abutments in each group, statistical differences were found at marginal and axial wall ( P  < 0.05). As for those on terminal and non-terminal abutments, statistical differences were found on second premolar ( P < 0.05)., Conclusion: Except for occlusal surface, the overall marginal gaps and internal gaps at axial wall of five-unit anterior zirconia-based FDPs with different pontic distribution were clinically acceptable. However, the percentage with qualified gaps were low (<30%). Greater gaps were noted when adjacent pontic existed. Different pontic size and distribution with curvature had an influence on the gaps., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Objectives: To investigate the shrinkage-induced damage at the composite-tooth interface by finite element analysis (FEA) using the cohesive zone model (CZM)., Methods: Axisymmetric models of Class I restorations were created to illustrate the interfacial damage around composite resin restorations of different dimensions, with polymerization shrinkage modeled analogously to thermal shrinkage. The damage to the adhesive interface was determined using a CZM based on the fracture strength and fracture energy. To show the effects of damage, conventional models with perfectly bonded composite resin restorations were created as controls., Results: The results indicated interfacial damage at the butt-joint cavosurface margin, dentinoenamel junction, and internal line angle. The percentage of damaged interfacial area was found to increase with decreasing diameter for restorations of the same height. For a given diameter, the damage was more severe for restorations of greater depth. The effects of the damage were further illustrated in the model with a restoration of 2-mm diameter and height. The interfacial damage occurred primarily at the internal line angle (83.3 % of all the damaged interfacial area), leading to local stress relief (from 18.3 MPa to 12.8 MPa), but also higher stress at the damage fronts. Greater local shrinkage was found in composites adjacent to the damage., Significance: The damage mechanics-based CZM is an essential refinement of the FEA to predict interfacial damage and its implications. The extent of damage was found to be greater around restorations with smaller diameters and greater depths. The entire simulation is available via an open-source platform to facilitate further applications in adhesive dentistry., (Copyright © 2023 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Conventional direct pulp capping, such as calcium hydroxide (Ca(OH) 2 ) or silicate products, usually induces an inflammatory reaction to provoke pulp regeneration. Phosphophoryn (PP) and dentin sialoprotein (DSP), the two most abundant non-collagenous proteins in the dentin matrix, are responsible for dentin mineralization, pulp cell migration, and differentiation. Here we examined the PP and combined DSP/PP as bio-inductive pulp capping materials by in vitro and in vivo tests. Firstly, the effects of the PP dose on pulp cell migration and matrix protein expression were examined by an agarose bead test. Secondly, the role of recombinant DSP (recDSP) and recDSP/PP on stimulating DSP-PP transcript expression was examined by RT-PCR. DSPP mRNA was also knocked down by RNA interference (RNAi) to examine their functions on dentin matrix mineralization. Finally, we used ferret animal models to test PP and recDSP/PP acting as capping agents on in vivo pulp responses and reparative dentin formation. The result showed that intermediate-dose PP was the most effective to enhance cell migration and differentiation. RecDSP/PP strongly enhanced the DSP-PP transcript expression, while inhibition of DSPP mRNA expression by siRNAs partially or completely affected dental pulp cell mineralization. The in vivo results showed that intermediate-dose PP and recDSP/PP proteins induced less pulp inflammation and promoted reparative dentin formation. Contrarily, conventional calcium hydroxide induced severe pulp inflammation. With these findings, DSP and PP could serve as capping agents for pulp capping therapy.

The combinations of alumina particle air abrasion (AA) and a 10-methacryloyloxyidecyl-dihyidrogenphosphate (MDP) primer and a tribochemical silica coating (TSC) and a silane-base primer are contemporary pre-cementation treatments for zirconia restorations for bonding with resin cements. However, the stability of zirconia resists the mechanical or chemical preparations. The purpose of this study was to develop an atmospheric-pressure oxygen plasma (OP)-aided silicatization method to enhance the adhesion of resin cements to zirconia. Zirconia discs were prepared to receive surface treatments of different combinations: (1) AA or TSC (2) with or without OP treatment, and (3) a chemical primer (no primer, silane, or a silane-MDP mixture). The surface morphology, hydrophilicity, and chemical compositions were characterized, and the resin-zirconia bond strengths were examined either after 24 h or a thermocycling test. The results indicated that the OP treatment after the TSC facilitated the homogeneous distribution of silane and crosslinking of silica particles, and effectively improved the hydrophilicity. The OP increased the O and Si and reduced the C elemental contents, while the combination of TSC, OP, and silane induced SiO x generation. Among the groups, only the TSC-OP-silane treatment effectively enhanced the bond strength and maintained the adhesion after thermocycling. With these results, the OP aided the silicatization protocol effectively, generated silane crosslinking, and resulted in superior resin-zirconia bond strength and durability compared to the current treatments.

Objective: To investigate the effect of silane contents on their chemical interaction with 10-methacryloyloxydecyl-dihydrogen phosphate (MDP), and affecting the bonding of MDP to zirconia by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and solid-state nuclear magnetic resonance (SSNMR) spectroscopy., Methods: Zirconia (Cercon ht, Dentsply) slabs were prepared and fully sintered. Experimental primers SE-5 and SE-10 were formulated by adding 5 wt% and 10 wt% γ-methacryloxypropyltrimethoxysilane to an MDP-based primer SE BOND (SE), respectively. SE, SE-5, and SE-10 were applied on the assigned zirconia slabs. The chemical compositions on the surface and adhesive interfaces were examined by TOF-SIMS in a depth-profiling mode. Hydrophilicity and resin affinity of treated zirconia were analyzed. The bond strengths to resin cylinder were examined either after 24-h storage or thermocycles. In addition, zirconia powders treated with three primers were assessed by SSNMR spectrometry for the adsorption of MDP., Results: TOF-SIMS analysis showed that SE treatment generated the greatest amount of P-O-Zr related ions, which reduced in SE-5 and SE-10 groups. The 3D ion-images illustrated the generation of ZrO 2 (OH) - ions with silane contents. The SSNMR analysis revealed that the chemical bonding was mainly P-O-Zr ionic bonds in SE but shifted to P-OH-Zr hydrogen bonds in SE-5 and SE-10. SE-5 and SE-10 treated zirconia presented higher hydrophilicity and affinity to resin compared to Zr did. SE showed the highest initial bond strength which significantly decreased after thermocycling., Significance: MDP adsorption onto zirconia via P-O-Zr ionic bond promotes bonding with resin. The silane enhances the hydroxylation of zirconia and impairs the adsorption of MDP, but does not adversely affect the bond durability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The purposes of this study were to investigate whether the presence of silane in universal adhesives affects the functions of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and adhesion to zirconia., Methods: Two silane-containing universal adhesives (Scotchbond Universal (SBU) and Clearfil Universal-Bond (CUB)) and two silane-free adhesives (All-Bond Universal (ABU) and SE-Bond primer (SE)) were individually applied on zirconia disks. Time-of-flight secondary-ion-mass-spectrometry (ToF-SIMS) examined the distributions of MDP- and silane-related ions, as well as evidence of zirconium phosphate (ZrP) compounds, on the surface and interfacial regions using a depth profiling mode. The hydrophilicity and resin wettability of the treated zirconia were examined using a contact angle test. For the shear bond strength (SBS) test, the zirconia disks were air-blasted, treated with the assigned adhesives, and bonded with pre-cured composite cylinders using a resin cement. These resin-zirconia assemblies received a bond test after 24-h storage., Results: Both SBU and CUB exhibited silane-related ions and ZrO 2 (OH) - , but fewer PO - ions in the interfacial regions. CUB had more siloxane-related ions. SE-treated zirconia had abundant PO - ions and particularly high PO 3 - - and ZrP- related ions in the interfacial regions. The silane-free adhesives exhibited a higher affinity to both water and adhesive liquids. SE showed significantly higher SBSs compared to ABU, while SBU and CUB were not statistically different., Significance: The silane content may cause hydroxylation of zirconia and affect MDP adsorption. An acidic pH accelerated the condensation of silanol. The bond performance of the MDP-based adhesive could be influenced by the silane content and other components., (Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Blue light (BL) curing on dental resin composites results in gradient polymerization. By incorporating upconversion phosphors (UP) in resin composites, near-infrared (NIR) irradiation may activate internal blue emission and a polymerization reaction. This study was aimed to evaluate the competency of the NIR-to-BL upconversion luminance in polymerizing dental composites and to assess the appropriate UP content and curing protocol. NaYF 4 (Yb 3+ /Tm 3+ co-doped) powder exhibiting 476-nm blue emission under 980-nm NIR was adapted and ball-milled for 4-8 h to obtain different particles. The bare particles were assessed for their emission intensities, and also added into a base composite Z100 (3M EPSE) to evaluate their ability in enhancing polymerization under NIR irradiation. Experimental composites were prepared by dispensing the selected powder and Z100 at different ratios (0, 5, 10 wt% UP). These composites were irradiated under different protocols (BL, NIR, or their combinations), and the microhardness at the irradiated surface and different depths were determined. The results showed that unground UP (d50 = 1.9 μm) exhibited the highest luminescence, while the incorporation of 0.4-μm particles obtained the highest microhardness. The combined 20-s BL and 20-120-s NIR significantly increased the microhardness on the surface and internal depths compared to BL correspondents. The 5% UP effectively enhanced the microhardness under 80-s NIR irradiation but was surpassed by 10% UP with longer NIR irradiation. The combined BL-NIR curing could be an effective approach to polymerize dental composites, while the intensity of upconversion luminescence was related to specific UP particle size and content. Incorporation of 5-10% UP facilitates NIR upconversion polymerization on dental composites.

Background: Liver transplantation (LT) is one of the widely recognised and leading treatments for end-stage liver disease. Nutrition impacts its success. Total parenteral nutrition (TPN) is usually prescribed for patients recommended prolonged fasting after LT. The supplement of SMOFlipid (soybean oil, MCT oil, olive oil, and fish oil) is easily metabolised to produce energy, and it possesses anti-inflammatory effects; however, SMOFlipid emulsion use raises concerns regarding coagulopathy after LT. This study investigated the postoperative correlation between SMOFlipid and coagulation in LT., Materials and Methods: The medical records of 54 recipients of living donor LT between January 2012 and June 2015 were retrospectively reviewed. Patients with pretransplant platelet count <40,000/μL and >40,000/μL were assigned to the non-SMOFlipid (n = 23) group and the SMOFlipid (n = 31) group, respectively., Results: The coagulation and nutrition profile of patients improved significantly after TPN support. No significant difference was observed in the coagulation profile between SMOFlipid and non-SMOFlipid groups. Although the SMOFlipid group exhibited a higher platelet count than the non-SMOFlipid group on day 7 (P < 0.001), no significant differences were observed in the platelet count on 14 and 30 days after TPN support between the 2 groups., Conclusion: TPN using SMOFlipid after LT is a good strategy for improving nutritional status without increasing the risks of bleeding and coagulation in patients intolerant of early enteral nutrition. Moreover, SMOFlipid use may not cause coagulopathy up to 14 days after LT. Overall, SMOFlipid provides nutritional benefits without increasing the risk of bleeding., Competing Interests: All of authors in this study declared that there were no conflicts of interest., (© 2021 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

Aims/introduction: Obesity and metabolic syndrome are well-known to be associated with multiple chronic diseases. Currently, high-dose liraglutide has been used for weight control in non-diabetic patients. Considering incretin-based therapy is more effective in Asian populations, the effect of low-dose liraglutide in weight control among these non-diabetic groups has not been well evaluated. Our study aimed to evaluate the efficacy of low-dose liraglutide in weight control among Taiwan patients., Materials and Methods: From July 2017 to December 2018, 46 non-diabetic patients with metabolic syndrome were included. They had received low-dose liraglutide at 0.6 or 1.2 mg per day for weight reduction for 12 weeks. After then, changes in bodyweight, waist and metabolic factors were examined. Overt bodyweight reduction was defined as a decrease of >5% within 12 weeks., Results: With 12 weeks of medication use, both groups showed statistical weight reduction. Higher doses of liraglutide had better efficacy, and 44.4% of patients in the liraglutide 1.2 mg group reached overt weight reduction, whereas just 32.1% in the 0.6 mg group had achieved this. Young age was found to be a predictor factor for a positive finding (odds ratio 0.941, P = 0.037). Early responders with decreased bodyweight of >4.2% within the first 4 weeks indicated a better chance to achieve measurable weight reduction., Conclusions: Low-dose liraglutide still has high efficacy in weight reduction in Taiwanese people, especially for those of younger age., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Spinocerebellar ataxia (SCA) type 1 (SCA1) is a rare autosomal dominant disorder that is characterized by worsening of disordered coordination, ataxia of the trunk, and other neurological symptoms. Physical activity improves both mobility and the daily living activities of patients with SCA. Intervention with daily regular treadmill exercise may slow the deterioration of cerebellar neurons in SCA1. Therefore, the signal changes and performance of cerebellar neurons after exercise in SCA1 was investigated in this study. We employed a transgenic mouse model of SCA1, generated by amplifying the cytosine-adenine-guanine trinucleotide repeat expansions, and the mice underwent 1 month of moderate daily treadmill exercise for 1 hour. The rotarod test revealed that the motor function of the SCA1 mice that underwent training was superior to that of the control SCA1 mice, which did not undergo training. Moreover, the cerebellar pathology revealed preserved Purkinje neurons stained by carbindin with an increase of the neuronal Per Arnt Sim domain protein 4, a key regulation in the structural and functional plasticity of neurons, in the excised SCA1 mice relative to the controls. The mechanism was related to an increase of phosphorylation of ribosomal protein S6, a downstream target of the mammalian target of rapamycin pathway, but not to autophagy activation. This study determined that regular treadmill exercise may play a crucial role in the viable support of cerebellar neurons in SCA1., (© 2019 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Introduction: Dental pulp stem cells (DPSCs) are multipotent progenitors for biotechnological practices, but the influences of existing restorations on their viability and differentiation are not well-known. This study was aimed to investigate in vivo and in vitro responses of DPSCs to restorative materials., Methods: Class I cavities were prepared on molars scheduled to be extracted and then restored with a resin-based composite (RBC), a glass ionomer cement, or zinc oxide eugenol. Intact teeth were used as controls. Twelve molars in each group were extracted on day 7 or day 30 after restorations to assess the early or intermediate pulp responses and were then cut in half. One half was processed for histopathological analysis, and the other was used to isolate DPSCs for a colony-forming unit assay and real-time polymerase chain reaction for NANOG, OCT4, and CD44 expression., Results: All restored teeth showed pulp damage at various levels, whereas mild to moderate inflammation persisted in the RBC group until day 30. The existence of DPSCs in the pulp cores of all groups was revealed based on CD44 immunoreactivity. Glass ionomer cement and zinc oxide eugenol did not affect the relative percentages of DPSCs in either early or intermediate stages, whereas RBCs reduced the percentage. The colony-forming units in all restoration groups were comparable with those in the control. Nevertheless, the restorations significantly enhanced OCT4 expression, especially in RBC/day 30., Conclusions: Dental restorations cause mild pulp damage but do not affect DPSC viability. RBC decreases DPSC densities but might increase the stemness of surviving DPSCs through an inflammation-stimulation process., (Copyright © 2019 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disease resulting from the misfolding and accumulation of a pathogenic protein, causing cerebellar dysfunction, and this disease currently has no effective treatments. Far-infrared radiation (FIR) has been found to protect the viability of SCA3 cells by preventing mutant ataxin-3 protein aggregation and promoting autophagy. However, this possible treatment still lacks in vivo evidence. This study assessed the effect of FIR therapy on SCA3 in vivo by using a mouse model over 28 weeks. Control mice carried a healthy wild-type ATXN3 allele that had a polyglutamine tract with 15 CAG repeats (15Q), whereas SCA3 transgenic mice possessed an allele with a pathological polyglutamine tract with expanded 84 CAG (84Q) repeats. The results showed that the 84Q SCA3 mice displayed impaired motor coordination, balance abilities, and gait performance, along with the associated loss of Purkinje cells in the cerebellum, compared with the normal 15Q controls; nevertheless, FIR treatment was sufficient to prevent those defects. FIR significantly improved performance in terms of maximal contact area, stride length, and base support in the forepaws, hindpaws, or both. Moreover, FIR treatment supported the survival of Purkinje cells in the cerebellum and promoted the autophagy, as reflected by the induction of autophagic markers, LC3II and Beclin-1, concomitant with the reduction of p62 and ataxin-3 accumulation in cerebellar Purkinje cells, which might partially contribute to the rescue mechanism. In summary, our results reveal that FIR confers therapeutic effects in an SCA3 transgenic animal model and therefore has considerable potential for future clinical use.

Phosphophoryn (PP) and dentin sialoprotein (DSP) are two of the most abundant dentin matrix non-collagenous proteins, and are derived from dentin sialoprotein-phosphophoryn (DSP-PP) mRNA. Mutations in the DSP-PP gene are linked to dentinogenesis imperfecta II and III. Previously, we reported transient DSP-PP expression in preameloblast cells first, followed by co-expression in preameloblasts and young odontoblasts, and finally sustained expression in odontoblasts. This phenomenon raised the possibility that DSP/PP proteins secreted by preameloblasts might promote dental pulp cell migration toward the dental pulp border and promote dental pulp cell differentiation. To examine the effects of DSP/PP proteins on dental pulp cell development, we investigated:(1) native PP effects on dental pulpcell migration and matrix protein expression; and (2) recombinant DSP/PP protein effects on cell proliferation and differentiation. We found that PP promoted cell migration and the expression of high levels of Col type I and PP in dental pulp cells. The addition of recombinant DSP/PP proteins affected cell proliferation and differentiation in a dental pulp cell line. These findings strongly suggest that DSP/PP may modulate cell migration, cell proliferation and differentiation, thus leading to dentin formation. DSP/PP protein may be useful clinically for pulp tissue regeneration.

Objectives: To evaluate the effects of different atmospheric-pressure plasma (APP) on the physicochemical properties of yttria-stabilized zirconia, and promoting the adhesion of veneering porcelain., Methods: Cercon base zirconia disks were prepared to receive different treatments: as-polished, three APPs (oxygen, OP; argon, AP; and CF 4 , CP), and grit-blasted (GB). Their surface roughness and hydrophilicity were measured, and surface morphology was examined either after treatments, after simulated porcelain firing, or additional thermal etching. X-ray photoelectron spectroscopy (XPS) analysis characterized the surface chemical compositions. Shear bond strength (SBS) tests examined the adhesion between veneering porcelain and zirconia either before or after thermocycling. The layered ceramic disks were also sectioned to inspect the porcelain-zirconia interfaces. Statistical analysis was performed with one-way ANOVA and post hoc Duncan's test., Results: Grit-blasting caused surface damage and increased roughness. All APP-treated disks exhibited deeper grain boundaries and enlarged grain sizes after thermal etching, while CP disks revealed additional particle dispersions. Three APPs rendered the zirconia surface superhydrophilic. XPS spectra of three APP groups revealed increased hydroxyl groups and reduced C-C contents, and CP group especially showed the existence of Z-F bonds. CP exhibited the highest SBS both before and after thermocycling, while AP and GB also showed improved SBSs compared to the as-polished. OP presented reduced SBS, and its cross-sections showed increased microporosities in the veneering porcelain., Significance: APP did not change surface morphology but enhanced wettability. CP and AP improved porcelain-zirconia SBSs, primarily through surface hydroxylation. OP induced the microporosities in porcelain and adversely affected the adhesion., (Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the 3-methacryloyloxypropyltrimethoxysilane (MPS)- and 10-methacryloyloxydecyl-dihydrogen-phosphate (MDP)-base primers, in their single or sequential applications, with regard to modifying zirconia surfaces and improving resin-zirconia adhesion., Methods: Zirconia disks received different treatments: without primer (Zr), MPS-base primer (S), MDP-base primer (M), MPS/MDP mixture (SMmix), MPS followed by MDP (SM), and MDP followed by MPS (MS). The compositions and chemical interactions of the coatings to zirconia were analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and reconstructed 3D ion images. Surface wettability of these coatings to water and resin adhesive was assessed. The shear bond strength (SBS) between resin and the treated zirconia was also examined before and after thermocycling., Results: Groups S and MS presented substantial OH - ions in the coatings and zirconia substrate. PO 2 - and PO 3 - fragments existed in all MDP-treatment groups with various proportions and distributions, while groups M and SM showed higher proportions of PO 3 - and the zirconium phosphate related ions. In 3D ion images, PO 3 - in groups M and SM was denser and segregated to the interface, but was dispersed or overlaid above PO 2 - in SMmix and MS. All the primers increased the surface wettability to water and resin, with M and SM presenting superhydrophilic surfaces. All MDP-treatment groups showed improved SBS before thermocycling, while M and SM retained higher SBS after this., Significance: The MDP-base primer shows a relevant function in facilitating POZr bonding and enhancing resin-zirconia bonding. The co-treated MPS impairs the chemical activity of MDP, especially if it is the final coat., (Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate the effects of light curing protocols on the shrinkage behaviors, contraction stress, and microleakage in composite restorations by an experimental-numerical hybrid analysis., Methods: Three groups of human molars were collected to receive different light-curing protocols: vertical or oblique curing at regular intensity, and vertical curing at reduced intensity. For each tooth, the composite fillings were consecutively placed under unbonded and bonded states, and their shrinkage behaviors were examined with a digital image correlation (DIC) technique. The strains of the unbonded restorations were input into two finite element analysis (FEA) models with settings of the composite as either homogeneous or hardened along polymerization gradients. The preliminary solutions were verified by their individual deformations in the bonded restorations. The interfacial microleakage of restorations was also determined by micro-CT scanning and compared with the FEA results., Results: The bonded restorations showed centripetal shrinkage patterns with greater downward displacements than their unbonded restorations. Vertical curing at regular intensity caused the greatest shrinkage strain, contraction stress, and microleakage among the three protocols. Low-intensity curing reduced overall shrinkage strain and displacements at cervical margin, but did not prevent the formation of microleakage. Oblique curing caused asymmetric shrinkage with the tooth-shielded side revealing less deformation. Setting the polymerization-dependent elastic moduli of the composite enhanced the reliability of FEA., Significance: This hybrid analysis comprehensively examined the polymerization shrinkage behaviors. Both the light intensity and direction affect the shrinkages and contraction stress. Oblique curing decreases shrinkage due to the attenuated irradiation by tooth-shielding rather than modulations of shrinkage direction., (Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients with cardiac arrhythmia were more likely to develop stroke than general population. The therapeutic effect of traditional Chinese medicine (TCM) on the risk of stroke in patients with cardiac arrhythmia was unknown. The aim of this study is to investigate the risk of stroke in patients with cardiac arrhythmia receiving TCM., Methods: From the one million cohort of the Taiwan's National Health Insurance Research Database, we identified cohort of cardiac arrhythmia included 2029 patients who received TCM treatment in 2000-2004. The matching methods with propensity score was used to select 2029 appropriate control cohort for comparison. Incident events of stroke were identified during the follow-up period at the end of 2010. Cox proportional hazard model was used to calculate adjusted hazard ratios and 95% confidence intervals of stroke associated with TCM treatment., Results: During the follow-up period, patients with cardiac arrhythmia who underwent TCM treatment (11.4 per 1000 person-years) had a lower incidence of new-onset stroke than those without TCM treatment (17.7 per 1000 person-years), with an HR of 0.62 (95% CI=0.50-0.78). The association between TCM treatment and decreased new-onset stroke was both significant in women and men. The young patients aged 45-54 years who received TCM had the lowest risk of stroke (HR=0.48, 95% CI=0.27-0.87)., Conclusions: Receiving TCM treatment was associated with a lower risk of stroke in patients with cardiac arrhythmia. However, this study was limited by lack of information regarding lifestyles, biochemical profiles, the dose of herbal medicine, and acupuncture points used in treatments., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Whether acupuncture protects stroke patients from acute myocardial infarction (AMI) has not been studied previously. The purpose of this study was to investigate the risk of AMI among stroke patients receiving acupuncture treatment., Methods: Taiwan's National Health Insurance Research Database was used to conduct a retrospective cohort study of 23475 stroke patients aged 40-79 years receiving acupuncture treatment and 46950 propensity score-matched stroke patients not receiving acupuncture treatment who served as controls from 2000 to 2004. Both stroke cohorts were followed until the end of 2009 and were adjusted for immortal time to measure the incidence and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset AMI in multivariate Cox proportional hazard models., Results: Stroke patients who received acupuncture treatment (9.2 per 1000 person-years) exhibited a lower incidence of AMI compared with those who did not receive acupuncture treatment (10.8 per 1000 person-years), with an HR of 0.86 (95 % CI, 0.80-0.93) after adjusting for age, sex, low income, coexisting medical conditions and medications. The relationship between acupuncture treatment and AMI risk was investigated in female stroke patients (HR, 0.85; 95 % CI, 0.76-0.95), male stroke patients (HR, 0.87; 95 % CI, 0.80-0.95), patients from 50 to 59 years of age (HR, 0.75; 95 % CI, 0.63-0.90), patients from 60 to 69 years of age (HR, 0.85; 95 % CI, 0.75-0.95), patients suffering from ischemic stroke (HR, 0.87; 95 % CI, 0.79-0.95), and patients suffering from hemorrhagic stroke (HR, 0.62; 95 % CI, 0.44-0.88)., Conclusions: We raised the possibility that acupuncture may be effective in lowering the risk of AMI in stroke patients aged 50-69 in this study, which was limited by a lack of information regarding stroke severity and acupuncture points. Our results suggest that prospective randomized trials are needed to establish the efficacy of acupuncture in preventing AMI.

Dentin is the main supporting structure of teeth, but its mechanical properties may be adversely affected by pathological demineralization. The purposes of this study were to develop a quantitative approach to characterize the viscoelastic properties of dentin after de- and re-mineralization, and to examine the elastic properties using a nanoindentation creep test. Dentin specimens were prepared to receive both micro- and nano-indentation tests at wet and dry states. These tests were repeatedly performed after demineralization (1% citric acid for 3 days) and remineralization (artificial saliva immersion for 28 days). The nanoindentation test was executed in a creep mode, and the resulting displacement-time responses were disintegrated into primary (transient) and secondary (viscous) creep. The structural changes and mineral densities of dentin were also examined under SEM and microCT, respectively. The results showed that demineralization removed superficial minerals of dentin to the depth of 400 μm, and affected its micro- and nano-hardness, especially in the hydrate state. Remineralization only repaired the minerals at the surface layer, and partially recovered the nanohardness. Both the primary the secondary creep increased in the demineralized dentin, while the hydration further enhanced creep deformation of untreated and remineralized dentin. Remineralization reduced the primary creep of dentin, but did not effectively increase the viscosity. In conclusion, water plasticization increases the transient and viscous creep strains of demineralized dentin and reduces load sustainability. The nanoindentation creep test is capable of analyzing the elastic and viscoelastic properties of dentin, and reveals crucial information about creep responses., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study uses the fluid-structure interaction (FSI) method to investigate the fluid flow in dental pulp. First, the FSI method is used for the biomechanical simulation of dental intrapulpal responses during force loading (50, 100 and 150 N) on a tooth. The results are validated by comparison with experimental outcomes. Second, the FSI method is used to investigate an intact tooth subjected to a mechanical stimulus during loading at various loading rates. Force loading (0-100 N) is applied gradually to an intact tooth surface with loading rates of 125, 62.5, 25 and 12.5 N/s, respectively, and the fluid flow changes in the pulp are evaluated. FSI analysis is found to be suitable for examining intrapulpal biomechanics. An external force applied to a tooth with a low loading rate leads to a low fluid flow velocity in the pulp chamber, thus avoiding tooth pain.

Mitochondrial transfer has been demonstrated to a play a physiological role in the rescuing of mitochondrial DNA deficient cells by co-culture with human mesenchymal stem cells. The successful replacement of mitochondria using microinjection into the embryo has been revealed to improve embryo maturation. Evidence of mitochondrial transfer has been shown to minimize injury of the ischemic-reperfusion rabbit heart model. In this mini review, the therapeutic strategies of mitochondrial diseases based on the concept of mitochondrial transfer are illustrated, as well as a novel approach to peptide-mediated mitochondrial delivery. The possible mechanism of peptide-mediated mitochondrial delivery in the treatment of the myoclonic epilepsy and ragged-red fiber disease is summarized. Understanding the feasibility of mitochondrial manipulation in cells facilitates novel therapeutic skills in the future clinical practice of mitochondrial disorder., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

This study uses fluid-structure interaction (FSI) simulation to investigate the relationship between the dentinal fluid flow in the dental pulp of a tooth and the elastic modulus of masticated food particles and to investigate the effects of chewing rate on fluid flow in the dental pulp. Three-dimensional simulation models of a premolar tooth (enamel, dentine, pulp, periodontal ligament, cortical bone, and cancellous bone) and food particle were created. Food particles with elastic modulus of 2,000 and 10,000 MPa were used, respectively. The external displacement loading (5 μm) was gradually directed to the food particle surface for 1 and 0.1 s, respectively, to simulate the chewing of food particles. The displacement and stress on tooth structure and fluid flow in the dental pulp were selected as evaluation indices. The results show that masticating food with a high elastic modulus results in high stress and deformation in the tooth structure, causing faster dentinal fluid flow in the pulp in comparison with that obtained with soft food. In addition, fast chewing of hard food particles can induce faster fluid flow in the pulp, which may result in dental pain. FSI analysis is shown to be a useful tool for investigating dental biomechanics during food mastication. FSI simulation can be used to predict intrapulpal fluid flow in dental pulp; this information may provide the clinician with important concept in dental biomechanics during food mastication.

Objectives: To evaluate the collagen cross-linkers, riboflavin-ultraviolet-A (RF/UVA) and glutaraldehyde, with regard to their efficacy in cross-linking the dentinal collagen and improving dentin bonding., Methods: Glutaraldehyde and different RF/UVA protocols (0.1%RF/1-minUV, 0.1%RF/2-minUV, and 1%RF/1-minUV) were first evaluated by gel electrophoresis to determine their abilities of collagen cross-linking. The mechanical properties of acid-etched dentin receiving these cross-linking treatments were examined in either dry or wet condition by a nanoindentation test. Fifteen teeth with exposed occlusal dentin received the microtensile bond strength (μTBS) test. The teeth were primed either with RF/UVA or glutaraldehyde, followed by adhesive treatment and composite restorations, and then cut into resin-dentin microbeams. Half of the microbeams received the μTBS test after 24h, and the other half received test after 5000 thermocycles. Nanoleakage at the bond interface was examined under TEM. The alignments of collagen fibrils in the hybrid layers were also defined by an image analysis., Results: Gel electrophoresis showed that glutaraldehyde induced strong collagen gelation, while RF/UVA generated milder collagen cross-linking. Glutaraldehyde, 0.1%RF/2-min-UVA, and 1%RF/1-minUV showed higher stiffness compared to untreated and 0.1%RF/1-minUV in wet condition. All the crosslinking treatments improved early μTBS, but 0.1%RF/2-minUVA treatment maintained high μTBS after theromocycles. Under TEM, glutaraldehyde-treated dentin showed dense and enclosed collagen network on the adhesive interface. 0.1%RF/2-minUVA showed the least nanoleakage, and this could be associated with the suspended collagen fibrils in the hybrid layer., Significance: 0.1%RF/2-minUVA treatment enhanced resin-dentin bond possibly through enhancing the stiffness and maintaining the expanding collagen matrix in the hybrid layer., (Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study uses a fluid-structure interaction (FSI) simulation to evaluate the fluid flow in a dental intrapulpal chamber induced by the deformation of the tooth structure during loading in various directions., Methods: The FSI is used for the biomechanics simulation of dental intrapulpal responses with the force loading gradually increasing from 0 to 100N at 0°, 30°, 45°, 60°, and 90° on the tooth surface in 1s, respectively. The effect of stress or deformation on tooth and fluid flow changes in the pulp chamber are evaluated., Results: A horizontal loading force on a tooth may induce tooth structure deformation, which increases fluid flow velocity in the coronal pulp. Thus, horizontal loading on a tooth may easily induce tooth pain., Conclusion: This study suggests that experiments to investigate the relationship between loading in various directions and dental pain should avoid measuring the bulk pulpal fluid flow from radicular pulp, but rather should measure the dentinal fluid flow in the dentinal tubules or coronal pulp. The FSI analysis used here could provide a powerful tool for investigating problems with coupled solid and fluid structures in dental biomechanics., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: A low-temperature low-energy capillary-tube-based argon micro-plasma system was applied to disinfect Streptococcus mutans-containing biofilm., Materials and Methods: The micro-plasma system uses a hollow inner electrode that is ignited by a radio-frequency power supply with a matching network. The energy content was analyzed using optical emission spectroscopy. The micro-plasma-induced effect on a biofilm cultured for 24 or 48 h with a working distance of ≈3 mm at low temperature was evaluated. The morphologies of the treated live/dead bacteria and the produced polysaccharides after micro-plasma treatment were examined., Results: Scanning electron microscopy images and staining results show that most of the S. mutans on the treated biofilm were acutely damaged within a micro-plasma treatment time of 300 s., Conclusions: The number of living bacteria underneath the treated biofilm greatly decreased with treatment time. The proposed micro-plasma system can thus disinfect S. mutans on/in biofilms.

A model whose porosity does not vary with compression depth is developed for evaluating the mechanical properties of dentin tubules with various orientation angles from micro-pillar nanocompression tests. Experimental results for a range of loading rates indicate that the yielding parameters and the elastic modulus are little affected by the creep behavior. For a given compression depth, the hardness, elastic modulus, and yielding strength decrease with increasing orientation angle of dentin. The mechanical properties obtained using the proposed model are consistent with the reported data, and are actually more precise since they consider the orientation angle. The proposed testing method can be applied to materials that yield a negative value of the elastic modulus due to creep behavior., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The protozoan Giardia lamblia differentiates from a pathogenic trophozoite into an infectious cyst to survive outside of the host. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately induced. Pax family transcription factors are involved in a variety of developmental processes in animals. Nine Pax proteins have been found to play an important role in tissue and organ development in humans. To understand the progression from primitive to more complex eukaryotic cells, we tried to identify putative pax genes in the G. lamblia genome and found two genes, pax1 and pax2, with limited similarity. We found that Pax1 may transactivate the encystation-induced cwp genes and interact with AT-rich initiatior elements that are essential for promoter activity and transcription start site selection. In this study, we further characterized Pax2 and found that, like Pax1, Pax2 was present in Giardia nuclei and it may specifically bind to the AT-rich initiator elements of the encystation-induced cwp1-3 and myb2 genes. Interestingly, overexpression of Pax2 increased the cwp1-3 and myb2 gene expression and cyst formation. Deletion of the C-terminal paired domain or mutation of the basic amino acids of the paired domain resulted in a decrease of nuclear localization, DNA-binding activity, and transactivation activity of Pax2. These results are similar to those found in the previous Pax1 study. In addition, the profiles of gene expression in the Pax2 and Pax1 overexpressing cells significantly overlap in the same direction and ERK1 associated complexes may phosphorylate Pax2 and Pax1, suggesting that Pax2 and Pax1 may be downstream components of a MAPK/ERK1 signaling pathway. Our results reveal functional redundancy between Pax2 and Pax1 in up-regulation of the key encystation-induced genes. These results illustrate functional redundancy of a gene family can occur in order to increase maintenance of important gene function in the protozoan organism G. lamblia.

The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA) and neuraminidase (NA) of pH1N1 strains that spread in two metropolitan areas--Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post-peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K) was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001). E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure). In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post-peak (p = 0.000004) in seven districts with higher spatial clusters (p<0.001). This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001) and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001). Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at exponential and peak phases in areas with high cluster cases.

The resistance of nanoporous dentin biomaterial to CO₂ laser irradiation was investigated by experiment and simulation for potential tooth hypersensitivity treatment. The controlled parameters including laser power of 0.03-0.150 W, scanning speeds of 11.4-34.2 mm/s and focus/defocus modes were used for studying interaction between laser energy and dentin of human tooth. Most of the dentin specimens were etched after CO₂ laser irradiation with the power larger than 0.12 W at a scanning speed of 11.4 mm/s. Compared with the simulation results of temperature distribution, the maximum temperature at laser powers from 0.12 to 0.15 W is increased from 1961 to 2245°C, which exceeded the melting point (1570°C) of dentin's main content hydroxyapatite (HA). Increasing scanning speed can reduce the linear density of laser output energy for just locally melting porous microstructure of dentin surface without etching. Varying focus mode can also improve the damage of nanoporous dentin microstructure. At parameters of 0.150 W power and 34.2 mm/s scanning speed under defocus operation, laser treatment was successfully performed on the nano-HA coated dentin with well-molten sealing on tubules of porous microstructure at a simulate surface temperature of about 574°C, which was the potential for dentin hypersensitivity cure application.

The objective of this study was to examine the effects of cavity configuration on the polymerization shrinkage and stress of light-cured composite restorations by combining local strain measurement and a finite element analysis (FEA). Dental mesio-occluso-distal cavities of various widths and depths (each for 2 vs. 4 mm), representing different configuration factors, were prepared on extracted molars. The displacements of the bonded tooth cusps and cavity floors, caused by polymerization shrinkage of composite restorations, were assessed utilizing a digital-image-correlation (DIC) technique. The cervical marginal microleakage was investigated by examining the resin replicas of these restorations under SEM. The local material properties of the polymerized composite along the curing depth were defined by the nanoindentation test and applied in the subsequent FEA. In the FEA, four models were generated to correspond with the experimental restorations. In the DIC measurement results, the 4(w)×4(D) mm cavity presented the greatest values of inward displacements at the cusp and floor. The cavity depth, rather than the cavity width, was found to significantly correlate to the floor deformation, the location of shrinkage centers, and also the cervical microleakage ratio. The FEA simulation results showed that the 2(w)×4(D) mm cavity presented the maximal von Mises and principal stress located respectively on the cervical margins and cavity floor. Additional safety factor analysis showed a high risk of bond failure over the cavity floor in the 4-mm deep cavity. With the experimental validation, the simulation revealed that the cavity depth was significant to the formation of contraction stress and the incidence of interfacial debonding., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Giardia lamblia differentiates into resistant walled cysts for survival outside the host and transmission. During encystation, synthesis of cyst wall proteins is coordinately induced. The E2F family of transcription factors in higher eukaryotes is involved in cell cycle progression and cell differentiation. We asked whether Giardia has E2F-like genes and whether they influence gene expression during Giardia encystation. Blast searches of the Giardia genome database identified one gene (e2f1) encoding a putative E2F protein with two putative DNA-binding domains. We found that the e2f1 gene expression levels increased significantly during encystation. Epitope-tagged E2F1 was found to localize to nuclei. Recombinant E2F1 specifically bound to the thymidine kinase and cwp1-3 gene promoters. E2F1 contains several key residues for DNA binding, and mutation analysis revealed that its binding sequence is similar to those of the known E2F family proteins. The E2F1-binding sequences were positive cis-acting elements of the thymidine kinase and cwp1 promoters. We also found that E2F1 transactivated the thymidine kinase and cwp1 promoters through its binding sequences in vivo. Interestingly, E2F1 overexpression resulted in a significant increase of the levels of CWP1 protein, cwp1-3 gene mRNA, and cyst formation. We also found E2F1 can interact with Myb2, a transcription factor that coordinate up-regulates the cwp1-3 genes during encystation. Our results suggest that E2F family has been conserved during evolution and that E2F1 is an important transcription factor in regulation of the Giardia cwp genes, which are key to Giardia differentiation into cysts.

Objectives: To evaluate the proximal contact on class II composite restorations constructed using various restorative approaches by a morphological analysis., Methods: Sixty plastic premolar teeth were prepared for class II cavities. These teeth were divided into six groups and restored using different materials and matrix systems. Two composite materials used were a microhybrid composite Filtek Z100 (3M/ESPE) and a packable composite P60 (3M/ESPE). Three interproximal matrix systems were two circumferential metal matrices (0.05 mm and 0.03 mm thin, respectively) combined with a Tofflemire retainer, and a pre-contoured sectional matrix system (Palodent). The contact morphologies of the restorations were visually inspected with regard to their buccolinugal and mesiodistal aspects. The contact tightness was measured by inserting different amounts of metal strips. For quantitatively morphologic analysis, three-dimensional (3D) scans of proximal contacts were performed. The results were analysed with two-way ANOVA and the Tukey test., Results: Under visual observation, contact surfaces in sectional matrix groups showed anatomic profile but concave in the centre, whilst the circumferential matrix groups showed flat profiles. The sectional matrix improved the contact tightness. The 3D analysis revealed that the matrix system was correlated with the contact morphology, since the sectional matrix generated significantly deeper and wider surface concavity., Conclusions: All the interproximal matrix systems presented some deficiency in either the contact tightness or contours. Although the sectional matrix system enhanced contact tightness, it caused contact concavity by formation of interproximal marginal overhang. The quantitative morphologic analysis helps to examine improper proximal contact and the associated problems., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Endodontically-treated teeth are prone to fracture due to loss of tooth structure and altered mechanical behaviors. The stability and rigidity of post-restored teeth, particularly in cases involving periodontal destruction, has not been adequately investigated. This study examined the influence of post material on teeth with simulated bone reduction by a multiparametric evaluation. Sixty extracted premolars of similar sizes were endodontically treated then divided into six groups. Each group was restored with one of the combinations of three posts (a glass-fiber, a prefabricated titanium post, and a cast post) and two simulated bone conditions (2 or 6 mm below crown margins). After crown restorations, they were loaded with a 100 N force then the displacements were examined by the digital-image-correlation technique. Marginal integrity on the buccal and lingual crown margins was examined before and after the thermocycling. Finally, the teeth were loaded until failure to examine the strength and fracture patterns. The digital-image-correlation measurements revealed that tooth deformation was related to the support conditions, especially for the fiber post groups. The cast post groups showed less altered marginal integrity after thermomechanical loading than the fiber and titanium post groups did. In the fracture test, the fiber-post/reduced-support group exhibited inferior fracture strength. The reduced support significantly affected fracture strength and incidence of repairable root fracture. The marginal integrity was not correlated with tooth deformation, since the tooth flexed at the crest of the simulated bone. The root fracture resistance was determined mainly by post materials but was concurrently affected by the support conditions., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objectives: To analyze the influence of cavity geometry and lining materials in MOD composite restorations by characterizing the polymerization shrinkage and cusp deflection., Methods: Eighty intact molars with similar sizes were collected and randomly divided into eight groups. MOD cavities with various widths and depths were prepared on these teeth: Group I, 2((W)) × 2((D)) mm; Group II, 4((W)) × 2((D)) mm; Groups III, IIIf, IIIg, 2((W)) × 4((D)) mm; and Groups IV, IVf, IVg, 4((W)) × 4((D)) mm. In Groups IIIf and IVf, flowable composite liner was placed prior to composite restoration, while glass-ionomer liner was used in Groups IIIg and IVg. Deformations of restorations resulted from composite shrinkage were recorded for 30 min following light irradiation using a digital-image-correlation (DIC) method to subpixel level. The displacements at the boundaries of the restorations were analyzed using one-way ANOVA and the post hoc test at a 5% significance level. The correlation between the geometric factors and the displacements was also analyzed., Results: The inward displacements on free surfaces were greater than those on the bonded surfaces. Groups with flowable composite linings showed greater amount of displacements on free and bonded surfaces compared to the unlined and glass ionomer lining groups. The correlation analysis showed that the free surface shrinkage was related with the cavity width and C-factor, while cusp deflections were correlated with the cavity depth and the cusp compliance., Significance: The DIC technique measures composite shrinkage on different boundaries of restorations to facilitate the investigation of polymerization kinetics. Using flowable composite lining and increased cusp depth may aggravate the cusp flexure., (Copyright © 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Statement of Problem: Cast posts require sufficient length for prosthesis retention and root strength. For prefabricated metal and fiber posts, the effects of different post lengths on the strength and internal stress of the surrounding root need evaluation., Purpose: The purpose of this study was to examine, using both experimental and finite element (FE) approaches, the influence of post material and length on the mechanical response of endodontically treated teeth., Material and Methods: Sixty extracted incisors were endodontically treated and then restored with 1 of 3 prefabricated posts: stainless steel (SS), carbon fiber (CF), and glass fiber (GF), with intraradicular lengths of either 5 or 10 mm (n=10). After composite resin core and crown restorations, these teeth were thermal cycled and then loaded to fracture in an oblique direction. Statistical analysis was performed for the effects of post material and length on failure loads using 2-way ANOVA (α=.05). In addition, corresponding FE models of an incisor restored with a post were developed to examine mechanical responses. The simulated tooth was loaded with a 100-N oblique force to analyze the stress in the root dentin., Results: The SS/5 mm and all fiber post groups presented no statistical differences, with mean (SD) fracture loads of 1247 to 1339 (53 to 121) N. The SS/10 mm group exhibited a lower fracture load, 973 (115) N, and a higher incidence of unfavorable root fracture (P<.05). The FE analysis showed high stress around the apical end of the long SS post, while stress was concentrated around the crown margins in the fiber post groups., Conclusions: Both long and short fiber posts provided root fracture resistance comparable to that of SS posts. For metal posts, extending the post length does not effectively prevent root fracture in restored teeth., (Copyright © 2010 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.)

ΔNp63, the N-terminal truncated isoform of p63, has been found to be overexpressed in several human epithelial cancers, including nasopharyngeal carcinomas (NPCs), suggesting a function in carcinogenesis. Trans-resveratrol (RSV) has been shown to exert proapoptotic activities through a p53-dependent or p53-independent pathway in various cancer cells. However, the effects of RSV on NPC are still unexplored. In this study, we investigated the apoptotic effects of RSV on ΔNp63-overexpressing NPC cell lines. We showed that RSV (12-100 μ) induced dose-dependent growth suppression, cell-cycle arrest in the S phase and caspase-dependent apoptosis in NPC-TW076 and NPC-TW039 cells. The RSV effect was accompanied by the downregulation of ΔNp63 and the upregulation of p53 protein in a dose-dependent manner. By using small-interfering RNA (siRNA) technology, we found that the targeted silencing of ΔNp63 induced apoptosis and sensitized the NPC cells to RSV-induced apoptosis through caspase-3 activation, whereas suppression of p53 by siRNA did not inhibit RSV-induced apoptosis. Furthermore, transfection with p53 siRNA or pretreatment with caspase inhibitors (Z-VAD-fmk or Z-DEVD-fmk) had no influence on the RSV downregulation of ΔNp63. Interestingly, ecoptic expression of ΔNp63 did not significantly block RSV-induced cell death and was also downregulated after RSV treatment. Downregulation of ΔNp63 by RSV was shown to occur at the mRNA transcript and post-translational levels. Importantly, RSV enhanced chemotheraptic drug-induced apoptosis in NPC and two human carcinoma cell lines, HT1376 and Hep3B cells. These results suggested that ΔNp63, but not p53, is a molecular target of RSV-induced apoptosis and the regulation of ΔNp63 expression by RSV may provide a therapeutic effect of RSV in human NPC.

The aim of this study was to examine the resin bond strength on enamel treated with different fluoridated bleaching agents. Forty-eight bovine incisors were divided into four groups to receive bleaching treatments, over a 14-d period, as follows: no treatment; 10% carbamide peroxide (CP) bleaching; 10% CP containing 0.11% fluoride; and 10% CP containing 0.37% fluoride. Immediately, and 7 and 14 d after bleaching, the enamel surfaces were respectively bonded with composite and sectioned to create resin-enamel beams. These beams were subjected to the microtensile bond strength (microTBS) test, then assessed for failure mode under scanning electron microscopy. The results showed that the 0.37% fluoridated group demonstrated a microTBS equivalent to that of the unbleached group at all stages. Non-fluoridated and 0.11% fluoridated groups showed a weaker microTBS after bleaching but regained the bond strength after 14 or 7 d of storage, respectively. In the non-fluoridated group, adhesive failure was the predominant fracture pattern that comprised the enamel prism demineralization change and widely dispersed voids on the resin-enamel interfaces. No evident enamel erosion and fewer microporosities were found in the 0.37% fluoridated group. Accordingly, treatment with 0.37% fluoridated CP maintained the microTBS as effectively as the unbleached enamel. Additional fluoride in the bleaching agents may facilitate subsequent restorative treatment by inhibiting enamel demineralization.

The purpose of this study was to assess the effectiveness of a behavioral parent therapy (BPT) program in children with attention-deficit hyperactivity disorder (ADHD) using multidimensional evaluations, the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). Between 2001 and 2005, the parents of 21 preschool children with ADHD were divided into six groups and participated in a series of 11 BPT sessions. Before and after BPT, the parents completed the CBCL, and the teachers completed the TRF. The behavioral and emotional problems of the children showed improvement after the BPT sessions, specifically for the following categories: internalizing problems, anxious/depressed syndromes, somatic complaints, externalizing problems, rule-breaking behaviors, aggressive behaviors, social problems, thought problems, and attention problems. In the DSM-oriented scale of the CBCL, affective problems, anxiety problems, somatic problems, ADHD problems, oppositional defiant disorder problems, and conduct disorder problems showed significant improvements. On the DSM scale of the TRF, Inattention syndrome improved significantly after the BPT sessions, while other syndromes showed non-significant changes. We conclude that the BPT program significantly improved the childrens behavioral problems at home and inattention problems at school.

Objectives: To evaluate the effects of fluoridated bleaching agents and post-bleaching fluoridation treatment on the whitening efficiency and microhardness of bovine enamel., Methods: Twenty five freshly extracted bovine incisors were cut into halves, embedded and then divided into the following five groups: Group 1, untreated controls; Group 2, treatment with 10% carbamide peroxide (CP) bleaching agent; Group 3, treatment with 10% CP followed by a 0.9% sodium fluoride gel application, Group 4, treatment with 10% CP containing 0.11% fluoride; Group 5, treatment with an experimental bleaching agent consisting of 10% CP and 0.37% fluoride. Groups 2-5 were treated 8h per day for 14 days then immersed in saliva for 2 weeks. Enamel morphology changes were evaluated under SEM on Day 14. Changes in enamel color and microhardness were evaluated on Days 7 and 14, and compared with the baseline data. Additionally, microhardness was determined on post-bleaching Days 21 and 28., Results: After 2 weeks, an erosion pattern was noted on the specimens in Groups 2 and 3. Groups 4 and 5 showed a milder demineralized pattern. All the bleached enamel specimens revealed increased whiteness and overall color value. Groups 2 and 3 showed significantly decreased enamel microhardness compared to their baseline data. The specimens treated with fluoridated bleaching agents showed relatively less reduction in enamel microhardness than those treated with nonfluoridated agents during the bleaching treatment., Conclusions: The fluoridated bleaching agents produced less demineralization of surface morphology and microhardness. The addition of fluoride did not impede the whitening effect.

Background: Factors influencing the percentage of daily interdialytic weight gain (IDWG%) and their interactions in haemodialysis (HD) patients have not been well-defined, especially in diabetic patients. We analysed contributing factors for the increase of IDWG%, particularly xerostomia (oral dryness), among diabetic and non-diabetic HD patients., Methods: We collected 3 month prospective data in 184 stable HD patients (116 non-diabetic and 68 diabetic), including assessments of xerostomia by 100 mm visual analog scales (VASs), and the unstimulated whole salivary (UWS) flow rate was measured in 91 patients by a spitting method., Results: Diabetic patients have higher IDWG% (P = 0.042) and VAS oral dryness score (P = 0.021), whereas, have lower UWS (P = 0.032). In non-diabetic patients, the VAS oral dryness score, age, Kt/V and blood urea nitrogen (BUN) level correlated independently with IDWG%. In diabetic patients, the haemoglobin A(1C) (HbA(IC)) correlated significantly with IDWG% after controlling for age, Kt/V and BUN level; however, when VAS oral dryness score was introduced into the regression model, the effect of HbA(IC) became marginally significant (P = 0.073) while the VAS oral dryness score became significantly correlated with IDWG%. The increases in IDWG% per unit change in VAS oral dryness score did not show significant difference between the non-diabetic and total diabetic patients; however, it was larger in patients with HbA(IC) >or=9%., Conclusions: Xerostomia plays a significant role in increasing IDWG% among diabetic and non-diabetic HD patients. In diabetic patients, the increased IDWG% associated with the increasing HbA(1C) level is largely dependent on the severity of xerostomia, and we speculate that insulin deficiency may operate synergistically with xerostomia in increasing IDWG% in patients with HbA(1C) >or=9%.

Objectives: To investigate the bond strength and fracture characteristics of various dentine bonding agents (DBAs) on wet or dry enamel., Methods: Forty molar halves with enamel flattened were divided into 5 groups. Groups 1-4, teeth were acid-etched and treated separately with either an ethanol-based adhesive (Single Bond) or an acetone-based adhesive (Prime & Bond NT) on dry or wet enamel. Group 5 was treated with a self-etching adhesive (Clearfil SE Bond). The treated enamel surfaces were bonded with Z 250 composite with metal rings. The composite-ring assemblies were subjected to shear bond test until failure. Failure patterns on the debonded surfaces were inspected under a scanning electron microscope. The bonded enamel thickness was measured on sectioned specimens to investigate their statistical evidence. Results of open margin and enamel microcrack ratios from Part I of this study were compared with these fracture characteristics. Data was analyzed statistically., Results: There was no difference in the bond strength between paired groups using the same DBA on wet or dry enamel. The teeth restored with self-etching adhesive exhibited lower bond strength and higher adhesive-enamel failure rate than the other groups. No correlation between enamel thickness, microcrack, bond strength, and failure patterns was revealed., Conclusion: The self-etching adhesive had a lower enamel bond strength than the other bonding systems. The difference in the failure patterns of groups with ethanol- and acetone-based DBAs on wet or dry enamel was indistinct. The frequently observed enamel microcrack cannot be directly correlated with the bond strength of bonding systems.

Objectives: To investigate the influence of enamel wetness on marginal quality and enamel microcrack formation using various dentine bonding adhesives; and to determine the changes of marginal quality and enamel microcracks over time., Methods: Forty extracted molars were each prepared with a cylindrical cavity and divided into five groups. Groups 1-4 were acid-etched and treated separately with either an ethanol-based adhesive (Single Bond) or an acetone-based adhesive (Prime&Bond NT) on either dry or wet enamel. Teeth in Group 5 were treated with a self-etching adhesive (Clearfil SE Bond). Epoxy replicas of different stages were taken after cavity preparation, after restoration, after 24 h storage, and after thermocycling test. These replicas were examined under a scanning electron microscope for their restorative marginal quality and enamel microcrack. Quantitative measurement was performed to measure the length ratio of different margin patterns, and enamel microcracks., Results: There was no difference in the marginal quality when ethanol-base adhesive was applied on dry or wet dentin. The group using acetone-based adhesive on the dry enamel presented higher intact margin ratio than the group on wet enamel did only after restoration. Using self-etching primer led to higher open margin ratio at all stages. Enamel microcracks were found in all five groups and were higher in groups using acetone-based adhesives., Conclusion: Enamel wetness did not show a significantly adverse effect on the marginal quality of the restorations using either acetone- or ethanol-based adhesive. Using self-etching adhesive may lead to high incidence of margin deterioration.

Decreased salivary flow rate causes xerostomia (symptoms of oral dryness) in patients who undergo hemodialysis (HD); however, whether it thus contributes to thirst and excess interdialytic weight gain (IDWG) remains undetermined. In the observational study, 3 mo of data of 90 stable HD patients were collected, and sensations of thirst and xerostomia were assessed by 100-mm visual analog scales (VAS). Multivariate analyses revealed that the VAS oral dryness score was an independent determinant for thirst, daily IDWG, and IDWG%. Unstimulated whole salivary flow rate (UWS) was measured in 45 participants and was negatively correlated with VAS oral dryness score (r = -0.690, P 2%/d) were randomly assigned to either the sequence pilocarpine (2 wk)-washout (3 wk)-placebo (2 wk)-washout (2 mo)-placebo (3 mo) or placebo (2 wk)-washout (3 wk)-pilocarpine (2 wk)-washout (2 mo)-pilocarpine (3 mo) with 35 participants completing the trial. During the 2-wk crossover period (the first to seventh weeks), pilocarpine increased UWS and decreased xerostomia and thirst. The IDWG(2d) decreased (by approximately 0.2 kg; P = 0.013) but not IDWG(3d). During the 3-mo interventional period, pilocarpine increased UWS but decreased both IDWG(2d) (by 0.76 kg; P = 0.021) and IDWG(3d) (by 1.07 kg; P = 0.007). It also modestly increased serum albumin and decreased mean BP. Pilocarpine-related adverse effects were generally mild. In conclusion, decreased salivary flow is a dipsogenic factor in HD patients, and pilocarpine can alleviate it.

Objective: The aim of this study was to examine the dental condition and oral manifestations in diabetic and nondiabetic uremic patients undergoing hemodialysis., Study Design: A total of 128 patients undergoing hemodialysis therapy were classified into the diabetic and nondiabetic groups and examined for uremic oral manifestations, dental caries, and the periodontal status. All the patients received predialytic salivary pH examination. In the diabetic group, the correlation between oral findings and glycemic controlled levels, which was collected based on Hb A1C values, were further studied., Results: The diabetic group exhibited significantly higher prevalence of caries and more severe dry mouth, taste change, and mucosa pain than the nondiabetic group. The diabetic group tended to have lower predialytic salivary pH, and patients with poor glycemic control (ie, Hb A1C > 9%) showed higher incidence of dry mouth, mucosal pain, and tongue coating. However, the DMFT and CPI index were not associated with glycemic control in the diabetic group., Conclusions: This study reveals that diabetic uremic patients undergoing maintained hemodialysis exhibited a potentially higher risk for dental decay and xerostomia. Lower salivary pH and poor glycemic control may affect oral manifestations. Further research is needed to clarify the combined influence of diabetic nephropathy on oral health.

The aims of this study were to compare initial and 24 hour shear bond strengths of plastic brackets with a mechanical base (Spirit MB) and metal brackets, using two different adhesives (System 1+ and Enlight), and to examine the modes of failure after debonding. Eighty extracted human premolars were used. After bonding, shear bond strengths in half the sample were tested within 30 minutes. The remaining 50 per cent were placed in a 37 degrees C distilled water bath for 24 hours before testing. The results showed that the effects of the two adhesives and the interaction of the two time intervals and the two bracket types on shear bond strength were significantly different (P < 0.05 and P < 0.0001, respectively). Six of the 10 groups were found to have less than 50 per cent of the adhesive remaining on the tooth surface after debonding in the 24 hour metal bracket-System 1+ group, but most specimens in the other seven groups had more than 50 per cent of the adhesive left. It is concluded that System 1+ cannot provide sufficient initial bond strengthfor Spirit MB and may increase the risk of enamel fracture for metal brackets.