Melatonin Mitigates iNOS-Related Effects of HEMA and Camphorquinone in Human Dental Pulp Cells: Relevance for Postoperative Sensitivity Mechanism in Type 2 Diabetes.

High elution and diffusion of 2-hydroxylethyl methacrylate (HEMA) and camphorquinone (CQ) through dentinal tubules may induce pulp injury and postoperative sensitivity. We aimed to investigate the melatonin protective effect in HEMA- and CQ-treated human dental pulp cells (hDPCs) as well as its relevance in a mechanism for postoperative sensitivity in diabetic patients. hDPCs were exposed to HEMA (5 mM) and/or CQ (1 mM) in the absence and presence of melatonin (MEL) (0.1 mM and 1 mM). Heme oxygenase-1 (HMOX1), NADPH oxidase-4 (NOX4), BCL-2-associated X-protein (BAX), B-cell lymphoma-2 (BCL-2) and caspase-3 (CASP3) gene expression levels, and superoxide dismutase (SOD) activity were measured in hDPCs while inducible nitric oxide synthase (iNOS) and melatonin protein expression were measured in human dental pulp as well, by RT-PCR, by ELISA, and spectrophotometrically. Bioinformatic analyses were performed by using the ShinyGO (v.0.75) application. Type 2 diabetic patients showed a higher incidence of postoperative sensitivity and lower melatonin and higher iNOS content in dental pulp tissue compared with non-diabetic patients. Melatonin, when co-added in hDPC culture, reverses HEMA and CQ cytotoxic effects via anti-apoptotic and anti-inflammatory/antioxidant iNOS-related effects. Enrichment analyses showed that genes/proteins, altered by HEMA and CQ and normalized by melatonin, are the most prominently overrepresented in type 2 diabetes mellitus pathways and that they share subcellular localization in different oligomeric protein complexes consisting of anti- and pro-apoptotic regulators. This is the first evidence of the ability of melatonin to counteract iNOS-mediated inflammatory and stress effects in HEMA- and CQ-treated hDPCs, which could be of significance for the modulation of presently observed immediate postoperative sensitivity after composite restoration in type 2 diabetic patients.

Evaluation of the Selected Mechanical and Aesthetic Properties of Experimental Resin Dental Composites Containing 1-phenyl-1,2 Propanedione or Phenylbis(2,4,6-trimethylbenzoyl)-phosphine Oxide as a Photoinitiator.

The goal of this study was to compare the mechanical properties of experimental resin dental composites containing a conventional photoinitiating system (camphorquinone CQ and 2-(dimethylami-no)ethyl methacrylate (DMAEMA)) to a photoinitiator system containing 1-phenyl-1,2 propanedione (PPD) with 2-(dimethylami-no)ethyl methacrylate) or acting alone phenylbis(2,4,6-trimethylbenzoyl)-phosphine oxide (BAPO). The manually produced composites consisted of an organic matrix: bis-GMA (60 wt. %), TEGDMA (40 wt. %), and silanized silica filler (45 wt. %). The composites contained 0.4/0.8 wt. %, 0.8/1.6 wt. %, and 1/2 wt. % of PPD/DMAEMA and another group included 0.25, 0.5, or 1 wt. % of BAPO. Vickers hardness, microhardness (in the nanoindentation test), diametral tensile strength, and flexural strength were assessed, and CIE L* a* b* colorimetric analysis was conducted for each composite produced. The highest average Vickers hardness values were obtained for the composite containing 1 wt. % BAPO (43.73 ± 3.52 HV). There was no statistical difference in the results of diametral tensile strength for the experimental composites tested. The results of 3-point bending tests were the highest for composites containing CQ (77.3 ± 8.84 MPa). Despite the higher hardness of experimental composites including PPD or BAPO, compared with composites with CQ, the overall results indicate that the composite with CQ still represents a better solution when used as a photoinitiator system. Moreover, the composites containing PPD and DMAEMA are not promising in terms of color or mechanical properties, especially as they require significantly longer irradiation times.

Can TPO as Photoinitiator Replace "Golden Mean" Camphorquinone and Tertiary Amines in Dental Composites? Testing Experimental Composites Containing Different Concentration of Diphenyl(2,4,6-trimethylbenzoyl)phosphine Oxide.

The aim of this research was to compare the biomechanical properties of experimental composites containing a classic photoinitiating system (camphorquinone and 2-(dimethylami-no)ethyl methacrylate) or diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO) as a photoinitiator. The produced light-cured composites consisted of an organic matrix-Bis-GMA (60 wt.%), TEGDMA (40 wt.%) and silanized silica filler (45 wt.%). Composites contained 0.27; 0.5; 0.75 or 1 wt.% TPO. Vickers hardness, microhardness (in the nanoindentation test), diametral tensile strength, resistance to three-point bending and the CIE L* a* b* colorimetric analysis was performed with each composite produced. The highest average Vickers hardness values were obtained for the composite containing 1 wt.% TPO (43.18 ± 1.7HV). The diametral tensile strength remains on regardless of the type and amount of photoinitiator statistically the same level, except for the composite containing 0.5 wt.% TPO for which DTS = 22.70 ± 4.7 MPa and is the lowest recorded value. The highest average diametral tensile strength was obtained for the composite containing 0.75 wt.% TPO (29.73 ± 4.8 MPa). The highest modulus of elasticity characterized the composite containing 0.75 wt.% TPO (5383.33 ± 1067.1 MPa). Composite containing 0.75 wt.% TPO has optimal results in terms of Vickers hardness, diametral tensile strength, flexural strength and modulus of elasticity. Moreover, these results are better than the parameters characterizing the composite containing the CQ/DMAEMA system. In terms of an aesthetic composite containing 0.75 wt.%. TPO is less yellow in color than the composite containing CQ/DMAEMA. This conclusion was objectively confirmed by test CIE L* a* b*.

Computational simulation of vibrationally resolved spectra for spin-forbidden transitions.

In this computational study, we illustrate a method for computing phosphorescence and circularly polarized phosphorescence spectra of molecular systems, which takes into account vibronic effects including both Franck-Condon and Herzberg-Teller contributions. The singlet and triplet states involved in the phosphorescent emission are described within the harmonic approximation, and the method fully takes mode-mixing effects into account when evaluating Franck-Condon integrals. Spin-orbit couplings, which are responsible for these otherwise forbidden phenomena, are accounted for by means of a relativistic two-component time-dependent density functional theory method. The model is applied to two types of chiral systems: camphorquinone, a rigid organic system that allows for an extensive benchmark, and some members of a class of iridium complexes. The merits and shortcomings of the methods are discussed, and some perspectives for future developments are offered.

Development of Novel Photoinitiators as Substitutes of Camphorquinone for the LED Induced Polymerization of Methacrylates: A Bis-Silyl Ketone.

A new photoinitiator based on a bis-silylketone (BSK) structure is proposed as a novel compound leading to highly efficient initiating silyl radicals for the polymerization of methacrylates (e.g., a bisphenol A-glycidyl methacrylate/triethyleneglycol dimethacrylate blend (70%/30% w/w)) upon exposure to a blue light emitting diode and a green laser diode. The polymerization profiles are recorded by real time Fourier transform IR (FTIR) spectroscopy. Absorption, fluorescence, electron spin resonance (ESR), and steady state experiments are used to investigate the involved chemical mechanisms. Molecular orbital calculations are also carried out. Remarkably, BSK efficiently works in the presence of an iodonium salt. The overall mechanism for the initiation step is clarified. This novel class of silyl radical generating photoinitiators is really promising for the photopolymerization of methacrylates, e.g., in dental materials.

The effect of photoinitiator type and filler load on physicochemical and mechanical properties of experimental light-cured resin cements through lithium disilicate ceramics of different shades and thicknesses.

OBJECTIVE: This study investigated the influence of photoinitiator types on degree of conversion (DC), rate of polymerization (RP), flexural strength (FS), flexural modulus (FM), and light transmittance (LT) of filled and unfilled light-curable resin cements through different thicknesses and shades of lithium disilicate ceramics. METHODS: Lithium disilicate ceramic discs (IPS Emax Press, background [0.0], 0.5, 1.0, 2.0, 3.0, and 4.0 mm, shades A1 and BL3) were prepared. Experimental resin-based cements [TEGDMA/BisGMA (50/50 mass%)] were prepared using either camphorquinone (CQ)/amine (0.44/1.85 mol%) or TPO (0.44 mol%)], and a micro and nanofiller loads of nil (unfilled); 40/10 mass%; and 50/10 mass%). Resin cements (0.2 mm thick) were placed on the lower surface of the ceramic specimens and light-activated for 30 s from the upper surface using a Bluephase Style curing light (exitance at tip: 1236 mW/cm2 ± 1.20). LT and distribution of irradiance through the ceramics were measured using a UV-vis spectrometer and a beam profile camera, respectively (n = 3). The DC and RP were measured in real-time using mid infrared spectroscopy in attenuated total reflectance (ATR) mode (n = 3). FS and FM were measured using a universal testing machine (n = 5). Statistical analyses were performed on LT, DC, RP, FS, and FM data using a general linear model, and supplementary ANOVA and post hoc Tukey multiple comparison test were also performed (α = .05). RESULTS: Thicknesses, shades, photoinitiator type, and fillers load significantly influenced the optical and mechanical characteristics of the resin-based materials (p < 0.05). The BL3 shade ceramic provided higher values of DC, RP, FS, FM, and LT compared with the A1 shade (p < 0.05). Increasing ceramic thickness decreased the properties of the resin-based materials (p < 0.05). Generally, TPO improved mechanical properties of the resin cement compared with CQ (p < 0.05). SIGNIFICANCE: The luting process of indirect restorations may be improved by using high molar absorptivity, more reactive, and more efficient photoinitiators such as TPO, as opposed to conventional CQ. The use of such initiator may allow the placement of thicker and more opaque indirect restorations.

Degree of Conversion and Mechanical Properties of a Commercial Composite with an Advanced Polymerization System.

Advanced Polymerization System (APS) technology in a commercial composite resin enables reduction of the concentration of camphorquinone without altering composite physicochemical properties. AIM: The aim of this study was to evaluate the degree of conversion and mechanical properties of a commercial composite with an advanced polymerization system (APS) and compare it to other composites that do not use this system. MATERIALS AND METHOD: Five groups were analyzed. Group 1 (VT: Vittra APS - FGM); G2 (AU: Aura - SDI); G3 (ES: Quick Sigma Stelite - TOKOYAMA); G4 (FZ: Filtek Z350 XT - 3M ESPE); G5 (OP: Opallis -FGM). Degree of conversion (DC, n=3) was analyzed immediately and after 24h by analysis with FTIR spectroscopy. For Knoop hardness (KHN, n=3), 5 indentations were made at the top and bottom of specimens 2 mm thick. Flexural strength (FS, n=10) was determined by the three-point method in a universal testing machine. Polymerization stress (PS) was determined by light-curing the material (1.0 mm high) between polymethylmethacrylate rods in a universal testing machine. Light curing was performed with a Valo Cordless LED (1,000 mW/cm2 x 20 s: 20J). The results were analyzed using ANOVA and complemented by Tukey's test (α=0.05). RESULTS: The highest DC values (immediate and 24h after) were observed for VT and OP resins, followed by FZ, AU and ES. FZ (top and bottom) had the highest KHN values, similar to VT top. AU, ES, OP and VT had statistically different KHN between their top and bottom surfaces. The highest RF values were observed for FZ, followed by OP/VT, ES and AU. The highest TP values were observed for FZ, OP and VT. CONCLUSION: The Vittra APS resin with a new polymerization system presents satisfactory performance for the parameters evaluated.

A tecnologia Advanced Polymerization System (APS) presente em uma resina composta comercial permite reduzir a concentração de canforoquinona sem alterar as propriedades físico-químicas do compósito. Objetivo: o objetivo deste estudo foi avaliar o grau de conversão e as propriedades mecânicas de um compósito comercial com sistema avançado de polimerização (SAP) e comparálo com outros compósitos que não utilizam esse sistema. Materiais e Método: cinco grupos foram analisados. Grupo 1 (VT: Vittra APS - FGM); G2 (AU: Aura ­ SDI); G3 (ES: Quick Sigma Stelite ­ TOKOYAMA); G4 (FZ: Filtek Z350 XT ­ 3M ESPE); G5 (OP: Opallis -FGM). O grau de conversão (GC, n=3) foi analisado imediatamente e após 24h através da análise com espectroscopia FTIR; para dureza Knoop (DK, n=3), foram feitas 5 indentações no topo e na base de corpos de prova de 2 mm de espessura; para determinar a resistência à flexão (RF, n=10), o método de três pontos foi realizado em uma máquina universal de ensaios; a tensão de polimerização (TP) foi determinada pela fotopolimerização do material (1,0 mm de altura) entre hastes de polimetilmetacrilato em uma máquina de teste universal. A fotopolimerização foi realizada com um Valo Cordless LED (1.000 mW/cm2 x 20 s: 20J). Os resultados foram analisados por ANOVA e complementados pelo teste de Tukey (α=0,05). Resultados: os maiores valores de GC (imediato e 24h após) foram observados para as resinas VT e OP, seguidas de FZ, AU e ES. A resina FZ (superior e inferior) apresentou os maiores valores de DK, semelhante ao VT superior. As resinas AU, ES, OP e VT apresentaram DK estatisticamente diferente entre suas superfícies de topo e base. Os maiores valores de RF foram observados para FZ, seguido de OP/VT, ES e AU. Os maiores valores de TP foram observados para FZ, OP e VT. Conclusão: com base nos resultados, pode-se concluir que a resina Vittra APS com um novo sistema de polimerização apresenta desempenho satisfatório para os parâmetros avaliados.

Extension of the working time of dental composites due to a new type of white operating lamp.

OBJECTIVES: Dental composite materials for filling teeth are usually hardened by polymerisation lamps emitting blue light. However, the same wavelength is also emitted by light of dental operating lamps for lighting the oral cavity. Thus, the hardening of the composite is already initiated earlier, shortening the time of formability. The objective of this study is to develop a specific white LED for dental operating lamps. When restoring teeth, it enables dentists to work longer on light-curing composites in the same brightness. METHODS: Based on a short-wave blue coloured LED and a fluorescent substance, a white luminescent LED with a colour temperature of approx. 3,000 K is produced as a prototype. The formable working times of three composites are measured for this LED and two dental head lamps at an illuminance of 10,000 lx. RESULTS: Shorter working times of 98-237 s were measured for the headlamps and 409-807 s for the new LED. This light of the new LED is perceived by the human eye as warm white. CONCLUSIONS: The new LED extends the working time by the factor of 3.0 to 5.8 compared to the head lamps. This enables more precise modelling of fillings.

Inducing cathepsin L expression/production, lysosomal activation, and autophagy of human dental pulp cells by dentin bonding agents, camphorquinone and BisGMA and the related mechanisms.

Camphorquinone (CQ) and resin monomers are included in dentin bonding agents (DBAs) and composite resin to restore tooth defects due to abrasion, crown fracture, or dental caries. DBAs, CQ, and bisphenol A-glycidyl methacrylate (BisGMA) applications influence the biological activities of the dental pulp. The current investigation aimed to delineate the effect of DBAs, CQ, and BisGMA on cathepsin L production/expression, lysosomal activity, and autophagy induction in human dental pulp cells (HDPCs). HDPCs were exposed to DBAs, CQ, or BisGMA with/without inhibitors for 24 h. Enzyme-linked immunosorbent assay was employed to determine the cathepsin L level in culture medium. The cell layer was utilized to measure cell viability by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl -tetrazolium bromide (MTT) assay. Real-time PCR was used to evaluate the mRNA expression. Western blotting or immunofluorescent staining was used to study protein expression. Lysosomal density was evaluated by lysotracker red staining. We found that DBAs, CQ, and BisGMA stimulated cathepsin L mRNA, protein expression, and production in HDPCs. In addition, CQ and BisGMA induced lysosomal activity, Beclin1, ATG12, LC3B, Bax, and p53 expression in HDPCs, indicating the stimulation of autophagy. Glutathione (GSH) prevented CQ- and BisGMA-induced cytotoxicity. Moreover, E64d, cathepsin L inhibitor (two cathepsin inhibitors), and Pifithrin-α (a p53 inhibitor) showed little preventive effect toward CQ- and BisGMA-induced cytotoxicity. Autophagy inhibitors (NH4Cl, Lys05) mildly enhanced the CQ- and BisGMA-induced cytotoxicity. These results indicate that DBAs stimulated cathepsin L, possibly due to their content of CQ and BisGMA that may induce cathepsin L in HDPCs. CQ and BisGMA stimulated lysosomal activity, autophagy, and apoptosis, possibly via induction of Beclin 1, ATG12, LC-3B, Bax, and p53 expression. In addition, CQ and BisGMA cytotoxicity was related to redox change and autophagy. These events are important role in pulpal changes after the restoration of tooth decay using CQ- and BisGMA-containing DBAs and resin composite.

Lignin-derived new hydrogen donors for photoinitiating systems in dental materials.

OBJECTIVES: The aim of this study is to develop amine free photo-initiating system (PIs) for the photopolymerization of dental methacrylate resins, using seven new hydrogen donors HDA-HDG derived from ß-O-4 lignin model. METHODS: Seven experimental CQ/HD PIs were formulated with Bis-GMA/TEGDMA (70 w%/30 w%). CQ/EDB system was chosen as the comparison group. FTIR-ATR was used to monitor the polymerization kinetics and double bond conversion. Bleaching property and color stability were evaluated using a spectrophotometer. Molecular orbitals calculations were used to demonstrate C-H bond dissociation energies of the novel HDs. Depth of cure of the HD based systems were compared to the EDB based one. Cytotoxicity was also studied by CCK8 assay using tissue of mouse fibroblasts (L929 cells). RESULTS: Compared to CQ/EDB system, the new CQ/HD systems show comparable or better photopolymerization performances (1 mm-thick samples). Comparable or even better bleaching properties were also obtained with the new amine-free systems. Comparing to EDB, all HDs exhibited significantly lower C-H bond dissociation energies by molecular orbitals calculations. Groups with new HD showed higher depth of cure. OD and RGR values were similar to that of the CQ/EDB group, ensuring the feasibility of the new HDs in dental materials. CLINICAL SIGNIFICANCE: The new CQ/HD PI systems could be potentially useful in dental materials, presenting improvements in restorations' esthetic and biocompatibility.

Pore Structure Tuning of Poly-EGDMA Biomedical Material by Varying the O-Quinone Photoinitiator.

Porous polymer monoliths with thicknesses of 2 and 4 mm were obtained via polymerization of ethylene glycol dimethacrylate (EGDMA) under the influence visible-light irradiation in the presence of a 70 wt% 1-butanol porogenic agent and o-quinone photoinitiators. The o-quinones used were: 3,5-di-tret-butyl-benzoquinone-1,2 (35Q), 3,6-di-tret-butyl-benzoquinone-1,2 (36Q), camphorquinone (CQ), and 9,10-phenanthrenequinone (PQ). Porous monoliths were also synthesized from the same mixture but using 2,2'-azo-bis(iso-butyronitrile) (AIBN) at 100 °C instead o-quinones. According to the results of scanning electron microscopy, all the resulting samples were conglomerates of spherical, polymeric particles with pores between them. Use of mercury porometry showed that the interconnected pore systems of all the polymers were open. The average pore size, Dmod, in such polymers strongly depended on both the nature of the initiator and the method of initiation of polymerization. For polymers obtained in the presence of AIBN, the Dmod value was as low as 0.8 µm. For polymers obtained via photoinitiation in the presence of 36Q, 35Q, CQ, and PQ, the Dmod values were significantly greater, i.e., 9.9, 6.4, 3.6, and 3.7 µm, respectively. The compressive strength and Young's modulus of the porous monoliths increased symbatically in the series PQ < CQ < 36Q < 35Q < AIBN with decreasing proportions of large pores (over 12 µm) in their polymer structures. The photopolymerization rate of the EGDMA and 1-butanol, 30:70 wt% mixture was maximal for PQ and minimal for 35Q. All polymers tested were non-cytotoxic. Based on the data from MTT testing, it can be noted that the polymers obtained via photoinitiation were characterized by their positive effect on the proliferative activity of human dermal fibroblasts. This makes them promising osteoplastic materials for clinical trials.

Synthesis and photooxidation of styrene copolymer bearing camphorquinone pendant groups.

(±)-10-Methacryloyloxycamphorquinone (MCQ) was synthesized from (±)-10-camphorsulfonic acid either by a known seven-step synthetic route or by a novel, shorter five-step synthetic route. MCQ was copolymerized with styrene (S) and the photochemical behavior of the copolymer MCQ/S was compared with that of a formerly studied copolymer of styrene with monomers containing the benzil (BZ) moiety (another 1,2-dicarbonyl). Irradiation (λ > 380 nm) of aerated films of styrene copolymers with monomers containing the BZ moiety leads to the insertion of two oxygen atoms between the carbonyl groups of BZ and to the formation of benzoyl peroxide (BP) as pendant groups on the polymer backbone. An equivalent irradiation of MCQ/S led mainly to the insertion of only one oxygen atom between the carbonyl groups of camphorquinone (CQ) and to the formation of camphoric anhydride (11) covalently bound to the polymer backbone. While the decomposition of pendant BP groups formed in irradiated films of styrene copolymers with pendant BZ groups leads to crosslinking, only small molecular-weight changes in irradiated MCQ/S were observed.

Effect of monowave and polywave light curing on the degree of conversion and microhardness of composites with different photoinitiators: An in vitro study.

Aim: The purpose of this study was to evaluate the effect of light-curing units (LCUs) on the degree of conversion (DC) and microhardness of composites with varying photoinitiator systems. Materials and Methodology: Two groups were formed based on LCU - monowave (Group M) and polywave (Group P). Each group was further divided into two subgroups based on photoinitiator systems - combination of camphorquinone (CQ), Ivocerin, and 2,4,6-trimethylbenzoyl diphenylphosphine oxide (Subgroup CIT) and only CQ (Subgroup C) in the composite. Samples prepared were 4 mm thick. Microhardness was measured at bottom surface by Vickers hardness tester, and DC was evaluated by Fourier transformation infrared spectroscopy. Statistical Analysis: Kolmogorov-Smirnov test was used. Results: Both the mean microhardness and DC of composite in subgroup C were similar (P > 0.05) in Group M (52.42 ± 2.67 and 48.30 ± 5.81) and Group P (51.77 ± 1.96 and 48.50 ± 4.87). The mean microhardness of composite containing a combination of photoinitiators was more in Group P (57.09 ± 2.61) as compared to Group M (47.37 ± 3.51). The mean DC was higher in Group P (59.75 ± 5.30) as compared to Group M (39.70 ± 3.57), and these differences were statistically significant (P < 0.05). Conclusion: The type of LCU affects DC and microhardness only in the case of composites containing a combination of photoinitiators.

Alternative co-initiators for photocurable dental resins: Polymerisation, quantum yield of conversion and cytotoxicity.

OBJECTIVE: Cyclic acetals such as are naturally occurring compounds capable of acting as co-initiators during free-radical polymerisation, and potentially serve to offer non-allergic and biologically less toxic alternatives to conventional (tertiary) amines. The current study aimed to evaluate the polymerisation efficiency and potential toxicity of cyclic acetals compared with conventional photoinitiator systems in photocurable dental resins. METHODS: Both, 1,3 benzodioxole (BZD) and piperonyl alcohol (PA) were used in 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 6.0 mol% concentrations. Whereas, N-phenyl glycine (NPG) was utilised in 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 mol% concentrations for photopolymerisation of an unfilled model resin system, BisGMA and TEGDMA (1:1 mass %), involving three separate camphorquinone (CQ) concentrations of 0.5 (Low), 1.0 (Intermediate) and 1.5 (High) mol%. Conventional tertiary amines; ethyl-4-dimethyamino benzoate (EDMAB) and dimethylaminoethyl methacrylate (DMAEMA) were utilised for comparison. Real-time degree of conversion (DC, %) was evaluated using Fourier transform near-infra-red spectroscopy and quantum yield of conversion of CQ was calculated using UV-Vis spectroscopy. Cytotoxicity of NPG and cyclic acetals were assessed using MTT to determine metabolic activity of human dental pulp cells (HDPCs). RESULTS: The cyclic acetals were capable of facilitating free radical polymerisation as co-initiators at all three CQ concentrations. Furthermore, the use of NPG as a co-initiator resulted in post-irradiation DC (%) that were comparable to both EDMAB and DMAEMA for all CQ concentrations. Alternative compounds facilitated the hydrogen abstraction process, which provided high conversion of CQ molecules. Quantum yield increased from 0.009 ± 0.0001 (0.5 mol%) to 0.03 ± 0.006 (6.0 mol%), and 0.01 ± 0.0003 (0.5 mol%) to 0.04 ± 0.001 (6.0 mol%), for respective BZD and PA formulations involving 1.0 mol% CQ. The use of NPG led to relatively higher quantum yield values (Up to 0.09 ± 0.007 at 4.0 mol%), though it exhibited competitive effects in absorbing blue light, which might be attributed to the photolytic degradation of NPG and the formation of N-methylaniline. MTT assay indicated alternative co-initiators to be comparatively less cytotoxic than EDMAB and CQ. Relative metablic activity of HDPCs treated with BZD, PA, and NPG eluates were 58.3 ± 15.7, 57.5 ± 17.4 and 64.6 ± 12.2 %, when compared with untreated HDPCs group (Control), respectively. Exposure to DMAEMA-based eluate led to relative metabolic activity (60.0 ± 0.5 %) that was comparable to that of cyclic acetals. Treatment with neat model resin eluate displayed the highest relative reduction in metabolic activity (28.9 ± 22.4) (P < 0.05), suggesting bisGMA and TEGDMA monomers played significant role in the overall cytotoxicity of photocurable systems involving HDPCs. SIGNIFICANCE: Cyclic acetals were capable of facilitating photo-induced free radical polymerisation reactions with relatively less cytotoxicity compared with their amine counterparts, which might realise reduced cytotoxicity of photocurable materials used for dentistry and biomaterial applications.

New hydrogen donors for amine-free photoinitiating systems in dental materials.

OBJECTIVES: The two-component Camphorquinone (CQ)/aromatic amine system is well-established and clearly corresponds to the reference system used in all photopolymerizable dental adhesives and composites. However, this CQ/amine system still suffers from the presence of aromatic amines that can be referenced as toxic. Therefore, the aim of this work is to develop amine-free photoinitiating systems (PISs) for the polymerization of a representative dental methacrylate resins upon blue light irradiation. The proposed strategy is based on the in-silico design (by molecular modelling) of new hydrogen donors (amine-free) bearing a copolymerizable moiety (methacrylate functionality) to ensure their low migration/leaching properties from the synthesized polymer. The new proposed PISs are compared to the well-established CQ/amine system for the polymerization of different methacrylate blends upon exposure to a commercial blue dental LED centered at 477 nm. METHODS: Molecular orbitals calculations are used to design new hydrogen donors exhibiting low C-H bond dissociation energies. Based on this in-silico design, the syntheses of new co-initiators are reported here for the first time. Real-time FTIR experiments are used to monitor the photopolymerization profiles. Color indexes measurements were also carried out to investigate the bleaching properties of the new proposed systems. RESULTS: Three new co-initiators are proposed as alternatives to aromatic amines in dental materials in combination with camphorquinone. The performances of the new proposed amine-free PISs for the photopolymerization of thick (1.4 mm) samples of methacrylate upon exposure to a blue dental LED under air are excellent. Similar or better polymerization performances are obtained with the new proposed amine-free systems compared to those reached with the CQ/amine reference. Excellent bleaching properties are also found. The involved chemical mechanisms are investigated through molecular orbitals calculations.

Camphorquinone Promotes the Antisenescence Effect via Activating AMPK/SIRT1 in Stem Cells and D-Galactose-Induced Aging Mice.

Terpenoids are a wide class of secondary metabolites with geroprotective properties that can alter the mechanism of aging and aging-related diseases. Camphorquinone (CQ) is a bicyclic monoterpenoid compound that can be efficiently synthesized through the continuous bromination and oxidation reaction of camphor. The purpose of this study is to investigate the effects of CQ on oxidative-stress-induced senescence and its underlying mechanisms. To generate oxidative stress in human bone marrow mesenchymal stem cells (hBM-MSCs) and mice, we used hydrogen peroxide (200 µM twice) and D-galactose (D-Gal) (150 mg/kg for 10 weeks), respectively. Our findings suggest that CQ potentially reduces senescence in hBM-MSCs and mouse heart tissue. In addition, we found that CQ boosted AMPK/SIRT1 activation and autophagy in both models. These results were subsequently verified in hBM-MSCs using compound C (an AMPK inhibitor) but AMPK inhibition by CC did not significantly reduce the SIRT1 and the autophagy markers. CQ treatment also reduced the gene expression of inflammation markers in D-Gal-induced aging mouse heart tissue. Furthermore, we determined that CQ fits all of the pharmacological parameters using the freely available SwissADME Web tool. Collectively, our findings demonstrate that CQ possesses antisenescence and cardioprotective properties, and that oxidative-stress-induced senescence could be suppressed by AMPK/SIRT1 and autophagy mechanisms.

The Photoinitiators Used in Resin Based Dental Composite-A Review and Future Perspectives.

The presented paper concerns current knowledge of commercial and alternative photoinitiator systems used in dentistry. It discusses alternative and commercial photoinitiators and focuses on mechanisms of polymerization process, in vitro measurement methods and factors influencing the degree of conversion and hardness of dental resins. PubMed, Academia.edu, Google Scholar, Elsevier, ResearchGate and Mendeley, analysis from 1985 to 2020 were searched electronically with appropriate keywords. Over 60 articles were chosen based on relevance to this review. Dental light-cured composites are the most common filling used in dentistry, but every photoinitiator system requires proper light-curing system with suitable spectrum of light. Alternation of photoinitiator might cause changing the values of biomechanical properties such as: degree of conversion, hardness, biocompatibility. This review contains comparison of biomechanical properties of dental composites including different photosensitizers among other: camphorquinone, phenanthrenequinone, benzophenone and 1-phenyl-1,2 propanedione, trimethylbenzoyl-diphenylphosphine oxide, benzoyl peroxide. The major aim of this article was to point out alternative photoinitiators which would compensate the disadvantages of camphorquinone such as: yellow staining or poor biocompatibility and also would have mechanical properties as satisfactory as camphorquinone. Research showed there is not an adequate photoinitiator which can be as sufficient as camphorquinone (CQ), but alternative photosensitizers like: benzoyl germanium or novel acylphosphine oxide photoinitiators used synergistically with CQ are able to improve aesthetic properties and degree of conversion of dental resin.

The Influence of Various Photoinitiators on the Properties of Commercial Dental Composites.

The aim of this article was to compare the biomechanical properties of commercial composites containing different photoinitiators: Filtek Ultimate (3M ESPE) containing camphorquinone (CQ); Estelite Σ Quick (Tokuyama Dental) with CQ in RAP Technology®; Tetric EvoCeram Bleach BLXL (Ivoclar Vivadent AG) with CQ and Lucirin TPO; and Tetric Evoceram Powerfill IVB (Ivoclar Vivadent AG) with CQ and Ivocerin TPO. All samples were cured with a polywave Valo Lamp (Ultradent Products Inc.) with 1450 mW/cm2. The microhardness, hardness by Vicker's method, diametral tensile strength, flexural strength and contraction stress with photoelastic analysis were tested. The highest hardness and microhardness were observed for Filtek Ultimate (93.82 ± 17.44 HV), but other composites also displayed sufficient values (from 52 ± 3.92 to 58,82 ± 7.33 HV). Filtek Ultimate not only demonstrated the highest DTS (48.03 ± 5.97 MPa) and FS (87.32 ± 19.03 MPa) but also the highest contraction stress (13.7 ± 0.4 MPa) during polymerization. The TetricEvoCeram Powerfill has optimal microhardness (54.27 ± 4.1 HV), DTS (32.5 ± 5.29 MPa) and FS (79.3 ± 14.37 MPa) and the lowest contraction stress (7.4 ± 1 MPa) during photopolymerization. To summarize, Filtek Ultimate demonstrated the highest microhardness, FS and DTS values; however, composites with additional photoinitiators such as Lucirin TPO and Ivocerin have the lowest polymerization shrinkage. These composites also have higher FS and DTS and microhardness than material containing CQ in Rap Technology.

Camphorquinone alters the expression of extracellular proteases in a 3D co-culture model of the oral mucosa.

OBJECTIVE: Objective of our investigation was to determine the influence of CQ on the expression of antioxidant proteins and extracellular proteases in a 3D co-culture model (3DCCM) of the oral mucosa and to analyze the distribution and stability of CQ within 3D-CCMs. METHODS: 3D-CCMs consist of confluent keratinocytes (OKF6/TERT2) on cell culture inserts on top of human gingival fibroblasts (HGFs) in collagen. The treatment was carried out by adding CQ to the cell culture inserts at two time points with declining concentrations. Mass spectrometry was used to analyze the CQ concentration above and underneath the OKF6/TERT2-layer. The expression of antioxidant genes was analyzed by qRT-PCR and western blot. The regulation of extracellular proteases from different families was analyzed by qRT-PCR and Proteome Profiler arrays. RESULTS: GC/MS analysis showed that CQ was evenly distributed within the model. Heme oxygenase-1, NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase 1 were induced on the mRNA and protein level in OKF6/TERT2 cells. In HGFs, only the transcription of NQO1 was induced. The transcription of extracellular proteases was increased mainly in OKF6/TERT2 cells 72 h after the initial treatment. The quantity of ten out of 25 analyzed extracellular proteases in the cell culture supernatant above and six underneath the keratinocyte-layer were modulated by CQ. SIGNIFICANCE: Despite its high reactivity, CQ is able to penetrate a dense keratinocyte-layer, presumably across plasma membranes. CQ initially induced the cellular defense machinery against oxidative stress and altered the expression of extracellular proteases. We assume a relationship between both processes.