3-methyl-1H-indol-1-yl dimethylcarbamodithioate attenuates periodontitis through targeting MAPK signaling pathway-regulated mitochondrial function.

Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.

Melatonin protects TEGDMA-induced preodontoblast mitochondrial apoptosis via the JNK/MAPK signaling pathway.

Resin monomer-induced dental pulp injury presents a pathology related to mitochondrial dysfunction. Melatonin has been regarded as a strong mitochondrial protective bioactive compound from the pineal gland. However, it remains unknown whether melatonin can prevent dental pulp from resin monomer-induced injury. The aim of this study is to investigate the effects of melatonin on apoptosis of mouse preodontoblast cells (mDPC6T) induced by triethylene glycol dimethacrylate (TEGDMA), a major component in dental resin, and to determine whether the JNK/MAPK signaling pathway mediates the protective effect of melatonin. A well-established TEGDMA-induced mDPC6T apoptosis model is adopted to investigate the preventive function of melatonin by detecting cell viability, apoptosis rate, expressions of apoptosis-related proteins, mitochondrial ROS (mtROS) production, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) level. Inhibitors of MAPKs are used to explore which pathway is involved in TEGDMA-induced apoptosis. Finally, the role of the JNK/MAPK pathway is verified using JNK agonists and antagonists. Our results show that melatonin attenuates TEGDMA-induced mDPC6T apoptosis by reducing mtROS production and rescuing MMP and ATP levels. Furthermore, mitochondrial dysfunction and apoptosis are alleviated only by the JNK/MAPK inhibitor SP600125 but not by other MAPK inhibitors. Additionally, melatonin downregulates the expression of phosphorylated JNK and counteractes the activating effects of anisomycin on the JNK/MAPK pathway, mimicking the effects of SP600125. Our findings demonstrate that melatonin protects mDPC6T cells against TEGDMA-induced apoptosis partly through JNK/MAPK and the maintenance of mitochondrial function, offering a novel therapeutic strategy for the prevention of resin monomer-induced dental pulp injury.

Mitochondrial biogenesis disorder and oxidative damage promote refractory apical periodontitis in rat and human.

AIM: To elucidate whether mitochondrial biogenesis disorder and damage from oxidative stress promote refractory apical periodontitis (RAP) in rat and human. METHODOLOGY: Twenty Enterococcus faecalis-induced RAPs were established in the maxillary first molars of male Wistar rats. Concurrently, 12 periapical lesion specimens from patients presenting with RAP were obtained by apicoectomy. Radiographic examination and histologic analysis were conducted to evaluate periapical bone tissue destruction and morphological changes. The expression of key regulators of mitochondrial biogenesis, PGC-1α and Nrf2, were detected by immunohistochemistry and double immunofluorescence staining, Western blot and real-time PCR were also assayed. Mitochondrial ROS (mtROS) was identified by MitoSOX staining. Mitochondrial function was detected by the quantification of ATP production, mitochondrial DNA (mtDNA) copy number and activities of mitochondrial respiratory chain complexes. Furthermore, mitochondrial oxidative stress was evaluated by the determination of 3-nitrotyrosine (3-NT), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-deoxyguanosine (8-OHdG) expression levels, as well as malondialdehyde (MDA) expression and antioxidant capacity. Student's t-test was performed to determine significance between the groups; p < .05 was considered significant. RESULTS: In the maxilla, significantly more bone resorption, greater number of periapical apoptotic cells and Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were observed in the RAP group compared with the control group (p < .01). PGC-1α and Nrf2 were significantly reduced in rat and human RAP lesions compared to the control group (p < .01) at both the mRNA and protein levels. Double immunofluorescence analysis of PGC-1α or Nrf2 with TOMM20 also indicated that mitochondrial biogenesis was impaired in RAP group (p < .01). Additionally, mitochondrial dysfunction was observed in RAP group, as reflected by increased mtROS, decreased ATP production, reduced mtDNA copy number and complexes of the mitochondrial respiratory chain. Finally, the expression levels of mitochondrial oxidative stress markers, 3-NT, 4-HNE and 8-OHdG, were significantly increased in the RAP group (p < .01). Consistent with this, systemic oxidative damage was also present in the progression of RAP, including increased MDA expression and decreased antioxidant activity (p < .01). CONCLUSIONS: Mitochondrial biogenesis disorder and damage from oxidative stress contribute to the development of RAP.

Application of digital virtual simulated design in the prosthodontic rehabilitation of a child with a novel EDA mutation in ectodermal dysplasia: A clinical report.

This clinical report presents a 7-year-old patient with ectodermal dysplasia and a newly identified ectodysplasin A (EDA) gene mutation (c.965 T>C). A removable partial denture combined with a complete denture was provided after considering the relevant factors. Based on digital smile design, resin crowns were fabricated to restore the cone-shaped teeth esthetically. Facial scan parameters and maxillofacial landmark localization on cone beam computed tomography (CBCT) images were combined for the registration of jaw relation, and a Gothic arch was subsequently 3-dimensionally printed for verification. Ultimately, dentures with accurate occlusion and satisfactory retention were delivered for this young patient with inadequate bone volume and poor fit that markedly improved his esthetics and function.

The role of mitochondrial dysfunction in periodontitis: From mechanisms to therapeutic strategy.

Periodontitis is an inflammatory and destructive disease of tooth-supporting tissue and has become the leading cause of adult tooth loss. The most central pathological features of periodontitis are tissue damage and inflammatory reaction. As the energy metabolism center of eukaryotic cells, mitochondrion plays a notable role in various processes, such as cell function and inflammatory response. When the intracellular homeostasis of mitochondrion is disrupted, it can lead to mitochondrial dysfunction and inability to generate adequate energy to maintain basic cellular biochemical reactions. Recent studies have revealed that mitochondrial dysfunction is closely related to the initiation and development of periodontitis. The excessive production of mitochondrial reactive oxygen species, imbalance of mitochondrial biogenesis and dynamics, mitophagy and mitochondrial DNA damage can all affect the development and progression of periodontitis. Thus, targeted mitochondrial therapy is potentially promising in periodontitis treatment. In this review, we summarize the above mitochondrial mechanism in the pathogenesis of periodontitis and discuss some potential approaches that can exert therapeutic effects on periodontitis by modulating mitochondrial activity. The understanding and summary of mitochondrial dysfunction in periodontitis might provide new research directions for pathological intervention or treatment of periodontitis.

The effect of periapical bone defects on stress distribution in teeth with periapical periodontitis: a finite element analysis.

BACKGROUND: Apical periodontitis directly affects the stress state of the affected tooth owing to the destruction of the periapical bone. Understanding the mechanical of periapical bone defects/tooth is clinically meaningful. In this study, we evaluate the effect of periapical bone defects on the stress distribution in teeth with periapical periodontitis using finite element analysis. METHODS: Finite element models of normal mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using a digital model design software. The edges of the mandible were fixed and the masticatory cycle was simplified as oblique loading (a 400 N force loaded obliquely at 45° to the long axis of the tooth body) to simulate the tooth stress state in occlusion and analyze the von Mises stress distribution and tooth displacement distribution in each model. RESULTS: Overall analysis of the models: Compared to that in the normal model, the maximum von Mises stresses in all the different periapical bone defect size models were slightly lower. In contrast, the maximum tooth displacement in the periapical bone defect model increased as the size of the periapical bone defect increased (2.11-120.1% of increase). Internal analysis of tooth: As the size of the periapical bone defect increased, the maximum von Mises stress in the coronal cervix of the tooth gradually increased (2.23-37.22% of increase). while the von Mises stress in the root apical region of the tooth showed a decreasing trend (41.48-99.70% of decrease). The maximum tooth displacement in all parts of the tooth showed an increasing trend as the size of the periapical bone defect increased. CONCLUSIONS: The presence of periapical bone defects was found to significantly affect the biomechanical response of the tooth, the effects of which became more pronounced as the size of the bone defect increased.

The effect of root canal treatment and post-crown restorations on stress distribution in teeth with periapical periodontitis: a finite element analysis.

AIM: To evaluate the effects of root canal treatment (RCT) and post-crown restoration on stress distribution in teeth with periapical bone defects using finite element analysis. METHODOLOGY: Finite element models of mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using digital model design software. The corresponding RCT and post-crown restoration models were constructed based on the different sizes of periapical bone defect models. The von Mises stress and tooth displacement distributions were comprehensively analyzed in each model. RESULTS: Overall analysis of the models: RCT significantly increased the maximum von Mises stresses in teeth with periapical bone defects, while post-crown restoration greatly reduced the maximum von Mises stresses. RCT and post-crown restoration slightly reduced tooth displacement in the affected tooth. Internal analysis of tooth: RCT dramatically increased the maximum von Mises stress in all regions of the tooth, with the most pronounced increase in the coronal surface region. The post-crown restoration balances the internal stresses of the tooth and is most effective in periapical bone defect - 20-mm model. RCT and post-crown restoration slightly reduced the tooth displacement in all regions of the affected tooth. CONCLUSIONS: Root canal treatment seemed not to improve the biomechanical state of teeth with periapical bone defects. In contrast, post-crown restoration might effectively balance the stress concentrations caused by periapical bone defects, particularly extensive ones.

Notoginsenoside R1 alleviates TEGDMA-induced mitochondrial apoptosis in preodontoblasts through activation of Akt/Nrf2 pathway-dependent mitophagy.

Incomplete polymerization or biodegradation of dental resin materials results in the release of resin monomers such as triethylene glycol dimethacrylate (TEGDMA), causing severe injury of dental pulp cells. To date, there has been no efficient treatment option for this complication, in part due to the lack of understanding of the mechanism underlying these phenomena. Here, for the first time, we found that notoginsenoside R1 (NR1), a bioactive ingredient extracted from Panax notoginseng, exerted an obvious protective effect on TEGDMA-induced mitochondrial apoptosis in the preodontoblast mDPC6T cell line. In terms of the mechanism of action, NR1 enhanced the level of phosphorylated Akt (protein kinase B), resulting in the activation of a transcriptional factor, nuclear factor erythroid 2-related factor 2 (Nrf2), and eventually upregulating cellular ability to resist TEGDMA-related toxicity. Inhibiting the Akt/Nrf2 pathway by pharmaceutical inhibitors significantly decreased NR1-mediated cellular antioxidant properties and aggravated mitochondrial oxidative damage in TEGDMA-treated cells. Interestingly, NR1 also promoted mitophagy, which was identified as the potential downstream of the Akt/Nrf2 pathway. Blocking the Akt/Nrf2 pathway inhibited mitophagy and abolished the protection of NR1 on cells exposed to TEGDMA. In conclusion, these findings reveal that the activation of Akt/Nrf2 pathway-mediated mitophagy by NR1 might be a promising approach for preventing resin monomer-induced dental pulp injury.

Effect of zirconia surface modification using dopamine polymerisation on the shear bond strength of resin cement.

This study evaluated the influence of polydopamine treatment on the surface properties and bond strength of yttria-stabilised tetragonal zirconia polycrystal (Y-TZP). Sixty-three zirconia blocks (10 × 10 × 2 mm) were randomly divided into three groups defined by surface treatment: (i) control group (C), (ii) grit-blasted with 110 µm alumina particles (GB), and (iii) polydopamine (PDA) coating. The surfaces of specimens subjected to different treatments were investigated by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and water contact angle measurements. After the surface treatments, the specimens were cemented to resin composite cylinders. After bonding, the shear bond strength of the ceramic to the resin was measured, and the failure mode of each specimen was analysed using a stereomicroscope. The results indicated that the shear bond strength is highest for the GB treatment and lowest for the controls. However, the difference between groups GB and PDA was not statistically significant. In the control group, adhesive failure was predominant, whereas in the treatment groups, mixed mode failure was predominant. The pre-treatment of Y-TZP ceramic with the polydopamine coating might improve the bond strength of the resin cement to the zirconia ceramic.

A combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia: a rare case report.

BACKGROUND: Supernumerary teeth (ST) is defined as an additional number of teeth compared to the normal dental formula. The prevalence rate of ST varies from 0.5 to 3.8% in the permanent dentition. When ST located distal to the third molar is acclaimed as distomolar. Moreover, kissing molar is an extremely scarce condition of distomolars, pointed in the opposite direction in a single follicular space. Meanwhile, macrodontia is also a rare shape anomaly characterized by a large crown and tapering root. CASE PRESENTATION: A 22-year-old Chinese man presented a combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia. Radiographically, two maxillary bilateral distomolars located at the buccal side of adjacent third molars. One mandibular distomolar with the adjacent third molar was contacted by occlusal surfaces while roots were pointed oppositely, which could be diagnosed as KM. Furthermore, the left mandibular third molar can be inferred to be a macrodontia, characterized by a large crown and tapering root. After a thorough investigation, we excluded the possibilities of systemic diseases and genetic inheritance. However, the etiology of this rare combination deserves to be further explored. CONCLUSION: The combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia is very rare, especially presented in the patient with no syndromes. As there were no complications with these conditions, long-term observation has been recommended for the patient. In addition, the true etiology need a further exploration.

A Digital Esthetic Rehabilitation of a Patient with Dentinogenesis Imperfecta Type II: A Clinical Report.

A 19-year-old female affected by dentinogenesis imperfecta type II (DI-II), a genetic disease that affects the structural integrity of the dentin, presented with a chief complaint of discolored teeth. For this patient, digital techniques, including digital smile design (DSD), the ARCUSdigma axiograph and computer-aided design/computer-aided manufacturing (CAD/CAM), were extensively used in all phases of the rehabilitation process. Compared to traditional analog methods, these digital techniques could reduce the constant confirmation of occlusion, promote communication between clinicians and dental technicians, achieve accurate occlusion with relatively high efficiency, and improve the efficacy of esthetic rehabilitation in the treatment of this patient with DI-II.

Oxidative stress-related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta-analysis.

AIM: Oxidative stress (OS) biomarkers have been detected in saliva and gingival crevicular fluid (GCF) during chronic periodontitis (CP) progression; however, the relationship between OS biomarkers and CP progression remains elusive. The purpose of this meta-analysis is to investigate the relationship between local OS biomarkers and CP. METHODS: This review was conducted through a systematic search from three databases. Studies on CP participants were included as an experimental group, and studies on periodontally healthy (PH) participants were included as a control. Mean effects were expressed as standardized mean difference with their associated 95% confidence intervals. RESULTS: From a total of 2,972 articles, 32 articles fulfilled the inclusion criteria. We found a significant decrease of total antioxidant capacity and a significant increase of malondialdehyde (MDA), nitric oxide, total oxidant status (TOS), and 8-hydroxy-deoxyguanosine levels in the saliva of CP patients. Moreover, we also found an elevation of MDA level in GCF of CP group when compared with the PH group. There were no significant differences of salivary and GCF superoxide dismutase levels, salivary glutathione peroxidase level, and GCF TOS level between two groups. However, a high heterogeneity was observed among evaluated studies. CONCLUSIONS: Despite the limitations of this study, the result of our meta-analysis supported the rationale that there was a direct link between CP and OS-related biomarkers' levels in the local site, indicating the important role of OS in the onset and development of CP.

A multidisciplinary approach to the functional and esthetic rehabilitation of dentinogenesis imperfecta type II: A clinical report.

A 20-year-old woman presented with an unesthetic appearance and severe wear of the anterior teeth. Definitive expected treatment was designed by multidisciplinary combination therapy. Meanwhile, gene sequencing was used diagnostically, and digital smile design (DSD) was used to design the esthetics of the anterior teeth. The 3-month follow-up showed an acceptable outcome. The whole-exon sequencing and direct sequencing of polymerized chain reaction products of dentin sialophosphoprotein were performed, but further sequencing was needed in the repeat region of dentin sialophosphoprotein exon 5 (the data were not shown). DSD assisted and improved the esthetic design of the definitive restoration, communication with the patient, and predictability of the treatment. This treatment demonstrates that the diagnosis and differential diagnosis of patients with dentinogenesis imperfecta (DGI)-II are essential and effective for implementing the definitive treatment plan. Gene screening can be used as an auxiliary method of diagnosing DGI-II. In terms of esthetic design, DSD played an important role in ensuring a satisfactory result. Moreover, a multidisciplinary treatment protocol focusing on prosthodontics, which is different from the traditional treatment of DGI-II and consists solely of prosthodontic rehabilitation, proved highly effective in the esthetic restoration of a patient with DGI-II.

Mitochondrial dysfunction is involved in the aggravation of periodontitis by diabetes.

AIM: To elucidate whether mitochondrial dysfunction contributes to aggravated periodontitis in diabetes. MATERIALS AND METHODS: Sixty-four wistar rats were randomly assigned into four groups: control, periodontitis, diabetes, and diabetic periodontitis. Two weeks after induction of diabetes, periodontitis was induced by silk ligation for 2 weeks and thereafter evaluated by assessing alveolar bone loss and apoptosis of periodontium cells. Mitochondrial oxidative stress was detected by MitoSOX staining. Mitochondrial function was determined by measuring ATP production, and by assessing mitochondrial DNA copy number, activities of electron transport chain complexes, and biogenesis with real-time PCR. RESULTS: Significantly severer bone loss, enhanced periodontium cell apoptosis, and mitochondrial oxidative stress were found in the rats with diabetic periodontitis than the others. Furthermore, diabetic rats with periodontitis presented severer mitochondrial dysfunction than lean rats with periodontitis, as reflected by compromised ATP production, decreased mitochondrial DNA copy number, reduced gene expression of electron transport chain complex I subunits, and impaired mitochondrial biogenesis (p < 0.05). Multiple regression analysis further indicated a close correlation between these mitochondrial events and bone loss in diabetic periodontitis. CONCLUSIONS: Mitochondrial dysfunction was positive correlated to aggravated periodontitis in diabetes and might represent a therapeutic target for diabetic periodontitis.

Effect of maleic acid on the bond strength of fibre posts to root dentine.

The aim of this study was to evaluate the effect of maleic acid (MA) on both the bond strength of fibre post to root dentine and smear layer removal after post space preparation. Sixty, single-canal premolars were endodontically treated and randomly assigned to four groups: group 1 [0.9% saline solution (control]); group 2 [2.5% sodium hypochlorite (NaOCl)]; group 3 [17% ethylenediaminetetraacetic acid (EDTA) followed by 2.5% NaOCl]; and group 4 (7% MA followed by 2.5% NaOCl). Self-adhesive resin cement was used to test the adhesion of a glass-fibre post to the root dentine through a micropush-out test. Scanning electron microscopy was performed to examine and score the treated specimens for smear layer removal, and stereomicroscopy was applied to investigate the failure modes of fibre posts. Maleic acid exhibited the highest mean bond-strength values in the apical regions among all the groups. Most failure modes (31.9%) were adhesive-type failures between the dentine and luting materials. Maleic acid performed statistically significantly better than the other groups regarding smear layer removal, especially in the apical region. Maleic acid is an effective irrigant that can remove the smear layer, open dentinal tubules, and act as a high-efficiency final irrigant in activation protocols.

Effect of application time of maleic acid on smear layer removal and mechanical properties of root canal dentin.

OBJECTIVES: To evaluate the effect of maleic acid (MA) on the cleaning efficacy and mechanical properties of root canal dentine with respect to different time exposure. MATERIALS AND METHODS: One hundred and eighty single-canal premolars were instrumented with rotary-files and then randomly assigned to test groups receiving 7% MA for 30 s, 45 s, 1 min, or 3 min or to control groups treated with 0.9% saline or 17% ethylenediaminetetraacetic acid for 45 s. The micro-hardness, nano-hardness and elastic modules were measured before and after treatment, while the amount of smear and erosion in the coronal, middle and apical thirds in root canal were evaluated by scanning electron microscopy, finally, the fracture strength was assessed by vertical root fracture testing. RESULTS: The efficacy of smear layer removal increased with increasing MA application time. The largest effect was observed at 45 s, even in the apical third, whereas the treatment for 1 min resulted in irreversible erosion of the dentine surface. The micro-hardness and nano-indentation testing confirmed that the micro- and nano-scale mechanical properties were significantly decreased after MA application for 1 min. Furthermore, the specimens treated with MA for 3 min presented the lowest fracture resistance among all groups. In contrast, the 45 s treatment appeared to increase the fracture resistance of the tooth. CONCLUSIONS: The cleaning efficacy and mechanical properties of root canal dentine varied with MA exposure time. The application of MA for 45 s was found to be the most promising for clinical use.

Effect of gamma irradiation on the wear behavior of human tooth dentin.

OBJECTIVES: The objective of this study was to evaluate the effect of gamma irradiation on the wear behavior of human tooth dentin in terms of possible alterations in crystallinity, grain size, and composition. MATERIALS AND METHODS: Human premolars (n = 19) were collected to obtain the perpendicular or parallel to the direction of the dentin tubule specimens. Each specimen was subjected to 60 Gy of gamma irradiation, in daily increments of 2 Gy. The nanoscratch tests were conducted. The scratch traces were observed via scanning electron microscope (SEM) and surface profilometer. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to investigate the alteration of crystallography and chemical composition of dentin after irradiation. The change of surface microhardness (SMH) was also evaluated. RESULTS: The nanoscratch results showed that the friction coefficient of dentin after irradiation became higher, and the depths and widths of scratch were greater than that of dentin before irradiation. Additionally, irradiation decreased the crystallinity of dentin and induced the formation of bigger crystals. The carbonate/mineral ratio was increased. Furthermore, a significant reduction in microhardness after irradiation was observed. The main damage mechanisms consisted of the formation of delamination and crack in both the specimens cut perpendicular and parallel to tubule dentin after irradiation. CONCLUSION: Irradiation affected directly the wear behavior of tooth dentin, accompanied by the alterations in crystallography, chemical composition, and surface microhardness of dentin. CLINICAL RELEVANCE: This would help extend understanding the influence of irradiation on dentin and provide suggestions for selecting more suitable materials for irradiated tooth.

Changes in composition and enamel demineralization inhibition activities of gallic acid at different pH values.

BACKGROUND: Gallic acid (GA) has been shown to inhibit demineralization and enhance remineralization of enamel; however, GA solution is highly acidic. This study was to investigate the stability of GA solutions at various pH and to examine the resultant effects on enamel demineralization. METHODS: The stability of GA in H2O or in phosphate buffer at pH 5.5, pH 7.0 and pH 10.0 was evaluated qualitatively by ultraviolet absorption spectra and quantified by high performance liquid chromatography with diode array detection (HPLC-DAD). Then, bovine enamel blocks were subjected to a pH-cycling regime of 12 cycles. Each cycle included 5 min applications with one of the following treatments: 1 g/L NaF (positive control), 4 g/L GA in H2O or buffered at pH 5.5, pH 7.0 and pH 10.0 and buffers without GA at the same pH (negative control), followed by a 60 min application with pH 5.0 acidic buffers and a 5 min application with neutral buffers. The acidic buffers were analysed for dissolved calcium. RESULTS: GA was stable in pure water and acidic condition, but was unstable in neutral and alkaline conditions, in which ultraviolet spectra changed and HPLC-DAD analysis revealed that most of the GA was degraded. All the GA groups significantly inhibited demineralization (p < 0.05) and there was no significant difference of the inhibition efficacy among different GA groups (p > 0.05). CONCLUSIONS: GA could inhibit enamel demineralization and the inhibition effect is not influenced by pH. GA could be a useful source as an anti-cariogenic agent for broad practical application.

The Influence of Erbium Laser Pretreatment on Dentin Shear Bond Strength and Bond Failure Modes: A Systematic Review and Network Meta-Analysis.

PURPOSE: To systematically review in-vitro studies that evaluated the influence of erbium laser pretreatment on dentin shear bond strength (SBS) and bond failure modes. MATERIALS AND METHODS: Electronic databases (PubMed, Cochrane Central, Embase, and Web of Science) were searched. Only in-vitro studies involving erbium laser irradiation of the dentin surface and SBS testing of the bonded resin block were included. The three common modes of bond failure (1. adhesive, 2. cohesive, and 3. mixed) were observed and analyzed. The network meta-analysis (NMA) was performed by Stata 15.0 software, the risk of bias was evaluated, and the certainty of the evidence was assessed by the Confidence in Network Meta-analysis (CINeMA). RESULTS: Forty studies with nine pretreatments (1. blank group: BL; 2. phosphoric acid etch-and-rinse: ER; 3. self-etch adhesive: SE; 4. Er:YAG laser: EL; 5. Er,Cr:YSGG laser: ECL; 6. ER+EL; 7. ER+ECL; 8. SE+EL; 9. SE+ECL) were included in this analysis. The NMA of SBS showed that ER+EL [SMD = 0.32, 95% CI (0.11, 0.98)] had the highest SBS next to ER, especially when using one of the 3M ESPE adhesives, followed by EL, ECL, SE and SE+EL. The Ivoclar Vivadent adhesives significantly increased the SBS of the ECL [SMD = 0.37, 95% CI (0.16,0.90)] and was higher than ER+EL [SMD = 0.25,95% CI (0.07,0.85)]. Finally, the surface under the cumulative ranking curve (SUCRA) value indicated that ER+EL (SUCRA = 71.0%) and EL (SUCRA = 62.9%) were the best treatments for enhancing dentin SBS besides ER. ER+EL (SUCRA = 85.3%), ER (SUCRA = 83.7%) and ER (SUCRA = 84.3%) had the highest probability of occurring in adhesive, cohesive and mixed failure modes, respectively. CONCLUSION: Er:YAG and Er,Cr:YSGG lasers improved dentin SBS compared to the blank group, especially when the acid etch-and-rinse pretreatment was combined with Er:YAG laser. Shear bond strength and failure mode do not appear to be directly related.

The role of oxidative stress biomarkers in the development of peri-implant disease: A systematic review and meta-analysis.

OBJECTIVES: To analyze the role of oxidative stress (OS) biomarkers in peri­implant diseases using a systematic review and meta-analysis approach. DATE: The review incorporated cross-sectional studies, randomized controlled trials, and case-control trials to evaluate the differences in OS biomarkers of peri­implant disease. SOURCES: A comprehensive literature search was conducted in electronic databases such as PubMed, Scopus, Embase, Web of Science, and CNKI, and no restrictions were applied during the search process. STUDY SELECTION: A total of 452 studies were identified, of which 18 were eligible for inclusion. Risk of bias and sensitivity analysis were assessed using Egger's test and funnel plots. RESULTS: We found that the levels of glutathione peroxidase (GSH-Px) in the peri­implant sulcus fluid (PISF) of patients with peri­implant diseases were significantly reduced (SMD = -1.40; 95 % CI = 1.70, -1.11; p < 0.001), while the levels of total myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly increased (SMD = 0.46; 95 % CI = 0.12, 0.80; p = 0.008; SMD = 0.28; 95 % CI = 0.01, 0.56; p = 0.043). However, there were no significant differences of MPO concentration (SMD = 0.38; 95 % CI = -0.39, 1.15; p = 0.331) and superoxide dismutase (SOD)(SMD = -0.43; 95 % CI = -1.94, 1.07; p = 0.572) in PISF between peri­implant disease group and control group. Similarly, salivary MPO did not show significant differences (SMD = 1.62; 95 % CI = -1.01, 4.24; p = 0.227). CONCLUSIONS: Our results supported that the level of local OS biomarkers was closely related to peri­implant diseases. GSH-Px, total MPO and MDA may be PISF biomarkers with good capability to monitor the development of peri­implant disease. CLINICAL SIGNIFICANCE: This study found significant differences in the levels of local OS biomarkers (GSH-Px, total MPO, and MDA) between patients with peri­implant diseases and healthy subjects, which may be ideal candidate biomarkers for predicting and diagnosing peri­implant diseases.