Physical training attenuates systemic cytokine response and tissue damage triggered by apical periodontitis.

Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.

Dental findings frequently overlooked in sinus computed tomography reports.

OBJECTIVES: Computed tomography (CT) and cone beam computed tomography (CBCT) represent the main imaging modalities used in rhinosinusitis patients and are also important in odontogenic sinusitis (OS) diagnostics. Reports, however, often lack information on dentition. Here, we aimed to determine how maxillary dentition is initially interpreted in rhinosinusitis patients' CT/CBCT reports and which dental findings in particular are potentially missed, thus needing more attention. STUDY DESIGN: CT/CBCT scans and radiological reports from 300 rhinosinusitis patients were analysed focusing specifically on dental findings. An experienced oral and maxillofacial radiologist re-evaluated the scans and the assessment was compared to the original reports using the McNemar test. RESULTS: From the 300 original reports, 233 (77.7%) mentioned the maxillary teeth. The most frequent statement (126/300, 42.0%) was 'no apical periodontitis'. Apical periodontitis and severe alveolar bone loss were significantly overlooked (p < 0.001). Amongst the 225 patients for whom the CT/CBCT report initially lacked information on dental pathology, 22 patients were diagnosed with apical periodontitis and 16 with severe alveolar bone loss upon re-evaluation. CONCLUSIONS: Dental pathology remains underreported in rhinosinusitis patients' CT/CBCT reports. Because these reports affect OS diagnostics, a routine and structured review of the maxillary teeth by a radiologist is necessary. Such examinations should encompass the maxillary teeth.

Pathogenic factors of maxillary sinus mucosal thickening observed by cone-beam computed tomography (CBCT).

OBJECTIVE: To explore the pathogenic factors associated with maxillary sinus mucosal thickening with Cone-beam computed Tomography (CBCT). METHODS: From 2016 through 2020, 93 patients with periapical periodontitis or periodontitis in the maxillary posterior dental region were selected. RESULTS: The preoperative thickness of the periodontitis group was significantly higher than that of the periapical periodontitis group (P < 0.05). The difference achieves statistical significance for the comparison of the thickness change with various severity of inflammation (F = 54.824, P = 0.000), the change with time (F = 312.741, P = 0.000). and the change with the interaction severity of inflammation and time（F = 86.132, P = 0.000). CONCLUSIONS: Patients with maxillary sinus mucosa thickening caused by periodontitis and periapical periodontitis should be extracted their infectious teeth and get thoroughly debridement. Maxillary sinus augmentation can perform favorable efforts 3-6 months after extracting teeth.

Characterization of cells in blood evoked from periapical tissues in immature teeth with pulp necrosis and their potential for autologous cell therapy in Regenerative Endodontics.

OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.

Platelet rich fibrin and MTA in the treatment of teeth with open apices.

BACKGROUND: The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical lesions and open apices. METHODS: Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance. RESULTS: All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments. CONCLUSIONS: PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.

Allogeneic Bone Marrow Mesenchymal Stromal Cell Transplantation Induces Dentin Pulp Complex-like Formation in Immature Teeth with Pulp Necrosis and Apical Periodontitis.

INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.

High-Fat Diet Influences Dendritic Cells and T-Cell Infiltration in Apical Periodontitis in Mice.

INTRODUCTION: Diet-induced metabolic syndrome may influence the progression and healing of apical periodontitis (AP). The aim of this study was to evaluate the inflammatory immune response of dendritic cells (DCs) and T helper (Th) cells in normal versus obese mice with AP. METHODS: Twenty male C57BL/6 mice were divided into 2 groups: normal chow (NC) and high-fat diet (HFD) for 12 wk. AP was induced in both groups by creating pulp exposure of the right first maxillary molar to the oral environment. Contralateral first molars from each mouse were used as a control. The animal's body mass was recorded on a weekly basis, and they were euthanized after 30 d. The maxillae were removed and processed for micro-computed tomography (micro-CT), histologic analysis, and immunofluorescence staining for DCs (CD11c), Th17 (IL-17A), and T regulatory cells (FOXP3 and IL-10). Different groups were analyzed by Mann-Whitney U test, Student t test, and ordinary 1-way analysis of variance followed by Tukey's multiple comparisons test. The level of significance (α) was set at 0.05. RESULTS: The HFD group showed larger AP lesions than the NC group from micro-CT analysis. For the NC group, induction of AP significantly increased immune cell infiltration when compared with control. HFD showed increased DCs and Th17 infiltration in the control group without AP. In addition, there was no significant change in the amount of DCs and Th17 in the HFD-AP group when compared with the NC-AP and HFD-control groups. CONCLUSIONS: HFD resulted in an increased immune cell infiltration in the periapical area without AP. Despite the larger AP lesion observed in HFD-AP than that of NC-AP, the amount of infiltrated inflammatory cells did not differ significantly. The results of this study suggest that the DCs and Th17 inflammatory pathways are affected by HFD in the periapical region, but their contribution toward AP complicated by metabolic syndrome requires further investigation.

Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs.

BACKGROUND: Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to limitations in successful therapy. Thus, the aim of this study was to examine the effect of residual bacteria on the outcome of pulp regeneration in mature teeth with apical periodontitis in dogs. METHODS: Periapical lesions were induced in 32 root canals of 4 dogs in two different models in severities, model A and model B. Model A (moderate infection): the canal exposed to the oral cavity for 2 weeks and then closed for 2 weeks. Model B (severe infection): the canal exposed to the oral cavity for 2 months and then closed for 5 months. All root canals were irrigated with 6% sodium hypochlorite, and 3% EDTA and further with 0.015% levofloxacin-containing nanobubbles, which was also used as an intracanal medicament. The aseptic conditions were examined by bacterial anaerobic culture and/or PCR analyses. The root canal treatment was repeated several times, and allogeneic dental pulp stem cells were transplanted into the root canals. The radiographic evaluation of periapical lesions was performed by cone-beam computed tomography before the first treatment, just after cell transplantation, and after 2 months and 6 months in both model A, model B, respectively. The animals were then sacrificed and the jaw blocks were harvested for histological and histobacteriological evaluations of pulp regeneration and periapical tissue healing. Furthermore, the DiI-labelled DPSCs were transplanted into the root canals after complete disinfection (n = 4) or without root canal treatment (n = 4) in the apical periodontitis model (model A) in one dog, and cell localization was compared 72 h after transplantation. RESULTS: In 8 out of 12 canals from model A, and 10 out of 15 canals from model B, pulp regeneration with good vascularization, innervation, and a significant reduction in the radiolucent area of the periapical lesions were observed. However, in the other 4 canals and 5 canals from model A and model B, respectively, no pulp tissue was regenerated, and inflammation in the periapical tissue, and external resorption or healed external resorption were detected. The presence of residual bacteria in the periapical tissues and severe inflammation were significantly associated with inhibition of regenerated pulp tissue in these 9 unsuccessful canals (P < 0.05, each) (OR = 0.075, each) analyzed by multiple logistic regression analysis. For cellular kinetics, transplanted cells remained in the disinfected root canals, while they were not detected in the infected root canals, suggesting their migration through the apical foramen under the influence of inflammation. CONCLUSIONS: A true pulp-dentin complex was regenerated in the root canal by the pulp regenerative therapy in mature teeth with apical lesions. The successful pulp regeneration was negatively associated both with residual bacteria and inflammation in the periapical tissue.

Clinically Oriented CBCT Periapical Lesion Evaluation via 3D CNN Algorithm.

Apical periodontitis (AP) is one of the most prevalent disorders in dentistry. However, it can be underdiagnosed in asymptomatic patients. In addition, the perioperative evaluation of 3-dimensional (3D) lesion volume is of great clinical relevance, but the required slice-by-slice manual delineation method is time- and labor-intensive. Here, for quickly and accurately detecting and segmenting periapical lesions (PALs) associated with AP on cone beam computed tomography (CBCT) images, we proposed and geographically validated a novel 3D deep convolutional neural network algorithm, named PAL-Net. On the internal 5-fold cross-validation set, our PAL-Net achieved an area under the receiver operating characteristic curve (AUC) of 0.98. The algorithm also improved the diagnostic performance of dentists with varying levels of experience, as evidenced by their enhanced average AUC values (junior dentists: 0.89-0.94; senior dentists: 0.91-0.93), and significantly reduced the diagnostic time (junior dentists: 69.3 min faster; senior dentists: 32.4 min faster). Moreover, our PAL-Net achieved an average Dice similarity coefficient over 0.87 (0.85-0.88), which is superior or comparable to that of other existing state-of-the-art PAL segmentation algorithms. Furthermore, we validated the generalizability of the PAL-Net system using multiple external data sets from Central, East, and North China, showing that our PAL-Net has strong robustness. Our PAL-Net can help improve the diagnostic performance and speed of dentists working from CBCT images, provide clinically relevant volume information to dentists, and can potentially be applied in dental clinics, especially without expert-level dentists or radiologists.

Influence of IgA nephropathy on the progression of pulpitis and apical periodontitis in HIGA mice.

OBJECTIVES: Immunoglobulin (Ig)A nephropathy has been associated with oral infections such as periodontitis, but its pathogenesis is not fully understood; no treatments exist. This study analyzes the influence of IgA nephropathy, an autoimmune disease, on the pathogenesis of pulpitis and apical periodontitis. METHODS: Two groups of mice were used in pulp infection experiments: high serum IgA nephropathy model mice (HIGA) and control mice (BALB/c). Histologic analyses of the pulp and apical periodontal tissues were performed on days 3, 5, 7, 14, and 28 following oral bacterial infection. The dynamics of odontoblasts, apoptotic cells, and IgA expression were analyzed using anti-Nestin, TUNEL, and anti-IgA staining, respectively. RESULTS: Inflammatory cells infiltrated the exposed pulp at day three in both groups and by 14 days, these cells had infiltrated from the pulp to the apical periodontal tissue. The area of necrotic pulp tissue increased significantly in the control group at seven days. Odontoblasts decreased from day three onwards and disappeared by 28 days in both groups. The number of apoptotic cells in the pulp and apical periodontal tissues was significantly higher in the experimental group at day 28. The experimental group exhibited a significant increase in IgA production in the pulp after 14 days. Bone resorption in the apical periodontal tissue was significantly decreased in the experimental group at day 28. CONCLUSIONS: The results of this study suggest that IgA nephropathy may modulate the inflammatory response and sustain long-term biological defense responses in pulpitis and apical periodontitis in HIGA mice.

Effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats.

OBJECTIVE: To evaluate the effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats. METHODOLOGY: In total, 32 male Wistar rats were divided into four groups (n = 8): AP-induced apical periodontitis; S-cigarette smoke inhalation; APS-induced AP and cigarette smoke inhalation; and C (control)-neither AP nor cigarette smoke inhalation. To induce cigarette smoke inhalation, the animals were kept in a chamber filled with tobacco smoke for 8 min thrice a day for 50 days. AP was induced 20 days after inhalation initiation by exposing their coronary pulp to their oral environment for 30 days. After animals were euthanized, their right hemimaxillae were removed for histopathological, semi-quantitative and immunohistochemical (F4/80, CD206 and iNOS) analyses. RESULTS: Quantitative data showed a moderate number of inflammatory infiltrates in AP and an intense number in APS (p < .05). Comparing F4/80+ cells showed no statistically significant differences among groups, but we found more CD206+ cells in AP than in C and S (p > .05). INOS+ immunostaining showed a significant increase in AP and APS, when compared with C and S (p < .05). APS had more iNOS+ cells than AP (p < .05). CONCLUSION: Cigarette smoke inhalation worsened AP, leading to a predominantly pro- inflammatory profile in our experimental model.

Nociceptors regulate osteoimmune transcriptomic response to infection.

Osteoimmune diseases, such as apical periodontitis, are prevalent, often painful, inflammatory conditions resulting in bone loss and reduced quality of life. There is growing evidence that the nociceptive fibers densely innervating affected tissues regulate disease progression; therefore, we hypothesized that nociceptors regulate the transcriptomic profile of the periapical osteolytic lesion in a mouse model of apical periodontitis. Male control and nociceptor-ablated mice underwent pulp exposures, and after 0, 7, or 14 days, total RNA from periapical tissues was submitted for sequencing and bioinformatic analysis. Pulp exposure triggers the differential expression of hundreds of genes over the course of infection. At 14 days post pulp exposure, 422 genes, including Tnf, Il1a, and Il1b, were differentially expressed between nociceptor-ablated and control mice with greater enrichment of biological processes related to inflammation in nociceptor-ablated mice. Nociceptor ablation regulates the transcriptomic profile of periapical lesions in a mouse model of apical periodontitis, shifting the gene expression profile to a greater enrichment of inflammatory genes, suggesting nociceptors play a role in the kinetics of the immune response. This newly uncovered neuro-immune axis and its mechanisms in apical periodontitis can be an important therapeutic target for the treatment of this prevalent disease.

A novel analysis of the formation and resorption changes in dental hard tissue using longitudinal in vivo micro computed tomography.

This study was to investigate the new analysis manner of dental hard tissue change using in vivo micro-computed tomography (CT) in rat. Scanning, registration, analyzing, and presenting method to track longitudinal in vivo micro-CT data on dental hard tissues were validated in murine models: formative, dentin thickness after direct pulp capping with mineral trioxide aggregate; resorptive, development of apical bone rarefaction in apical periodontitis model. Serial in vivo micro-CT scans were analyzed through rigid-registration, active-contouring, deformable-registration, and motion vector-based quantitative analyses. The rate and direction of hard tissue formation after direct pulp capping was datafied by tracing coordinate shift of fiducial points on pulp chamber outline in formative model. The development of apical periodontitis could be monitored with voxel counts, and quantitatively analyzed in terms of lesion size, bone loss, and mineral density in resorptive model. This study supports the application of longitudinal in vivo micro-CT for resorptive- and formative-phase specific monitoring of dental hard tissues.

Necroptosis in apical periodontitis: A programmed cell death with multiple roles.

Programmed cell death (PCD) has been a research focus for decades and different mechanisms of cell death, such as necroptosis, pyroptosis, ferroptosis, and cuproptosis have been discovered. Necroptosis, a form of inflammatory PCD, has gained increasing attention in recent years due to its critical role in disease progression and development. Unlike apoptosis, which is mediated by caspases and characterized by cell shrinkage and membrane blebbing, necroptosis is mediated by mixed lineage kinase domain-like protein (MLKL) and characterized by cell enlargement and plasma membrane rupture. Necroptosis can be triggered by bacterial infection, which on the one hand represents a host defense mechanism against the infection, but on the other hand can facilitate bacterial escape and worsen inflammation. Despite its importance in various diseases, a comprehensive review on the involvement and roles of necroptosis in apical periodontitis is still lacking. In this review, we tried to provide an overview of recent progresses in necroptosis research, summarized the pathways involved in apical periodontitis (AP) activation, and discussed how bacterial pathogens induce and regulated necroptosis and how necroptosis would inhibit bacteria. Furthermore, the interplay between various types of cell death in AP and the potential treatment strategy for AP by targeting necroptosis were also discussed.

Metformin Reduces Bone Resorption in Apical Periodontitis Through Regulation of Osteoblast and Osteoclast Differentiation.

INTRODUCTION: We have previously demonstrated that auxiliary metformin therapy promotes healing of apical periodontitis. Here we aimed to investigate the effects of metformin on osteoblast differentiation and osteoclast formation in cultured cells and rat apical periodontitis. METHODS: Murine pre-osteoblasts MC3T3-E1 and macrophages RAW264.7 were cultured under hypoxia (2% oxygen) or normoxia (21% oxygen) and stimulated with receptor activator of nuclear factor-κB ligand (RANKL) when indicated. Metformin was added to the cultures to evaluate its anti-hypoxic effects. Expressions of osteoblast differentiation regulator runt-related transcription factor 2 (RUNX2), RANKL, and osteoclast marker tartrate-resistant acid phosphatase (TRAP) were assessed by Western blot. Apical periodontitis was induced in mandibular first molars of 10 Sprague-Dawley rats. Root canal therapy with or without metformin supplement was performed. Periapical bone resorption was measured by micro-computed tomography. Immunohistochemistry was used to examine RUNX2, RANKL, and TRAP expressions. RESULTS: Hypoxia suppressed RUNX2 expression and enhanced RANKL synthesis in pre-osteoblasts. TRAP production increased in macrophages after hypoxia and/or RANKL stimulation. Metformin reversed hypoxia-induced RUNX2 suppression and RANKL synthesis in pre-osteoblasts. Metformin also inhibited hypoxia and RANKL-enhanced TRAP synthesis in macrophages. Intracanal metformin diminished bone loss in rat apical periodontitis. Comparing with vehicle control, cells lining bone surfaces in metformin-treated lesions had significantly stronger expression of RUNX2 and decreased synthesis of RANKL and TRAP. CONCLUSIONS: Alleviation of bone resorption by intracanal metformin was associated with enhanced osteoblast differentiation and diminished osteoclast formation in rat apical periodontitis. Our results endorsed the role of metformin as an effective medicament for inflammatory bone diseases.

Reparative Dentin Formation Following Dental Pulp Capping is Mediated by TNFR1 In Vivo.

INTRODUCTION: Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine that promotes biomineralization in vitro in dental pulp cells. However, the role of TNF-α-TNF receptor 1 (TNFR1) signaling in reparative dentin formation and related inflammatory pathways is not known. Therefore, the aim of this study was to evaluate the role of the TNF-α-TNFR1 axis in dental pulp repair following pulp capping in vivo. METHODS: Dental pulp repair response of genetically deficient TNF-α receptor-1 mice (TNFR1-/-; n = 20) was compared with that of C57Bl6 mice (wild type [WT]; n = 20). Pulp capping was performed with mineral trioxide aggregate on the mandibular first molars of mice. After 7 and 70 days, tissues were collected and stained with hematoxylin and eosin for histopathological and histometric evaluation, and assessed by the Brown and Brenn methods for histomicrobiological analysis and by immunohistochemistry to localize TNF-α, Runt-related transcription factor 2, Dentin Sialoprotein (DSP) and Osteopontin (OPN) expression. RESULTS: Compared with WT mice, TNFR1-/- mice showed significantly decreased reparative dentin formation with a lower mineralized tissue area (P < .0001). Unlike WT mice, TNFR1-/- mice also exhibited significant dental pulp necrosis, neutrophil recruitment, and apical periodontitis formation (P < .0001) without bacterial tissue invasion. TNFR1-/- animals further exhibited decreased TNF-α, DSP, and OPN expression (P < .0001), whereas Runt-related transcription factor 2 expression was unchanged (P > .05). CONCLUSION: The TNF-α-TNFR1 axis is involved in reparative dentin formation following dental pulp capping in vivo. Genetic ablation of TNFR1 modified the inflammatory process and inhibited the expression of the DSP and OPN mineralization proteins, which culminated in dental pulp necrosis and development of apical periodontitis.

Histologic and Electron Microscopic Characterization of a Human Immature Permanent Premolar with Chronic Apical Abscess 16 Years after Regenerative Endodontic Procedures.

Previous studies have reported successful clinical outcomes after regenerative endodontic procedures (REPs) for immature permanent teeth with pulpal infection. However, it remains unclear whether the procedures promote true regeneration or repair. This case report describes the histologic and electron microscopic characteristics of a human immature permanent premolar with a chronic apical abscess that was treated with an REP. Tooth #20 of a 9-year-old girl underwent an REP. At the 6-year follow-up, the patient was asymptomatic, and closure of the apex and thickening of the dentinal walls were observed. However, 16 years after the procedure, apical periodontitis recurred, necessitating apical surgery. The resected root fragments were obtained during the surgery and analyzed using micro-computed tomography, light microscopy, and scanning electron microscopy. Distinct dentinal tubules and interglobular dentin were observed in the regenerated hard tissue. Cementum-like tissue and a root canal were also observed in the apical fragment. The regenerated root tissue in this case exhibited a structure similar to the native root structure. Therefore, we believe that cell-free REPs possess regenerative potential for teeth diagnosed with pulp necrosis and chronic apical abscess.

Modulatory influence of melatonin on apical periodontitis in Wistar rats fed a high-fat diet.

OBJECTIVE: This study aimed to evaluate the influence of high-fat diet (HFD) and melatonin (MEL) treatment on the progression of inflammation and alveolar bone resorption (ABR) in rats with AP. DESIGN: Forty male Wistar rats were divided into four groups: apical periodontitis (AP), HFDAP, APMEL and HFDAPMEL. The animals were fed an HFD or standard diet for 107 days. On the 7th day, the rats were subjected to AP, and after 70 days, the rats in the MEL groups were treated with MEL for 30 days. Post treatment, the animals were euthanized, and their jaws were retrieved for evaluation of bone resorption, intensity of the inflammatory response, and immunohistochemical analysis including tartrate-resistant acid phosphatase (TRAP) and interleukin-1ß (IL-1ß) levels and tumor necrosis factor (TNF)-α expression. RESULTS: The APMEL group showed reduction in the inflammatory infiltrate and IL-1ß expression relation to HFDAP, while the TNF-α levels did not differ among the groups. The HFDAP group showed an increase in the ABR. MEL reduced the TRAP levels in the APMEL and HFDAPMEL groups. CONCLUSIONS: while MEL could reduce TRAP levels in the APMEL and HFDAPMEL groups, the reduction in the HFDAPMEL group was smaller than that in the APMEL group, demonstrating that the interaction between AP and HFD decreased the anti-resorptive effects of MEL.

Evaluating the efficacy of endodontic microsurgery for teeth with an undeveloped root apex and periapical periodontitis after nonsurgical treatment failure.

AIM: To determine the efficacy of endodontic microsurgery for teeth with an undeveloped root apex and periapical periodontitis caused by an abnormal central cusp fracture after failed nonsurgical treatment. METHODOLOGY: Eighty teeth in 78 patients were subjected to endodontic microsurgery. All patients were clinically and radiologically examined 1 year postoperatively. The data were statistically analyzed using SPSS 27.0 software. RESULTS: Of the 80 teeth in 78 patients, periapical lesions had disappeared in 77 teeth at 1-year postoperative follow-up, with a success rate of approximately 96.3% (77/80). The efficacy of endodontic microsurgery was not affected by sex, age, extent of periapical lesions, and presence of the sinus tract. Between-group differences were not statistically significant (P > 0.05). CONCLUSIONS: Endodontic microsurgery can be an effective alternative treatment option for teeth with an undeveloped root apex and periapical periodontitis caused by an abnormal central cusp fracture after nonsurgical treatment failure.

Diagnostic Test Accuracy of Artificial Intelligence in Detecting Periapical Periodontitis on Two-Dimensional Radiographs: A Retrospective Study and Literature Review.

This study aims to evaluate the diagnostic accuracy of artificial intelligence in detecting apical pathosis on periapical radiographs. A total of twenty anonymized periapical radiographs were retrieved from the database of Poznan University of Medical Sciences. These radiographs displayed a sequence of 60 visible teeth. The evaluation of the radiographs was conducted using two methods (manual and automatic), and the results obtained from each technique were afterward compared. For the ground-truth method, one oral and maxillofacial radiology expert with more than ten years of experience and one trainee in oral and maxillofacial radiology evaluated the radiographs by classifying teeth as healthy and unhealthy. A tooth was considered unhealthy when periapical periodontitis related to this tooth had been detected on the radiograph. At the same time, a tooth was classified as healthy when no periapical radiolucency was detected on the periapical radiographs. Then, the same radiographs were evaluated by artificial intelligence, Diagnocat (Diagnocat Ltd., San Francisco, CA, USA). Diagnocat (Diagnocat Ltd., San Francisco, CA, USA) correctly identified periapical lesions on periapical radiographs with a sensitivity of 92.30% and identified healthy teeth with a specificity of 97.87%. The recorded accuracy and F1 score were 96.66% and 0.92, respectively. The artificial intelligence algorithm misdiagnosed one unhealthy tooth (false negative) and over-diagnosed one healthy tooth (false positive) compared to the ground-truth results. Diagnocat (Diagnocat Ltd., San Francisco, CA, USA) showed an optimum accuracy for detecting periapical periodontitis on periapical radiographs. However, more research is needed to assess the diagnostic accuracy of artificial intelligence-based algorithms in dentistry.