Search

Aim Methods Results Conclusions The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27‐hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model.Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C‐C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme‐linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un‐operated rats receiving high‐fat/high‐cholesterol diet (HFHCD) or normal diet (ND). Micro‐computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene.Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (p < .05 versus the ND group). Lesion size, infiltration of CD68+ cells, and iNOS+ monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro‐inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (p < .05 versus the vehicle control group).Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions To evaluate M1 and M2 macrophage polarization in radicular cysts and periapical granulomas through an immunohistochemical analysis and the correlation between macrophage polarization and histopathological diagnosis, clinical characteristics and lesion volume using cone‐beam computed tomography.Periapical biopsies diagnosed as radicular cysts (n = 52) and periapical granulomas (n = 51) were analysed by immunohistochemical method. Teeth with periapical lesion with no history of root canal treatment (primary lesion) and lesions persistent to root canal treatment (persistent lesions) were included. Pathological diagnosis, patients' age, gender and clinical characteristics were obtained from treatment records. A cone‐beam computed tomographic periapical volume index (CBCTPAVI) score was assigned to each periapical lesion based on the volume of the lesion. Immuno‐expressions of CD68 and CD163 were quantified. The CD68/CD163 ratio was adopted to represent M1 or M2 macrophage polarization. Mann–Whitney U test was used to determine the different CD68/CD163 ratio between groups of radicular cyst and periapical granuloma. Spearman's correlation test was performed to assess the correlation between the CD68/CD163 ratio and lesion volume and CBCTPAVI score.Radicular cysts and periapical granulomas had CD68/CD163 median of 2.05 (IQR = 1.33) and 1.26 (IQR = 0.81), respectively. A significantly higher CD68/CD163 ratio was observed in radicular cysts (p < .001). In contrast, periapical granulomas had significantly lower median of CD68/CD163 ratio. Larger lesions had a higher median of CD68/CD163 ratio, while smaller lesions had lower median of CD68/CD163 ratio (p = .007, rs = .262). CD68/CD163 ratio was significantly correlated with the CBCTPAVI score in the overall periapical lesions (p = .002, rs = .306). The higher CD68/CD163 ratio in larger lesions indicated a higher degree of M1 polarization compared to smaller lesions. Regarding the pathological diagnosis, there was a significant positive correlation between CBCTPAVI score and CD68/CD163 ratio in periapical granulomas (p < .001, rs = .453), whereas the negative correlation was observed for radicular cysts (p < .001, rs = −.471).Periapical granulomas are characterized by a M2‐dominant macrophage polarization, while radicular cysts have significantly higher M1 macrophages. The higher degree of M1 macrophage polarization was significantly correlated with larger volume and higher CBCTPAVI scores of overall periapical lesion and periapical granuloma. [ABSTRACT FROM AUTHOR]

The aim of the study was to collect data about the prevalence and risk factors of apical periodontitis in a population of endodontically treated patients. The study group included 151 patients (52 males, 99 females; mean age 48.36 ± 15.708 yrs.) with 391 endodontically treated teeth (mean follow-up of 5.25 ± 1.759 yrs.). According to the initial tooth diagnosis, root-filled teeth were divided into Group A, root-filled teeth treated for pulpitis or for the purpose of prosthetic pulpectomies (vital pulp group), and Group B, root-filled teeth with non-vital pulp (necrotic pulp). Clinical and radiographic evaluation of the root and its periapical area were performed to establish the success/failure of endodontic therapy, the quality of the root canal fillings (length, density, taper), and coronal restoration. The presence of recurrent caries, periodontal pathology, or endo-periodontal lesions were also recorded. Univariate and multivariate analyses were used to determine the risk factors for apical periodontitis and calculate their odds ratios (ORs). For the root-filled vital pulp tooth group, the highest risks for apical periodontitis are associated with inadequate homogeneity (OR 30.938), periodontitis (OR 9.226), and over-filling (OR 8.800). For the root-filled non-vital pulp tooth group, the highest risks are associated with periodontitis (OR 4.235) and age over 60 yrs. (OR 4.875). For the necrotic pulp tooth group, multivariate analysis identified an age > 60 yrs., filled molars, intracanal posts, poor coronal restoration quality, under-filling, and periodontitis as significant combined risk factors. Inadequate root canal filling and periodontitis in both groups were risk factors associated with most cases of apical periodontitis. Other risk factors include age > 60 yrs., poor coronal restoration quality, and the presence of intracanal posts in root-filled teeth with necrotic pulp. [ABSTRACT FROM AUTHOR]

Apical periodontitis (AP) is the most prevalent chronic inflammatory disease of the teeth. Bone resorption dynamics in symptomatic and asymptomatic AP are still unrecognized. This study examined different inflammatory markers within gingival crevicular fluid, including matrix metalloproteinases 8 (MMP8), tissue inhibitors of metalloproteinases 1 (TIMP1), receptor activator of nuclear factor κB (RANK), its ligand (RANKL), and osteoprotegerin (OPG), to be used in comparing symptomatic apical periodontitis (SAP) and asymptomatic apical periodontitis (AAP) versus healthy teeth. Subjects with SAP, AAP, and a control group were recruited and GCF samples were collected by Periopaper strips. Clinical and radiographical measures were used for diagnosing AP. Levels of MMP8, TIMP, RANK, RANKL, and OPG were determined by ELISA and their abilities to discriminate between examined sites were evaluated by receiver operator characteristic (ROC) curves. All examined biomarkers were statistically significant higher (p < 0.05) in SAP than AAP and the control group, apart from RANK. Significant positive correlations (p < 0.05) were identified between all SAP and AAP biomarkers except TIMP1 and RANK in AAP teeth. TIMP1 and OPG exhibited the highest ability to distinguish between SAP and AAP with areas under the curve of 0.824 and 0.763 in comparing SAP and the control group, and 0.732 and 0.73 when comparing AAP and the control group, respectively. Additionally, TIMP1 and OPG showed the highest AUC of 0.778 and 0.747 when SAP and AAP were compared, respectively. This study concluded that GCF levels of TIMP1 and OPG can be used to differentiate between SAP, AAP, and healthy teeth. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor‐κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. Methodology: Twenty‐four female Sprague–Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3‐methyladenine (An autophagy inhibitor, 3‐MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3‐MA group received intraperitoneal injections of saline and 3‐MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro‐CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one‐way analysis of variance (p <.05). Results: Micro‐CT showed greater bone loss in the EAP + 3‐MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p <.05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3‐MA groups. Compared with EAP + saline group, the EAP + 3‐MA group showed weaker expression of LC3B (p <.01) and OPG (p <.05), more intense expression of RANK (p <.01) and RANKL (p <.01), and a higher RANKL/OPG ratio (p <.05). Conclusion: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss. [ABSTRACT FROM AUTHOR]

Aim: Endothelial cells (EDs) play a key role in angiogenesis and are associated with granulomatous lesions in patients with chronic apical periodontitis (CAP). This study aimed to investigate the diversity of EDs using single‐cell ribonucleic acid sequencing (scRNA‐seq) and to evaluate the regulation of intercellular adhesion molecule 1 (ICAM1) on the ferroptosis‐related protein, prostaglandin‐endoperoxide synthase 2 (PTGS2), in CAP. Methodology: EDs from the uploaded scRNA‐seq data of five CAP samples (GSE181688 and GSE197680) were categorized using distinct marker genes. The interactions between vein EDs (veinEndo) and other cell types were analysed using CellPhoneDB. Differentially expressed proteins in the proteomics of human umbilical vein EDs (HUVECs) and THP‐1‐derived macrophages infected with Porphyromonas gingivalis were compared with the differentially expressed genes (DEGs) of VeinEndo in scRNA‐seq of CAP versus healthy control periodontal tissues. The protein–protein interaction of ICAM1–PTGS2 in macrophages and HUVECs was validated by adding recombinant ICAM1, ICAM1 inhibitor and PTGS2 inhibitor using real‐time polymerase chain reaction (PCR), western blotting, and immunofluorescence staining. Results: EDs in patients with CAP were divided into eight subclusters: five vein ED, capillaries, arterials and EC (PLA). There were 29 mutually upregulated DEGs and two mutually downregulated DEGs in vein cells in the scRNA‐seq data, as well as differentially expressed proteins in the proteomics of HUVECs. Real‐time PCR and immunofluorescence staining showed that ICAM1 and PTGS2 were highly expressed in CAP, infected HUVECs, and macrophages. Recombinant protein ICAM1 may improve PTGS2 expression, reactive oxygen species (ROS), and Fe2+ levels and decrease glutathione peroxidase 4 (GPX4) and SLC7A11 protein levels. ICAM1 inhibitor may inverse the above changes. Conclusions: scRNA‐seq revealed the diversity of EDs in CAP and identified the possible regulation of ICAM1 by the ferroptosis‐related protein, PTGS2, in infected HUVECs and macrophages, thus providing a basis for therapeutic approaches that target the inflammatory microenvironment of CAP. [ABSTRACT FROM AUTHOR]

Aim: To investigate what happens to cross‐sectionally identified root‐filled teeth over a 6‐year period, regardless of the time that elapsed since primary root canal treatment, in a cohort of adult patients regularly attending a Public Dental Service. A secondary aim was to investigate how the cumulative events affecting root‐filled teeth over the same time were associated with variables obtained from a baseline examination. Methodology: Adult patients with ≥1 previously root‐filled tooth and regularly attending the Public Dental Service in Örebro County were enrolled for study participation in 2015. General dental practitioners examined all identified root‐filled teeth in this cohort at baseline using a standardized protocol and were also responsible for further decision‐making and treatments. After six years, information on events of the root‐filled teeth was collected from dental records. The highest rating (most invasive treatment) on a 5‐point ordinal scale was used in the analyses. Regression analyses with stepwise selection were performed for associations between patient‐ and tooth‐related factors and events. Results: A total of 445 patients with 1007 root‐filled teeth were followed the entire observation time. Twenty (2.0%) of the root‐filled teeth had endodontic retreatment and 150 (14.9%) were extracted over six years. Among teeth with periapical radiolucency or pain, the majority did not undergo retreatment or extraction; however, the multivariate analysis demonstrated that retreatment or extraction was associated with baseline recordings of teeth with periapical radiolucency (p <.0001), tenderness to percussion (p <.0001), and poor coronal restoration (p <.0001). Conclusions: This study corroborates the notion that in general dentistry, root‐filled teeth with radiological signs of apical disease often remain untreated over time. Furthermore, it also reveals that root‐filled teeth presenting with mild pain do not necessarily receive any intervention. However, teeth with baseline signs of apical periodontitis, pain, or inadequate coronal restoration were more likely to have received intervention during the six‐year period. [ABSTRACT FROM AUTHOR]

A growing body of research supports an association between periapical inflammation and an increased risk of developing systemic diseases. There is currently no scientific evidence to support a causal effect of inflammation on the onset of insulin resistance (IR) in patients with apical periodontitis (AP). The aim of this in vitro study was to evaluate any association between AP and levels of serum inflammatory factors potentially associated with the onset of IR, and to investigate the effect of root canal treatment (RCT) on these systemic inflammation markers and on the response in vitro to insulin. A total of 27 control subjects and 27 patients with AP were enrolled. Patients with AP underwent RCT and were followed-up 6 and 12 months post-treatment. Enzyme-linked immunosorbent assays were used to evaluate serum levels of proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α. The response in vitro to insulin was assessed by measuring glucose consumption in a human pancreatic epithelioid carcinoma cell line treated with sera from healthy and AP subjects. At baseline AP was associated with significant higher levels of IL-1, IL-6, and IL-8 in the serum of untreated (AP) patients vs controls (P <.001). Glucose consumption decreased in pancreatic cells incubated with baseline serum from patients with AP, in a manner proportional to total cytokines amount. Notably, endodontic treatment was associated with reduced levels of cytokines (P <.001) and improved response to insulin in AP group (P <.001). Our findings suggest that AP may promote inflammatory-driven IR in an in vitro model, and that RCT may ameliorate inflammatory mediators in vivo and the cellular response to insulin in vitro. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusions The objectives of current study were to investigate the role and related mechanism of Ginsenoside Rb1 (GRb1) on regulating apical periodontitis (AP) prognosis.Clinical specimens were used to determine the involvement of calcium overload‐induced macrophage pyroptosis in periapical tissues. Next, a calcium ion‐chelating agent (BAPTA‐AM) was applied to detect the suppression of intracellular calcium overload in macrophage pyroptosis. Then, network pharmacology, western blot (WB) analysis, and Fluo‐4 calcium assay were conducted to explore the role of GRb1 on intracellular calcium overload. To gain a better understanding of GRb1 in calcium overload‐induced macrophage pyroptosis linked AP, GRb1‐treated AP models were established.We discovered clinically and experimentally that calcium overload‐dependent macrophage pyroptosis is involved in AP pathogenesis, and reducing calcium overload greatly decreased macrophage pyroptosis in an AP cell model. Next, based on GRb1's inhibitory role in aberrant intracellular calcium accumulation, we discovered that GRb1 alleviates AP by suppressing calcium‐dependent macrophage pyroptosis in both in vitro and in vivo models.GRb1 is an effective therapeutic strategy to rescue the periapical tissues from inflammation due to its anti‐pyroptosis function. Thus, the present study supports further investigation of GRb1 as an adjuvant therapy for AP. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionGremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment.Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed.Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results.Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP. [ABSTRACT FROM AUTHOR]

Aim Methodology Results Conclusions To evaluate the 6‐year outcome of root canal treatment irrigated with 0.5% or 3% sodium hypochlorite (NaOCl).The baseline trial was designed as a quasi‐randomized clinical trial. Patients referred for root canal treatment to an endodontic specialist clinic were recruited to the study (n = 298). The concentration of NaOCl was allocated quasi‐randomized to 271 subjects (0.5% [n = 139], 3% [n = 132]). Bacterial sampling was performed immediately before root canal filling. Samples were cultured and evaluated as growth or no growth. Patients were invited to a clinical and radiological follow‐up >5 years postoperatively. The clinical outcome measurements were tooth survival, cumulative incidence of endodontic retreatments, patients' assessment of pain, clinical findings and radiological signs of apical periodontitis (AP).Tooth survival was 85.6% in the 0.5% NaOCl group and 81.1% in the 3% NaOCl group (p = .45). There was no record of retreatment in 94.4% in the 0.5% NaOCl group and in 92.2% in the 3% NaOCl group (p = .76). The percentage of asymptomatic cases were 87.8% in the 0.5% group and 85.3% in the 3% NaOCl group (p = .81). Absence of clinical signs of AP was seen in 86.6% in the 0.5% NaOCl group and in 83.6% in the 3% NaOCl group (p = .80). Absence of radiological signs of AP was seen in 74.0% in the 0.5% NaOCl group and 64.1% in the 3% NaOCl group (p = .20). Subjects with positive culture before root filling reported subjective pain with a significantly higher frequency as compared to negative‐culture subjects (p = .014).The use of 0.5% or 3% NaOCl for irrigation during root canal treatment resulted in similar clinical outcomes 5–7 years postoperatively. Persisting bacteria immediately before root filling may predict future episodes of subjective pain. [ABSTRACT FROM AUTHOR]

Background: Chronic apical periodontitis is a persistent inflammatory condition affecting the periapical tissues of a tooth. Effective disinfection of the root canal system is crucial for successful endodontic treatment. This study aims to compare the efficacy of ultrasonic irrigation (UI) and laser-activated irrigation (LAI) in promoting healing in chronic apical periodontitis. Materials and Methods: A total of 100 patients diagnosed with chronic apical periodontitis were randomly assigned to two groups: the UI group (n=50) and the LAI group (n=50). Patients in the UI group received endodontic treatment using ultrasonic irrigation, while those in the LAI group received treatment with laser-activated irrigation. The primary outcome measure was the reduction in periapical lesion size, assessed using digital radiographs at baseline, 3 months, and 6 months post-treatment. Secondary outcomes included pain reduction and overall treatment success, defined as the absence of clinical symptoms and radiographic evidence of healing. Results: At the 3-month follow-up, the UI group showed a 60% reduction in periapical lesion size, while the LAI group exhibited a 75% reduction. At the 6-month follow-up, the UI group demonstrated an 80% reduction, and the LAI group achieved a 90% reduction in lesion size. Pain scores decreased significantly in both groups, with the LAI group reporting a more rapid decline in pain levels. Overall treatment success was observed in 85% of patients in the UI group and 95% in the LAI group at the 6-month follow-up. Conclusion: Both ultrasonic irrigation and laser-activated irrigation are effective in promoting healing in chronic apical periodontitis. However, laser-activated irrigation showed superior outcomes in terms of periapical lesion size reduction and overall treatment success. These findings suggest that LAI may be a more effective adjunctive technique in endodontic therapy for chronic apical periodontitis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the bacteriome present in teeth with primary endodontic infection (PEI) and apical periodontitis (AP) and to determine quantitatively and qualitatively the impact of chemomechanical preparation (CMP) using 2.5% sodium hypochlorite NAOCl on the bacteriome found in PEI with AP using the Illumina MiSeq platform. Methodology: Thirty‐six paired samples from 18 patients were successfully sequenced and analysed. Samples were collected at two sampling times: before (s1) and after (s2) CMP using 2.5% NaOCl. The DNA was extracted from s1 and s2 samples and quantified using quantitative PCR (qPCR). All 36 samples were sequenced using the Illumina MiSeq platform. Raw V3–V4 amplicon sequencing data were processed with the DADA2 pipeline to generate amplicon sequence variants (ASVs). Alpha diversity metrics representing abundance (Chao1) and diversity and evenness (Shannon, Simpson) were computed. The paired‐sample Wilcoxon's test was used to compare alpha diversity metrics and qPCR counts between s1 and s2. The PERMANOVA method (with 999 permutations) was applied to compare community composition between sample types (s1 versus s2) and between patient IDs. ALDEx2 (ANOVA‐like differential expression tool for high‐throughput sequencing data) to investigate differentially abundant taxa between s1 and s2. A paired‐sample Wilcoxon's test was used to compare alpha diversity metrics and qPCR counts between s1 and s2. Results: The qPCR counts were significantly higher in s1 compared to s2 (p =.0007). The Chao1 index indicated no difference in alpha diversity (p <.7019); whereas Shannon (p =.0056) and Simpson (p =.02685) indexes showed higher values in s2. The PERMANOVA test using Adonis2 showed a significant effect of sample time on community composition (R2 =.0630, p =.012). Patient ID also showed a significant effect on community composition (R2 =.6961, p =.001). At the genus level, Dialister, Mogibacterium, Prevotella, and Olsenella were differentially enriched at s1, while Actinomyces, Stenotrophomonas_unclassified, Enterococcus_unclassified, and Actinomyces_unclassified were differentially enriched in s2. Conclusion: The bacteriome present in teeth with PEI with AP is complex and diverse. CMP using 2.5% NaOCl showed a high quantitatively and qualitatively disinfectant impact on the bacteriome present in PEI with AP. [ABSTRACT FROM AUTHOR]

Background: Regenerative techniques are increasingly being advocated in endodontic apical surgery (AS) to enhance the healing of periapical lesions. Various grafting and membrane materials are employed as adjuncts to modern AS. Objectives: This systematic review aimed to answer the following PICO question: In patients with apical periodontitis (P) what is the impact of bone grafting with/without barrier membrane materials (I) compared with surgery without grafting materials (C) on the outcome of AS evaluated clinically and radiographically (O). Methods: A systematic search was conducted in four databases (Embase, Web of Science, PubMed and Cochrane Central Register of Controlled Trials) until 1 August 2023. Google Scholar was also manually searched. Studies with a prospective randomized design were included. Cochrane risk‐of‐bias (RoB) tool 2.0 assessed bias. Two independent reviewers performed the study selection, data extraction and appraisal of studies. Meta‐analysis was performed using R3.5.1 software. Results: From the identified 2582 studies, eight randomized clinical trials were included for meta‐analysis. Two studies had low RoB, while six had some concerns. Analysis revealed significantly better outcomes when surgery involved bone regeneration techniques than conventional surgery (OR = 2.18, 95% CI: 1.32–4.31, p =.004). Subgroup analyses on individual grafts (OR = 0.22, 95% CI: −0.99 to 1.44, p =.720) (OR = −0.09, 95% CI: −1.42 to 1.23, p =.885) and membranes (OR = −1.09, 95% CI: −2.94 to 0.76, p =.247) and their combinations (OR = 0.03, 95% CI: −1.50 to 1.55, p =.970) did not yield any significant results. The type of membrane used did not significantly impact the outcome (OR = −1.09, 95% CI: −2.94 to 0.76, p =.247) nor did altering the combination of graft/membrane. Discussion: This systematic review examined the effects of bone grafting with/without membrane placement on the outcome of AS. It highlights the potential advantages of regenerative techniques and the need for further research in this area. Conclusions: Based on current evidence, bone grafting with/without barrier membrane placement significantly improves healing after AS. Subgroup analysis of resorbable membranes or grafting did not significantly influence the outcome. The combination of membrane and graft was also not significant. Future well‐designed, randomized controlled trials in this area are essential before these materials can be recommended for routine use to enhance healing outcomes in AS. Registration: PROSPERO (CRD42021255171). [ABSTRACT FROM AUTHOR]

Aim: This prospective cohort study was undertaken to evaluate the success rate of root canal treatment (RCT) in type 2 diabetes mellitus (T2DM) patients with targeted level and unachieved targeted level of glycaemic control as well as the impact of RCT on the glucose blood level in T2DM patients. Methodology: Patients needing RCT were divided into three groups: these without T2DM, that is, the control group (CG), those with targeted level of glycated haemoglobin HbA1c < 7% (TL A1c) and the third ones with unachieved targeted level (UTL A1c), that is, with HbA1c ≥ 7%. Before RCT, HbA1c and the periapical index (PAI) score were assessed, as well as 1 year later. Results: Our results showed less favourable treatment results of RCT such as a reduction of radiographic lesions in T2DM patients, particularly in subjects with UTL A1c. The intergroup analysis of PAI score at the 12‐month follow‐up revealed a significant difference in TL A1C (p =.022) and CG (p =.001) with respect to UTL A1c. Total number of healed teeth (PAI≤2) at the 12‐month after RCT in UTL A1c was significantly lower in comparison to CG (p =.008). Contrariwise, RCT may improve the glycaemic control in diabetic patients with UTL A1c after 12 months of posttreatment. Regression analysis showed that UTL A1c patients were more likely to have AP persistence after endodontic treatment (OR = 4.788; CI: 1.157–19.816; p =.031). Conclusions: T2DM retards the AP healing and conversely AP contributes to increasing the inflammatory burden in T2DM. RCT reduces the cumulative inflammatory burden in T2DM and thus may contribute to improvement of glycaemic control particularly in patients with UTL A1c. [ABSTRACT FROM AUTHOR]

Background: The European Society of Endodontology published in 2023, the S3‐level clinical practice guidelines, which supersede the Quality Guidelines for Endodontic Treatment published in 2006. Objectives: This review aims to summarize and compare the above guidelines to support their dissemination. Method: A narrative synthesis of the main differences alongside tabulation according to the main themes. Results: Three tables were prepared according to the following themes: diagnosis of pulpal and apical condition; treatment of pulpitis; and treatment of nonvital pulp and apical periodontitis. Conclusions: A compared and simplified message regarding the most recent clinical practice guidelines has been prepared. Registration: Not applicable as a narrative review. [ABSTRACT FROM AUTHOR]

Background: Microorganisms colonizing the apical root canal system are conceivably the ones directly involved with the causation and maintenance of apical periodontitis. Objectives: This article systematically reviews the reports on the microbiome occurring exclusively at the apical root canal of teeth with primary and posttreatment apical periodontitis. Methods: The electronic databases PubMed, Embase, Web of Science, Science Direct, and Proquest were searched up to August 2023. Clinical studies using culture and molecular microbiology methods to identify the microbial taxa present exclusively in the apical root canal segment of infected teeth with apical periodontitis were included. Studies were critically assessed using the Joanna Briggs Institute Critical Prevalence Assessment Checklist. Results: From 2277 articles initially detected, 52 were selected for full reading and 21 were eventually included in this review. Of these, molecular methods were used in 19 and culture in 2 studies. Ten studies evaluated primary infections, 8 evaluated posttreatment infections, and 3 included both. Cryopulverization of the apical root specimens was conducted in 11 studies. All studies evaluated the prevalence and diversity of bacteria, and only one also reported on fungi. Overall, the most frequent/abundant bacterial taxa found in the apical canal of primary infections were Pseudoramibacter alactolyticus, Olsenella uli, Fusobacterium species, Streptococcus species, Porphyromonas endodontalis, Prevotella species, Actinomyces species, Parvimonas micra, Treponema denticola, Synergistetes species, and an as‐yet uncharacterized taxon. In posttreatment infections, the most prevalent/abundant bacterial taxa included species of Streptococcus, Enterococcus, Fusobacterium, Actinomyces, Pseudoramibacter, Pseudomonas, and Propionibacterium. At the phylum level, Firmicutes was the most represented. The average apical bacterial load ranged from 105 to 106 in primary infections and from 103 to 104 in posttreatment infections. Discussion: Microbial diversity in the apical part of the root canal system was examined encompassing data from both primary and posttreatment infections. Heterogeneity amongst the studies, especially in sample collection and microbial identification methods, is an important limitation that prevented a meta‐analysis. Conclusions: There is a pronounced bacterial diversity in the infected apical canal, with a high interindividual variability. Different microbiome compositions at the species/genus level are observed according to the infection type. Registration: PROSPERO CRD42021275886. [ABSTRACT FROM AUTHOR]

Aim: Apical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome‐mediated immune response on the apical periodontitis was investigated. Methodology: RNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through in vitro experiments. In vivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis. Results: Our findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune‐related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL‐dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF‐κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3‐deficient and wild‐type Treg cells effectively prevent the bone erosion during apical periodontitis. Conclusions: Together, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion. [ABSTRACT FROM AUTHOR]

Objective: One key factor in determining endodontic treatment outcome is the clinicians’ comprehension of tooth anatomy, as missed canals may harbor bacteria ultimately leading to apical periodontitis. The study aimed to investigate the prevalence of middle mesial canal (MMC) in Mandibular first molars (MFMs) of Saudi subpopulation. Methods: The cross-sectional retrospective study was conducted at Qassim University Dental College from June to August 2023. Overall, 302 CBCT images with 604 bilateral lower first molars were examined by two calibrated assessors. The existence of MMC was noted. The data were coded, and analysis was done in SPPS-24. The reliability of interevaluator and intra-evaluator agreement for detecting MMC were estimated using Cohen’s kappa. Results: The patients’ average age was 30.95±11.61years. The sample’s female to male ratio was 1:1.75. The overall frequency of MMC was 14.2%. The differences in the frequency of MMC on the basis of gender, quadrants and age groups were found to be insignificant. Inter-evaluator and intra-evaluator reliability was noted to be 0.78 and 0.74, depicting acceptable reliability. Conclusions: The MMC is an uncommon occurrence with rare bilateral presentation in MFMs of Saudi population. Endodontists performing endodontic treatment in such subjects should mindfully investigate inter mesiobuccalmesiolingual canals area for locating, negotiating, and managing any present MMC’s. [ABSTRACT FROM AUTHOR]

Periapical lesions are common pathologies affecting the alveolar bone, often initiated by intraradicular lesions resulting from microbial exposure to dental pulp. These microorganisms trigger inflammatory and immune responses. When endodontic treatment fails to eliminate the infection, periapical lesions persist, leading to bone loss. The RANK/RANKL/OPG pathway plays a crucial role in both the formation and the destruction of the bone. In this study, the objective was to inhibit the RANK/RANKL pathway in vitro within exposed Thp-1 macrophages to endodontic microorganisms, specifically Enterococcus faecalis, which was isolated from root canals of 20 patients with endodontic secondary/persistent infection, symptomatic and asymptomatic, and utilizing an α-IRAK-4 inhibitor, we introduced endodontic microorganisms and/or lipoteichoic acid from Streptococcus spp. to cellular cultures in a culture plate, containing thp-1 cells and/or PBMC from patients with apical periodontitis. Subsequently, we assessed the percentages of RANK+, RANKL+, and OPG+ cells through flow cytometry and measured the levels of several inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) in the cellular culture supernatant through a CBA kit and performed analysis by flow cytometry. A significant difference was observed in the percentages of RANK+RANKL+, OPG+ RANKL+ cells in thp-1 cells and PBMCs from patients with apical periodontitis. The findings revealed significant differences in the percentages of the evaluated cells, highlighting the novel role of the IRAK-4 inhibitor in addressing this oral pathology, apical periodontitis, where bone destruction is observed. [ABSTRACT FROM AUTHOR]

The severity of periodontitis can be analyzed by calculating the loss of alveolar crest (ALC) level and the level of bone loss between the tooth's bone and the cemento-enamel junction (CEJ). However, dentists need to manually mark symptoms on periapical radiographs (PAs) to assess bone loss, a process that is both time-consuming and prone to errors. This study proposes the following new method that contributes to the evaluation of disease and reduces errors. Firstly, innovative periodontitis image enhancement methods are employed to improve PA image quality. Subsequently, single teeth can be accurately extracted from PA images by object detection with a maximum accuracy of 97.01%. An instance segmentation developed in this study accurately extracts regions of interest, enabling the generation of masks for tooth bone and tooth crown with accuracies of 93.48% and 96.95%. Finally, a novel detection algorithm is proposed to automatically mark the CEJ and ALC of symptomatic teeth, facilitating faster accurate assessment of bone loss severity by dentists. The PA image database used in this study, with the IRB number 02002030B0 provided by Chang Gung Medical Center, Taiwan, significantly reduces the time required for dental diagnosis and enhances healthcare quality through the techniques developed in this research. [ABSTRACT FROM AUTHOR]

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP‐associated tissue destruction. [ABSTRACT FROM AUTHOR]

Often there is the need of moving endodontically treated teeth. Orthodontic movement may have no effect on the prognosis of teeth with root canal treatment (RCT). To verify this subject, we evaluated the effect of orthodontic movement on the prognosis of RCT teeth using cone-beam computed tomography (CBCT) and further explored the influence of orthodontic movement on the prognosis of RCT teeth with and without apical periodontitis (AP). This retrospective study was conducted by evaluating 169 RCT teeth of 100 patients who had undergone fixed orthodontic treatment. AP was assessed and classified using the CBCT periapical index. Univariate analysis of RCT outcome was performed for the total RCT group, RCT without AP group and RCT with AP group. Multivariate logistic regression was performed for the total RCT group and RCT without AP group, respectively, but not for the RCT with AP group. Variables related to the prognosis of RCT were included, such as age, gender, tooth position, RCT quality, coronal restoration quality, periodontal condition, orthodontic traction distance, and orthodontic rotation angle. The orthodontic traction distance and rotation angle were not significantly correlated to the RCT outcomes, regardless of the presence of AP. Among the total RCT group, teeth with unqualified RCT (odds ratio = 3.42, P =.004) and inadequate coronal restoration (odds ratio = 4.40, P =.031) had a lower success rate. Of the 97 RCT teeth without AP, unqualified RCT was a risk factor for treatment failure (odds ratio = 3.55, P =.041). Of the 72 RCT teeth with AP, the univariate analysis showed that RCT quality were significantly related to the outcome (P =.042). Orthodontic movement had no effect on the prognosis of RCT teeth regardless of the presence of AP. [ABSTRACT FROM AUTHOR]

Microbiota associated with primary endodontic infection (PEI) and secondary/persistent endodontic infection (SPEI) must be characterized to elucidate pathogenesis in apical periodontitis and bacterial biomarkers identified for diagnostic and therapeutic applications. This study analyzed the microbial community profiles of root canals and gingival sulci (sulcus-E) for teeth with PEI (n = 10) or SPEI (n = 10), using the Illumina MiSeq platform. Bacterial samples from gingival sulci (sulcus-C) of healthy contralateral teeth served as controls. There were 15 phyla, 177 genera, and 340 species identified. The number and diversity of bacteria in root canals did not differ significantly between PEI and SPEI. Proteobacteria, Firmicutes, Fusobacteria, Bacteroidetes, and Actinobacteria were the dominant phyla in both groups. At the genus level, Lancefieldella , Bifidobacterium , Stomatobaculum , and Schaalia were enriched in root canals with SPEI. Of significance, Lancefieldella was observed in both root canals and sulcus-E of teeth with SPEI. At the species level, Neisseria macacae, Streptococcus gordonii, Bifidobacterium dentium, Stomatobaculum longum , and Schaalia odontolytica were increased significantly in root canals with SPEI compared to PEI. Oribacterium species , Streptococcus salivarius, Lancefieldella parvula, Prevotella denticola , and Oribacterium asaccharolyticum were more abundant in sulcus-E of teeth with SPEI compared to PEI. There were distinctive and differing predominant bacterial species associated with the root canals and gingival sulci between teeth with PEI and SPEI. Specific bacteria identified in sulcus-E and root canals of teeth with SPEI could serve as noninvasive diagnostic biomarkers for detecting SPEI. [ABSTRACT FROM AUTHOR]

Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual's quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis. [ABSTRACT FROM AUTHOR]

This report aims to present a treatment of retrograde peri-implantitis originating from apical periodontitis of an adjacent tooth in an 84-year-old male. Apical periodontitis of the maxillary left central incisor (#9) extended to the apex of the maxillary left lateral incisor implant (#10), which had been functioning for 16 years. Root canal treatment for #9 was performed, followed by root end surgery to treat the apical periodontitis, which showed a periapical radiolucency measured 1 cm in its greatest dimension. After the root end filling was placed, neither bone substitute materials nor barrier membranes were used to fill and cover the bony defect area. A 2-year postoperative radiograph confirmed the osseous healing around the apices of #9 and #10. [ABSTRACT FROM AUTHOR]

Osteoporosis is a common systemic bone disorder in the elderly, characterized by low bone mineral density and deterioration of bone structure. Apical periodontitis is an inflammatory response to the microbial infection of root canals, typically characterized by apical bone destruction surrounding the tooth's apex. This systematic review aimed to determine if osteoporosis affects the prevalence of apical periodontitis in adults. PRISMA guidelines have been followed. It included randomized clinical trials, cross-sectional, cohort, and case-control studies, and excluded non-relevant investigations and various secondary sources. A comprehensive search was performed in PubMed, Scopus, and Web of Science, until 13 March 2024. The Newcastle–Ottawa Scale was used to assess the quality of the three selected studies: two cross-sectional studies and one case-control study. One investigation only included post-menopausal women recruited at a dental university clinic, the other integrated data from the total hospital patients' population, and the third selected patients referred to the university dental clinic from the university hospital. The findings varied: one study noted a marginal association between low bone mineral density and apical periodontitis, another found a significant association, and the third, with the lowest risk of bias, reported no link. The main limitations were the scarcity of eligible studies and their overall quality. The review was registered in the PROSPERO database (CRD42024523705), applied strict inclusion criteria and thorough searches by experienced and independent reviewers. There is no strong evidence that adult individuals with osteoporosis have a higher probability of developing apical periodontitis. However, clinicians should remain cautious of osteoporosis's potential impact on apical periodontitis development. [ABSTRACT FROM AUTHOR]