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Background: Apical periodontitis (AP) is a chronic inflammatory response of microbial aetiology. Pathological changes associated with AP may not be visible on radiographic images and may linger without causing any symptoms. Clinicians rely mostly on clinical examination and imaging techniques to establish a diagnosis. Objectives: The aim of this review was to answer the following question using the PICO format: In the adult human permanent dentition (P), what is the efficacy of diagnostic imaging of the periapical tissues (I) using histopathology as a reference standard (C) in the diagnosis of apical periodontitis, in terms of diagnostic accuracy (O). Methods: MEDLINE, EMBASE, Scopus and Cochrane Library were searched for English articles published through October 2021. At least two independent reviewers evaluated the study design, imaging modality used, histopathological assessment, outcome measures, results and conclusions for each article. The risk of bias was assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies‐2. Results: The initial search strategy identified 544 articles. Seven articles were included for analysis in the final review, all of which involved tissue samples obtained from cadavers. No clinical studies were identified that met the eligibility criteria. A consistently low sensitivity score and negative predictive value were reported for periapical radiography, especially in comparison to CBCT, which scored highly. Both modalities achieved high scores for specificity and positive predictive value. Diagnostic accuracy of CBCT was lower for root‐filled teeth in comparison to non‐root‐filled teeth. Discussion: Assessment of the periapical tissues using periapical radiographs was shown to have a low to moderate agreement with the histopathological assessment. CBCT was reported to be more accurate than PR and demonstrated a good agreement with histopathology, especially for non‐root‐filled teeth. Conclusions: This review identified a need for greater standardization in methodology and reporting, and as the findings are based on cadaver studies, their clinical relevance must be interpreted with caution. Registration: PROSPERO (CRD42021272147). [ABSTRACT FROM AUTHOR]

Aim: To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis. Methodology: The Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t‐test or ANOVA with the level of significance set at p ≤.05. Results: Pulpitis gene signatures were created using differential gene expression analysis at cutoff points p =.0001 and.000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C‐C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures (p =.0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 (p <.001) and MMP9 (p <.05) in the ex vivo pulpitis model, while dequalinium chloride reduced AQP9 (p <.001) but had no significant effect on the other biomarkers. Conclusions: AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licenced drugs is warranted. [ABSTRACT FROM AUTHOR]

Abstract Background Microbial biofilms are known to cause an increasing number of chronic inflammatory and infectious conditions. A classical example is chronic periodontal disease, a condition initiated by the subgingival dental plaque biofilm on gingival epithelial tissues. We describe here a new model that permits the examination of interactions between the bacterial biofilm and host cells in general. We use primary human gingival epithelial cells (HGEC) and an in vitro grown biofilm, comprising nine frequently studied and representative subgingival plaque bacteria. Results We describe the growth of a mature 'subgingival' in vitro biofilm, its composition during development, its ability to adapt to aerobic conditions and how we expose in vitro a HGEC monolayer to this biofilm. Challenging the host derived HGEC with the biofilm invoked apoptosis in the epithelial cells, triggered release of pro-inflammatory cytokines and in parallel induced rapid degradation of the cytokines by biofilm-generated enzymes. Conclusion We developed an experimental in vitro model to study processes taking place in the gingival crevice during the initiation of inflammation. The new model takes into account that the microbial challenge derives from a biofilm community and not from planktonically cultured bacterial strains. It will facilitate easily the introduction of additional host cells such as neutrophils for future biofilm:host cell challenge studies. Our methodology may generate particular interest, as it should be widely applicable to other biofilm-related chronic inflammatory diseases.

Abstract Background The oral pathogen Porphyromonas gingivalis has been shown to modulate apoptosis in different cell types, but its effect on epithelial cells remains unclear. Results We demonstrate that primary human gingival epithelial cells (HGECs) challenged with live P. gingivalis for 24 hours exhibit apoptosis, and we characterize this by M30 epitope detection, caspase-3 activity, DNA fragmentation and Annexin-V staining. Live bacteria strongly upregulated intrinsic and extrinsic apoptotic pathways. Pro-apoptotic molecules such as caspase-3, -8, -9, Bid and Bax were upregulated after 24 hours. The anti-apoptotic Bcl-2 was also upregulated, but this was not sufficient to ensure cell survival. The main P. gingivalis proteases arginine and lysine gingipains are necessary and sufficient to induce host cell apoptosis. Thus, live P. gingivalis can invoke gingival epithelial cell apoptosis in a time and dose dependent manner with significant apoptosis occurring between 12 and 24 hours of challenge via a gingipain-dependent mechanism. Conclusion The present study provides evidence that live, but not heat-killed, P. gingivalis can induce apoptosis after 24 hours of challenge in primary human gingival epithelial cells. Either arginine or lysine gingipains are necessary and sufficient factors in P. gingivalis elicited apoptosis.

Background and Objective: Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to evaluate the presence of biomarkers in pulpitis. Methods: The electronic databases of MEDLINE, EMBASE, Scopus and other sources were searched for English and non-English articles published through February 2015. Two independent reviewers extracted information regarding study design, tissue or analyte used, outcome measures, results and conclusions for each article. The quality of the included studies was assessed using a modification of the Newcastle-Ottawa-Scale. Results and Conclusions: From the initial 847 publications evaluated, a total of 57 articles were included in this review. In general, irreversible pulpitis was associated with different expression of various biomarkers compared to normal controls. These biomarkers were significantly expressed not only in pulp tissue, but also in gingival crevicular fluid that can be collected non-invasively, and in dentin fluid that can be analyzed without extirpating the entire pulpal tissue. Such data may then be used to accurately differentiate diseased from healthy pulp tissue. The interplay of pulpal biomarkers and their potential use for a more accurate and biologically based diagnostic tool in endodontics is envisaged. [ABSTRACT FROM AUTHOR]

Mineral trioxide aggregate (MTA) has been a revolutionary material in endodontics. Since its introduction in the 1990s several studies have demonstrated its use in various clinical applications. MTA has been extensively studied and is currently used for perforation repairs, apexifications, regenerative procedures, apexogenesis, pulpotomies, and pulp capping. This article will review the history, composition, research findings, and clinical applications of this versatile endodontic material. [ABSTRACT FROM AUTHOR]

Background: Host defense against invading pathogens is triggered by various receptors including toll-like receptors (TLRs). Activation of TLRs is a pivotal step in the initiation of innate, inflammatory, and antimicrobial defense mechanisms. Human β-defensin 2 (HBD-2) is a cationic antimicrobial peptide secreted upon Gram-negative bacterial perturbation in many cells. Stimulation of various TLRs has been shown to induce HBD-2 in oral keratinocytes, yet the underlying cellular mechanisms of this induction are poorly understood. Principal Findings: Here we demonstrate that HBD-2 induction is mediated by the Sphingosine kinase-1 (Sphk-1) and augmented by the inhibition of Glycogen Synthase Kinase-3β (GSK-3β) via the Phosphoinositide 3-kinase (PI3K) dependent pathway. HBD-2 secretion was dose dependently inhibited by a pharmacological inhibitor of Sphk-1. Interestingly, inhibition of GSK-3β by SB 216763 or by RNA interference, augmented HBD-2 induction. Overexpression of Sphk-1 with concomitant inhibition of GSK-3β enhanced the induction of β-defensin-2 in oral keratinocytes. Ectopic expression of constitutively active GSK-3β (S9A) abrogated HBD-2 whereas kinase inactive GSK-3β (R85A) induced higher amounts of HBD-2. Conclusions/Significance: These data implicate Sphk-1 in HBD-2 regulation in oral keratinocytes which also involves the activation of PI3K, AKT, GSK-3β and ERK 1/2. Thus we reveal the intricate relationship and pathways of toll-signaling molecules regulating HBD-2 which may have therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: The oral pathogen Porphyromonas gingivalis has been shown to modulate apoptosis in different cell types, but its effect on epithelial cells remains unclear. Results: We demonstrate that primary human gingival epithelial cells (HGECs) challenged with live P. gingivalis for 24 hours exhibit apoptosis, and we characterize this by M30 epitope detection, caspase-3 activity, DNA fragmentation and Annexin-V staining. Live bacteria strongly upregulated intrinsic and extrinsic apoptotic pathways. Pro-apoptotic molecules such as caspase-3, -8, -9, Bid and Bax were upregulated after 24 hours. The anti-apoptotic Bcl-2 was also upregulated, but this was not sufficient to ensure cell survival. The main P. gingivalis proteases arginine and lysine gingipains are necessary and sufficient to induce host cell apoptosis. Thus, live P. gingivalis can invoke gingival epithelial cell apoptosis in a time and dose dependent manner with significant apoptosis occurring between 12 and 24 hours of challenge via a gingipain-dependent mechanism. Conclusion: The present study provides evidence that live, but not heat-killed, P. gingivalis can induce apoptosis after 24 hours of challenge in primary human gingival epithelial cells. Either arginine or lysine gingipains are necessary and sufficient factors in P. gingivalis elicited apoptosis. [ABSTRACT FROM AUTHOR]

El artículo trata el rol de los polimorfismos genéticos en la periodontitis. Afirma que la genética puede determinar la gravedad y grado de la periodontitis y que se está aplicando tecnología genética en el diagnóstico y tratamiento de esta enfermedad. Sugiere que la periodontitis puede explicarse en base a varias polimorfismos de alto riesgo que tienen perfiles de alta susceptibilidad.