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Journal of Acupuncture and Meridian... Feb 2023Root canal treatment (RCT) employed for painful endodontic conditions like apical periodontitis and irreversible pulpitis is associated with a high incidence of... (Review)
Review
Root canal treatment (RCT) employed for painful endodontic conditions like apical periodontitis and irreversible pulpitis is associated with a high incidence of postoperative pain. Pharmacological management for this purpose is effective, but not entirely free from side effects and in some cases may fail to provide adequate relief. Furthermore, concerns have been raised regarding the transmission of coronavirus disease-2019 (COVID-19) as a result of the aerosols generated and prolonged chair side time required for RCT. Acupuncture is a traditional Chinese therapy commonly employed as an alternative for the treatment of pain. And what's more, the use of acupuncture has been recently reported as treatment for the management of endodontic pain as well as on the anesthetic success in patients with irreversible pulpitis. This review aims to evaluate the current evidence for acupuncture in endodontics and its potential role in emergency pain relief and management for patients. To combat this, a thorough search for literature within the field was performed in five electronic databases. Retrieved studies were screened according to the pre-defined eligibility criteria. After both an electronic and manual search, five studies were selected for review. These studies reported the beneficial effects of acupuncture in reducing the failure of nerve block in patients with irreversible pulpitis and in controlling both intraoperative and postoperative pain following RCT. In addition, it was also reported to reduce anxiety surrounding the dental procedure and minimized the intake of analgesics after the endodontic procedure, which can result in some unwanted side effects. However, more in depth clinical research is required before any recommendation regarding the application of acupuncture in endodontic patients can be made.
Topics: Humans; Pulpitis; Emergencies; COVID-19; Pain, Postoperative; Acupuncture Therapy
PubMed: 36804816
DOI: 10.51507/j.jams.2023.16.1.1 -
Journal of Applied Oral Science :... 2021Apical periodontitis is an inflammatory disorder of periradicular tissues developed from endodontic infections. Understanding its pathophysiology and the underlying... (Review)
Review
Apical periodontitis is an inflammatory disorder of periradicular tissues developed from endodontic infections. Understanding its pathophysiology and the underlying molecular mechanisms is key to the advancement of endodontics. MicroRNAs (miRNAs), a group of evolutionarily conserved small non-coding RNAs, may be phenotypically and functionally associated with the pathogenesis of apical periodontitis. Several studies have focused on the role of miRNAs in the pulp and periradicular biology, and they have demonstrated their essential functions, such as initiating odontogenic differentiation and promoting pro- or anti-inflammatory responses in pulpitis. Up to date, over 2,000 miRNAs have been discovered in humans; however, only few have been reported to associate with apical periodontitis. Therefore, identifying miRNAs involved in diseased apical tissues and conducting functional studies are important in expanding our current knowledge of pulp and periradicular biology and exploring novel therapeutic avenues. In this review, we revisit current models of apical periodontitis and miRNA biogenesis, analyze existing evidence of the involvement of miRNAs in diseased apical tissues, and discuss their diverse functions and potential values. Based on their sheer abundance, prolonged stability in biofluid, and relative ease of sampling, miRNAs may be a useful tool to be developed as diagnostic biomarkers for apical periodontitis. Furthermore, it can be used as therapeutic targets in conjunction with conventional endodontic therapies.
Topics: Dental Pulp; Endodontics; Humans; MicroRNAs; Periapical Periodontitis; Pulpitis
PubMed: 33886945
DOI: 10.1590/1678-7757-2020-1058 -
International Endodontic Journal Oct 2023The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and... (Review)
Review
BACKGROUND
The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and well-executed clinical trials on the diagnosis of the true status of the pulp.
OBJECTIVES
Three PICO questions were formulated and agreed a priori by the European Society of Endodontology to evaluate the clinical tests for sensibility testing, determination of biomarkers and pulp bleeding with regard to their suitability to correctly diagnose the condition of the pulp tissue for the development of S3-Level guidelines.
METHODS
A literature search was conducted using PubMed, Clarivate Analytics' Web of Science, Scopus, Google Scholar and Cochrane Central Register of Controlled Trials from inception to 21 January 2022. Additionally, a hand search was performed, and the contents of the major subject journals were also examined. Eligibility criteria followed the proposed PICO questions. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The risk of bias was assessed by the QUADAS-2 tool for diagnostic accuracy studies, the Newcastle-Ottawa scale for noncomparative, nonrandomized studies and the Newcastle-Ottawa Quality Assessment scale adapted for cross-sectional studies.
RESULTS
In total, 28 studies out of 29 publications were considered eligible and were included in the review. Twelve studies were identified to investigate the diagnostic accuracy of the pulp vitality. Ten studies fulfilled the criteria to evaluate the diagnostic accuracy of the pulpal conditions, while 6 studies investigating the expression of biomarkers were eligible. Three studies addressing the prognostic factors and therapeutic interventions relating to pulpal status were included.
DISCUSSION
The core problem in pulp diagnostics is that a reliable reference standard is lacking under clinical conditions. Based on limited evidence, the most promising current approach seems to define a combination of different clinical tests and symptoms, probably in future including molecular diagnosis ("diagnostic package") will be required to ascertain the best possible strategy to clinically diagnose true pulpal conditions.
CONCLUSIONS
The effectiveness of diagnosing pulpitis is low due to limited scientific evidence regarding the accuracy and reproducibility of diagnostic tests. There is a lack of evidence to determine the true status of the pulp or to identify prognostic indicators allowing for a reliable pre-operative estimation of the outcome of vital pulp treatment.
REGISTRATION
PROSPERO database (CRD42021265366).
Topics: Humans; Pulpitis; Cross-Sectional Studies; Reproducibility of Results; Dental Pulp; Dental Pulp Diseases; Biomarkers
PubMed: 35536159
DOI: 10.1111/iej.13762 -
Journal of Endodontics May 2021Proresolving lipid mediators are specialized molecules (SPMs) involved in the active resolution of the inflammatory process by regulating tissue homeostasis. The aim of... (Review)
Review
INTRODUCTION
Proresolving lipid mediators are specialized molecules (SPMs) involved in the active resolution of the inflammatory process by regulating tissue homeostasis. The aim of this study was to investigate the scientific literature to assess the potential of SPMs as an adjunct in the treatment of endodontic infection.
METHODS
Three electronic databases (PubMed, Web of Science, and Scopus) were searched from their inception until February 2020 (PROSPERO CRD42020164743). Supplemental research was performed by screening the references of the relevant studies eligible for inclusion. A quality assessment of animal studies was performed using the Animal Research: Reporting of In Vivo Experiments guidelines, whereas the Systematic Review Centre for Laboratory animal Experimentation Risk of Bias tool was used to assess the risk of bias.
RESULTS
A total of 3295 records were screened, and 8 articles meeting the criteria were included for this qualitative review. The eligible studies showed a high to moderate overall quality and a low to moderate risk of bias. SPMs positively affected the development of pulpitis and apical periodontitis in experimental animal models. The early treatment of pulpitis with the topical application of SPMs was beneficial to control inflammation within 24 hours from contamination. In addition, SPMs delivered within the root canals after disinfection were found effective in promoting periapical healing.
CONCLUSIONS
Our findings suggest that SPMs may play a role in the inception and treatment of pulpal-periapical diseases, and they should be considered for future research for developing new therapeutics as an adjunct to endodontic treatment.
Topics: Animals; Dental Care; Endodontics; Humans; Inflammation; Periapical Periodontitis; Pulpitis
PubMed: 33548330
DOI: 10.1016/j.joen.2021.01.008 -
International Endodontic Journal Jan 2021As one of the most densely innervated tissues, the dental pulp contains abundant nerve fibres, including sensory, sympathetic and parasympathetic nerve fibres. Studies... (Review)
Review
As one of the most densely innervated tissues, the dental pulp contains abundant nerve fibres, including sensory, sympathetic and parasympathetic nerve fibres. Studies in animal models and human patients with pulpitis have revealed distinct alterations in protein expression and histological appearance in all types of dental nerve fibres. Various molecules secreted by neurons, such as classical neurotransmitters, neuropeptides and amino acids, not only contribute to the induction, sensitization and maintenance of tooth pain, but also regulate non-neuronal cells, including fibroblasts, odontoblasts, immune cells and vascular endothelial cells. Dental nerves are particularly important for the microcirculatory and immune responses in pulpitis via their release of a variety of functional substances. Further, nerve fibres are found to be involved in dental soft and hard tissue repair. Thus, understanding how dental nerves participate in pulpitis could have important clinical ramifications for endodontic treatment. In this review, the roles of dental nerves in regulating pulpal inflammatory processes are highlighted and their implications for future research on this topic are discussed.
Topics: Animals; Dental Pulp; Endothelial Cells; Humans; Microcirculation; Odontoblasts; Pulpitis
PubMed: 32880979
DOI: 10.1111/iej.13400 -
British Dental Journal Jul 2020
Topics: Dexamethasone; Humans; Mandibular Nerve; Pulpitis
PubMed: 32651493
DOI: 10.1038/s41415-020-1907-x -
Cell Biochemistry and Function Aug 2021Autophagy is an evolutionarily conserved cellular process, in which damaged organelles and proteins are engulfed in autophagic vesicles and subsequently fuse with... (Review)
Review
Autophagy is an evolutionarily conserved cellular process, in which damaged organelles and proteins are engulfed in autophagic vesicles and subsequently fuse with lysosomes for degradation. Autophagy is widely involved in different physiologic or pathologic processes in human. Accumulating evidence indicates that autophagy operates as a critical quality control mechanism to maintain pulp homeostasis and structural integrity of the dentin-pulp complex. Autophagy is activated during stresses and is involved in the pathogenesis of pulpitis and periapical infection. Recent discoveries have also provided intriguing insights into the roles of autophagy in tooth development, pulp aging and stress adaptation. In this review, we provide an update on the multifaceted functions of autophagy in physiology and pathophysiology of tooth. We also discuss the therapeutic implications of autophagy modulation in diseases and the regeneration of dentin-pulp complex.
Topics: Animals; Autophagy; Dental Implants; Humans; Periapical Diseases; Pulpitis
PubMed: 33929054
DOI: 10.1002/cbf.3636 -
International Endodontic Journal Sep 2021To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity...
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.
Topics: Biomarkers; Computational Biology; Dental Pulp; Humans; Pulpitis; Real-Time Polymerase Chain Reaction
PubMed: 33964033
DOI: 10.1111/iej.13547 -
Frontiers in Immunology 2023The role of ferroptosis in irreversible pulpitis (IP) remains unclear. The competing endogenous RNA (ceRNA) theory that has been widely investigated is rarely used...
BACKGROUND
The role of ferroptosis in irreversible pulpitis (IP) remains unclear. The competing endogenous RNA (ceRNA) theory that has been widely investigated is rarely used studied in IP. Hub lncRNAs selected from a ceRNA network may provide a novel hypothesis for the interaction of ferroptosis and IP.
METHODS
Differentially expressed genes (DEGs) were intersected with 484 ferroptosis markers to identify differentially expressed ferroptosis-related genes (DE-FRGs). Functional analysis and protein-protein interaction (PPI) networks were constructed to reveal the functions of DE-FRGs. Then, coexpression analyses were conducted between DE-FRGs and DElncRNAs to define ferroptosis-related DElncRNAs (FR-DElncRNAs). Predictions of DE-FRG- and FR-DElncRNA-related miRNAs were obtained, and members of both groups were selected. Additionally, two ceRNA networks consisting of FR-DElncRNAs, miRNAs and DE-FRGs from upregulated and downregulated groups were built. Finally, the hub lncRNAs of the ceRNA networks were used for immuno-infiltration analysis and qPCR verification.
RESULTS
According to the results of PCA and clustering analysis, 5 inflamed and 5 healthy pulp tissue samples were selected for analysis. The intersection of DEGs with 484 ferroptosis marker genes identified 72 DE-FRGs. The response to stimulus, cellular process, signaling, localization, and biological regulation pathways related to DE-FRGs were enriched. In total, 161 downregulated and 40 upregulated FR-DElncRNAs were chosen by coexpression analysis for further investigation. The MultimiR package and starBase were used to predict miRNAs of DE-FRGs and FR-DElncRNAs, respectively. The upregulated ceRNA network contained 2 FR-DElncRNAs (↑), 19 miRNAs (↓) and 22 DE-FRGs (↑). The downregulated network contained 44 FR-DElncRNAs (↓), 251 miRNAs (↑) and 10 DE-FRGs (↓). Six hub lncRNAs were identified based on the MCC method (LUCAT1 and AC106897.1 ↑; LINC00943, AL583810.1, AC068888.1, and AC125257.1↓). In addition, strong relationships between hub lncRNAs and immune cells were shown by immune infiltration analysis. Finally, validated by qPCR assays of the pulp tissue of IP patients, the expression levels in clinical samples were consistent with the microarray data.
CONCLUSION
Two ceRNA networks were comprehensively constructed, and 6 hub lncRNAs were identified. These genes provide novel insights into the relationship between ferroptosis and IP. Intriguingly, the LINC00943/hsa-miR-29a-3p/PDK4 axis was deemed to be the key node in this network.
Topics: Humans; Ferroptosis; Pulpitis; RNA, Long Noncoding; MicroRNAs; Biological Assay
PubMed: 37275855
DOI: 10.3389/fimmu.2023.1198053 -
International Endodontic Journal Jul 2023To investigate the regulatory role of miR-155 and Kinesin Superfamily Proteins-5C (KIF-5C) in the progression of pulpitis based on bioinformatic analysis.
AIM
To investigate the regulatory role of miR-155 and Kinesin Superfamily Proteins-5C (KIF-5C) in the progression of pulpitis based on bioinformatic analysis.
METHODOLOGY
Normal pulp tissues and pulpitis pulp tissues were collected and subjected to high-throughput sequencing and the differentially expressed miRNAs were determined. An in vitro and in vivo pulpitis model was established. HE, IHC staining and histological evaluation were used to verify the inflammatory state of human and mouse pulp tissues. The mRNA expression of IL-1β and TGF-β1 were determined by RT-qPCR and protein expression of IL-1α, IL-4, IL-8, IL-13, IFN-γ, IL-6, IL-10 and MCP-1 were determined by protein chip. The target genes of miR-155 were predicted by miRanda database and verified by Dual-luciferase reporter assay, RT-qPCR and western blotting. MiR-155 lentivirus were used to upregulate or downregulate miR-155 and the siRNA of KIF-5C was used to downregulate KIF-5C. The expression of miR-155 or KIF-5C was determined by RT-qPCR. All statistics were analysed using GraphPad prism 8.2.
RESULTS
The high-throughput sequencing results showed that 6 miRNAs (miR-155, miR-21, miR-142, miR-223, miR-486, miR-675) were significantly upregulated in diseased human pulp tissues, and miR-155 was significantly elevated among the six miRNAs. RT-qPCR results demonstrated that miR-155 expression was upregulated in human pulpitic tissue, mice pulpitic tissue and LPS-HDPCs. IL-1β was increased while TGF-β1 was decreased in lenti-miR-155 transfected LPS-HDPCs. Analysis of protein chip results indicated that lenti-miR-155 transfected LPS-HDPCs produced higher levels of IL-8, IL-6, MCP-1. The opposite results were obtained when miR-155 was inhibited. Through miRanda database screen and Dual-luciferase reporter assay, the target gene (KIF-5C) of miR-155 was identified. In lenti-miR-155 transfected LPS-HDPCs, the expression of KIF-5C was downregulated. However, when shRNA-miR-155 was transfected to LPS-HDPCs, the opposite result was obtained. Silent RNA was used to knock down KIF-5C, the results showed that when both KIF-5C and miR-155 were knocked down simultaneously, the downregulated expression of inflammatory factors observed in LPS-HDPCs following miR-155 knockdown was rescued.
CONCLUSION
MiR-155 plays an important role in promoting pulpitis through targeting KIF-5C and may serve as a potential therapeutic target.
Topics: Humans; Mice; Animals; Pulpitis; Transforming Growth Factor beta1; Kinesins; Lipopolysaccharides; Interleukin-6; Interleukin-8; MicroRNAs; Dental Pulp; Luciferases
PubMed: 37070646
DOI: 10.1111/iej.13923