{"title":"Letter to Editor for “Potential predisposing features of external cervical resorption: An observational study (Patel et al., 2025)”","authors":"John Rong Hao Tay, Upul Cooray","doi":"10.1111/iej.14215","DOIUrl":"https://doi.org/10.1111/iej.14215","url":null,"abstract":"","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 5","pages":"797-798"},"PeriodicalIF":5.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Horn Troian-Michel, Bruna Barcelos Só, Lauren Frenzel Schuch, Grazielle Oliveira Stelter, Tuany Rafaeli Schmidt, Joana Letícia Schorr, Daniela Campagnol, Tuane Nerissa Alves Garcez, Gabriel Barcelos Só, Thalita Ayres Arrué, Theodoro Weissheimer, Manoela Domingues Martins, Marcus Vinicius Reis Só
Aim: Osteoporosis is a disease that is related to a higher prevalence and greater volumes of apical periodontitis. The purpose of this study was to evaluate the effect of ovariectomy-induced osteoporosis and high- or low-level laser photobiomodulation (PBM) on the repair of apical periodontitis (AP) in adult female Wistar rats.
Methodology: Sixty female Wistar rats (n = 120) were randomly allocated into four control (n = 6 teeth) and 8 experimental (n = 12 teeth) groups, according to procedure and time of evaluation: healthy control (GCS14/GCS28), osteoporotic control (GCO14/GCO28), sham (SHAM14/SHAM28), osteoporotic (OVX14/OVX28), low-level laser (OVX-LLL14/OVX-LLL28) and high-level laser (OVX-GEM14/OVX-GEM28). All groups were submitted to bilateral ovariectomy, except for the healthy control and sham. Eight weeks later, AP was induced bilaterally in mandibular first molars' mesial roots in experimental groups, and after 21 days, their endodontic treatment (RCT) was conducted. For 14 or 28 days, PBM was applied three times/week, as follows: sham application (SHAM and OVX groups); low-level laser (OVX/LLL groups); defocused high-power laser (OVX/GEM groups). After the respective experimental periods, the animals were euthanized. Tibias and hemi-mandibula were obtained and submitted to computed microtomography. Bone volume fraction (BV/TV), trabeculae number (Tb.N), spacing (Tb.Sp) and thickness (Tb.Th) were obtained for tibias, while RCT apical limit, periodontal ligament and AP volumes (APvol) were recorded for hemi-mandibula. Data were subjected to statistical analysis through generalized estimating equations (GEE), ANOVA and chi-square tests (5% significance level).
Results: Ovariectomy tibias showed lower BV/TV and Tb.N (p < .0001) and higher Tb.Th (p = .020) and Tb.Sp (p < .0001) when compared to sham groups. For hemi-mandibula, lower APvol values were found in SHAM14 when compared to OVX/LLL14 and OVX/GEM14 groups (p < .05), which were not different from each other. Over the 28-day period, the OVX/LLL28 group showed higher AP volumes when compared to OVX28 and OVX/GEM28 (p < .05). Analysing variables effects on APvol, time, PBM and RCT apical limit showed no effect (p > .05), while ovariectomy showed a significant increase (p = .004).
Conclusions: Ovariectomy-induced osteoporosis in Wistar rats led to a reduction in AP repair, and PBM was unable to counteract this effect.
{"title":"Effects of ovariectomy-induced osteoporosis and two photobiomodulation protocols on the repair of apical periodontitis in Wistar rats: A microCT study.","authors":"Carolina Horn Troian-Michel, Bruna Barcelos Só, Lauren Frenzel Schuch, Grazielle Oliveira Stelter, Tuany Rafaeli Schmidt, Joana Letícia Schorr, Daniela Campagnol, Tuane Nerissa Alves Garcez, Gabriel Barcelos Só, Thalita Ayres Arrué, Theodoro Weissheimer, Manoela Domingues Martins, Marcus Vinicius Reis Só","doi":"10.1111/iej.14234","DOIUrl":"https://doi.org/10.1111/iej.14234","url":null,"abstract":"<p><strong>Aim: </strong>Osteoporosis is a disease that is related to a higher prevalence and greater volumes of apical periodontitis. The purpose of this study was to evaluate the effect of ovariectomy-induced osteoporosis and high- or low-level laser photobiomodulation (PBM) on the repair of apical periodontitis (AP) in adult female Wistar rats.</p><p><strong>Methodology: </strong>Sixty female Wistar rats (n = 120) were randomly allocated into four control (n = 6 teeth) and 8 experimental (n = 12 teeth) groups, according to procedure and time of evaluation: healthy control (GCS14/GCS28), osteoporotic control (GCO14/GCO28), sham (SHAM14/SHAM28), osteoporotic (OVX14/OVX28), low-level laser (OVX-LLL14/OVX-LLL28) and high-level laser (OVX-GEM14/OVX-GEM28). All groups were submitted to bilateral ovariectomy, except for the healthy control and sham. Eight weeks later, AP was induced bilaterally in mandibular first molars' mesial roots in experimental groups, and after 21 days, their endodontic treatment (RCT) was conducted. For 14 or 28 days, PBM was applied three times/week, as follows: sham application (SHAM and OVX groups); low-level laser (OVX/LLL groups); defocused high-power laser (OVX/GEM groups). After the respective experimental periods, the animals were euthanized. Tibias and hemi-mandibula were obtained and submitted to computed microtomography. Bone volume fraction (BV/TV), trabeculae number (Tb.N), spacing (Tb.Sp) and thickness (Tb.Th) were obtained for tibias, while RCT apical limit, periodontal ligament and AP volumes (APvol) were recorded for hemi-mandibula. Data were subjected to statistical analysis through generalized estimating equations (GEE), ANOVA and chi-square tests (5% significance level).</p><p><strong>Results: </strong>Ovariectomy tibias showed lower BV/TV and Tb.N (p < .0001) and higher Tb.Th (p = .020) and Tb.Sp (p < .0001) when compared to sham groups. For hemi-mandibula, lower APvol values were found in SHAM14 when compared to OVX/LLL14 and OVX/GEM14 groups (p < .05), which were not different from each other. Over the 28-day period, the OVX/LLL28 group showed higher AP volumes when compared to OVX28 and OVX/GEM28 (p < .05). Analysing variables effects on APvol, time, PBM and RCT apical limit showed no effect (p > .05), while ovariectomy showed a significant increase (p = .004).</p><p><strong>Conclusions: </strong>Ovariectomy-induced osteoporosis in Wistar rats led to a reduction in AP repair, and PBM was unable to counteract this effect.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaolin Li, Sanjun Zhao, Yao Liu, Yu Gu, Lihong Qiu, Xu Chen, Alastair J Sloan, Bing Song
Aim: This study examined the impact of direct current electric fields (DCEFs) on the biological properties of stem cells derived from the apical papilla (SCAP) and further elucidated the underlying mechanisms involved in odontogenic differentiation induced by DCEFs stimulation.
Methodology: The measurement of endogenous currents in wounded dentine was achieved using a non-invasive vibrating probe system. Two-dimensional (2D) and three-dimensional (3D) systems were developed to apply DCEFs of varying strengths. The migration direction and trajectories of SCAP within DCEFs were analysed using time-lapse imaging. Cell proliferation was assessed through Hoechst staining and the CCK-8 assay. Changes in cell morphology, arrangement, and polarization were examined using fluorescence staining. The odontogenic differentiation of SCAP in vitro was assessed using quantitative polymerase chain reaction (qPCR), western blot analysis, alkaline phosphatase staining, and Alizarin Red S staining. In vivo evaluation was conducted through Haematoxylin and eosin staining, immunohistochemistry staining, and Sirius Red staining after transplantation experiments.
Results: Injured dentine demonstrated a significantly increased outward current, and DCEFs facilitated the migration of SCAP towards the anode. DCEFs at a magnitude of 100 mV/mm promoted SCAP proliferation, whereas DCEFs at 200 mV/mm enhanced both polarization and odontogenic differentiation of SCAP. The application of cytoskeletal polymerization inhibitors mitigated the odontogenic differentiation induced by DCEFs. In vivo studies confirmed that DCEFs promoted the differentiation of SCAP into odontoblast-like cells in an orderly arrangement, as well as the formation of collagen fibres and dentine-like tissue.
Conclusions: DCEFs of varying intensities exhibited an enhanced capacity for migration, proliferation, odontogenic differentiation, and polarization in SCAP. These findings provide substantial insights for the advancement of innovative therapeutic strategies targeting the repair and regeneration of immature permanent teeth and dentine damage.
{"title":"Electric field promoted odontogenic differentiation of stem cells from apical papilla by remodelling cytoskeleton.","authors":"Xiaolin Li, Sanjun Zhao, Yao Liu, Yu Gu, Lihong Qiu, Xu Chen, Alastair J Sloan, Bing Song","doi":"10.1111/iej.14213","DOIUrl":"https://doi.org/10.1111/iej.14213","url":null,"abstract":"<p><strong>Aim: </strong>This study examined the impact of direct current electric fields (DCEFs) on the biological properties of stem cells derived from the apical papilla (SCAP) and further elucidated the underlying mechanisms involved in odontogenic differentiation induced by DCEFs stimulation.</p><p><strong>Methodology: </strong>The measurement of endogenous currents in wounded dentine was achieved using a non-invasive vibrating probe system. Two-dimensional (2D) and three-dimensional (3D) systems were developed to apply DCEFs of varying strengths. The migration direction and trajectories of SCAP within DCEFs were analysed using time-lapse imaging. Cell proliferation was assessed through Hoechst staining and the CCK-8 assay. Changes in cell morphology, arrangement, and polarization were examined using fluorescence staining. The odontogenic differentiation of SCAP in vitro was assessed using quantitative polymerase chain reaction (qPCR), western blot analysis, alkaline phosphatase staining, and Alizarin Red S staining. In vivo evaluation was conducted through Haematoxylin and eosin staining, immunohistochemistry staining, and Sirius Red staining after transplantation experiments.</p><p><strong>Results: </strong>Injured dentine demonstrated a significantly increased outward current, and DCEFs facilitated the migration of SCAP towards the anode. DCEFs at a magnitude of 100 mV/mm promoted SCAP proliferation, whereas DCEFs at 200 mV/mm enhanced both polarization and odontogenic differentiation of SCAP. The application of cytoskeletal polymerization inhibitors mitigated the odontogenic differentiation induced by DCEFs. In vivo studies confirmed that DCEFs promoted the differentiation of SCAP into odontoblast-like cells in an orderly arrangement, as well as the formation of collagen fibres and dentine-like tissue.</p><p><strong>Conclusions: </strong>DCEFs of varying intensities exhibited an enhanced capacity for migration, proliferation, odontogenic differentiation, and polarization in SCAP. These findings provide substantial insights for the advancement of innovative therapeutic strategies targeting the repair and regeneration of immature permanent teeth and dentine damage.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hossein Mohammad-Rahimi, Frank C Setzer, Anita Aminoshariae, Paul Michael Howell Dummer, Henry F Duncan, Ali Nosrat
The integration of artificial intelligence (AI) into education is transforming learning across various domains, including dentistry. Endodontic education can significantly benefit from AI chatbots; however, knowledge gaps regarding their potential and limitations hinder their effective utilization. This narrative review aims to: (A) explain the core functionalities of AI chatbots, including their reliance on natural language processing (NLP), machine learning (ML), and deep learning (DL); (B) explore their applications in endodontic education for personalized learning, interactive training, and clinical decision support; (C) discuss the challenges posed by technical limitations, ethical considerations, and the potential for misinformation. The review highlights that AI chatbots provide learners with immediate access to knowledge, personalized educational experiences, and tools for developing clinical reasoning through case-based learning. Educators benefit from streamlined curriculum development, automated assessment creation, and evidence-based resource integration. Despite these advantages, concerns such as chatbot hallucinations, algorithmic biases, potential for plagiarism, and the spread of misinformation require careful consideration. Analysis of current research reveals limited endodontic-specific studies, emphasizing the need for tailored chatbot solutions validated for accuracy and relevance. Successful integration will require collaborative efforts among educators, developers, and professional organizations to address challenges, ensure ethical use, and establish evaluation frameworks.
{"title":"Artificial intelligence chatbots in endodontic education-Concepts and potential applications.","authors":"Hossein Mohammad-Rahimi, Frank C Setzer, Anita Aminoshariae, Paul Michael Howell Dummer, Henry F Duncan, Ali Nosrat","doi":"10.1111/iej.14231","DOIUrl":"https://doi.org/10.1111/iej.14231","url":null,"abstract":"<p><p>The integration of artificial intelligence (AI) into education is transforming learning across various domains, including dentistry. Endodontic education can significantly benefit from AI chatbots; however, knowledge gaps regarding their potential and limitations hinder their effective utilization. This narrative review aims to: (A) explain the core functionalities of AI chatbots, including their reliance on natural language processing (NLP), machine learning (ML), and deep learning (DL); (B) explore their applications in endodontic education for personalized learning, interactive training, and clinical decision support; (C) discuss the challenges posed by technical limitations, ethical considerations, and the potential for misinformation. The review highlights that AI chatbots provide learners with immediate access to knowledge, personalized educational experiences, and tools for developing clinical reasoning through case-based learning. Educators benefit from streamlined curriculum development, automated assessment creation, and evidence-based resource integration. Despite these advantages, concerns such as chatbot hallucinations, algorithmic biases, potential for plagiarism, and the spread of misinformation require careful consideration. Analysis of current research reveals limited endodontic-specific studies, emphasizing the need for tailored chatbot solutions validated for accuracy and relevance. Successful integration will require collaborative efforts among educators, developers, and professional organizations to address challenges, ensure ethical use, and establish evaluation frameworks.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: Recent findings suggest that mitigating ferroptosis could serve as an effective strategy for treating inflammation. This study aimed to investigate the role that the enhancer of zeste homologue 2 (EZH2) mediated the signal transducer and activator of transcription 3 (stat3) methylation plays in the modulation of ferroptosis in pulpitis. The study results offer potential advancements in the therapeutic approaches for pulpitis and provide new insights and strategies for managing this condition.
Methodology: Bioinformatics analysis combined with methylation capture sequencing of EZH2fl/flCre+/- pulp tissue was used to explore the association between pulpitis and ferroptosis. In this study, we used an EZH2 knockout model prepared through lentiviral transduction and an LPS-induced inflammatory model of endometrial mesenchymal stromal cells to confirm the role that the EZH2/STAT3 axis plays in ferroptosis.
Results: Bioinformatics analysis identified a link between pulpitis and DNA methylation. Methylation sequencing further revealed the association of methylation with ferroptosis and the regulation of STAT3 methylation by EZH2. In vitro, lipopolysaccharide (LPS) stimulation induced ferroptosis, whereas EZH2 disruption suppressed STAT3 expression but increased Glutathione Peroxidase 4 (GPX4) expression, leading to the escalation of oxidative stress and exacerbation of ferroptosis. This illustrates the complex interactions between methylation, ferroptosis and oral inflammation, highlighting potential therapeutic targets.
Conclusions: Overall, pulpitis plays a crucial role in EZH2-mediated STAT3 methylation and activates ferroptosis by regulating GPX4 expression. This study provides new insights and strategies for treatment and advances our understanding of the pathogenesis of pulpitis.
{"title":"EZH2 knockout in mice activates STAT3 signalling via STAT3 methylation and modulates ferroptosis in pulpitis-affected dental pulp vascular endothelial cells: A laboratory investigation.","authors":"Weilin Zhou, Weili Huang, Hongjing You, Minyi Zhang, Yue Ma, Lingjie Liu, Mengxuan Lin, Shuqi He, Yi Huang","doi":"10.1111/iej.14232","DOIUrl":"https://doi.org/10.1111/iej.14232","url":null,"abstract":"<p><strong>Aim: </strong>Recent findings suggest that mitigating ferroptosis could serve as an effective strategy for treating inflammation. This study aimed to investigate the role that the enhancer of zeste homologue 2 (EZH2) mediated the signal transducer and activator of transcription 3 (stat3) methylation plays in the modulation of ferroptosis in pulpitis. The study results offer potential advancements in the therapeutic approaches for pulpitis and provide new insights and strategies for managing this condition.</p><p><strong>Methodology: </strong>Bioinformatics analysis combined with methylation capture sequencing of EZH2<sup>fl/fl</sup>Cre<sup>+/-</sup> pulp tissue was used to explore the association between pulpitis and ferroptosis. In this study, we used an EZH2 knockout model prepared through lentiviral transduction and an LPS-induced inflammatory model of endometrial mesenchymal stromal cells to confirm the role that the EZH2/STAT3 axis plays in ferroptosis.</p><p><strong>Results: </strong>Bioinformatics analysis identified a link between pulpitis and DNA methylation. Methylation sequencing further revealed the association of methylation with ferroptosis and the regulation of STAT3 methylation by EZH2. In vitro, lipopolysaccharide (LPS) stimulation induced ferroptosis, whereas EZH2 disruption suppressed STAT3 expression but increased Glutathione Peroxidase 4 (GPX4) expression, leading to the escalation of oxidative stress and exacerbation of ferroptosis. This illustrates the complex interactions between methylation, ferroptosis and oral inflammation, highlighting potential therapeutic targets.</p><p><strong>Conclusions: </strong>Overall, pulpitis plays a crucial role in EZH2-mediated STAT3 methylation and activates ferroptosis by regulating GPX4 expression. This study provides new insights and strategies for treatment and advances our understanding of the pathogenesis of pulpitis.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junkai Zeng, Yeqing Yang, Chong Jiang, Buling Wu, Ming Chen
Aim: Dental pulp stem cells (DPSCs) are essential for pulp regeneration but face low survival rates after transplantation. Genetic modification before transplantation is a promising solution to this issue. We aim to elucidate the biological function and regulatory mechanism of hypoxic lncRNA HRL-SC in DPSCs.
Methodology: The biological functions of HRL-SC and hypoxia inducible factor-1α (HIF-1α) in DPSCs were evaluated in vitro by cell proliferation, migration and tube formation assays. Subcutaneous transplantation in nude mice was used to evaluate the effect of HRL-SC on DPSC viability in vivo. RNA sequencing and bioinformatics analysis, RNA immunoprecipitation, dual luciferase reporter gene assay, co-immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence and RNA and protein stability assays were used to explore the potential mechanism of HRL-SC in DPSCs. Data were analysed by one-way analysis of variance (anova) or Student's t-test, with a p <.05 indicating statistical significance.
Results: HRL-SC, a hypoxia-responsive lncRNA, enhanced the proliferation, migration and tube formation abilities of DPSCs. Subcutaneous transplantation of dental blocks revealed that HRL-SC-mediated DPSCs exhibited improved cell viability and elevated expression of Ki-67 and CD31, along with the capacity to form vascular-like structures. HIF-1α was observed to induce transcription of HRL-SC. Reciprocally, HRL-SC bound to VHL, thereby inhibiting VHL-mediated HIF-1α ubiquitination, which resulted in a positive feed-forward loop of HRL-SC/HIF-1α. RNA-sequencing and functional analyses revealed that HRL-SC was closely associated with hypoxia, angiogenesis, regeneration, integrin and PI3K/AKT signalling pathways. Furthermore, HRL-SC was shown to stabilize ITGAV and ITGB3 through PTBP1. Finally, it was confirmed that HRL-SC activated the PI3K/AKT signalling pathway via the integrin αvβ3/FAK and HIF-1α/PDK1 axes.
Conclusions: DPSCs modified with HRL-SC demonstrated enhanced cell viability via the PI3K/AKT signaling pathway and exhibited functional characteristics of endothelial cells, which may provide a novel strategy for the application of DPSCs in pulp regeneration.
{"title":"An HRL-SC/HIF-1α positive feedback loop enhances cell proliferation, migration and angiogenesis in dental pulp stem cells via PI3K/AKT signalling pathway.","authors":"Junkai Zeng, Yeqing Yang, Chong Jiang, Buling Wu, Ming Chen","doi":"10.1111/iej.14229","DOIUrl":"https://doi.org/10.1111/iej.14229","url":null,"abstract":"<p><strong>Aim: </strong>Dental pulp stem cells (DPSCs) are essential for pulp regeneration but face low survival rates after transplantation. Genetic modification before transplantation is a promising solution to this issue. We aim to elucidate the biological function and regulatory mechanism of hypoxic lncRNA HRL-SC in DPSCs.</p><p><strong>Methodology: </strong>The biological functions of HRL-SC and hypoxia inducible factor-1α (HIF-1α) in DPSCs were evaluated in vitro by cell proliferation, migration and tube formation assays. Subcutaneous transplantation in nude mice was used to evaluate the effect of HRL-SC on DPSC viability in vivo. RNA sequencing and bioinformatics analysis, RNA immunoprecipitation, dual luciferase reporter gene assay, co-immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence and RNA and protein stability assays were used to explore the potential mechanism of HRL-SC in DPSCs. Data were analysed by one-way analysis of variance (anova) or Student's t-test, with a p <.05 indicating statistical significance.</p><p><strong>Results: </strong>HRL-SC, a hypoxia-responsive lncRNA, enhanced the proliferation, migration and tube formation abilities of DPSCs. Subcutaneous transplantation of dental blocks revealed that HRL-SC-mediated DPSCs exhibited improved cell viability and elevated expression of Ki-67 and CD31, along with the capacity to form vascular-like structures. HIF-1α was observed to induce transcription of HRL-SC. Reciprocally, HRL-SC bound to VHL, thereby inhibiting VHL-mediated HIF-1α ubiquitination, which resulted in a positive feed-forward loop of HRL-SC/HIF-1α. RNA-sequencing and functional analyses revealed that HRL-SC was closely associated with hypoxia, angiogenesis, regeneration, integrin and PI3K/AKT signalling pathways. Furthermore, HRL-SC was shown to stabilize ITGAV and ITGB3 through PTBP1. Finally, it was confirmed that HRL-SC activated the PI3K/AKT signalling pathway via the integrin αvβ3/FAK and HIF-1α/PDK1 axes.</p><p><strong>Conclusions: </strong>DPSCs modified with HRL-SC demonstrated enhanced cell viability via the PI3K/AKT signaling pathway and exhibited functional characteristics of endothelial cells, which may provide a novel strategy for the application of DPSCs in pulp regeneration.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rania Nassar, Mohannad Nassar, Lobna Mohamed, Abiola Senok, David Williams
Aim: The microbiota of endodontic infections in patients from the Arabian Gulf region (AGR) is largely unexplored. While research in different global regions has investigated the microbial composition of such infections, studies using shotgun metagenomic sequencing (SMS) alongside culture-dependent techniques (CDT) are limited. There are also few in vitro biofilm models that reflect the microbial profiles of endodontic infections. Therefore, by employing SMS and CDT, this research aimed to explore compositional and functional microbial profiles of endodontic infections from the AGR. The research also sought to develop ex vivo biofilms directly from endodontic infection samples.
Methodology: SMS and CDT were used to analyze 32 root canal samples from necrotic pulp. Patients' samples were categorized into two cohorts: symptomatic (n = 19) and asymptomatic (n = 13). Samples underwent sequencing followed by bioinformatic analysis to investigate microbial composition, resistome, virulome, and functional differences. Two representative samples (8R, 15R) were selected to develop ex vivo biofilms on hydroxyapatite coupons. Similarity between inoculum and developed biofilms was assessed using SMS and CDT. The reproducibility of developed biofilms was assessed based on microbial composition and relative abundance at the species level using correlation coefficient analysis.
Results: Endodontic samples had high bacterial diversity, with a total of 366 bacterial species detected across the two cohorts. Several antibiotic resistance (n = 59) and virulence (n = 82) genes were identified, with no significant differences between the cohorts. CDT identified 28 bacterial species, with 71.4% of the isolated bacteria having phenotypic resistance to clinically relevant antibiotics. SMS showed that the ex vivo biofilms were polymicrobial. Biofilm derived from sample 15R had 9 species and was dominated by Enterococcus faecalis, while sample 8R had 12 species and was dominated by Streptococcus mutans. Pearson correlation analysis demonstrated a significant positive correlation between biological biofilm replicates, confirming the reproducibility of biofilm formation.
Conclusions: There was high bacterial diversity in root canal samples from necrotic pulp. Samples were shown to contain antibiotic resistance and virulence genes, with no differences evident between symptomatic and asymptomatic infections. A high number of isolated bacteria were resistant to clinically used antibiotics. Ex vivo biofilm models from clinical samples were successfully developed and reproducibly reflected a polymicrobial composition.
{"title":"Characterization and ex vivo modelling of endodontic infections from the Arabian Gulf region.","authors":"Rania Nassar, Mohannad Nassar, Lobna Mohamed, Abiola Senok, David Williams","doi":"10.1111/iej.14227","DOIUrl":"https://doi.org/10.1111/iej.14227","url":null,"abstract":"<p><strong>Aim: </strong>The microbiota of endodontic infections in patients from the Arabian Gulf region (AGR) is largely unexplored. While research in different global regions has investigated the microbial composition of such infections, studies using shotgun metagenomic sequencing (SMS) alongside culture-dependent techniques (CDT) are limited. There are also few in vitro biofilm models that reflect the microbial profiles of endodontic infections. Therefore, by employing SMS and CDT, this research aimed to explore compositional and functional microbial profiles of endodontic infections from the AGR. The research also sought to develop ex vivo biofilms directly from endodontic infection samples.</p><p><strong>Methodology: </strong>SMS and CDT were used to analyze 32 root canal samples from necrotic pulp. Patients' samples were categorized into two cohorts: symptomatic (n = 19) and asymptomatic (n = 13). Samples underwent sequencing followed by bioinformatic analysis to investigate microbial composition, resistome, virulome, and functional differences. Two representative samples (8R, 15R) were selected to develop ex vivo biofilms on hydroxyapatite coupons. Similarity between inoculum and developed biofilms was assessed using SMS and CDT. The reproducibility of developed biofilms was assessed based on microbial composition and relative abundance at the species level using correlation coefficient analysis.</p><p><strong>Results: </strong>Endodontic samples had high bacterial diversity, with a total of 366 bacterial species detected across the two cohorts. Several antibiotic resistance (n = 59) and virulence (n = 82) genes were identified, with no significant differences between the cohorts. CDT identified 28 bacterial species, with 71.4% of the isolated bacteria having phenotypic resistance to clinically relevant antibiotics. SMS showed that the ex vivo biofilms were polymicrobial. Biofilm derived from sample 15R had 9 species and was dominated by Enterococcus faecalis, while sample 8R had 12 species and was dominated by Streptococcus mutans. Pearson correlation analysis demonstrated a significant positive correlation between biological biofilm replicates, confirming the reproducibility of biofilm formation.</p><p><strong>Conclusions: </strong>There was high bacterial diversity in root canal samples from necrotic pulp. Samples were shown to contain antibiotic resistance and virulence genes, with no differences evident between symptomatic and asymptomatic infections. A high number of isolated bacteria were resistant to clinically used antibiotics. Ex vivo biofilm models from clinical samples were successfully developed and reproducibly reflected a polymicrobial composition.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: Endodontic Access Cavity (EAC) opening is a critical step in Root Canal Treatment. yet, a robust formative assessment tool for this procedure is lacking in the literature. Therefore, the overarching goal of our study was to develop and validate an OSATS tool specifically for the formative assessment of EAC opening skill. The specific objectives of our study were (1) to evaluate the ability of the performance ratings on the newly developed OSATS tool in differentiating between different levels of dental students (Final year students [FY] and House officers [HO]) in the EAC opening procedure on extracted natural teeth and (2)-to determine the inter-rater reliability of the newly developed OSATS tool in assessing the EAC opening procedure.
Methodology: Conducted over 6 months in 2024, the tool was developed collaboratively by an endodontic expert (EE) and two medical educationists, following an extensive literature review. Performance rubrics and guidelines were devised, and the tool underwent two review cycles by 11 EEs, achieving satisfactory Content Validity Index scores (Scale-CVI: 0.9, Universal agreement: 0.7). Two trained assessors applied the tool to evaluate 30 students (15 FY, 15 HO) across three tooth types (anterior, premolar, molar), generating 180 OSATS forms. Data analysis in IBM SPSS v24 assessed inter-rater reliability (intraclass correlation), internal consistency (Cronbach's alpha) and group performance differences (Mann-Whitney U, Kruskal-Wallis H-tests).
Results: Inter-rater reliability (0.83) and internal consistency (Cronbach's alpha = 0.83) were strong. HO significantly outperformed FY (p < .05) on pre-access, initial access and final access sub-scales, with superior global ratings on premolars (p = .003). HO exhibited significant performance differences across sub-scales for anterior, premolar and molar teeth (p < .05), excelling on premolars and anteriors compared to molars.
Conclusions: The newly developed OSATS tool demonstrated strong internal consistency and inter-rater reliability. It effectively differentiated performance ratings across various student levels and tooth types, establishing itself as a reliable and effective instrument for formative assessment of access cavity opening skill in endodontics.
{"title":"Development and validation of OSATS tool for formative assessment of dental students' endodontic access cavity opening skills.","authors":"Juzer Shabbir, Qamar Riaz, Shanila Sohail","doi":"10.1111/iej.14230","DOIUrl":"https://doi.org/10.1111/iej.14230","url":null,"abstract":"<p><strong>Aim: </strong>Endodontic Access Cavity (EAC) opening is a critical step in Root Canal Treatment. yet, a robust formative assessment tool for this procedure is lacking in the literature. Therefore, the overarching goal of our study was to develop and validate an OSATS tool specifically for the formative assessment of EAC opening skill. The specific objectives of our study were (1) to evaluate the ability of the performance ratings on the newly developed OSATS tool in differentiating between different levels of dental students (Final year students [FY] and House officers [HO]) in the EAC opening procedure on extracted natural teeth and (2)-to determine the inter-rater reliability of the newly developed OSATS tool in assessing the EAC opening procedure.</p><p><strong>Methodology: </strong>Conducted over 6 months in 2024, the tool was developed collaboratively by an endodontic expert (EE) and two medical educationists, following an extensive literature review. Performance rubrics and guidelines were devised, and the tool underwent two review cycles by 11 EEs, achieving satisfactory Content Validity Index scores (Scale-CVI: 0.9, Universal agreement: 0.7). Two trained assessors applied the tool to evaluate 30 students (15 FY, 15 HO) across three tooth types (anterior, premolar, molar), generating 180 OSATS forms. Data analysis in IBM SPSS v24 assessed inter-rater reliability (intraclass correlation), internal consistency (Cronbach's alpha) and group performance differences (Mann-Whitney U, Kruskal-Wallis H-tests).</p><p><strong>Results: </strong>Inter-rater reliability (0.83) and internal consistency (Cronbach's alpha = 0.83) were strong. HO significantly outperformed FY (p < .05) on pre-access, initial access and final access sub-scales, with superior global ratings on premolars (p = .003). HO exhibited significant performance differences across sub-scales for anterior, premolar and molar teeth (p < .05), excelling on premolars and anteriors compared to molars.</p><p><strong>Conclusions: </strong>The newly developed OSATS tool demonstrated strong internal consistency and inter-rater reliability. It effectively differentiated performance ratings across various student levels and tooth types, establishing itself as a reliable and effective instrument for formative assessment of access cavity opening skill in endodontics.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carla Moretto, Patrícia Maria Poli Kopper, Eliseu Aldrighi Münchow, Roberta Kochenborger Scarparo
Background: Summarizing the association between patient age and vital pulp therapy (VPT) outcomes is important to improve clinical decision-making.
Objectives: To investigate whether patient age is a predictor of VPT success/survival, using a research question based on the PICOTS acronym: (P) participants presenting mature permanent teeth undergoing VPT; (I) participants age; (C) gender, systemic condition, preoperative symptoms/diagnosis, caries extent/location, restoration extent/type, bleeding time; (O) clinical and radiographic success/survival; (T) data collected immediately before and during the clinical procedure and follow-up performed at least 1 year later; (S) clinical trials and observational studies developed in dental schools and services.
Methods: PubMed, EMBASE, Lilacs and Web of Science databases were searched for studies published from inception to 29 June 2024. Two independent reviewers selected and extracted data; senior reviewers resolved disagreements. Study characteristics were tabulated, and a meta-analysis was conducted, using RevMan software. The QUIPS tool assesses the risk of bias, whilst the GRADE criteria assess the certainty of evidence.
Results: Thirty-four studies were included in the qualitative synthesis, and 23 in the meta-analysis. Bivariate associations showed higher direct pulp capping (DPC) success rates for participants younger than 40 years [OR = 4.85, 95% CI (2.27-10.39)]. The association between age and full pulpotomy (FP) + partial pulpotomy (PP) survival was not significant in multivariate meta-analysis [HR = 1.02, 95% CI (0.98-1.05)]. Bias related to outcome measurements, confounding/statistical analysis and reporting were the main concerns of the studies' quality, and the overall risk of bias was moderate to high. The certainty of the evidence was very low for the analysis of the DPC 25-year-old cut point, high for the multivariate analysis and moderate for the other analysis.
Discussion: Age did not influence PP and FP outcomes. In contrast, it is associated with DPC success, probably influenced by difficulties during direct inspection of pulp tissue. Further studies with multivariate-adjusted analyses are required to improve the certainty of the evidence.
Conclusions: Patient age is not associated with the outcomes of PP and FP in permanent teeth but should be considered a risk predictor for patients over 40 years.
Registration: CRD42021273826 (PROSPERO).
{"title":"Association between patient age and vital pulp therapy outcomes: A systematic review and meta-analysis of prognostic studies.","authors":"Carla Moretto, Patrícia Maria Poli Kopper, Eliseu Aldrighi Münchow, Roberta Kochenborger Scarparo","doi":"10.1111/iej.14223","DOIUrl":"https://doi.org/10.1111/iej.14223","url":null,"abstract":"<p><strong>Background: </strong>Summarizing the association between patient age and vital pulp therapy (VPT) outcomes is important to improve clinical decision-making.</p><p><strong>Objectives: </strong>To investigate whether patient age is a predictor of VPT success/survival, using a research question based on the PICOTS acronym: (P) participants presenting mature permanent teeth undergoing VPT; (I) participants age; (C) gender, systemic condition, preoperative symptoms/diagnosis, caries extent/location, restoration extent/type, bleeding time; (O) clinical and radiographic success/survival; (T) data collected immediately before and during the clinical procedure and follow-up performed at least 1 year later; (S) clinical trials and observational studies developed in dental schools and services.</p><p><strong>Methods: </strong>PubMed, EMBASE, Lilacs and Web of Science databases were searched for studies published from inception to 29 June 2024. Two independent reviewers selected and extracted data; senior reviewers resolved disagreements. Study characteristics were tabulated, and a meta-analysis was conducted, using RevMan software. The QUIPS tool assesses the risk of bias, whilst the GRADE criteria assess the certainty of evidence.</p><p><strong>Results: </strong>Thirty-four studies were included in the qualitative synthesis, and 23 in the meta-analysis. Bivariate associations showed higher direct pulp capping (DPC) success rates for participants younger than 40 years [OR = 4.85, 95% CI (2.27-10.39)]. The association between age and full pulpotomy (FP) + partial pulpotomy (PP) survival was not significant in multivariate meta-analysis [HR = 1.02, 95% CI (0.98-1.05)]. Bias related to outcome measurements, confounding/statistical analysis and reporting were the main concerns of the studies' quality, and the overall risk of bias was moderate to high. The certainty of the evidence was very low for the analysis of the DPC 25-year-old cut point, high for the multivariate analysis and moderate for the other analysis.</p><p><strong>Discussion: </strong>Age did not influence PP and FP outcomes. In contrast, it is associated with DPC success, probably influenced by difficulties during direct inspection of pulp tissue. Further studies with multivariate-adjusted analyses are required to improve the certainty of the evidence.</p><p><strong>Conclusions: </strong>Patient age is not associated with the outcomes of PP and FP in permanent teeth but should be considered a risk predictor for patients over 40 years.</p><p><strong>Registration: </strong>CRD42021273826 (PROSPERO).</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Nosrat, Yuke Tian, Prashant Verma, Nardin Mossad, Di Wu, Ashraf F Fouad
Aim: The COVID-19 pandemic affected practice in endodontic offices. Same-day endodontic emergencies are cases with moderate or severe self-reported pain who request an unscheduled visit on the day they contact the office. The aims of this observational study were to: (A) analyse the rate of same-day endodontic emergencies in two endodontists' private offices, with respect to their demographic, aetiologic, diagnostic and procedural data; and (B) investigate the changes in characteristics of same-day emergencies between March 16 and May 31 annually over five years: 2019-2023.
Methodology: Records of 5795 patients were reviewed and 892 same-day emergencies were identified. Overall and year-to-year comparisons of proportions of same-day emergencies, as well as demographic, aetiologic, diagnostic and procedural data were performed using chi-square test of independence followed by adjustments for multiple testing using the Benjamini-Hochberg method.
Results: The rate of same-day endodontic emergencies significantly increased during the initial outbreak of COVID-19 in 2020 and remained high in 2021 (p < .05; Q < .05). The rate of same-day emergencies in 2022 subsided to levels comparable to 2019 (p > .05). Year-to-year comparisons of aetiologic factors (caries, restorative, persistent infection and cracks) showed a significant increase only in the rate of cracks in 2020, 2021and 2022 compared with 2019 (p < .05), but this increase did not reach the significance level after adjusting for multiple comparisons throughout the 5 years (Q > .05).
Conclusions: The COVID-19 pandemic was associated with a significant increase in the rate of same-day endodontic emergencies for 2 years. The spike in endodontic emergencies associated with the COVID-19 pandemic lasted well beyond the initial period of the outbreak. Further national and international studies are recommended to better understand the long-term impacts of pandemics of respiratory diseases on the public's oral health.
{"title":"Same-day emergencies in endodontic specialists' practice: Before, during and after the COVID-19 pandemic.","authors":"Ali Nosrat, Yuke Tian, Prashant Verma, Nardin Mossad, Di Wu, Ashraf F Fouad","doi":"10.1111/iej.14228","DOIUrl":"https://doi.org/10.1111/iej.14228","url":null,"abstract":"<p><strong>Aim: </strong>The COVID-19 pandemic affected practice in endodontic offices. Same-day endodontic emergencies are cases with moderate or severe self-reported pain who request an unscheduled visit on the day they contact the office. The aims of this observational study were to: (A) analyse the rate of same-day endodontic emergencies in two endodontists' private offices, with respect to their demographic, aetiologic, diagnostic and procedural data; and (B) investigate the changes in characteristics of same-day emergencies between March 16 and May 31 annually over five years: 2019-2023.</p><p><strong>Methodology: </strong>Records of 5795 patients were reviewed and 892 same-day emergencies were identified. Overall and year-to-year comparisons of proportions of same-day emergencies, as well as demographic, aetiologic, diagnostic and procedural data were performed using chi-square test of independence followed by adjustments for multiple testing using the Benjamini-Hochberg method.</p><p><strong>Results: </strong>The rate of same-day endodontic emergencies significantly increased during the initial outbreak of COVID-19 in 2020 and remained high in 2021 (p < .05; Q < .05). The rate of same-day emergencies in 2022 subsided to levels comparable to 2019 (p > .05). Year-to-year comparisons of aetiologic factors (caries, restorative, persistent infection and cracks) showed a significant increase only in the rate of cracks in 2020, 2021and 2022 compared with 2019 (p < .05), but this increase did not reach the significance level after adjusting for multiple comparisons throughout the 5 years (Q > .05).</p><p><strong>Conclusions: </strong>The COVID-19 pandemic was associated with a significant increase in the rate of same-day endodontic emergencies for 2 years. The spike in endodontic emergencies associated with the COVID-19 pandemic lasted well beyond the initial period of the outbreak. Further national and international studies are recommended to better understand the long-term impacts of pandemics of respiratory diseases on the public's oral health.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}