To evaluate the association between genetic polymorphisms in SOD2 and SOD3 and oral health-related quality of life (OHRQoL).  Material and methods: The cohort study included 109 participants, all of whom underwent root canal treatment on a single-rooted maxillary or mandibular tooth with asymptomatic periapical periodontitis. The OHRQoL was assessed using the Oral Health Impact Profile-14 at three intervals: prior to root canal treatment (T0), 7 (T7), and 30 (T30) days post-treatment. Genomic DNA was extracted from buccal cells for genotyping of polymorphisms in SOD2 (rs5746136, rs4880, and rs10370) and SOD3 (rs2855262 and rs13306703) using real-time PCR. Both Univariate and Multivariate Poisson Regression analyses were conducted, with p < 0.05 indicating statistical significance.  Results: The rs2855262 polymorphism in the SOD3 gene showed a significant difference in the functional limitation domain in both codominant (p = 0.037) and recessive (p = 0.040) models. The rs13306703 polymorphism in SOD3 demonstrated a significant difference in physical pain [in codominant (p = 0.001) and recessive (p < 0.001) models], psychological discomfort [in codominant (p = 0.002) and recessive (p = 0.002) models], handicap [in codominant (p = 0.011) and dominant (p = 0.015) models], and total score [in codominant (p = 0.011) and recessive (p = 0.007) models]. In the Multivariate Poisson Regression analysis, SOD2 (rs5746136) was associated with the psychological disability domain [in codominant (p = 0.049) and recessive (p = 0.040) models] and SOD3 (rs13306703), in the handicap domain [in codominant (p = 0.028) and dominant (p = 0.037) models].  Conclusions: Genetic polymorphisms in SOD2 and SOD3 genes can influence the OHRQoL response in patients with asymptomatic periapical periodontitis.

In this editorial, we critically evaluate the recent article by Niu et al, which explores the potential of phospholipase D2 (PLD2) as a biomarker for stratifying disease severity in acute pancreatitis (AP). AP is a clinically heterogeneous inflammatory condition that requires reliable biomarkers for early and accurate classification of disease severity. PLD2, an essential regulator of neutrophil migration and inflammatory responses, has emerged as a promising candidate. Although current biomarkers such as C-reactive protein and procalcitonin provide general indications of inflammation, they lack specificity regarding the molecular mechanisms underlying AP progression. Recent studies, including the research conducted by Niu et al, suggest an inverse correlation between PLD2 expression and AP severity, offering both diagnostic insights and mechanistic understanding. This editorial critically evaluates the role of PLD2 as a biomarker in the broader context of AP research. Evidence indicates that decreased levels of PLD2 are associated with increased neutrophil chemotaxis and cytokine release, contributing to pancreatic and systemic inflammation. However, several challenges remain, including the need for large-scale validation and functional studies to establish causation, and standardization of measurement protocols. Additionally, further investigation into the temporal dynamics of PLD2 expression and its variability across diverse populations is warranted. Looking ahead, PLD2 holds the potential to revolutionize AP management by integrating molecular diagnostics with precision medicine. The utilization of large-scale multi-omics approaches and advancements in diagnostic platforms could position PLD2 as a fundamental biomarker for early diagnosis, prognosis, and potentially therapeutic targeting. While promising, it is crucial to conduct critical evaluations and rigorous validations of PLD2's role to ensure its efficacy in improving patient outcomes.

To evaluate and correlate the expression of REDOX enzymes and NET markers during the development of periapical lesions (PLs) in mice.

PLs were experimentally induced by pulpal exposure of first molars. In all, 42 mice were involved in a negative control and five periods (after 2, 5, 7, 21 and 42 days) (n = 7 in each period). Microscopic analysis of the specimens was carried out, considering inflammatory response and the PL area (mm2). In addition, qRT-PCR (genes) and immunohistochemistry assay (proteins) were performed for REDOX enzymes (NOS2, SOD1, CAT, and GSR) and NET markers (MPO, H3CIT, and ELANE). The significance level was set at 5%.

Pulpal exposure led to the formation of PLs, especially after 21 and 42 days, when there was significantly increased bone resorption compared to previous periods (P < 0.001). There was an increased expression of all REDOX enzymes, as well as MPO and H3CIT markers after pulpal exposure in at least one time point in relation to the negative control, especially after 5 days (P = 0.002 or less). NOS2, SOD1, ELANE and H3CIT were significantly correlated with the PL area (P < 0.05). In addition, there was also a correlation between REDOX enzymes and NET markers (P < 0.05), such as all REDOX enzymes with H3CIT, CAT and GSR with MPO, and CAT and GSR with ELANE (P < 0.05).

Pulpal exposure modified the expression of REDOX enzymes and NET markers throughout the development of PLs, as well as some of these enzymes and markers were correlated, which may suggest the association of different molecular pathways.

The association between REDOX activity and NETs, including their molecular signaling, may modify the development of PLs after pulpal exposure and should be investigated as a possible therapeutic target in periapical bone repair.

Background/Objectives: This study aims to compare the effects of conventional surgical techniques and laser-assisted methods on salivary oxidative stress biomarkers following third molar extraction, in order to evaluate the potential benefits of laser surgery in reducing oxidative stress and promoting faster recovery. Methods: A total of 154 patients, aged 16-30, undergoing third molar extractions were included in the study. Patients were divided into two groups: conventional surgery (n = 75) and laser-assisted surgery (n = 79). Saliva samples were collected at baseline, and 24, 48, 72, and 168 h postoperatively. The levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured as indicators of oxidative stress. Results: Initial biomarker levels were similar across all participants. Postoperative oxidative stress increased in both groups, with significantly higher levels in the conventional surgery group at 48 and 72 h. Salivary biomarkers of oxidative stress were significantly lower in the laser group at 48 and 72 h post-surgery (p < 0.05), indicating a faster recovery. By 168 h, biomarker levels in the laser group had nearly returned to baseline, whereas levels in the conventional group remained slightly elevated. Conclusions: Laser-assisted surgery significantly reduces oxidative stress and promotes faster recovery when compared with conventional methods, as evidenced by the more rapid normalization of salivary biomarkers. These findings suggest that laser techniques may offer superior clinical outcomes in third molar extractions.

Oxidative stress (OS) is a ubiquitous process for protecting against microorganisms' challenges. This review maps the most used methods for obtaining samples and analysing reactive oxygen species levels in apical periodontitis, following the PRISMA Extension for Scoping Reviews and is registered in Open Science Framework ([https://doi.org/10.17605/OSF.IO/D5U76]). A systematic search was conducted in electronic databases MEDLINE (PubMed), Embase, Scopus, Web of Science, LILACS, SciElo, OATD and DANS up to 17 July 2023. A total of 18 studies were included, with periapical tissue being the most common sample. Twenty-eight different oxidative stress markers were identified, with inducible nitric oxide synthase being the most prevalent. The use of diverse biomarkers for oxidative stress assessment lacks specificity in identifying particular OS species for evaluating apical periodontitis and potential systemic effects. Studies are necessary to compare results obtained from less invasive methods (such as saliva and crevicular fluid) with those from periapical lesion samples.

This study aimed to evaluate the effects of excessive and episodic consumption of ethanol (EtOH, a high-intensity drinking manner) on induced apical periodontitis in rats. Thirty-two animals were divided into the following four groups: control, EtOH, apical periodontitis, and EtOH + apical periodontitis. Ethanol exposure (3 g/kg 20 % w/v EtOH) was performed by orogastric gavage for 3 consecutive days, followed by 4 days of withdrawal for 4 weeks. Lesions were induced by exposing the dental pulp of the lower first molar and by the absence of any treatment/curative for 28 days. Finally, the animals were euthanized, and mandibles were collected. The mandible was divided medially, with one hemimandible being used for micro-computed tomography analysis of the volume of the periapical lesion and bone quality parameters, such as bone volume and trabecular bone assessments; the other hemimandible was used for histological analysis, with a descriptive histopathological analysis of the tissue and the pattern of bone loss presented, as well as an assessment of the collagen content present. The data were subjected to statistical analysis (one-way analysis of variance with Tukey's post-hoc test). Our results showed that the EtOH + apical periodontitis group had a larger volume of periapical lesions than animals that were not exposed to ethanol. Additionally, bone quality parameters showed a reduction in bone volume and thickening of the trabeculae, associated with increased tissue destruction and reduced collagen content in the remnant region of the alveolar bone. These results suggest that exposure to EtOH in a pattern of excessive alcohol consumption is an aggravating factor in apical periodontitis and, consequently, in its progression, the quality and quantity of the alveolar bone remaining in the region of the periapical lesion are the modulating aspects.

This study aimed to investigate the impact of alcohol (A), secondhand cigarette smoking (ShS), and their combined effect on liver antioxidant activity and hepatic damage in rats with induced apical periodontitis (AP). Thirty-five female Wistar rats were randomly allocated into five groups (n = 7): (1) control (rats without ShS, alcoholic diet, or AP), (2) control-AP (induced AP only), (3) ShS-AP (ShS exposure and induced AP), (4) A-AP (alcoholic diet and induced AP), and (5) A+ShS-AP (alcoholic diet, ShS exposure, and induced AP). Alcohol was administered through semi-voluntary intake, while ShS exposure involved the daily inhalation of cigarette smoke. The experimental period lasted 8 weeks, with AP induction occurring in the 4th week following molar pulp exposure. Liver samples were collected post-euthanasia for histomorphometric and antioxidant marker analyses. All AP-induced groups exhibited increased liver sinusoidal dilation compared to the control group (p < 0.05). AP significantly reduced total antioxidant capacity (FRAP) across all groups (p < 0.05). In AP-induced groups, FRAP levels were further decreased in ShS-AP and A+ShS-AP compared to control-AP (p < 0.05). AP also led to a decrease in the glutathione defense system (p < 0.05). Rats with alcohol exposure (A-AP and A+ShS-AP) showed reduced glutathione peroxidase activity (p < 0.05). Glutathione reductase activity was comparable in the control and control-AP groups (p > 0.05), but significantly decreased in the alcohol and ShS-exposed groups (p < 0.05). Apical periodontitis can relate to morphological changes in the liver's sinusoidal spaces and impairment of liver's antioxidant capacity of rats, particularly when combined with chronic alcohol consumption and exposure to cigarette smoke.

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.

The aim of this systematic review and meta-analysis was to furnish evidence-based recommendations for the utilization of bioceramic-based and resin-based sealers in clinical endodontics, with a focus on reducing postoperative discomfort.

The investigation's methodology was registered on the International Prospective Database of Systematic Reviews (PROSPERO: CRD42022355506) and executed using the 2020 PRISMA protocol. Articles were selected utilizing the PICO technique and applying specific inclusion and exclusion criteria. Articles published between January 2000 and August 2022, PubMed, MEDLINE, and DOAJ were utilized as primary data sources. After the identification of studies, two autonomous reviewers evaluated the titles and abstracts, and data from qualifying studies were extracted.

Nine published studies were included in this analysis. The findings indicate that there were no significant differences in the Visual Analog Scale (VAS) scores between resin-based and bioceramic root canal sealers at intervals of 6 hours, 12 hours, 24 hours, and 48 hours after treatment.

The findings of this systematic review and meta-analysis suggest that after the utilization of bioceramic sealers during root canal therapy, the pain and discomfort levels were not significantly different from those experienced pain after the use of resin-based sealers.

To elucidate whether mitochondrial biogenesis disorder and damage from oxidative stress promote refractory apical periodontitis (RAP) in rat and human.

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.

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).

Mitochondrial biogenesis disorder and damage from oxidative stress contribute to the development of RAP.

Apical periodontitis (AP) has been associated with systemic inflammatory biomarkers that have also been associated with COVID-19 severity. This study was designed to test the hypothesis that the presence of apical periodontitis could be associated with increased risk of COVID-19 complications.

A case control study (N = 949) was performed using the medical and dental records of patients diagnosed with COVID-19 in the State of Qatar between March 2020 and February 2021. Cases comprised COVID-19 patients (n = 63) who experienced complications (death, intensive care unit admissions, mechanical ventilation), and controls were COVID-19 patients (n = 886) who recovered without such complications. The presence of periapical apical periodontitis was assessed on the radiographic records taken prior to COVID-19 infection. Associations between apical periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood biomarkers were assessed in both groups and compared using the Kruskal-Wallis test.

COVID-19 complications were found to be associated with the presence of apical periodontitis (adjusted odds ratio = 2.72; 95% CI, 1.30-5.68; P = .008). Blood analyses revealed that COVID-19 patients with apical periodontitis had higher levels of white blood cells and haemoglobin A1c than the patients without apical periodontitis.

The presence of apical periodontitis could be associated with increased risk of COVID-19 complications.

This study was performed to determine the therapeutic effects of diosgenin (DG) which is a steroidal saponin, administered at different doses on alveolar bone loss (ABL) in rats with experimental periodontitis using immunohistochemical and cone-beam computed tomography (CBCT).

Thirty-two male Wistar rats divided into four equal groups: control (non-ligated), periodontitis (P), DG-48, and DG-96. Sutures were placed at the gingival margin of the lower first molars to induce experimental periodontitis. Then, 48 and 96 mg/kg of DG was administered to the study groups by oral gavage for 29 days. At day 30, the animals were sacrificed and ABL was determined via CBCT. The expression patterns of osteocalcin (OCN), alkaline phosphatase (ALP), type I collagen (Col-1), B cell lymphoma 2 (Bcl 2), Bcl 2-associated X protein (Bax), bone morphogenetic protein 2 (BMP-2), and receptor activator of NF κB ligand (RANKL) were examined immunohistochemically.

Histopathologic examination showed all features of the advanced lesion in the P group. DG use decreased all these pathologic changes. It was observed that periodontitis pathology decreased as the dose increased. DG treatment increased the ALP, OCN, Bcl 2, Col-1, and BMP-2 levels in a dose-dependent manner, compared with the P group (p < 0.05). DG decreased the expression of RANKL and Bax in a dose-dependent manner (p < 0.05). ABL was significantly lower in the DG-48 and DG-96 groups than in the P group (p < 0.05).

Collectively, our findings suggest that DG administration protects rats from periodontal tissue damage with a dose-dependent manner, provides an increase in markers of bone formation, decreases in Bax/Bcl-2 ratio and osteoclast activation.

Boric acid (BA) has been found to have therapeutic effects on periodontal disease through beneficially affecting antibacterial, anti-viral, and anti-inflammatory actions.

This study was conducted to determine the effect of BA on cell viability and on mRNA expressions of proinflammatory and anti-inflammatory cytokines and on oxidative stress enzymes induced by IL-1β (1 ng/mL) in Human Gingival Fibroblasts (HGF) cultured for 24 and 72 h in DMEM media. The BA concentrations added to the media were 0.09 %, 0.18 %, 0.37 %, and 0.75 %.

All of the BA concentrations increased the viability of cell cultured in DMEM media only, indicating that these concentrations were not toxic and actually beneficial to cell viability. The addition of 1 ng/m: of IL-1β decreased cell viability that was overcome by all concentrations of BA at both 24 and 72 h. The IL-1β addition to the media increased the expressions of the proinflammatory cytokines IL-1β, IL-6, IL-8, and IL-17; the anti-inflammatory cytokine IL-10; and the oxidative stress enzymes superoxide dismutase (SOD0 and glutathione peroxidase (GPX). The IL-1β induced increase mRNA expression of IL-1β was decreased at 24 h by the 0.37 % and 0.75 % BA additions to the media and decreased in a dose-dependent manner by all concentrations of BA at 72 h. The IL-1β induced increase in the expression of IL-6 was decreased in dose-dependent manner at 72 h by BA. All BA concentrations decreased the IL-1β induced expression of IL-8 at both 24 and 72 h. The induced increase in IL-17 by IL-1β was not significantly affected by the BA additions. The increase in the anti-inflammatory cytokine IL10 induced by IL-1β was increased further by all BA additions in dose dependent manner at both 24 and 72 h. The mRNA expressions of SOD and GPX increased by IL-1β were further increased by the 0.37 % and 0.75 % BA concentrations at 72 h.

These findings indicate that BA can significantly modulate the cytokines that are involved in inflammatory stress and reactive oxygen species action and thus could be an effective therapeutic agent in the treatment of periodontal disease.

This systematic review aimed to verify whether there is evidence of an association between apical periodontitis and the presence of systemic biomarkers. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA. For this, the acronym PECO was used; population (P) of adult humans exposed (E) to the presence of apical periodontitis, compared (C) to adult humans without apical periodontitis, and the outcome (O) of the presence of biomarkers was observed. The articles were searched in PubMed, Scopus, Web of Science, LILACS, Cochrane Library, OpenGray, and Google Scholar grey databases. Subsequently, studies were excluded based on title, abstract, and full article reading, following the eligibility criteria. The methodological quality of the selected studies was evaluated using the Newcastle-Ottawa qualifier. After exclusion, 656 studies were identified, resulting in 17 final articles that were divided into case-control, cross-sectional, and cohort studies. Eight studies were considered to have a low risk of bias, one had a medium risk of bias, and eight had a high risk of bias. In addition, 12 articles evaluated biomarkers in blood plasma, four evaluated them in saliva, and only one evaluated them in gingival crevicular fluid. The results of these studies indicated an association between apical periodontitis and the systemic presence of biomarkers. These markers are mainly related to inflammation, such as interleukins IL-1, IL-2, and IL-6, oxidative markers, such as nitric oxide and superoxide anions, and immunoglobulins IgG and IgM.

https://www.crd.york.ac.uk/prospero/, identifier (CRD42023493959).

Periodontitis is a prevalent inflammatory periodontal disease that has an impact on the overall quality of life. Although several studies have indicated an association between individual vitamin intake and periodontitis risk, the associations of the multivitamins with periodontitis risk remain unclear.

This study aimed to explore the joint effect of multivitamins (including vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K) on periodontitis.

For this cross-sectional study, data were collected from participants aged ≥ 30 years in the National Health and Nutrition Examination Surveys 2009-2014 (n = 9,820). We employed weighted multivariate logistic regression models to evaluate the single association between individual vitamin intakes and periodontitis, and Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp) models to assess the joint effect of nine vitamins on periodontitis.

The overall prevalence of periodontitis was approximately 35.97%. After adjustment of covariates, vitamin B6 [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.72-0.94] and vitamin E (OR = 0.79, 95%CI: 0.69-0.92) were negatively related to the likelihood of developing periodontitis, respectively. The result of three models indicated that, mixture of vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K had a significant negative combined effect on the risk of periodontitis. In the BKMR model, when all remaining vitamins were at their median levels, the periodontitis risk decreased with increased concentration levels of vitamin E and vitamin B2. WQS analysis indicated the highest weighted chemical was vitamin E, followed by vitamin B12 and vitamin D. In the qgcomp model, vitamin E received the highest negative weights for the periodontitis risk, followed by vitamin B2 and vitamin D, respectively.

Both dietary vitamin B6 and vitamin E were associated with decreased odds of periodontitis. Additionally, the mixture-exposed analyses consistently showed the negative correlations between nine dietary vitamins mixtures and periodontitis.

Periodontitis, the sixth most prevalent epidemic disease globally, profoundly impacts oral aesthetics and masticatory functionality. Hypoxia-inducible factor-1α (HIF-1α), an oxygen-dependent transcriptional activator, has emerged as a pivotal regulator in periodontal tissue and alveolar bone metabolism, exerts critical functions in angiogenesis, erythropoiesis, energy metabolism, and cell fate determination. Numerous essential phenotypes regulated by HIF are intricately associated with bone metabolism in periodontal tissues. Extensive investigations have highlighted the central role of HIF and its downstream target genes and pathways in the coupling of angiogenesis and osteogenesis. Within this concise perspective, we comprehensively review the cellular phenotypic alterations and microenvironmental dynamics linking HIF to periodontitis. We analyze current research on the HIF pathway, elucidating its impact on bone repair and regeneration, while unraveling the involved cellular and molecular mechanisms. Furthermore, we briefly discuss the potential application of targeted interventions aimed at HIF in the field of bone tissue regeneration engineering. This review expands our biological understanding of the intricate relationship between the HIF gene and bone angiogenesis in periodontitis and offers valuable insights for the development of innovative therapies to expedite bone repair and regeneration.

This study aimed to investigate if apical periodontitis in different periods changes systemic levels of the antioxidant and pro-oxidant parameters in Wistar rats. Twenty-four rats were randomly allocated into healthy animals, apical periodontitis at 14 days (AP14) and apical periodontitis at 28 days (AP28). The first mandibular molars were accessed in the AP groups, and the pulp chamber was exposed to the oral environment, inducing the apical lesion. After 14 and 28 days, the animals were anesthetized, euthanized, and hemimandibles were collected for micro-computed tomography (micro-CT) analysis to measure lesion volume, bone volume (BV), percent of bone to total tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular space (Tb.Sp). A histological examination of the remaining bone was also performed. Finally, blood samples were collected for oxidative biochemistry analysis, investigating glutathione (GSH), Trolox equivalent antioxidant capacity (TEAC), and lipid peroxidation (TBARS). The lesion volume was greater at 28 than at 14 days, as shown by micro-CT. AP14 and AP28 had decreased BV and Tb.Th, but only AP28 showed a reduction in BV/TV. Tb.N and Tb. Sp were increased in apical periodontitis at 28 days. In the histopathological analysis, AP14 had focal regions of moderate mononuclear inflammatory infiltrate, and AP28 had an intense inflammatory infiltrate with bacterial colonies. In the biochemical evaluation, GSH, TEAC, and TBARS were increased after 14 days. However, GSH returned to control levels, TEAC was similar to AP14, and TBARS increased significantly after 28 days. Therefore, the oxidative biochemistry response was modulated according to the progression of periapical damage. After 14 days, the organism could still react to the injury. However, at 28 days, the antioxidant response decreased, associated with an increase in TBARS.

Apical periodontitis is an inflammatory response caused by pulp infection. It induces bone resorption in the apical and periapical regions of the tooth. The most conservative approach to treat this condition is nonsurgical endodontic treatment. However, clinical failure has been reported with this approach; thus, alternative procedures are required. This review highlights recent literature regarding advanced approaches for the treatment of apical periodontitis. Various therapies, including biological medications, antioxidants, specialized pro-resolving lipid mediators, and stem cell therapy, have been tested to increase the success rate of treatment for apical periodontitis. Some of these approaches remain in the in vivo phase of research, while others have just entered the translational research phase to validate clinical application. However, a detailed understanding of the molecular mechanisms that occur during development of the immunoinflammatory reaction in apical periodontitis remains unclear. The aim of this review was to summarize advanced approaches for the treatment of apical periodontitis. Further research can confirm the potential of these alternative nonsurgical endodontic treatment approaches.

The presence of Gram-negative anaerobic bacteria, in particular, Porphyromonas gingivalis (P. gingivalis) in periapical granulomas predicts the generation of citrullinated proteins in the lesion. Citrullination of proteins may lead to the formation of anti-citrullinated autoantibodies (ACPA-s) initiating the formation of an autoimmune loop which may contribute to the perpetuation of inflammatory reactions and tissue damage in chronic apical periodontitis. The objective of this study was to demonstrate the formation of citrullinated proteins in chronic apical periodontitis and whether they can act as autoantigens.

Twenty-five periapical granulomas (n = 25) were investigated in the study. Healthy periodontal tissue samples served as normal control tissue (n = 6). The peptidyl-citrulline level was determined with the dot blot method. ACPA levels were analysed using anti-citrullinated cyclic peptide (anti-CCP) EDIA kit. Differences between periapical granuloma and control samples were assessed using Mann-Whitney U tests. p Values <.05 were considered as statistically significant.

Protein concentrations, peptidyl-citrulline levels and anti-CCP ratios were compared between periapical granuloma and healthy control groups. Multiple linear regression analysis revealed significant (p = .042) hypercitrullination in periapical granuloma samples. Moreover, there was a significant difference in the ACPA ratios between periapical granuloma (2.03 ± 0.30) and healthy control (0.63 ± 0.17) groups (p = .01). Seventeen of 25 periapical granuloma samples (17/25; 68%), whereas one out of six control samples (1/6; 17%) were shown to be positive for the presence of ACPA.

This is the first study detecting the presence of citrullinated peptides and APCA in periapical granuloma, suggesting the contribution of autoimmune reactions in the pathogenesis and perpetuation of chronic apical periodontitis.

The aim of this cone-beam computed tomography (CBCT)-based study was to evaluate the outcome of nonsurgical root canal treatment (RCT) performed for the management of large cyst-like periapical lesions (LCPL) and to identify the predictive factors affecting healing.

Fifty-four subjects (77 permanent maxillary anterior teeth) with LCPL (>10 mm) of endodontic origin were included. A single operator performed standardized multi-visit RCT. Patients were clinically and radiographically examined at 6, 12 months, and a CBCT scan was taken at 24 months. Two independent blinded evaluators measured the pre- and postoperative volume of periapical lesions on CBCT scans using ITK snap software (version 3.8.0-beta-20181028-win64). The outcome was assessed as a percentage change in lesion volume and dichotomized as success (resolved/reduced) or failure (unchanged/enlarged). Ten preoperative (gender; age; intraoral draining sinus, soft tissue swelling, tooth discoloration, pulp canal obliteration, open apex, root resorption, cortical bone defect and lesion volume) and four intraoperative (apical extent and density of root filling; number of treatment visits and type of root filling) predictive factors were observed. Bivariate and stepwise multivariable linear regression analysis was performed to identify independent predictors affecting treatment outcomes. The significance level was set at 5%.

A recall rate of 88% was achieved. The success rate of RCT was 82.2% (8.9% resolved, 73.3% reduced). Median lesion volume reduction was 75% (IQR 61%-93%). No pre- or intra-operative factors were related to treatment failure. However, presence of preoperative cortical bone defect (palatal versus no cortical defect, β = -51.5; 95% CI: -86.9 to -16, p = .006) and apical extent of obturation (long versus flush, β = -27.2; 95% CI: -53.8 to -0.6, p = .04) were negatively associated with reduction in lesion volume (%).

Large cyst-like periapical lesions may be successfully managed with RCT. Preoperative cortical bone defect and apical extent of obturation may negatively influence osseous healing.

The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP) as well as periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly due to the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered post-treatment healing to exacerbation of chronic periradicular immune response, that compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment, however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. Interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of non-conventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect, without any host tissue damages. Herein, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobials intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics.