Background
Recent findings about the differential gene expression signature of periodontal lesions have raised the hypothesis of distinctive biological phenotypes expressed by generalized chronic ...periodontitis (GCP) and generalized aggressive periodontitis (GAgP) patients. Therefore, this cross‐sectional investigation was planned, primarily, to determine the ability of nuclear magnetic resonance (NMR) spectroscopic analysis of unstimulated whole saliva to discriminate GCP and GAgP disease‐specific metabolomic fingerprint and, secondarily, to assess potential metabolites discriminating periodontitis patients from periodontally healthy individuals (HI).
Methods
NMR‐metabolomics spectra were acquired from salivary samples of patients with a clinical diagnosis of GCP (n = 33) or GAgP (n = 28) and from HI (n = 39). The clustering of HI, GCP, and GAgP patients was achieved by using a combination of the Principal Component Analysis and Canonical Correlation Analysis on the NMR profiles.
Results
These analyses revealed a significant predictive accuracy discriminating HI from GCP, and discriminating HI from GAgP patients (both 81%). In contrast, the GAgP and GCP saliva samples seem to belong to the same metabolic space (60% predictive accuracy). Significantly lower levels (P < 0.05) of pyruvate, N‐acetyl groups and lactate and higher levels (P < 0.05) of proline, phenylalanine, and tyrosine were found in GCP and GAgP patients compared with HI.
Conclusions
Within the limitations of this study, CGP and GAgP metabolomic profiles were not unequivocally discriminated through a NMR‐based spectroscopic analysis of saliva.
Introduction
Early diagnosis of periodontitis by means of a rapid, accurate and non-invasive method is highly desirable to reduce the individual and epidemiological burden of this largely prevalent ...disease.
Objectives
The aims of the present systematic review were to examine potential salivary metabolic biomarkers and pathways associated to periodontitis, and to assess the accuracy of salivary untargeted metabolomics for the diagnosis of periodontal diseases.
Methods
Relevant studies identified from MEDLINE (PubMed), Embase and Scopus databases were systematically examined for analytical protocols, metabolic biomarkers and results from the multivariate analysis (MVA). Pathway analysis was performed using the MetaboAnalyst online software and quality assessment by means of a modified version of the QUADOMICS tool.
Results
Twelve studies met the inclusion criteria, with sample sizes ranging from 19 to 130 subjects. Compared to periodontally healthy individuals, valine, phenylalanine, isoleucine, tyrosine and butyrate were found upregulated in periodontitis patients in most studies; while lactate, pyruvate and
N
-acetyl groups were the most significantly expressed in healthy individuals. Metabolic pathways that resulted dysregulated are mainly implicated in inflammation, oxidative stress, immune activation and bacterial energetic metabolism. The findings from MVA revealed that periodontitis is characterized by a specific metabolic signature in saliva, with coefficients of determination ranging from 0.52 to 0.99.
Conclusions
This systematic review summarizes candidate metabolic biomarkers and pathways related to periodontitis, which may provide opportunities for the validation of diagnostic or predictive models and the discovery of novel targets for monitoring and treating such a disease (PROSPERO CRD42020188482).
The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the ...distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.
Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral microbiome and immune-inflammatory ...pathways related to periodontitis may impact the pathophysiology of the gastrointestinal tract and its accessory organs through the so-called “gum–gut axis”. In addition to the hematogenous spread of periodontal pathogens and inflammatory cytokines, recent research suggests that oral pathobionts may translocate to the gastrointestinal tract through saliva, possibly impacting neoplastic processes in the gastrointestinal, liver, and pancreatic systems. The exact mechanisms by which oral pathogens contribute to the development of digestive tract cancers are not fully understood but may involve dysbiosis of the gut microbiome, chronic inflammation, and immune modulation/evasion, mainly through the interaction with T-helper and monocytic cells. Specifically, keystone periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, are known to interact with the molecular hallmarks of gastrointestinal cancers, inducing genomic mutations, and promote a permissive immune microenvironment by impairing anti-tumor checkpoints. The evidence gathered here suggests a possible role of periodontitis and oral dysbiosis in the carcinogenesis of the enteral tract. The “gum–gut axis” may therefore represent a promising target for the development of strategies for the prevention and treatment of gastrointestinal cancers.
The aim of this randomized split-mouth study was to assess the influence of primary flap position on the amount of coronal soft tissue regrowth and keratinized tissue (KT) 6 months after osseous ...resective surgery with fiber retention technique (FibReORS).
Two contralateral posterior sextants in 16 patients were treated with FibReORS and randomly assigned to flap positioning either 2 mm below the bone crest (apical group) or at the level of bone crest (crestal group). Clinical parameters were recorded at 1, 3 and 6 months and patient-related outcomes during the first two post-operative weeks.
Healing period was uneventful. Patient's discomfort was similar in both groups. The overall soft tissue rebound was higher in the apical than in the crestal group (2.0 ± 1.3 mm versus 1.3 ± 0.7 mm), but the difference was statistically significant only interproximally (2.2 ± 1.3 mm versus 1.6 ± 0.8 mm). Multilevel analyses showed higher soft tissue rebound in sites with normal compared to thin phenotype (1.5 mm, p < 0.0001) and treated with flap positioned 2 mm apically to the bone crest (0.7 mm, p < 0.001). An additional 0.5 mm KT increase was observed at interdental sites in the apical group.
Apical flap positioning increases soft tissue rebound and KT width, mainly at the interdental sites, with reduced patient discomfort.
The trial was registered at ClinicalTrials.gov (ID: NCT05140681, Registration date: 1/12/2021, retrospectively registered).
This work investigated whether the anti-resorptive drugs (ARDs) zoledronic acid (Zol) and denosumab (Dmab) affect differently the levels of circulating immune cell subsets, possibly predicting the ...risk of developing medication-related ONJ (MRONJ) during the first 18 months of treatment. Blood samples were collected from 10 bone metastatic breast cancer patients receiving cyclin inhibitors at 0, 6, 12, and 18 months from the beginning of Dmab or Zol treatment. Eight breast cancer patients already diagnosed with MRONJ and treated with cyclin inhibitors and ARDs were in the control group. PBMCs were isolated; the trend of circulating immune subsets during the ARD treatment was monitored, and 12 pro-inflammatory cytokines were analyzed in sera using flow cytometry. In Dmab-treated patients, activated T cells were stable or increased, as were the levels of IL-12, TNF-α, GM-CSF, IL-5, and IL-10, sustaining them. In Zol-treated patients, CD8+T cells decreased, and the level of IFN-γ was undetectable. γδT cells were not altered in Dmab-treated patients, while they dramatically decreased in Zol-treated patients. In the MRONJ control group, Zol-ONJ patients showed a reduction in activated T cells and γδT cells compared to Dmab-ONJ patients. Dmab was less immunosuppressive than Zol, not affecting γδT cells and increasing activated T cells.
The present systematic review was performed to assess the application of orally derived stem cells in periodontal regenerative therapy, and because of this, the following PICO question was proposed: ..."In patients with periodontitis, can the adjunctive use of orally derived stem cells provide additional clinical and radiographic benefits for periodontal regeneration?". Randomized clinical studies were electronically and manually searched up until December 2023. Quantitative analyses were performed with the aim of evaluating the mean differences (MDs) between the treatment and control groups in terms of clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, gingival recession (GR), and radiographic bone gain (RBG) using random effect models. A total of seven studies were selected for the systematic review. Meta-analyses excluding studies with a high risk of bias highlighted a non-statistically significant result for the use of stem cells when compared to the control groups in terms of CAL gain MD = 1.05; 95% CI (-0.88, 2.97)
= 0.29 and PPD reduction MD = 1.32; 95% CI (-0.25, 2.88)
= 0.10. The same also applied to GR MD = -0.08; 95% CI (-0.79, 0.63)
= 0.83 and RBG MD = 0.50; 95% CI (-0.88, 1.88)
= 0.48. Based on the high heterogeneity, there is not enough evidence to consider the adjunctive application of orally derived mesenchymal stem cells as a preferential approach for periodontal regenerative treatment, as compared to standard procedures.
This retrospective study described the clinical and radiographic long-term outcomes of combined periodontal and orthodontic treatment (OT) with fixed appliances in patients with Stage IV ...periodontitis and pathologic tooth migration (PTM) in the anterior sextants. OT was performed in either one or both arches, using tooth-supported or skeletal anchorage, following completion of active periodontal treatment and accurate planning of tooth movement biomechanics. Twenty-nine patients were identified and retrospectively examined when presenting for a supportive periodontal care (SPC) appointment. The mean SPC duration was 8.9 years (range 5 to 12 years). All anterior-migrated teeth showed statistically significant periodontal improvement compared to baseline values and stable radiographic bone levels at the final follow-up. Residual probing depths were 2.9 ± 0.5 mm at the end of active periodontal treatment, and they remained stable at the completion of OT (2.9 ± 0.6 mm) and at the last follow-up visit (2.8 ± 0.5 mm). These findings suggest that OT is a safe and effective treatment in improving the long-term prognosis of teeth with PTM in Stage IV periodontitis provided that periodontal health has been re-established and maintained with individualized SPC sessions.
Periodontal ligament (PDL) has become an elective source of mesenchymal stem cells (PDLSCs) in dentistry. This research aimed to compare healthy PDLSCs (hPDLSCs) and periodontitis PDLSCs (pPDLSCs) to ...ascertain any possible functional differences owing to their milieux of origin. Cells were tested in terms of colony-forming unit efficiency; multi differentiating capacity; immunophenotype, stemness, and senescent state were studied by flow cytometry, immunofluorescence, and β-galactosidase staining; gene expression using RT-PCR. Both hPDLSCs and pPDLSCs were comparable in terms of their immunophenotype and multilineage differentiation capabilities, but pPDLSCs showed a senescent phenotype more frequently. Thus, a selective small molecule inhibitor of DNA methyltransferase (DNMT), RG108, known for its effect on senescence, was used to possibly reverse this phenotype. RG108 did not affect the proliferation and apoptosis of PDLSCs, and it showed little effect on hPDLSCs, while a significant reduction of both p16 and p21 was detected along with an increase of SOX2 and OCT4 in pPDLSCs after treatment at 100 μM RG108. Moreover, the subset of PDLSCs co-expressing OCT4 and p21 decreased, and adipogenic potential increased in pPDLSCs after treatment. pPDLSCs displayed a senescent phenotype that could be reversed, opening new perspectives for the treatment of periodontitis.
Objectives
The aim of this
in vitro
study was to compare the efficacy of chemical and mechanical methods for decontamination of titanium dental implant surfaces previously infected with polymicrobial ...biofilms in a model simulating a peri-implant defect. Furthermore, the effect of each decontamination protocol on MG-63 osteoblast-like cells morphology and adhesion to the treated implants was assessed.
Background
Peri-implantitis is a growing issue in dentistry, and evidence about implant surface decontamination procedures is lacking and inconclusive.
Methods
A total of 40 previously biofilm-contaminated implants were placed into a custom-made model simulating a peri-implant defect and randomly assigned to five treatment groups: (C) control (no treatment); (AW) air abrasion without any powder; (ESC) air abrasion with powder of erythritol, amorphous silica, and 0.3% chlorhexidine; (HBX) decontamination with a sulfonic/sulfuric acid solution in gel; and (HBX + ESC) a combination of HBX and ESC. Microbiological analysis was performed on five implants per treatment group, and the residual viable bacterial load measured in log 10 CFU/mL was counted for each bacterial strain and for the total number of colonies. The remaining three implants per group and three noncontaminated (NC) implants were used to assess surface biocompatibility using a scanning electron microscope and a backscattered electron microscope after seeding with MG-63 cells.
Results
A significant decontaminant effect was achieved using HBX or HBX + ESC, while no differences were observed among other groups. The percentage of implant surface covered by adherent MG-63 cells was influenced by the treatment method. Progressive increases in covered surfaces were observed in groups C, AW, ESC, HBX, HBX + ESC, and NC.
Conclusions
A combination of mechanical and chemical decontamination may provide more predictable results than mechanical cleaning alone.