Bisphosphonates are the most widely marketed drugs in the world to treat osteoporosis but their anti-remodeling effect can cause osseointegration to fail. Objective this study aimed to evaluate bone quality during peri-implant repair in osteopenic rats, adopting an approach inverse to the conventional one in which prolonged treatment with alendronate sodium was initiated only after the installation of titanium implants.Methodology implants were installed in the tibias of 32 rats 14 days after ovariectomy (osteopenia). After 14 days, systemic treatment was initiated by gavage with a saline solution or alendronate. At 28 and 56 days after implantation, the rats received calcein (20 mg/kg, i.m.). They were administered alizarin red (20 mg/kg, i.m.) seven days before euthanasia. Euthanasia occurred in two periods, 42 and 70 post-implantation days.Results the highest implant removal torques were observed for the OVX ALE at 70 days (13.35 Ncm) and the OVX SAL at 42 days (11.63 Ncm). The expression of bone remodeling and resorption proteins (OPG/ RANKL) was higher in the alendronate-treated animals. In contrast, osteocalcin and bone sialoprotein were similar between the control and alendronate-treated groups. No parameter showed statistically significant variations (BV, BV.TV, Tb.Th, Tb. N, Tb.Sp, and i.S), with similar measurements between groups. Fluorochrome analysis showed active bone remodeling at the implant interface.Conclusion the alendronate treatment stabilized the bone-implant interface over time, suggesting a protective effect against osteoporotic bone loss despite a delayed initial response. In the long term, the group systemically treated with alendronate showed improved bone formation around the implants, outperforming the control group. However, future research is essential to prevent possible negative impacts on osseointegration in patients taking this medication.

Bioceramic materials are developed based on their biological properties and bioactive potential. NeoSealer Flo (NeoFlo, NuSmile, Houston) is a ready-to-use bioceramic endodontic sealer. Objective The aim of this study was to evaluate the biocompatibility and bioactivity of NeoFlo compared to Bio-C Sealer (BC, Angelus) and AH Plus (AHP, Dentsply).Methodology The tissue reaction induced by materials in rat subcutaneous tissues was assessed at seven, 15-, 30-, and 60-days post-implantation (n=6/group). The number of inflammatory cells (ICs), fibroblasts, and osteocalcin (OCN)-labelled cells were recorded. Amorphous calcite was identified using the von Kossa method and polarized light. The data were evaluated using two-way ANOVA followed by Tukey’s test, with a 5% significance level. OCN data were submitted to the Kruskal-Wallis test, with Dunn, Friedman, and Nemenyi post-hoc tests.Results NeoFlo capsules showed higher number of IC than BC and AHP (p<0.05) in all periods, with a reduction over time, and was considered moderate at 60 days. Moreover, significant reduction in the number of IC and an increase in the fibroblasts was accompanied by an increase in the amount of collagen in the capsules around all materials over time. Immunoexpression of OCN was only observed in the capsules of NeoFlo and BC, but the capsules of BC showed the highest values in all periods (p<0.05).Conclusion In the present study, NeoFlo showed lower biocompatibility than BC, however, NeoFlo shows bioactivity in connective tissue.

Dental pulp stem cells (DPSCs) are widely available sources of stem cells that have been extensively studied for its capacity to differentiate into osteoblasts and endothelial cells and to support bone repair and regeneration. Collagen type 1 (Col-1) is a well-known extracellular matrix component, which plays a vital role in regulating the signaling pathway for osteoinduction of bone progenitor cells. However, the exact mechanism of Col-1 activation during stem cell osteogenesis remains unclear. Objectives This study aims to identify the key signalling pathway and proteins interaction associated with Col-1-induced osteogenesis of DPSCs.Methodology The localization of OCN protein was assessed by immunocytochemistry analysis, followed by Western blot analysis on OCN, AKT, p- AKT, Smad2/3, p-Smad2/3, ERK1/2, and p-ERK1/2 pathways. Protein profiling was performed using gel-free digestion and LC-MS/MS, followed by protein-protein interaction analysis using STRING online tools to assist in determination of link between various pathways.Results The data indicated that the PI3K/AKT pathway is the key signaling pathway involved in Col-1-induced DPSC, showing a significant impact and potential crosstalk with TGF-b/Smad and MAPK/ERK mainly via focal adhesion protein complexes.Conclusion The evidence suggests that PI3K/AKT signaling pathway is more dominant than the TGF-β/Smad and MAPK/ERK pathways, acting via stimulation of the focal adhesion protein complex. Together, these findings may provide deeper insight into cellular biology of differentiated cells for potential manipulation in bone tissue repair and regeneration.

Objective To evaluate factors influencing the response to periodontal therapy in patients with periodontitis and type 2 diabetes mellitus (DM) using machine learning (ML) techniques, considering periodontal parameters, metabolic status, and demographic characteristics.Methodology We applied machine learning techniques to perform a post hoc analysis of data collected at baseline and a 6-month follow-up from a randomized clinical trial (RCT). A leave-one-out cross-validation strategy was used for model training and evaluation. We tested seven different algorithms: K-Nearest Neighbors, Decision Tree, Support Vector Machine, Random Forest, Extreme Gradient Boosting, and Logistic Regression. Model performance was assessed using accuracy, specificity, recall, and the area under the Receiver Operating Characteristic (ROC) curve (AUC).Results a total of 75 patients were included. Using the first exploratory data analysis, we observed three clusters of patients who achieved the clinical endpoint related to HbA1c values. HbA1c ≤ 9.4% was correlated with lower PD (r=0.2), CAL (r=0.1), and the number of sites with PD ≥5 mm (r=0.1) at baseline. This study induced AI classification models with different biases. The model with the best fit was Random Forest with a 0.83 AUC. The Random Forest AI model has an accuracy of 80%, a sensitivity of 64%, and a specificity of 87%. Our findings demonstrate that PD and CAL were the most important variables contributing to the predictive performance of the Random Forest model.Conclusion The combination of nine baseline periodontal, metabolic, and demographic factors from patients with periodontitis and type 2 DM may indicate the response to periodontal therapy. Lower levels of full mouth PD, CAL, plaque index, and HbA1c at baseline increased the chances of achieving the endpoint for treatment at 6-month follow-up. However, all nine features included in the model should be considered for treatment outcome predictability. Clinicians may consider the characterization of periodontal therapy response to implement personalized care and treatment decision-making. Clinical trial registration ID: NCT02800252

Background Certain genes present variants associated with molar-incisor hypomineralization (MIH) pathogenesis, especially genes encoding enamel development proteins related to morphogenesis, immune response, and hormone transcription and reception, demonstrating that MIH is likely a gene-environment issue with multiple genes having small individual effects.Objective To evaluate the association between single nucleotide polymorphisms (SNPs) and MIH.Methodology A sample of 90 children with MIH and 262 children without MIH were included in this study. Calibrated examiners diagnosed MIH (Kappa≥0.75) using the European Academy of Paediatric Dentistry (EAPD) criteria and modified DDE index in clinical exams. SNPs in the IL-6 (rs2069840 and rs2069833), ESR (rs9340799, rs1256049, rs4986938, and rs2234693), VDR (rs739837 and rs2228570), and 5-HTT genes (rs1042173 and rs38133034) were genotyped by real-time polymerase chain reaction from oral mucosa cells collected. Associations between MIH and SNPs genotypes (recessive and dominant models) and allele frequencies were tested using the chi-square test. Odds ratio (OR) and confidence intervals (CI) were calculated. A significance level of 5% was adopted. Genotypes were tested by the Hardy–Weinberg Equilibrium using chi-square.Results In rs4986938 (ESR2 gene), children with CT/TT presented significantly lower odds of MIH than CC (OR=0.57, CI 95% [0.35-0.92]). There was no significant association between MIH and other evaluated genes.Conclusion The genetic polymorphism in the ESR gene is associated with MIH, suggesting that MIH etiology presents a polygenetic involvement.

Aim This cross-sectional study investigated the salivary proteomic profile associated with generalized gingivitis in pregnant women with obesity.Methodology Pregnant women in the third trimester (≥27 weeks of gestation) were divided into two groups based on bleeding on probing (BOP): G1 (BOP>50%; n=9) and G2 (BOP 0–30%; n=9). Collected unstimulated saliva samples were individually analyzed using nano liquid chromatography electron spray ionization tandem mass spectrometry. Identified proteins were classified according to gene ontology for biological processes, molecular functions, immune system involvement, and cellular components. Differential protein expression was determined using thresholds of p<0.05 for downregulation and 1-p>0.95 for up-regulation proteins.Results Of the 183 identified proteins, 100 were shared between groups, totaling 57 up-regulated and 27 downregulated proteins in G1. Key biological processes included antimicrobial humoral response and hydrogen peroxide catabolism, with proteins linked to immune function and endopeptidase regulation. Functional analysis showed that Lactotransferrin (5-fold increase in G1), Haptoglobin (4-fold), and Immunoglobulin J chain (3-fold) were up-regulated, whereas Statherin (5-fold) and Protein S100-A8 (4-fold) were downregulated in G1.Conclusions Pregnant women with obesity and generalized gingivitis exhibited a distinct salivary proteomic profile characterized by the up-regulation of immune-related proteins and downregulation of tissue-protective proteins. These findings suggest potential salivary biomarkers for detection and targeted management of periodontal inflammation in this high-risk population.

ObjectiveThis study sought to investigate the relationship between clinical response to nonsurgical periodontal therapy (NSPT) and serum changes in leukocyte count, fasting blood glucose, hemoglobin, hematocrit, creatinine, and uric acid in kidney transplant recipients (KTR).MethodologyA prospective study was performed on 20 KTRs. Periodontal and serum data were collected before and 90 days after NSPT, and delta values (Δ = after NSPT - before) were calculated. Periodontal assessment included periodontal probing depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP). Patients were classified based on the presence of periodontitis and then categorized into stages.ResultsPatients showed a reduction in the percentage of sites with PPD≥3mm, PPD≥4 mm and BOP, after NSPT. There was a direct correlation between the deltas of leukocyte count and CAL ≥3 mm (r=0.645, P=0.002) and BOP (r=0.663, P=0.001), and the deltas of uric acid and CAL ≥3 mm (r=0.562, P=0.010).ConclusionA good clinical response to NSPT may affect the reduction of serum levels of leukocyte count and uric acid, suggesting a beneficial effect on systemic health in KTR.

Objective To analyze the effect of mast cells (MCs) in neurogenic inflammation and the neuroimmune response of trigeminal ganglia (TG) due to pulpitis and detect the regulatory effect of curcumin (Cur) on neuroimmune responses induced by pulpitis.Methodology Immunohistochemistry, toluidine blue staining (TB), and other methods were used to detect the dynamic changes of MCs, as well as tryptase expression changes and protease activated receptor 2 (PAR2) and calcitonin gene-related peptide (CGRP) levels in the neuroimmune response induced by pulpitis. After administering Cur by intraperitoneal injection, the expression levels of Toll-like receptor 4 (TLR4), CGRP, glial fibrillary acidic protein (GFAP), fractalkine (CX3CL1), Tumor necrosis factor (TNF-α), and other factors were examined in the TG of pulpitis-induced rats.Results After pulpitis induction, the expression of CGRP-positive neurons and GFAP-positive soluble guanylate cyclase (SGC) in the TG significantly increased. A large number of MCs underwent degranulation. MCs were scattered between the CGRP-positive nerve fibers. MCs showing a typical degranulated state within the TG significantly increased and tryptase-positive MCs surrounded the TG nerve fibers and neurons. After treatment with Cur, the inflammatory response in the periodontal bone induced by pulpitis decreased and promoted early tissue repair. The expression of TNF-α significantly decreased as did degranulation of MCs. In contrast, the expression of CGRP, TLR4-positive neurons, activated SGCs, and PAR2-positive TG neurons significantly decreased. MCs could participate in the neuroimmune response induced by pulpitis by the tryptase signaling pathway.Conclusion Importantly, Cur inhibited the degranulation of MCs, downregulated the expression of tryptase and PAR2 in the TG, and attenuated the activation response of osteoclasts in the apical periodontium.

Research would be important for obtaining a better understanding of voice complaints among patients with temporomandibular disorders (TMD). Objective The identification of predictors of voice disorders associated with TMD pain was made according to Diagnostic Criteria for TMD (DC/TMD) Axis I.Methodology Functional limitations were measured using the Jaw Functional Limitation Scales for mastication (JFLS-M), jaw mobility (JFLS-JM), and verbal and emotional expression (JFLS-VEE). Patients also completed the Hospital Anxiety and Depression Scale (HADS). The primary outcome was social-emotional and physical functioning as indicated by scores on the Voice-Related Quality of Life (V-RQOL) questionnaire. Multiple linear regression was used to model the relationship between the domains on the V-RQOL questionnaire and scores on the HADS and JFLS after adjusting for age, gender, DC/TMD diagnosis, pain intensity, and time since pain onset.Results The HADS-D (B=-1.15; 95% CI, -1.718 to -0.587; p<.001) and JFLS-VEE (B=-0.22; 95% CI, -0.40 to -0.06; p=.008) were significant predictors of scores on the V-RQOL questionnaire.Conclusion Higher scores on depression measures and limitations in verbal and emotional expression could exacerbate voice problems among TMD pain patients. Future research should promote multidisciplinary treatments for TMD pain-related voice disorders.

Objective the aim of this study was to analyze the influence of ozone therapy (OZN) on peri-implant bone repair in critical bones by installing osseointegrated implants in the tibia of ovariectomized rats.Methodology ovariectomy was performed on 30 Wistar rats, aged six months (Rattus novergicus), and, after 90 days, osseointegrated implants were installed in each tibial metaphysis. The study groups were divided into the animals that received intraperitoneal ozone at a concentration of 700 mcg/kg — OZ Group (n=15) — and a control group that received an intraperitoneal saline solution and, for this reason, was named the SAL group (n=15). The applications for both groups occurred during the immediate post-operative period on the 2nd, 4th, 6th, 8th, 10th, and 12th day post-surgery. At various stages (14, 42, and 60 days), the animals were euthanized, and tests were performed on their tibiae. These tests include histomorphometric and immunohistochemical analyses, computerized microtomography, sampling in light-cured resin for calcified sections, and confocal microscopy. The obtained data were then analyzed using One-way ANOVA and the Shapiro-Wilk, Kruskal-Wallis, and student t-tests (P<0.05).Results our findings indicate that the OZ group (3.26±0.20 mm) showed better cellular organization and bone neoformation at 14 days (SAL group, 0.90±1.42 mm) (P=0.001). Immunohistochemistry revealed that osteocalcin labeling was moderate in the OZ group and mild in the SAL group at 14 and 42 days post-surgery. The data from the analysis of calcified tissues (microtomography, histometric, and bone dynamism analysis) at 60 days showed no statistically significant differences between the groups (P=0.32).Conclusion it was concluded that ozone therapy anticipated the initial phases of the peri-implant bone repair process.