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Abstract The acquired enamel pellicle (AEP) consists of an organic, acellular, and bacteria-free film, formed in vivo as a result of biomolecules adsorption onto the tooth surface. It is composed of proteins, glycoproteins, lipids, phospholipids, and other macromolecules, such as carbohydrates. The AEP formation process is complex and can be divided into three stages: initiation, development, and maturation. The pellicle has two main layers: the globular and basal layers. The basal layer offers the most protection against demineralization, as the subsequent globular layer is weaker and less tenacious. The formation of the AEP can be influenced by various factors, such as the physicochemical properties of the teeth, location in the oral cavity, pathologies, and even the oral microbiota. With the advancement of “omics” techniques, it has been possible to observe the presence of acid-resistant proteins in the AEP, which allowed the development of the “acquired pellicle engineering” strategy. This strategy involves enriching and modifying the basal layer with acid-resistant proteins. Among these proteins, hemoglobin, statherin-derived peptide, and a protein derived from sugarcane stand out. The objective of this literature review is to provide a comprehensive overview of the AEP, detailing its composition, formation process, and protective functions. Additionally, the review aims to explore recent advances in the field of “acquired pellicle engineering,” highlighting the acid-resistant proteins of the AEP and their potential applications in dentistry. Finally, the review intends to highlight the clinical implications of these findings and how they may contribute to the development of new strategies for the prevention and treatment of dental pathologies according to published studies.

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Abstract Amelogenesis imperfecta (AI) encompasses a group of conditions characterized by abnormalities in the development or function of tooth enamel. Clinical manifestations include different forms and degrees of enamel frailty, associated with sensitivity, tooth fractures, stains, abnormal tooth morphology, missing teeth, etc. AI is genetically heterogeneous, with over 70 genes associated with autosomal dominant, autosomal recessive, X-linked, and oligogenic inheritance. Objective To identify genetic variants associated with AI in a single family. Methodology We describe the clinical findings of a family affected by AI, composed of five individuals: four affected (the father and three daughters) and one unaffected (the mother). The observed segregation pattern suggests a dominant, X-linked inheritance. Genetic variants were screened using whole-exome sequencing. The initial bioinformatic analysis was conducted using Qiagen QCI, and variants were selected based on their presence in all four affected family members and absence in the unaffected mother. Search terms included “amelogenesis imperfecta,” “tooth,” and “enamel.” Several types of software were used to classify variants according to pathogenicity. Results Candidate variants were identified in six genes. Three of these variants were detected in autosomal genes: NM_031889.3(ENAM):c.1726T>C (p.F576L), NM_022168.4(IFIH1):c.1764dupA, (p.A589fs*21), and NM_032383.5(HPS3):c.1897A>T (p.M633L). Three variants were detected in X-linked genes: NM_006150.5(PRICKLE3):c.8C>G (p.A3G), NM_004484.4(GPC3):c.584A>G (p.N195S), and NM_152787.5(TAB3):c.1936G>A (p.V646M). None of these variants were classified as pathogenic or likely pathogenic in AI. Discussion Among the identified genes, only ENAM has previously been associated with AI; however, IFIH1, PRICKLE3, and GPC3 are associated with dental/enamel development. The relatively high number of candidate genes and variants detected may reflect an oligogenic component already proposed for AI. Conclusions This study provides a set of new candidate genes and genetic variants for AI. Despite sharing the same variants, AI-affected family members show considerable phenotypic variant, suggesting the involvement of non-shared genetic or environmental factors.

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Abstract Calcium carbonate (CaCO₃) has garnered increasing attention in dental research due to its versatile bioactive properties and expanding applications in preventive, restorative, and regenerative therapies. Objective This study aims to comprehensively assess the bibliometric features of articles evaluating the utilization of calcium carbonate (CaCO₃) in dentistry by conducting a bibliographic search on the Web of Science databases until March 2025. Methodology The following data were collected: number and density of citations; authorship; year, journal of publication, and impact factor; study design and theme; keywords; institution and country of origin. VOSviewer software was used to generate collaborative network maps for authors and keywords. Results A total of 91 highly cited articles were identified, with citation counts ranging from 123 to zero. Most articles (74%) were published after 2010, with the highest prevalence in Asia (44%), especially China (10%). The most frequent study design was in vitro (55%), primarily focused on restorative dentistry (29%) and cariology (23%). The most common keywords were “Calcium Carbonate” and “Hydroxyapatite”. DeVizio W. was the most prolific author, with four publications. Conclusions Bibliometric analysis highlights a growing interest in the application of calcium carbonate in dentistry, with a progressive increase in scientific output over the years. The findings underscore the global distribution of research and emphasize the relevance of this biomaterial in various dental specialties. This study reinforces several key points for research groups worldwide engaged in the development of innovative dental materials, providing valuable direction for future investigations, which remain limited in scope, especially regarding clinical applications and long-term outcomes.

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Abstract Submandibular salivary gland inflammation has been suggested as one of the mechanisms underlying impaired salivary secretion associated with sleep deprivation (SD). However, whether the salivary inflammatory response occurs to the same extent in paradoxical sleep deprivation with or without sleep recovery remains unknown. Objective: This study evaluated the extent to which inflammation influences salivary impairments associated with paradoxical sleep deprivation with or without sleep recovery. Methodology: Male Wistar rats were randomly assigned into three groups as control, partial SD (PSD) with sleep recovery for four hours a day and total SD (TSD). Paradoxical SD was carried out for seven days in the SD groups, after which saliva, blood, and submandibular gland samples were taken. Levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and nitrite were determined in saliva, serum, and the submandibular salivary gland. Leucocyte count and neutrophil-lymphocyte ratio were determined in all groups. One-way ANOVA and the Tukey's post hoc tests were used for data analysis. P-values < 0.05 were considered statistically significant. Results: Levels of TNF-α, IL-6, and nitrite in the submandibular salivary glands were significantly higher in the TSD groups (p=0.04,p<0.001, p=0.03, respectively) than in the control. Saliva level of TNF-α was higher in the PSD and TSD groups (p=0.003 and p=0.01 respectively) than in the control. Neutrophil-lymphocyte ratio was significantly higher in both PSD and TSD groups than in the control (p<0.01 for both). Conclusion: While total SD produced higher inflammatory response in the submandibular salivary gland, four-hour sleep recovery ameliorated this impact. This finding suggests that sleep recovery is crucial to improve inflammatory salivary gland dysfunction induced by sleep deprivation.

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Abstract Objectives: Depth of invasion (DOI) in oral squamous cell carcinoma (OSCC) guides treatment and prognosis but lacks three-dimensional (3D) insight. Thus, this study aimed to investigate the feasibility and accuracy of Lugol's iodine-enhanced micro-computed tomography (CT) for the 3D measurement of DOI in OSCC samples. Methodology: In total, 50 in vitro OSCC samples from Nanjing Stomatological Hospital (July 2022 to January 2024) were subjected to micro-CT imaging with a slice thickness of 50 μm following 3% Lugol iodine staining for 12 h, followed by pathological examination and staining. The panoramic diagnostic scanner digitally measured pathological DOI. The micro-CT DOI was measured by evaluating the voxel value of the boundary of the tumor lesion and comparing it with the pathological examination results. Experienced physicians analyzed both measurements, and statistical analyses were performed to determine their correlation. Results: Lugol iodine-enhanced micro-CT imaging distinguishes various tissue structures, such as tumor tissue, epithelial tissue, muscle tissue, blood vessel structure, and other major tissue structures in 3D space. This imaging technique found and localized micro-tumor lesions (1.82×1.5×1 mm3) when in conjunction with pathological sections. Statistical analysis indicated a strong correlation between pathological DOI and micro-CT DOI (P<.001; r=0.986). During DOI measurement, Lugol iodine-enhanced micro-CT imaging effectively compensated for the loss of 3D space information in the pathological measurements, improving the accuracy of the DOI measurement. Conclusions: Lugol iodine-enhanced micro-CT improves OSCC DOI 3D measurements, enhances pathological staging accuracy, and aids treatment decisions and prognosis.

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Abstract Guided bone regeneration (GBR) is an alternative treatment for craniofacial bone defects reconstruction through membrane barrier adaptation, such as demineralized dentin material membrane (DDMM). DDMM is used as a substitute for GBR material, which aligns with Green Economy principles, it has a good biological osteoinductive and osteoconductive effects, and its structure resembles bones. The balance of bone remodeling when experiencing craniofacial defects will be altered and allow changes to resorption activity, so the mechanisms of osteoclastogenesis and bone resorption are vital. Objective: this article aims to analyze the expression of TNF-α, RANKL, and osteoclast cells count after application of DDMM as GBR in mandibular bone defects. Methodology: this is an experimental study with a post-test only control group design, which began with the randomization of 120 rats into five groups: K(−), without membrane implantation; K(+), PPCM; P1, DDMM; P2, DDMM + bone graft; P3, PPCM + bone graft. The expression of TNF-α, RANKL, and osteoclast cells count were observed, followed by analysis using a one-way ANOVA and post hoc Tukey HSD comparison test. Results: there were significant differences in the expression of TNF-α, RANKL, and osteoclast cells count in all study groups (p=0.000). TNF-α showed a decreasing difference with the highest expression in the K(−) group on day 3 of 12.00±2.16. RANKL expression increased on day 14 and decreased on day 21 in all groups. The osteoclast cells count generally showed a critical period with the highest increase in the K(−) group on day 14 of 73.00±0.00. Conclusion: DDMM has the potential to be a superior membrane substitute compared to PPCM as GBR in alternative treatment for craniofacial bone defects reconstruction.

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Abstract Aim To evaluate the clinical effectiveness of ozonated sunflower oil (Oz) as an adjunctive of non-surgical periodontal therapy in patients with type 2 diabetes mellitus (DM2), on fibroblast cell viability and migration and the effectiveness of Oz on a Candida albicans (C. albicans) culture. Methodology In total, 32 sites in 16 DM2 with moderate to advanced periodontal disease with periodontal pocket depths ≥5mm were selected. The treatments were divided into two groups: control, saline solution (SS) as an adjunctive of scaling and root planing (SRP+SS), and test, Oz as an adjunctive of SRP (SRP+Oz). Hematological [fasting glucose level (FGL) and hemoglobin A1c (HbA1c)] and microbiological samples were collected from the participants at baseline and three months after periodontal treatment and the microbiological samples were analyzed by PCR. C. albicans was previously tested by the agar diffusion test. The effect of Oz was tested on cell viability and fibroblast migration. Results The groups showed no statistically significant differences (paired t-test-p>0.05) regarding hematological parameters, FGL (median - baseline 171.41, 3 months 164mg/dL), and HbA1c (baseline 8%, 3 months 7.5%) (Kruskal-Wallis One-Way Nonparametric-p>0.05) after periodontal therapy. The groups showed statistical differences for periodontal parameters between baseline and three months (paired t-test-p<0.05). PCR analysis showed a reduction in the percentage of C. albicans in the SRP+Oz group after three months (McNemar’s test-p=0.002). Cell viability was lower in the high glucose Dulbecco’s modified Eagle’s medium (4500 mg/L) than in low glucose (1000 mg/L) (RM-ANOVA-p<0.0001). The wound healing test showed reduced fibroblast migration (one-way ANOVA with Dunnett’s post-test-p<0.01). Oz showed high C. albicans antifungal inhibition (Kruskal-Wallis test-p=0.0001). Conclusions SRP+Oz effectively reduced C. albicans in-vitro and in-vivo but showed no clinical improvements compared to the control. Cell viability and wound healing of fibroblasts showed no improvements.

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Abstract Objective This study evaluated whether hypoglycemic drug metformin enhances the anti-cancer effects of cisplatin in YD-9 cells. Methodology YD-9 cells, derived from oral mucosal squamous cell carcinoma of oral mucosa, were used to assess the combined effects of metformin and cisplatin by means of MTT assay, live and dead cell staining, and colony formation assays to evaluate cell viability and proliferation. Reactive oxygen species level was measured using a Muse cell analyzer. Apoptosis, epithelial-mesenchymal transition, and related molecular pathways were analyzed by western blot. Wound healing assays and Transwell migration assays examined cell migration, whereas monophosphate-activated protein kinase inhibitor Compound C, was utilized to investigate the AMPK pathway. Results Sequential treatment of YD-9 cells with metformin and cisplatin resulted in decreased cell viability and proliferation, increased ROS levels, and elevated apoptosis compared with the individual drugs. Moreover, the treatment inhibited EMT, wound healing, and cell migration. These results correlated with increased AMPK phosphorylation, a key regulator of cellular energy homeostasis. Introduction of Compound C pre-treatment upregulated N-cadherin and α-smooth muscle actin along with enhanced cell migration. Conclusion This study found synergism in anti-cancer effects between metformin and cisplatin. Additionally, introduction of Compound C confirmed that EMT inhibition is AMPK dependent. These findings indicate the potential use of metformin as an adjunct drug in anti-cancer treatments, warranting further investigation.

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Abstract Circadian rhythm disorders and NF-κB are closely linked and can exacerbate periodontitis. However, the mechanisms via which circadian rhythm-related genes influence periodontitis are not yet fully understood. Objective We investigated the effect of brain and muscle Arnt-like protein-1 (BMAL1) on the NF-κB pathway and downstream inflammatory factors on periodontitis. In this study, Bmal1 homozygous knockout and periodontitis mouse models were established. Methodology Bone marrow-derived macrophages (BMDMs) from Bmal1-/- mice were cultured and stimulated with lipopolysaccharides. Bone resorption was detected using micro-computed tomography and histological analyses. Gene and cytokine expression was assessed using quantitative reverse-transcription PCR and ELISA. The nuclear translocation of p65 was detected using immunofluorescence. Results Our findings indicate that Bmal1 knockout exacerbates periodontitis severity in mice by activating the NF-κB signaling pathway with increased nuclear translocation of p65 (p<0.05), as well as increased expression of Il-1b, Il-6, and Tnfα (p<0.01), along with decreased Nr1d1 expression (p<0.05) in BMDMs under inflammation. Conclusion The results highlight the protective role of Bmal1 in periodontitis and suggest its potential link to the circadian clock's influence on the disease.

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Abstract Ionizing radiation directly affects hard dental tissues, compromising the dental structure, which results in damage to dentin collagen fibers and impacts the integrity of the dentin-enamel junction (DEJ). Objective To evaluate the effects of radiotherapy on the chemical composition and mechanical properties of human cervical dentin. Methodology Ten third molars were divided into control/non-irradiated and irradiated groups (n=5). The irradiated teeth were subjected to in vitro radiotherapy with the following protocol: 1.8 Gy daily, five days per week for eight weeks, totaling 72 Gy. The dentin in the cervical region was evaluated for each group. The chemical composition was assessed using Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy, focusing on the mineral/matrix ratio (M:M), carbonate/mineral ratio (C:M), and amide I/amide III ratio. Amide I/CH2 ratio was used to assess collagen quality, as amide I reflects protein conformation and hydrogen bonding, while CH2 indicates side-chain vibrations with low sensitivity to molecular orientation. Nanohardness and elastic modulus were evaluated by instrumented indentation. Scanning electron microscopy (SEM) was used to assess the enamel’s morphology. Statistical analysis of each parameter was performed using a t-test. Results The FTIR analysis showed statistically significant differences in the C:M ratio (p=0.004) and amide I/amide III ratio (p=0.007). Raman spectroscopy revealed significant differences in the M:M ratio (p<0.001), as well as in the amide I/amide III (p<0.001) and amide I/CH2 ratios (p<0.001). Additionally, nanohardness (p=0.04) and the elastic modulus (p=0.003) showed statistically significant differences. SEM images revealed sound dentin shows normal tissue organization, whereas irradiated dentin showed no clear limit between peri and intertubular dentin. Conclusions Radiotherapy induced significant changes in dentin composition and mechanical properties, characterized by increased organic content and phosphate levels, reduced carbonate, and decreased nanohardness and elastic modulus. These findings highlight the adverse effects on dentin's structural integrity.

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Abstract Objective To evaluate the association between non-syndromic cleft lip with or without cleft palate (NSCL±P) and tooth agenesis (TA), as well as the association of both conditions with polymorphisms in genes encoding growth factors. Methodology This cross-sectional study included children with NSCL±P and a control group of children without NSCL±P. Permanent teeth TA (excluding third molars) was evaluated using panoramic radiographs by a trained examiner. Only TA located outside the cleft was considered in the NSCL±P group. Genetic polymorphisms in Transforming Growth Factor Beta 1 (TGFB1)–rs1800470 and rs4803455–Transforming Growth Factor Beta Receptor 2 (TGFBR2)–rs3087465 and rs764522–Epidermal Growth Factor (EGF)–rs4444903 and rs2237051–and Epidermal Growth Factor Receptor (EGFR)–rs2227983– were genotyped by real-time PCR allele discrimination from buccal cell samples. Associations were tested by uni and multivariable Poisson regression models (5% significance level). Results A total of 243 children–127 with NSCL±P (mean age = 8.80±2.14 years) and 116 without NSCL±P (mean age = 8.58±2.03 years) were included. TA was more frequent in the NSCL±P group (23.8%) than in the control group (6.2%) (p<0.01). The EGF rs2237051 was significantly associated with NSCL±P, independently of the other variables (PRa=1.41; p=0.042). Regarding TA, only the cleft presence was associated with a higher prevalence of TA regardless of different variables (PRa=3.70; p=0.001). There was no association between TA and the investigated genetic polymorphisms. When TA and NSCL±P were considered together, a borderline association was observed with rs1800470 in TGFB1 (p=0.06). Conclusion NSCL±P is associated with TA outside the cleft area. The EGF rs2237051 was associated with NSCL±P. Polymorphisms in genes encoding growth factors are not associated with TA.

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This article is derived from Irisvaldo Lima Guedes's Master's dissertation and is available at the address: https://sigaa.ufpi.br/sigaa/public/programa/noticias_desc.jsf?lc=pt_BR&id=370¬icia=519307121

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Abstract Inflammation, oxidative damage, and adenosine triphosphate (ATP) depletion play a role in the pathogenesis of cisplatin (CIS)-induced oral mucositis. Objective: The purpose of this research is to examine the impact of ATP against potential oral mucositis development in cisplatin-treated rats. Methodology All rats were randomly assigned to four groups, namely healthy control group (HG), ATP group (ATPG), Cisplatin group (CISG), and ATP + Cisplatin group (ATCS). Firstly, ATP 4 mg/kg was administered via intraperitoneal injection (IP) to both ATPG and ATCS groups. The same volume of normal saline was injected into HG and CISG groups. After 1 h, cisplatin 5 mg/kg was administered via IP to CISG and ATCS groups. The drugs were taken 1x1 for 7 d. Later, tongue tissues were collected from all groups. Biochemical, macroscopic, and histopathological examinations were performed on all tissues. Results: ATP inhibited cisplatin-induced oxidative damage and pro-inflammatory cytokines levels in tongue tissue. In the CIS group, a significant number of distinct sulcus formations were found in the apex and corpus, as well as a few ulcer foci in the corpus, significant papilla loss, and bleeding. Meanwhile, in the ATP group, a similar appearance to healthy tissue was observed. Histopathologically, it was determined that in cisplatin-aggravated tongue tissue damage, filiform papillae decreased when ATP was administered, and the arrangement and structures of the epithelium, blood capillaries, muscle groups, and adipose cell groups were normal. Conclusions: Oral mucositis caused by cisplatin is alleviated by ATP. These findings may be useful for developing new therapeutic approaches to prevent or treat mucositis, a side effect so severe that can lead to treatment discontinuation.

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Abstract Introduction: According to the latest international consensus in 2018, sleep bruxism is the activity of the masticatory muscles during sleep characterized by rhythmic or non-rhythmic teeth clenching or grinding. Regarding its harmful effects, bruxism is considered one of the predisposing factors of tooth wear and temporomandibular joint diseases. Occlusal splint therapy is the most frequently used treatment for minimizing these harmful effects. Objectives: This study compared the volumetric wear loss and pain scores between digitally and conventionally manufactured occlusal splints for individuals with sleep bruxism. Methodology: A total of 30 individuals diagnosed with sleep bruxism were selected following the inclusion criteria and randomly divided into two groups. Pain scores were subjectively reported using a visual analog scale. Volumetric wear loss of the occlusal splint surface was measured using the Geomagic software. Data were analyzed with SPSS version 25.0. Results: At the six-month follow-up, conventionally manufactured splints (103.53±41.23) showed a volumetric loss significantly higher than that the digital ones (62.33±26.29) (p=0.005). We found no significant difference between the two splint types regarding VAS scores. Conclusion: Occlusal splint wear can gradually alter the balance of occlusal contact and potentially reduce its therapeutic effectiveness, highlighting the importance of using wear-resistant materials. Our findings indicate that digital manufacturing processes provide advantages due to their long-term clinical outcomes.

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Abstract Chitosan nanoparticles suspension (ChNPs) showed antimicrobial effects in the oral cavity, but its effects on enamel erosion prevention remain little explored. Objective This study synthesized ChNPs and evaluated their effect on enamel after erosive challenge. Design ChNPs were synthesized by ionic gelation and characterized using scanning electron microscopy (SEM), infrared spectrophotometry (FTIR), dynamic light scattering methods (DLS) and zeta potential (ZP). In total, 56 human enamel blocks were divided into four groups (n=14/group): (i) ChNPs suspension (4.4mg/mL); (ii) 0.05% sodium fluoride solution (NaF); (iii) chitosan solution (5.0 mg/mL); and (iv) distilled water. After incubation in freshly collected human saliva (3h), the samples were exposed to erosive challenge in 1% citric acid (90s) and remineralizing solution (2h) performed four times a day. After the 1st and 4th acid exposures, solutions were applied for 2 min. After 7 days, % Vickers surface hardness change (% SMH) was obtained using 300 g load applied for 15s. Enamel surface loss was evaluated using optical profilometer by subtracting the final profile values from baseline ones. Data were analyzed by ANOVA and post-hoc T tests (α=0.05). Surface topography was obtained by optical profilometer. Results SEM revealed the formation of spherical nanoparticles. DLS showed nanoparticles with 85.7±10.5 nm diameter and ZP value of +45.5±5.4mV. Enamel surface loss was significantly lower in ChNPs and NaF groups, exhibiting a less rough surface in the treated areas. ChNPs, NaF and chitosan groups showed lower % SMH values. Conclusions ChNPs suspension minimized enamel loss after in vitro erosive challenge and appears to be a promising material for enamel erosion prevention.

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Abstract Objective: To evaluate the possible clinical association between dental fracture and the presence of amalgam restorations, including other restorative treatments in the control group. The potential association of fractures with dental wear facets and the restoration size was also assessed as a secondary objective. Methodology: Patients with fractured teeth restored with silver amalgam or not were included as the case group (n=25). The control group, with non-fractured teeth, was selected after considering the case group aspects, with twice as many patients (n=50) with posterior teeth sound or restored (amalgam, composite resin, or another restorative material). For both groups, the type of restorative material, extension of the restorations, remaining tooth structure, and the presence or absence of wear facets were analyzed. The teeth were impressed with alginate, and from the plaster models, the extent of fractures or restorations was measured by two calibrated examiners with a digital caliper at the cervico-occlusal and bucco-lingual directions. The data were subjected to the Chi-square test (5%) and odds ratio. Results: There was no statistical difference between the presence or absence of amalgam restorations regarding the risk of tooth fracture. Regarding fractures larger than 3.5mm, the chances of failure are 0.53 for amalgam restorations with no statistical differences (p=0.433), and, regarding the presence of wear facets, the odds ratio of failure is 1.357 for amalgam restorations (p=0.65). Conclusion: It can be deduced that, within the conditions of the study, no discernible association exists between dental fractures and the presence of silver amalgam restorations. Clinical Trial Register: (ReBEC) UNT code U1111-1215-7255.

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Abstract Pulpitis, which is often triggered by caries and trauma, is a significant clinical challenge due to its prevalence. This research aims to uncover potential metabolic biomarkers for pulpitis and map out the implicated metabolic pathways, thereby laying a foundation for enhanced diagnostic and preventive strategies. Methodology We analyzed pulp samples from 12 participants (six who had pulpitis and six who had healthy teeth) using serum metabolomics via ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry. Important biomarkers were pinpointed via multivariate analysis and orthogonal partial least squares discriminant analysis. Additionally, correlation and biomarker pathway enrichment analyses were conducted to explore the relations between differentially expressed biomarkers and their associated biological pathways. Specific metabolites of interest were further examined via alkaline phosphatase (ALP) staining, Alizarin Red staining, and RT-qPCR analysis. Results We identified 22 significant biomarkers (13 increased, nine decreased) related to 18 metabolic pathways in pulpitis cases. Key biomarkers included ascorbic acid, inosine, allopurinol riboside, and L-asparagine, in which ascorbic acid and inosine showed the most substantial downregulation and strongest association with pulpitis. Notably, aminoacyl-tRNA biosynthesis and retrograde endocannabinoid signaling pathways were closely linked with pulpitis. Ascorbic acid enhanced the osteogenic differentiation, calcium deposition, as well as the expression of osteogenic genes of human dental pulp stem cells (DPSCs).Conclusions: The identified biomarkers and metabolic pathways offer insights into the pathogenesis of pulpitis and have potential applications in developing preventive treatments.

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Abstract The nasopalatine duct cyst (NPDC) is the most common nonodontogenic jaw cyst, with a higher prevalence reported in males. Diagnosing jaw cysts remains challenging for general dentists due to their overlapping clinical and radiographic presentations. An updated case series and integrative literature review may assist in improving the accurate diagnosis of NPDC. Objective This study aimed to describe the clinicopathological and imaging characteristics of 63 NPDC cases and to review previously reported cases in the literature. Methodology An international, multicenter, retrospective NPDC case series was conducted. Demographic, radiographic, and histopathological data were collected from clinical records. Additionally, a PubMed/MEDLINE search was performed to identify articles on NPDC. Results A total of 63 NPDC cases were evaluated, with a mean patient age of 47 years and no significant sex predilection. Twenty-one cases were asymptomatic, while 34 presented with symptoms such as pain and swelling. Radiographically, NPDC appeared as a well-defined radiolucent lesion located between the upper central incisors, bordered by a radiopaque margin. The integrative literature review identified 67 studies, comprising 51 case reports, 12 retrospective studies, and four case series, totaling 1,003 reported NPDC cases. The clinicopathological and radiographic findings from the literature aligned with those in this case series. Conclusion The 63 cases analyzed in this study showed consistent findings across six international centers, with no sex predilection observed, contrasting with the male dominance reported in the literature. NPDC should be considered in the differential diagnosis of intraosseous lesions in the anterior maxilla. Accurate diagnosis requires a combination of radiographic and histopathological evaluations to prevent misdiagnosis and improper treatment.

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Abstract 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.

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Abstract Objectives This in vitro study evaluated implant-supported single crowns with external connections fabricated using different techniques (cast and CAD/CAM) and materials (metal-ceramic and translucent zirconia) regarding vertical and horizontal marginal fit and torque loss before and after mechanical cycling. Methodology A total of 50 specimens prepared using cast (lost wax) and CAD/CAM were divided into five groups—MC (metal–ceramic crowns), ZrB (Co-Cr base, coping milled in zirconia and feldspathic ceramic veneering), Zr (coping milled in zirconia and feldspathic ceramic veneering), MZrB (Co-Cr base and monolithic translucent zirconia crown), and MZr (monolithic translucent zirconia crown)—and subjected to 5×10⁶ mechanical cycles at a 30° angle at 37°C, and an applied load of 150N at 2Hz. All crowns were screwed with a 30Ncm torque. Vertical and horizontal marginal misfit (measured using a 3D optical microscope) and torque loss were assessed before and after mechanical cycling. Statistical analyses used a significance value of 0.05. Results Before cycling, MC (93.93±22.84µm) and MZrB (66.12±11.87µm) (p<0.05) crowns showed significantly higher vertical marginal misfit values than Zr (49.92±3µm) and MZr (49.76±3,9µm). ZrB (59.96±4.66µm) crowns exhibited no statistically significant difference when compared with the other groups. MC crowns presented the highest horizontal marginal misfit values before and after cycling in group comparisons (p<0.05). MZrB had the highest torque loss (10N), with a statically significant difference when compared with MZr and Zr (p<0.05). Comparison between all groups showed no significant difference regarding the effect of mechanical cycling (p>0.05). Conclusion CAD/CAM manufacturing resulted in lower vertical and horizontal marginal misfit values, especially for monolithic translucent zirconia crowns (MZr) before and after mechanical cycling. All groups presented torque loss before and after mechanical cycling.

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Abstract Objective: To investigate the effects of concentrated platelet-rich fibrin (C-PRF), injectable platelet-rich fibrin (i-PRF), and platelet-rich plasma (PRP) on cellular activity of human primary osteoblasts. Methodology: C-PRF, i-PRF, and PRP were prepared from five donors and pre-cultured in 5 mL of culture medium for three days. Human primary osteoblasts were seeded and cultured with 20% conditioned medium derived from the three platelet concentrates. Then, osteoblast viability was assessed at 24 h; proliferation at one, three, and five days; differentiation at seven days; mineralization at 14 days; and gene expression RUNX family transcription factor 2 (RUNX2), alkaline phosphatase, biomineralization associated (ALPL), collagen type I alpha 1 chain (COL1A1), and osteocalcin (OCN) at three and 14 days were investigated. Results: Osteoblasts cultured with C-PRF, i-PRF, and PRP demonstrated excellent biocompatibility. Proliferation was significantly higher in all platelet concentrates compared to the controls at one, three, and five days, with no significant differences among them, except on day one. Alkaline phosphatase and Alizarin Red S staining were significantly higher in the C-PRF and i-PRF groups compared to the PRP and control groups. However, RUNX2, ALPL, COL1A1, and OCN mRNA levels did not differ significantly among the three platelet concentrates throughout the study period. Conclusion: Our study indicates that the three liquid platelet concentrates enhance human osteoblast activity. C-PRF and i-PRF promoted greater differentiation and mineralization than PRP. These findings show that all liquid platelet concentrates positively influence human osteoblast proliferation and differentiation, making them suitable for clinical applications requiring bone regeneration.

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Abstract Objectives To investigate the effects of sodium fluoride (NaF), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), and titanium tetrafluoride (TiF4) on the prevention of demineralization in irradiated bovine enamel and dentin in vitro. Methodology The enamel and dentin sample blocks were subjected to 50 Gy of radiation and divided into five groups (n=13): the deionized distilled water group, the NaF group, the CPP-ACP group, the NaF + CPP-ACP group, and the TiF4 group. After being treated with various materials for 30 minutes, the samples were remineralized for 12 hours and demineralized for 48 hours. The samples were then evaluated by scanning electron microscope (SEM), atomic force microscope (AFM), energy dispersive spectrometer (EDS), and transverse microradiography (TMR). Data were analyzed by ANOVA and the Kruskal-Wallis H test (α=0.05). Results SEM and TMR indicated that the TiF4 group promoted more mineral deposits on the enamel and dentin samples, showing the least mineral loss and the lowest lesion depth. AFM results showed that the NaF + CPP-ACP group had the lowest enamel roughness (p<0.05), whereas the TiF4 group showed the lowest roughness in dentin samples (p<0.05). EDS showed that titanium (Ti) was deposited on the surface of the TiF4 group samples, whereas the NaF + CPP-ACP group more greatly aggregated fluorine. Conclusion TiF4 significantly impacted the prevention of demineralization in irradiated dental hard tissues. Combining NaF and CPP-ACP more effectively prevented demineralization than either agent used alone.

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Abstract This work aimed to evaluate the effect of ibuprofen on amelogenesis using a model of continuously growing incisors in Wistar rats. Methodology A total of eight female Wistar rats at weaning age were assigned to one of two groups (IBU and control). They were administered an 80 mg/kg dose of ibuprofen or an equivalent volume of distilled water for three weeks, then euthanized on day 16 of the experiment. Right hemimandibles were used to assess the mineral density of enamel using microtomography. The left hemimandibles were decalcified and processed to obtain sections, stained with Hematoxylin Eosin or immunohistochemical detection of amelogenin. Based on photomicrographs of hemimandibles, ameloblast and papillary layer height of the enamel and enamel organic matrix width were determined. The percentage of positive amelogenin was determined in immunohistochemically processed sections. Results were analyzed using Student’s t test. Results IBU-treated animals showed lower body weight gain throughout the experiment (p<0.05). Mineral density and enamel thickness showed no significant differences. No significant differences in the height of the papillary layer or the width of the organic matrix were observed. Amelogenin expression in the ameloblast layer was lower in the experimental group. No significant difference was found between groups. Conclusion The results obtained in this study model suggest that ibuprofen itself might not alter the amelogenesis process.

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Abstract Objective This study analyzed the synergistic effect between a recombinant Maquiberry (MaquiCPI-3) protein, sodium fluoride (NaF), and stannous chloride (SnCl2) against initial dental erosion in vitro. Methodology A total of 98 bovine enamel samples were prepared and allocated to seven treatment groups (n=14/group) as follows: deionized water (Water); commercial solution, 800 ppm Sn+2, 500 ppm F-, ElmexTM, Erosion, GABA, Therwil, BL, CH (Elmex); 500 ppm of fluoride (F-) from NaF (NaF); 500 ppm of F- from NaF and 800 ppm of tin (Sn+2) from SnCl2 (NaF+SnCl); 0.5 mg/mL MaquiCPI-3 (MaquiCPI-3); combination of MaquiCPI-3 and NaF (Maqui+NaF) and; combination of MaquiCPI-3, NaF and SnCl (Maqui+NaF+SnCl). Samples were treated with the respective solutions (250 μl, 2 min, 37°C, 250 rpm). After forming the acquired enamel pellicle (AEP) by adding human saliva from nine volunteers (250 μl, 1 h, 37°C, 250 rpm), the samples underwent acid challenge (1 mL, 1% citric acid, pH 3.6, 1 min, 25°C, 250 rpm). All procedures were performed in triplicate. Surface microhardness change percentage (%SMC) and relative surface reflection intensity (%SRI) were measured and analyzed by One-way ANOVA/Tukey’s tests (p<0.05). Results The Elmex, NaF, NaF+SnCl, MaquiCPI-3, Maqui+NaF, and Maqui+NaF+SnCl groups showed significantly lower %SMC compared with Water. The NaF, Sn+2, NaF+SnCl, MaquiCPI-3, Maqui+NaF and Maqui+NaF+SnCl groups exhibited significantly greater protection compared with Elmex. Maqui+NaF+SnCl revealed better enamel protection (significant) when compared with the MaquiCPI-3 and Maqui+NaF groups. Elmex, NaF+SnCl, MaquiCPI-3, Maqui+NaF, and Maqui+NaF+SnCl had a significantly higher %SRI compared to the Water and NaF groups, which did not differ between each other. Conclusion All treatment solutions provided protection against initial dental erosion in vitro. Formulations containing Maqui+NaF+SnCl2 offered superior enamel protection compared with MaquiCPI-3 alone.

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Abstract Background: Enhancer of zeste homolog 2 (EZH2) configures a histone methyl transferase enzyme that mediates the epigenetic silencing of target genes. Its overexpression has been related to tumor proliferation, metastasis, and poor prognoses. However, the study of this protein in salivary gland tumors (SGTs) remains limited. Objective: This study aimed to investigate EZH2 expression in common intra-oral SGTs, including pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC). Methodology: A total of 48 formalin-fixed paraffin-embedded tissue samples were analyzed, including 17 PA, 21 MEC, and 10 ACC cases. Immunohistochemical staining was performed using a rabbit recombinant monoclonal EZH2 antibody. EZH2 expression was described and quantified by the percentage of stained tumor cells. Results: Nuclear EZH2 expression occurred in most malignant SGTs (90.00% of ACC and 80.95% of MEC cases), whereas only one benign case of PA (5.88%) showed positive mild staining. Statistical analysis showed a significant difference in the mean of percentage positive cells in SGTs (p<0.001), particularly between benign and malignant SGTs (p<0.001). However, this study observed no significant differences between MEC and ACC (p=0.457). Conclusion: EZH2 expression significantly differed between malignant and benign SGTs, supporting its potential as a diagnostic marker for malignancy in these tumors.

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Abstract Objective: This study aimed to assess the risk of obstructive sleep apnea (OSA) in different types of cleft using the Pediatric Sleep Questionnaire (PSQ). The influence of sex, age, body mass index (BMI), and history of adenotonsillectomy surgery were also evaluated. Methodology: Parents or legal guardians of 195 patients with nonsyndromic cleft lip, lip and palate, and isolated palate aged from 5 to 18 years (9.11±3.09 years) were invited to answer the PSQ. The sample included 94 individuals with unilateral or bilateral complete cleft lip and palate, 56 individuals with cleft lip, and 45 individuals with isolated cleft palate. The frequency of high and low risk was estimated for the complete sample. Multiple logistic regression analysis was used to assess the association between sex, age, cleft type, adenotonsillectomy surgery, and BMI with the occurrence of high-risk of OSA. Significance was considered at 5%. Results: A high risk of OSA was observed in 51.3% of the sample. The high risk of OSA was present in 51.8%, 53.1%, and 46.6% of subjects with cleft lip, cleft lip and palate, and isolated cleft palate, respectively. History of adenotonsillectomy surgery was a predictor of high risk of OSA (OR=6.94). The other variables were not associated with OSA high risk. Conclusion: Different cleft types had similar frequency of OSA high risk. Patients with history of adenotonsillectomy surgery still presented high risk of OSA.

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Abstract Objectives Deproteinized bovine bone minerals (DBBMs) are effective for bone regeneration. However, their limited plasticity can hinder extensive bone defects treatment. This study aimed to develop a composite bone grafting material that is easy to deploy surgically and promotes robust bone regeneration. Methodology DBBM particles were mixed with a clinical-grade gelatin-based hemostatic gel (w/v ratio of 2/3) to create a composite material referred to as synthetic sticky bone (SSB). Structural properties were assessed using confocal laser scanning microscopy and scanning electron microscopy. To evaluate bone regenerative capacity, 20 male Sprague Dawley rats (eight to ten weeks old) with critical-size jawbone defects were treated with SSB, DBBM, or gelatin gel alone, with an empty defect as a control. Samples were collected at two and four weeks for microcomputed tomography (μCT) analysis of bone volume/total tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and trabecular separation (Tb. Sp). Histological analyses were conducted to examine material remnants and bone formation. Results SSB showed a binary paste-like composite property with enhanced injectability and plasticity. μCT and histological assessments confirmed that the SSB-treated group had significantly greater new bone formation compared to the DBBM-treated group after four weeks. Conclusions SSB, which is a paste-like composite of DBBM particles, and a clinical-grade gelatin-based hemostatic gel demonstrated improved structural plasticity and enhanced bone regeneration, offering a promising solution for treating extensive irregular bone defects.

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Abstract Objective To evaluate whether the presence of molar-incisor hypomineralization (MIH) is associated with a greater number of decayed teeth in schoolchildren. Methodology A cross-sectional study was conducted with a random sample of 347 children aged from seven to ten years in the Brazilian city of Diamantina. The International Caries Detection and Assessment System (ICDAS) criteria were used to determine the number of teeth with moderate/extensive caries (ICDAS codes 3-6). MIH was assessed according to the criteria of the European Academy of Paediatric Dentistry (EAPD). Sociodemographic data and data regarding children's habits were obtained via a questionnaire sent to parents/guardians. Descriptive analyses, Mann Whitney and Kruskal Wallis tests, and Poisson regression were performed. Results The prevalence of MIH was 20.5% and that of moderate/extensive caries was 39.2%. The mean number of teeth with moderate/extensive caries was 1.80 (SD±2.67). The mean number of decayed permanent teeth was 0.69 (SD=1.21), and the mean number of decayed primary teeth was 1.11 (SD=1.89). The number of teeth with moderate/extensive caries was associated with the presence of MIH in children (PR=1.45; 95% CI=1.03-2.04; p=0.031). Furthermore, the number of teeth with moderate/extensive caries was associated with lower monthly family income, high frequency of sugar consumption, and visible plaque (p<0.05). Conclusion The presence of MIH is associated with a greater number of decayed teeth in schoolchildren. Clinical relevance This study suggests that children with MIH are at higher risk of developing caries, emphasizing the importance of specific preventive care and early treatments for this condition. This can influence clinical practices, public health policies, and parental education.

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Abstract Objective this study aims to evaluate the sexual dimorphism of the morphometric features of the frontal sinus via cone beam computed tomography (CBCT) reconstructions, using a predictive formula and an artificial neural network (ANN). Methodology the morphometric features of the frontal sinuses obtained from 1,000 CBCT scans, equally distributed by sex, were assessed by two examiners. The frontal sinus morphometric features from 800 CBCT scans were analyzed using Mann-Whitney tests and a multivariate logistic regression model to identify key morphometric features for sex determination and to develop the predictive formula. These features were subsequently used to validate the predictive formula and the machine learning-based classification system. The predictive formula was evaluated using a set of 200 CBCT scans. The machine learning-based classification system consisted of a three-layer ANN trained with 80% of the CBCT scans and tested with the remaining 20%. Results Except for the higher frontal sinus index in females, males exhibited higher numerical values for height, width, and anteroposterior (AP) length. The significance level for all statistical tests was set at 0.05. Multivariate logistic regression identified the following four essential morphometric features: sinus height, anteroposterior length (depth) of the sinus, sinus width, and total sinus width. Both the predictive formula and the ANN demonstrated sexual dimorphism. The accuracy, specificity, sensitivity, precision, and F1- score values were 73.50%, 74.00%, 73.00%, 73.74%, and 73.37% for the regression model, and 76.00%, 84.00%, 68.00%, 80.95%, and 73.91% for the ANN, respectively. Except for sensitivity, the ANN outperformed the predictive formula regarding maximum specificity, accuracy, precision, and F1 score. Conclusion both methods, particularly the ANN, can potentially support sex estimation in the Brazilian forensic context.

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Abstract Background This study evaluated the altered expression levels of genes and cytokines associated with M1 and M2 macrophages during the development of periapical lesion (PL). Methodology PL was induced in the lower first molars of 96 mice. After the experimental periods of two, seven, 14, 21, and 42 days, the animals were euthanized and their jaws were dissected and submitted to the following analyses: microscopic descriptive analysis and fluorescence microscopy morphometry of PL size (mm2); quantitative gene expression analysis by qRT-PCR for M1 (Cxcl10, Cxcl9, and Nos2) and M2 phenotypes (Arg1, Fizz1, Ym1, and Mrc1); and M1- (GM-CSF, IFN-γ, IL-6, IL-1β, TNF-α) and M2- (IL-4, IL-13, and IL- 10) related cytokines quantification by Luminex. Data were statistically compared by ANOVA, Tukey post-test, Kruskal-Wallis, and Dunn post-test (α=5%). Results PL area and inflammatory infiltrate increased over experimental periods. From a contextual view, a pro-inflammatory profile and a higher activation of M1 phenotype markers in the initial periods of two and seven days could be observed. On day 21, microscopic features and M2 subtype predominance indicated a repair attempt. However, on day 42, an acute exacerbation of immunoinflammatory process and return to the M1 macrophage profile were evidenced. Conclusion M1 and M2 macrophage polarization-related markers were expressed alternately throughout the experimental periods, according to the stage of PL progression.

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Abstract Objective This study aimed to describe and compare morphofunctional orofacial aspects between subjects with and without Zika virus-related microcephaly. Methodology This was a descriptive, cross-sectional, case-control study with both qualitative and quantitative components. All subjects were born between 2015 and 2016, during the Zika virus outbreak in the Northeast region of Brazil. A total of 48 children were included: 24 with Zika-related microcephaly (MG) and 24 without the condition (CG). We performed the Preliminary Expanded Protocol of Orofacial Myofunctional Evaluation with Scores (OMES-E) for all subjects. Orofacial anthropometric measurements were obtained from 36 of the 48 participants, including 18 from the MG and 18 from the CG. Results We found lower swallowing efficiency scores in children with microcephaly aged 13–18 months. Significant differences (p<.001) were found between the MG and CG for scores related to the face, cheeks, and total stomatognathic functions. When stratified by age group, differences (p<.001) were found in total scores between MG and CG subjects in the age groups up to 24 months. We found lower scores in the 13–18-month group with microcephaly for swallowing efficiency: 1.3 (SD: .8) versus 5.3 (SD: 1.2); and in the 19–24-month group; for bite: 1 (SD: 0) and 3.9 (SD: .3), and 1.9 (SD: 2.7) and 9.5 (SD: .9); in addition to facial changes: 9.8 (SD: 1.2) and 11.8 (SD: .6). Differences were found in anthropometric orofacial measurements for the upper third of the face (d=-1.215, p<.001) (MG<CG); proportion between the upper third/middle third (d=.463, p=.018) (MG<CG); and upper lip and philtrum (MG>CG) (d=-.679, p<.001). Conclusion Subjects with microcephaly had altered orofacial myofunction, especially related to swallowing and chewing difficulties in early ages.

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Abstract Pharmaceutical agents targeting distinct therapeutic pathways can differently influence bone metabolism, notably exemplified by nitrogen-containing bisphosphonates and glucocorticoids. Objective This investigation sought to elucidate the effects of a low-dose administration of zoledronate (ZL) and dexamethasone (DX) on post-tooth extraction sockets healing in a murine model. Methodology In total, 40 young male C57BL/6J mice were assigned to four distinct groups by weight-stratified randomization: Control (C) - 0.9% saline solution, ZL - 0.05 mg/kg ZL, DX - 5 mg/kg DX, and ZL+DX - combined regimen of 0.05 mg/kg ZL and 5 mg/kg DX. All substances were intraperitoneally delivered on a weekly basis from four weeks before right upper incisor extraction and up to seven and 30 days after it, when blood was collected for biochemical analysis of bone markers and the maxillae were removed and prepared for microcomputed analysis of the trabecular architecture of the healing sockets and to set histological slices to be stained with hematoxylin and eosin and immunohistochemistry for TRAP and Runx2. Results Histopathology and microCT showed that DX administration correlated with impaired bone formation, manifesting as reduced bone volume/total volume and trabecular thickness. Conversely, ZL exposure disrupted bone viability. However, the combination of both showed enhanced maturation in bone remodeling at day 30. Notably, DX treatment notably reduced serum calcium and phosphate levels and total TRAP. Runx-2+ cells significantly increased in the Control group at day seven when compared to ZL and DX-ZL and at day 30 when compared to ZL. Conclusions Our findings showed that co-administering low doses of ZL and DX in young male mice augmented the recuperative processes of their post-extraction sockets when juxtaposed with either agent in isolation. Nevertheless, further comprehensive inquiries are needed to delineate the precise underlying mechanisms in a more controlled experimental context.

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Abstract Molar-incisor hypomineralisation (MIH) significantly impacts children's quality of life due to dental hypersensitivity, anxiety, and aesthetic concerns. Few studies have investigated these factors within the same sample, comparing varying levels of MIH severity to MIH-free controls. Objectives: This study evaluated dental hypersensitivity, anxiety, and aesthetic self-perception in children with mild MIH, severe MIH, and controls, and explored correlations between the studied variables. Methodology: A total of 605 students from a single school were evaluated: 110 children with MIH and 214 controls matched by age and sex. MIH severity was clinically assessed using the Ghanim criteria. Hypersensitivity was measured with the visual analogue scale (VAS) and the Schiff Cold Air Sensitivity Scale (SCASS). Anxiety and aesthetic concerns were assessed using the CFSS-DS and CQATA questionnaires, respectively. Results: Overall, 78 children had mild MIH and 32 had severe MIH. Median for dental hypersensitivity (p<0.001) and aesthetic self-perception (p=0.002) were significantly higher in the severe MIH group compared to both the control and mild MIH groups. No differences were found for anxiety. Elevated VAS-measured dental hypersensitivity levels and impaired self-perceived aesthetics were significantly correlated with greater MIH severity (p<0.05). Spearman's correlation analysis further revealed significant positive correlations between anxiety/fear and VAS scores (p=0.023, r=0.239), between anxiety/fear and aesthetic self-perception scores (p=0.007, r=0.282), and between dental appearance classification and VAS hypersensitivity scores (p=0.035, r=0.222). In contrast, SCASS hypersensitivity scores did not significantly correlate with either anxiety/fear or dental appearance classification (p>0.05). Conclusions: Children with severe MIH showed higher dental hypersensitivity and greater perceived aesthetic impairment than children with mild MIH or without MIH.

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Abstract The infectious and inflammatory process of the periodontal tissues can contribute to hyperglycemia in patients with diabetes. Objective The objective of this study was to evaluate the effect of non-surgical periodontal therapy on glycemic control in individuals with type 2 diabetes mellitus. Methodology In this clinical trial with two months of follow-up, 31 participants were included, with 15 having adequate glycemic control and 16 inadequate glycemic control. The participants underwent non-surgical periodontal therapy. Biological, social, and behavioral variables were collected. Periodontal clinical examination was performed at baseline and two months after the intervention. Laboratory tests to assess serum levels of glycated hemoglobin, fasting glucose, and C-reactive protein were requested for all participants at baseline and two months after periodontal treatment. Results The difference in glycated hemoglobin levels between baseline and two months after non-surgical periodontal therapy was statistically significant in the total sample (p=0.045) and in the group of individuals with adequate glycemic control (p=0.016). No significant difference was observed in glycated hemoglobin levels in the group of individuals with inadequate glycemic control. No significant variation was observed in fasting glucose and C-reactive protein levels after treatment in the studied sample. A reduction in probing depth, gingival inflammation, and gain in clinical attachment was observed in the total sample and in both groups according to glycemic control. Conclusion Periodontal intervention may contribute to improved glycemic control in individuals with type 2 diabetes mellitus and periodontitis (Brazilian Clinical Trials Registry RBR-9fvwk4m).

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Abstract 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.

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Abstract 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

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Abstract Objectives Finding certain biomarkers and threshold values of periodontitis and incorporating them into classifications can further highlight its impact on systemic health. This cross-sectional observational study aims to evaluate the efficacy of some biomarkers in grading periodontitis using artificial intelligence (AI) models. Methodology AI models were developed to automatically classify periodontal status (N=240) and grades in periodontitis patients (n=120) using Python based on sociodemographic, anthropometric, clinical, radiological, and biochemical attributes. A total of 35 serum levels of whole blood attributes (white blood cell (WBC), platelet, erythrocyte, neutrophil, lymphocyte counts, and mean platelet volume), lipid profile [triglycerides; high-, low-, and very low-density lipoproteins (HDL, LDL, VLDL), and total cholesterol levels], salivary and serum interleukin (IL)-1β and matrix metalloproteinase (MMP)-8 levels), and 11 other attributes were used in the current classification. Results In total, 23 out of 46 attributes achieved a 0.967 classification accuracy, whereas nine, a 0.858 classification accuracy. Attributes such as WBC, serum IL- 1β, triglyceride/HDL ratio, neutrophil/lymphocyte ratio, and HDL were instrumental in periodontal status classification. HDL, LDL, neutrophil/lymphocyte ratio, total cholesterol, salivary IL-1β, and MMP-8 were key attributes in grading. Conclusions AI models showed significant classification accuracy, particularly with serum and salivary IL-1β levels and other blood parameters, underscoring the potential of these biomarkers, which could be integrated into the current classification.

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Abstract The success of orthodontic treatment depends on several factors that may influence the desired outcome, such as patient motivation and cooperation. Objective: This study compared patient compliance during the first year of orthodontic treatment using aligners and conventional fixed appliances. Methodology: The sample included 39 participants (22.1±4.62 years, 25 males, 14 females) randomized into two groups: orthodontic aligners (OA, 20 patients, 23.7±5.6 years, 12 males, 8 females) and fixed appliances (FA, 19 patients, 20.5±4.5 years, 12 males, 7 females). Patient compliance was measured using the Orthodontic Patient Cooperation Scale (OPCS) composed of 10 questions related to attitudes and attendance of patients in relation to treatment. The questionnaire was applied at three different points: at 3 months (T1), at 6 months (T2), and at 12 months (T3) of treatment. The psychosocial profile of the patients was assessed using the anxiety (IDATE) and stress (PSS-14) questionnaires. Both groups were comparable in age, gender and psychosocial profile. Compliance comparisons between groups at T1, T2 and T3, as well as between genders, were performed using the Mann-Whitney test. Comparison between T1, T2 and T3 were performed using the Friedman test. The correlation between age and compliance scores was assessed using the Spearman's correlation coefficient. The psychosocial profile was analyzed using the Independent t-test. All tests considered p<0.05. Results: The type of appliance (OA or FA) and the time of assessment did not significantly influence patient compliance. The age and gender of patients were not correlated with their degree of compliance. Patient compliance was similar in the first 12 months of treatment, regardless of the protocol used, the patient's gender and age. Conclusions: The level of patient compliance with orthodontic treatment was not influenced by the type of appliance (conventional fixed appliances or aligners), nor by the patient's age or gender.

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Abstract Objective Tongue squamous cell carcinoma (TSCC) is an aggressive oral cancer with notable treatment resistance. This in vitro study investigated anti-cancer effects of honey bee venom (BV)—a mixture of bioactive compounds—on the human TSCC cell line. Methodology The cytotoxicity of serial BV concentrations (0.01–100 µg/mL) was tested on the cultured human TSCC cell line (HNO-97) to determine the half-maximal inhibitory concentration (IC50) value. Group I (BV) included cells treated with IC50 of BV, and Group II (control) received no treatment; both were incubated for 48 hours. The apoptotic effect of BV was evaluated using the Annexin V assay and the BAX and BCL-2 gene expression. The BV effect on cell viability, proliferation, and division was evaluated by cell cycle assay. Additionally, Transwell migration assays were performed to demonstrate the potential impact of BV on cell migration. Results BV showed dose-dependent cytotoxicity and anti-proliferative activity on HNO-97 cells (IC50: 12.96 μg/mL). The treated group exhibited cell cycle arrest, reduced cell migration, significantly decreased BCL-2 gene expression (p=0.001), and increased BAX gene expression (p=0.03) compared to the untreated group. Conclusion BV demonstrated anti-cancer activity on human TSCC by inducing apoptosis and inhibiting cell migration. These findings warrant further preclinical investigations to evaluate BV as an alternative for current tongue carcinoma therapies.

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Abstract Objective: To investigate the effects of dealcoholized red wine supplementation on blood cells and the redox state in male rats with established apical periodontitis (AP). Methodology: Thirty-two male Wistar rats were assigned to one of four groups: control (C), dealcoholized red wine (DRW), red wine (RW), and alcohol (AL). AP was induced, and supplementation was administered for 30 days, starting 30 days after AP induction. At the end of the 60th day, the maxillae were removed for AP radiographic analysis and blood was collected for blood cell and redox state analysis. Statistical tests were applied (p<0.05). Results: The C and DRW groups showed higher weight gain percentages (p<0.05). The DRW and AL groups exhibited the smallest and the largest periapical lesion areas, respectively (p<0.05). The RW and DRW groups showed similar red blood cell parameters to the C group but different from the AL group (p<0.05). Lymphocyte counts were smaller in the DRW and RW groups compared to the AL and C groups (p<0.05), and the neutrophil count was lower in the AL group (p<0.05). No significant differences were found in monocytes and in lipid and protein oxidative damage. Superoxide dismutase activity was lower in the AL group (p<0.05). The DRW group presented a higher glutathione concentration compared to the RW and AL groups (p<0.05). Conclusion: DRW reduced periapical lesion size and altered the blood profile by reducing the lymphocyte count and increasing the concentration of endogenous antioxidants such as GSH in male rats with established AP.

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Abstract The scanned abutment file for the digital design of restorations can be either obtained directly using the intraoral scanner (IOS) or scanning the impression or the working model with the extraoral scanner (EOS). The trueness of the scanned file pertains to its effect on the accuracy of the restoration. Objective This study aimed to compare the trueness of scan files from different intraoral scanners (IOSs) and the hybrid workflow using the E3 extraoral scanner (EOS) for ceramic restoration. Methodology The model of the mandibular right first molar was prepared for the ceramic crown, and it was scanned with the EOS in reference Standard Tessellation Language (STL) file format. The following seven experimental groups were investigated. The IOSs—iTero Element 5D (IT), Trios 4 (TF), Medit i700 (MI), Primescan (PM), Virtuo Vivo (VV)—were directly scanned on the prepared model. The silicone impression of the prepared model was scanned with EOS (IS). The working model poured from the impression was scanned with the EOS (WS). The test STL file was trimmed and superimposed on the reference STL file for the trueness assessment using Geomagic Control X. The point deviation at the surface and margin of each group were compared. The mean deviation was calculated and statistically analyzed with One-way ANOVA (α=0.05). The minimum and maximum deviation of each area were also recorded. Results Compared with the other groups, the impression scan group had a significantly greatest deviation (p<0.05) in surface (37.65±1.14 µm), margin (63.57±5.85 µm) and overall (50.61±3.28 µm). The WS group showed significantly greater deviation (p<0.05) in surface (23.93±1.20 µm), margin (46.18±2.00 µm) and overall (35.05±1.16 µm) than the IOS groups. In some IOS groups, the deviation was also significantly different (p<0.05). Conclusion The IOS is recommended for obtaining the scanned file due to its lesser deviation when compared to the hybrid workflow. While statistical differences exist among IOSs, the clinical relevance of these differences appears minimal. If the IOS does not exist, scanning the working model is preferred over scanning impressions directly. However, further clinical validation studies are necessary to confirm this finding.

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Abstract 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.

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Abstract Considering that a single passive application of hydrochloric acid (HCl) as a resin infiltration pretreatment can remove between 20 and 45 µm of enamel and cause etching that extends up to 2 mm beyond the white spot lesions (WSLs), it is plausible that its repeated and active applications could result in a greater amount of dental tissue being removed. Objective To evaluate the enamel surface loss and micromorphology after etching with 15% HCl using two application methods (passive-P and active-A) and varying numbers of applications (C-placebo – 120 s; 1x HCl – 120 s; 2x HCl – 120 s + 120 s; 3x HCl – 120 s + 120 s + 120 s). Methodology Bovine incisors with ≤0.3 µm initial curvature were randomized into eight groups (n=12) based on microhardness, followed by WSL simulation. A central window was etched according to experimental conditions, and surface loss was assessed using optical profilometry and micromorphology via scanning electron microscopy (SEM). Two-way ANOVA and Tukey's test were used for surface loss, and the chi-square test evaluated the association of experimental conditions with etching patterns (α=0.05). Results 1xP generated intermediate mean surface loss, positioned between the values observed for passive control (PC) and active control (AC), and those for 2xP and 3xP. Losses from active applications were significantly higher than passive ones and were increased by the number of applications. SEM showed Types II and III etching patterns and Type II was more frequent. There was no association between treatment and etching pattern. Conclusion Multiple and active HCl applications may raise concerns about removal of the remaining tooth structure, challenging the principles of minimal intervention dentistry.

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Abstract Menopause causes specific hormonal alterations in women that make them more susceptible to salivary changes, such as decreased saliva flow, which can lead to xerostomia, modified taste, and a burning sensation in the mouth. Objectives This study aimed to determine which of two treatments—bone marrow-derived mesenchymal stromal cells (BM-MSCs) or estrogen—more effectively ameliorate the postmenopausal degenerative effects on the parotid salivary glands of ovariectomized rats by histological, immunohistochemical, and malondialdehyde (MDA) evaluations. Methodology The study specimen involved 70 female albino rats. Group I received saline, and were subdivided into sham-operated and vehicle-treated. Group II was subjected to bilateral ovariectomy and received no treatment. Group III was subjected to bilateral ovariectomy and, one week later, treatment with subcutaneous injections of 1 mg/kg/daily estrogen for 12 weeks. Group IV underwent bilateral ovariectomy and, one week later, received a single intraglandular injection of a BM-MSC solution. At the end of the experiment, the rats were euthanized, and their parotid glands were dissected and processed for H&E stain, caspase 3, and MDA evaluations. Results The histological and immunohistochemical findings in Group II showed marked degenerative changes in the parotid gland. However, in Groups III and IV, regeneration was observed following treatment with estrogen and BM-MSCs, respectively. The estrogen and BM-MSCs groups showed significant decrease in MDA levels in the parotid gland relative to the ovariectomized group and nearly comparable to control. Conclusion BM-MSCs and estrogen show histological efficacy in regenerating the parotid salivary glands of ovariectomized rats.

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Abstract 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.

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Abstract Artificial intelligence (AI) is transforming access to dental information via large language models (LLMs) such as ChatGPT and Google Gemini. Both models are increasingly being used in endodontics as a source of information for patients. Therefore, as developers release new versions, the validity of their responses must be continuously compared to professional consultations. Objective: This study aimed to evaluate the validity of the responses provided by the most advanced LLMs [Google Gemini Advanced (GGA) and ChatGPT-4o] to frequently asked questions (FAQs) in endodontics. Methodology: A cross-sectional analytical study was conducted in five phases. The top 20 endodontic FAQs submitted by users to chatbots and collected from Google Trends were compiled. In total, nine academically certified endodontic specialists with educational roles scored GGA and ChatGPT-4o responses to the FAQs using a five-point Likert scale. Validity was determined using high (4.5-5) and low (≥4) thresholds. The Fisher's exact test was used for comparative analysis. Results: At the low threshold, both models obtained 95% validity (95% CI: 75.1%- 99.9%; p=.05). At the high threshold, ChatGPT-4o achieved 35% (95% CI: 15.4%- 59.2%) and GGA, 40% (95% CI: 19.1%- 63.9%) validity (p=1). Conclusions: ChatGPT-4o and GGA responses showed high validity under lenient criteria that significantly decreased under stricter thresholds, limiting their reliability as a stand-alone source of information in endodontics. While AI chatbots show promise to improve patient education in endodontics, their validity limitations under rigorous evaluation highlight the need for careful professional monitoring.

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Abstract Objective This randomized, parallel-group clinical trial aimed to evaluate the one-year clinical performance of the Beautibond Xtreme adhesive system (Shofu Inc., Kyoto, Japan) applied with different bonding strategies in Class I and Class II posterior restorations. Methodology A total of 22 patients (14 female and 8 male, aged ≥18 years) requiring restorative treatment provided 152 teeth with Class I or Class II carious lesions or defective restorations. Restorations were randomly assigned to six groups, including two control groups (Class I and II using the total-etch technique) and four test groups (Class I and II using either the self-etch technique or selective enamel etching). All restorations were performed using Beautibond Xtreme adhesive combined with Beautifill LS composite resin. Clinical performance was assessed at baseline, six months, and one year using modified United States Public Health Service (USPHS) criteria, including anatomic form, marginal adaptation, marginal discoloration, color match, surface texture, secondary caries, postoperative sensitivity, and retention. Randomization was performed with a computer-generated sequence, and two calibrated, blinded examiners (Kappa = 0.84) conducted all evaluations. Results No significant changes were observed in anatomic form, color match, surface texture, secondary caries, postoperative sensitivity, or retention over time in any group (p>0.05). However, restorations performed using the self-etch technique showed significant deterioration in marginal adaptation and marginal discoloration from baseline to six months and one year (p<0.05). Significant differences were also observed when comparing these restorations to the total-etch and selective enamel etching groups (p<0.05). Conclusion The Beautibond Xtreme adhesive system demonstrated better clinical performance when applied with total-etch or selective enamel etching techniques compared to the self-etch mode for both Class I and Class II restorations after one year of follow-up.

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Abstract 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.

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Abstract Dentures containing nanoparticles must maintain appropriate ion dynamics and physio-mechanical properties. Objective this study evaluated the effects of incorporating 5wt% and 10wt% surface pre-reacted glass-ionomer S-PRG nanoparticles into a polymethylmethacrylate (PMMA) resin on multiple-ion exchange rates following recharge with an S-PRG solution, flexural strength, surface roughness, and hardness. Methodology In total, 72 disc-shaped and 32 rectangular specimens were fabricated from PMMA resin containing 0, 5, and 10% S-PRG nanoparticles, and 20% S-PRG microparticles by weight. In total, six-disc specimens per group were tested for surface roughness and hardness using a contact profilometer and the Vickers hardness test, respectively. The remaining discs were immersed in 11 ml of deionized water for 24 hours, followed by an analysis of their aluminum, boron, sodium, silicate, strontium, and fluoride concentrations. They were then recharged with a 10% S-PRG solution for 24 hours, alternating with deionized water for five cycles, before their ion levels were reanalyzed. Rectangular specimens underwent flexural strength testing via the three-point bending method. Data were analyzed using two-way repeated-measures analysis of variance with a significance level of p<0.05. Results PMMA resin modified with S-PRG nanoparticles released all ions except aluminum. The 10wt% nanoparticle group showed significantly higher ion release than the 5wt% nanoparticle and control groups. While the initial ion release from the 10wt% nanoparticle was comparable to the 20wt% microparticle, recharge resulted in slower ion release from nanoparticles. Incorporating S-PRG nanoparticles altered the surface characteristics and flexural strength of the resin (which remained within international standards). Conclusion Incorporating 5 and 10wt% S-PRG nanoparticles into PMMA resin facilitated the release of boron, silicate, strontium, sodium, and fluoride ions, but not of aluminum ones following recharge with an S-PRG solution and maintained compliance with standards. The 10wt% nanoparticles achieved a balance between enhanced ion release and the physio-mechanical properties required for denture base resins.

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Abstract Periodontitis involves complex immune, epithelial, and metabolic disruptions. High-throughput transcriptomic approaches can reveal key regulatory networks underpinning disease progression. Objective To investigate the transcriptomic profile and dysregulated molecular pathways associated with severe periodontitis. Methodology Gingival tissues from patients with severe periodontitis (n=11) and periodontally healthy controls (n=11) were compared using RNA sequencing in this cross-sectional study. Differentially expressed genes (DEGs) were identified and analyzed using Ingenuity Pathway Analysis (IPA). Selected DEGs were validated at the protein level via immunohistochemistry (IHC). Results A total of 909 DEGs were upregulated and 742 were downregulated in periodontitis versus healthy tissues. Highly upregulated genes included MT-RNR1, MTRNR2L12, pseudogenes, long non-coding RNAs, and immunoglobulins. Downregulated genes included ADGRG7, C6orf15, members of enzyme families, keratin family members, loricrin (LOR), and immune modulators, such as CD207 (Langerin) and DEFB4A. IPA predicted the Wnt/β-catenin pathway as the most upregulated and the IL-17 signaling pathway as the most suppressed canonical pathway in periodontitis. The expression of the level of protein of LOR, Wnt10b, JUN, and FOS was confirmed by IHC. Conclusion Dysregulation in key canonical signaling pathways and the altered expression of genes critical to cell chemotaxis, innate immunity, and epithelial barrier integrity seem to play a pivotal role in the pathogenesis of periodontitis.

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Abstract Diabetic periodontitis (DP) features accelerated alveolar bone destruction driven by impaired immune regulation and compromised bone metabolism. Objective This study investigated the therapeutic potential of Panax notoginseng saponins (PNS) against alveolar bone loss in a rat DP model and elucidated its mechanisms of action. Methodology Male Sprague-Dawley rats were allocated to four groups: control, periodontitis control (CP), diabetic periodontitis (DP), and DP + PNS (80 mg/kg/day). Diabetes was induced by streptozotocin injection, followed by ligature-induced periodontitis at the maxillary first molar. After 4 weeks of PNS treatment, alveolar bone samples were analyzed by micro-CT, histomorphometry, immunohistochemistry, and immunofluorescence. Results Micro-CT and H&E analyses revealed severe alveolar bone resorption in DP rats, whereas PNS treatment substantially mitigated these destructive changes. TRAP staining demonstrated that PNS significantly suppressed osteoclast formation and activity. Immunohistochemistry detected upregulated expression of OCN in PNS-treated groups, indicating enhanced osteogenic differentiation. Immunofluorescence analysis showed that PNS promoted a phenotypic shift in macrophages, reducing pro-inflammatory M1 polarization (iNOS+) while increasing anti-inflammatory M2 populations (Arg-1+). This shift correlated with decreased interleukin-6 (IL-6) and elevated interleukin-10 (IL-10) levels. Conclusions PNS attenuates alveolar bone loss in diabetic periodontitis by inhibiting osteoclastogenesis, stimulating osteogenic activity, and modulating macrophage polarization toward an anti-inflammatory M2 phenotype. These actions collectively reduce inflammation and promote tissue regeneration, highlighting PNS as a promising candidate for managing DP-related bone destruction.

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Abstract Background Temporomandibular disorders (TMDs) comprise a heterogeneous group of musculoskeletal conditions affecting the temporomandibular joint, masticatory muscles, and associated structures. Growing evidence highlights the role of genetic predisposition as a significant contributor to TMD. Aim This study aimed to investigate genetic aspects involved in TMDs etiology. Methodology A cross-sectional study was conducted with 249 adolescents, of whom 149 were affected by TMD. Genomic DNA was extracted from buccal cells, and single nucleotide polymorphisms (SNPs) in DRD2 (rs6275 and rs6276), ANKK1 (rs1800497), COMT (rs6269 and rs4818), and 5-HTT genes (rs3813034 and 1042173) were analyzed. Allelic and genotypic distribution, haplotype, and diplotype analysis were performed using PLINK software version 1.06. Multifactor dimensionality reduction (MDR) was applied to identify SNP-SNP interactions and generate an interaction graph. Results In total, three possible single-locus allele combinations were obtained for haplotype and diplotype analyses (rs6275|rs6276 in DRD2, rs6269|rs4818 in COMT and rs3813034|rs1042173 in 5-HTT), but no associations with TMD were observed (p>0.05). However, MDR analysis for gene-gene interactions revealed a synergistic relationship between rs6275 (DRD2), rs6269 (COMT), and rs1042173 (5-HTT) that predisposes to TMD (p=0.050). Conclusion MDR analysis suggests a possible synergistic interaction among SNPs in the DRD2, COMT, and 5-HTT genes that may contribute to TMD susceptibility in adolescents.

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Abstract Objective This study investigates the role of peroxisome proliferator-activated receptor alpha (PPARα) in regulating macrophage polarization and inflammatory signaling under stimulation by periodontal pathogens. Methodology THP-1-derived macrophages were stimulated with Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in the presence or absence of PPARα agonists fenofibrate and WY14643, or the antagonist GW6471. Protein expression levels of TNF-α, IL-10, and phosphorylated NF-κB were assessed by Western blot. Immunofluorescence staining was used to evaluate IL-10, NF-κB, and CD36 expression. Flow cytometry quantified changes in macrophage polarization markers, including CD14+CD86+ (M1) and CD68+CD206+/CD163+ (M2) populations. THP-1 cells transfected with a secreted embryonic alkaline phosphatase (SEAP) reporter plasmid were treated with Pg-LPS (1 μg/mL) ± fenofibrate (50 μM) to assess NF-κB/AP-1 activity. PPARα reporter cells were treated with increasing concentrations of GW590735 or WY14643 and exposed to TNF-α, LPS, or GW6471+LPS to evaluate PPARα transcriptional activity. Results PPARα activation by fenofibrate reduced TNF-α expression in Pg-LPS-stimulated macrophages and attenuated NF-κB signaling via both TLR2 and TLR4 pathways. Fenofibrate significantly increased IL-10 and CD36 expression, inhibited Pg-LPS-induced NF-κB nuclear translocation, and promoted a phenotypic shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages. Moreover, inflammatory stimuli such as TNF-α and LPS suppressed PPARα activity, which could be restored by potent PPARα agonists. Conclusion These findings suggest that PPARα activation modulates macrophage polarization and suppresses inflammatory signaling in response to periodontal bacterial antigens.

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Abstract Objective This study used three-dimensional (3D) stereophotogrammetry to compare changes in facial soft tissues of patients with skeletal class II malocclusion with mandibular retrognathia treated with orthognathic surgery (OS) or Herbst appliance (HA). Methodology This retrospective study included 15 adults treated with bilateral sagittal split osteotomy without genioplasty (OS) and 16 adults treated with HA. The patients were treated successfully, with class I occlusal relationships with normal overjet and overbite. Three-dimensional stereophotogrammetric records acquired in habitual occlusion from before and after fixed orthodontic treatment were analyzed. Lateral cephalometric radiographs were used to evaluate skeletal parameters and sagittal oropharyngeal airway length. Results In HA-group, mandibular corpus length, anterior facial height, posterior facial height, Bº, vertical angle, and mentolabial angle increased; lower facial width, mandibular angle, mandibular convexity angle, ANBº, and Aº decreased. In OS-group, mandibular length, mandibular corpus length, and facial convexity angle increased significantly compared with those in HA-group; posterior facial height, Bº, vertical angle, and mentolabial angle also increased, but mandibular angle and ANBº decreased significantly. Only a significant difference in coordinate changes was observed for the pogonion in the sagittal direction. According to the cephalometric analysis, SNBº and Pg-NA perpendicular measurements increased significantly in the OS group compared with the HA group. In both groups, sagittal oropharyngeal airway length increased significantly post-treatment, with no significant intergroup difference. Conclusion In patients treated with OS, skeletal advancement resulted in greater increases in mandibular and corpus lengths, along with forward positioning of the pogonion. Based on 3D soft tissue and cephalometric comparisons, the Herbst appliance seems to be a viable non-surgical alternative for young adults with moderate Class II malocclusion. Both treatment modalities also contributed to significant improvements in sagittal oropharyngeal airway length.

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Abstract Objective Vagus nerve stimulation (VNS) can inhibit inflammation in various diseases by activating the cholinergic anti-inflammatory pathway. However, whether VNS could attenuate periodontitis by activating α7-nicotinic acetylcholine receptor (α7-nAChR) remains unknown. Methodology Ligature induction was utilized to establish the periodontitis rat model. Periodontal indices like bleeding, tooth mobility, and probing depth, were measured. Bone mineral density, trabecular thickness, and length of the cement-enamel junction to the alveolar bone crest were analyzed using micro-CT. Immunohistochemistry assessed bone morphology and inflammatory levels. Inflammatory cytokines were detected using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. For the in vitro inflammation model, RAW264.7 cells were stimulated with lipopolysaccharides and acetylcholine to study inflammatory responses. Results VNS significantly improved periodontal health and reduced alveolar bone loss in periodontitis rats. VNS alleviated inflammation by suppressing pro-inflammatory cytokines, including IL-1β, IL-6, and IL-18, enhanced bone formation, and activated the cholinergic anti-inflammatory pathway, as evidenced by increased α7-nAChR expression. Additionally, acetylcholine activation of α7-nAChR in RAW264.7 cells inhibited pro-inflammatory responses and promoted anti-inflammatory responses. Conclusion These findings suggest that VNS can effectively reduce inflammation and improve periodontal outcomes in periodontitis.

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Abstract Objectives: To evaluate the effect of wavelength and radiant emittance on light transmittance and heat generation through dental resin-based composites. Methodology: Light-emitting diodes on the blue, green, and red wavelength spectra were assembled and characterized using a spectrometer (MARC Resin Calibrator, BlueLight Analytics). Voltage (V) and amperage (A) from each LED was set up to emit a 500-, 1000-, 2000-, 3000-, or 4000-mW/cm2 radiant emittance. A self-cured resin-based composite model was fabricated in two pastes, one with benzoyl peroxide and another with ethyl 4-dimethylaminobenzoate. The two pastes were mixed and placed into a mold (ø=10 mm, 2 mm thick) until completely hardened. A power analysis was conducted to determine the sample size to provide a power of at least 0.8 and α=0.05. Light transmittance through the 2-mm thick composite-based sample was evaluated using a spectrometer (n=10). Heat generation (oC) in the resin-based composite sample induced by the exposure to the tested wavelength spectra and radiant emittances were recorded using an infrared camera (FLIR ONE PRO, FLIR Systems) (n=10). Statistical analyses were performed using analysis of variance and the Tukey's test for multiple comparisons. Results: Light transmission systematically increased based on radiant and wavelength emittances (p<0.0001). Heat generation was directly proportional to radiant emittance but indirectly proportional to wavelength emittance (p<.0.0001). Conclusions: Despite its limitations, this study found that increasing wavelength emittance seems to configure a great alternative to increase light transmittance through resin-based composite restorations while reducing heat generation.

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Abstract Diabetes significantly impairs bone healing via several mechanisms, including sustained inflammation, oxidative stress, and poor osteogenic responses. Fully reduced isoform of High Mobility Group Box 1 with three serine substitutions (3S-HMGB1) has shown regenerative properties while being resistant to oxidative degradation. Objective: This study evaluated the therapeutic potential of a single local injection of 3S-HMGB1 in early osseointegration under diabetic conditions in mice. Methodology: A total of 48 male 129/Sv mice (24 non-diabetic [ND], 24 diabetic [D]) received titanium implants following maxillary first molar extraction. ND and D mice (n:12) were injected with either saline (control) or 3S-HMGB1 (0.75 mg/kg) into the fresh extraction socket. Osseointegration was evaluated at 7 and 21 days post-implantation using microCT, histology (bone-to-implant contact [BIC] and birefringence), and immunohistochemistry for Runx2 and CXCR4. Results: ND controls exhibited early osteogenic activity, with a predominance of Runx2-positive cells at 7 days and successful osseointegration by 21 days. In contrast, D controls showed reduced numbers of Runx2-positive cells and markedly lower BV/TV, indicating compromised bone healing at 21 days. Treatment with 3S-HMGB1 resulted in significantly increased bone volume at the implant site in D animals (55.6±7.20% vs. 44.6±6.23%) and restored BIC from 44.9±9.32% (D controls) to 61.78±11.31% (D 3S-HMGB1), near ND levels (65.16±7.64%). Both ND and D groups treated with 3S-HMGB1 presented enhanced collagen organization. No significant differences were found in CXCR4 between groups; however, in D animals, a distinct peri-implant staining pattern suggested impaired recruitment despite preserved stem cell niches in the bone marrow. Conclusions: Collectively, our findings indicate that a single injection of redox-stable 3S-HMGB1 may represent a promising regenerative strategy to mitigate early implant failure in diabetes. Future studies should explore sustained delivery approaches to enhance long-term outcomes.

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Abstract Immune cells play diverse roles in cancer development. Myeloid cells are key drivers of tumor-escape mechanisms as they suppress immune responses, facilitate metastasis, and contribute to therapy resistance. In particular, macrophages can be polarized into an inflammatory M1 (anti-tumor) or anti-inflammatory M2 (pro-tumor) phenotype. M2 macrophages are associated with tumor progression, as they secrete factors that promote tumor angiogenesis, suppress T-cell activity, and correlate with poor clinical outcomes in squamous cell carcinoma (SCC). Given this context, this study aims to demonstrate the biological effects of monocytes and both M1 and M2 macrophages in squamous cell carcinoma. Our data indicate higher CD163 immunoreactivity in biopsies from SCC patients. Furthermore, we found that a conditioned medium (CM) containing bioactive compound generated by M2 macrophages enhances the proliferation and invasion of the SCC-25 cell line in vitro. Surprisingly, CM derived from blood CD14+ monocytes increased SCC-25 proliferation at the same rate of M2 macrophages-CM. M1 macrophages conditioned medium significantly enhanced the motility and decreased proliferation in Detroit 562 cells. The analysis of tumor-associated transcripts showed that both M1 and M2 conditioned medium induced high levels of EPCAM mRNA and significantly decreased the expression of MYC, an epithelial-to-mesenchymal transition marker, in SCC cell lines. Detroit cells exposed to conditioned medium from monocytes and macrophage also showed elevated SOX2 mRNA levels. The findings suggest that monocytes and macrophage mediators exert distinct biological effects on SCC cell lines.

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Abstract Objective The oral microbiome is one of the most complex microbial ecosystems in the host. This study aimed to investigate and characterize the oral microbiome composition in Kazakhstani adolescents associated with dental caries. Methodology The study included 312 adolescents, with 241 individuals presenting with caries and 71 caries-free, aged 12-15 years. Dental caries assessment was performed using DMFT (Decayed, missed, filled teeth) index. Oral samples were collected, and 16S rRNA (16S ribosomal ribonucleic acid) gene sequencing targeting the V3-V4 hypervariable regions on an Illumina MiSeq platform was performed to profile the microbial communities. Functional metagenomic predictions were generated using PICRUSt2 v2.5.0, using the KEGG database for bacterial pathway abundance estimation. Data analysis was conducted using Python 3.9.16 and R 4.2.2. Results The alpha diversity was insignificant, while beta diversity analysis demonstrated clear distinctions by Bray-Curtis (F=2.5, p=0.003) and weighted UniFrac distances (F=4.4, p=0.002). The Neisseria and Prevotella genera, and Gammaproteobacteria class showed significant associations with dental caries (MaAsLin2 p≤0.05, LDA≥2), stronger predictive power (AUC=0.65, F1=0.83), and higher predicted functional activity through glutathione metabolism, RNA degradation, and unsaturated fatty acid metabolism pathways. Conclusions This study identified specific oral microbiome patterns associated with dental caries in Kazakhstani adolescents, revealing interactions between key bacterial taxa and metabolic pathways.

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Abstract Periodontitis is an inflammatory disease characterized by producing alterations in periodontal tissues, but it has been associated with the manifestation of systemic alterations, related to those produced in liver tissue. This study aims to evaluate the progression of liver damage caused by ligation-induced periodontitis in rats with time intervals of ten to 80 days. Methodology Overall, 40 rats were divided into five groups: control (no ligatures), P10, P20, P40, and P80 (teeth with ligatures at intervals of ten, 20, 40, and 80 days) in which we verified liver disease caused by periodontitis. Oral parameters were evaluated: gingival bleeding index (GBI), probing pocket depth (PPD), dental mobility (TM), myeloperoxidase activity (MPO), alveolar bone height (ABH). Liver parameters were evaluated: liver weight, histopathological scores for steatosis, inflammation, and necrosis in the liver; glutathione (GSH) and malondialdehyde (MDA). Serum parameters were also evaluated: concentrations in liver tissues, blood levels of albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, total cholesterol, and total proteins. Results The results showed that the hepatic steatosis score gradually increased (P<0.05) in rats with induced periodontitis for up to 20 days (P20); and the rats with ligatures for 40 (P40) and 80 days (P80) had stable scores compared to the P20, without any further worsening, similarly occurred with GSH, MDA, and total cholesterol. Conclusions This study indicated that liver alterations caused by ligature-induced periodontitis are progressive in early stages (0-20 days) and reach a plateau in later stages (40-80 days).

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Abstract Objective This study aimed to evaluate the clinical performance of posterior resin composite restorations (Class I and II), bonded with a universal adhesive using three application modes over 26 months, comparing the adapted FDI and USPHS criteria. Methodology In total, 138 Class I and II cavities were restored using Scotchbond Universal adhesive (3M ESPE) in three application modes: etch-and-rinse (ER); selective enamel etch (SEE), and self-etch (SE). All cavities were restored with FiltekTM Supreme composite resin (3M ESPE). The restorations were evaluated by two trained and calibrated evaluators using FDI and adapted USPHS criteria at baseline (12.02±5.68 days) and after 26 (± 2.36) months. The obtained data were subjected to statistical analysis between the groups using the Friedman and Wilcoxon test for intra-group analysis and the McNemar test for comparisons between FDI and USPHS criteria (α=0.05). Results No statistically significant differences were observed between the ER, SEE, and SE groups after 26 months, except for marginal discoloration between the ER and SE groups (p≤0.05). Conclusion Class I and II resin composite restorations performed with Scotchbond Universal adhesive using ER, SEE, and SE modes showed acceptable clinical performance over a 26-month evaluation period. Moreover, the adapted FDI and adapted USPHS criteria yielded comparable results. Brazilian Clinical Trials Registry (Rebec) — RBR-9p3hdp

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Abstract Fractalkine (CX3CL1) is expressed by various cells, contributing to the pathogenesis of diseases such as diabetes mellitus, vascular pathologies, and rheumatoid arthritis via immunological mechanisms. The CX3CL1–CX3CR1 axis regulates cellular responses such as proliferation and collagen production, which are implicated in gingival overgrowth (GO). Objectives This study aimed to assess the levels of CX3CL1, tumor necrosis factor-α (TNF-α), and transforming growth factor-beta (TGF-β) in both gingival crevicular fluid (GCF) and gingival tissues among patients with biofilm- and amlodipine-induced GO. Additionally, the potential relationship between these biomarkers and clinical periodontal parameters was evaluated. Methods The study included 17 participants with biofilm-induced GO (Group I), 18 participants with amlodipine-induced GO (Group A), and 10 systemically healthy participants without GO (Control). CX3CL1, TNF-α, and TGF-β levels in GCF samples were assessed using enzyme-linked immunosorbent assay (ELISA). Moreover, mRNA expression levels of CX3CL1, TNF-α, and TGF-β in tissue samples were determined by quantitative real-time PCR (qPCR). Results The total GCF CX3CL1 level was significantly higher in Group I and Group A compared to controls. However, tissue CX3CL1 and TNF-α levels were significantly higher in Group I than Group A (p<0.05). In Group A, total GCF CX3CL1 levels showed a positive correlation with the gingival index (GI) (r=0.644), bleeding on probing (BOP) (r=0.622), and GCF volume (r=0.720). A significant positive correlation was observed between tissue CX3CL1 and TNF-α levels (r=0.762) (p<0.05). In Group I, a significant correlation was observed between total GCF CX3CL1 and TNF-α, TGF-β, and GCF volume levels, respectively (r=0.865, r=0.845, r=0.651). A positive correlation (p<0.05) was also found between tissue CX3CL1 and TNF-α and TGF-β levels, respectively (r=0.689, r=0.903). Conclusion CX3CL1 may have a potential role in the development of GO-associated tissue fibrosis and its inflammatory mechanisms.

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Abstract The incorporation of bioactive agents into resin-modified glass ionomer cement (RMGIC) is a promising strategy to improve its mechanical strength and biofilm control, especially for patients with active dental caries. Objective This study aimed to evaluate the effects of incorporating ZnONPs and CaGP into RMGIC on its mechanical and microbiological properties. Design Six groups were tested: 1) RMGIC (without CaGP/ZnONPs); 2) RMGIC-1.0%ZnONPs; 3) RMGIC-2.0%ZnONPs; 4) RMGIC-3.0%CaGP; 5) RMGIC-3.0%CaGP-1.0%ZnONPs; and 6) RMGIC-3.0%CaGP-2.0%ZnONPs. The compressive strength (CS), diametral tensile strength (DTS), and surface hardness (SH) were evaluated after 24 hours and 7 days. Antimicrobial and antibiofilm activity were evaluated using agar diffusion and biofilm metabolic activity (XTT) assays. Results After 24 hours, all the groups showed similar DTS values (p>0.05), except for RMGIC-3.0%CaGP-1.0%ZnONPs, which showed the highest DTS value (p<0.05). Comparing 24 hours and 7 days, the DTS values of RMGIC-3.0%CaGP-2.0%ZnONPs, RMGIC-3.0%CaGP, and RMGIC-3.0%CaGP-2.0%ZnONPs were similar (p=0.360). After 24 hours, the RMGIC group showed the CS highest value, followed by RMGIC-2.0%ZnONPs (p < 0.05). After 7 days, the RMGIC-3.0%CaGP-1.0%ZnONPs group exhibited the highest CS value, approximately 15% higher than RMGIC (p<0.05). The RMGIC-1.0%ZnONPs group exhibited significantly higher SH at 24 hours (p=0.621). At 7 days, the highest SH value was observed for the RMGIC-3.0%CaGP-1.0%ZnONPs group (p<0.05). Regarding antimicrobial and antibiofilm activity, including results from biofilm metabolism assays, the RMGIC-3.0%CaGP-1.0%ZnONPs group demonstrated the most effective antimicrobial and inhibitory effects (p<0.05). Conclusion This study demonstrated that adding ZnONPs and CaGP to RMGIC enhanced its mechanical and antimicrobial and antibiofilm properties, suggesting enhanced mechanical performance and improved protection against cariogenic biofilms—critical factors for successful restorative treatments. Therefore, the addition of ZnONPs and CaGP is a promising strategy to develop advanced restorative materials that improve clinical outcomes, especially for patients with active dental caries.

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Abstract Background Vital pulp therapy is limited by incomplete dentin regeneration and dose-limiting toxicities of current histone deacetylase (HDAC) inhibitors. Previous structural studies have identified critical determinants of HDAC4-silencing mediator for retinoid and thyroid hormone receptor (SMRT) protein interactions, providing a rationale for developing selective inhibition strategies. Objective This study evaluated SMRT peptide 1-protein transduction domain (SP1-PTD), which is a cell-penetrating peptide designed to selectively disrupt HDAC4–SMRT interaction based on structural insights, for promoting odontoblast differentiation with improved safety compared to pan-HDAC inhibitors. Methodology SP1-PTD comprises an SMRT-derived sequence fused to a PTD, enabling targeted inhibition without affecting HDAC catalytic activity. Effects on odontoblast differentiation were assessed in murine dental papilla cell lines and primary human dental pulp cells using gene expression analysis, functional mineralization assays, and mechanistic studies including chromatin immunoprecipitation and RUNX2 acetylation analysis. Cytotoxicity was directly compared with suberoylanilide hydroxamic acid (SAHA) and trichostatin A. Results SP1-PTD treatment significantly enhanced odontoblast differentiation with 15.9-fold increase in dentin sialophosphoprotein (Dspp) expression alongside upregulation of RUNX2, osteocalcin, and bone sialoprotein. Functional analysis revealed 1.8-fold increased mineralization capacity. Mechanistically, SP1-PTD increased RUNX2 protein acetylation and histone acetylation at the Dspp promoter, indicating derepression of RUNX2-mediated transcription. Importantly, SP1-PTD did not show cytotoxicity across a wide therapeutic range (0.1-20 μM) and promoted cell proliferation, contrasting sharply with dose-dependent toxicity of pan-HDAC inhibitors. Direct comparison revealed SP1-PTD induced 14-fold increase in Dspp expression while SAHA suppressed it despite comparable Runx2 induction. Conclusions SP1-PTD represents a first-in-class selective HDAC4 inhibitor that achieves robust pro-differentiation effects with an exceptional safety profile. By specifically targeting HDAC4–SMRT interactions, SP1-PTD overcomes limitations of conventional HDAC inhibitors and offers translational promise for dental regenerative medicine.

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Abstract Composite resins containing S-PRG fillers may degrade under pH fluctuations and abrasion, influenced by their composition, particle size, exposure time, and solution acidity. Objective: This study evaluated the ability of resin composites containing S-PRG fillers to modulate the pH of the surrounding medium, as well as their surface roughness and gloss following an erosive/abrasive challenge. Methodology: Resin disks (⌀4mm × 2mm) (n=15) were prepared using Filtek Z350 XT (control), Beautifil II, Beautifil II Enamel, and Beautifil II LS (the latter three containing S-PRG fillers). To assess buffering capacity, disks (n=5) were immersed in a demineralizing solution, and pH was measured at baseline and after 1, 3, 7, 14, and 21 days. Separate specimens (n=10) underwent daily erosion cycles using 0.3% citric acid, combined with abrasion via toothbrushing, conducted over a 5-day period to simulate an acidic diet and twice-daily oral hygiene. Surface roughness (Ra) and gloss (GU) were assessed at baseline, after polishing, and following the challenge; surface topography was analyzed by a scanning electron microscope (SEM). Data were analyzed using a generalized linear mixed model for repeated measures over time, in addition to Tukey–Kramer, Kruskal–Wallis, Dunn, Friedman, and Nemenyi tests (α=0.05). Results: All materials showed a significant increase in the pH of the surrounding medium over time (p<0.05). After 24 hours, Beautifil II exhibited a significantly higher pH than the others (p<0.05). Filtek Z350 XT demonstrated lower surface roughness than the other materials after the erosive/abrasive challenge (p<0.0001). Following the challenge, Beautifil II and Beautifil II Enamel presented higher gloss values (p<0.05). Conclusions: Resin composites containing S-PRG fillers slightly increased the pH of the surrounding medium over time. Surface roughness increased after the erosive/abrasive challenge, although the gloss of the S-PRG-containing composites also improved.