O Journal of Applied Oral Science é uma continuação da Revista da Faculdade de Odontologia de Bauru. O Journal of Applied Oral Science opera na modalidade de publicação contínua eletrônica, formato que permite a publicação de volumes anuais sem especificações de fascículos. A Revista da Faculdade de Odontologia de Bauru foi publicada no período de 1993-2001, sendo continuada, em 2002, pelo Journal of Applied Oral Science, volume 11, número 1, mantendo a numeração de sua antecessora. O Journal of Applied Oral Science tem como objetivo principal publicar resultados de pesquisas originais, e a convite do editor, revisões nos campos da Odontologia, Fonoaudiologia e áreas correlatas. A abreviatura de seu título é J. Appl. Oral Sci., que deve ser usada em bibliografias, notas de rodapé e referências.
Universidade de São Paulo. Faculdade de Odontologia de Bauru
Todo o conteúdo do periódico, exceto onde está identificado, está licenciado sob uma Licença Creative Commons do tipo atribuição CC-BY.
Resin composites containing S-PRG fillers: effects on pH modulation of the surrounding medium, surface roughness, and gloss following erosive/abrasive challenge
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.
Copyright (c) 2025 Carlos Alberto Campos de Oliveira Neto, Mayara Zaghi Dal Picolo, Flávia Lucisano Botelho do Amaral, Carlos Rocha Gomes Torres, Kamila Rosamilia Kantovitz, Thomas Attin, Roberta Tarkany Basting https://creativecommons.org/licenses/by/4.0
Microstructures and mechanical characteristics of primary teeth affected by regional odontodysplasia
Regional odontodysplasia (ROD) is a rare, localized disorder of tooth hard tissues that can affect primary and permanent dentitions. However, its definitive etiology remains unclear and only a few studies have reported the detailed microstructures and mechanical characteristics of the affected teeth. Objective This study investigates the microstructural and mechanical characteristics of primary teeth affected by ROD. Methodology A total of two ROD-affected primary teeth from two different cases underwent clinical examinations. In addition to control samples of caries-free retained primary teeth, the affected samples were examined using micro-computed tomography (micro-CT), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and nanoindentation analysis. Results Clinical findings revealed yellowish discoloration, rough surfaces, and root resorption on the affected teeth. Radiographs indicated hypocalcified enamel, widened pulp chambers, and delayed development of permanent teeth. Micro-CT showed affected teeth with thinner and uneven enamel, disordered dentin, and reduced mineral density. XRD analysis found reduced crystallinity. SEM and TEM analyses revealed hypoplastic and loosely packed enamel crystals, whereas dentin exhibited disorganized collagen fibrils and poorly mineralized crystals. EDS analysis showed a reduced calcium/phosphorus ratio and an increased magnesium/calcium ratio in the affected enamel. Nanoindentation tests found reduced hardness and elastic modulus in ROD-affected enamel compared with control teeth. Conclusion ROD-affected primary teeth display significant microstructural abnormalities and compromised mechanical properties, underscoring the need for early intervention and long-term monitoring to prevent complications.
Copyright (c) 2026 Wenxian Jiang, Minjian Shen, Jian Wang, Mengyao Bian, Haiyan Zheng, Zihuai Zhou, Ying Shi, Zhifang Wu https://creativecommons.org/licenses/by/4.0
Selective HDAC4 inhibition by SP1-PTD promotes odontoblast differentiation
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.
Copyright (c) 2025 Yeo-Kyeong Shin, Jung-Sun Moon, Su-Kyeong Son, Bin-Na Lee, Chungoo Park, Sun-Hun Kim, Young Chu Lee, Min-Seok Kim https://creativecommons.org/licenses/by/4.0
Modification of restorative glass ionomer cement with zinc oxide nanoparticles and calcium glycerophosphate microparticles: in vitro assessment of mechanical properties and antimicrobial activity
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.
Copyright (c) 2025 Maria Fernanda Cavalcante Meira, Gabriela Leal Peres Fernandes, Andréa Simone Stucchi de Camargo, Leandro Piaggi Ravaro, Marylyn Setsuko Arai, Maria Fidela de Lima Navarro, Fernanda Lourenção Brighenti, Analú Barros de Oliveira, Marcelle Danelon https://creativecommons.org/licenses/by/4.0
Evaluation of the levels of Fractalkine (CX3CL1), TNF-α, and TGF-β in the gingival crevicular fluid/tissue of patients with gingival overgrowth: a cross-sectional observational study
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.
Copyright (c) 2025 Nazife Hamurcu, Ahu Uraz Çörekci, Rahşan Ilikçi Sağkan, Serpil Cula, Deniz Özbay Çetiner https://creativecommons.org/licenses/by/4.0
Clinical performance of posterior resin composite restorations bonded with universal adhesive system using three different application modes: a 26-month randomized clinical trial
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
Copyright (c) 2025 Thaís Silva Mendonça, Andreia Assis Carvalho, Jéssica Karla Maia Zago, Terezinha de Jesus Esteves Barata, Érica Miranda Torres, Gersinei Carlos de Freitas, Lawrence Gonzaga Lopes https://creativecommons.org/licenses/by/4.0
Oral microbiome patterns of dental caries in Kazakhstani adolescents
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.
Copyright (c) 2025 Argul Issilbayeva, Zharkyn Jarmukhanov, Samat Kozhakhmetov, Yermekbayeva Bakytgul, Laura Chulenbayeva, Graciela Muniz-Terrera, Masae Furukawa, Hiroki Nikawa, Adil Supiyev, Almagul kushugulova, Anara Zhumadilova https://creativecommons.org/licenses/by/4.0
Development of liver disease caused by chronic periodontitis in rats
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).
Any Carolina Cardoso Guimarães Vasconcelos
Copyright (c) 2025 Karen Neisman Rodriguez Ayala, Vinícius da Silva Caetano, Any Carolina Cardoso Guimarães Vasconcelos, Maria Vitoria Pereira de Sousa, Nikaely Brandão Barbosa, Luanna Maria Soares Mesquita, Paulo Roberto Carneiro Gomes, André Luis dos Reis Barbosa, Hélio Mateus Silva Nascimento , Daniel Fernando Pereira Vasconcelos https://creativecommons.org/licenses/by/4.0
Monocytes and Macrophage-derived mediators influence the behavior of squamous cell carcinoma cell lines
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.
Copyright (c) 2025 Graziela Perri, Raíssa Gabrieli Candido, Luiz Henrique Camargo Soares, Rafael Carneiro Ortiz, Izabel de Camargo, Maria Renata Sales Nogueira, Edgard José Franco Merllo Júnior, Ana Lucia Coelho, Edwin M Posadas, Cory Hogaboam, Karen A Cavassani, Ana Paula Campanelli https://creativecommons.org/licenses/by/4.0
Three-dimensional soft tissue comparison in non-growing patients treated for skeletal Class II Division I malocclusion: mandibular advancement surgery vs. Herbst Appliance
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.
Copyright (c) 2025 Gökhan Çoban, Taner Öztürk, Gökhan Türker, Ebru Topcuoğlu Hashimli, Yusuf Nuri Kaba https://creativecommons.org/licenses/by/4.0
Vagus nerve stimulation alleviates alveolar bone loss and inflammation in ligature-induced periodontitis rat model
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.
Copyright (c) 2025 Honghui Xie, Ping Huang, Aihong Tan, Zhijian Su, Ying Fu https://creativecommons.org/licenses/by/4.0
Effect of wavelength and radiant emittance on light transmittance and temperature increase in dental resin-based composites
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.
Copyright (c) 2025 Sharanya Singh, Mateus Garcia Rocha, Shannon M Roulet, Jean-François Roulet, Mario Alexandre Coelho Sinhoreti, Dayane Oliveira https://creativecommons.org/licenses/by/4.0
Single local injection of 3S-HMGB1 enhances early bone healing and titanium implant osseointegration in type 2 diabetic mice
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.
Copyright (c) 2025 Bhuvana Lakkasetter Chandrashekar, Alexandra Arteaga, Evelin Rios, Jimena Mora, Gustavo Pompermaier Garlet, Danieli C. Rodrigues, Claudia Cristina Biguetti https://creativecommons.org/licenses/by/4.0
Calcium carbonate in dentistry: a bibliometric review of emerging applications and trends
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.
Copyright (c) 2025 Andressa da Silva Barboza, Samira Schons de Oliveira, Adriana Poli Castilho Dugaich, Maurício Malheiros Badaró, Ana Paula Varela Brown Martins, Rafael Guerra Lund, Sheila Cristina Stolf, Juliana Silva Ribeiro de Andrade https://creativecommons.org/licenses/by/4.0
A randomized prospective clinical study evaluating the effectiveness of the Beautibond Xtreme adhesive system using different bonding techniques in class I and II restorations: one-year results
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.
Copyright (c) 2025 Walter Raucci Neto, Ana Flávia Simões Barbosa, Adrielle Fracaroli Baltazar, Larissa Fernanda Pereira, Yara Teresinha Corrêa Silva Sousa, Danielle Cristine Furtado Messias, Taylane Soffener Berlanga de Araujo https://creativecommons.org/licenses/by/4.0
PPARα modulation of macrophage polarization and inflammatory signaling in mimic periodontitis
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.
Copyright (c) 2025 Arthur Hu, Yvette Y Chen https://creativecommons.org/licenses/by/4.0
Association between single nucleotides polymorphisms in the DR2D, ANKK1, COMT, and 5-HTT genes with temporomandibular disorder
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.
Copyright (c) 2025 Otavio Augusto Pozza, Fernanda Mara de Paiva Bertoli, Franciele Topolski, Paula Porto Spada, Marilisa Carneiro Leão Gabardo, Juliana Feltrin de Souza, Erika Calvano Küchler, João Armando Brancher https://creativecommons.org/licenses/by/4.0
Panax notoginseng saponins alleviate alveolar bone loss and reprogram macrophages in diabetic periodontitis rats
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.
Copyright (c) 2025 Xue-wei Jiang, Jun Zhu, Wen Cheng, De-sheng Fan, Lei Zhen https://creativecommons.org/licenses/by/4.0
Comprehensive analysis of transcriptome and pathway interactions in periodontitis
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.
Copyright (c) 2025 Bruno César de Vasconcelos Gurgel, Nathalia Vilela, Kaio Henrique Soares, Ikramuddin Aukhil, Poliana Mendes Duarte, Luiz Eduardo Rodrigues Juliasse https://creativecommons.org/licenses/by/4.0
The impact of surface pre-reacted glass-ionomer nanoparticles on ion dynamics and the physio-mechanical properties of denture base resin
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.
Copyright (c) 2025 Kwanchanok Ratanakupt, Toshiyuki Nakatsuka, Kritirat Kiatsirirote https://creativecommons.org/licenses/by/4.0
Assessing the validity of ChatGPT-4o and Google Gemini Advanced when responding to frequently asked questions in endodontics
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.
Copyright (c) 2025 Nicolás Dufey-Portilla, Ana Billik Frisman, Maximiliano Gallardo Robles, Fernando Peña-Bengoa, Consuelo Cabrera Ávila, Venkateshbabu Nagendrababu, Paul M. H Dummer, Marc Garcia-Font, Francesc Abella Sans https://creativecommons.org/licenses/by/4.0
The systemic effect of prolonged use of sodium alendronate on the peri-implant bone repair process
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.
Copyright (c) 2025 Paula Buzo Frigério, Daniel Silva Leão, Pedro Henrique Silva Gomes-Ferreira, Naara Gabriela Monteiro, Daniele Botticelli, Roberta Okamoto https://creativecommons.org/licenses/by/4.0
Biocompatibility and bioactivity of bioceramic endodontic sealer: NeoSealer Flo
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.
Copyright (c) 2025 Evelin Carine Alves Silva, Jéssica Arielli Pradelli, Guilherme Ferreira da Silva, Paulo Sérgio Cerri, Mario Tanomaru-Filho, Juliane Maria Guerreiro-Tanomaru https://creativecommons.org/licenses/by/4.0
Estrogen versus bone marrow mesenchymal stromal cells in the regeneration of the parotid gland in ovariectomized rats
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.
Copyright (c) 2025 Sally Hassan Abo Baker, Amira Ahmed R. Moawad https://creativecommons.org/licenses/by/4.0
Intra-familial phenotype variant in hypoplastic amelogenesis imperfecta under a complex genetic component: a family report, whole-exome sequencing, and literature review
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.
Copyright (c) 2025 Célia Regina Moreira Lanza, Artur Melo Rodrigues, Iasmin Fonseca Tolentino Mascarenhas, Talita Roberta Ferreira de Souza, Matheus Oliveira Reis, Felipe Morando Avelar, Maria Raquel Santos Carvalho, Vasco Ariston Carvalho de Azevedo, Debmalya Barh https://creativecommons.org/licenses/by/4.0
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.
Copyright (c) 2025 Maria Paula Novaes Camargo Manna, Talita Portela Pereira, Bruna de Oliveira Iatarola, Mariele Vertuan, Ana Carolina Magalhães, Denise Maria Zezell, Luciana Fávaro Francisconi-dos-Rios https://creativecommons.org/licenses/by/4.0
Antioxidant potential of wine polyphenols on hematological indices and apical periodontitis in male rats
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.
Copyright (c) 2025 Romulo de Oliveira Sales-Junior, Julissa Denisse Arguello Alvarado, Bharbara de Moura Pereira, Rafaela Ricci, Nathália Evelyn da Silva Machado, Murilo Catelani Ferraz, Rayara Nogueira de Freitas, Renan Jose Barzotti, Antonio Hernandes Chaves-Neto, Luciano Tavares Ângelo Cintra, João Eduardo Gomes-Filho https://creativecommons.org/licenses/by/4.0
Bee venom exhibits anti-cancer effects on tongue carcinoma cells by arresting cell cycle, inducing apoptosis, and suppressing cell migration
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.
Copyright (c) 2025 Enas Sabry, Hagar M Zayed, Ola M Ezzatt, Iman Fathy, Hebatt-Allah S Elsayeh, Nashwa El-Khazragy, Suzan SeifAllah Ibrahim https://creativecommons.org/licenses/by/4.0
Patient compliance with braces vs. Invisalign®: a secondary data analysis from a randomized clinical trial
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.
Copyright (c) 2025 Graziela Hernandes Volpato, Paula Vanessa Pedron Oltramari, Renata Rodrigues de Almeida-Pedrin, Thais Maria Freire Fernandes, Marcio Rodrigues de Almeida, Gabriela Utrago, João Poiani https://creativecommons.org/licenses/by/4.0
Classification success of salivary interleukin-1β in periodontitis grading with artificial intelligence models: a cross-sectional observational study
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.
Copyright (c) 2025 Erensu Uzar, Ihsan Pence, Melike Siseci Cesmeli, Zuhal Yetkin Ay https://creativecommons.org/licenses/by/4.0