OBJECTIVES: This study examined whether early-life stress events can be detected and chronologically dated through microscopic analysis of deciduous teeth. A unique case of monozygotic twins was used-one born with cleft...OBJECTIVES: This study examined whether early-life stress events can be detected and chronologically dated through microscopic analysis of deciduous teeth. A unique case of monozygotic twins was used-one born with cleft lip and palate (CLP) who underwent early surgical interventions, and the other born without major health conditions. DESIGN: Histological thin sections of four naturally shed deciduous incisors were analyzed using polarized light microscopy. Accentuated growth lines-microscopic features that form in response to systemic stress during tooth development-were compared with medical records and parental reports to assess correspondence with known stressful episodes. RESULTS: Both twins exhibited similar accentuated line formations for shared events (prenatal maternal stress, birth, routine vaccinations), and unique responses to individual issues. The CLP twin showed additional lines related to surgical interventions and associated care, while the non-CLP twin had markers corresponding to aspiration episodes and weaning. Mild lines were also observed in periods without recorded events, suggesting high sensitivity of dental tissues to physiological perturbations. CONCLUSION: Deciduous teeth preserve a high-resolution chronological record of stress and may serve as a biomarker and tool for early life history and adversity revelation. Our findings highlight the value of analyzing dentin and mildly accentuated lines across multiple time-overlapping teeth per individual in polarized light. By utilizing odontochronology, researchers and clinicians can retrospectively assess the timing and impact of developmental disruptions. In children with conditions such as cleft lip and palate, this non-invasive approach could support targeted early interventions and improve understanding of stress-related outcomes.
AIM: To explore how statherin's hydrophobic properties affects its binding behaviour. DESIGN: Synthetized statherin with or without phosphorylation (Statherin (±p)) or calcium was incubated with defined hydrophobic and h...AIM: To explore how statherin's hydrophobic properties affects its binding behaviour. DESIGN: Synthetized statherin with or without phosphorylation (Statherin (±p)) or calcium was incubated with defined hydrophobic and hydrophilic charged particles. Bound protein was eluted by TBST (tris buffered saline with tween 20) and EDTA buffers to break hydrophobic and hydrophilic interactions. Statherin (±p) diluted in different pH (3.0/4.2/7.0) were incubated with hydrophobic particles followed by TBST elution to study how pH affects its hydrophobic interaction. Film formation ability was assessed by resolubilizing any visible film at the air-liquid interface and quantifying by electrophoresis after leaving Statherin (±p) solutions in petri dishes for 30 mins. Statherin (±p) self-association behaviour with or without calcium was also assessed by transmission electron microscope (TEM) and particle size spectroscopy. RESULTS: Greatest binding was seen for Statherin (+p) to hydrophobic particles which was decreased by 35% after adding calcium and increased by 30% by increasing solution acidity. On positively charged particles, binding was increased by 30% with calcium and uniquely was eluted by EDTA. Interestingly, only Statherin (+p) with calcium formed a visible film. Size detection showed that calcium induced large associations of Statherin (±p) and TEM revealed Statherin (+p) with calcium formed oval micelles (200 nm), while Statherin (-p) formed small round and rod micelles regardless of calcium. CONCLUSION: This study demonstrates statherin's hydrophobic properties are affected by calcium and pH and dominates its physical properties. This may shed light on how statherin assembles in saliva which may affect its binding and remineralization ability with teeth.
OBJECTIVES: This review aims to summarize the roles of RNA binding proteins (RBPs) in post-transcriptional regulation in craniofacial bone, tooth, and periodontal tissues. DESIGN: PubMed and Web of Science were searched...OBJECTIVES: This review aims to summarize the roles of RNA binding proteins (RBPs) in post-transcriptional regulation in craniofacial bone, tooth, and periodontal tissues. DESIGN: PubMed and Web of Science were searched from inception to November 2025 for original research, reviews, and clinical studies. Key terms combined RBP concepts ("RNA binding protein" or RBP) with craniofacial/dental terms (craniofacial or maxillofacial or tooth or dental or enamel or dentin or odontogenesis or periodontal or periodontium or alveolar bone) and process terms (splicing or "RNA modification" or mA or "mRNA stability" or translation or microRNA or miRNA or "noncoding RNA"). INCLUSION CRITERIA: studies linking RBPs to craniofacial bone, tooth, or periodontal tissues with mechanistic, functional, or clinical evidence. EXCLUSION CRITERIA: non-relevant tissues, non-RBP regulators, or studies lacking interpretable post-transcriptional evidence. Duplicates were removed; titles/abstracts were screened followed by full-text assessment, and reference lists were checked. RESULTS: RBP mechanisms were summarized across alternative splicing, RNA modification and mRNA stability regulation, translation control, and noncoding RNA regulation. Reported outcomes were tissue- and cell-type dependent, spanning osteogenesis/osteoclastogenesis, enamel/odontoblast lineage programs, and periodontal homeostasis and regeneration. CONCLUSIONS: RBPs coordinate multiple post-transcriptional steps that shape craniofacial bone remodeling, tooth development, and periodontal repair. Evidence remains uneven across tissues and models, supporting the need for more cell-resolved and in vivo validation.
OBJECTIVES: The objective of this study was to evaluate the impact of vitamin D (1,25VitD3) and orthodontic tooth movement (OTM) on alveolar bone, tooth movement type, and root structure. DESIGN: Sprague Dawley rats (n =...OBJECTIVES: The objective of this study was to evaluate the impact of vitamin D (1,25VitD3) and orthodontic tooth movement (OTM) on alveolar bone, tooth movement type, and root structure. DESIGN: Sprague Dawley rats (n = 32) were divided into four groups (n = 8 per group): control gavage (CG), experimental gavage (EG), control injection (CI), and experimental injection (EI). OTM was induced using a NiTi spring. Micro-CT scans were performed at 5 time points: T0 (before 1,25VitD3 administration), T1 (OTM initiation), T2 (OTM completion), T3 (7 days post-OTM), T4 (30 days post-OTM) to measure alveolar bone height and tooth tipping. Root resorption was evaluated histologically. RESULTS: A significant decrease in buccal alveolar height was observed during and after OTM for 1,25VitD3 groups. Lingual alveolar bone decreased throughout the whole experiment for CI and EI, while it decreased only during OTM for EG. A significant increase in mesial tipping was observed between T0 and T2 for all groups. Root resorption was significantly higher for the OTM side than the control side for all groups (p < 0.05). CONCLUSIONS: Alveolar bone height decreased with OTM across all dental surfaces, with 1,25VitD3 enhancing this reduction at the buccal and lingual sites. The OTM also lead to significant mesial tipping and root resorption, which were not affected by 1,25VitD3.
OBJECTIVE(S): The research aimed to investigate the impact of hsa-miR-514a-3p on the proliferation and invasion of oral squamous cell carcinoma (OSCC), and to identify its potential target gene COL1A1. DESIGN: The expres...OBJECTIVE(S): The research aimed to investigate the impact of hsa-miR-514a-3p on the proliferation and invasion of oral squamous cell carcinoma (OSCC), and to identify its potential target gene COL1A1. DESIGN: The expression patterns, functional enrichment (Gene Set Enrichment Analysis, GSEA), and copy number variations (CNV) of miR-514a-3p and COL1A1 were analyzed using public datasets (E_MTAB_8588, GSE75538, TCGA-HNSC, and Human Protein Atlas, HPA). The expressions of miR-514a-3p and COL1A1 in clinical samples were detected by immunohistochemistry (IHC) and RT-qPCR. Lentiviral vectors (oe-miR-514a-3p, sh-miR-514a-3p, oe-COL1A1, and sh-COL1A1) were transfected into SCC-25 cells. The expressions of COL1A1, epithelial-mesenchymal transition (EMT)-related molecules, and matrix metalloproteinases (MMPs) were detected by RT-qPCR, Western blotting, and ELISA. Cell functions were evaluated using colony formation assay, Transwell assay, flow cytometry, and CCK-8 assay. A dual-luciferase reporter assay was used to verify the binding between miR-514a-3p and COL1A1. RESULTS: Hsa-miR-514a-3p showed a significant downregulation in OSCC tissues compared to adjacent controls. Hsa-miR-514a-3p overexpression led to reduced OSCC cell proliferation and invasion, whereas its downregulation resulted in increased these processes. hsa-miR-514a-3p directly targeted COL1A1, with negative correlation in OSCC samples. Silencing COL1A1 mimicked the suppressive effects of hsa-miR-514a-3p, and COL1A1 overexpression partially reversed them. CONCLUSION: This study demonstrates that hsa-miR-514a-3p inhibits malignant phenotypes of OSCC cells by targeting COL1A1, providing insights into potential therapeutic targets for OSCC management.
OBJECTIVE: This study aimed to evaluate the effect of blue light therapy on tumor behavior and cancer stem cells properties in oral squamous cell carcinoma (OSCC). DESIGN: The OSCC cell lines SCC9 and HSC3 were exposed t...OBJECTIVE: This study aimed to evaluate the effect of blue light therapy on tumor behavior and cancer stem cells properties in oral squamous cell carcinoma (OSCC). DESIGN: The OSCC cell lines SCC9 and HSC3 were exposed to blue light irradiation at 105, 168, and 210 J/cm². After 24 h, cell viability was evaluated using MTS and crystal violet assays. Apoptosis and necrosis were analyzed by Annexin V and DAPI staining through flow cytometry; migration was assessed by wound-healing assay; and cancer stem cells properties were examined by colony and sphere formation assays, RT-qPCR for cancer stem cells biomarkers (BMI1, CD44, OCT4, NANOG), and flow cytometry for CD44 and ESA expression. RESULTS: Blue light irradiation reduced cellular viability in both cell lines and increased apoptosis in SCC9 cells, while no change was observed in HSC3. Blue light irradiation significantly decreased migration in both cell lines. Regarding cancer stem cells characteristics, blue light reduced colony formation in SCC9 at 105 and 210 J/cm² and sphere formation in both cell lines. Expression of BMI1, OCT4, NANOG, and CD44 genes was not altered, as well as the frequency of CD44/ESA cells. However, at 210 J/cm², SCC9 showed an increase in CD44 cells, associated with a more differentiated phenotype. CONCLUSION: Blue light irradiation reduced viability and migration in both OSCC cell lines and induced apoptosis only in non-metastatic SCC9 cells. Blue light exerted anti-tumor effects without promoting cancer stem cells properties, while decreasing their ability to self-renew.
OBJECTIVE: This narrative review aims to examine the role of an acidic microenvironment in the pathogenesis of dental caries, pulpitis, and apical periodontitis. DESIGN: The references in English language of this narrati...OBJECTIVE: This narrative review aims to examine the role of an acidic microenvironment in the pathogenesis of dental caries, pulpitis, and apical periodontitis. DESIGN: The references in English language of this narrative review were sourced from PubMed and Web of Science by using the relevant keywords and by manually searching the bibliography of the included publications. RESULTS: Acidic microenvironment in dental caries promotes the proliferation and adaptation of acidogenic and aciduric cariogenic bacteria, thereby accelerating the disease process and impairing treatment outcomes. In pulpitis, when pH drops in the microenvironment, normal pulpal functions are impaired, and pathogenic bacteria exhibit heightened virulence. Furthermore, acidic microenvironment in periapical tissue affects the activity of osteoblasts, osteoclasts and enzymatic processes, thereby increasing the bone resorption in apical periodontitis. Acidic microenvironment also compromises the effectiveness of endodontic treatment. Although many strategies have been developed to mitigate acid-related damage in dental caries, comparable approaches have received less attention for pulpal and periapical diseases. CONCLUSION: An acidic environment causes demineralization of dental hard tissues and disrupts the function of cells and microorganisms. This promotes the progression of dental caries, pulpitis, and apical periodontitis, and also reduces the effectiveness of their treatment.
UNLABELLED: The emergence of multidrug-resistant Candida highlights a pressing threat to global public health. OBJECTIVE: To evaluate in vitro the antifungal activity, mechanism of action, drug association, and anti-biof...UNLABELLED: The emergence of multidrug-resistant Candida highlights a pressing threat to global public health. OBJECTIVE: To evaluate in vitro the antifungal activity, mechanism of action, drug association, and anti-biofilm effect of the essential oil of Lippia sidoides Cham. (EO-LS) against Candida albicans and Candida auris. DESIGN: EO-LS was extracted, and its chemical profile was determined by GC-MS. Assays were performed to determine the Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC), mechanism of action, drug interaction with nystatin and ketoconazole, time-kill kinetics, and biofilm inhibition by confocal microscopy. RESULTS: The compound exhibited fungicidal activity, with MIC and MFC values of 125 µg/mL against C. albicans and 62.5 µg/mL against C. auris. The exogenous ergosterol assay indicated that EO-LS exerts antifungal activity by interfering with fungal plasma membrane functions. The combination of EO-LS with ketoconazole demonstrated pharmacological synergism, while its combination with nystatin resulted in an antagonistic effect. EO-LS significantly inhibited fungal growth (p < 0.005) and promoted a marked reduction of mature C. auris biofilm at a concentration of 125 µg/mL (p < 0.0001), as confirmed by confocal microscopy imaging. CONCLUSION: The essential oil of Lippia sidoides exhibits antifungal activity against Candida spp., including C. auris, likely through an action on the cell membrane, and shows potential as an anti-biofilm agent with pharmacological synergism when combined with ketoconazole.
OBJECTIVE: To analyze oropharyngeal dynamics during mastication and swallowing in a minipig model with volumetric enlargement and reduction of the tongue base. DESIGN: Six same-sex sibling pairs of 8-9-months-old Yucatan...OBJECTIVE: To analyze oropharyngeal dynamics during mastication and swallowing in a minipig model with volumetric enlargement and reduction of the tongue base. DESIGN: Six same-sex sibling pairs of 8-9-months-old Yucatan minipigs were analyzed. Of each pair one minipig was fed with high-calorie pellets to reach obesity (BMI > 51) for volumetric enlargement of the tongue base while the other was normal-weighted (BMI < 37) receiving surgical coblation for volumetric reduction. At baseline and week-5 post-surgery x-ray video fluoroscopy was recorded during unrestrained feeding with barium-mixed diet at 30-frames-per-second for 5-10 min. Chewing cycles and swallowing episodes were traced using video-analysis software calibrated by implanted 2 mm ultrasonic-crystals. Tracing points were located at the soft palate (posterior-1/3), epiglottis (anterior-1/3), tongue base (midpoint), and pharyngeal wall (posterior-1/3). The coordinate was set at the alveolar ridge of the upper molar for X-axis and perpendicularly over the distal surface of the last molar for Y-axis. Directional movements over the coordinate, distance changes of each structure (structural), and between structures (inter-structural) were measured. RESULTS: The structural dynamics during early chewing were significantly higher at baseline compared to week-5 in the volume-enlarged group (p < 0.05). At baseline, movements of the pharyngeal wall in the normal-weighted minipigs were larger than those of obese ones during jaw opening (p < 0.05). At week-5, both groups showed different inter-structural dynamics (epiglottis-pharyngeal wall) during swallowing, significantly wider in the volume-reduced compared to the volume-enlarged groups (p < 0.05). CONCLUSION: Volumetric alterations of the tongue base substantially modify the pharyngeal dynamics during chewing and swallowing evidenced by decreasing structural and inter-structural moving distances overtime for both groups.
OBJECTIVES: To investigate the effects of galactomannan extracted from Caesalpinia ferrea seeds on dentin permeability and its cytocompatibility with oral cells. DESIGN: Sixty dentin discs were treated with EDTA for 5 mi...OBJECTIVES: To investigate the effects of galactomannan extracted from Caesalpinia ferrea seeds on dentin permeability and its cytocompatibility with oral cells. DESIGN: Sixty dentin discs were treated with EDTA for 5 min and, after determining maximum permeability, randomly assigned to four groups (n = 12): distilled water (DW), potassium oxalate (PO), 1% juca seed galactomannan (JSG1), and 2% juca seed galactomannan (JSG2). Dentin permeability was measured again after treatment and after a 5-day erosive-abrasive cycle (four daily immersions in 0.3% citric acid for 5 min, followed by 60 min in artificial saliva, with brushing after the first and last challenges). Treatments were reapplied daily. The percentage of dentin permeability (%Lp) was calculated relative to maximum permeability. Surface morphology was examined by scanning electron microscopy (SEM), and cytotoxicity was tested in human gingival fibroblasts (HGF) and dental pulp stem cells (DPSC). Data were analyzed using ANOVA and Bonferroni test (p < 0.05). RESULTS: After treatment, no significant differences in permeability were observed among groups (p > 0.05). Following cycling, JSG2 showed significantly lower permeability than DW (p < 0.05). Only DW exhibited a significant increase in permeability over time (p < 0.05). SEM images revealed that PO and JSG2 maintained partially obliterated tubules even after cycling. Cytotoxicity assays showed cell viability near 100% for HGF and 88% for DPSC at the highest juca seed galactomannan (JSG) concentration, confirming cytocompatibility. CONCLUSIONS: JSG at 2% concentration partially occluded dentinal tubules, preserved dentin permeability under erosive-abrasive conditions, and demonstrated cytocompatibility with HGF and DPSC.
OBJECTIVE: Neuralgia-Inducing Cavitational Osteonecrosis (NICO) is a debated diagnostic entity proposed as a cause of chronic orofacial pain. Despite ongoing clinical use, systematic evaluations integrating historical fo...OBJECTIVE: Neuralgia-Inducing Cavitational Osteonecrosis (NICO) is a debated diagnostic entity proposed as a cause of chronic orofacial pain. Despite ongoing clinical use, systematic evaluations integrating historical foundations and methodological gaps remain limited. DESIGN: A comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science mapped NICO's development from 1979 to 2024. The search yielded 603 records; 41 studies were included after screening. Data extraction categorized studies by type, methodology, diagnostic criteria, and limitations. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. RESULTS: The 41 studies revealed recurrent methodological limitations: absence of control groups, non-standardized diagnostic criteria, limited histological evidence, and interpretive bias. Proposed mechanisms such as RANTES/CCL5 overexpression lack independent validation. Diagnostic tools remain unvalidated, and surgical interventions continue based on unclear criteria. Evidence consists predominantly of low to moderate quality retrospective case series, with no randomized controlled trials. Many patients diagnosed with NICO may be more appropriately classified as having persistent idiopathic facial pain or trigeminal neuropathic pain according to International Classification of Orofacial Pain criteria. CONCLUSIONS: Current evidence is insufficient to support NICO as a distinct, validated clinical entity. The substantial physical and psychological risks of surgical intervention underscore the ethical imperative to base treatment decisions on validated evidence. Rigorous, prospective research with standardized diagnostic frameworks and appropriate controls is urgently needed. Clinicians should exercise caution, prioritizing evidence-based non-surgical management and avoiding irreversible surgical interventions without clear justification.
OBJECTIVE: Deep carious lesions can cause severe damage to the dental pulp, potentially progressing to irreversible pulpitis. While bacterial involvement in this process has been extensively investigated, fungal particip...OBJECTIVE: Deep carious lesions can cause severe damage to the dental pulp, potentially progressing to irreversible pulpitis. While bacterial involvement in this process has been extensively investigated, fungal participation has received comparatively less attention. Therefore, this study aimed to investigate the presence of six Candida species and their association in infected dentine (ID) and root canals (RC) of teeth with symptomatic irreversible pulpitis (SIP) using Nested PCR. DESIGN: Twenty patients with SIP were included in this study. Samples were collected from ID and RC. DNA was extracted from the samples for microbial detection via PCR using species-specific 18S rDNA and the downstream intergenic spacer region primers. Candida spp were detected by Nested PCR. McNemar and Fisher's exact tests were used to test different null hypotheses at a significance level of 5%. RESULTS: Candida spp. were simultaneously detected in ID and RC in 6 of 8 teeth with carious lesions; and in 9 of 12 restored teeth. C. albicans was the most frequently detected species in ID and RC samples.There was a significant difference between the presence of C. glabrata in ID and RC (p = 0.004); a positive association between C. glabrata and C. dubliniensis (p = 0.005; OR=36; and a negative association between C. glabrata and C. parapsilosis (p = 0.011; OR=0) in the ID. A positive association between C. dubliniensis and C. tropicalis was identified in the RC (p = 0.013; OR=45). CONCLUSION: Candida spp. are commonly found in ID and the RC of SIP, with C. albicans being the most prevalent fungal species.
OBJECTIVE: To evaluate the potential of tumor-suppressor microRNAs delivered via exosomes, especially those from human dental pulp stem cells, as a targeted therapy for oral cancer and to examine recent strategies that i...OBJECTIVE: To evaluate the potential of tumor-suppressor microRNAs delivered via exosomes, especially those from human dental pulp stem cells, as a targeted therapy for oral cancer and to examine recent strategies that improve their delivery and clinical application. Although extensive preclinical evidence supports the anticancer functions of TS-miRNAs, the robustness and reproducibility of their effects vary substantially across experimental models. Exosome-based delivery has emerged as a biologically attractive strategy to improve miRNA stability, targeting specificity, and therapeutic efficacy. DESIGN: This review examines preclinical and translational studies on the delivery of tumor-suppressor microRNAs using exosomes, focusing on human dental pulp stem cell derived exosomes and recent strategies that enhance their targeting and therapeutic effectiveness. Relevant studies were identified through PubMed, Scopus, Web of Science, and Google Scholar. RESULTS: Studies show that using exosomes to deliver tumor-suppressor microRNAs can make them more stable, help them enter cells more efficiently, and reach tumors more effectively. Among multiple clinically relevant sources, including bone marrow and adipose-derived mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and tumor-derived vesicles, human dental pulp stem cell (hDPSC)-derived exosomes represent a promising, though not yet potential advantages suggested by preclinical studies. Exosomes from human dental pulp stem cells are especially promising, as they are highly compatible with the body and naturally target cancer cells better than other above sources. Engineering these exosomes can further improve their precision and reduce unwanted effects. However, challenges like producing them on a large scale, maintaining consistency, and applying them in real-world clinical settings still remain. CONCLUSION: Exosome-mediated delivery of tumor-suppressor miRNAs offers an exciting and promising direction in oral cancer therapy. By combining the regulatory power of miRNAs with the natural delivery capacity of exosomes, this strategy could open new possibilities for safer, more effective, and personalized treatment of oral cancer. This review critically evaluates mechanistic evidence, compares exosome sources, and outlines realistic translational barriers, avoiding overstatement of near-term clinical applicability.
OBJECTIVES: Stem cells from human exfoliated deciduous teeth (SHED) represent a minimally invasive source of mesenchymal stem cells for dental tissue regeneration. Although amelogenin, a major enamel matrix protein, is k...OBJECTIVES: Stem cells from human exfoliated deciduous teeth (SHED) represent a minimally invasive source of mesenchymal stem cells for dental tissue regeneration. Although amelogenin, a major enamel matrix protein, is known to enhance the regenerative potential of various dental-derived stem cells, the mechanism-particularly the involvement of the CD63 receptor and extracellular signal-regulated kinase (ERK)1/2 signaling pathway- through which it activates SHED remains unclear. This study aimed to evaluate the effects of amelogenin on cell proliferation and migration in SHED and elucidate the mechanism of signaling via the CD63 receptor. DESIGN: Primary SHED were isolated from exfoliated deciduous teeth and cultured. Cellular activation by amelogenin (1000 ng/mL) was assessed via migration (scratch assay), proliferation (live-cell imaging and 5-bromo-2'-deoxyuridine incorporation), immunofluorescence for CD63 expression, western blotting, and enzyme-linked immunosorbent assay for ERK1/2 phosphorylation. The functional roles of CD63 and ERK1/2 were analyzed using an anti-CD63 neutralizing antibody and MEK1/2 inhibitor U0126. RESULTS: Amelogenin significantly enhanced both the migration and proliferation of SHED compared to the controls. Immunostaining demonstrated that amelogenin increased CD63 expression in SHED. Amelogenin also elevated ERK1/2 phosphorylation, and blockade of CD63 or MEK1/2 abrogated amelogenin-induced increases in cell proliferation, DNA synthesis, and ERK1/2 phosphorylation. CONCLUSIONS: Amelogenin promotes the migration and proliferation of SHED through CD63-mediated ERK1/2 signaling, highlighting a promising approach for enhancing cell-based repair of refractory bone defects in dental regenerative medicine.
OBJECTIVE: The functional profile and fibre characteristics of masticatory muscles may change depending on their functional demands. This in vivo experimental animal study aimed to evaluate the influence of diet consiste...OBJECTIVE: The functional profile and fibre characteristics of masticatory muscles may change depending on their functional demands. This in vivo experimental animal study aimed to evaluate the influence of diet consistency on fibre-type distribution and cross-sectional area in adult masticatory muscles using a rat model. DESIGN: Twenty-four male Wistar rats were divided into two groups of 12 and fed exclusively either a hard or soft diet following weaning. At 38 weeks, corresponding to adulthood, the masseter and digastric muscles were dissected. Immunofluorescence staining was performed to identify muscle fibre types (I, IIA, IIB, IIX), and morphometric analysis performed to measured fibre cross-sectional area and minimum diameter. RESULTS: In the masseter muscle, rats fed a soft diet exhibited a lower percentage of type IIA fibres (p = 0.006) and a higher percentage of type IIX fibres (p = 0.007) than rats fed a hard diet. No significant differences were found between groups in average fibre cross-sectional area or minimum diameter. In the digastric muscle, differences were detected only in fibre-size and not in fibre-type distribution. Rats fed a soft diet had larger average cross-sectional area and minimum diameter of type I fibres (p = 0.004; p = 0.003) and type IIB fibres (p = 0.007; p = 0.007) than those fed a hard diet. CONCLUSIONS: Following soft-diet feeding, the masseter muscle was composed of less fast, fatigue-resistant fibre types (less IIA and more IIX). No such fibre-type distribution differences were observed in the digastric muscle, although some fibre types were larger in soft-diet-fed animals. These results indicate an adaptive response to reduced masticatory loading.
OBJECTIVE: Amelogenesis imperfecta (AI) refers to a group of rare yet complex genetic disorders that affect the quantity and/or quality of tooth enamel. Recently, in AI patients, we identified mutations that disrupt a co...OBJECTIVE: Amelogenesis imperfecta (AI) refers to a group of rare yet complex genetic disorders that affect the quantity and/or quality of tooth enamel. Recently, in AI patients, we identified mutations that disrupt a conserved alternative splicing pattern of the AMELX gene, which encodes amelogenin, the most abundant enamel matrix protein. These mutations led to the retention of exon 4, which is normally skipped during the pre-mRNA splicing process, resulting in the characteristic pitted, hypoplastic, and hypomineralized enamel defects. To observe the impact of retention of exon 4 within AMELX, a gene edited knock-in mouse model was generated. DESIGN: A single-nucleotide knock-in mouse model was generated using CRISPR/Cas9 technology to introduce a silent mutation (NM_001415990.1: c.120 T>C, p.(Ala40=)) that abrogated alternative splicing of exon 4. Following genomic sequence validation, the successfully-targeted mice were propagated, and their offspring genotyped for characterization. Micro-computed tomography analysis and immunohistochemistry analysis were performed on the hemi-mandibles of the wild-type and the knock-in mice. RESULTS: The enamel of the knock-in mice was chalky white and lacked translucency, due to faulty mineralization. This defective enamel broke down soon after tooth eruption. During the maturation stage, the ameloblast layer lost its cellular polarity and homogeneity, and intermingled with adjacent cell types to form disorganized clusters. CONCLUSIONS: The validated and characterized Amelx c.120 T>C mouse model provides a useful platform for investigating the molecular pathophysiology associated with retention of the exon 4 sequence. Following systemic characterization, this mouse model will serve as an important tool for assessing therapeutic strategies aimed at ameliorating the disease phenotype.
OBJECTIVE: This scoping review aimed to map and summarize the evidence on the antimicrobial and antibiofilm efficacy of flavonoid-based solutions or formulations for endodontic applications. DESIGN: The review was conduc...OBJECTIVE: This scoping review aimed to map and summarize the evidence on the antimicrobial and antibiofilm efficacy of flavonoid-based solutions or formulations for endodontic applications. DESIGN: The review was conducted in accordance with the PRISMA-ScR guidelines. A comprehensive search was performed across databases for articles published up to April 2025. Eligible studies included those evaluating the antimicrobial effects of flavonoids on microorganisms associated with endodontic infections. Relevant data were extracted, and a descriptive synthesis of the findings was carried out. RESULTS: The results showed that fifteen studies met the inclusion criteria, demonstrating significant antimicrobial and antibiofilm activity of various flavonoids. Epigallocatechin-3-gallate was the most extensively studied compound, showing dose-dependent activity against E. faecalis, F. nucleatum, A. israelii, S. mutans, and C. albicans, with enhanced efficacy when combined with agents such as fosfomycin or the peptide KR-12-a5. Quercetin also displayed concentration-dependent antibiofilm effects and gene modulation in E. faecalis. Proanthocyanidin showed superior efficacy compared to conventional irrigants, especially at higher concentrations. Rutin, although limited in standalone efficacy, showed promising results when used as a photosensitizer. Other flavonoids such as apigenin, theaflavin, isoquercitrin, ampelopsin, chalcone, and chrysin also demonstrated varying degrees of antimicrobial activity, often similar to or surpassing conventional agents like chlorhexidine and calcium hydroxide in specific models. CONCLUSIONS: Flavonoids exhibit significant potential as alternative or adjunctive agents for endodontic disinfection, especially in biofilm-related infections. Their efficacy is influenced by compound type, concentration, formulation, and synergistic combinations. Further research, especially clinical trials, is warranted to validate their therapeutic applicability and optimize delivery systems for clinical use in endodontics.
OBJECTIVE: Probiotic-mediated therapy has potential role in influencing bone remodeling. In this study, we aim to explore the impact of microorganisms on accelerating orthodontic tooth movement (OTM). DESIGN: Potential p...OBJECTIVE: Probiotic-mediated therapy has potential role in influencing bone remodeling. In this study, we aim to explore the impact of microorganisms on accelerating orthodontic tooth movement (OTM). DESIGN: Potential probiotic candidates were identified through 16S rRNA gene sequencing in a mouse model of OTM. To investigate the osteoimmunomodulatory impact, primary mouse periodontal ligament cells (PDLCs) were cultured with or without conditioned media (CM) derived from macrophages post-incubation with microorganisms. The microbiota of the mice has be depleted using broad-spectrum antibiotic mixture (ABX) before being administered with microorganisms. The distance of OTM have been measured, and the alveolar bone have been analyzed using micro-CT and immunohistochemical staining. RESULTS: The relative abundance of Enterococcus faecalis (E. faecalis) increased in the move group. The results demonstrated that E. faecalis increased the number of M1-polarized macrophages, and a decreased osteogenic level in PDLCs treated with CM E. faecalis group. The distance of OTM in ABX mice has been increased via administration of E. faecalis. CONCLUSIONS: This study has explored the potential effects of E. faecalis administration on the OTM process through immunomodulation. By elucidating this mechanism, our work lays the groundwork for developing future microorganism-interventions that could safely accelerate OTM with non-invasive strategy.
OBJECTIVE: The purpose of this study was to investigate whether mitochondrial unfolded protein response (UPR) was induced in Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)-treated osteoblasts and to stud...OBJECTIVE: The purpose of this study was to investigate whether mitochondrial unfolded protein response (UPR) was induced in Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)-treated osteoblasts and to study the relationship among UPR, mitochondrial function and bone resorption in periodontitis. DESIGN: Osteoblasts were treated with P.gingivalis-LPS. Nicotinamide riboside (NR) and doxycycline (DOX) were used to enhance UPR, while small interference RNA was transfected to knock down activating transcription factor 5 (ATF5). Protein and mRNA levels of genes involved in UPR and bone metabolism were measured. Intracellular reactive oxygen species (ROS), mitochondrial ROS and mitochondrial membrane potential were detected by flow cytometry and confocal imaging. RESULTS: UPR and receptor activator of NF-κB ligand (RANKL) expression were induced in P. gingivalis-LPS-treated osteoblasts. Enhancement of UPR by NR or DOX decreased RANKL and RANKL/osteoprotegerin (OPG) ratio in osteoblasts. UPR inhibition by ATF5 knockdown aggravated mitochondrial dysfunction and promoted RANKL expression in P.gingivalis-LPS-treated osteoblasts. CONCLUSIONS: ATF5-mediated UPR regulates RANKL expression through mtROS and mitochondrial membrane potential. UPR could be a potential target involved in the regulation of bone resorption in periodontitis.