OBJECTIVE: Bone grafting materials are widely used in the treatment of critical-sized bone defects, and pharmacological agents with the potential to enhance their regenerative potential have been of great interest. The p...OBJECTIVE: Bone grafting materials are widely used in the treatment of critical-sized bone defects, and pharmacological agents with the potential to enhance their regenerative potential have been of great interest. The purpose of this study was to investigate the effect of the glucagon-like peptide-1 receptor agonist Liraglutide on bone regeneration when combined with different grafting materials. DESIGN: Critical-sized calvarial defects with a 5 mm diameter were created bilaterally in rats, and eight experimental groups were formed: Control, autogenous graft, allograft, xenograft, and the combination of each graft material with Liraglutide. Bone healing was evaluated through histomorphometric analyses and micro-computed tomography (micro-CT). ANALYSES: Immunohistochemical analyses for β-catenin, BMP-2, osterix, osteoprotegerin, RANKL, and Runx2 were performed. RESULTS: Histomorphometric data demonstrated that Liraglutide significantly enhanced the osteogenic performance of the grafts, resulting in greater new bone formation and defect closure (p < 0.05). The Liraglutide-Autogenous graft group showed the highest levels of new bone formation and defect closure. Immunohistochemical results revealed that Liraglutide promoted osteoblastic activity while suppressing osteoclastic activity. Micro-CT findings supported these outcomes, indicating significant improvements in bone volume, trabecular thickness, and structural integrity. CONCLUSION: Liraglutide enhances bone healing and exerts a synergistic effect when used in combination with bone grafts. These findings suggest that Liraglutide serves as a promising adjunct in bone tissue engineering and regenerative medicine.
OBJECTIVE: Recent evidence highlights a fundamental link between masticatory function and brain health. Once regarded solely as a peripheral motor activity for food processing and occlusal balance, mastication is now rec...OBJECTIVE: Recent evidence highlights a fundamental link between masticatory function and brain health. Once regarded solely as a peripheral motor activity for food processing and occlusal balance, mastication is now recognized as a key factor in maintaining and enhancing cognitive function across the lifespan. DESIGN: This narrative review was conducted using relevant keywords through searches in PubMed, Scopus, and Web of Science, as well as manual searching of the bibliographies of journal articles. RESULTS: Basic research has shown that chewing stimulates neurogenesis in the hippocampus, resulting in increased neuronal and synaptic density, as well as the upregulation of brain-derived neurotrophic factor (BDNF), which leads to improvements in memory and cognition. This effect has been documented in both animal and clinical research, particularly among the elderly, and is supported by data from national health programs, which indicate that adequate prosthodontic rehabilitation can help preserve cognitive function. Etiopathogenetic insights suggest that loss of posterior teeth, rather than overall tooth count, is particularly detrimental, as these teeth are essential for effective mastication. Proposed mechanisms involve exercise-induced myokines, such as Cathepsin B, and chewing-induced neprilysin production, which may mediate hippocampal neuroprotection. CONCLUSIONS: Collectively, these findings support a paradigm shift: mastication should be promoted as a preventive strategy for both oral and neural health. Public health efforts and clinical practices should integrate education on maintaining posterior dentition, promoting diets with adequate texture, and supporting prosthetic rehabilitation to sustain neuromuscular activity, thereby protecting cognitive function from early development through old age.
OBJECTIVE: This review presents an integrative framework of the "Mastication-Respiration Axis," proposing that the masticatory and respiratory systems interact to form a functional axis essential for the development and...OBJECTIVE: This review presents an integrative framework of the "Mastication-Respiration Axis," proposing that the masticatory and respiratory systems interact to form a functional axis essential for the development and maintenance of cognitive health in brain circuits. DESIGN: We narratively synthesized studies identified by structured searches of PubMed from inception to September 1, 2025, using predefined keywords related to mastication/chewing, nasal respiration/breathing, and cognition, and including peer-reviewed human and animal studies published in English. RESULTS: Evidence shows that mastication and respiration are coordinated at the brainstem through central pattern generators. Dysfunction in this axis-such as reduced chewing or oral breathing-activates stress and inflammatory pathways. The prefrontal cortex, hippocampus, and cerebellum depend on rhythmic inputs from both systems, with nasal respiration acting as a cortical pacemaker. Animal studies demonstrate that masticatory deficiency impairs hippocampal memory, while respiratory disruption during critical developmental periods causes long-lasting cerebellar and affective-motor deficits, offering a neurobiological basis for clinical links between oral breathing and neurodevelopmental disorders. CONCLUSIONS: Mastication and respiration are not merely peripheral functions but are deeply integrated with the central nervous system, forming a critical axis for brain development, plasticity, and function. Dysfunction in this axis, particularly during sensitive developmental windows, may lead to long-term impairments in memory, motor control, and affective regulation. This integrated model highlights the clinical importance of early interventions in dental, orthodontic, and respiratory health to support lifelong neurological well-being.
OBJECTIVE: This study aimed to establish matched patient-derived organoids from oral squamous cell carcinoma (PDO-T) and adjacent normal mucosa (PDO-N), characterize their distinct features, and evaluate their impact on...OBJECTIVE: This study aimed to establish matched patient-derived organoids from oral squamous cell carcinoma (PDO-T) and adjacent normal mucosa (PDO-N), characterize their distinct features, and evaluate their impact on drug response. DESIGN: PDOs were generated from primary OSCC tissues and matched adjacent normal mucosa obtained from 18 patients. Morphological and histological characteristics were assessed using brightfield microscopy and phalloidin staining. Immunohistochemistry was performed to evaluate differential marker expression. Drug response assays were conducted in paired PDO-T and PDO-N to assess chemotherapeutic sensitivity. RESULTS: We successfully established 5 PDO-T and 15 PDO-N lines, with PDO-N exhibiting a higher success rate (∼80 %). Morphological analysis showed that PDO-N formed spherical structures with a central cavity and polarity, while PDO-T displayed irregular structures with heterogeneous cell arrangements. Immunohistochemistry revealed broad distribution of Ki-67, p63 and YAP/TAZ in PDO-T, contrasting with their basal layer restriction in PDO-N. p53 was strongly positive in PDO-T. CK5 and CK13 exhibited a stratified pattern in PDO-N. Importantly, drug testing in paired PDO-T and PDO-N revealed divergent responses, with PDO-N generally more resistant and able to maintain morphological integrity under high-dose treatment. CONCLUSION: Our comparative analysis delineates distinct features between PDO-T and PDO-N in morphology, biomarker expression, and drug response. These findings provide an intuitive framework for their identification, thereby improving the accuracy of drug screening and enhancing the translational value of PDOs.
OBJECTIVES: To map and synthesise current evidence on how lifelong biological, environmental, and social exposures, collectively conceptualised as the exposome, interact with the human oral microbiome to influence oral d...OBJECTIVES: To map and synthesise current evidence on how lifelong biological, environmental, and social exposures, collectively conceptualised as the exposome, interact with the human oral microbiome to influence oral disease development and progression within a One Health framework. DESIGN: A scoping review was conducted to identify peer-reviewed studies published in English that examined the relationships between the exposome and the human oral microbiome. The review followed the Arksey and O'Malley framework, applying its five-stage methodological approach. Comprehensive searches were performed in MEDLINE, Embase, PsycInfo, Scopus, Web of Science, and CINAHL. Study quality was assessed using the Joanna Briggs Institute (JBI) tools, and results were reported in accordance with PRISMA-ScR guidelines. RESULTS: A total of twenty-nine studies were included in this review. These showed that health status, non-communicable diseases, medication use, and psychosocial factors influence the biodiversity, abundance, and function of the human oral microbiome. Other studies suggested that animal interactions and physical and chemical exposures can alter host-microbiome interactions, as well as microbial community dynamics within the oral cavity. While the studies reviewed used reliable methods and standardized protocols, they were of moderate quality due to small sample sizes, potential reverse causality, and limited control for confounding and multiple testing. CONCLUSION: This review highlights the complexity of the human oral microbiome and its interactions with the various components of the exposome, emphasizing the focus on disease impact and health behaviours, while noting a gap in research on non-bacterial communities, interaction mechanisms, and long-term effects on dysbiosis.
Teodosio LM, Barbosa AFS, de Queiroz AM
… +8 more, de Oliveira HF, Zamperini CA, Mazzi-Chaves JF, Sousa-Neto MD, Silva-Sousa YTC, Rached-Junior FJA, Alfredo E, Lopes-Olhê FC
OBJECTIVE: This study evaluated a novel methodology for assessing dentin wear resistance and morphological changes in teeth submitted to conventional (CR) or hypofractionated radiotherapy (HR). DESIGN: Fifteen maxillary...OBJECTIVE: This study evaluated a novel methodology for assessing dentin wear resistance and morphological changes in teeth submitted to conventional (CR) or hypofractionated radiotherapy (HR). DESIGN: Fifteen maxillary canines were divided into three groups: control, CR (60 Gy, 2 Gy/day) and HR (55 Gy, 2.75 Gy/day). The roots were sectioned 3 mm from the apex and 3 mm above and fixed in acrylic resin and tested on a universal testing machine by measuring the force required to wear away the dentin. The specimens were submitted to microhardness analysis with indentations at 50, 100 and 150 µm from the radicular canal surface, scanning electron microscopy (SEM) to identify cracks and energy dispersive X-ray spectroscopy (EDS-X) to quantify calcium (Ca) and phosphorus (P) and analyze the Ca/P ratio. RESULTS: No significant difference in wear resistance (MPa) was detected between the irradiated groups (CR: 0.102 ± 0.01, HR: 0.111 ± 0.01) and the control group (0.114 ± 0.02) (p > 0.05). Lower microhardness values were observed in the irradiated groups (CR: 37.92 ± 5.78, HR: 32.71 ± 4.37) compared to the control (50.00 ± 3.31), with no difference between them (p > 0.05). The irradiated groups had a higher number of cracks compared to the control, and there was no statistically significant difference in the Ca/P ratio values between the groups tested (p > 0.05). CONCLUSIONS: The new method assessed the wear resistance of dentin after radiotherapy reliably. Although wear resistance and the Ca/P ratio were not altered, both radiotherapy protocols reduced dentin microhardness.
BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues. Berberine (BBR), a natural alkaloid with anti-inflammatory and antioxidant properties, has shown potent...BACKGROUND: Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues. Berberine (BBR), a natural alkaloid with anti-inflammatory and antioxidant properties, has shown potential in treating inflammatory diseases. METHODS: Differentially expressed genes (DEGs) between periodontitis and healthy gingival tissues were identified using the GSE23586 and GSE173078 datasets, while chronic periodontitis-related genes were retrieved from the GeneCards database. Key genes were screened through support vector machine (SVM) and random forest (RF) algorithms, molecular docking, and normal mode analysis. In vitro, human gingival fibroblast-1 (HGF-1) cells were treated with lipopolysaccharide (LPS) to simulate periodontitis. RESULTS: Six key genes (KRT14, IGFBP6, LRG1, MZB1, DEFB103A, and CD79A) were identified by both SVM and RF algorithms. LRG1 was selected for further study due to its significant downregulation after BBR treatment in LPS-treated HGF-1 cells. LPS treatment increased LRG1 expression and the p-p38/p38 ratio, whereas these effects reversed by BBR treatment. Overexpression of LRG1 diminished BBR's inhibitory effect on p-p38/p38, while the p38 MAPK pathway inhibitor restored BBR's efficacy. BBR treatment suppressed LPS-induced inflammatory response, oxidative stress, and ECM degradation, but these effects were relieved by ectopic LRG1 expression. CONCLUSION: BBR alleviated LPS-induced periodontitis by inhibiting inflammation, oxidative stress, and ECM degradation through inactivation of the LRG1/p38 MAPK signaling pathway. These findings highlight BBR's potential as a therapeutic agent for periodontitis, offering a novel molecular target for clinical intervention. Further in vivo studies are warranted to validate its clinical application.
BACKGROUND: Antimicrobial peptides are integral components of the innate immune system and play a vital role in maintaining oral homeostasis. LL-37, the only human cathelicidin antimicrobial peptide, has gained increasin...BACKGROUND: Antimicrobial peptides are integral components of the innate immune system and play a vital role in maintaining oral homeostasis. LL-37, the only human cathelicidin antimicrobial peptide, has gained increasing attention due to its broad-spectrum antimicrobial activity and diverse immunomodulatory functions within the oral cavity. OBJECTIVE: This narrative review aims to characterise the molecular structure, biological functions, and clinical relevance of LL-37 in oral health and disease. MATERIALS AND METHODS: A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, and Google Scholar, to identify relevant in vitro, in vivo, and clinical studies evaluating the expression, mechanisms of action, and pathological implications of LL-37 in oral tissues. RESULTS: LL-37 is expressed by various oral tissues, including the gingival epithelium, salivary glands, and inflammatory cells, contributing to host defence against microbial challenges. In addition to its direct antimicrobial effects, LL-37 modulates inflammatory responses, promotes wound healing, and influences cellular proliferation and angiogenesis. Altered expression of LL-37 has been associated with the pathogenesis of several oral diseases, such as periodontitis, dental caries, endodontic infections, and oral squamous cell carcinoma. CONCLUSION: LL-37 plays a multifaceted role in oral immunity by integrating antimicrobial, immunomodulatory, and tissue-regenerative functions. Enhanced understanding of its molecular characterisation and biological activities may support the development of LL-37 as a diagnostic biomarker and a potential therapeutic target in oral pathology.
OBJECTIVE: HOXD10 is implicated in the carcinogenesis and progression of various cancers, including oral cancer. However, its regulatory mechanism and functional role remain unclear. DESIGN: Matched normal and oral cance...OBJECTIVE: HOXD10 is implicated in the carcinogenesis and progression of various cancers, including oral cancer. However, its regulatory mechanism and functional role remain unclear. DESIGN: Matched normal and oral cancer tissue samples from patients stratified into oral potentially malignant disorders (OPMD, n = 25), lymph-node negative (LN(-), n = 25), and lymph-node positive (LN(+), n = 25) groups were analysed along with a panel of oral cancer cell lines. Expression was quantified by qRT-PCR and DNA methylation was profiled by methyl-capture sequencing followed by correlation analysis with expression. The DNA methyltransferase inhibitor(DNMTi): Decitabine(5-Aza-CdR) and histone deacetylase inhibitors(HDACi) - suberoylanilide hydroxamic acid(SAHA) and sodium butyrate(NaB) were used to evaluate epigenetic regulation in SCC9 cells. Promoter regions were characterized by dual luciferase assay and sodium butyrate effects on cell proliferation, migration and cell cycle were assessed. RESULTS: HOXD10 was significantly upregulated in OPMD and LN(+) groups and oral cancer cell lines but not in the LN(-) samples or across cancer stages/grades compared with normal controls. Promoter hypermethylation correlated positively, though not significantly, with expression. 5-Aza-CdR treatment did not alter HOXD10 levels, while HDACi treatment reduced expression. Two promoter regions were identified as active regulatory elements modulated by histone acetylation. Functionally, NaB impaired cell proliferation, migration and induced G2-M arrest. Survival analysis demonstrated modest prognostic value of HOXD10 alone but improved predictive accuracy for disease recurrence when integrated with tumor stage and grade. CONCLUSION: HOXD10 expression in oral cancer is regulated predominantly via histone acetylation. These findings highlight its epigenetic regulation and suggest potential clinical relevance with tumor stage and grade although further studies are needed to confirm diagnostic or prognostic value.
OBJECTIVE: In this study, we examine the role of the leucine-rich pentatricopeptide repeat-containing gene (LRPPRC) as a new m6A reader in head and neck squamous cell carcinoma (HNSCC). We also analyze its expression pat...OBJECTIVE: In this study, we examine the role of the leucine-rich pentatricopeptide repeat-containing gene (LRPPRC) as a new m6A reader in head and neck squamous cell carcinoma (HNSCC). We also analyze its expression pattern, prognostic significance, and response to immunotherapy. DESIGN: LRPPRC expression was comprehensively analyzed in HNSCC using data from The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) and then validated in an independent patient cohort using real-time qPCR. The study further investigated the correlations between LRPPRC expression and methylation status, as well as their associations with clinicopathological features, patient prognosis, and immune profiles. Additionally, the impact of LRPPRC expression on the response to immunotherapy was assessed. RESULTS: We found that LRPPRC is significantly upregulated in HNSCC tissues and correlates with advanced clinicopathological features, nodal metastasis, and poor survival outcomes. In contrast, the DNA methylation level of LRPPRC was found to be reduced in HNSCC. Furthermore, LRPPRC expression is significantly correlated with infiltration of immune cells, specifically in CD4⁺ T cells, macrophages, and dendritic cells. Importantly, the expression of LRPPRC has been found to be a predictor of resistance to immunotherapy in patients with HNSCC. CONCLUSION: Our findings suggest that LRPPRC may serve as a promising biomarker for HNSCC prognosis and a therapeutic target for controlling cancer metastases and enhancing patient outcomes, while being a predictor for immune therapy response as well.
OBJECTIVES: Oral live microbial therapeutics (LMTs) show promise for halitosis, caries, and adjunctive periodontal care, yet benefits often fade after dosing stops. We synthesized evidence across indications and reframed...OBJECTIVES: Oral live microbial therapeutics (LMTs) show promise for halitosis, caries, and adjunctive periodontal care, yet benefits often fade after dosing stops. We synthesized evidence across indications and reframed development around quantifying and engineering persistence at intraoral sites, while outlining safety-by-design and delivery considerations for the oral niche. DESIGN: This narrative review integrated randomized trials, observational studies, and in vitro/ex vivo investigations to characterize clinical outcomes, persistence-related metrics, and engineering principles relevant to oral LMT development. Sources included PubMed/MEDLINE, Web of Science, Embase, and ClinicalTrials.gov, with backward/forward citation tracking. We included studies on LMTs in oral or gut contexts when mechanistically informative for oral applications (e.g., persistence, delivery, or biocontainment). Eligibility required clinical outcomes or persistence-related readouts. Two reviewers screened records and resolved disagreements by consensus. Reporting and assay principles were informed by STORMS and MIQE to support transparent, reproducible methods. RESULTS: Across indications, effects typically peak during dosing and attenuate after cessation, varying with strain, delivery format, and co-interventions (e.g., tongue dorsum debridement; standardized periodontal care). Persistence is rarely co-measured with clinical endpoints, limiting mechanistic interpretation. We outline a site-resolved measurement set, including time above the limit-of-detection, colonization area under the curve, apparent half-life (t½), and t½ under oral-mimetic shear, together with an engineering toolkit combining mucoadhesive/enamel-interactive carriers, single-cell coatings, and multilayer biocontainment (e.g., logic-gated/CRISPR kill switches, synthetic auxotrophy), and chemistry, manufacturing, and controls considerations. CONCLUSIONS: Embedding persistence metrics and safety-by-design into study protocols may support more durable outcomes, and standardized, site-resolved reporting will be essential for clinical translation.
OBJECTIVE(S): We compared the antimicrobial and antivirulence activities of juglone, a plant-derived naphthoquinone, with chlorhexidine (CHX), a widely used dental antiseptic, against Enterococcus faecalis, a pathogen as...OBJECTIVE(S): We compared the antimicrobial and antivirulence activities of juglone, a plant-derived naphthoquinone, with chlorhexidine (CHX), a widely used dental antiseptic, against Enterococcus faecalis, a pathogen associated with persistent oral and endodontic infections. DESIGN: Antimicrobial efficacy was evaluated using well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. Possible interactions between juglone and CHX were investigated using well diffusion and checkerboard methods. Antivirulence activity was assessed by measuring secreted enzymes (caseinase, gelatinase, and hemolysin), biofilm formation, metabolic activity, extracellular polymeric substance (EPS) production, and disruption of mature biofilms. Oxidative stress responses were examined through lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC). RESULTS: Juglone showed antibacterial activity with MICs in a similar range to CHX; however, no synergistic interaction between the two agents was observed. Juglone strongly inhibited caseinase, gelatinase, and hemolysin, whereas CHX showed no effect on caseinase and weaker inhibition of the others. CHX more effectively reduced early biofilm formation, metabolic activity, and mature biomass, whereas both agents similarly decreased EPS production and viability during biofilm development. Notably, in preformed biofilms, juglone at 16 ×MIC caused greater killing (∼4-log CFU) than CHX (∼2-log). Both compounds increased LDH release and reduced SOD activity and T-AOC, while juglone uniquely decreased MDA levels, indicating additional redox-modulating effects. CONCLUSIONS: Juglone impairs E. faecalis virulence by reducing enzymatic activity, oxidative stress tolerance, and biofilm viability, with stronger effects on established biofilms, highlighting its potential for further investigation in oral infection management.
OBJECTIVE: This study assessed peri-implantitis risk by measuring odor using a novel device capable of identifying odorous components and bacteria specific to peri-implantitis. DESIGN: Implants from eight peri-implantiti...OBJECTIVE: This study assessed peri-implantitis risk by measuring odor using a novel device capable of identifying odorous components and bacteria specific to peri-implantitis. DESIGN: Implants from eight peri-implantitis patients and superstructures from 20 maintenance patients were evaluated using organoleptic testing and an odor detection device (nose@MEMS, I-PEX, Kyoto, Japan). In the maintenance group, 13 superstructures emitted odor, while 7 did not. Plaque samples were collected from peri-implant sites, and bacterial composition was analyzed via 16S rRNA sequencing. RESULTS: Principal component analysis of odor measurements obtained with the I-PEX system revealed that implants from peri-implantitis patients and odor-positive superstructures during maintenance formed a distribution distinct from odor-negative superstructures. Comparative analysis of bacterial composition between samples in the odor-associated region (Region A) and those including odor-negative superstructures (Region B) showed that Region A had a higher proportion of anaerobic bacteria, while Region B was enriched in commensal oral bacteria. Among 14 bacterial species previously linked to peri-implantitis, Porphyromonas gingivalis, Tannerella forsythia, and Porphyromonas endodontalis were significantly more abundant in Region A, whereas Fretibacterium fastidiosum and Mogibacterium were significantly lower. CONCLUSIONS: The odor characteristics of peri-implantitis and odor-positive superstructures were similar and clearly distinguishable from odor-negative counterparts. The shared odor profile was associated with higher proportions of bacterial species previously linked to peri-implantitis. These findings imply that odor analysis using this novel device may provide a promising strategy for implant maintenance and peri-implantitis risk prediction.
OBJECTIVE: This systematic review and meta-analysis (SRM) investigated the potential of garlic (Allium sativum) against cariogenic oral microorganisms. DESIGN: The SRM was conducted following PRISMA guidelines and regist...OBJECTIVE: This systematic review and meta-analysis (SRM) investigated the potential of garlic (Allium sativum) against cariogenic oral microorganisms. DESIGN: The SRM was conducted following PRISMA guidelines and registered in PROSPERO (CRD420251133140). Randomized clinical trials (RCTs) evaluating garlic or garlic-derived compounds on cariogenic oral microorganisms were included. A literature search was performed in the main scientific databases. Meta-analyses were performed using RevMan software, with standardized mean difference (SMD) as the effect measure, and a random-effects model was applied with 95 % confidence intervals. Risk of bias was assessed using the Cochrane tool, and the certainty of evidence was graded according to the GRADE approach. RESULTS: Nine RCTs fulfilled the inclusion criteria, predominantly assessing S. mutans, followed by Lactobacillus spp. and C. albicans. All included trials employed garlic-based mouthwashes as the intervention and consistently demonstrated significant antimicrobial activity. In meta-analysis, compared to chlorhexidine, garlic reduced S. mutans at 1 week (SMD = -0.73, 95 % CI = -1.39 to -0.07, I² = 73 %; p = 0.03), had a slightly lower effect at 2 weeks (SMD = 1.27, 95 % CI = 0.09-2.44, I² = 90 %; p = 0.03), and showed no difference at 1 month (SMD = -0.54, 95 % CI = -2.78-1.70, I² = 96 %; p = 0.64). Compared to sodium fluoride, it demonstrated superior activity at 2 weeks (SMD = -0.79, 95 % CI = -1.22 to -0.36, I² = 0 %; p = 0.0003). Most studies had a low risk of bias, and the certainty of the evidence was rated low. CONCLUSIONS: Garlic-based mouthrinses show significant antimicrobial activity against cariogenic microorganisms, supporting their potential as a phytotherapeutic strategy for biofilm control. However, the evidence remains limited, demonstrating the need for further high-quality clinical trials to confirm long-term efficacy.
OBJECTIVES: To investigate the influence of lack of sclerostin on craniofacial morphology in sclerostin gene (Sost) knockout (Sost) mice. DESIGN: Micro computed tomography (micro-CT) was performed on both 60-day-old wild...OBJECTIVES: To investigate the influence of lack of sclerostin on craniofacial morphology in sclerostin gene (Sost) knockout (Sost) mice. DESIGN: Micro computed tomography (micro-CT) was performed on both 60-day-old wild-type and Sost mice to analyze changes in craniofacial morphology. Ten anatomical landmarks and eight measurement parameters as well as the total mandibular volume were used to assess craniofacial features. In addition, the femora of both wild-type and Sost mice were examined using micro-CT and histological analysis. Cancellous bone volume, cortical bone volume, and the number of osteoclasts beneath the growth plate in the femora were evaluated. RESULTS: The neurocranium was significantly smaller in the Sost mice than in the wild-type mice, while the length of the angular process of the mandible was significantly greater. The total mandibular volume was significantly larger in the Sost mice than in the wild-type mice. The volume of cancellous bone and cortical bone in the femora were significantly larger in the Sost mice than in the littermate wild-type mice. Histological observation showed no statistically significant difference in the number of osteoclasts present in the femora between wild-type mice and Sost mice. CONCLUSIONS: The present study showed a significant decrease in neurocranium and a significant increase in mandibular bone in Sost mice compared to wild-type mice, along with increased volumes of cancellous and cortical bone in the femora.
BACKGROUND: The adverse effects of postnatal maternal separation (MS) on offspring development are well documented; however, its specific impact on dental enamel formation remains inadequately explored. This study examin...BACKGROUND: The adverse effects of postnatal maternal separation (MS) on offspring development are well documented; however, its specific impact on dental enamel formation remains inadequately explored. This study examines the effects of maternal-separation-induced toxic stress on dental enamel formation in a murine model. METHODS: A total of 24 Wistar rat offspring (Rattus norvegicus) were utilized, divided into a control group (n = 12) and an MS group (n = 12). The MS group underwent 4 h of daily separation from their mothers from postnatal day 2 to day 21, while the control group remained undisturbed with their mothers. Throughout the experimental period, body weight, length, and key developmental milestones (including incisor eruption, eye opening, and ear opening) were monitored. At postnatal day 28, the animals were euthanized, and the incisors were collected for analysis. Incisor photographs were conducted for macroscopic evaluation. Volumetric assessment of the enamel layer was performed using micro-computed tomography (micro-CT) imaging. Microhardness testing quantified enamel resistance, while scanning electron microscopy (SEM) provided insights into the morphology and ultrastructure of incisor enamel. In addition, energy-dispersive X-ray spectroscopy (EDS) was performed to evaluate mineral content and identify possible compositional alterations in dental enamel. Data were statistically analyzed using Student's t-test (α = 0.05). RESULTS: The findings revealed an increase in body weight within the MS group (p < 0.05), while normal growth and developmental milestones exhibited no significant changes (p > 0.05). No macroscopic alterations were observed in the dental enamel of incisors of MS group. SEM analysis of the incisors indicated that the enamel structure of incisors in the MS group maintained an organized arrangement of enamel rods, characterized by densely packed, elongated structures extending from the underlying dentin to enamel surface. Furthermore, structural integrity, microhardness, and mineral composition remained largely unaffected (p > 0.05). CONCLUSION: Under the given experimental conditions, postnatal maternal separation does not significantly compromise dental enamel formation in rat offspring.
OBJECTIVE: Insulin-like growth factor-binding protein 3 (IGFBP3) is a multifunctional protein involved in various cellular functions. However, the function of IGFBP3 in periodontal ligament (PDL) tissue remains unclear....OBJECTIVE: Insulin-like growth factor-binding protein 3 (IGFBP3) is a multifunctional protein involved in various cellular functions. However, the function of IGFBP3 in periodontal ligament (PDL) tissue remains unclear. In this study, we investigated the localization and function of IGFBP3 in PDL tissues and human PDL-derived cell line. DESIGN: Small interfering RNA (siRNA) and recombinant protein of IGFBP3 were used to examine the effect of IGFBP3 in human PDL-derived cell line. mRNA expression was determined by quantitative reverse transcription-polymerase chain reaction. Protein expression was determined using immunohistochemical staining, immunofluorescence staining, and Western blotting analyses. WST-1 and migration assays were used to analyze the effects on proliferation and migration. Collagen production was examined using picrosirius red staining. Calcium nodule formation was examined using Alizarin Red S staining. RESULTS: IGFBP3 was expressed in both mouse PDL tissues and human PDL-derived cell line (2-23 cells). Mechanical stretch and Transforming growth factor-beta 1 (TGF-β1) stimulation upregulated IGFBP3 expression in 2-23 cells. Knockdown of IGFBP3 using siRNA significantly suppressed PDL-related gene expression, collagen production, and inhibited Smad2/3 phosphorylation induced by TGF-β1, while IGFBP3 knockdown enhanced calcium chloride-induced osteogenic differentiation in 2-23 cells and activated Akt phosphorylation. Furthermore, treatment with exogenous rhIGFBP3 showed the opposite trend. CONCLUSIONS: IGFBP3 plays a dual role in PDL homeostasis, by promoting collagen production and inhibiting osteogenic differentiation. IGFBP3 is involved in TGF-β-Smad2/3 pathway and related with phosphorylation of Akt, highlighting IGFBP3 as a potential therapeutic target for periodontal regeneration.
OBJECTIVES: To evaluate whether fluoride secretion by labial minor salivary glands exhibits a pharmacokinetic pattern comparable to that of major salivary glands after oral fluoride intake. DESIGN: In a randomized, blind...OBJECTIVES: To evaluate whether fluoride secretion by labial minor salivary glands exhibits a pharmacokinetic pattern comparable to that of major salivary glands after oral fluoride intake. DESIGN: In a randomized, blind and crossover study, eight healthy adult participants ingested aqueous NaF solutions containing 5, 10, or 20 mg of fluoride after overnight fasting. Saliva samples were collected at baseline (time 0) and at 5, 15, 30, 60, and 120 min post-ingestion from four sources: labial minor glands (LG), parotid glands (PG), floor of the mouth (FS), and whole saliva (WS). LG saliva and FS were collected using pipette tips under gentle suction, while PG saliva was obtained using the Carlson-Crittenden device and WS was obtained by asking participants to expectorate directly into a 1.5 mL microtube. Fluoride concentrations were determined using a validated micro-method with an inverted fluoride ion-selective electrode. Pharmacokinetic parameters - maximum concentration (Cmax) and area under the curve (AUC) - were calculated. Data were analyzed by two-way ANOVA and linear regression (α=0.05). RESULTS: Fluoride secretion from LG demonstrated a dose-dependent response, with Cmax values of 0.37 ± 0.04, 0.45 ± 0.04, and 0.76 ± 0.19 µg/mL, and AUC values of 29.0 ± 6.2, 33.6 ± 3.4, and 52.7 ± 11.5 µg F/mL × min for 5, 10, and 20 mg doses, respectively. These parameters did not differ significantly from those obtained from other salivary glands. A significant linear correlation was observed between the ingested fluoride dose and LG fluoride secretion (R² = 0.6469, p < 0.0001). CONCLUSION: The pharmacokinetic profile of fluoride secretion in labial minor salivary glands is quantitatively comparable to that of major salivary glands. Their use as an alternative source in fluoride pharmacokinetic studies appears valid, offering a non-invasive and practical sampling method.
OBJECTIVE: The aim of this study is to evaluate the effect of topical sevoflurane, which has recently been reported to possess analgesic, anti-inflammatory and antibacterial properties, on secondary wound healing in rat...OBJECTIVE: The aim of this study is to evaluate the effect of topical sevoflurane, which has recently been reported to possess analgesic, anti-inflammatory and antibacterial properties, on secondary wound healing in rat palatal mucosa. DESIGN: Thirty male Wistar Albino rats were randomly divided into three groups: Control, Saline (0.9 % NaCl) and Sevoflurane. Standardized full-thickness excisional wounds (4 mm) were created on the hard palate, and treatment was applied once daily for 14 days. Wound closure, histopathological healing and immunohistochemical expression of vascular endothelial growth factor, interleukin-17A, interleukin-22 and signal transducer and activator of transcription 3 were evaluated on days 5 and 14. RESULTS: On day 5, the sevoflurane group exhibited smaller wound areas (p < 0.05) and greater angiogenesis, epithelialization, and granulation than the control group. On day 14, epithelial integrity and vascular remodeling were most pronounced in the sevoflurane group. IL-22 and pSTAT3 expression levels were higher, while IL-17A expression was lower (p < 0.05). VEGF expression decreased over time, indicating progression toward tissue remodeling. CONCLUSIONS: Topical sevoflurane enhances early-stage wound healing by modulating inflammatory and regenerative pathways, promoting angiogenesis, and reducing wound size. These findings suggest that sevoflurane may serve as a novel adjunct for periodontal wound healing.