Search Results (71)

(1) Background: Orthodontic tooth movement (OTM) during sliding mechanics is influenced by a multitude of interactions. Studies suggest that vibration induced by mastication or usage of electric tooth brushes might impact resistance to sliding (${\mathrm{R}}_{\mathrm{S}}$) in conventional brackets. In superelastic brackets, archwire sliding might also be altered due to deformation of the bracket wings during mastication. Therefore, the aim of this study was to investigate how the superelastic properties of Nickel–Titanium (NiTi) brackets affect archwire sliding during mastication. (2) Methods: Orthodontic superelastic NiTi archwires with diameters of 0.014” and 0.016” were ligated into four superelastic NiTi brackets. One bracket was positioned with a vertical offset of 1 mm to simulate clinical vertical leveling. A weight force was applied to axially preload the archwire. The occlusal and axial forces affecting the movement of the archwires through the bracket were measured. (3) Results: Low chewing forces caused a measurable axial movement of the 0.014” wire. Increased chewing forces resulted in higher axial movements. The archwire diameter had an impact: 0.014” NiTi required lower masticatory forces to initiate wire motion as compared to the 0.016” NiTi. (4) Conclusions: The superelastic NiTi brackets examined showed that under simulated continuous dynamic masticatory loading, obstacles such as friction or binding could be overcome. Full article

Streptococcus mutans is the primary etiological agent of dental caries due to its ability to form acidogenic biofilms on tooth surfaces. Natural monoterpenes have attracted considerable interest as potential antibiofilm agents for oral healthcare. The present study investigated the antibiofilm activity and possible mechanism of action of (+)-endo-borneol isolated from the essential oil of Achillea millefolium against S. mutans. The chemical composition of the essential oil was characterized by gas chromatography–mass spectrometry (GC–MS), and (+)-endo-borneol was isolated by chromatographic separation. Antibiofilm activity was evaluated using the crystal violet biofilm assay, while antimicrobial activity was determined by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The influence of subinhibitory concentrations of (+)-endo-borneol on the expression of the biofilm-associated genes gtfB and yycF was assessed by quantitative real-time PCR. Molecular docking was performed to investigate ligand–protein interactions, using a ligand geometry pre-optimized by density functional theory (DFT, B3LYP/6-31G**). The essential oil inhibited S. mutans biofilm formation by up to 98%, whereas isolated (+)-endo-borneol reduced biofilm biomass by 97–98% at concentrations of 2–10 mg/mL. The MIC and MBC values of (+)-endo-borneol were 2.5 and 5.0 mg/mL, respectively. Gene expression analysis demonstrated that subinhibitory concentrations of (+)-endo-borneol modulated the transcription of gtfB and yycF, indicating activation of bacterial regulatory responses. Molecular docking revealed favorable binding of (+)-endo-borneol to biofilm-related protein targets. These findings demonstrate that (+)-endo-borneol is a promising natural antibiofilm compound with potential application in the development of novel preventive and therapeutic oral healthcare products targeting S. mutans biofilms. Full article

Endodontic irrigant solutions act as crucial pretreatment conditioning agents in dentin biomimetic remineralization, preparing the collagen scaffold for calcium phosphate infiltration and subsequent tooth structure reconstruction. In this study, root dentin discs were exposed for 10 min to five irrigant solutions: sodium hypochlorite (NaClO, 3%), EDTA (17%), citric acid (CA, 10%), chlorhexidine (CHX, 2%), and an innovative experimental formulation containing citric acid (7%) and surfactants. Samples were then aged in Hank’s Balanced Salt Solution (HBSS) at 37 °C for three months to simulate long-term clinical conditions. Physicochemical modifications of the collagen and apatite phases were assessed at each experimental stage using ATR-FTIR spectroscopy, with the A_CaP/A_{Amide I} and A₈₇₀/A_CaP absorbance ratios as markers of the degree of mineralization and apatite carbonate content, respectively. Results indicated that CHX- and EDTA-treated dentin exhibited the highest remineralization after ageing, while NaClO impeded remineralization due to collagen degradation. The experimental irrigant produced the most pronounced demineralization, followed by CA; however, it also facilitated significant remineralization, attributed to citrate–collagen binding and surfactant-enhanced apatite nucleation. NaClO selectively degraded collagen and increased apatite crystallinity; CA inhibited apatite nucleation through adsorbed citrate ions, and CHX and EDTA induced minimal alterations. These findings provide molecular-level evidence linking short-term irrigant effects to the long-term potential for dentin biomineralization, with direct implications for irrigant selection in regenerative endodontic protocols. It should be noted that this study was conducted on dentin discs obtained from a single tooth; all findings should therefore be regarded as preliminary and require confirmation in studies with larger, biologically independent sample sizes. Full article

Dental fluorosis (DF) is a common endemic disease that damages dental enamel. Traditionally, DF has been attributed to environmental fluoride overload. Accumulating evidence has demonstrated that genetic factors also modulate individual susceptibility. No dedicated fluoride ion channels have been identified in mammalian cells; fluoride uptake is believed to occur mainly through passive diffusion of HF and nonspecific anion pathways, including chloride channels. Different types of chloride channels are expressed in dental tissues, such as CFTR and voltage-gated chloride channels (ClCs), but it remains unknown whether these channels transport fluoride and whether their variants influence DF risk. This study combined human population-based investigations, mouse and zebrafish models, and in vitro experiments to confirm the significant genetic association of CFTR and CLCN3 variants with DF. A total of 889 DF cases and 834 matched controls were recruited from the same fluoride-contaminated region. Tag SNP screening of CFTR and eight ClC chloride channel genes (CLCNs) revealed that rs213950 in CFTR and three SNPs in CLCN3 were significantly associated with DF. CFTR and ClC-3 showed different fluoride tolerances. rs213950 in CFTR affected the efficiency of fluoride ion transport in Xenopus oocytes. ClC-3 enabled yeast cells to resist fluoride toxicity, whereas clcn3 deficiency disrupted tooth and craniofacial development in zebrafish. Fluoride exposure altered nucleoprotein binding to the rs10520161 region and changed the mRNA levels of various ClC-3 transcripts. These transcripts displayed different subcellular locations and fluoride conductances and acted synergistically to confer fluoride resistance. Together, these findings raise the possibility that variants in CFTR and CLCN3 may act synergistically to influence DF susceptibility. This potential interplay highlights DF as a complex trait involving dysregulated fluoride handling and underscores the multifactorial, gene-directed regulation of fluoride transport. Full article

The demineralization of tooth enamel is the primary consequence of dental caries, leading to cavities and finally tooth loss. Erosive tooth wear from acidic beverages and food is another factor that degrades enamel. In both cases, an acidic environment leads to etching and the final dissolution of tooth mineral, i.e., hydroxyapatite. Here, this process is discussed from a chemical perspective, taking into account the solubility of calcium phosphate and the presence of the pellicle (protein layer) and plaque (bacterial biofilms), which both affect the dissolution rate. While low pH is definitely decisive, calcium-binding ligands (e.g., acid anions, proteins) contribute to dissolution by removing calcium ions from the equilibrium. This is an important effect in the oral cavity where the concentration of biomolecules is high. The situation is complicated by the fact that the composition of saliva and the oral microbiome vary considerably between individuals. The state of current knowledge on the demineralization of enamel is summarized and discussed, also in the context of approaches to prevent dental caries and erosive tooth wear. Full article

The C-terminal binding protein 1 (CTBP1) is a transcriptional corepressor with a major role in nervous system growth and development. There are only 20 published cases with CTBP1 mutations, displaying a phenotype of Hypotonia, Ataxia, Developmental Delay and Tooth enamel defect Syndrome (HADDTS). Histochemical evidence of decreased mitochondrial respiratory chain activity has been previously reported, but comprehensive data on the metabolic phenotype assessed by various cellular respiration parameters are still missing. We present a 10-year-old female with typical HADDTS features, harboring the most reported de novo heterozygous CTBP1 mutation c.991C>T. To elucidate her metabolic phenotype, we quantified mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) utilizing an analyzer for assessing mitochondrial function (Seahorse XFp). Real-time metabolic assays revealed profound mitochondrial dysfunction with significantly attenuated maximal respiration and spare respiratory capacity compared to neurotypical controls. Following mitochondria-targeted nutritional support for one-year measurable bioenergetic improvements and reduced number of respiratory infections were registered. However, neurological recovery and new skill acquisition were not observed. We present a novel case of CTBP1-related neurodevelopmental disorder and demonstrate, for the first time, the application of non-invasive, real-time mitochondrial functional assessment in this setting, providing additional evidence for mitochondrial dysfunction in HADDTS. Full article

Periodontitis represents a primary etiological factor in tooth mobility, with oxidative stress contributing critically to periodontal tissue destruction. Evodiamine (EVO), a quinazolinocarboline alkaloid, exhibits multiple biological activities; however, its antioxidant effects and mechanism in periodontitis have not been elucidated. The aim of this study was to investigate the regulatory effect of EVO on oxidative stress in periodontitis and to explore the associated molecular mechanism. The results indicate that EVO exhibits potent antimicrobial activity against key periodontal pathogens and suppresses pathogen-induced ROS generation as well as the release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) under periodontitis conditions. EVO binds specifically to the Kelch domain of KEAP1 with a strong binding energy (−11.67 kcal/mol), inhibits KEAP1–NRF2 interaction, and consequently upregulates the expression of antioxidant enzymes (HO-1, NQO1, GCLC, and SOD2), while downregulating the expression of iNOS, COX2, and NOX2. Furthermore, EVO inhibits the pro-apoptotic effect of the JAK2/STAT3 signaling axis and mitigates inflammation, alleviates cell cycle arrest, and promotes the migration and repair of periodontal ligament cells. Collectively, these findings suggest that EVO acts as a potential binder of KEAP1 that alleviates periodontal inflammation through modulation of oxidative stress and regulation of the JAK2/STAT3 pathway. Full article

Periodontitis is a chronic infectious disease characterized by the destruction of the tooth-supporting tissues, including the gingiva, periodontal ligament, and alveolar bone, which may ultimately lead to tooth loss. However, blood-based biomarkers reflecting systemic inflammation in periodontitis remain poorly defined. We analyzed plasma proteomic data from the UK Biobank using Olink Explore proteomics to identify systemic protein signatures distinguishing chronic periodontitis patients (n = 90) from healthy controls (n = 2234). Among 2151 proteins passing quality control, 29 proteins showed significant differential expression (FDR < 1.0 × 10⁻⁵). Growth differentiation factor 15 (GDF15) exhibited the strongest upregulation (mean NPX: −0.183 to 0.157, effect size = 0.337, FDR = 2.82 × 10⁻¹²), followed by N-terminal pro-B-type natriuretic peptide (NT-proBNP) (effect size = 0.594), Interleukin-6 (IL-6) (effect size = 0.450), and Insulin-like growth factor binding protein-(4IGFBP4) (effect size = 0.269). Multiple TNF receptor superfamily members (TNFRSF1A/1B, TNFRSF10A/10B) and proteins involved in extracellular matrix remodeling (COL6A3, ADAM12) and vascular stress (ADM) were significantly elevated. In contrast, EGFR and DNER showed decreased expression. Protein–protein interaction network analysis revealed IL-6 as a central hub protein forming a tightly interconnected cluster with TNF receptor family members. These findings indicate systemic plasma protein profiles associated with chronic periodontitis within this population-based cohort. The identified proteins may provide a basis for future evaluation of blood-based biomarkers for chronic periodontitis, pending further validation. Full article

ATP-binding cassette A1 (ABCA1) is a critical molecule in facilitating cholesterol transport in a variety of organs. In the nervous system, cholesterol supply is essential and rate-limiting for myelin biogenesis, which underlies efficient conduction of nerve impulses. When myelin is damaged or improperly formed due to genetic defects, a host of neurological symptoms may arise. A rare form of peripheral neuropathy in Tangier disease (TD) patients is associated with autosomal recessive mutations in ABCA1. Accordingly, when ABCA1 loses its function due to misexpression, the neuropathic phenotype is over-represented. Independently, studies have revealed the altered expression of ABCA1 and dysregulation of cholesterol metabolism in a host of inherited peripheral neuropathies engaging the Peripheral Myelin Protein 22 (PMP22), suggesting shared pathophysiology. While the role of ABCA1 has not been investigated broadly in peripheral nerves, the transporter molecule is a therapeutic target for human disorders, including multiple sclerosis and Alzheimer’s disease. Investigations in rodent models of type 1 Charcot–Marie–Tooth (CMT) neuropathies support the candidacy of this cholesterol transporter as a therapeutic target in efforts of peripheral myelin repair. Ongoing preclinical studies in central and peripheral nervous system disease models will provide critical information on the importance of ABCA1 as a target for disease modifying intervention. Full article

Background: Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobic, immobile oral bacterium responsible for the secretion of virulence factors, namely leukotoxin (LtxA), a large exotoxin of the RTX family that enables the bacterium to evade the immune system by destroying leukocytes, resulting in aggressive periodontitis (AP) leading to tooth loss. Methods: This study aimed to screen 106 molecules derived from Moroccan propolis in order to identify potential inhibitors of the active sites of LtxA based on molecular docking, ADMET property evaluation, and molecular dynamics (MD) simulation. Results: Epigallocatechin gallate (EGCg), used as a reference compound, showed binding energies of −6.9 kcal/mol, −6.1 kcal/mol, −6.5 kcal/mol, and −5.9 kcal/mol with the four active sites P1, P2, P3, and P4, respectively. By establishing conventional hydrogen bonds, pi-alkyl bonds, and non-covalent pi–pi bonds. Chrysin and luteolin showed favorable binding affinities with the four active sites, named as follows: P1–P4 (P1–chrysin = −7.5 kcal/mol; P2–chrysin = −7.9 kcal/mol; P3–chrysin = −8.1 kcal/mol; P4–chrysin = −6.9 kcal/mol; P1–luteolin = −7.3 kcal/mol; P2–luteolin = −7.6 kcal/mol; P3–luteolin = −8.1 kcal/mol; P4–luteolin = −7.3 kcal/mol). The binding affinity of these two propolis derivatives was stabilized by pi−sigma bonds, pi−alkyl bonds, conventional hydrogen bonds, pi-cation interactions, non-covalent pi–pi bonds, and carbon–hydrogen bonds. According to free energy calculations performed with Prime MM-GBSA, the complexes formed by chrysin demonstrated the most stable interactions due to Van der Waals and lipophilic forces. Luteolin formed significant interactions, but slightly weaker than those of chrysin. These results reveal the inhibitory potential of chrysin and luteolin with protein active sites. MD simulations corroborated the excellent stability of complexes formed by chrysin, as indicated by low RMSD values, suggesting favorable dynamic behavior. Conclusions: These results highlight the potential of chrysin as a versatile inhibitor capable of interacting with the four active sites. These findings are a strong foundation for further experimental confirmations. Full article

Background/Objectives: Orthodontic tooth movement is a biological process involving coordinated bone resorption and formation in response to mechanical stimulation. The aim of this study was to evaluate the temporal changes in C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (PINP), and vitamin D-binding protein (VDBP) levels in gingival crevicular fluid (GCF) and saliva during fixed orthodontic treatment, as well as to assess the relationships among these biomarkers. Methods: The study included a total of 27 systemically and periodontally healthy individuals comprising 14 males and 13 females. Clinical periodontal parameters were assessed at three time points: before treatment (T0), at 24–48 h (T1), and on day 40 (T2). GCF and saliva samples were collected at the same time points. Levels of CTX, PINP and VDBP in GCF and saliva were quantified using enzyme-linked immunosorbent assay. The data were analyzed using both parametric and non-parametric statistical tests. Temporal changes across the three time points were evaluated using mixed-effects models, differences between GCF and saliva biomarker levels were assessed using paired tests, and correlations were examined using Spearman correlation analysis. Results: GCF and salivary CTX levels demonstrated a significant increase from T0 to T1, while PINP levels exhibited a substantial rise from T1 to T2 (p < 0.001). Levels of VDBP in both GCF and saliva did not demonstrate significant temporal changes (p > 0.05). Higher VDBP levels in both fluids were found to be negatively associated with increases in CTX and positively associated with increases in PINP (p < 0.05). Furthermore, salivary CTX and VDBP levels exhibited a consistent increase compared to those measured in GCF at all time points (p < 0.05). Conclusions: Fixed orthodontic forces elicit sequential resorptive and formative responses in both GCF and saliva. The potential of VDBP to function as a local modulator is indicated, with the capacity to influence the balance between osteoclastic and osteoblastic activity. The evaluation of these biomarkers in non-invasive biological samples may offer a valuable approach for monitoring bone metabolism throughout orthodontic treatment. Full article

Background/Objectives: Non-syndromic tooth agenesis (NSTA) is a congenital condition that causes the absence of one or more teeth without accompanying systemic abnormalities, which significantly affects quality of life. Genetic factors, including mutations in several specific genes, contribute to the pathogenesis of NSTA. This study investigates a novel EVC2 mutation in a patient with NSTA and explores its potential pathogenic mechanism, with the aim of enriching the spectrum of pathogenic genes. Methods: Whole-exome sequencing (WES) was performed on peripheral blood samples from a patient diagnosed with NSTA. Bioinformatics analysis was utilized to identify the mutation and assess its potential impact on protein structure and function. Molecular dynamics simulations were conducted to analyze structural alterations in the EVC2 protein. The binding affinity between EVC2, EVC, and Smoothened (SMO) was to determine the effect of mutation on protein–protein interaction. Protein localization and expression were analyzed using immunofluorescence and Western blotting. Reverse transcription quantitative PCR (RT-qPCR) was employed to evaluate downstream signaling pathway alterations. Results: A novel EVC2 mutation (c.1657_1660delinsA, p.Glu553_leu554delinsMet) was identified in the proband, and the mutation was maternally inherited. Molecular dynamics simulations revealed that the mutation resulted in a decrease in α-helical content and significant conformational changes in the protein structure. This led to reduced binding affinity between EVC2 and its ligands EVC and SMO, destabilizing the structural integrity of the protein complex. Despite these structural changes, EVC2 protein localization and expression were unaffected. Furthermore, a downregulation of GLI1 and SHH expression was observed, indicating impaired Hedgehog (Hh) signaling. The downregulation of the Hh signaling pathway impairs the tooth development process and may lead to the occurrence of tooth agenesis. Conclusions: A novel EVC2 mutation was identified in a patient with NSTA. Based on molecular dynamics simulations, it is hypothesized that this EVC2 variant could contribute to the pathogenesis of NSTA by impairing the EVC2-EVC-SMO complex formation, which may lead to downregulation of downstream GLI1 and SHH. These findings provide new insights into the molecular mechanisms underlying EVC2-mediated NSTA, suggesting that disruption of Hh signaling may represent a critical pathogenic mechanism. Full article

Tooth agenesis (TA), the congenital absence of one or more teeth, is the most common manifestation of defective dental morphogenesis in humans. TA can occur as an isolated (non-syndromic) condition or as part of a broader syndromic presentation. In this review, we analyzed a total of 73 manuscripts to provide a comprehensive update on the genetic landscape of TA. To investigate the genes, variants, and associated phenotypes, we reviewed data from curated databases including Human Phenotype Ontology (HPO), OMIM, ClinVar and MalaCards. Based on the current evidence, the genes most frequently implicated in TA are MSX1, EDA, and PAX9. However, chromosomal abnormalities, such as those seen in Down syndrome and Williams syndrome, along with structural variations (e.g., deletions and duplications), also contribute significantly to TA etiology. The most involved pathways include TNF receptor binding, encompassing genes such as EDA, EDA2R, EDAR, and EDARADD, and the mTOR signaling pathway, which includes AXIN2, FGFR1, LRP6, WNT10A, and WNT10B. The aim of this review is to provide an critical synthesis of the genetic mechanisms underlying TA, highlighting the contribution of major signaling pathways, regulatory networks, and emerging molecular insights that may inform diagnostic and therapeutic advances. Full article

The periodontal ligament (PDL) is a dynamic connective tissue that absorbs and transmits mechanical forces, playing a critical role during orthodontic tooth movement (OTM). This study aimed to characterize the proteomic profile of rat PDLs subjected to OTM. Ten Holtzman rats were allocated into Control and OTM groups. After 15 days of force application, hemimaxillae were harvested, and PDL tissues from the first maxillary molars were isolated via laser capture microdissection. Protein extracts were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS), followed by quantitative and enrichment analyses. Immunohistochemistry was performed to validate selected proteins. The full proteomic datasets supporting these findings are available in the PRIDE repository under the identifiers PXD055817 and PXD033647. A total of 1121 proteins were identified; 101 were exclusive to the OTM group, 324 to the control, and 696 shared. Among the 335 proteins with differential abundance, 334 were downregulated and one (Prelp) was upregulated in the OTM group. Enrichment analysis revealed that differentially abundant proteins were associated with molecular functions such as protein binding, and cellular components including extracellular exosomes, focal adhesions, and the extracellular matrix. Immunohistochemical analysis confirmed the presence of Prelp, Rbm3, and Cirbp in PDL tissues. These findings demonstrate that OTM significantly alters the proteomic landscape of the PDL and identify key proteins potentially involved in periodontal remodeling. Full article

This review paper presents a comprehensive overview of DNA preservation in hard tissues (bones and teeth) for applications in forensic and archaeogenetic analyses. It presents bone structure, DNA location in bones and teeth, and extensive information about postmortem DNA location and preservation. Aged bones are a challenging biological material for DNA isolation due to their low DNA content, degraded DNA, and the potential presence of PCR inhibitors. In addition, the binding of DNA to the mineral matrix necessitates the inclusion of a demineralization process in extraction, and its contribution to the resulting increase in both DNA quality and quantity is explained. Guidelines and recommendations on bone sample selection to obtain higher DNA yields are discussed in terms of past, recent, and possible future recommendations. Interskeletal and intraskeletal differences in DNA yield are also explained. Recent studies have shown that current recommendations for the genetic identification of skeletal remains, including femurs, tibias, and teeth, may not be the most effective sampling approach. Moreover, when mass disasters and mass graves with commingled skeletal remains are considered, there is a greater possibility that the recommended set of skeletal elements will not be available for sampling and subsequent genetic testing. This review highlights interskeletal and intraskeletal variability in DNA yield, with a focus on studies conducted on poorly preserved skeletal remains, including both postwar (1945) victims from Slovenia and ancient human skeletons. Special emphasis is placed on anatomical differences and potential mechanisms influencing DNA preservation, as demonstrated in research on both modern and historical skeletons. Finally, the petrous part of the temporal bone and tooth cementum were reviewed in greater detail because they have been recognized as an optimal sampling type in both ancient DNA studies and routine forensic case analyses. Our experiences with the Second World War and archaeological petrous bones are discussed and compared to those of other bone types. Full article