OBJECTIVES:Copper-magnesium nanoparticles (Cu-Mg NPs) have attracted increasing interest in dentistry because of their reported biological and antibacterial properties. This study evaluated the cytocompatibility of hybrid Cu-Mg NPs with oral fibroblasts, osteoblasts, and dental pulp stem cells (DPSCs) and investigated their antibacterial activity against Streptococcus mutans and Enterococcus faecalis, two clinically relevant oral pathogens associated with cariogenic and endodontic infections. METHODS:Cytocompatibility was assessed at 24, 48, and 72 h using the MTT assay, live/dead staining, and phase-contrast microscopy after exposing cells to Cu-Mg NP suspensions (0.05-6.4 mg/mL). Antibacterial activity was evaluated using NP suspensions ranging from 0.025 to 12.8 mg/mL to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Bacterial survival was further quantified by colony counting at 0.8 and 1.6 mg/mL. RESULTS:Cu-Mg NPs maintained cell viability above 70% above at concentrations of 0.05-1.6 mg/mL across all cell types and at concentrations up to 3.2 mg/mL for DPSCs. Higher concentrations (3.2 and 6.4 mg/mL) produced dose-dependent reductions in cell viability, consistent with the live/dead staining results and observed morphological changes. The MIC for both bacterial species and the MBC were 1.6 mg/mL and 12.8 mg/mL, respectively. Colony counting assays confirmed reduced bacterial survival at 0.8 and 1.6 mg/mL. CONCLUSIONS:Cu-Mg NPs exhibited antibacterial activity against S. mutans and E. faecalis while maintaining cytocompatibility at lower concentrations. These findings demonstrate a concentration-dependent response and support further evaluation of Cu-Mg NPs in applications requiring antimicrobial activity and cytocompatibility.
BACKGROUND:Alzheimer's disease (AD) is a progressive neurological condition for which current therapeutic efficacy remains limited. This narrative review evaluates AD as a system-level biological disruption and proposes a mechanistic framework that utilises small extracellular vesicles (sEVs) derived from stem cells from human exfoliated deciduous teeth (SHEDs) as neuroimmune modulators of AD. HIGHLIGHT:Databases including PubMed, Scopus, and Web of Science were used to identify relevant studies. This search strategy primarily focused on SHED-derived extracellular vesicles (EVs) and their therapeutic relevance in AD. Preclinical in vivo and in vitro studies investigating SHEDs or SHED-derived EVs in a neurological context were examined. SHED-derived EVs exhibited neurotrophic, immunomodulatory, and metabolic regulatory properties in preclinical models. Heterogeneity in the study design and the absence of direct AD validation preclude conclusions regarding their efficacy as a therapeutic strategy for AD. However, the effects of SHED-derived sEVs have shown consistent features across various neurodegenerative disease models, suggesting that their therapeutic relevance is underexplored. Broader evidence from mesenchymal stem cell (MSC)-derived sEVs in AD transgenic models provides a mechanistic foundation for this research gap. With specific microRNA loading, SHED-derived sEVs may modulate AD-relevant pathological pathways. CONCLUSION:Good Manufacturing Practice-compliant SHED expansion, standardised EV isolation, careful dose evaluation, and effective delivery systems are essential for advancing SHED-derived EV strategies. However, direct validation of SHED-derived sEVs in AD-specific in vivo models remains necessary. Therefore, the current findings should be viewed as a mechanistic roadmap for future research rather than as evidence of therapeutic efficacy.
OBJECTIVE:Burning mouth syndrome (BMS), a heterogeneous idiopathic orofacial pain disorder mainly affecting postmenopausal females, is frequently accompanied by anxiety and sleep disturbances. Existing BMS molecular studies have focused primarily on oral bacterial DNA, whereas systematic human salivary transcriptomic profiling remains poorly explored. This study aimed to characterize salivary mRNA and lncRNA signatures in postmenopausal patients with BMS and uncover the transcriptomic mechanisms underlying the pathogenesis of BMS and associated comorbidities. METHODS:Twenty-one patients with BMS and 21 age-matched postmenopausal healthy controls were enrolled. Salivary samples were pooled into three sequencing replicates per group. Whole-transcriptome sequencing was performed to identify differentially expressed RNAs (|log2FoldChange|>1, p < 0.05). GO/KEGG enrichment and lncRNA-mRNA ceRNA network analyses were performed, and core transcripts were validated using RT-qPCR. RESULTS:BMS-associated transcripts were enriched in neuroinflammation, nociceptive sensitization, hormonal signaling, neuronal function, and sleep and emotional regulation. Key hub genes (TLR4, IL1B, PTGS2, FOS) mediate oral neuroinflammatory pain, whereas other transcripts are correlated with BMS-associated comorbidities. NEAT1 and lncRNA105310 form a core inflammation-metabolism ceRNA network, and key changes in expression were experimentally validated. These salivary signatures reflect local oral pathogenesis and systemic physiological and psychological alterations in patients with BMS. CONCLUSIONS:This study establishes a novel salivary transcriptomic profile and ceRNA regulatory network for postmenopausal BMS, providing molecular links between oral neuroinflammatory pain, and hormonal and emotional comorbidities. The non-invasive RNA signatures offer promising auxiliary diagnostic biomarkers and therapeutic targets for BMS, awaiting further prospective cohort validation and refined transcriptomic analyses for clinical translation.
OBJECTIVES:Bone formation in murine femoral cancellous bone is attenuated in Gb3 synthase knockout (Gb3S KO) mice deficient in Gb4 (globoside), a globo-series glycosphingolipid. However, whether Gb3S promotes bone wound healing is unclear. Therefore, we investigated the role of Gb3S in bone wound healing. METHODS:The expression of Gb4 was analyzed using flow cytometry. The number of calvarial osteoblasts was measured in 8-week-old wild-type (WT) and Gb3S KO mice using hematoxylin and eosin-stained slides. A calvarial bone defect, namely, a 5-mm hole in the parietal region of the calvaria, was created in 8-week-old WT and Gb3S KO mice using a trephine bur. Micro computed tomography was performed at 0 and 12 weeks post-operatively to assess the bone wound healing. Cell proliferation and migration were analyzed using bromodeoxyuridine and wound healing motility assays, respectively. To investigate the regulation of Gb4-induced osteoblast proliferation, calvarial osteoblasts from Gb3S KO mice were treated with Gb4. RESULTS:The number of calvarial osteoblasts from Gb3S KO mice was significantly lower than that from WT mice. Furthermore, bone wound healing was significantly delayed in Gb3S KO mice. The proliferation and migration of calvarial osteoblasts from Gb3S KO mice were significantly lower than those from WT mice. Moreover, the proliferation of calvarial osteoblasts from Gb3S KO mice was promoted by Gb4 treatment. CONCLUSIONS:The results revealed that the expression of Gb3S promoted the proliferation and migration of osteoblasts, which accelerated bone wound healing.
OBJECTIVES:Periodontitis is an inflammatory disease driven by dysbiotic dental plaque and is the leading cause of tooth loss in adults. We aimed to develop a reactive oxygen species (ROS)-responsive drug delivery system based on polydopamine (PDA)-functionalized bovine serum albumin (BSA) nanoparticles (NPs) for the controlled release of minocycline hydrochloride (MH) and to evaluate its synergistic antibacterial and antioxidant effects. METHODS:MH-loaded BSA NPs were prepared using a desolventization method followed by PDA coating. The resulting PDA@BSA NPs@MH were characterized in terms of size, morphology, drug loading, and release kinetics. Antibacterial activity against Porphyromonas gingivalis, Streptococcus gordonii, and Fusobacterium nucleatum was assessed using live/dead staining, colony counting, and biofilm assays. ROS-scavenging activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and intracellular ROS assays. Biocompatibility was assessed via cytotoxicity, migration, and hemolysis tests. RESULTS:PDA@BSA NPs@MH exhibited a uniform spherical morphology (180-200 nm) with 5.68% drug loading. The PDA coating enabled sustained MH release and concentration-dependent DPPH scavenging. The nanoparticles demonstrated potent antibacterial activity (mortality > 77% at high concentrations) and biofilm inhibition (>96%). Intracellular ROS levels were significantly reduced in LPS-stimulated macrophages. Furthermore, no evident cytotoxicity was observed, cell migration was enhanced, and hemolysis rates were <5%. CONCLUSIONS:The PDA@BSA NPs@MH platform integrates MH-mediated antibacterial activity with PDA-mediated antioxidant activity, effectively addressing both bacterial infection and oxidative stress in periodontitis.
OBJECTIVES:Oral microbiomes are associated with the progression of oral squamous cell carcinoma (OSCC). Prevotella intermedia is associated with tumor progression; however, the direct effects of P. intermedia on OSCC cells have not been elucidated. In this study, the aim was to elucidate the direct effects of P. intermedia on OSCC cells. METHODS:HSC-2, HSC-3, and SAS cells were treated with P. intermedia OMA14 at multiplicities of infection of 10 and 100, and cell viability was then assessed using a cell-counting kit (CCK)-8 assay. The effects of heat-killed P. intermedia OMA14 and protein fractions prepared from SDS-PAGE-separated membrane strips on HSC-3 cell viability were assessed using the CCK-8 assay. Cell migration, cell cycle, and lactate dehydrogenase (LDH) cytotoxicity assays were performed using HSC-3 cells treated with P. intermedia OMA14. RESULTS:Treatment with P. intermedia OMA14 reduced HSC-3 cell viability, whereas there were no significant changes in SAS or HSC-2 cell viability. Heat-killed P. intermedia did not reduce HSC-3 cell viability. P. intermedia also suppressed HSC-3 cell migration, and it induced G0/G1-phase cell-cycle arrest without increasing LDH release. In addition, among the P. intermedia-derived protein fractions, the fractions corresponding to approximately 75 kDa and 15-20 kDa had the strongest inhibitory effects on HSC-3 cell viability. CONCLUSION:P. intermedia OMA14 reduced HSC-3 cell viability through an anti-proliferative mechanism associated with G0/G1-phase cell-cycle arrest rather than overt cytotoxicity. Protein fractions of approximately 75 kDa and 15-20 kDa showed the strongest inhibitory effects on HSC-3 cell viability.
BACKGROUND:Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are endogenous ligands of PTH type I receptor (PTH1R), which are essential for skeletal development and homeostasis. Since the intermittent application of these molecules to organisms exerts bone anabolic effects, they are used pharmacologically to increase bone mass and stimulate bone formation. Teriparatide, an N-terminal 34 amino acid fragment of human PTH, and abaloparatide, a derivative of the N-terminal 34 amino acid of human PTHrP, have been pharmaceutically developed and clinically applied to treat severe osteoporosis and are categorized as PTH1R agonists. An increasing number of clinical and preclinical studies have demonstrated that PTH1R agonists can be used in dental medicine, including jaw bone regeneration and orthodontic treatment, periodontitis, and the management of medication-related osteonecrosis of the jaw (MRONJ). However, it is unclear whether the mandibular bone responds pharmacologically to PTH1R agonists in the same way as other trunk bones, such as the limb and axial bones. HIGHLIGHT:Compared with studies using long and vertebral bones, the beneficial effects of PTH1R agonists on the mandibular bone appear to require higher doses and longer treatment durations. CONCLUSION:Clinical application of PTH1R agonists in dental medicine may result in promising outcomes. However, dosing regimens and the timing of their application should be further investigated with knowledge of the biological uniqueness of the mandibular bone.
OBJECTIVES:Metformin (MET), a widely used antidiabetic drug, has recently gained attention for its anti-bone-resorptive properties. This study evaluated these effects in apical periodontitis (AP) and explored its underlying molecular mechanisms particularly its role in osteoclastogenesis. METHODS:AP was induced in the mandibular first molars of nine 6-week-old male C57BL/6 JJcl mice by pulp exposure for 21 days. MET (50 mg/kg/day) was administered intraperitoneally beginning 1 d before the procedure. Periapical bone resorption was evaluated using micro-computed tomography and tartrate-resistant acid phosphatase (TRAP) staining. In vitro, RAW264.7 murine macrophages were stimulated into osteoclasts using receptor activator of nuclear factor κB ligand (RANKL; 100 ng/mL) for 7 days, whereas the suppressive effect of MET (0.5 mM) on osteoclastogenesis was evaluated using TRAP staining. The mRNA expression of osteoclastogenesis-related genes was measured by real-time quantitative polymerase chain reaction. The effects of MET on extracellular signal-regulated kinase (ERK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) signaling were determined using western blotting and luciferase assays, respectively. RESULTS:MET significantly reduced the lesion size and number of TRAP-positive osteoclasts in vivo at day 21. In vitro, MET significantly inhibited RANKL-induced osteoclastogenesis and decreased the number of TRAP-positive osteoclasts (≥3 nuclei). MET significantly suppressed the RANKL-induced mRNA expression of the osteoclastogenesis-related genes osteoclast-associated receptor, acid phosphatase 5, tartrate resistant, and osteoclast stimulatory transmembrane protein. Moreover, it reduced RANKL-induced p-ERK and NFATc1 signaling. CONCLUSIONS:MET suppresses bone resorption in AP in vivo. In vitro, MET inhibited RANKL-induced osteoclastogenesis by suppressing the ERK-NFATc1 axis, suggesting a potential mechanism for the anti-bone-resorptive effects of MET in AP.
OBJECTIVES:To clarify the relationship between ear canal deformation and mandibular condyle movement, and to evaluate the feasibility of estimating jaw movement with an earplug-type sensor. METHODS:Sixteen healthy individuals participated in the study. Ear canal deformation was recorded using an earplug-type sensor equipped with a barometric pressure sensor. Mandibular condyle movement was recorded simultaneously using a six-degree-of-freedom jaw-tracking system. Cross-correlation analysis was performed to examine the relationships between ear canal deformation and the anteroposterior, mediolateral, and vertical components of condyle movement, during opening-closing, lateral, and chewing movements. RESULTS:During opening-closing movements, strong correlations were observed for all directional components (0.84-0.88). During lateral and chewing movements, correlation coefficients were significantly greater on the balancing side than on the working side (p < 0.05). The mediolateral component showed weaker correlations than the anteroposterior and vertical components. CONCLUSIONS:Ear canal deformation recorded using an earplug-type sensor was strongly correlated with mandibular condyle movement. These findings suggest that monitoring ear canal deformation may provide a simple, non-invasive method for assessing mandibular movement.
BACKGROUND:Zinc is an essential trace element that plays pivotal roles in development, immunity, inflammation, and aging. Precise regulation of intracellular zinc distribution is mediated by zinc transporters of the ZIP (SLC39) and ZnT (SLC30) families, and their functions are increasingly recognized as tissue- and organelle-specific. Among these transporters, ZIP13 (SLC39A13) is a key regulator of mesenchymal biology. Genetic studies have demonstrated that loss of ZIP13 function causes connective tissue abnormalities, impaired bone and tooth development, and spondylodysplastic Ehlers-Danlos syndrome Type 3 in humans. HIGHLIGHT:ZIP13 is predominantly localized to the Golgi apparatus, where it regulates metal homeostasis and modulates zinc-dependent signalling pathways, including transforming growth factor beta and bone morphogenic protein signalling. Recent studies have expanded the functional landscape of ZIP13 beyond connective tissues, demonstrating its involvement in adipose tissue biology, skeletal muscle maintenance, cardiac homeostasis, and stem cell differentiation. In addition, patient-derived induced pluripotent stem cell models have provided new insights into ZIP13-dependent mesenchymal differentiation and regenerative biology. Emerging evidence indicates that ZIP13 can transport not only zinc but also iron, suggesting that ZIP13 functions as a metal distributor that regulates intracellular metal allocation in a context-dependent manner. CONCLUSION:The findings in this review support the concept that ZIP13-mediated metal homeostasis is indispensable for mesenchymal development, aging, and disease. By integrating evidence from animal models, human genetic disorders, and stem-cell-based studies, this review highlights the implications of ZIP13 biology in oral and systemic health, and it underscores the importance of intracellular metal allocation in development and regenerative medicine.
OBJECTIVES:Masticatory function may influence the gut microbial metabolism via mechanical and neurohumoral mechanisms. However, the relationship between microbial metabolites and systemic indicators in healthy adults remains unclear. METHODS:This cross-sectional study included 20 healthy young adults (mean age: 27.6 ± 2.5 years). Masticatory performance was assessed using a validated chewing examination with gummy jelly as the test food. Fecal short-chain fatty acids were quantified by gas chromatography. Microbial metabolic functions were inferred using PICRUSt2 based on 16S rRNA gene sequences. Defecation frequency and body mass index were assessed using questionnaires and anthropometry, respectively. Correlation, regression, and mediation analyses were performed using 2,000 bootstrap samples. RESULTS:Masticatory performance showed nominal positive associations with several microbial metabolic pathways (p < 0.05), but none remained significant after false discovery rate correction (q ≥ 0.05). Propionate concentration and masticatory performance showed trends toward associations with defecation frequency, although these associations did not reach statistical significance. The mediation pathway involving propionate and defecation frequency was suggested but not significant. CONCLUSION:Overall, masticatory performance was associated with fecal propionate levels in healthy young adults. Associations among defecation frequency, BMI, and predicted microbial metabolic pathways are exploratory and require confirmation in larger studies.
BACKGROUND:Orofacial neuropathic pain has a complex pathophysiology beyond simple neuronal hyperexcitability. In this review, recent evidence is synthesized on the multi-level cascade of neuro-glial plasticity-from the trigeminal ganglion (TG) to higher brain centers-and its role in pain chronicity and affective distress is examined. HIGHLIGHT:Peripheral nerve injury activates satellite glial cells in the TG and microglia/astrocytes in the trigeminal sensory nuclear complex, driving central sensitization and circuit reorganization. These changes extend to affective circuits and the descending pain modulatory system, where astrocytes in the rostral ventromedial medulla facilitate pro-nociceptive states. Emerging perspectives also highlight the potential role of meningeal lymphatic dysfunction in prolonging neuroinflammation. CONCLUSION:Orofacial neuropathic pain is conceptualized as a "multi-level gliopathy". A more detailed understanding of these stage-specific neuro-glial interactions and homeostatic clearance systems will provide a novel framework for the development of mechanism-based therapeutic strategies.
OBJECTIVES:Hypophosphatasia (HPP) is a congenital disease caused by mutations in the tissue non-specific alkaline phosphatase gene. HPP is characterized by impaired hard tissue mineralization and premature tooth loss. Mild-type HPP includes childhood-, adult, and odonto-HPP. Mild-type HPP is difficult to diagnose because individuals with mild-type HPP do not have characteristic symptoms. The effects of applying mechanical stress, such as that caused by orthodontic force, on the teeth and jawbones of patients with mild-type HPP are unknown; therefore, in this study these effects were examined in mild-type HPP model mice. METHODS:A 10 gf nickel-titanium closed-coil spring was placed on the maxillary incisors and left first molar (M1) of mild-type HPP model mice (Akp2+/-). The M1 moved mesially to the maxillary incisors 14 days before sampling. RESULTS:Tooth movement distance, serum alkaline phosphatase (ALP) and serum C-terminal telopeptide of Type I collagen (CTX-1) levels did not differ between Akp2+/- and normal (Akp2+/+) mice. However, alveolar bone resorption on the compressed side was higher in Akp2+/- mice than that in normal mice. The cancellous bone quality on the compressed was side was lower in Akp2+/- than in Akp2+/+ mice. Fibrous structures infiltrated the bone resorption sites, and the number of osteoclasts was markedly higher in Akp2+/- mice. CONCLUSIONS:The application of orthodontic force to mice with mild-type HPP did not affect the serum ALP and bone resorption marker CTX-1 levels, or tooth movement. However, compression induced alveolar bone resorption due to an increase in osteoclasts. These findings support the importance of differentially diagnosing mild-type HPP before initiating treatment.
BACKGROUND:Leptin receptor (LepR)+ stromal cells are widely recognized as skeletal stem/progenitor cells (SSPCs) in the bone marrow that generate osteolineage cells, and contribute to skeletal homeostasis under steady-state conditions and tissue repair. By expressing representative niche factors, including stem cell factor and C-X-C motif chemokine ligand 12, LepR+ SSPCs function as key microenvironmental components of the hematopoietic stem cell (HSC) niche. Over the past decade, genetic cell-labeling studies have identified LepR+ SSPCs in craniofacial tissues, including in the periodontal ligament and alveolar bone marrow, where they differentiate into osteoblasts and cementoblasts. HIGHLIGHT:Emerging evidence indicates that periodontal LepR + cells contribute to orthodontic remodeling, periodontal repair, and extraction socket healing. Independent SSPC populations may coexist with LepR+ SSPCs in oral tissues and contribute in parallel to tissue homeostasis. Periodontal LepR+ cells also express HSC niche-associated factors, suggesting their possible role in the regulation of local immune and hematopoietic environments. Because oral tissues are continuously exposed to mechanical forces and the oral microbiome, LepR+ SSPCs in the oral environment may function through unique regulatory mechanisms that influence skeletal homeostasis and hematopoiesis. CONCLUSION:In this review, current knowledge regarding LepR+ SSPCs in periodontal tissues is summarized, and their emerging roles in skeletal maintenance, tissue repair, and hematopoietic regulation is discussed. Further elucidation of the regulatory mechanisms governing these cells will advance understanding of oral skeletal and hematopoietic biology, and may provide new insights into oral health and regenerative strategies.
Objectives Sodium chloride (NaCl), an important mineral for human homeostasis, is perceived by taste receptors. The objective of this study was to investigate how perceived intensity and preference for NaCl by taste receptors were affected after mixing with thickeners in electrophysiological and behavioral experiments in Wistar/ST rats. Methods Chorda tympani nerve responses to 0.1 M NaCl, 0.1 M sucrose, 3 mM hydrochloride, and 1 mM quinine hydrochloride, with and without thickeners, were measured by electrophysiology. Commercially available grades of 3% xanthan gum-based (X), 2% guar gum-based (G), and 4.7% starch-based (S) thickeners were used. To investigate the effect of thickener concentration, responses to 0.1 M NaCl mixed with 1%, 2%, and 3% X were measured. A two-bottle preference test and a brief-access test were performed using the following stimuli: 0.1 M NaCl, distilled water, and their mixture with one of the three thickeners. Results The degree of suppression varied depending on taste stimuli and thickeners; however, in most instances, chorda tympani nerve responses to the tested taste stimuli were suppressed by mixing with thickeners. The response and preference for 0.1 M NaCl were suppressed by mixing with X and G. The brief-access test demonstrated that the suppression was caused by the taste effect. Conclusion Mixing thickeners, such as X and G, but not S, with NaCl, suppressed perceived intensity and preference for NaCl.
Objectives Circadian rhythms in peripheral organs undergo dynamic reorganization during postnatal development. However, the mechanisms underlying the maturation of circadian clocks in the salivary glands, particularly in relation to feeding behavior, remain poorly understood. In this study, we aimed to characterize the developmental maturation of circadian rhythms in the mouse submandibular gland (SMG). Methods PERIOD2::LUCIFERASE bioluminescence rhythms were recorded from cultured suprachiasmatic nucleus (SCN) and SMG tissues isolated from mice at postnatal days 0, 1, 7, 14, 21, and 28, and 8 weeks. Maternal behavior and pup feeding activity were continuously monitored using infrared video recording. Peak phases and circadian periods were analyzed to evaluate developmental changes. Results Robust circadian oscillations were observed in the SCN tissue at all developmental stages, with stable periods and peak phases. In contrast, rhythms in the SMG were rapidly damped in culture, and exhibited a progressive phase shift from the light phase to the middle of the dark phase during postnatal development. Circadian periods in both tissues remained close to 24 h throughout development. Behavioral analyses revealed that developmental changes in maternal care and feeding activity were closely associated with the phase realignment of SMG rhythms. After weaning, SMG peak phases resembled those in adult mice. Conclusions Postnatal maturation of circadian rhythms in the SMG is characterized by progressive phase realignment that parallels the transition from suckling to independent feeding. These findings suggest that developmental coordination between feeding behavior and peripheral clock machinery contributes to the establishment of circadian regulation of salivary function.
BACKGROUND:Porphyromonas gingivalis is a periodontal pathogen that primarily mediates its interactions with host tissues and other bacteria through fimbrial structures. The diversity and assembly mechanisms of its fimbriae are fundamental to understanding its pathogenicity, and its roles in periodontal and systemic diseases. This bacterium mainly expresses two types of fimbriae, FimA and Mfa1. Recent structural and genetic studies have demonstrated that these fimbriae conform to the conserved assembly principles of Type V fimbriae shared by Bacteroidia-class bacteria. HIGHLIGHTS:This review focuses on Mfa1 fimbriae, and it summarizes the current knowledge on their assembly mechanisms, genetic diversity, components, and strain-dependent structural variations. In particular, the balance between conserved structural features and strain-specific variations is discussed, focusing on the molecular basis of fimbrial formation and incorporation of accessory proteins. The discussion centers on the major fimbrillin Mfa1 anchor protein, Mfa2, accessory proteins, Mfa3 and Mfa4, and the variable Type IX secretion system-dependent accessory protein, Mfa5. CONCLUSION:By integrating recent findings, this review emphasizes how a conserved Type V assembly framework, combined with variations in accessory components, enables Mfa1 fimbriae to maintain structural stability, while accommodating strain-dependent diversity. This synthesis provides an updated perspective on the balance between stability and strain-dependent structural adaptability in Mfa1 fimbrial systems, and their potential implications for fimbrial assembly, bacterial adhesion, and host-microbe interactions.
Objectives Oral squamous cell carcinoma (OSCC) is characterized by aggressive biological behavior and limited therapeutic responsiveness. In this study, the objectives were to investigate the effects of cinobufagin (CBG) on the progression of OSCC, and to elucidate the underlying molecular mechanisms. Methods The effects of CBG on OSCC cells were evaluated using in vitro assays to assess cell proliferation, clonogenic growth, apoptosis, migration, and invasion. Nuclear factor-kappa B (NF-κB) signaling activity was determined by immunoblotting, luciferase reporter assay, and p65 subcellular localization. The antitumor activity of CBG was further assessed in a xenograft mouse model, and its potential toxicity was evaluated by histological examination of the major organs. Results CBG treatment suppressed proliferation and clonogenic capacity of OSCC cells, while promoting apoptotic cell death. In addition, CBG significantly reduced the migratory and invasive abilities of OSCC cells. Mechanistically, CBG attenuated NF-κB signaling by decreasing p65 phosphorylation and inhibiting its nuclear translocation, resulting in reduced NF-κB transcriptional activity. Pharmacological activation of NF-κB partially reversed the antitumor effects of CBG. Moreover, CBG markedly inhibited in vivo tumor growth, and no histological toxicity was observed. Conclusions CBG suppressed the malignant progression of OSCC, in vitro and in vivo. Its antitumor effects are associated with inhibition of p65 nuclear translocation and attenuation of NF-κB signaling, suggesting that CBG may represent a potential therapeutic candidate for OSCC.
