OBJECTIVE: The potential role of autoantibodies targeting desmosomal proteins, particularly desmoglein 1 (Dsg-1) and desmoglein 3 (Dsg-3), in modulating disease severity and epithelial integrity in oral lichen planus (OL...OBJECTIVE: The potential role of autoantibodies targeting desmosomal proteins, particularly desmoglein 1 (Dsg-1) and desmoglein 3 (Dsg-3), in modulating disease severity and epithelial integrity in oral lichen planus (OLP) remains a subject of growing interest. Distinct patterns of anti-Dsg-1 and anti-Dsg-3 autoantibodies across OLP subtypes may correlate with disease progression. This scoping review investigates the expression patterns of circulating anti-Dsg-1 and anti-Dsg-3 autoantibodies in reticular, erosive, and ulcerative forms of OLP to elucidate their potential roles in epithelial disruption and disease advancement. DESIGN: Following PRISMA guidelines, a systematic search of four electronic databases was conducted. Eligible studies included case reports, case series, case-control and cross-sectional studies that reported serum levels of anti-Dsg-1 and anti-Dsg-3 autoantibodies in OLP patients. RESULTS: Reticular-type OLP showed variable anti-Dsg-1 and anti-Dsg-3 autoantibody levels, with some patients testing positive while others were negative, indicating an inconsistent involvement of desmosomal autoimmunity in this milder form of the disease. In erosive-type OLP, the presence of both autoantibodies indicated deeper epithelial damage and an active autoimmune response. Interestingly, ulcerative-type OLP consistently tested negative for both antibodies despite extensive epithelial breakdown, implying a potential shift from desmosomal autoimmunity to chronic inflammation-driven tissue destruction that could compromise human health. CONCLUSION: These findings suggest a potential continuum in which reticular OLP may progress to erosive OLP, with Dsg-3 autoantibodies as a possible early marker of worsening pathology. Ulcerative OLP appears to represent a late-stage, inflammation-driven phenotype with minimal autoantibody involvement. Given the limited and heterogeneous data, these observations are preliminary and should be interpreted cautiously.
OBJECTIVES: In this study, we aimed to explore the protein content of bacterial extracellular vesicles (bEVs) from three strains of Porphyromonas gingivalis, an anaerobic gram-negative bacterium closely associated with p...OBJECTIVES: In this study, we aimed to explore the protein content of bacterial extracellular vesicles (bEVs) from three strains of Porphyromonas gingivalis, an anaerobic gram-negative bacterium closely associated with periodontitis. Additionally, we aimed to investigate the effects of bEV uptake on human oral fibroblasts, to better understand the role of these vesicles in the pathogenesis of periodontitis. DESIGN: Liquid chromatography-mass spectrometry was performed on bEVs from three strains of P. gingivalis with different virulence: ATCC 33277, A7A1-28, and W83. Three key proteins associated with virulence were validated using dot blot. Proliferation and viability of human oral fibroblasts after incubation with bEVs were assessed at different timepoints and different concentrations of bEVs. RESULTS: A total of 307 proteins were identified in the bEVs from the three strains of P. gingivalis. Among those were several relevant for virulence, for example gingipains, fimbriae, and peptidyl-arginine deiminase (PPAD). When oral fibroblasts were exposed to bEVs from A7A1-28 or W83, proliferation was significantly affected after 12 and 24 h at one bEV concentration. Furthermore, viability was significantly affected by bEVs from W83 at several timepoints and bEV concentrations. bEVs from ATCC 33277 did not induce any significant changes. CONCLUSION: Several proteins associated with virulence were detected in bEVs from all three strains of P. gingivalis, with varying abundance. Uptake of these bEVs can influence human cells, as exemplified by changes in viability and proliferation.
OBJECTIVES: This systematic review and meta-analysis aimed to investigate the potential of fucose as a biomarker for oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). DESIGN: Relevant...OBJECTIVES: This systematic review and meta-analysis aimed to investigate the potential of fucose as a biomarker for oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). DESIGN: Relevant articles were searched across multiple databases, including PubMed, Scopus, Google Scholar, Science Direct, and Clinical Key. Twenty-three studies that met the eligibility criteria were included for qualitative review; out of which, 20 studies that provided data for comparison between study and control groups were further subjected to meta-analysis. RESULTS: The analysis revealed significantly high fucose levels in the saliva of OPMD patients (p = 0.013) and OSCC patients (p = 0.003) compared to healthy controls. Additionally, fucose levels were elevated in the serum of patients with OSCC (p < 0.001) and oral leukoplakia (p = 0.027) compared to controls. CONCLUSION: The findings of this meta-analysis suggest that fucose could serve as a potential biomarker for OPMDs and OSCC. However, the presence of significant heterogeneity in serum evaluation and the limited studies focusing on saliva indicate the need for further investigation.
OBJECTIVE: To evaluate, in vitro, the topical effect of polysaccharide cashew gum (PLS-cg) on dentine subjected to erosive cycles that simulate refluxate contact in the oral cavity. DESIGN: Human dentine blocks were prep...OBJECTIVE: To evaluate, in vitro, the topical effect of polysaccharide cashew gum (PLS-cg) on dentine subjected to erosive cycles that simulate refluxate contact in the oral cavity. DESIGN: Human dentine blocks were prepared, standardized, and randomly assigned to one of three treatment groups (n = 10): control group (C) without treatment, commercial dental varnish (CDV) 5 % NaF fluoride varnish, and PLS-cg extract (experimental group). The baseline enamel superficial microhardness (HK) and roughness (Ra) were assessed. The dentin was subjected to erosive cycles (6 × 5 min/day for 9 days) using a hydrochloric acid-pepsin solution (pH 2; 0.75-mg/mL pepsin). Surface roughness (Ra), microhardness (HK), percentage surface hardness loss (%SHL), and topographic analysis with scanning electron microscopy (SEM) were used to evaluate the protective heteropolysaccharide effect. Predictive molecular docking simulations were used to investigate possible interactions between PLS-cg and metalloproteinases (MMP2 and MMP9). The data were analyzed with two-way analysis of variance, t test, Pearson's correlation, and Tukey's test (p < 0.05). RESULTS: PLS-cg preserved HK significantly better than the control group (p < 0.001), with the lowest %SHL (-14.04 ± 8.22) and minimal Ra changes (0.124 ± 0.005). Pearson's correlation between Ra and %SHL was significant and positive (0.7740, p < 0.001). SEM analysis revealed more prominent dentinal tubule openings in the control group, whereas CDV and PLS-cg showed tubule obliteration. Molecular docking identified possible interactions between PLS-cg and MMPs. CONCLUSION: The findings indicate that PLS-cg may reduce dentine erosion caused by supraesophageal manifestations of gastroesophageal reflux disease.
OBJECTIVES: This study aimed to elucidate the regulatory effects and mechanisms of Ganoderic acid A (GAA) on Porphyromonas gingivalis (P. gingivalis)-induced expression of adhesion molecules in human gingival fibroblasts...OBJECTIVES: This study aimed to elucidate the regulatory effects and mechanisms of Ganoderic acid A (GAA) on Porphyromonas gingivalis (P. gingivalis)-induced expression of adhesion molecules in human gingival fibroblasts (hGFs) and periodontal tissues, focusing on NLRP6 inflammasome modulation. DESIGN: HGFs were stimulated with P. gingivalis strain W83. The expression levels of NLRP6, caspase-1, IL-1β,IL-18 and adhesion molecules ICAM-1 & VCAM-1 were analyzed by RT-PCR, Western blotting and ELISA, with or without GAA pretreatment. To further explore the regulatory role of GAA on the NLRP6 inflammasome, NLRP6 overexpression assays were performed in hGFs, followed by assessment of ICAM-1 and VCAM-1 expressions. Additionally, a ligature-induced periodontitis mice model was established to evaluate the effects of GAA on NLRP6 expression and inflammatory cell infiltration in periodontal tissues. RESULTS: GAA exhibited no cytotoxicity toward hGFs at low concentrations (within 16 μM). GAA pretreatment significantly inhibited P. gingivalis-induced activation of the NLRP6 inflammasome. Beyond IL-1β and IL-18, it also reduced ICAM-1 and VCAM-1 expression at both mRNA and protein levels. Overexpression of NLRP6 increased the expression of NLRP6 inflammasome components and adhesion molecules, whereas GAA treatment effectively suppressed these elevations. Furthermore, GAA administration markedly downregulated NLRP6 expression and attenuated inflammatory cell infiltration and periodontal inflammation in the mice periodontitis model. CONCLUSIONS: GAA attenuates P. gingivalis-induced expression of adhesion molecules by inhibiting NLRP6 inflammasome activation in gingival fibroblasts and periodontal tissues, thereby alleviating inflammatory cell infiltration. These findings suggest the potential of GAA as a therapeutic agent for the management of periodontal inflammation.
OBJECTIVE: To identify m1A-modified genes with diagnostic potential linking periodontitis and type 2 diabetes mellitus (T2DM) by integrating bioinformatics and experimental validation. DESIGN: Transcriptomic data for per...OBJECTIVE: To identify m1A-modified genes with diagnostic potential linking periodontitis and type 2 diabetes mellitus (T2DM) by integrating bioinformatics and experimental validation. DESIGN: Transcriptomic data for periodontitis and T2DM patients were integrated from the GEO database to analyze m1A-related gene expression. A diagnostic model was constructed using ridge and logistic regression. Gene function enrichment, immune infiltration, and protein-protein interaction analyses explored m1A regulatory mechanisms based on m1A scoring and patient clustering models. Gingival tissue samples were collected from periodontitis patients and healthy controls, and a streptozotocin-induced diabetic β-cell model was established. qRT-PCR was performed to validate candidate genes (RRP8, ALKBH3, MAK16, and DDX18). Statistical comparisons were conducted using the non-parametric Mann-Whitney U test. RESULTS: Several m1A-related genes were differentially expressed in both periodontitis and T2DM. RRP8 and ALKBH3 had high predictive value, with area under the curve (AUC) values of 0.80 (periodontitis) and 0.72 (T2DM). m1A scoring and patient clustering models effectively distinguished patient groups with distinct transcriptomic and immune profiles. Hub genes MAK16 and DDX18 showed consistent expression patterns and strong correlations with immune infiltration. qRT-PCR confirmed significant downregulation of RRP8, ALKBH3, MAK16, and DDX18 in inflamed gingival tissues, and upregulation in the diabetic cell model (p < 0.05), supporting the bioinformatics findings. CONCLUSIONS: This integrative study identifies key m1A-modified genes potentially linking periodontitis and diabetes. The combination of bioinformatics analysis and experimental validation highlights their potential as diagnostic biomarkers and provides novel insights into shared molecular mechanisms of these comorbid conditions.
OBJECTIVES: Previous articles have shown that tooth loss is associated with cognitive decline in animal and human studies. Additionally, poor nutritional status including low-protein diet is associated with dementia. The...OBJECTIVES: Previous articles have shown that tooth loss is associated with cognitive decline in animal and human studies. Additionally, poor nutritional status including low-protein diet is associated with dementia. The evidence of the association of tooth loss and nutritional status is uncertain. The purpose of this study was to investigate the relationship between low-protein diet intake and cognitive decline following tooth loss in mice. DESIGN: Male senescence-accelerated mouse-prone 8 mice were randomly allocated into sham-operated control and tooth loss groups with extracted maxillary molars: control with normal-protein diet; control with low-protein diet; bilateral maxillary molar extraction with normal-protein diet; and bilateral maxillary molar extraction with low-protein diet. After 6 months, a behavioral test was conducted, and mRNA expression and immunohistochemistry in the brain were analyzed. RESULTS: Behavioral test revealed no effect of the interaction between tooth loss and low-protein diet intake on cognitive decline; however, tooth loss had a marked effect on cognitive decline. Real-time polymerase chain reaction showed no interaction between tooth loss and low-protein intake for Bax/Bcl-2 mRNA expression; however, tooth loss had a significant effect on Bax/Bcl-2 mRNA expression. Immunohistochemical analysis showed that the effect of tooth loss in neuronal inflammation and neuronal loss were observed in CA1 and DG region, but the effect of low-protein diet was limited in CA3. CONCLUSION: The present study revealed that the impact of tooth loss on cognitive decline was not dependent on the low-protein diet condition.
OBJECTIVES: To characterize the oral microbiome of substance users (primarily tobacco, alcohol, and opioids) compared to healthy controls in the high-incidence Mizo tribal community of Northeast India, and to examine the...OBJECTIVES: To characterize the oral microbiome of substance users (primarily tobacco, alcohol, and opioids) compared to healthy controls in the high-incidence Mizo tribal community of Northeast India, and to examine their association with food and lifestyle habits. METHODS: Saliva samples from 53 substance users and 35 healthy controls were subjected to 16S rRNA (V3-V4 region) sequencing. Alpha and beta diversity analyses, differential abundance testing, and microbial functional prediction were conducted. Statistical analyses were corrected for multiple comparisons using false discovery rate (FDR) adjustment where applicable. Associations with food and lifestyle habits were also examined. RESULTS: Substance users exhibited significantly lower alpha diversity, and beta diversity analyses revealed distinct clustering between the two groups. Firmicutes_D, Actinobacteria, Rothia, and Streptococcus were more abundant in substance users, whereas Bacteroidota, Proteobacteria, Neisseria, and Prevotella were enriched in healthy controls. Functional predictions indicated upregulation of biofilm formation and xenobiotic degradation pathways in substance users. Exposure to Jhum cultivation, prenatal smoking, and consumption of fermented pork fat (saum) were correlated with microbial composition. CONCLUSIONS: Substance use and associated environmental exposures were linked to oral microbiome dysbiosis. Certain bacterial taxa may serve as potential microbial biomarkers of substance use in this high-risk tribal population, warranting further investigation.
OBJECTIVE: To investigate the effect of the HN019 probiotic on the modulation of inflammation and the resorption of mineralized tissues in experimentally induced periapical lesions in an animal model, evaluating its impa...OBJECTIVE: To investigate the effect of the HN019 probiotic on the modulation of inflammation and the resorption of mineralized tissues in experimentally induced periapical lesions in an animal model, evaluating its impact on the expression of cementum protein 1 (CEMP-1). DESIGN: Periapical lesion was induced in 45 Wistar rats. The animals were divided into groups according to the irrigating solution used. Root canals were irrigated on days 7 and 14. After 21 days, the animals were euthanized, and mandibles were processed for histological analysis. Descriptive and semi-quantitative evaluations of the inflammatory infiltrate, periodontal ligament, bone and cementum resorption, as well as counts of inflammatory cells were performed using HE staining. Also, to assess cementum formation, tissue sections were stained with an antibody for CEMP-1 and analyzed by immunohistochemistry. RESULTS: In the Infection + Probiotic Group, the inflammatory infiltrate was mixed and diffuse, ranging from mild to severe, with no statistically significant difference compared to the Control Group (p > 0.05). However, in the Infection + Probiotic Group, cementum resorption was significantly lower compared to Control Group (p < 0.001). Moreover, CEMP-1 expression was significantly higher in Infection + Probiotic-Group compared with all other groups (p < 0.0001). CONCLUSION: The probiotic HN019 significantly increased CEMP-1 expression, indicating cementum formation in periapical lesions in vivo. These findings suggest that B. lactis HN019 may have regenerative potential in clinical scenarios. Furthermore, this strain appears to modulate the inflammatory state of periapical lesions toward a reparative phenotype, characterized by reduced bone resorption. Also, inflammatory infiltrate was like control group.
OBJECTIVES: Human gingival fibroblasts (HGFs) are important cells that maintain the structure and integrity of periodontal tissues. Circular RNAs (circRNAs) play critical roles in cellular processes of periodontitis; how...OBJECTIVES: Human gingival fibroblasts (HGFs) are important cells that maintain the structure and integrity of periodontal tissues. Circular RNAs (circRNAs) play critical roles in cellular processes of periodontitis; however, their roles in HGFs remain unclear. This study aimed to elucidate the function and mechanism of a novel circRNA, hsa_circ_0007349, in periodontitis progression by validating its existence, establishing its role in a ceRNA network (targeting miR-127-5p/GLUL), assessing its regulatory effects on HGF functions in vitro, and confirming its pathological impact in a murine periodontitis model. DESIGN: We performed circRNA sequencing to identify differentially expressed circRNAs between periodontitis and healthy gingival tissues. We selected hsa_circ_0007349, and confirmed its circular structure by Sanger sequencing, RNase R and actinomycin D assays. hsa_circ_0007349/miR-127-5p/glutamate-ammonia ligase (GLUL) interactions were explored using bioinformatics analysis, dual-luciferase reporter assays, RT-qPCR, and western blotting, and their effects on HGF functions were assessed via transcriptome sequencing, Cell Counting Kit-8, cell scratch, and Transwell assays. To further investigate the pathogenic mechanisms, we established a standardized murine periodontitis model using female C57BL/6 mice, followed by histopathological evaluation of periodontal tissue destruction. RESULTS: Hsa_circ_0007349 expression significantly increased in gingival tissues of patients with periodontitis and in HGFs treated with Porphyromonas gingivalis lipopolysaccharide. hsa_circ_0007349 regulates miR-127-5p to affect cell proliferation, migration, and wound healing, and affects extracellular matrix metabolism and periodontal tissue damage via GLUL. CONCLUSION: Hsa_circ_0007349 acts as a competing endogenous RNA to promote HGF proliferation, migration, wound healing and extracellular matrix turnover by targeting miR-127-5p and GLUL.
OBJECTIVES: The long noncoding RNA (lncRNA) myocardial infarction-associated transcript 2 (Mirt2) has been confirmed to affect several inflammatory diseases. This study was conducted to explore the functional mechanism o...OBJECTIVES: The long noncoding RNA (lncRNA) myocardial infarction-associated transcript 2 (Mirt2) has been confirmed to affect several inflammatory diseases. This study was conducted to explore the functional mechanism of Mirt2 in inflammatory alveolar bone loss and its possibility of being a therapeutic target. DESIGN: The expression level and potential role of Mirt2 in chronic inflammatory alveolar bone loss in mouse models of periodontitis and periapical periodontitis were investigated using micro-CT and qPCR. The characteristics of Mirt2 were evaluated by FISH, qPCR, ELISA, and alkaline phosphatase staining to confirm its function and mechanism of action in inflammatory response. RESULTS: Mirt2 expression was significantly enriched in inflammatory alveolar bone diseases. Mirt2 expression increased upon LPS stimulation in MC3T3-E1 cells (P < 0.05), located at the cell cytoplasm. Mirt2 knockdown exacerbated the LPS-stimulated inflammatory response in MC3T3-E1 cells, whereas Mirt2 overexpression attenuated this effect and rescued LPS-impaired osteogenic differentiation. CONCLUSIONS: lncRNA Mirt2 suggests a potential role in chronic inflammation-related bone loss, providing potential therapeutic target worthy of future investigation for inflammation-related bone loss.
OBJECTIVES: Although cell-based therapies using human dental pulp stem cells (hDPSCs) with other cell lineages and growth factors show promise in regenerative endodontics, combining hDPSCs with induced pluripotent stem c...OBJECTIVES: Although cell-based therapies using human dental pulp stem cells (hDPSCs) with other cell lineages and growth factors show promise in regenerative endodontics, combining hDPSCs with induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) is unexplored. Moreover, iPSC-ECs overcome ethical and practical challenges related to primary endothelial cells. This study explored the odontogenic and angiogenic potential of hDPSCs and iPSC-ECs in direct coculture. DESIGN: hDPSCs were isolated from extracted human teeth, and iPSC‑ECs were generated via episomal reprogramming of hDPSCs followed by endothelial differentiation. Four groups were established for differentiation assays: hDPSCs in basal medium, osteogenic medium, modified osteogenic medium (D‑MOD), and coculture with iPSC‑ECs (1:5) in D‑MOD. Mineralization was assessed by alkaline phosphatase and alizarin red S staining; gene expression of odontogenic (DSPP, IBSP, ALPL) and angiogenic (PECAM1, MCAM, KDR) markers was measured by RT‑qPCR; protein levels were evaluated by Western blot and nestin immunofluorescence; and angiogenic capacity in the D‑MOD and coculture groups was quantified via Matrigel tube‑formation assay. RESULTS: The coculture group showed enhanced mineralization and significantly increased expression of DSPP, IBSP, and PECAM1. Protein analysis confirmed elevated DSPP and nestin levels. Tube formation assays revealed significantly more junctions, segments, and meshes in the coculture group. CONCLUSIONS: This study demonstrated in vitro that coculturing hDPSCs with iPSC-ECs enhances both odontogenic and angiogenic differentiation compared to hDPSCs cultured alone. These findings highlight the potential of iPSC technology in regenerative endodontics and indicate a promising cell-based approach for future therapeutic applications.
OBJECTIVE: To evaluate the prevalence, morphological traits, and caries susceptibility of the Cusp of Carabelli (CoC) in permanent maxillary molars among patients in Lahore, Pakistan. DESIGN: A descriptive cross-sectiona...OBJECTIVE: To evaluate the prevalence, morphological traits, and caries susceptibility of the Cusp of Carabelli (CoC) in permanent maxillary molars among patients in Lahore, Pakistan. DESIGN: A descriptive cross-sectional study was conducted among 432 participants aged 12 years or older at Lahore Medical and Dental College. Clinical examination of maxillary first and second molars was performed using the Arizona State University Dental Anthropology System (ASUDAS) for CoC traits and the International Caries Detection and Assessment System (ICDAS) for caries assessment. Inter- and intra-examiner calibration ensured diagnostic reliability (Cohen's Kappa >0.90). RESULTS: CoC (ASUDAS grades 1-7) was observed in 201 individuals (46.5 %) on maxillary first molars and in 7 individuals (1.6 %) on second molars, with bilateral expression more common than unilateral. The right first molar showed a higher prevalence of CoC and caries incidence. Morphological traits ranged from subtle grooves to pronounced cusps, with small vertical grooves (ASUDAS 1) being the most frequent. Caries susceptibility correlated positively with CoC prominence (p < 0.001). Multivariate logistic regression identified CoC grade as the strongest predictor of caries, overshadowing age, side, and molar position, and substantially improving model sensitivity (0 % to 97.2 %). CONCLUSION: CoC is a prevalent trait and is significantly associated with early-stage dental caries in maxillary first molars. Its presence, particularly in prominent forms, may pose an increased risk of caries. These findings underscore the need for enhanced preventive strategies and clinical attention in individuals with CoC.
OBJECTIVE: This study explores the potential of postbiotic metabolites from lactic acid bacteria (LAB) isolated from human milk and tempeh against Porphyromonas gingivalis, a key pathogen in periodontitis. DESIGN: Select...OBJECTIVE: This study explores the potential of postbiotic metabolites from lactic acid bacteria (LAB) isolated from human milk and tempeh against Porphyromonas gingivalis, a key pathogen in periodontitis. DESIGN: Selected LAB strains and their treated cell-free supernatants (TCFS), lyophilized TCFS (L-TCFS), and bacteriocin-like inhibitory substances (BLIS) were tested individually and in combination using agar well diffusion, MIC, MBC, autoaggregation, coaggregation, and biofilm inhibition assays. LAB identification was performed using the API 50 CHL kit and 16S rDNA sequencing. RESULTS: Strain S2, a mixture of Lactiplantibacillus sp. SUK1 and T2 showed the highest inhibitory activity (20.06 ± 4.14 mm) using the agar well diffusion method. It demonstrated strong autoaggregation compared to the individual T2 strain but lacked significant coaggregation ability. The L-TCFS of S2 also exhibited the strongest antibacterial effect, with a minimum inhibitory concentration (MIC) of 50 mg/mL, although no minimum bactericidal concentration (MBC) was detected for any bacteriocin-like inhibitory substances (BLIS). L-TCFS from strain S2 significantly reduced P. gingivalis biofilm formation at a minimum concentration of 25 mg/mL, compared to the untreated control. Strain T2 was identified as Lactiplantibacillus plantarum using the API 50CHL test and 16S rDNA gene sequencing. CONCLUSION: The combination metabolite S2 demonstrates promising inhibitory activity against P. gingivalis and may serve as an effective adjunctive therapy for periodontal infections, outperforming individual and other combination LAB strains tested.
OBJECTIVE: This review aims to summarize the molecular architecture of endoplasmic reticulum (ER) stress signaling networks and their mechanistic involvement in temporomandibular joint osteoarthritis (TMJOA) progression,...OBJECTIVE: This review aims to summarize the molecular architecture of endoplasmic reticulum (ER) stress signaling networks and their mechanistic involvement in temporomandibular joint osteoarthritis (TMJOA) progression, and current therapeutic strategies targeting ER stress mediators and the obstacles from bench to bedside. DESIGN: The related literatures of the roles of ER in TMJOA were searched through PubMed database by different combinations of the following keywords including animal models, ER, unfolded protein response (UPR), ER-associated degradation (ERAD), ER-phagy, TMJ, and OA. No filters were used in the search. The references of eligible studies were also analyzed and reviewed comprehensively. RESULTS: This review discussed how ER stress signaling orchestrated TMJOA pathogenesis, including UPR, ERAD, and ER-phagy. It was also summarized how biomechanical stress and hypoxic microenvironment synergistically exacerbated ER stress, and the current therapeutic strategies for TMJOA based on ER stress modulators and the obstacles in bench-to-bedside research. CONCLUSIONS: ER proteostasis represented a pivotal but underexplored therapeutic axis in TMJOA. Bridging the gap between mechanistic understanding of ER stress adaptation and TMJ-specific pathobiology is essential for developing novel therapeutic strategies for TMJOA.
OBJECTIVES: Charcoal-containing dentifrices are increasingly popular for their whitening claims, but data on antimicrobial effects are limited. This study compared the antibacterial efficacy of charcoal dentifrices versu...OBJECTIVES: Charcoal-containing dentifrices are increasingly popular for their whitening claims, but data on antimicrobial effects are limited. This study compared the antibacterial efficacy of charcoal dentifrices versus non-charcoal dentifrices containing sodium fluoride (NaF), stannous fluoride (SnF₂), or sodium monofluorophosphate (NaMFP) against multi-species oral biofilms. METHODS: Biofilms of Streptococcus mutans, S. gordonii, and S. sanguinis were grown on hydroxyapatite discs and treated for 60 s with 6 dentifrice slurries (3 charcoal, 3 non-charcoal dentifrices) or controls (saline and 0.12 % chlorhexidine, CHX). Antibacterial effects were assessed by CFU/mL; (n = 9/group) and qPCR (n = 3/group). For fluoride-type analyses, charcoal and non-charcoal dentifrices were combined (CFU n = 18/type; qPCR n = 6/type). Percent reduction was compared across groups using one-way ANOVA with post-hoc tests. RESULTS: NaF dentifrices exhibited the greatest overall antibacterial activity (46.8 % reduction), followed by NaMFP (34.9 %), while SnF₂ showed minimal effect (≤ 5.7 %). Charcoal inclusion did not enhance efficacy and slightly reduced NaF activity. Species-specific responses varied: NaF eliminated S. gordonii, and significantly reduced S. mutans and S. sanguinis. Charcoal inclusion did not significantly alter species-level viability. qPCR supported CFU trends but showed limited between-group differences. Overall, fluoride type - not charcoal - primarily determined efficacy (NaF > NaMFP > SnF). CONCLUSIONS: Fluoride type had a greater impact on antibacterial efficacy than charcoal. NaF was most effective, while SnF₂ least. Charcoal offered no benefit and may slightly diminish NaF performance. Fluoride choice is more critical than charcoal additives for caries prevention.
OBJECTIVE: Desmocollin-3 (Dsc3), a desmosomal cadherin, is critical in maintaining epithelial cohesion and integrity. Despite its recognized function in skin and mucosal epithelium, its contribution to tooth development...OBJECTIVE: Desmocollin-3 (Dsc3), a desmosomal cadherin, is critical in maintaining epithelial cohesion and integrity. Despite its recognized function in skin and mucosal epithelium, its contribution to tooth development remains poorly understood. The study aims to identify stratum intermedium (SI)-specific markers using single-cell RNA-sequence (scRNA-seq) and to investigate the functional role of Dsc3 in maintaining SI cell integrity and differentiation. DESIGN: In this study, we pursued the marker genes of SI cells using scRNA-seq analysis of post-natal day 12 molar. Furthermore, we examined the role of the SI marker gene using dental epithelial cell line SF2. RESULTS: We found that desmosome family genes are highly expressed in SI cluster and among them, Dsc3 showed specific expression in SI cluster. Knockdown of Dsc3 in the SF2 epithelial cell line led to significantly smaller cell size, indicating impaired epithelial differentiation. The expression of SI marker genes was suppressed by the knockdown of Dsc3 with a marked loss of tight junction protein Tjp1 (ZO-1), indicating disrupted intercellular junctions and impaired epithelial barrier function. This disruption correlated with altered expression of key ameloblast differentiation markers, suggesting a failure in proper ameloblast lineage commitment, highlighting a disruption in the SI's ability to support ameloblast lineage specification. CONCLUSION: These findings indicate that Dsc3 is essential for SI structural integrity and its signaling support to ameloblasts.
OBJECTIVES: To investigate the expression patterns of long non-coding RNA OIP5-AS1 across various stages of oral squamous cell carcinoma (OSCC) and assess its potential as a biomarker and therapeutic target. DESIGN: A co...OBJECTIVES: To investigate the expression patterns of long non-coding RNA OIP5-AS1 across various stages of oral squamous cell carcinoma (OSCC) and assess its potential as a biomarker and therapeutic target. DESIGN: A comprehensive review of recent literature focusing on OIP5-AS1's role in OSCC was conducted. Analysis included OIP5-AS1 expression levels in cancerous versus non-cancerous tissues and exploration of its interactions with tumor-suppressing microRNAs (miRNAs). RESULTS: OIP5-AS1 was found to be significantly upregulated in advanced stages of OSCC compared to non-cancerous tissues. Its function as a molecular sponge for miRNAs contributes to the promotion of tumorigenic pathways, complicating therapeutic responses and highlighting its role as an oncogene. CONCLUSIONS: OIP5-AS1 is a critical player in the progression of OSCC, influencing tumor dynamics and mechanisms of resistance. Elucidating its expression patterns and functional roles suggests that OIP5-AS1 could serve as a valuable biomarker for early diagnosis and personalized treatment strategies.
OBJECTIVE: To define how Z-DNA binding protein 1 (ZBP1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling regulate lipopolysaccharide (LPS)-induced inflammation, PANoptosis, and ferroptosis in huma...OBJECTIVE: To define how Z-DNA binding protein 1 (ZBP1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling regulate lipopolysaccharide (LPS)-induced inflammation, PANoptosis, and ferroptosis in human dental pulp fibroblasts (HDPFs). DESIGN: HDPFs were treated with LPS, and ZBP1 and NLRP3 were silenced using small interfering RNA (siRNA), individually or in combination. Inflammatory mediators and death-pathway markers were quantified by quantitative real-time PCR (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), and biochemical assays; Annexin V/propidium iodide flow cytometry assessed cell-death distributions. RESULTS:: LPS significantly increased ZBP1 and NLRP3 expression and elevated cytokine/chemokine release; each was attenuated by ZBP1 or NLRP3 knockdown, with the greatest reduction after dual silencing. LPS triggered PANoptosis, as indicated by increased Annexin V⁺/PI⁺ cell populations and upregulation of caspase-1, cleaved caspase-8, RIPK3, GSDMD, and p-MLKL/MLKL, which were significantly reduced by inhibition of the ZBP1-NLRP3 axis. Ferroptosis features were also evident after LPS, including impaired iron homeostasis (downregulated ferritin heavy chain 1 [FTH1] and ferroportin [FPN1] with Fe²⁺ accumulation), enhanced lipid peroxidation (upregulated ALOX15, LPCAT3, PTGS2 with increased malondialdehyde and lipid reactive oxygen species), and weakened antioxidant defenses (reduced glutathione peroxidase-4 [GPX4], solute carrier family 7 member 11 [SLC7A11], glutathione, and GPX4 activity). These changes were mitigated by single-gene silencing and most effectively by dual knockdown. CONCLUSION: The ZBP1-NLRP3 axis acts upstream to coordinate LPS-induced PANoptosis and ferroptosis in HDPFs. Targeting this axis dampens inflammatory cell death and oxidative-metabolic dysregulation, highlighting a potential therapeutic strategy for pulpitis-related tissue injury.