Oral health is fundamental to overall well-being, especially in childhood, when dental structures and lifelong habits are established. This review provides a comprehensive analysis of children’s dental development, common oral health challenges, and evidence-based preventive strategies. Key topics include the mechanisms of tooth development, the eruption processes of primary and permanent dentition, and the management of developmental abnormalities. The prevalence, risk factors, and health impacts of dental caries in children are examined, underscoring the need for early intervention and targeted prevention. This review evaluates the effectiveness of preventive measures such as dental sealants, fluoride varnishes, and fluoride mouth rinses while highlighting the influence of dietary habits, toothbrush selection, and parental involvement on oral health outcomes. Additionally, it explores the synergistic benefits of combining preventive approaches, such as the concurrent use of dental sealants and fluoride applications, which have demonstrated superior caries prevention compared to either method alone. The effectiveness of these strategies is analyzed across different age groups, from early childhood to adolescence, with tailored recommendations for each developmental stage. Furthermore, the role of education, policy interventions, and community-based programs in addressing oral health disparities is discussed. By integrating developmental insights with epidemiological data and clinical evidence, this review provides a comprehensive framework for advancing pediatric dentistry, informing best practices, and enhancing preventive strategies to reduce the burden of oral diseases in diverse pediatric populations.

Background/purpose The 3D printer and post-curing unit are important factors in producing the best 3D printed crowns. To explore the effects of different combinations of 3D-printers and manufacturer-specified post-curing units on the dimensional accuracy, compressive strength, and degree of conversion (DC%) of 3D-printable resin for fixed dental prostheses. Materials and methods Specimens were designed in 2 sizes and additively-manufactured using 2 digital light processing (DLP) 3D-printers (NextDent 5100, ND and PrintinDLP+, PN). The 3D-printed samples were polymerized using 2 different post curing units (LC-3D Print box, N and PrintInCure+, P). Dimensional accuracy was evaluated under an optical microscope, while compressive strength was determined using a universal testing machine. Fourier transform infrared spectroscopy was used to analyze the resin molecular bond characteristics and DC%. Statistical analysis, including ANOVA and Tukey's HSD post-hoc tests (P < 0.05). Results Significant dimensional variations were observed for both square and rectangular samples (P < 0.001). The ND-P showed the greatest ductility and relatively high maximum stress. The fracture strengths were ND-N: 181.55 ± 8.37 MPa, ND-P: 151.54 ± 2.06 MPa, PN-N: 175.51 ± 12.44 MPa, and PN-P: 127.84 ± 10.10 MPa (P < 0.001). Surface inspection at 200 × magnification revealed subtler fault lines in ND-N and PN-P. FTIR analyses confirmed DC% was highest for ND-N (79.70 ± 1.02%) and PN-N (78.12 ± 0.94%), intermediate for ND-P (73.24 ± 0.89%) and PN-P (71.06 ± 1.67%). Conclusion Post-curing units had a greater impact on dimensional accuracy, strength, and polymerization than the choice of 3D-printer. Optimal resin properties require careful optimization of post-curing parameters and equipment.

This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma (OSCC), a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis. Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes. Various salivary biomarkers, including microRNAs, cytokines, proteins, metabolites, and exosomes, have been linked to oncogenic signaling pathways involved in tumor progression, immune modulation, and therapeutic resistance. Advances in quantitative polymerase chain reaction, mass spectrometry, and next-generation sequencing have enabled comprehensive biomarker profiling, while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation. Remaining challenges include variability in salivary composition, lack of standardized collection protocols, and insufficient validation across large patient cohorts. This review highlights the mechanistic relevance, diagnostic potential, and translational challenges of salivary biomarkers in OSCC.

OBJECTIVE:Periodontitis is a chronic inflammatory disease associated with systemic conditions, including cardiovascular diseases. Porphyromonas gingivalis (Pg), a key periodontal pathogen, contributes to vascular endothelial dysfunction through its virulence factors. This study aimed to investigate the protective effects of Taiwanese green propolis (TGP) against Pg-derived lipopolysaccharide (Pg-LPS)-induced endothelial inflammation, focusing on its modulation of the NLRP3 inflammasome and Nrf2/HO-1 signaling pathways. DESIGN:Human aortic endothelial cells (HAECs) were stimulated with Pg-LPS in the presence or absence of TGP. The expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) was assessed using real-time PCR and ELISA. ROS production was evaluated using fluorescence-based assays, while NF-κB activation and Nrf2 transcriptional activity were analyzed via luciferase reporter assays. Pharmacological inhibitors were used to confirm the involvement of these pathways. RESULTS:TGP significantly reduced Pg-LPS-induced IL-1β, TNF-α, and IL-6 expression in HAECs. It inhibited NF-κB activation, suppressed ROS generation, and attenuated NLRP3 inflammasome activation. Additionally, TGP upregulated HO-1 expression and enhanced Nrf2 transcriptional activity, as evidenced by ARE-driven luciferase reporter assays. Pharmacological inhibition of Nrf2 and HO-1 reversed TGP's anti-inflammatory effects, confirming that the Nrf2/HO-1 axis is critical for its protective function. CONCLUSIONS:These findings demonstrate that TGP exerts anti-inflammatory and cytoprotective effects by suppressing NLRP3 inflammasome activation and enhancing the Nrf2/HO-1 pathway, reducing Pg-LPS-induced endothelial inflammation. This study suggests that TGP could be a promising natural therapeutic agent for mitigating periodontal pathogen-induced systemic inflammation.

Background/purpose The uniqueness of human teeth necessitated that dental restorations be customized primarily through extensive manual labor. Therefore, this study explored the potential of AI designed dental restorations for clinical applications. Materials and methods Digital artificial design and AI design crown restorations were replicated 10 times, for a total of 20 samples. The zirconia crown restoration was completed by strengthening and glazing according to standard clinical procedures. Samples were digitally archived using a dental scanner to assess reproducibility, precision, and occlusion. The human trial portion included natural tooth preparations by clinical standards. Three participants each designed two crowns, resulting in a total of six crowns. Dental x-rays were used for image evaluation. Results The 3D accuracy showed that stereolithography (STL) and scan files of the AI design group were 3.4 and 6.6 times lower than the digital group, respectively (P < 0.05). The space of the occlusal surface of the AI-designed crown was 1.8-times higher than that of the digital design (P < 0.05). Intraoral optical images demonstrated that the AI designed crown closely resembled the human-designed counterpart in appearance. Comparison of color distribution showed more differences on the buccal and lingual sides between the two design patterns. Conclusion Clinical images indicate that the shape, precision, and space of AI designed crowns are comparable to those of digitally designed crowns. Despite the spatial differences in contact between AI designed and digitally designed crowns, the in vivo and in vitro test results demonstrated favorable realism and contact quality.

(1) Background: Eustachian tube dysfunction (ETD) is a frequently observed clinical manifestation of chronic rhinosinusitis (CRS). This systematic review aimed to evaluate the function of the Eustachian tube following endoscopic sinus surgery (ESS) in adult CRS patients with confirmed preoperative ETD symptoms. (2) Methods: A systematic search of PubMed, Cochrane, Embase, and MEDLINE electronic databases was conducted. The review was performed following the PRISMA guidelines. Studies investigating concurrent ETD in CRS patients who underwent ESS were retrieved. The changes in ETD outcomes were measured by the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7). We employed a random-effects model to conduct the meta-analysis (3) Results: We included seven observational studies that involved a total of 436 CRS patients with concurrent ETD. The pooled results revealed a statistically significant reduction (Standardized mean difference = −1.24; 95% CI = −1.64 to −0.84) in ETDQ-7 scores among the CRS with ETD patient cohort at the 3-month postoperative follow-up. (4) Conclusions: ESS serves as an effective intervention for improving E-tube function in adult CRS patients with concurrent ETD. Future prospective randomized controlled trials that incorporate various outcome predictors should be conducted to explore potential clinical factors for greater ETD improvement and normalization after ESS.

Lidocaine, a local anesthetic widely used in dentistry, is esteemed for its efficacy and safety. Recent research reveals its additional role in modulating the immune system, and particularly in reducing inflammation crucial for protecting tooth-supporting tissues. Notably, monocytes and macrophages, essential cellular components overseeing various physiological and pathological processes, stand as potential mediators of lidocaine's effects. Therefore, this study aimed to investigate how lidocaine influences cell behavior using RNA sequencing. To investigate the effect of lidocaine on THP-1 cells' behavior, we performed an MTT assay and RNA-Seq along with qPCR analyses to evaluate the transcriptomic and proteomic changes in THP-1 cells. Our results showed that a high dose of lidocaine (>1 mM) had a significant cytotoxic effect on THP-1 cells. However, a lidocaine dose lower than 0.5 mM induced a mixed anti-inflammatory profile by significantly upregulating tissue remodeling (GDF15, FGF7, HGF, COL4A3, COL8A2, LAMB2, LAMC2, PDGFRA, and VEGFA) and through the resolution of inflammation (Cpeb4, Socs1, Socs2, Socs3, Dusp1, Tnfaip3, and Gata3) gene cassettes. This study explores the effect of lidocaine on the THP-1 in the M2-like healing phenotype and provides potential applications of lidocaine's therapeutic effectiveness in dental tissue repair.

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.

ObjectiveTo compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis.Study DesignProspective cohort study.SettingUnicenter, Tertiary referral hospital.MethodsIncluded patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy)ResultsTotal of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT).ConclusionsThis is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.

The skin is subjected to various external factors that contribute to aging including oxidative stress from hydrogen peroxide (H2O2). This study investigated the distribution of aquaporin-8 (AQP8), a protein that transports H2O2 across biological membranes, in skin cells, and its effects in mitigating H2O2-induced oxidative damage. Human dermal fibroblasts were treated with increasing concentrations of H2O2 to evaluate oxidative damage. Cell viability, reactive oxygen species (ROS) generation, and the expression of specific genes associated with skin aging (IL-10, FPR2, COL1A1, KRT19, and Aggrecan) were evaluated and AQP8 expression was assessed via quantitative polymerase chain reaction and western blotting. Small-interfering RNA was used to silence the AQP8 gene and evaluate its significance. The results show that H2O2 treatment reduces cell viability and increases ROS generation, leading to oxidative damage that affects the expression of target molecules. Interestingly, H2O2-treated cells exhibit high levels of AQP8 expression and gene silencing of AQP8 reverses high levels of ROS and low levels of COL1A1, KRT19, and Aggrecan expression in stressed cells, indicating that AQP8 plays a vital role in preventing oxidative damage and consequent aging. In conclusion, AQP8 is upregulated in human dermal fibroblasts during H2O2-induced oxidative stress and may help prevent oxidative damage and aging. These findings suggest that AQP8 could be a potential therapeutic target for skin aging. Further research is necessary to explore the feasibility of using AQP8 as a preventive or therapeutic strategy for maintaining skin health.

Background: Incidence of fungal rhinosinusitis has increased in recent few years. We investigated the differences in microbiological findings between patients with fungal and non-fungal rhinosinusitis by growing microbiological cultures from samples obtained from sinus surgery. Methods: Using the Chang Gung Research Database, we enrolled all chronic rhinosinusitis (CRS) patients who had ever undergone sinus surgery from 2001 to 2019 and had microbiological culture during sinus surgery. Enrolled patients were divided into fungal and non-fungal groups, based on fungal culture and surgical pathology. Results: A total of 898 patients were diagnosed with fungal rhinosinusitis and 2884 with non-fungal rhinosinusitis. The fungal group had a higher age distribution (56.9 ± 13.1 vs. 47.0 ± 14.9), a larger proportion of females (62.4% vs. 37.0%), more unilateral lesions (80.4% vs. 41.6%), a lower incidence of the need for revision surgery (3.6% vs. 6.0%, p = 0.004), and a higher proportion of Pseudomonas aeruginosa in the culture (14.3% vs. 4.6%, p < 0.001). Conclusions: This large-scale study showed that Pseudomonas aeruginosa are more commonly found in patients with fungal rhinosinusitis and in patients who needed revision surgery, suggesting that efforts aimed at eliminating Pseudomonas are needed in order to improve the disease outcomes of patients with fungal rhinosinusitis.

(1) Background: Oral squamous cell carcinoma (OSCC) is a significant health burden worldwide. This study aimed to determine the potentials of Refametinib, an orally bioavailable selective MEK1/2 inhibitor, to increase the effectiveness of 5-Fluorouracil (5-FU), a common cytotoxic drug, in the SCC4 cell line. (2) Methods: SCC4 cells were treated with increasing concentrations of 5-FU, either alone or in combination with Refametinib. The chemosensitivity to treatment was assessed via cell viability assay, microscopic observation, colony formation assay, and detection of apoptotic markers using Western blotting. The whole-cell expression and surface expression of programmed death-ligand 1 (PD-L1), an immune checkpoint protein which contributes to chemoresistance and affects treatment response, were also determined using Western blotting and flow cytometry, respectively. (3) Results: The combined treatment suppressed cell proliferation and promoted apoptosis in a more potent way than 5-FU treatment alone did. Additionally, MEK/ERK inhibition mitigated 5-FU-induced PD-L1 upregulation. (4) Conclusions: This is the first report of an enhanced anticancer effect and reduced PD-L1 expression for the combination of 5-FU with Refametinib in OSCC, suggesting a new promising combination strategy.

Background Research studies have demonstrated that Midkine (MDK) can influence the expression and activity of Renin-angiotensin system (RAS) components. Angiotensin II is involved in tumor growth and angiogenesis in different cancers. We previously observed Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with oral cancers. These findings have prompted us to investigate whether MDK can influence the RAS pathway, mainly through its association with angiotensin II type 1 receptor (AT1R), which contributes to the observed poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients. Methods MDK and AT1R expressions were examined in 150 HNSCC patients post-operation by immunohistochemical staining between 1 January 2010 and 31 December 2016. We tested the over-expression and silencing of MDK to evaluate the AT1R expression and functional biological assays in HNSCC cell lines HSC-3 and SAS. Results Positive expression of MDK is correlated with positive AT1R expression. MDK predicted poor NSCC patients’ survival. Silencing MDK could suppress AT1R and pAKT expression and reduce the growth, migration, and invasion of HNSCC cells. ARB also inhibits MDK stimulating HNSCC cell proliferation. Overexpression of MDK could upregulate AT1R and pAKT. Conclusions MDK is an independent prognostic factor of HNSCC post-operation, and AT1R regulates HNSCC cell growth, invasion, and migration. Positive MDK and AT1R expressions are highly correlated. Mechanistically, the interaction between MDK and AT1R is crucial for MDK-mediated cell viability, and inhibiting AT1R can effectively counteract or abolish these effects. Furthermore, MDK exerts a regulatory role in the expression of AT1R, as well as in the growth and motility of HNSCC cells. These findings highlight the involvement of the interaction between MDK, AT1R, and the pAkt signaling pathways in HNSCC cell viability growth.

Oral cancer, constituted up to 90% by squamous cell carcinomas, is a significant health burden globally. Grape seed proanthocyanidins (PA) have been suggested as a potential chemopreventive agent for oral cancer. However, their efficacy can be restricted due to the low bioavailability and bioaccessibility. Inspired by sandcastle worm adhesive, we adapted the concept of complex coacervation to generate a new type of drug delivery platform. Complex coacervates are a dense liquid phase formed by the associative separation of a mixture of oppositely charged polyelectrolytes, can serve as a drug delivery platform to protect labile cargo. In this study, we developed a complex coacervates-based delivery of PA. The release kinetics was measured, and anticancer effects were determined in two human tongue squamous cell carcinoma cell lines. The results showed that complex coacervate successfully formed and able to encapsulate PA. Additionally, PA were steadily released from the system in a pH-dependent manner. The drug delivery system could significantly inhibit the cell proliferation, migration, and invasion of cancer cells. Moreover, it could markedly reduce the expression of certain matrix metalloproteinases (MMP-2, 9, and 13) crucial to metastatic processes. We also found that suppression of protein kinase B (Akt) pathway might be the underlying mechanism for these anticancer activities. Taken together, complex coacervates-based delivery of PA can act as an effective anticancer approach for oral cancer therapy.

The generation of hepatic spheroids is beneficial for a variety of potential applications, including drug development, disease modeling, transplantation, and regenerative medicine. Natural hydrogels are obtained from tissues and have been widely used to promote the growth, differentiation, and retention of specific functionalities of hepatocytes. However, relying on natural hydrogels for the generation of hepatic spheroids, which have batch to batch variations, may in turn limit the previously mentioned potential applications. For this reason, we researched a way to establish a three-dimensional (3D) culture system that more closely mimics the interaction between hepatocytes and their surrounding microenvironments, thereby potentially offering a more promising and suitable system for drug development, disease modeling, transplantation, and regenerative medicine. Here, we developed self-assembling and bioactive hybrid hydrogels to support the generation and growth of hepatic spheroids. Our hybrid hydrogels (PC4/Cultrex) inspired by the sandcastle worm, an Arg-Gly-Asp (RGD) cell adhesion sequence, and bioactive molecules derived from Cultrex BME (Basement Membrane Extract). By performing optimizations to the design, the PC4/Cultrex hybrid hydrogels can enhance HepG2 cells to form spheroids and express their molecular signatures (e.g., Cyp3A4, Cyp7a1, A1at, Afp, Ck7, Ck1, and E-cad). Our study demonstrated that this hybrid hydrogel system offers potential advantages for hepatocytes in proliferating, differentiating, and self-organizing to form hepatic spheroids in a more controllable and reproducible manner. In addition, it is a versatile and cost-effective method for 3D tissue cultures in mass quantities. Importantly, we demonstrate that it is feasible to adapt a bioinspired approach to design biomaterials for 3D culture systems, which accelerates the design of novel peptide structures and broadens our research choices on peptide-based hydrogels.

Increasing clinical evidence supports the use of direct oral anticoagulants (DOACs) as a potential new therapeutic option for patients suffering from cancer-associated thromboembolism. However, the clinical impact of DOACs compared with traditional anticoagulants on the survival of patients with head and neck cancer has not been well studied. A total of 1025 patients diagnosed as having head and neck cancer, including 92 DOAC users, 113 warfarin users, and 820 nonusers of anticoagulants, were selected from the Chang Gung Research Database between January 2001 and December 2019. The patients were matched using the propensity-score method. The survival rates were estimated among the three groups using the Kaplan–Meier method. The protective effects and side effects of the two anticoagulants were compared using the chi-square test. The death rate (18 patients, 19.57%) in patients using DOACs was significantly lower than that in patients using warfarin (68 patients, 60.18%) and those not using any anticoagulant (403 patients, 49.15%). DOAC users had significantly better disease-specific survival (DSS) than warfarin users (p = 0.019) and those who did not use any anticoagulant (p = 0.03). Further, DOAC users had significantly higher overall survival (OS) rates than warfarin users and those who did not use any anticoagulant (p = 0.003). Patients with oropharyngeal and laryngeal cancer and DOAC users had a significantly lower hazard ratio for survival, whereas patients with American Joint Committee on Cancer stage IV disease and those receiving multidisciplinary treatment (e.g., surgery with radiotherapy or concurrent radiochemotherapy) had a significantly higher hazard ratio for survival. Among them, patients with laryngeal cancer (HR = 0.47, 95% CI = 0.26–0.86, p = 0.0134) and DOAC users (HR = 0.53, 95% CI = 0.29–0.98, p = 0.042) had the lowest hazard ratio from DSS analysis. Similarly, patients with laryngeal cancer (HR = 0.48, 95% CI = 0.30–0.76, p = 0.0018) and DOAC users (HR = 0.58, 95% CI = 0.36–0.93, p = 0.0251) had the lowest hazard ratio from OS analysis. As for the protective effects or side effects of anticoagulants, there were no significant differences in the occurrence rate of bleeding or ischemic events between DOAC and warfarin users. In our study, DOACs were found to be better than warfarin in terms of survival in patients with head and neck cancer. As regards thromboembolism prevention and side effects, DOACs were comparable to warfarin in our patients. DOACs can be a treatment choice or prophylaxis for tumor emboli in head and neck cancer patients and they might be a better choice than traditional anticoagulants according to the results of our study.

The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.