Background:Streptococcus mutans (S. mutans) is a primary cariogenic pathogen responsible for acid production, exopolysaccharides (EPS) production and biofilm formation. Two-component systems (TCS) regulate EPS metabolism, especially the VicRK TCS. Overexpression of antisense vicR (ASvicR) can reduce EPS production and thereby weaken the cariogenicity of S. mutans. Although the antimicrobial monomer dimethylaminohexadecyl methacrylate (DMAHDM) exhibits potent antibacterial properties, mature S. mutans biofilms can protect themselves by extracellular matrix. Emerging evidence suggests that genetic intervention enhances drug efficacy, yet the underlying regulatory mechanisms remain largely unexplored. Objective:To investigate the chemical-genetic cooperative antibiofilm strategy inhibition and mechanisms of ASvicR overexpression combined with DMAHDM on S. mutans biofilm formation, acid and EPS metabolism, and cariogenicity through the VicRK system. Methods:The minimal inhibitory concentration and minimal bactericidal concentration of DMAHDM and chlorhexidine were determined. Biofilm properties were evaluated via biomass assessment, EPS quantification, lactate production measurement, and colony-forming unit counting. Biofilm structures were examined by scanning electron microscopy. Mechanisms were investigated using RT-qPCR, zymography, and western blot. Rat caries model was employed to assess caries formation under different treatment conditions. Results:The ASvicR strain exhibited an approximate 2-fold increase in susceptibility to DMAHDM and chlorhexidine. The combination treatment reduced biofilm CFU by approximately 4 log units, significantly lowered lactate and EPS levels, and resulted in a loose, porous biofilm structure. The expression levels of cariogenic virulence factors as well as the VicRK TCS genes and proteins were significantly downregulated. In vivo, the combined treatment reduced the overall caries severity score to 12.7% of the control group (p<0.05) without observing any systemic adverse effects. Conclusion:The strategy of combining ASvicR overexpression with DMAHDM effectively modulates EPS metabolism and cariogenicity in S. mutans by interfering with the VicRK TCS, providing a potential therapeutic approach for clinical caries management.

Angiogenesis, the formation of new blood vessels from preexisting vasculature, is often impaired in pathological conditions, such as a hyperglycemic environment. Angiogenesis is tightly regulated by a balance of proangiogenic and antiangiogenic factors. CD93, a glycoprotein expressed on endothelial cells (ECs), has been identified as a significant proangiogenic factor. However, the specific impact of its glycosylation, particularly O-GlcNAcylation, on endothelial cell function and angiogenesis remains entirely unexplored. Therefore, this study aimed to elucidate the role of CD93 glycosylation in angiogenesis and uncover the underlying molecular mechanism, especially under high glucose conditions. siCD93 was used to evaluate the role of CD93 in endothelial cell angiogenesis. Tube formation, spheroid sprouting assays, Transwell assays, and adhesion assays were used to assess the angiogenic capability, migration, and adhesion, respectively. Co-immunoprecipitation coupled with mass spectrometry (Co-IP-MS) was employed to identify CD93-interacting proteins. A murine dorsal skin wound model was used to elucidate its role in angiogenesis during wound healing. siCD93 significantly impaired angiogenesis by inhibiting migration and adhesion without affecting proliferation or cell cycle in ECs. CD93 O-GlcNAcylation modulated its proangiogenic function, whereas high-glucose treatment downregulated both CD93 expression and its O-GlcNAcylation. CD93 overexpression partially rescued the angiogenic impairment induced by high glucose. In vivo studies further indicated that CD93 knockout exacerbated wound healing delay in diabetic wounds. Mechanistically, heat shock protein 90 (HSP90) interacted with the extracellular domain of CD93 to stabilize CD93 O-GlcNAcylation and protect it from ubiquitin–proteasomal degradation. The HSP90–CD93 interaction enabled CD93 to activate the downstream focal adhesion kinase (FAK) signaling pathway, thereby promoting angiogenesis. In vivo experiments further confirmed that HSP90 inhibition impaired the proangiogenic effects of recombinant CD93 protein (rCD93) in skin wound healing. CD93 promotes angiogenesis dependent on O-GlcNAcylation. Under high glucose, CD93 expression and its O-GlcNAcylation are downregulated, leading to impaired angiogenesis. Mechanistically, HSP90 interacts with CD93 to stabilize it against ubiquitin–proteasomal degradation, thereby maintaining O-GlcNAcylation homeostasis and activating the downstream FAK signaling pathway. Our findings identify the HSP90–CD93 interaction as a potential therapeutic target for angiogenesis-related disorders.

Objective: Periodontitis adversely affects oral and overall health. Bone marrow–derived mesenchymal stem cells (BMMSCs) play regulatory roles in the immune system, and the exploration of therapeutic strategies involving BMMSCs has garnered significant attention in the context of inflammatory pathological processes. Interleukin-6 can regulate microRNA expression by activating the signal transducer and activator of transcription 3 (STAT3) and functions in some systemic diseases. Notably, the regulatory mechanisms between IL-6 and miR-181a-5p in BMMSCs underlying periodontitis are still unknown. This study aims to uncover the regulatory mechanisms between IL-6 and miR-181a-5p and create a new treatment strategy for periodontal tissue regeneration. Methods: In this study, Western blot was used to assess IL-6 and STAT3 levels. Quantitative real-time polymerase chain reaction assessed the expression of miR-181a-5p and the relative genes. Enzyme-linked immunosorbent assay detected the content of IL-6. The Cell Counting Kit-8 was used to evaluate cell viability. Alkaline phosphatase staining was used to analyse the osteogenesis of cells. Chromatin immunoprecipitation and dual luciferase activity assays were used to verify the binding relationship between miR-181a-5p, STAT3, and IL-6. Flow cytometry was used for identifying cell types. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology analysed potential signal pathways of genes targeted by miR-181a-5p. In addition, the present research was further investigated using a ligature-induced periodontitis model in mice. The micro–computed tomography, haematoxylin and eosin, and tartrate-resistant acid phosphatase (TRAP) assays were used for histologic analysis of the degree of inflammation and bone recovery in the experimental periodontitis and treatment group. Results: IL-6 and miR-181a-5p were upregulated in experimental periodontitis in mice. The IL-6 recombinant protein promoted mBMMSC proliferation and upregulated miR-181a-5p levels via STAT3. Functional inhibition of miR-181a-5p alleviated the T helper 17 (Th17) cell/regulatory T cell (Treg) immune imbalance triggered by IL-6 stimulation. Injection of miR-181a-5p inhibitor preconditioned mBMMSCs significantly promoted periodontal tissue regeneration, and osteoclasts and bone resorption were reduced significantly. Conclusion: IL-6 may contribute to the progression of experimental periodontitis in mice via modulating STAT3‑mediated miR‑181a‑5p expression in mBMMSCs and may potentially influence periodontal tissue regeneration through regulating the Th17/Treg balance.

A member of the secretory calcium-binding phosphoprotein (SCPP) family, scpp5 is specifically expressed in zebrafish tooth germ. Although preliminary data indicates that scpp5 deficiency impairs tooth mineralization, its molecular mechanism and role in tooth repair remain unclear. In this study, we generated scpp5-/- knockout and Tg(hsp70l:scpp5-GFP; cryaa:venus) overexpression zebrafish lines. Tooth germ cells were labeled using Tg(dlx2b:Dendra2-NTR), and a tooth injury model was established via the nitroreductase (NTR)/metronidazole (MTZ) system. Loss-of-function studies showed that scpp5 knockout inhibited tooth mineralization and tooth germ cell development during normal development, attenuated Wnt/β-catenin signaling, downregulated calcium efflux channel gene expression, and suppressed both enameloid and dentin matrix-related genes. Rescue of Wnt pathway activity restored calcium efflux channel and dentin matrix gene expression, but not enameloid matrix gene expression. Gain-of-function studies revealed that scpp5 overexpression did not affect normal tooth development, but during repair after injury, it accelerated mineralization and cell regeneration. Mechanistically, scpp5 overexpression during repair activated Wnt/β-catenin signaling, specifically enhancing calcium channel and dentin matrix gene expression, without affecting enameloid matrix gene expression. Collectively, these findings demonstrate that scpp5 promotes tooth mineralization during normal development via Wnt/β-catenin-dependent regulation of both enameloid and dentin matrix genes, whereas during injury repair, scpp5 facilitates regeneration by selectively activating Wnt/β-catenin to drive dentin matrix and calcium channel gene expression, independent of enameloid matrix genes.

Although the role of retinoic acid (RA) signalling in odontogenesis is well established, its involvement in the repair of injured tooth germs remains unclear. To investigate this, we generated a Tg(scpp5:Dendra2-NTR) zebrafish line for labelling tooth germ cells and established a tooth germ injury model using the nitroreductase (NTR)/metronidazole (MTZ) system. We then modulated RA signalling by exogenous activation with RA, retinol, retinal, talarozole (TZ) or Tg(hsp70l:aldh1a2-p2a-mCherry; cryaa:venus), and by suppression with 4-diethylaminobenzaldehyde (DEAB) or Tg(hsp70l:dnRARAA-p2a-DsRed; cryaa:venus), to examine its function in tooth germ repair. Following targeted ablation of tooth germ cells, RA signalling was activated, with aldh1a2 showing the most pronounced upregulation. Exogenous RA promoted injury-induced tooth germ repair, whereas its precursors (retinol and retinal) had no significant effect on aldh1a2 expression or repair. Pharmacological inhibition of RA degradation with TZ enhanced repair, while dominant-negative inhibition of RA signalling impaired it. Furthermore, modulation of aldh1a2 revealed its essential role: inhibition with DEAB attenuated repair, whereas genetic activation facilitated tissue restoration. In summary, this study clarifies the regulatory role of RA signalling in tooth germ injury repair, offering a theoretical foundation and potential therapeutic targets for the treatment of injured tooth germs.

Periodontitis is a formidable chronic inflammatory disorder, marked by pathological oxidative stress, persistent inflammation, and alveolar bone resorption. The simultaneous management of these interrelated pathological processes poses significant challenges to conventional therapeutic modalities. In this study, we developed a multifunctional nanotherapy, EXO@Lip-Res, constructed from exosome-liposome hybrid nanoparticles. By synergistically integrating resveratrol-loaded liposomes with exosomes derived from dental pulp stem cells, this approach was designed to address the multifaceted nature of periodontitis. The synthesized EXO@Lip-Res exhibited favorable physicochemical properties and retained distinct exosomal markers, facilitating a reactive oxygen species (ROS)-responsive to trigger programmed drug release. In vitro evaluations demonstrated that EXO@Lip-Res exhibited superior antioxidant and anti-inflammatory activities. Specifically, EXO@Lip-Res treatment significantly scavenged H2O2-induced intracellular ROS in both RAW264.7 cells and PDLSCs (p < 0.05). In the context of inflammation, the nanoplatform markedly downregulated the expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated PDLSCs compared to the LPS-only group. Quantitative analysis revealed a 50

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers.

An in vitro model intended to mimic the cariogenic conditions found in the oral cavity is the tristreptococcal species biofilms. Extracellular polysaccharides are the main pathogenic element in these biofilms. Owing to the obstruction of dental surface extracellular polysaccharides, conventional antibiotics have a limited residence time in cariogenic biofilms, leading to poor inhibition of dental plaque. To overcome this problem, we drew inspiration from cell membrane-coated nanoparticles (CMCNPs) and synthesized LA/TCS@PLGA by encapsulating triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA) with a Lactobacillus acidophilus (LA) outer membrane. The aim of this investigation was to examine how LA/TCS@PLGA penetrate Streptococcus sanguinis, Streptococcus gordonii, and Streptococcus mutans (S.s + S.g + S.m) cariogenic biofilms and inhibit the cariogenic extracellular polymeric substances (EPS) in these biofilms. The LA/TCS@PLGA were stable in terms of size, zeta potential, and sustained drug release kinetics. Moreover, the LA/TCS@PLGA inherited the adhesion ability of the L. acidophilus outer membrane, and compared with the uncoated TCS@PLGA, the LA/TCS@PLGA could adhere to and reside in tristreptococcal species biofilms more extensively and penetrate the inner biofilm layer more deeply with time. Additionally, the LA/TCS@PLGA disrupted the structure of the tristreptococcal species biofilms and reduced the levels of the virulence factor EPS, lactic acid, biomass, total protein, and dry weight. Furthermore, in vivo, LA/TCS@PLGA alleviated the degree or even prevented the occurrence of caries. The nanoparticles also exhibited favorable safety in vivo. The results indicate the excellent application potential of LA/TCS@PLGA in the treatment of oral diseases caused by biofilms.

Background:Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an immunosuppressive microenvironment. Although CD93 promotes angiogenesis in tumor endothelial cells, its role in HNSCC tumor cells and the impact of CD93-mediated regulation of tumor cells on the tumor microenvironment are unclear. This study investigates whether CD93 promotes the malignant progression of HNSCC by enhancing tumor cell malignancy and contributing to macrophage-associated and angiogenic remodeling of the tumor microenvironment, elucidating the underlying mechanisms. Methods:Bioinformatics analyses assessed CD93 expression, clinical relevance, immune infiltration, and signaling pathways in HNSCC. CD93 expression was validated in clinical specimens and cell lines. CD93 knockdown and overexpression models were used to examine invasion, migration, proliferation, and epithelial-mesenchymal transition (EMT). Conditioned media from CD93-modulated tumor cells were applied to THP-1-derived macrophages and HUVECs to assess macrophage-associated markers and endothelial tube formation. Wnt/β-catenin signaling was pharmacologically activated or inhibited. Xenograft growth and macrophage depletion were evaluated in BALB/c nude mice. Protein-protein docking was used to explore predicted spatial compatibility between CD93 and receptor-proximal Wnt pathway components. Results:CD93 was upregulated in HNSCC and associated with poor prognosis and an immunosuppressive, pro-angiogenic TME. CD93 knockdown inhibited invasion, migration, proliferation, EMT-associated changes, CD206 expression, changes in macrophage-associated markers, and endothelial tube formation, whereas CD93 overexpression produced opposite effects. CD93 expression was associated with Wnt/β-catenin activation; CHIR99021 reversed the effects of CD93 knockdown, whereas XAV939 attenuated changes induced by CD93 overexpression. In vivo, CD93 knockdown suppressed xenograft growth, proliferation, angiogenesis, EMT-associated changes, CD206-positive macrophage-associated signals, and β-catenin expression. Clodronate liposome-mediated macrophage depletion reduced HSC3-shNC tumor growth and narrowed the difference between HSC3-shNC and HSC3-shCD93 tumors. Docking analysis indicated that CD93 showed the most favorable predicted spatial compatibility with LRP6 E1E2 among the tested Wnt receptor-related components. Conclusion:CD93 may promote HNSCC progression by enhancing tumor-cell aggressiveness and tumor microenvironment remodeling, at least partly through Wnt/β-catenin-related signaling. Docking analysis provides a preliminary structural hypothesis for a potential CD93-LRP6 E1E2 spatial association. CD93 may represent a prognostic biomarker and candidate therapeutic target in HNSCC.

BACKGROUND:Computer-Aided Design (CAD) combined with 3-dimensional (3D) printing technology has been extensively applied in the treatment of endodontic diseases. The goal of this novel report is to highlight a fully guided autotransplantation with CAD and 3D printing technology for treatment of tooth fracture. CASE PRESENTATION:The maxillary left first molar #26 had a vertical fracture that severely affected occlusion and life quality of the patient. Clinical examination showed an oblique crack across the mesiobuccal cusp and the distopalatal cusp of #26, cone-beam computed tomography (CBCT) showed a vertical fracture line reaching the floor of pulp chamber, a subtle increase in the palatal periodontal ligament space, and hypodensity in the distobuccal apex area. Due to the strong desire to preserve natural tooth and financial considerations, the patient declined conventional prosthetic restoration and chose autotransplantation of mandibular left third molar #38 to the site of #26. A 3D printed guide was used to precisely prepare the extraction socket, facilitating the immediate and accurate autotransplantation of #38 into the site of #26. Root canal therapy was performed 3 weeks after surgery. RESULTS:During the 3-year follow-up, the patient could chew normally without any discomfortable feelings, X-ray radiographs showed a significant increase in bone density around the root and a superior periodontal ligament healing without root resorption. CONCLUSIONS:For patients who do not choose prosthetic restoration due to socio-economic conditions, we propose tooth autotransplantation as an alternative treatment for tooth fractures under the help of modern CAD and 3D printing technology.

ObjectiveTumors remain a major cause of death worldwide due to late-stage presentation and late diagnosis. Cell therapies have revolutionized the landscape in the precision treatment of tumors. However, there are still many challenges that limit the therapeutic efficacy. Additionally, cancer treatment also entails a major financial burden throughout the entire phase, making it preferable to find a specific biomarker for the early prognosis of the tumor.MethodsIn this study, the role of CD248 in pan-cancer was analyzed through diverse tumor-associated databases, such as the Human Protein Atlas Database, the GEPIA2 Database, the cBioPortal Database, the TIMER Database, the STRING tool, and so on. In addition, CD248 mRNA and protein levels were assessed in a series of head and neck squamous cell carcinoma (HNSC) cell lines using qRT-PCR and Western blot. Furthermore, siCD248 was used to detect the effect of CD248 on the invasion, migration, and proliferation of HNSC cells by transwell assay, scratch wound healing assay, and EdU assay, respectively.ResultsCD248 expression was significantly increased and correlated with advanced stage and poor prognosis in various tumors. Genetic alterations of CD248 were also associated with a poor prognosis of patients. Single-cell sequencing revealed that CD248 was mainly expressed on fibroblasts within the stroma, and its expression was positively correlated with the infiltration of immune cells in tumors. In addition, CD248 interacted with 11 common tumor biomarkers. Experiment results indicated that CD248 mRNA and protein expression were upregulated in HNSC cell lines, and inhibition of CD248 suppresses the invasion, migration, and proliferation of HNSC cells.ConclusionHigh CD248 expression played a crucial role in pan-cancer, including immune cell infiltration, tumor progression and metastasis, and patient prognosis. CD248 plays a crucial role in tumor cells’ functions, including invasion, migration, and proliferation. All these findings indicated that CD248 may be a novel oncoprotein and a potential therapeutic target for pan-cancer.

The dental caries remains a globally prevalent disease. Although its incidence has decrease due to enhancements in sanitation policies and public health measures, the treatment and prevention of dental caries still pose significant challenges. Within the oral cavity, traditional drug delivery systems suffer from limitation such as inadequate tissue penetration, short duration of action at target site, and low specificity, which minimally affect the prevention and treatment of dental caries. Consequently, nanosystem for drug delivery, offering enhanced drug stability, solubility, and bio-availability while reducing side effects, garnering attention increasing attention in the fight against dental caries. Therefore, this review examines the role of nanosystems for drug delivery in combating dental caries by inhibiting bacteria survival, biofilm formation, demineralization, and promoting remineralization, and exploring their potential to become the mainstream means of prevention and treatment of dental caries in future.

Aim or purpose: Our group previously found that mTORC1 signaling is activated during tooth regeneration after injury, and this study will explore the regulatory mechanisms of mTORC1 and its associated molecular effectors in this process. Materials and methods: 1) Targeted ablation of tooth germs in zebrafish Tg(dlx2b:Dendra2-NTR) using the NTR/Mtz system. mTORC1 was activated via L-Leucine or tsc2 mutants and regeneration was assayed by antibody staining; 2) Mandibular incisors of ICR mice were mechanically injured and treated with intraperitoneal rapamycin to inhibit mTORC1. Newborn incisors were analyzed by SEM, micro-CT, and histological staining; 3) Zebrafish urb2 mutants and the Tg(Hsp70L:urb2-flag) were generated. Rescue effects were evaluated using FISH, in situ hybridization, and alizarin red assays to validate the molecular axis of mTORC1/Urb2 in tooth regeneration; 4) Tg(hsp70l:dnFGFR-GFP) was used to inhibit FGF signaling, and potential molecular mechanisms linking FGF and the mTORC1/Urb2 were explored. Results: 1) mTORC1 activation promotes zebrafish cell proliferation and tooth regeneration; 2) Rapamycin disrupted enamel column organization. Histological staining revealed that mTORC1 regulates incisal restoration via cellular function modulation in the cervical ring; 3) FISH revealed that mTORC1 inhibition decreased urb2 transcripts, while urb2 overexpression rescued rapamycin-induced tooth regeneration defects: enhanced Dendra2 fluorescence, upregulated tooth-specific gene expression, and accelerated tooth mineralization. 4) FGF signaling inhibition impaired tooth regeneration, while activation of the mTORC1/Urb2 axis alleviated the phenotypic impairments. Conclusions: FGF/mTORC1/Urb2 signaling cascade governs tooth regeneration after injury, providing new therapeutic targets for tooth tissue engineering.

We tracked lineage map of the Ins2 cells in mice and insulin expression in migration sites of cells. We studied effect of the Wnt/β-catenin signaling pathway on the migration. We studied insulin secretion status in submandibular gland of mice under hyperglycemia stress. Cre/loxp system was used to observe migration sites and timing of the Ins2-cre lineage cells. Immunohistochemistry and immunofluorescence was used to detecte presence of insulin in the Ins2-cre lineage cells. Knockout mice from E9.5 to adulthood was studied to explore role of the Wnt/β-catenin on the migration. Immunofluorescence and the QRT-PCR (Quantitative Real-time Polymerase Chain Reaction) was used to study insulin secretion in submandibular gland under hyperglycemic conditions. Expression sites of the Ins2-cre gene in adult mice decreased compared with postnatal mice, including the pancreas, tongue, submandibular, and brain. In the migration tissues of ins-cre cells, positive insulin expression was detected in the submandibular acinus, vessel element and pancreatic islets. In comparison to wild-type mice, Wnt/β-catenin signaling knockout mice displayed a slight rise of INS2 expression during the neonatal stage, with a notable increase in adulthood, particularly in areas near the oral cavity. Expression of insulin in submandibular gland of mice increased after 6 h of hyperglycemic stimulation (P < 0.05). Ins2 lineage cells can migrate to multiple organs in mice, where insulin may expressed. Inhibition or knockout of the Wnt/β-catenin signaling pathway may indirectly enhance the migratory capacity of INS2 cells. Submandibular glands may secrete insulin under stress of maintaining organismal homeostasis. Wnt/β-catenin may be the therapeutic target of diabetes. Submandibular glands may be a new target organ of gene therapy for diabetic patients.

Macrophages are vital for regulating periodontal health, and numerous studies have extensively investigated their role in periodontitis progression. This study employs bibliometric analysis to identify research trends and hotspots related to macrophages in periodontitis from 2004 to 2024, thereby guiding future investigations and exploring potential clinical applications. Literature retrieval and dataset export were conducted via the Web of Science Core Collection database. Subsequently, bibliometric analysis was performed and the results were visualized using Microsoft Office Excel, VOSviewer, CiteSpace, and GraphPad Prism. A total of 1542 papers from 2004 to 2024 on the macrophages associated with periodontitis were identified. The annual number of publications and citations has steadily increased. China and the United States were the primary collaborators and drivers of research. Sichuan University had the largest number of published studies. The Journal of Periodontal Research published the most papers, while the Journal of Periodontology had the most citations. Daniel Grenier was the most prolific author and George Hajishengallis was the most frequently co-cited author. Co-citation analysis indicated that researchers primarily investigate the mechanisms of macrophages in periodontitis through both in vivo and in vitro experiments. Emerging research hotspots encompass keywords such as “macrophage polarization,” “extracellular vesicles,” and “regeneration.” Research on macrophages in periodontitis is progressing quickly, and their strategic targeting offers a new and promising direction for future studies on regenerating periodontal tissues. The utilization of extracellular vesicles derived from diverse sources to regulate M1/M2 macrophage polarization presents a promising strategy for the treatment of periodontitis.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient’s general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.

Schematic illustration of the preparation of skin secretion of Andrias davidianus (SSAD) hydrolysate. Remineralization of dentin and the occlusion of dentinal tubules (DTs) induced by SSAD hydrolysate.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.

Aim or purpose: The symbiosis of Candida albicans and Streptococcus mutans plays an important role in the progression of dental caries. Bafilomycin A1 (BAF) is the specific inhibitor of vacuolar proton-translocating ATPase, which is a key enzyme regulating the growth and virulence of Candida albicans. The aim of this study was to investigate the effect of BAF against C. albicans cell and C. albicans-S. mutans dual-species biofilm. Materials and methods: C. albicans cells were treated with different concentrations of BAF (0, 0.1, and 0.5 μM). The growth rate, colony morphology and cell morphology were observed, and the acid production and reactive oxygen species accumulation were detected. With construction of C. albicans-S. mutans dual-species biofilm, the biofilm biomass, exopolysaccharides and lactic acid production were examined, and the biofilm structure was observed under CLSM and SEM. Results: Candida albicans cells treated with 0.5 μM BAF exhibited slow growth rate, decreased hyphal development and acid production, and enhanced reactive oxygen species accumulation. The C. albicans-S. mutans biofilm after BAF treatment showed reduced microorganisms, exopolysaccharides and lactic acid production. The biofilm structure was loose with decreased C. albicans cells and the proportion of hyphae, less tight adhesion between the two species, and decreased extracellular matrix. Conclusions: Bafilomycin A1 can inhibit the growth of C. albicans cells and destruct the structure of C. albicans-S. mutans cross-kingdom biofilm. This study may help to develop new methods for the prevention and treatment of fungal infections and dental caries.