Age-related bone diseases: Role of inflammaging.

Bone aging is characterized by an imbalance in the physiological and pathological processes of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis, resulting in exacerbated bone loss and the development of age-related bone diseases, including osteoporosis, osteoarthritis, rheumatoid arthritis, and periodontitis. Inflammaging, a novel concept in the field of aging research, pertains to the persistent and gradual escalation of pro-inflammatory reactions during the aging process. This phenomenon is distinguished by its low intensity, systemic nature, absence of symptoms, and potential for management. The mechanisms by which inflammaging contribute to age-related chronic diseases, particularly in the context of age-related bone diseases, remain unclear. The precise manner in which systemic inflammation induces bone aging and consequently contributes to the development of age-related bone diseases has yet to be fully elucidated. This article primarily examines the mechanisms underlying inflammaging and its association with age-related bone diseases, to elucidate the potential mechanisms of inflammaging in age-related bone diseases and offer insights for developing preventive and therapeutic strategies for such conditions.

Effects of exosomes derived from platelet-rich plasma on osteogenic differentiation of dental pulp stem cells.

Platelet-rich plasma (PRP) can cause osteogenic differentiation of dental pulp stem cells (DPSCs). However, the effect of exosomes derived from PRP (PRP-Exos) on osteogenic differentiation of DPSCs remains unclear. Herein, we evaluated the impact of PRP-Exos on osteogenic differentiation of DPSCs. PRP-Exos were isolated and identified by transmission electron microscopy (TEM) and western blotting (WB). Immunofluorescence staining was performed to evaluate endocytosis of PRP-Exos by DPSCs. Alkaline phosphatase staining, alizarin red staining, western blot and qRT-PCR were carried out to evaluate the DPSCs osteogenic differentiation. The sequencing microRNA (miRNA) was conducted to determine the microRNA profile of PRP-Exos treated and untreated DPSCs. The results showed that endocytosis of PRP-Exos stimulated DPSCs odontogenic differentiation by elevated expression of ALP, DMP-1, OCN, and RUNX2. ALP activity and calcified nodules formation of PRP-Exos treated DPSCs were considerably elevated relative to that of the control group. MicroRNA sequencing revealed that 112 microRNAs considerably varied in PRP-Exos treated DPSCs, of which 84 were elevated and 28 were reduced. Pathway analysis suggested that genes targeted by differentially expressed (DE) miRNAs were contributed to many signaling cascades, such as the Wnt cascade. 65 genes targeted by 30 DE miRNA were contributed to Wnt signaling. Thus, it can be infered that PRP-Exos could enhance osteogenic differentiation and alter the miRNA expression profile of DPSCs.

Oral microbial changes and oral disease management before and after the treatment of hematological malignancies: a narrative review.

OBJECTIVES: Patients with hematological malignancies have dynamic changes in oral microbial communities before and after treatment. This narrative review describes the changes in oral microbial composition and diversity, and discusses an oral microbe-oriented strategy for oral disease management. MATERIALS AND METHODS: A literature search was performed in PubMed/Medline, Web of Science, and Embase for articles published between 1980 and 2022. Any articles on the changes in oral microbial communities in patients with hematological malignancies and their effects on disease progression and prognosis were included. RESULTS: Oral sample detection and oral microbial sequencing analysis of patients with hematological malignancies showed a correlation between changes in oral microbial composition and diversity and disease progression and prognosis. The possible pathogenic mechanism of oral microbial disorders is the impairment of mucosal barrier function and microbial translocation. Probiotic strategies, antibiotic strategies, and professional oral care strategies targeting the oral microbiota can effectively reduce the risk of oral complications and the grade of severity in patients with hematological malignancies. CLINICAL RELEVANCE: This review provides dentists and hematologists with a comprehensive understanding of the host-microbe associated with hematologic malignancies and oral disease management advice.

Cleaning efficacy of EDDY versus ultrasonically-activated irrigation in root canals: a systematic review and meta-analysis.

BACKGROUND: Ultrasonically-activated irrigation (UAI) is effective in root canal irrigation but may damage canal walls. EDDY is a sonic activation system with flexible working tips that cause no harm to dentinal walls. This review explores the intracanal cleaning efficacy of EDDY compared with UAI in vitro. METHODS: The systematic review was registered in the PROSPERO database (CRD42021235826). A literature search was conducted in six electronic databases. In vitro studies that compared the removal of smear layer, debris, soft tissue or microbes in root canals between EDDY and UAI were included. Data extraction and quality assessment were performed. Meta-analyses were conducted on smear layer removal and debris elimination with the standardized mean difference (SMD). Heterogeneity was measured using the I2 test and the Chi2 test. The random-effect model was used when I2 > 50%, or p < 0.1, otherwise the fixed-effect model was applied. The level of significance was set at p < 0.05. RESULTS: 19 articles were included in this systematic review and 7 articles were included in meta-analyses. Meta-analyses on smear layer removal showed unimportant differences between EDDY and UAI at any canal third (coronal [SMD = 0.08, 95% confidence interval (95%CI): -0.29 to 0.45; p = 0.44, I2 = 0%]; middle [SMD = 0.02, 95% CI: -0.44 to 0.47; p = 0.94, I2 = 0%]; apical [SMD = 0.01, 95%CI: -0.35 to 0.38; p = 0.70, I2 = 0%]). Meta-analyses on debris removal evaluated by scanning electron microscope (coronal [SMD = 0.03, 95% CI: -0.41 to 0.46; p = 0.27, I2 = 23%]; middle [SMD = -0.24, 95% CI: -0.83 to 0.35; p = 0.80, I2 = 0%]; apical [SMD = 0.24, 95%CI: -0.20 to 0.67; p = 0.36, I2 = 2%]) and micro-CT (SMD = 0.36, 95% CI: -0.67 to 1.40; p = 0.03, I2 = 70%) both found insignificant differences. No meta-analysis was undertaken on soft-tissue removal and disinfection due to the various study designs, but the qualitative analyses implied that EDDY achieved similar performance to UAI in both aspects. CONCLUSIONS: Limited evidence indicated that EDDY was comparable to UAI in removing smear layer, debris, soft tissue and microbes ex vivo. Considering UAI may damage canal walls, EDDY might be a substitute for UAI in irrigation activation. But more randomized clinical trials are required to explore the clinical extrapolation of the results in this review.

mTORC1 promotes mineralization via p53 pathway.

The objectives of our study were to investigate the roles of mTORC1 in odontoblast proliferation and mineralization and to determine the mechanism by which mTORC1 regulates odontoblast mineralization. In vitro, MDPC23 cells were treated with rapamycin (10 nmol/L) and transfected with a lentivirus for short hairpin (shRNA)-mediated silencing of the tuberous sclerosis complex (shTSC1) to inhibit and activate mTORC1, respectively. CCK8 assays, flow cytometry, Alizarin red S staining, ALP staining, qRT-PCR, and western blot analysis were performed. TSC1-conditional knockout (DMP1-Cre+ ; TSC1f/f , hereafter CKO) mice and littermate control (DMP1-Cre- ; TSC1f/f , hereafter WT) mice were generated. H&E staining, immunofluorescence, and micro-CT analysis were performed. Transcriptome sequencing analysis was used to screen the mechanism of this process. mTORC1 inactivation decreased the cell proliferation. The qRT-PCR and western blot results showed that mineralization-related genes and proteins were downregulated in mTORC1-inactivated cells. Moreover, mTORC1 overactivation promoted cell proliferation and mineralization-related gene and protein expression. In vivo, the micro-CT results showed that DV/TV and dentin thickness were higher in CKO mice than in controls and H&E staining showed the same results. Mineralization-related proteins expression was upregulated. Transcriptome sequencing analysis revealed that p53 pathway-associated genes were differentially expressed in TSC1-deficient cells. By inhibiting p53 alone or both mTORC1 and p53 with rapamycin and a p53 inhibitor, we elucidated that p53 acts downstream of mTORC1 and that mTORC1 thereby promotes odontoblast mineralization. Taken together, our findings demonstrate that the role of mTORC1 in odontoblast proliferation and mineralization, and confirm that mTORC1 upregulates odontoblast mineralization via the p53 pathway.

Differential expression of lncRNA/miRNA/mRNA and their related functional networks during the osteogenic/odontogenic differentiation of dental pulp stem cells.

Dentin-pulp regeneration requires dental pulp stem cells (DPSCs), but the role of long noncoding RNAs (lncRNAs) during this process remains unclear. Here, we cultured human DPSCs in osteogenic/odontogenic medium for 14 days and analyzed cells via RNA-sequencing. The data were validated by quantitative reverse transcription-polymerase chain reaction and lncRNA-microRNA (miRNA)-messenger RNA (mRNA) networks were constructed to reveal the potential competing endogenous RNA regulatory role of lncRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were performed. One lncRNA, SNHG7, was identified and validated by genetic shRNA silencing. A total of 89 lncRNAs, 1,636 mRNAs, and 113 miRNAs were differentially expressed after differentiation. Bioinformatics identified an array of affected signaling pathways including phosphoinositide-3-kinase-protein kinase B, transforming growth factor-ß, and Wnt. mRNAs were enriched in cell migration, cell differentiation, stem cell development, ossification, and skeletal development. One lncRNA, SNHG7, was indentified to inhibit the odonto/osteogenic differentiation of DPSCs when silenced. In summary, we reveal several lncRNAs that significantly change during DPSC differentiation, including SNHG7. This reveals new targets for dentin-pulp complex regeneration and tissue engineering.

Cone-beam computed tomography investigation of middle mesial canals and isthmuses in mandibular first molars in a Chinese population.

BACKGROUND: While there is ample research into the anatomy of mandibular molars, little is known regarding isthmuses and middle mesial (MM) canals in Chinese populations. The goal of this study was to determine the prevalence of MM canals and isthmuses in the mesial root of mandibular first molars using Cone-beam Computed Tomography. METHODS: Cone-beam Computed Tomography images of 357 mature mandibular first molars were retrospectively analyzed. Presence of isthmuses and MM canals, and the length of isthmuses in the mesial root were recorded. Meanwhile, we also recorded possible correlated factors such as demographics, side of mandible, presence of separated distal-lingual roots. RESULTS: Of these 357 teeth, 209 showed evidence of either complete or partial communication in the mesial root. Of these, 11(3.1%) exhibited true MM canals while 198(55.5%) exhibited isthmuses. Sex or side of mandible was not correlated with the prevalence of isthmuses (P > 0.05). However, there was a significant association between the presence of a distal-lingual root and the prevalence of such communication (P < 0.001). The average length of isthmuses was 4.3 ± 3.1 mm. CONCLUSIONS: We detected high rate of isthmuses and low rate of MM canals in mesial roots of mandibular first molars, which is important as such areas should be identified and cleaned during root canal treatment.

Priming integrin α5 promotes human dental pulp stem cells odontogenic differentiation due to extracellular matrix deposition and amplified extracellular matrix-receptor activity.

Our previous study showed that knocking down integrin α5 (ITGA5) expression by using a lentiviral vector in human dental pulp stem cells (DPSCs) led to weakening proliferation and migration capacity while enhanced odontogenic differentiation. To seek for possible clinical application, we investigated the effect of the ITGA5 priming synthetic cyclic peptide (SCP; GA-CRRETAWAC-GA) on proliferation, migration, and the odontogenic differentiation of DPSCs. Remarkably, the involved mechanism was explored by isobaric tag for relative and absolute quantitation proteomic technique, and the in vivo effect of ITGA5 was investigated by nude mice subcutaneous transplantation of cell and hydroxyapatite/ß-tricalcium phosphate complex. Results showed that SCP weakened the proliferation and migration capacity while enhanced odontogenic differentiation of DPSCs as lentivirus. The phosphorylation of FAK, PI3K/AKT, and MEK1/2/ERK1/2, along with IGF2/IGFBP2 and Wnt/ß-catenin signaling pathway play an important role in this process. Proteomic Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the key role of extracellular matrix (ECM) and ECM-receptor activity pathway were involved. ECM constituents, secreted protein acidic and cysteine-rich (SPARC), lumican, vitronectin, prolargin, decorin, collagen type VI α1 chain (COL6A1), COL6A2, COL14A1, and COL5A1 were upregulated in the ITGA5-silenced group. Inhibited expression of ITGA5 in DPSCs increased osteoid tissue formation and stronger related genes expression in vivo. In conclusion, the ITGA5 priming peptide could promote DPSCs odontogenic differentiation as lentivirus. Proteomics and bioinformatic analysis revealed that this may be due to the deposition of ECM and amplified ECM-receptor activity, which could fuel the application process of utilizing priming ITGA5 on dental clinical practice.

Stathmin inhibits proliferation and differentiation of dental pulp stem cells via sonic hedgehog/Gli.

The mineralization of dental pulp stem cells is an important factor in the tissue engineering of teeth, but the mechanism is not yet obvious. This study aimed to identify the effect of Stathmin on the proliferation and osteogenic/odontoblastic differentiation of human dental pulp stem cells (hDPSCs) and to explore whether the Shh signalling pathway was involved in this regulation. First, Stathmin was expressed in the cytoplasm and on the cell membranes of hDPSCs by cell immunofluorescence. Then, by constructing a lentiviral vector, the expression of Stathmin in hDPSCs was inhibited. Treatment with Stathmin shRNA (shRNA-Stathmin group) inhibited the ability of hDPSCs to proliferate, as demonstrated by a CCK8 assay and flow cytometry analysis, and suppressed the osteogenic/odontoblastic differentiation ability, as demonstrated by alizarin red S staining and osteogenic/odontoblastic differentiation-related gene (ALP, BSP, OCN, DSPP) activity, compared to that of hDPSCs from the control shRNA group. Molecular analyses showed that the Shh/GLI1 signalling pathway was inhibited when Stathmin was silenced, and purmorphamine, the Shh signalling pathway activator, was added to hDPSCs in the shRNA-Stathmin group, real-time PCR and Western blotting confirmed that expression of Shh and its downstream signalling molecules PTCH1, SMO and GLI1 increased significantly. After activating the Shh signalling pathway, the proliferation of hDPSCs increased markedly, as demonstrated by a CCK8 assay and flow cytometry analysis; osteogenic/odontoblastic differentiation-related gene (ALP, BSP, OCN, DSPP) expression also increased significantly. Collectively, these findings firstly revealed that Stathmin-Shh/GLI1 signalling pathway plays a positive role in hDPSC proliferation and osteogenic/odontoblastic differentiation.

Association of Periodontitis with Rheumatoid Arthritis and the Effect of Non-Surgical Periodontal Treatment on Disease Activity in Patients with Rheumatoid Arthritis.

BACKGROUND The association of periodontitis (PD) with the prevalence of rheumatoid arthritis (RA) remains controversial. Therefore, the aim of this study was to evaluate their correlation and investigate the effects of non-surgical periodontal treatment on RA. MATERIAL AND METHODS A total of 64 patients were enrolled in this study and divided into 4 groups: 18 PD patients (PD+RA-), 18 RA patients (PD-RA+), 18 RA with PD patients (PD+RA+), and 10 healthy controls (PD-RA-). Periodontal and rheumatologic parameters were examined at baseline and 1 month following non-surgical periodontal treatment. RESULTS Our results showed that RA patients had similar periodontal status. However, patients in the PD+RA+ group had significantly higher levels of rheumatologic parameters such as C-reactive protein (CRP), anti-cyclic citrulline peptide antibody (ACPA), erythrocyte sedimentation rate (ESR), and Disease Activity Score 28 (DAS28) than those in the PD-RA+ group. In addition, non-surgical periodontal treatment was efficacious in improving rheumatologic parameters of patients in the PD+RA+ group. CONCLUSIONS The presence of PD might contribute to the progression of RA, while RA might have little effect on accelerating the development of PD. In addition, RA patients with PD receiving non-surgical periodontal treatment resulted in noteworthy improvement in the clinical outcome for RA.

The influence and therapeutic effect of microbiota in systemic lupus erythematosus.

Systemic erythematosus lupus (SLE) is an autoimmune disease involving multiple organs that poses a serious risk to the health and life of patients. A growing number of studies have shown that commensals from different parts of the body and exogenous pathogens are involved in SLE progression, causing barrier disruption and immune dysregulation through multiple mechanisms. However, they sometimes alleviate the symptoms of SLE. Many factors, such as genetic susceptibility, metabolism, impaired barriers, food, and sex hormones, are involved in SLE, and the microbiota drives the development of SLE either by depending on or interacting with these factors. Among these, the crosstalk between genetic susceptibility, metabolism, and microbiota is a hot topic of research and is expected to lay the groundwork for the amelioration of the mechanism, diagnosis, and treatment of SLE. Furthermore, the microbiota has great potential for the treatment of SLE. Ideally, personalised therapeutic approaches should be developed in combination with more specific diagnostic methods. Herein, we provide a comprehensive overview of the role and mechanism of microbiota in lupus of the intestine, oral cavity, skin, and kidney, as well as the therapeutic potential of the microbiota.

Effects of bacterial extracellular vesicles derived from oral and gastrointestinal pathogens on systemic diseases.

Oral microbiota and gastrointestinal microbiota, the two largest microbiomes in the human body, are closely correlated and frequently interact through the oral-gut axis. Recent research has focused on the roles of these microbiomes in human health and diseases. Under normal conditions, probiotics and commensal bacteria can positively impact health. However, altered physiological states may induce dysbiosis, increasing the risk of pathogen colonization. Studies suggest that oral and gastrointestinal pathogens contribute not only to localized diseases at their respective colonized sites but also to the progression of systemic diseases. However, the mechanisms by which bacteria at these local sites are involved in systemic diseases remain elusive. In response to this gap, the focus has shifted to bacterial extracellular vesicles (BEVs), which act as mediators of communication between the microbiota and the host. Numerous studies have reported the targeted delivery of bacterial pathogenic substances from the oral cavity and the gastrointestinal tract to distant organs via BEVs. These pathogenic components subsequently elicit specific cellular responses in target organs, thereby mediating the progression of systemic diseases. This review aims to elucidate the extensive microbial communication via the oral-gut axis, summarize the types and biogenesis mechanisms of BEVs, and highlight the translocation pathways of oral and gastrointestinal BEVs in vivo, as well as the impacts of pathogens-derived BEVs on systemic diseases.

Application of metal-organic framework materials in regenerative medicine.

In the past few decades, scaffolds manufactured from composite or hybrid biomaterials of natural or synthetic origin have made great strides in enhancing wound healing and repairing fractures and pathological bone loss. However, the prevailing use of such scaffolds in tissue engineering is accompanied by numerous constraints, including low mechanical stability, poor biological activity, and impaired cell proliferation and differentiation. The performance of scaffolds in wound and bone tissue engineering may be enhanced by some modifications in the synthesis of nanoscale metal-organic framework (nano-MOF) scaffolds. Nano-MOFs have attracted researchers' attention in recent years due to their distinctive features, which include tenability, biocompatibility, good mechanical stability, and ultrahigh surface area. The biological properties of scaffolds are enhanced and tissue regeneration is facilitated by the introduction of nano-MOFs. Moreover, the physicochemical characteristics, drug loading, and ion release capacities of the scaffolds are improved by the nanoscale structure and topological features of nano-MOFs, which also control stem cell differentiation, proliferation, and attachment. This review provides further comprehensive detail about the most recent uses of nano-MOFs in tissue engineering. The distinct characteristics of nano-MOFs are explored in enhancing tissue repair, wound healing, osteoinduction, and bone conductivity. Significant attributes include high antibacterial activity, substantial drug-loading capacity, and the ability to regulate drug release. Finally, this discussion addresses the obstacles, clinical impediments, and considerations encountered in the application of these nanomaterials to diverse scaffolds, tissue-mimicking structures, dressings, fillers, and implants for bone tissue repair and wound healing.

High concentrations of NaF aggravate periodontitis by promoting M1 polarization in macrophages.

High-concentration fluoride treatment is commonly used to prevent dental caries in the oral cavity, and fluorine-containing protective paint is used to alleviate common root sensitivity symptoms in patients with periodontitis after periodontal treatment. Recent studies have confirmed its safe use in normal oral environments. However, whether fluoride treatment affects the progression of periodontitis in an inflammatory microenvironment remains unclear. Immunometabolism is crucial for maintaining bone regeneration and repair in periodontitis, and the precise regulation of macrophage polarisation is crucial to this process. Fluoride can influence the immune microenvironment of bone tissue by regulating immune metabolic processes. Herein, we investigated the effects of high concentrations of sodium fluoride (NaF) on periodontal tissues. We examined the expression of osteogenic and M1/M2 macrophage polarisation markers and glucose metabolism in macrophages. RNA sequencing was used to study differentially expressed genes related to M1 polarisation and glucose metabolism in treated macrophages. The results showed that NaF indirectly affects human periodontal ligament cells (hPDLCs), aggravating bone loss, tissue destruction, and submandibular lymph node drainage. Furthermore, NaF promoted glycolysis in macrophages and M1 polarisation while inhibiting osteogenic differentiation. These findings suggest that NaF has a direct effect on hPDLCs. Moreover, we found that high concentrations of NaF stimulated M1 polarisation in macrophages by promoting glycolysis. Overall, these results suggest that M1 macrophages promote the osteoclastic ability of hPDLCs and inhibit their osteogenic ability, eventually aggravating periodontitis. These findings provide important insights into the mechanism of action of NaF in periodontal tissue regeneration and reconstruction, which is critical for providing appropriate recommendations for the use of fluoride in patients with periodontitis.

Hsa_Circ_0005044 Promotes Osteo/Odontogenic Differentiation of Dental Pulp Stem Cell Via Modulating miR-296-3p/FOSL1.

Circular RNAs (circRNAs) are a form of RNAs that lack coding potential. The role of such circRNAs in dental pulp stem cell (DPSC) osteo/odontogenic differentiation remains to be determined. In this study, circRNA expression profiles in DPSC osteo/odontogenic differentiation process were analyzed by RNA-seq. qRT-PCR was used to confirm the differential expression of circ_0005044, miR-296-3p, and FOSL1 in DPSC osteogenic differentiation process. Circ_0005044, miR-296-3p, and FOSL1 were knocked down or overexpressed. Osteoblastic activity and associated mineral activity were monitored via alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Interactions between miR-296-3p, circ_0005044, and FOSL1 were assessed through luciferase reporter assays. Finally, an in vivo system was used to confirm the relevance of circ_0005044 to osteoblastic differentiation. As results, we detected significant circ_0005044 and FOSL1 upregulation in DPSC osteo/odontogenic differentiation process, as well as concomitant miR-296-3p downregulation. When knocking down circ_0005044 or overexpressed miR-296-3p, this significantly inhibited osteogenesis. Luciferase reporter assay confirmed that miR-296-3p was capable of binding to conserved sequences in the wild-type forms of both the circ_0005044 and FOSL1. Furthermore, knocking down circ_0005044 in vivo significantly attenuated bone formation. Therefore, the circ_0005044/miR-2964-3p/FOSL1 axis regulates DPSC osteo/odontogenic differentiation, which may provide potential molecular targets for dental-pulp complex regeneration.

Immunotoxicity of metal and metal oxide nanoparticles: from toxic mechanisms to metabolism and outcomes.

The influence of metal and metal oxide nanomaterials on various fields since their discovery has been remarkable. They have unique properties, and therefore, have been employed in specific applications, including biomedicine. However, their potential health risks cannot be ignored. Several studies have shown that exposure to metal and metal oxide nanoparticles can lead to immunotoxicity. Different types of metals and metal oxide nanoparticles may have a negative impact on the immune system through various mechanisms, such as inflammation, oxidative stress, autophagy, and apoptosis. As an essential factor in determining the function and fate of immune cells, immunometabolism may also be an essential target for these nanoparticles to exert immunotoxic effects in vivo. In addition, the biodegradation and metabolic outcomes of metal and metal oxide nanoparticles are also important considerations in assessing their immunotoxic effects. Herein, we focus on the cellular mechanism of the immunotoxic effects and toxic effects of different types of metal and metal oxide nanoparticles, as well as the metabolism and outcomes of these nanoparticles in vivo. Also, we discuss the relationship between the possible regulatory effect of nanoparticles on immunometabolism and their immunotoxic effects. Finally, we present perspectives on the future research and development direction of metal and metal oxide nanomaterials to promote scientific research on the health risks of nanomaterials and reduce their adverse effects on human health.

Current Status, Opportunities, and Challenges of Exosomes in Oral Cancer Diagnosis and Treatment.

Oral cancer is one of the most common cancers in the world, with more than 300,000 cases diagnosed each year, of which oral squamous cell carcinoma accounts for more than 90%, with a 5-year survival rate of only 40-60%, and poor prognosis. Exploring new strategies for the early diagnosis and treatment of oral cancer is key to improving the survival rate. Exosomes are nanoscale lipid bilayer membrane vesicles that are secreted by almost all cell types. During the development of oral cancer, exosomes can transport their contents (DNA, RNA, proteins, etc) to target cells and promote or inhibit the proliferation, invasion, and metastasis of oral cancer cells by influencing the host immune response, drug-resistant metastasis, and tumour angiogenesis. Therefore, exosomes have great potential and advantages as biomarkers for oral cancer diagnosis, and as drug delivery vehicles or targets for oral cancer therapy. In this review, we first describe the biogenesis, biological functions, and isolation methods of exosomes, followed by their relationship with oral cancer. Here, we focused on the potential of exosomes as oral cancer biomarkers, drug carriers, and therapeutic targets. Finally, we provide an insightful discussion of the opportunities and challenges of exosome application in oral cancer diagnosis and treatment, intending to offer new ideas for the clinical management of oral cancer.

Hydrogels for the treatment of oral and maxillofacial diseases: current research, challenges, and future directions.

Oral and maxillofacial diseases such as infection and trauma often involve various organs and tissues, resulting in structural defects, dysfunctions and/or adverse effects on facial appearance. Hydrogels have been applied in the treatment of oral diseases and defect repair due to their three-dimensional network structure. With their biocompatible structure and unique stimulus-responsive property, hydrogels have been applied as an excellent drug-delivery system for treatments that mainly include oral mucosal diseases, wounds, periodontitis and cancer therapy. Hydrogels are also ideal scaffolds in regenerative engineering of dentin-pulp complex, periodontal tissue, bone and cartilage. This review discusses the fundamental structure of hydrogels in brief and then focuses on the characteristics and limitations in current research and applications of hydrogels. Finally, potential future directions are proposed.

Micromolar sodium fluoride promotes osteo/odontogenic differentiation in dental pulp stem cells by inhibiting PI3K/AKT pathway.

OBJECTIVE: Sodium fluoride (NaF) plays an important role in preventing dental caries. However, the regulatory effect of NaF on the committed differentiation of DPSCs is not fully understood. In this study, we characterized the impact of micromolar levels of NaF on the osteo/odontogenic differentiation of DPSCs. DESIGN: DPSCs were isolated from healthy human third molars and were cultured in conditioned media with different concentrations of NaF. RNA sequencing (RNA-seq) combined with Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was used to assess the pathways regulated by NaF. Alkaline phosphatase activity, Alizarin red staining, Western blotting, and real-time qRT-PCR were used to determine the osteo/odontogenic differentiation in DPSCs treated with NaF. RESULTS: NaF significantly promoted the osteo/odontogenic differentiation of DPSCs at micromolar levels. Furthermore, RNA-seq and KEGG pathway enrichment analysis indicated that the PI3K/AKT pathway was involved in the pro-osteoclastogenesis effect of NaF. Western blotting analysis exhibited that the phosphorylation of AKT was decreased in NaF-treated DPSCs. Chemical inhibition of the PI3K/AKT pathway abrogated the NaF-promoted DPSCs osteo/odontogenic differentiation. CONCLUSION: Micromolar NaF can promote the osteo/odontogenic differentiation of DPSCs by inhibiting the PI3K/AKT pathway. DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.

Periodontal Regeneration of Teeth with Radicular Developmental Groove after Intentional Replantation: Two Case Reports.

Our case reports probe whether intentional replantation is a feasible and successful treatment for teeth with radicular developmental groove. Radicular developmental groove is an anatomical malformation that often leads to combined periodontal-endodontic lesion. Treatment of complex radicular groove presents a great challenge to the operator. Two cases of periodontal compromised teeth with this developmental anomaly were treated with intentional replantation and followed up for 2 years. The teeth were asymptomatic and functional. The periodontal probing depths decreased from original 10 mm to 2-3 mm. The receded gingival papillae associated with the teeth was regenerated two years after intentional replantation. With careful case selection and treatment planning, intentional replantation may be a predictable alternative treatment modality for the combined endodontic-periodontal lesion accompanied with radicular developmental groove.