Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Antimicrobial Peptide- and Dentin Matrix-Functionalized Hydrogel for Vital Pulp Therapy via Synergistic Bacteriostasis, Immunomodulation, and Dentinogenesis.

The preservation of vital pulps is crucial for maintaining the physiological functions of teeth; however, vital pulp therapy (VPT) of pulpitis teeth remains a substantial challenge due to uncontrolled infection, excessive inflammation, and limited regenerative potential. Current pulp capping agents have restricted effects in the infectious and inflammatory microenvironment. To address this, a multifunctional hydrogel (TGH/DM) with antibacterial, immunomodulatory, and mineralization-promoting effects is designed. The antimicrobial peptide (AMP) and demineralized dentin matrix are incorporated into the hydrogel, achieving sustainable delivery of AMP and a cocktail of growth factors. In vitro results show that TGH/DM could kill endodontic microbiota, ameliorate inflammatory responses of human dental pulp stem cells (hDPSCs), and prompt odontogenic differentiation of inflammatory hDPSCs via activation of peroxisome proliferator-activated receptor gamma. In vivo results suggest that TGH/DM is capable of inducing M2 phenotype transformation of macrophages in mice and fostering the regeneration of the dentin-pulp complex in inflamed pulps of beagle dogs. Overall, this study first proposes the synergistic regulation of AMP and tissue-specific extracellular matrix for the treatment of pulpitis, and the advanced hydrogel provides a facile and effective way for VPT.

The spatial transcriptomic landscape of human gingiva in health and periodontitis.

The gingiva is a key oral barrier that protects oral tissues from various stimuli. A loss of gingival tissue homeostasis causes periodontitis, one of the most prevalent inflammatory diseases in humans. The human gingiva exists as a complex cell network comprising specialized structures. To understand the tissue-specific pathophysiology of the gingiva, we applied a recently developed spatial enhanced resolution omics-sequencing (Stereo-seq) technique to obtain a spatial transcriptome (ST) atlas of the gingiva in healthy individuals and periodontitis patients. By utilizing Stereo-seq, we identified the major cell types present in the gingiva, which included epithelial cells, fibroblasts, endothelial cells, and immune cells, as well as subgroups of epithelial cells and immune cells. We further observed that inflammation-related signalling pathways, such as the JAK-STAT and NF-κB signalling pathways, were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy individuals. Additionally, we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed gingiva. In conclusion, our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.

Restoring periodontal tissue homoeostasis prevents cognitive decline by reducing the number of Serpina3nhigh astrocytes in the hippocampus.

Cognitive decline has been linked to periodontitis through an undetermined pathophysiological mechanism. This study aimed to explore the mechanism underlying periodontitis-related cognitive decline and identify therapeutic strategies for this condition. Using single-nucleus RNA sequencing we found that changes in astrocyte number, gene expression, and cell‒cell communication were associated with cognitive decline in mice with periodontitis. In addition, activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was observed to decrease the phagocytic capability of macrophages and reprogram macrophages to a more proinflammatory state in the gingiva, thus aggravating periodontitis. To further investigate this finding, lipid-based nanoparticles carrying NLRP3 siRNA (NPsiNLRP3) were used to inhibit overactivation of the NLRP3 inflammasome in gingival macrophages, restoring the oral microbiome and reducing periodontal inflammation. Furthermore, gingival injection of NPsiNLRP3 reduced the number of Serpina3nhigh astrocytes in the hippocampus and prevented cognitive decline. This study provides a functional basis for the mechanism by which the destruction of periodontal tissues can worsen cognitive decline and identifies nanoparticle-mediated restoration of gingival macrophage function as a novel treatment for periodontitis-related cognitive decline.

Nicotinamide Riboside Modulates HIF-1 Signaling to Maintain and Enhance Odontoblastic Differentiation in Human Dental Pulp Stem Cells.

Human dental pulp stem cells (hDPSCs) play a vital role in the regeneration of the pulp-dentin complex after pulp disease. While the regeneration efficiency relies on the odontoblastic differentiation capacity of hDPSCs, this is difficult to regulate within the pulp cavity. Although nicotinamide riboside (NR) has been found to promote tissue regeneration, its specific role in pulp-dentin complex regeneration is not fully understood. Here, we aimed to explore the role of NR in the odontoblastic differentiation of hDPSCs and its underlying molecular mechanism. It was found that NR enhanced the viability and retarded senescence in hDPSCs with higher NAD+/NADH levels. In contrast to the sustained action of NR, the multi-directional differentiation of hDPSCs was enhanced after NR pre-treatment. Moreover, in an ectopic pulp regeneration assay in nude mice, transplantation of hDPSCs pretreated with NR promoted the formation of a dentin-like structure surrounded by cells positively expressing DMP-1 and DSPP. RNA-Seq demonstrated inhibition of the HIF-1 signaling pathway in hDPSCs pretreated with NR. The number of HIF-1α-positive cells was significantly decreased in hDPSCs pretreated by NR in vivo. Similarly, NR significantly downregulated the expression of HIF-1α in vitro. The findings suggested that NR could potentially regulate hDPSC odontoblastic differentiation and promote the development of innovative strategies for dental pulp repair.

Application of virtual reality and haptics system Simodont in Chinese dental education: A scoping review.

INTRODUCTION: Virtual reality (VR) and haptic simulation technology have been increasingly implemented in dental training. Since the first haptic VR dental simulator (Simodont) was introduced 10 years ago, it has been applied in more than 40 universities in mainland China. This scoping review aimed to review literature, showcasing the teaching reform of dental virtual simulation in mainland China to global dental education peers. METHODS: This scoping review was conducted using the PRISMA extension for scoping review guidelines. Seven electronic databases were searched, and two reviewers independently performed the selection and characterization of the studies. RESULTS: The final scoping review included 12 studies. Four studies focused on the G. V. Black class II cavity, three on manual dexterity skills training, two on full metal crown preparation, one on pulpal access and coronal cavity preparation, one on flipped classroom teaching, and one on 'doctor-patient communication' skills. DISCUSSION: The most critical scenarios, self-assessment, working posture, curriculum setting, training and cost are analysed and discussed. CONCLUSION: Haptic simulation technology is a valuable complementary tool to the phantom head in dental education. The combined utilization of these two training devices has been superior to either in isolation. However, there is a lack of research on the sequencing of the two systems, as well as the appropriate distribution of curriculum between them. It is necessary for educators to organize or engage in experience sharing, collaboration and knowledge dissemination. These actions are essential for promoting effective teaching within dental educational institutions.

Thioredoxin-1 promotes the restoration of alveolar bone in periodontitis with diabetes.

Treatment of periodontitis in people with diabetes remains challenging. The present study aimed to investigate the therapeutic potential of thioredoxin-1 (TRX1) in periodontitis with diabetes, as well as its role in modulating osteogenic differentiation. Our findings indicated that the production of reactive oxygen species (ROS) was elevated, while the expression of TRX1 was significantly reduced in the periodontal tissues of periodontitis mice with diabetes. Furthermore, knockdown of TRX1 in periodontal ligament stem cells (PDLSCs) resulted in the inhibition of osteogenic differentiation through disrupting Wnt/ß-catenin signaling. However, this inhibition was restored upon administration of recombinant human TRX1 (rhTRX1). Importantly, rhTRX1 treatment decreased ROS generation, activated Wnt/ß-catenin signal pathway and considerably promoted the alveolar bone repair of periodontitis mice with diabetes. These findings highlighted the crucial protective role of TRX1 in periodontitis with diabetes and suggested that it may serve as a potential therapeutic target for refractory periodontitis associated with oxidative stress.

Ferroptosis of macrophages facilitates bone loss in apical periodontitis via NRF2/FSP1/ROS pathway.

Apical periodontitis (AP) is an infectious disease that causes periapical tissue inflammation and bone destruction. Ferroptosis, a novel type of regulated cell death, is closely associated with inflammatory diseases and the regulation of bone homeostasis. However, the exact involvement of ferroptosis in the bone loss of AP is not fully understood. In this study, human periapical tissues were collected, and a mouse model was established to investigate the role of ferroptosis in AP. Colocalization staining revealed that ferroptosis in macrophages contributes to the inflammatory bone loss associated with AP. A cell model was constructed using RAW 264.7 cells stimulated with LPS to further explore the mechanism underlying ferroptosis in macrophages upon inflammatory conditions, which exhibited ferroptotic characteristics. Moreover, downregulation of NRF2 was observed in ferroptotic macrophages, while overexpression of NRF2 upregulated the level of FSP1, leading to a reduction in reactive oxygen species (ROS) in macrophages. Additionally, ferroptotic macrophages released TNF-α, which activated the p38 MAPK signaling pathway and further increased ROS accumulation in macrophages. In vitro co-culture experiments demonstrated that the osteogenic ability of mouse bone marrow stromal cells (BMSCs) was suppressed with the stimulation of TNF-α from ferroptotic macrophages. These findings suggest that the TNF-α autocrine-paracrine loop in ferroptotic macrophages can inhibit osteogenesis in BMSCs through the NRF2/FSP1/ROS signaling pathway, leading to bone loss in AP. This study highlights the potential therapeutic value of targeting ferroptosis in the treatment of inflammatory bone diseases.

Exploration of the shared gene signatures and molecular mechanisms between periodontitis and inflammatory bowel disease: evidence from transcriptome data.

Background: Periodontitis disease (PD) is associated with a systemic disorder of inflammatory bowel disease (IBD). The immune response is the common feature of the two conditions, but the more precise mechanisms remain unclear. Methods: Differential expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on PD and Crohn's disease (CD) data sets to identify crosstalk genes linking the two diseases. The proportions of infiltrating immune cells were calculated by using Single-sample Gene Set Enrichment Analysis. In addition, a data set of isolated neutrophils from the circulation was performed via WGCNA to obtain PD-related key modules. Then, single-cell gene set enrichment scores were computed for the key module and grouped neutrophils according to score order in the IBD scRNA-seq data set. Single-cell gene enrichment analysis was used to further explore the biological process of the neutrophils. Results: A total of 13 crosstalk genes (IL1B, CSF3, CXCL1, CXCL6, FPR1, FCGR3B, SELE, MMP7, PROK2, SRGN, FCN1, TDO2 and CYP24A1) were identified via DEGs analysis and WGCNA by combining PD and CD data sets. The enrichment analysis showed that these genes were involved in interleukin-10 signaling and inflammatory response. The immune infiltration analysis showed a significant difference in the proportion of neutrophils in PD and CD compared with healthy patients. Neutrophils were scored based on the expression of a periodontitis-related gene set in the scRNA-seq data set of IBD. The enrichment analysis demonstrated that inflammatory response, TNFα signaling via NF-κB and interferon-gamma response were upregulated in the high-score group, which expressed more pro-inflammatory cytokines and chemokines compared with the low-score group. Conclusions: This study reveals a previously unrecognized mechanism linking periodontitis and IBD through crosstalk genes and neutrophils, which provides a theoretical framework for future research.

TRAF-STOP alleviates osteoclastogenesis in periodontitis.

The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.

Multisensory Preclinical Training Strategy of Periodontal Scaling for Undergraduates.

BACKGROUND: Invisibility of subgingival scaling is the most important negative factor affecting the performance of periodontal treatment. A multisensory teaching strategy is used in the preclinical training of undergraduates in order to increase the haptic-auditory-visual feedback, aiming to overcome the invisibility and achieve minimal postoperative complications, improving patients' treatment experience. METHODS: One hundred undergraduate dental students in grade 5 were divided into a multisensory teaching strategy group (MTS: n = 50) and a conventional training pattern group (CTP: n = 50). All participants attended a lecture on using an ultrasonic subgingival scaler (USS) and Gracey curettes (GRA), followed by a 3-week training programme. Students in the MTS group were trained in a haptic/auditory-visual feedback manner, whereas students in the CTP group were trained conventionally. After the training phase, paired students in the 2 different groups performed subgingival scaling in paired patients with equivalent teeth of periodontitis using USS and GRA. Objective and subjective postoperative evaluations were recorded. Probing depth (PD) and gingival index (GI) were evaluated before and 4 weeks after scaling by the same periodontal specialist. RESULTS: MTS significantly reduced treatment time and ameliorated postoperative complications (gingival injury, haemorrhage and root surface roughness; P < .05). Postoperative sensitivity was reduced in the MTS group from day 1 to day 7 (D1-D5: P < .001; D6: P = .002; D7: P = .003), whereas postoperative pain was reduced on day 1 (P = .006), compared with that in the CTP group. The PD reduction was not significant between the groups (MTS: 3.17 ± 0.95 mm vs CTP: 3.07 ± 0.97 mm, P > .05), whereas the GI change showed a significant difference between the groups (MTS: 1.71 ± 0.41 vs CTP: 1.67 ± 0.41, P < .05). CONCLUSIONS: Multisensory teaching strategies in the preclinical periodontal training of undergraduates can reduce postoperative complications (gingival injury, postoperative haemorrhage, and root surface roughness) and provide a better treatment experience (decreased treatment time and postoperative pain and sensitivity) for patients.

Antibacterial, wet adhesive, and healing-promoting nanosheets for the treatment of oral ulcers.

The severe pain caused by oral ulcers seriously affects food intake and speech, bringing great inconvenience in daily life. Drug-loaded patches are mostly used to treat oral mucosal diseases such as oral ulcers and oral lichen planus, but their effects are limited because of the influences of saliva and muscle movement. To enhance the adhesion of drug-loaded patches used in the oral cavity, we designed antimicrobial peptides (AMPs)-modified polycaprolactone (PCL)-collagen nanosheets (APCNs). The internal layer is a bioactive and antibacterial collagen layer modified with antimicrobial peptides. The backing layer is a hydrophobic PCL layer with good mechanical strength that can reduce external influences. We have characterized and tested the APCNs. First, the APCNs exhibited continuous and strong adhesion to irregular buccal mucosa surfaces under wet conditions and external force action. Antibacterial experiments showed that the APCNs had high antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria. Moreover, the APCNs showed good biocompatibility and promoted the adhesion of fibroblasts in vitro. Furthermore, APCNs treatment accelerated ulcer healing in a Sprague Dawley rat oral ulcer model. Our study developed antibacterial, wet-adhesive, and healing-promoting PCL-collagen nanosheets and demonstrated that these nanosheets could be promising adhesive therapeutic agents for the treatment of oral mucosal ulcers.

Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands.

Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE's components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG.

Semi-flipped classroom-based learning interventions in a traditional curriculum of oral medicine: students' perceptions and teaching achievements.

BACKGROUND: In recent years, flipped classes have emerged and become popular in college medical education. However, due to the huge medical learning system and the limited pre-class study time of students, it is difficult to implement in all courses. And then we adopted the semi-flipped classes (SFCs) to evaluate its teaching effect. This study analysed three educational methods that can be used in oral medicine courses: online education, offline education, and semi-flipped classes. METHODS: We used two surveys to evaluate the three educational methods. In the first survey 46 teachers and 238 undergraduates shared their experience of the live-streaming and traditional offline courses offered in the different oral medicine curricula; we used anonymous questionnaires to evaluate their class experience. In the second survey 94 students shared their experience of the semi-flipped and traditional classrooms. Students who attended the SFCs in the experimental group learned about the oral mucosa disease by themselves using an online video course and then participated in offline interaction with teachers. The evaluation of the above educational methods was conducted using the anonymous questionnaires and final exam assessment. RESULTS: According to the first survey, teachers and students both agreed that the overall teaching experience and learning effectiveness in offline education are superior to those in online education. According to the second survey, students who participated in the SFCs performed better in the final exam than those who participated in the simple offline classes. Additionally, the survey showed that the new teaching method helped students gain more knowledge and positively influenced their clinical practice. CONCLUSIONS: Compared with the online and offline educational methods, the SFC showed better results in both the questionnaire and final exam assessment. Hence, the effectiveness of medical education can be improved by adopting a teaching mode that combines online and offline teaching methods. Scientific and logical SFCs designs, along with their effective implementation, would eventually make SFCs an important tool for medical education.

Targeting cariogenic pathogens and promoting competitiveness of commensal bacteria with a novel pH-responsive antimicrobial peptide.

Novel ecological antimicrobial approaches to dental caries focus on inhibiting cariogenic pathogens while enhancing the growth of health-associated commensal communities or suppressing cariogenic virulence without affecting the diversity of oral microbiota, which emphasize the crucial role of establishing a healthy microbiome in caries prevention. Considering that the acidified cariogenic microenvironment leads to the dysbiosis of microecology and demineralization of enamel, exploiting the acidic pH as a bioresponsive trigger to help materials and medications target cariogenic pathogens is a promising strategy to develop novel anticaries approaches. In this study, a pH-responsive antimicrobial peptide, LH12, was designed utilizing the pH-sensitivity of histidine, which showed higher cationicity and stronger interactions with bacterial cytomembranes at acidic pH. Streptococcus mutans was used as the in vitro caries model to evaluate the inhibitory effects of LH12 on the cariogenic properties, such as biofilm formation, biofilm morphology, acidurance, acidogenicity, and exopolysaccharides synthesis. The dual-species model of Streptococcus mutans and Streptococcus gordonii was established in vitro to evaluate the regulation effects of LH12 on the mixed species microbial community containing both cariogenic bacteria and commensal bacteria. LH12 suppressed the cariogenic properties and regulated the bacterial composition to a healthier condition through a dual-functional mechanism. Firstly, LH12-targeted cariogenic pathogens in response to the acidified microenvironment and suppressed the cariogenic virulence by inhibiting the expression of multiple virulence genes and two-component signal transduction systems. Additionally, LH12 elevated H2O2 production of the commensal bacteria and subsequently improved the ecological competitiveness of the commensals. The dual-functional mechanism made LH12 a potential bioresponsive approach to caries management.

The picture of undergraduate dental basic research education: a scoping review.

BACKGROUND: Undergraduate dental basic research education (UDBRE) is broadly regarded as an important approach for cultivating scientific research talent. This scoping review aims to summarize the current status of UDBRE in terms of educational goals, teaching program and content, assessment system, training outcomes, barriers, and reflections. METHODS: The authors performed a systematic literature search in PubMed, Web of Science, and Education Resources Information Center (ERIC) to identify peer-reviewed articles written in English from their inception to January 29, 2021. Articles were reviewed and screened according to the inclusion and exclusion criteria. Related data from the included publications were then collected and summarized. RESULTS: The authors searched 646 publications and selected 16 articles to include in the study. The education goals included cultivating five major dental basic research capabilities (n=10, 62.5%) and developing interest in basic research (n=2, 12.5%). As for the teaching program, the mentor-guided student research project was the most popular (n=11, 68.8%), followed by didactic courses (n=5, 31.3%), experimental skills training (n=1, 6.3%), and the combination of the above forms (n=3, 18.8%). However, the assessment system and training outcome diverged. Existing evidence showed that UDBRE reached satisfying education outcomes. Barriers included excessive curriculum burden (n=2, 12.5%), tutor shortage (n=3, 18.8%), lack of financial support (n=5, 31.3%), and inadequate research skills and knowledge (n=5, 31.3%). CONCLUSIONS: Although efforts were made, the variation between studies revealed the immature status of UDBRE. A practical UDBRE education system paradigm was put forward. Meanwhile, more research is required to optimize a robust UDBRE system with clear education goals, well-designed teaching forms, and convincing assessment systems.

The Regulatory Effect of Coaggregation Between Fusobacterium nucleatum and Streptococcus gordonii on the Synergistic Virulence to Human Gingival Epithelial Cells.

In subgingival plaque biofilms, Fusobacterium nucleatum is closely related to the occurrence and development of periodontitis. Streptococcus gordonii, as an accessory pathogen, can coaggregate with periodontal pathogens, facilitating the subgingival colonization of periodontal pathogens. Studies have shown that F. nucleatum can coaggregate with S. gordonii and colonize the subgingival plaque. However, most studies have focused on monocultures or coinfection of species and the potential impact of coaggregation between the two species on periodontal interactions to human gingival epithelial cells (hGECs) remains poorly understood. The present study explored the effect of coaggregation between F. nucleatum and S. gordonii on subgingival synergistic virulence to hGECs. The results showed that coaggregation inhibited the adhesion and invasion of F. nucleatum to hGECs compared with that in the F. nucleatum monoculture and coinfection group. Coaggregation and coinfection with F. nucleatum both enhanced S. gordonii adhesion to hGECs, but neither of the two groups affected S. gordonii invasion to hGECs compared with S. gordonii monoculture. The gene expression levels of TLR2 and TLR4 in hGECs in the coaggregation group were higher than those in the monoculture groups but lower than those in the coinfection group. Compared with coinfection, the coaggregation inhibited apoptosis of hGECs and promoted the secretion of the proinflammatory cytokines TNF-α and IL-6 by hGECs, showed a synergistic inflammatory effect, while coaggregation inhibited the secretion of the anti-inflammatory cytokine TGF-ß1. Coaggregation enhanced the phosphorylation of p65, p38, and JNK proteins and therefore activated the NF-κB and MAPK signaling pathways. Pretreatment with a pathway antagonist/inhibitor decreased the phosphorylation levels of proteins and the secretion of TNF-α and IL-6. In conclusion, coaggregation inhibited the adhesion and invasion of F. nucleatum to hGECs. However, it enhanced the adhesion of S. gordonii to hGECs. Compared with coinfection, coaggregation inhibited the apoptosis of hGECs. The coaggregation coordinately promoted the secretion of TNF-α and IL-6 by hGECs through the TLR/NF-κB and TLR/MAPK signaling pathways while inhibiting the secretion of TGF-ß1, thus aggravating the inflammatory response of hGECs.

Regulation of the unfolded protein response transducer IRE1α by SERPINH1 aggravates periodontitis with diabetes mellitus via prolonged ER stress.

The hyperglycemic microenvironment induced by diabetes mellitus aggravates the inflammatory response, in which the IRE1α signal transduction pathway of the unfolded protein response (UPR) participates. However, the mechanism by which hyperglycemia regulates the IRE1α signaling pathway and affects endoplasmic reticulum (ER) homeostasis in human gingival epithelium in periodontitis with diabetes mellitus remains unknown. Our current data provide evidence that diabetes mellitus causes a hyperinflammatory response in the gingival epithelium, which accelerates periodontal inflammation. Next, we assessed UPR-IRE1α signaling in periodontitis with diabetes mellitus by examining human clinical gingival epithelium samples from healthy subjects, subjects with periodontitis and subjects with periodontitis with diabetes mellitus and by in vitro challenge of human epithelial cells with a hyperglycemic microenvironment. The results showed that a hyperglycemic microenvironment inhibited the IRE1α/XBP1 axis, decreased the expression of a UPR target gene (GRP78), and ultimately impaired the UPR, causing ER stress to be prolonged or more severe in human gingival epithelium. Subsequently, RNA sequencing (RNA-seq) data was analyzed to investigate the expression of ER-related genes in human gingival epithelium. Experiments verified that the mechanism by which periodontitis is aggravated in individuals with diabetes mellitus may involve decreased SERPINH1 expression. Furthermore, experiments in SERPINH1-knockdown and SERPINH1-overexpression models established in vitro indicated that SERPINH1 might act as an activator of IRE1α, maintaining human gingival epithelium homeostasis and reducing proinflammatory cytokine expression by preventing prolonged ER stress induced by high-glucose conditions. In conclusion, regulation of the UPR transducer IRE1α by SERPINH1 alleviates periodontitis with diabetes mellitus by mitigating prolonged ER stress. This finding provides evidence for the further study of periodontitis with diabetes mellitus.

Oral multidisciplinary considerations for clinical strategies of endodontic microsurgery / 口腔疾病防治

@#Endodontic microsurgery is a vital treatment modality for teeth with persistent periradicular pathoses that have not responded to nonsurgical retreatment. The principle is to determine the reason for failure, completely eliminate the infection and promote periapical healing. Within recent years, endodontic microsurgery has evolved to become standardized and presents with a high success rate. However, its outcome is still influenced by many factors, including anatomy, periodontal condition, crown-to-root ratio, occlusion, the type of periradicular lesion, and prosthesis. Moreover, endodontists always concentrate on “the apex”, paying little attention to the general preoperative evaluation, accurate diagnosis, and comprehensive treatment plan. This article reviews the latest literature on these issues and the clinical experience of our research group and discusses the correlation between endodontic microsurgery and other oral disciplines, including periodontology, prosthodontics, oral implantology, oral and maxillofacial surgery and orthodontics. The oral interdisciplinary assessment should be made with comprehensive consideration of the root canal system, periradicular lesion, adjacent anatomical relationships, periodontal condition, occlusion, and esthetic rehabilitation. Based on these findings, the continuity of treatment will be optimized, and the best treatment plan will be proposed to provide clinical strategies for the diagnosis and treatment of complex periradicular diseases.

Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium.

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.