Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To evaluate the impact of different methods of harvesting palatal connective tissue on patients' postoperative pain at the palatal donor site.Methods A total of 30 patients were included.The control group was de-epithelialized free gingival graft technique group,and the experimental group was the single-incision technique group.The keratinized gingival width of the recipient site,number of vertical incisions,number of teeth,donor site mucosa thickness,graft width,graft length,graft thickness,operation time and amount of anesthetic were recorded.The postoperative quality of life rating scale and visual analog scale were completed and statistical analysiswas performedon the results by SPSS 26.0.Results The postoperative quality of life score of the experimental group was significantly lower than that of the control group,and there was no significant difference in the total VAS score of the donor site.In terms of the total postoperative pain level after mucogingival surgery,the number of vertical incisions and graft thickness were positively correlated with the pain.Palate mucosal thickness was negatively correlated with postoperative pain levels.Conclusion In mucogingi-val surgery,the degree of postoperative pain in the donor palatal region of the patient is independent of the choice of de-epithelialized free gingival graft technique or single-incision technique to obtain subepithelial connective tissue.The surgeon should also give compre-hensive considerationsto the anatomical factors of the patient's donor site,surgical technical level and experience,and aesthetic require-ments when selecting the surgical method.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective·To evaluate the effects of normally positioned flap(NPF)and coronally advanced flap(CAF)techniques on clinical results after epulis excision.Methods·A total of 55 patients with epulis who visited the Department of Periodontology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from August 2022 to December 2023 were included.The patients were divided into the NPF group and the CAF group.After epulis excision,the surgical area was closed using NPF or CAF technique.The following parameters were recorded:baseline epulis width(EW)and epulis height(EH);papilla width(PW)and papilla height(PH)at 6 months post-surgery;probing depth(PD),attachment loss(AL),and keratinized gingiva width(KGW)at both baseline and 6 months post-surgery.The esthetic outcomes were evaluated using a visual analog scale(VAS)by 2 periodontal specialists.t test was used to compare the differences in periodontal indices between baseline and 6 months post-surgery,as well as between the 2 flap techniques.Results·At 6 months post-surgery,PD of the CAF group was(1.68±0.79)mm,significantly lower than at baseline(P<0.001),but not significantly different from that in the NPF group(P=0.365);the AL in the CAF group was(1.26±1.18)mm,not significantly different from baseline(P=0.746),but significantly lower than in the NPF group(P<0.001).At 6 months post-surgery,PH of the CAF group was(3.74±0.62)mm,significantly higher than that in the NPF group(P<0.001),and the VAS score of the CAF group was significantly higher than that of the NPF group(P<0.001).Conclusion·Compared with NPF,CAF could effectively improve post-surgical KGW and reduce AL,which could prevent periodontal soft tissue defects,and improve esthetic outcome after epulis excision.

Objective To evaluate the impact of different methods of harvesting palatal connective tissue on patients' postoperative pain at the palatal donor site.Methods A total of 30 patients were included.The control group was de-epithelialized free gingival graft technique group,and the experimental group was the single-incision technique group.The keratinized gingival width of the recipient site,number of vertical incisions,number of teeth,donor site mucosa thickness,graft width,graft length,graft thickness,operation time and amount of anesthetic were recorded.The postoperative quality of life rating scale and visual analog scale were completed and statistical analysiswas performedon the results by SPSS 26.0.Results The postoperative quality of life score of the experimental group was significantly lower than that of the control group,and there was no significant difference in the total VAS score of the donor site.In terms of the total postoperative pain level after mucogingival surgery,the number of vertical incisions and graft thickness were positively correlated with the pain.Palate mucosal thickness was negatively correlated with postoperative pain levels.Conclusion In mucogingi-val surgery,the degree of postoperative pain in the donor palatal region of the patient is independent of the choice of de-epithelialized free gingival graft technique or single-incision technique to obtain subepithelial connective tissue.The surgeon should also give compre-hensive considerationsto the anatomical factors of the patient's donor site,surgical technical level and experience,and aesthetic require-ments when selecting the surgical method.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Objective·To evaluate the effects of normally positioned flap(NPF)and coronally advanced flap(CAF)techniques on clinical results after epulis excision.Methods·A total of 55 patients with epulis who visited the Department of Periodontology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from August 2022 to December 2023 were included.The patients were divided into the NPF group and the CAF group.After epulis excision,the surgical area was closed using NPF or CAF technique.The following parameters were recorded:baseline epulis width(EW)and epulis height(EH);papilla width(PW)and papilla height(PH)at 6 months post-surgery;probing depth(PD),attachment loss(AL),and keratinized gingiva width(KGW)at both baseline and 6 months post-surgery.The esthetic outcomes were evaluated using a visual analog scale(VAS)by 2 periodontal specialists.t test was used to compare the differences in periodontal indices between baseline and 6 months post-surgery,as well as between the 2 flap techniques.Results·At 6 months post-surgery,PD of the CAF group was(1.68±0.79)mm,significantly lower than at baseline(P<0.001),but not significantly different from that in the NPF group(P=0.365);the AL in the CAF group was(1.26±1.18)mm,not significantly different from baseline(P=0.746),but significantly lower than in the NPF group(P<0.001).At 6 months post-surgery,PH of the CAF group was(3.74±0.62)mm,significantly higher than that in the NPF group(P<0.001),and the VAS score of the CAF group was significantly higher than that of the NPF group(P<0.001).Conclusion·Compared with NPF,CAF could effectively improve post-surgical KGW and reduce AL,which could prevent periodontal soft tissue defects,and improve esthetic outcome after epulis excision.

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Objective·To observe the effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6.Methods·The HN6 cell line was selected,cultivated,and divided into different groups based on the protein concentration of gingipain extract from Porphyromonas gingivalis:control group,3.125 μg/mL group,6.25 μg/mL group,12.5 μg/mL group,25 μg/mL group,50 μg/mL group,and 100 μg/mL group.After 24 and 48 h of cultivation,CCK-8 assay was used to detect the effects of gingipain extract on HN6 cell proliferation activity.Subsequent experiments were divided into control group,25 μg/mL group and 50 μg/mL group.Flow cytometry was used to examine the effects of gingipain extract on cell cycle.Scratch assay and Transwell assay were performed to evaluate cell migration and invasion ability.Real-time PCR(RT-PCR)and Western blotting were used to measure the expression of E-cadherin and N-cadherin proteins and genes in cells.Results·Stimulated with gingipain extract for 24 h,the HN6 cells showed significantly increased proliferation activity in the 25 μg/mL(P=0.025),50 μg/mL(P=0.000),and 100 μg/mL(P=0.049)groups compared to the control group.After 48 h,proliferation activity was significantly higher in the 6.25 μg/mL(P=0.024),12.5 μg/mL(P=0.006),25 μg/mL(P=0.000),50 μg/mL(P=0.000),and 100 μg/mL(P=0.000)groups compared to the control group.Cell cycle analysis revealed that,after 24 h of gingipain stimulation,the proportion of HN6 cells in the G1 phase decreased,while the proportion in the S+G2 phase significantly increased compared to the control group(25 μg/mL group:P=0.024;50 μg/mL group:P=0.001).Compared to the control group,the scratch assay demonstrated a significant increase in the percentage of scratch closure as the concentration of gingipain extract increased(P=0.001).Compared to the control group,the Transwell invasion assay showed a significant increase in the number of cells passing through the bottom of the chamber as the concentration of gingipain extract increased.RT-PCR and Western blotting results indicated that as the concentration of gingipain extract increased,the expression levels of N-cadherin mRNA and protein in HN6 cells significantly increased,while the expression levels of E-cadherin mRNA and protein significantly decreased compared to the control group.Conclusion·Gingipain extract could promote proliferation,migration,and invasion of oral squamous cell carcinoma HN6 cells.