[A novel periodontal endoscopy-aided non-incisional periodontal regeneration technique：a case series study].

PURPOSE: To investigate the effect of endoscopy-aided non-incisional periodontal regeneration technique (NIT) in the treatment of alveolar bone angular resorption. METHODS: Thirteen patients with severe periodontitis(13 diseased teeth) were selected. All patients had alveolar bone angular resorption on adjacent surface. The patients received NIT treatment 6 weeks after periodontal primary therapy. The visualization of subgingival environment was acquired by the periodontal endoscopy. Following the removal of the subgingival plaque, calculus and intra-bony granulation tissue, bone grafting materials were placed into the intra-bony defects with the assistance of a delicate gingival protector. No flap was elevated and no sutures were applied. Probing depth (PD), gingival recession (GR), clinical attachment level (CAL), as well as radiographic parameters were evaluated at baseline and 2 years after treatment. SPSS 22.0 software package was used for data analysis. RESULTS: At 2-years follow-up, an average CAL gain of (3.65±2.10) mm (P＜0.001), PD reduction of (4.42±1.66) mm (P＜0.001), and minimal increase in GR of (0.38±0.87) mm (P=0.25) were observed. Alveolar bone was significantly improved at 2-years follow-up on radiographs (P＜0.001). CONCLUSIONS: For angular resorption site of alveolar bone, NIT treatment can obtain good periodontal regeneration results without flap inversion.

MAT2A inhibition suppresses inflammation in Porphyromonas gingivalis-infected human gingival fibroblasts.

Background: Methionine adenosyl transferase II alpha (MAT2A) is the key enzyme to transform methionine into S-adenosylmethionine (SAM), the main methylgroup donor involved in the methylation. The purpose of our study wasto explore whether MAT2A-mediated methionine metabolism affected theexpression of inflammatory cytokines in human gingival fibroblasts(hGFs). Methods: Both healthy and inflamed human gingiva were collected. HGFs werecultured and treated with P. gingivalis, with or without MAT2Ainhibitor (PF9366), small interference RNA (siRNA), or extrinsic SAMpretreatment. The levels of inflammatory cytokines were detected byreal-time PCR, western blotting, and ELISA. SAM levels were detectedby ELISA. The nuclear factor-kappa B (NF-κB) and mitogen-activatedprotein kinase (MAPK) pathway was explored by western blotting. Results: The expression of MAT2A was increased in the inflamed tissues. P.gingivalis infection promoted the expression of MAT2A and SAM inhGFs. Meanwhile, PF9366 and MAT2A-knockdown significantly decreasedexpression of inflammatory cytokines and SAM production. PF9366inhibited activation of NF-κB/MAPK pathway in P. gingivalis-treatedhGFs. Conclusions: MAT2A-mediated methionine metabolism promoted P. gingivalis-inducedinflammation in hGFs. Targeting MAT2A may provide a novel therapeuticmethod for modulating periodontitis.

Diagnostic accuracy of severe periodontitis for Ramfjord teeth based on different classifications.

OBJECTIVE: To evaluate the accuracy of Ramfjord teeth (RT) protocol for the diagnosis of severe periodontitis based on different classifications and explore the misclassification bias such as teeth loss. METHODS: Patients (n = 435) receiving full-mouth periodontal examination (FMPE) were included. Patients were classified as severe (stage III/IV) periodontitis and no/mild/moderate (no/stage I/II) periodontitis according to the case definition proposed by the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP)-(CDC/AAP), a new classification introduced by AAP and the European Federation of Periodontology (EFP)-(AAP/EFP), and consensus of Chinese experts (CCE). Sensitivity, specificity, positive predictive value, negative predictive value, Youden's index, and area under the receiver operating characteristic curve (AUROC) compared with FMPE were evaluated. RESULTS: The specificity of RT was 86.8%, 92.2%, and 77.1% when compared with FMPE protocol based on CDC/AAP, AAP/EFP, and CCE classifications, while the AUROC value was 0.934, 0.961, and 0.886 specifically. The loss of the first molar leads to the greatest reduction in the detection rate of severe periodontitis. CONCLUSIONS: RT showed the highest specificity based on the new AAP/EFP classification. The loss of the first molar leads to the greatest reduction in the detection rate of severe periodontitis.

Prophylactic effect of exogenous melatonin and melatonin receptor agonists on postoperative delirium in elderly patients: a systemic review and meta-analysis of randomized controlled trials.

BACKGROUND: The prophylactic effect of exogenous melatonin and melatonin receptor agonists (MMRAs) on postoperative delirium (POD) in elderly patients remains controversial. OBJECTIVE: This study aimed to assess the prophylactic effect of MMRAs on POD by conducting a systemic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We systematically searched four electronic databases including PubMed, Web of Science, Cochrane Library, and Embase for the eligible studies up to February 28, 2023. The Cochrane risk of bias tool was used for assessing the risk of bias in the included RCTs. The occurrence of POD was the primary outcome. The quality of evidence was evaluated by Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: A total of 11 RCTs comprising patients (MMRA group: 777 patients and placebo group: 781 patients) were included. The results of the meta-analysis showed that the MMRA group had a lower occurrence of POD than the placebo group (risk ratio = 0.70, 95% confidence interval: 0.51-0.97, P < 0.05, I2 = 59%). The subgroup analysis showed that melatonin significantly reduced the occurrence of POD (moderate-quality evidence), whereas ramelteon and tryptophan had no significant impact (moderate-quality evidence). CONCLUSION: Existing evidence suggested that perioperative use of melatonin can prevent POD in elderly patients.

The incidence and severity of open gingival embrasures in adults treated with clear aligners and fixed appliances: a retrospective cohort study.

BACKGROUND: To evaluate the incidence and severity of open gingival embrasures (OGEs) in adult patients treated with clear aligners and fixed appliances. METHODS: Two hundred non-extraction adult subjects with less than 5 mm of crowding (mean age, 24.6 ± 3.8 years) were enrolled in this retrospective study. The subjects were divided into the clear aligner (n = 100) and fixed appliance group (n = 100). The intraoral photographs were utilized to determine the incidence of OGEs in the upper arch between maxillary central incisors, as well as the lower arch between mandibular central incisors. Crown overlap, crown shape, posttreatment root angulation, the distance from the interproximal contact point (ICP) to the alveolar bone crest (ABC) after treatment and interproximal enamel reduction (IPR) were determined in the two groups. RESULTS: The incidence of OGEs between maxillary and mandibular central incisors after orthodontic treatment was 35.0% and 38.0% in the clear aligner group, respectively, significantly higher than that (18.0% and 24.0%) in the fixed appliance group (P < 0.05). The average area of an OGE after clear aligner treatment was larger both in the maxilla (0.16 ± 0.12mm2) and mandible (0.21 ± 0.24mm2) compared with that (0.05 ± 0.03mm2 and 0.05 ± 0.06mm2) after fixed appliance treatment (P < 0.05). No difference was found regarding pretreatment crown overlap, crown shape, treatment duration, posttreatment root angulation, amount and distribution of IPR and the distance from ICP to ABC. CONCLUSIONS: The incidence and severity of OGEs were higher in adults treated with clear aligners. Clinicians should be aware of the risk of OGEs during treatment with clear aligners.

In vitro research of oral microscope-assisted implant surface decontamination.

OBJECTIVES: To investigate the effect of oral microscope-assisted surface decontamination on implants in vitro. METHODS: Twelve implants that fell off because of severe peri-implantitis were collected, and decontamination was carried out on the surfaces of implants through curetting, ultrasound, titanium brushing, and sandblasting at 1×, 8×, or 12.8× magnifications. The number and sizes of residues on the implants' surfaces after decontamination were determined, and the decontamination effect was analyzed according to the thread spacing in the different parts of the thread. RESULTS: 1) The 8× and 12.8× groups scored lower for implant surface residues than the 1× group (P<0.000 1), and the 12.8× group scored lower than the 8× group (P<0.001); 2) no difference in residue score was found between the wide and narrow thread pitch (P>0.05), and the 8× and 12.8× groups had lower scores than the 1× group (P<0.001); 3) the lowest number of contaminants was observed at the tip of the thread, whereas the highest was observed below the thread, and the difference was significant (P<0.001). However, the thread pitch had no effect on the number of contaminants in different areas (P>0.05); 4) the residue scores of the 8× and 12.8× groups were lower than those of the 1× group at the thread tip and above, sag, and below the thread of the implants (P<0.05). CONCLUSIONS: Residues on the surfaces of contaminated implants can be effectively removed by using an oral microscope. After decontamination, the residues of pollutants were mainly concentrated below the thread of the implants, and the thread pitch of the implants had no significant effect on the residues.

Hexokinase 2-mediated glycolysis supports inflammatory responses to Porphyromonas gingivalis in gingival fibroblasts.

BACKGROUND: When infected with Porphyromonas gingivalis, gingival fibroblasts undergo metabolic reprogramming, and rely on aerobic glycolysis rather than oxidative phosphorylation for rapid energy replenishment. Hexokinases (HKs) are catalysts for glucose metabolism, and HK2 constitutes the major HK inducible isoform. The objective of this study is to determine whether HK2-mediated glycolysis promotes inflammatory responses in inflamed gingiva. METHODS: Levels of glycolysis-related genes were assessed in normal and inflamed gingiva. Human gingival fibroblasts were harvested and infected with Porphyromonas gingivalis in order to mimic periodontal inflammation. 2-deoxy-d-glucose, an analogue of glucose, was used to block HK2-mediated glycolysis, while small interfering RNA was used to knock down HK2 expression. The mRNA and protein levels of genes were analyzed by real-time quantitative PCR and western blotting, respectively. HK2 activity and lactate production were assessed by ELISA. Cell proliferation was assessed by confocal microscopy. The generation of reactive oxygen species was assessed by flow cytometry. RESULTS: Elevated expression of HK2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 was observed in the inflamed gingiva. P. gingivalis infection was shown to promote glycolysis in human gingival fibroblasts, as evidenced by increased gene transcription of HK2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, cell glucose consumption, and HK2 activity. Inhibition and knockdown of HK2 resulted in reduced cytokine production, cell proliferation, and reactive oxygen species generation. Furthermore, P. gingivalis infection activated the hypoxia-inducible factor-1α signaling pathway, thus promoting HK2-mediated glycolysis and proinflammatory responses. CONCLUSIONS: HK2-mediated glycolysis promotes inflammatory responses in gingival tissues, and therefore glycolysis can be targeted in order to inhibit the progression of periodontal inflammation.

PINK1-mediated mitophagy reduced inflammatory responses to Porphyromonas gingivalis in macrophages.

OBJECTIVE: Mitochondria are strained by microbial stimuli in the periodontal niche. Damaged mitochondria are cleared by mitophagy. The purpose of the study was to explore whether mitophagy participated in the progress of periodontitis and whether activation of mitophagy can inhibit inflammatory responses to bacterial infection in macrophages. METHODS: Mitophagy-related genes were measured in the healthy and inflamed human gingiva. Bone marrow-derived macrophages (BMDMs) were infected with Porphyromonas gingivalis. Dexmedetomidine, urolithin A, and resveratrol were used to activate mitophagy, while small interference RNA was utilized to knock down PTEN-induced putative protein kinase 1 (PINK1). Activation of mitophagy-related genes and colocalization of them were detected by Western blot and confocal imaging. Damages of mitochondria, accumulation of mitochondrial reactive oxygen species (mtROS), and production of IL-1ß, IL-6, and TNF-α were measured. RESULTS: Levels of mitophagy-related genes were decreased in inflamed periodontal tissues and P. gingivalis-infected BMDMs. Dexmedetomidine, urolithin A, and resveratrol activated mitophagy, leading to reduced mitochondria damages, decreased mtROS generation, and inhibited IL-1ß, IL-6, and TNF-α production. PINK1 knockdown reduced dexmedetomidine, urolithin A, and resveratrol-induced anti-inflammatory effect. CONCLUSION: Inhibited mitophagy participated in the progress of periodontitis. Activation of mitophagy may become a therapeutic target during the progress of periodontitis by reducing mtROS.

Periodontal-orthodontic interdisciplinary management of a "periodontally hopeless" maxillary central incisor with severe mobility: A case report and review of literature.

BACKGROUND: Treating periodontally hopeless teeth with advanced bone resorption and severe tooth mobility is a great challenge for both orthodontists and periodontists. Biofilm-induced periodontal inflammation and occlusal trauma-related inflammation may synergistically aggravate tooth mobility. This case report illustrates that even periodontally hopeless teeth can be saved and have long-term stability with comprehensive periodontal treatment to control periodontal inflammation and promote periodontal bone regeneration and intricate orthodontic mechanical control to correct cross bite and occlusal trauma. CASE SUMMARY: A 27-year-old female patient whose chief complaint was severe tooth mobility and discomfort of the maxillary incisor was diagnosed with severe aggressive periodontitis by clinical and radiographic examinations. To reduce tooth mobility and establish stable occlusion, we combined orthodontic treatment with periodontal therapy to preserve the tooth. Orthodontic treatment was performed after basic periodontal therapy and periodontal surgery. The loosened upper right central incisor was successfully retained, and the periodontal tissue remained stable during follow-up. CONCLUSION: Teeth with severe mobility and bone loss can be saved through interdisciplinary treatment when periodontal inflammation is strictly controlled.

Hexokinase 2-mediated glycolysis promotes receptor activator of NF-κB ligand expression in Porphyromonas gingivalis lipopolysaccharide-treated osteoblasts.

BACKGROUND: Glucose metabolism plays a pivotal role in sustaining the inflammatory response to microbial stimulation by providing sufficient energy in immune cells. The main purpose of our study was to explore whether hexokinase 2 (HK2)-mediated glycolysis affected the expression of receptor activator of NF-κB Ligand (RANKL) in Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS)-treated osteoblasts and evaluate the potential involvement of the AKT/PI3K pathway activation during HK2-mediated glycolysis. METHODS: Primary mice osteoblasts were treated with P. gingivalis-LPS, whereas the HK2 inhibitor (Lonidamine, LND) and small interference RNA were used to restrain HK2 expression. Conditioned medium from osteoblasts was utilized for culturing osteoclast precursors. The mRNA and protein levels of genes involved in glycolysis and bone metabolism including RANKL and osteoprotegerin (OPG) were detected by real-time PCR and western blotting. HK2 and lactate levels were detected by ELISA. Tartrate-resistant acid phosphatase (TRAP) staining was utilized to assess osteoclast formation. The involvement of the AKT/PI3K pathway in osteoblasts was explored by Western blotting. RESULTS: P. gingivalis-LPS enhanced HK2 expression along with rising glycolysis in osteoblasts. LND and HK2-knockdown decreased RANKL expression and the RANKL/OPG ratio in osteoblasts, leading to less osteoclast formation from osteoclast precursors as evidenced by TRAP staining, while the osteogenic potential and proliferation of osteoblasts were not affected by HK2-knockdown. Moreover, P. gingivalis-LPS activated the AKT/PI3K pathway, which could regulate HK2 and RANKL expression in osteoblasts. CONCLUSIONS: HK2-mediated glycolysis promoted RANKL in osteoblasts and enhanced osteoclast differentiation. Targeting glycolysis may provide novel therapeutic methods for reducing alveolar bone loss.

Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn.

Remifentanil-induced hyperalgesia (RIH) is known to be associated with oxidative stress and inflammation. Betulinic acid (BA) was reported to reduce visceral pain owing to its anti-oxidative and anti-inflammatory potential. Here, we -explored whether BA can attenuate RIH through inhibiting oxidative stress and inflammation in spinal dorsal horn. Sprague-Dawley rats were randomly divided into 4 groups: Control, Incision, RIH, and RIH pre-treated with BA. After pretreated with BA (25 mg/kg, i.g.) for 7 days, rats were subcutaneously infused with remifentanil (40 µg/kg) for 30 min during right plantar incision surgery to induce RIH. The paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), spinal oxidative stress and inflammatory mediators were determined. Intraoperative remifentanil infusion induced postoperative hyperalgesia, as evidenced by the significant decrease in PWMT and PWTL (p < 0.01), and the significant increase in oxidative stress and inflammation evidenced by up-regulations of malondialdehyde, 3-nitrotyrosine, interleukin-1ß and tumour necrosis factor-α (p < 0.01) in spinal dorsal horn and matrix metalloproteinase-9 (MMP-9) activity (p < 0.01) in dorsal root ganglion, as well as a decrease in manganese superoxide -dismutase activity (p < 0.01) compared with control and -incision groups. All these results mentioned above were markedly reversed by pre-treatment with BA (p < 0.01) compared with RIH group. These findings demonstrated that BA can effectively attenuate RIH, which associates with potentially inhibiting oxidative stress and subsequently down-regulating MMP-9-related pro-inflammatory cyokines in spinal dorsal horn.

PI3K contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.

There is accumulating evidence to implicate the importance of EphBs receptors and ephrinBs ligands were involved in modulation of spinal nociceptive information. However, the downstream mechanisms that control this process are not well understood. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K), as the downstream effectors, participates in modulation of spinal nociceptive information related to ephrinBs/EphBs. Intrathecal injection of ephrinB1-Fc produced a dose- and time-dependent thermal and mechanical hyperalgesia, accompanied by the increase of spinal PI3K-p110γ, phosphorylation of AKT (p-AKT) and c-Fos expression. Pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented activation of spinal AKT induced by ephrinB1-Fc. Inhibition of spinal PI3K signaling dose-dependently prevented and reversed pain behaviors and spinal c-Fos protein expression induced by intrathecal injection of ephrinB1-Fc. Inhibition of EphBs receptors by intrathecal injection of EphB1-Fc reduced formalin-induced inflammation and chronic constrictive injury-induced neuropathic pain behaviors accompanied by decreased expression of spinal PI3K,p-AKT and c-Fos protein. Furthermore, pre-treatment with PI3K inhibitor wortmannin or LY294002 prevented ephrinB1-Fc-induced ERK activation in spinal. These data demonstrated that PI3K and PI3K crosstalk to ERK signaling contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs.