Impact of circadian clock protein Bmal1 on experimentally-induced periodontitis-associated renal injury.

OBJECTIVES: To investigate the mechanism of circadian clock protein Bmal1 (Bmal1) on renal injury with chronic periodontitis, we established an experimental rat periodontitis model. METHODS: Twelve male Wistar rats were randomly divided into control and periodontitis groups (n=6, each group). The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires, whereas the control group received no intervention measures. After 8 weeks, clinical periodontal parameters, including probing depth, bleeding index, and tooth mobility, were evaluated in both groups. Micro-CT scanning and three-dimensional image reconstruction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption. Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. Renal function indicators, such as creatinine, albumin, and blood urea nitrogen levels, and oxidative stress markers, including superoxide dismutase, glutathione, and malondialdehyde levels, were measured using biochemical assay kits. MitoSOX red staining was used to detect reactive oxygen species (ROS) content in the kidneys. The gene and protein expression levels of Bmal1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in rat renal tissues were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining. RESULTS: Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group. Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group. The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress, whereas the renal function levels showed abnormalities without statistical significance. MitoSOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group, and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1, Nrf2, and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend. CONCLUSIONS: Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.

Melatonin-Derived Carbon Dots with Free Radical Scavenging Property for Effective Periodontitis Treatment via the Nrf2/HO-1 Pathway.

Periodontitis is a chronic inflammatory disease closely associated with reactive oxygen species (ROS) involvement. Eliminating ROS to control the periodontal microenvironment and alleviate the inflammatory response could potentially serve as an efficacious therapy for periodontitis. Melatonin (MT), renowned for its potent antioxidant and anti-inflammatory characteristics, is frequently employed as an ROS scavenger in inflammatory diseases. However, the therapeutic efficacy of MT remains unsatisfactory due to the low water solubility and poor bioavailability. Carbon dots have emerged as a promising and innovative nanomaterial with facile synthesis, environmental friendliness, and low cost. In this study, melatonin-derived carbon dots (MT-CDs) were successfully synthesized via the hydrothermal method. The MT-CDs have good water solubility and biocompatibility and feature excellent ROS-scavenging capacity without additional modification. The in vitro experiments proved that MT-CDs efficiently regulated intracellular ROS, which maintained mitochondrial homeostasis and suppressed the production of inflammatory mediators. Furthermore, findings from the mouse model of periodontitis indicated that MT-CDs significantly inhibited the deterioration of alveolar bone and reduced osteoclast activation and inflammation, thereby contributing to the regeneration of damaged tissue. In terms of the mechanism, MT-CDs may scavenge ROS, thereby preventing cellular damage and the production of inflammatory factors by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. The findings will offer a vital understanding of the advancement of secure and effective ROS-scavenging platforms for more biomedical applications.

Diosgenin alters LPS-induced macrophage polarization by activating PPARγ/NF-κB signaling pathway.

Diosgenin (DG) is a steroidal saponin derived from plants, and it exhibits anti-inflammatory properties. In this study, we employed an in vitro model of P.g.-LPS-stimulated mouse macrophage cell line RAW264.7 to investigate the anti-inflammatory effects and mechanism of DG under the condition of altered polarization of macrophages. The RAW264.7 cells were subjected to pre-treatment with DG with or without P.g.-LPS. In cultured macrophages, DG inhibited P.g.-LPS-induced pro-inflammatory M1 macrophages, and increased anti-inflammatory M2 macrophages. Notably, DG reduced the expression of phosphorylation levels of NF-κB p65 and IκB while increasing the expression of PPARγ. Further studies revealed that PPARγ inhibitor GW9662 or PPARγ siRNA reversed the inhibitory effect of DG on M1 phenotype. Collectively, the anti-inflammatory mechanism of DG is related to altering macrophage polarization by activating PPARγ and inhibiting NF-κB signaling pathways.

18-α-glycyrrhetinic acid alleviates oxidative damage in periodontal tissue by modulating the interaction of Cx43 and JNK/NF-κB pathways.

Objective: Periodontitis is a common chronic inflammatory disease in which oxidative stress is one of the key pathogenic factors. Connexin43 (Cx43) is the most critical and widely distributed connexin isoform. When the organism undergoes a severe and sustained stress response, Cx43-mediated gap junctions (GJs) are believed to underlie the biology of tissue injury exacerbation and amplification. Notably, 18-α-glycyrrhetinic acid (GA) is a classical pharmacological inhibitor of GJs and has antioxidant potential. However, the regulatory role of GA in the redox signaling of periodontal tissues and the potential mechanisms of Cx43 in the pathogenesis of periodontitis remain uncertain. Methods: In this study, we evaluated the effects and mechanisms of GA in alleviating oxidative damage of periodontal tissues and cells by constructing an H2O2-induced oxidative stress model in human periodontal ligament cells (hPDLCs) and a periodontitis model in rats. Results: Cellular experiments showed that GA effectively attenuated H2O2-induced oxidative damage in hPDLCs by inhibiting the expression and function of Cx43. In addition, pretreatment of hPDLCs with either GA or SP600125 (a JNK inhibitor) inhibited the Cx43/JNK/NF-κB pathway, restored cell viability, and reduced apoptosis. Animal experiment results showed that GA intervention reduced alveolar bone resorption and periodontal tissue destruction, inhibited osteoclast differentiation, improved mitochondrial structural abnormalities and dysfunction in periodontal tissue, and decreased oxidative stress levels and apoptosis in rats with periodontitis. Conclusion: Overall, our findings suggest that the Cx43/JNK/NF-κB pathway may play a vital role to promote periodontitis progression, while GA reduces oxidative stress and apoptosis by inhibiting the interaction of Cx43 and JNK/NF-κB pathways, thus alleviating oxidative damage in the periodontal tissues.

N-Acetyl-l-cysteine-Derived Carbonized Polymer Dots with ROS Scavenging via Keap1-Nrf2 Pathway Regulate Alveolar Bone Homeostasis in Periodontitis.

Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N-acetyl-l-cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H2 O2 stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.

Global trends in research on oxidative stress associated with periodontitis from 1987 to 2022: A bibliometric analysis.

Background: Oxidative stress has been implicated in many chronic inflammatory diseases, including periodontitis. To date, however, only a few bibliometric analyses have systematically studied this field. This work sought to visualize research hot spots and trends in oxidative stress associated with periodontitis from 1987 to 2022 through bibliometric approaches. Methods: The Web of Science Core Collection was searched to retrieve relevant publications. HistCite, VOSviewer, and CiteSpace were used to perform bibliometric analysis visually in terms of annual output, active countries, prolific institutions, authors, core journals, co-cited references, and co-occurrence of keywords. Results: A total of 1654 documents were selected for analysis. From 1 January 1987 to 11 June 2022, the number of annual publications related to oxidative stress in periodontitis exhibited an upward trend. The most prolific country was China with 322 documents, but the United States had 11334 citations. Okayama University, University of Birmingham, and Sichuan University were the most active and contributive institutions. The Journal of Periodontology ranked first in terms of numbers of publications and citations. Ekuni was the most prolific author, while Chapple ranked first among co-cited authors. The Role of Reactive Oxygen and Antioxidant Species in Periodontal Tissue Destruction published by Chapple was the most frequently co-cited reference. Keywords co-occurrence showed that oxidative stress was closely related to inflammation, antioxidants, and diabetes. Conclusion: Our research found that global publications regarding research on oxidative stress associated with periodontitis increased dramatically and were expected to continue increasing. Inflammation and oxidative stress, and the relationship between periodontitis and systemic diseases, are topics worthy of attention.

Circadian Rhythm Disorders Aggravate Periodontitis by Modulating BMAL1.

Circadian rhythms regulate the body's homeostasis through the temporal control of tissue-specific circadian rhythm control genes. Circadian rhythm disorders (CRD) affect the expression levels of circadian rhythms-associated genes in brain and muscle aryl hydrocarbon receptor nuclear translocator-like-1(BMAL1), which is thought to contribute to metabolic disorders and an altered immune system. However, the relationship between CRD and the development of periodontitis was poorly reported. Therefore, this study aimed to investigate the role played by BMAL1 in periodontitis. We used a modified multi-platform approach (MMPM) to induce circadian rhythm disturbances in rats to investigate the role of BMAL1 in periodontitis. Our results showed significant downregulation of BMAL1 in the CRD with periodontitis group, significant resorption of alveolar bone, increased osteoclast differentiation, and upregulation of the inflammatory signaling molecule NF-κB. In addition, apoptosis and oxidative stress levels were increased in periodontal tissues. Collectively, our study suggests that BMAL1 is a key regulator in periodontitis exacerbated by CRD and that CRD may lead to the downregulation of BMAL1, thereby exacerbating oxidative stress and apoptosis in periodontal tissues. Our study found that BMAL1 may be associated with the progression of periodontitis and provides a new perspective on the treatment of periodontitis.

Immediate implant placement in combination with platelet rich-fibrin into extraction sites with periapical infection in the esthetic zone: A case report and review of literature.

BACKGROUND: In this case, platelet-rich fibrin (PRF) was added to guided tissue regeneration as a biomaterial in proper order for immediate planting in aesthetic area with periapical infection. CASE SUMMARY: With the history of endodontic failure in maxillary central incisor, a 34-year-old female patient required the extraction of maxillary anterior residual root and immediate implantation. Cone beam computed tomography and clinical observation were used to assess the regeneration of soft and bone tissue. Before operation, cone beam computed tomography showed the anterior residual root had serious periapical periodontitis with insufficient labial bone in the aesthetic zone. The patient underwent immediate implant placement and reconstruction of the bone substitution by modified guided bone regeneration. The barrier was a three-layer structure of PRF-collagen membrane-PRF that covered the mixture of PRF and Bio-Oss to promote both osteogenesis and soft tissue healing. At 6 mo postoperatively, the definitive crown was placed after accomplished finial impression. One-year follow-up showed a satisfactory aesthetic effect with no obvious absorption of the labial bone and soft tissue. CONCLUSION: The use of PRF in combination with guided bone regeneration can serve as a reliable and simple adjuvant for immediate implanting in infected socket and result in a stable osteogenic effect with good aesthetic outcome.

[Development of tilted implant for free end of maxillary posterior teeth].

Vertical bone insufficiency in the maxillary posterior teeth is a common clinical situation. At present, the bone insufficiency in the maxillary posterior teeth is mainly overcome by bone grafting through maxillary sinus floor elevation. Compared with traditional axial implantation, tilted implantation can better avoid bone grafting, reduce complications, shorten the treatment cycle, reduce the treatment cost for patients, and gradually be promoted in clinical settings. This article reviews the concept, biomechanics, clinical evaluation, and digital trend of tilted implants of maxillary posterior teeth.

Tissue preservation through socket-shield technique and platelet-rich fibrin in immediate implant placement: A case report.

RATIONALE: In this report, a combination of socket-shield technique (SST) and platelet-rich fibrin (PRF) technique was used for immediate implant placement on a fractured central incisor. During the follow-up visit, cone beam computed tomography (CBCT) and clinical observation were used to evaluate the preservation outcome of peri-implant bone and gingiva. PATIENT CONCERNS: The patient was a 28-year-old healthy female patient who desired her fractured 21 to be replaced with an implant-supported single crown; the fractured 21 comprised a post-core crown with insufficient residual bone at the labial site. DIAGNOSIS: The root of 21 exhibited a complex root fracture; the labial portion of the alveolar ridge was thin (<1 mm) and partial ankylosis of the residual root was observed. INTERVENTIONS: Modified SST was applied to the labial portion of the residual root. The implant was placed immediately at the lingual site of the retained socket-shield root fragment; PRF was the placed in the gap between the root fragment and the implant. Final prosthodontic treatment was performed at 24 weeks after implant placement. OUTCOMES: Clinical examination and CBCT scanning at various follow-up visits time showed that the periodontal tissue was well- preserved. At 6 months after surgery, the average horizontal and vertical peri-implant bone resorption was 0.4 mm; a follow-up visit at 18 months post-loading indicated that peri-implant tissue was well preserved by the shield-technique and no significant peri-implant tissue resorption was displayed. LESSON SUBSECTIONS: In cases of anterior teeth with intact but insufficient residual alveolar ridge, the SST with PRF may be effective for preservation and maintenance of stable peri-implant tissue.