Role of connexin 43 in a rat model of periodontitis-induced renal injury.

OBJECTIVES: This study aims to investigate the role of gap junction mediated by connexin 43 (Cx43) in renal injury induced by periodontitis in rats. METHODS: Twelve SPF-grade Wistar male rats were divided into a control group and a periodontitis group by using a completely random number table method, with six rats in each group. The control group rats were not treated, while the periodontitis group rats were subjected to wire ligation of the neck of their bilateral maxillary first molars to construct a periodontitis model. After 8 weeks of modeling, the rats were examined for clinical indicators of the periodontium. micro-CT scanning of the maxilla reconstructed its 3D structure and analyzed the absorption of alveolar bone. Histopathological changes in periodontal and renal tissues were detected. MitoSOX red reagent was used to determine reactive oxygen species (ROS) content in renal tissues. A biochemical reagent kit was used to detect serum oxidative stress biomarkers. Real-time fluorescent quantitative-polymerase chain reaction (qRT-PCR) was employed to determine Cx43, nuclear factor kappa-B (NF-κB) , interleukin (IL)-1ß, IL-6, BCL2-Associated X (Bax), B-lymphomatoma-2 gene (Bcl-2), and Caspase-3 mRNA were determined. Western blot analysis was used to detect Cx43, NF-κB, IL-1ß, Bax, Bcl-2 and Caspase-3 protein. RESULTS: micro-CT 3D reconstruction showed significant bone resorption of the first molar alveolar bone in the periodontitis group rats and decreased height of the alveolar ridge. The distance from the enamel cementum boundary to the top of the alveolar ridge in the periodontitis group was significantly higher than that inthe control group. The histopathological results showed a large number of inflammatory cells that infiltrated the periodontal tissue of the periodontitis group, and the alveolar bone was significantly absorbed. Rats in the periodontitis group also exhibited mild thickening of the glomerular basement membrane, dilation of the Bowman's capsule, and destruction of the brush-like edge of the renal tubules in the renal tissue. The MitoSOX red staining results showed a significant increase in ROS content in the renal tissue of the periodontitis group. The biochemical test results showed that the levels of superoxide dismutase and glutathione in the serum of rats with periodontitis decreased, while that of malondialdehyde increased. The results of qRT-PCR and Western blot showed that the expression levels of Cx43, IL-1ß, IL-6, Bax, Caspase-3 mRNA and Cx43, IL-1ß, NF-κB, Bax, Caspase-3 proteins in the periodontitis group significantly increased compared with those in the control group, while the expression levels of Bcl-2 mRNA and protein decreased. CONCLUSIONS: Periodontitis may activate NF-κB signaling molecules by upregulating the expression of Cx43 in rat kidney tissues, leading to increased levels of inflammation and apoptosis and ultimately inducing kidney injury.

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.

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.

Metal-Mediated Polydopamine Nanoparticles-DNA Nanomachine Coupling Electrochemical Conversion of Metal-Organic Frameworks for Ultrasensitive MicroRNA Sensing.

The development of a robust sensing platform with an efficient probe assembly, and ingenious signal conversion is of great significance for bioanalytical application. In this work, a multipedal polydopamine nanoparticles-DNA (PDANs-DNA) nanomachine coupling electrochemical-driven metal-organic frameworks (MOFs) conversion-enabled biosensing platform was constructed. The PDANs-DNA nanomachine was designed based on Ca2+-mediated DNA adsorption and target-triggered catalytic hairpin assembly on PDANs, which not only maintained the DNA immobilization simplicity but also possessed a high walking efficiency. PDANs-DNA nanomachine could walk fast on the electrode via multiple legs under exonuclease III driving, resulting in the formation of DNA dendrimers through two hairpins assembly. The MOFs (Fe-MIL-88-NH2) probe was decorated on the DNA dendrimers to act as a porous metal precursor and converted into electroactive Prussian Blue by a controlled electrochemical approach, which was a facile, simple, and room-temperature approach compared with the commonly employed MOFs conversion methods. Using microRNA-21 (miRNA-21) as the model target, the proposed biosensor achieved miRNA-21 detection ranging from 10 aM to 10 pM with the detection limit of 5.8 aM. The proposed strategy presented a highly efficient walking platform with the ingenious electrochemical conversion of MOFs, providing more options for the design of an electrochemical platform and holding potential applications in clinical analysis and disease diagnosis.

Target-Driven Cascade-Amplified Release of Loads from DNA-Gated Metal-Organic Frameworks for Electrochemical Detection of Cancer Biomarker.

In this paper, a label-free and stimuli-responsive electrochemical biosensing platform was fabricated based on target-driven load release from DNA-gated metal-organic frameworks (MOFs) with cascade amplification. By using MOFs (UiO-66-NH2) as a nanocarrier of electroactive molecules (methylene blue; MB) and the programmably assembled DNA acted as the gatekeeper, the biofunctionalized MOFs (MB@DNA/MOFs) were not only used as an amplified signal label but also worked as three-dimensional tracks for biosensing. In the presence of a target, the nicking endonuclease cleavage process was triggered, leading to the generation of two strands (S1 and S2). Both S1 and S2 act as stimuli to participate in the strand displacement reaction on the MB@DNA/MOFs, which caused the unlocking of the pore to release MB, resulting in the decrease of the signal. Using carcinoembryonic antigen (CEA) as a model target, the cascade-amplified biosensor presented good performance for CEA detection, ranging from 50 fg/mL to 10 ng/mL with a detection limit of 16 fg/mL. The stimuli-responsive DNA-gated MOF-based electrochemical platform exhibited three-dimensional biosensing tracks with rational utilization of the cascade amplification, providing an effective method for cancer biomarker detection.