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1.
Clin Oral Investig ; 28(6): 354, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38833009

OBJECTIVES: This single-center randomized, parallel design, clinical trial with a 2-week follow-up involved patients affected by periodontitis undergoing periodontal surgery. The aim was to evaluate periodontal surgical wound healing with the use of chlorhexidine-based mouth rinses versus an untreated control group. MATERIALS AND METHODS: Periodontal surgery was performed following a standardized protocol. Patients were randomly prescribed i) chlorhexidine (CHX) + anti-discoloration system (ADS) + hyaluronic acid (HA), ii) CHX + ADS or iii) no treatment (control group). Plaque score, gingival inflammation, and Early Healing Index (EHI), assessing the degree of wound closure and the presence of fibrin and necrosis, were evaluated at 3, 7 and 14 days after surgery. RESULTS: In total, 33 patients were enrolled. Patients were comparable at baseline for all measured clinical parameters. At 3-days wound healing was significantly improved in all patients treated with CHX + ADS-based mouth rinses with a lower EHI score at the interdental papillae compared with control group (p < 0.01). CHX + ADS + HA group presented improved healing across all time points in terms of EHI, plaque containment, and gingival inflammation when compared to control group (p < 0.01). CONCLUSIONS: The usage of CHX-ADS following periodontal surgery improved early wound healing, reduced plaque accumulation and gingival inflammation. During the early post-operative period the adjunct of HA further improved soft tissue closure. CLINICAL RELEVANCE: This study aims at evaluating the response of gingival tissues to mouth rinsing with chlorhexidine and anti-discoloration system (CHX + ADS) or CHX + ADS + hyaluronic acid (CHX + ADS + HA) versus no rinse in terms of healing of the periodontal surgical wound. CHX + ADS mouth rinses enhanced early soft tissue closure after periodontal surgery and contributed to the reduction in plaque accumulation and gingival inflammation. The adjunct of HA may be beneficial especially in the early post-operative period. CHX + ADS administration following periodontal surgery may improve soft tissue healing in the first two post-operative weeks.


Chlorhexidine , Hyaluronic Acid , Mouthwashes , Wound Healing , Humans , Chlorhexidine/therapeutic use , Wound Healing/drug effects , Female , Male , Mouthwashes/therapeutic use , Middle Aged , Hyaluronic Acid/therapeutic use , Treatment Outcome , Anti-Infective Agents, Local/therapeutic use , Adult , Periodontitis/drug therapy , Periodontal Index , Dental Plaque Index
2.
BMC Oral Health ; 24(1): 530, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704553

OBJECTIVE: Explore the therapeutic mechanism of Coptidis Rhizome (CR) in periodontitis using network pharmacology, and validate it through molecular docking and in vitro experiments. METHODS: Screened potential active components and target genes of CR from TCMSP and Swiss databases. Identified periodontitis-related target genes using GeneCards. Found common target genes using Venny. Conducted GO and KEGG pathway analysis. Performed molecular docking and in vitro experiments using Berberine, the main active component of CR, on lymphocytes from healthy and periodontitis patients. Assessed effects on inflammatory factors using CCK-8, flow cytometry, and ELISA. RESULTS: Fourteen active components and 291 targets of CR were identified. 30 intersecting target genes with periodontitis were found. GO and KEGG analysis revealed oxidative stress response and IL-17 signaling pathway as key mechanisms. Molecular docking showed strong binding of Berberine with ALOX5, AKT1, NOS2, and TNF. In vitro experiments have demonstrated the ability of berberine to inhibit the expression of Th17 + and other immune related cells in LPS stimulated lymphocytes, and reduce the secretion of IL-6, IL-8, and IL-17. CONCLUSION: CR treats periodontitis through a multi-component, multi-target, and multi-pathway approach. Berberine, its key component, acts through the IL-17 signaling pathway to exert anti-inflammatory effects.


Berberine , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Periodontitis , Humans , Periodontitis/drug therapy , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Berberine/pharmacology , Berberine/therapeutic use , Coptis chinensis , Rhizome , Interleukin-17/metabolism , Signal Transduction/drug effects , In Vitro Techniques , Enzyme-Linked Immunosorbent Assay , Flow Cytometry
3.
Int J Oral Sci ; 16(1): 38, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734708

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.


Basic-Leucine Zipper Transcription Factors , Oxidative Stress , Periodontitis , Ubiquitination , Oxidative Stress/drug effects , Periodontitis/drug therapy , Periodontitis/prevention & control , Periodontitis/metabolism , Animals , Basic-Leucine Zipper Transcription Factors/metabolism , Ubiquitination/drug effects , Rats , Male , Disease Models, Animal , Antioxidants/pharmacology , Rats, Sprague-Dawley , Humans , Chromatin Immunoprecipitation , Blotting, Western , Real-Time Polymerase Chain Reaction , Molecular Docking Simulation , Periodontal Ligament/drug effects , Periodontal Ligament/metabolism , Periodontal Ligament/cytology
4.
Front Cell Infect Microbiol ; 14: 1368684, 2024.
Article En | MEDLINE | ID: mdl-38779565

Introduction: Quorum-quenching enzyme Est816 hydrolyzes the lactone rings of N-acyl homoserine lactones, effectively blocking the biofilm formation and development of Gram-negative bacteria. However, its applications in the oral field is limited. This study aimed to evaluate the efficacy of enzyme Est816 in combination with antibiotics against periodontitis induced by Aggregatibacter actinomycetemcomitans in vitro and in vivo. Methods: The antimicrobial efficacy of enzyme Est816 in combination with minocycline, metronidazole, and amoxicillin was determined using the minimum inhibitory concentration test. The anti-biofilm effect of enzyme Est816 was assessed using scanning electron microscopy, live/dead bacterial staining, crystal violet staining, and real-time quantitative PCR. Biocompatibility of enzyme Est816 was assessed in human gingival fibroblasts (HGF) by staining. A rat model of periodontitis was established to evaluate the effect of enzyme Est816 combined with minocycline using micro-computed tomography and histological staining. Results: Compared to minocycline, metronidazole, and amoxicillin treatment alone, simultaneous treatment with enzyme Est816 increased the sensitivity of biofilm bacteria to antibiotics. Enzyme Est816 with minocycline exhibited the highest rate of biofilm clearance and high biocompatibility. Moreover, the combination of enzyme Est816 with antibiotics improved the antibiofilm effects of the antibiotics synergistically, reducing the expression of the virulence factor leukotoxin gene (ltxA) and fimbria-associated gene (rcpA). Likewise, the combination of enzyme Est816 with minocycline exhibited a remarkable inhibitory effect on bone resorption and inflammation damage in a rat model of periodontitis. Discussion: The combination of enzyme Est816 with antibiotics represents a prospective anti-biofilm strategy with the potential to treat periodontitis.


Aggregatibacter actinomycetemcomitans , Anti-Bacterial Agents , Biofilms , Disease Models, Animal , Metronidazole , Microbial Sensitivity Tests , Periodontitis , Quorum Sensing , Animals , Aggregatibacter actinomycetemcomitans/drug effects , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Periodontitis/drug therapy , Periodontitis/microbiology , Rats , Humans , Metronidazole/pharmacology , Quorum Sensing/drug effects , Minocycline/pharmacology , Amoxicillin/pharmacology , Rats, Sprague-Dawley , Male , Fibroblasts/drug effects , Gingiva/microbiology
5.
Int J Mol Sci ; 25(10)2024 May 16.
Article En | MEDLINE | ID: mdl-38791469

Periodontitis is an inflammatory process that starts with soft tissue inflammation caused by the intervention of oral bacteria. By modulating local immunity, it is possible to supplement or replace current therapeutic methods. The aim of this study was to compare the effects of an immunostimulatory treatment with the antibiotherapy usually applied to periodontitis patients. On a model of periodontitis induced in 30 rats (divided into three equal groups) with bacterial strains selected from the human oral microbiome (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis), we administered antibiotics, bacterial lysates and saline for 10 days. Clinically, no significant lesions were observed between the groups, but hematologically, we detected a decrease in lymphocyte and neutrophil counts in both the antibiotic and lysate-treated groups. Immunologically, IL-6 remained elevated compared to the saline group, denoting the body's effort to compensate for bone loss due to bacterial action. Histopathologically, the results show more pronounced oral tissue regeneration in the antibiotic group and a reduced inflammatory reaction in the lysate group. We can conclude that the proposed bacterial lysate has similar effects to antibiotic therapy and can be considered an option in treating periodontitis, thus eliminating the unnecessary use of antibiotics.


Anti-Bacterial Agents , Periodontitis , Periodontitis/microbiology , Periodontitis/drug therapy , Periodontitis/therapy , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Rats , Male , Humans , Interleukin-6/metabolism , Disease Models, Animal , Rats, Wistar , Microbiota/drug effects , Bacteria/drug effects , Bacterial Lysates
6.
Mol Med Rep ; 30(1)2024 Jul.
Article En | MEDLINE | ID: mdl-38785151

Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti­inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase­1 (HO­1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription­quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)­2, TNF­α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ­2, TNF­α, RANKL and OPG. Following HO­1 knockdown, the same treatment was performed. The expression of COX­2 in rat gingival tissue was observed by immunohistochemistry. One­way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. With increase of Oroxylin A dose, the expression of HO­1 was gradually upregulated. When HO­1 was knocked down, Oroxylin A did not downregulate the expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. Immunohistochemical results showed that expression of COX­2 was downregulated by Oroxylin A, and the expression of TNF­α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS­induced RGFs and had a good inhibitory effect on periodontitis in rats.


Cyclooxygenase 2 , Fibroblasts , Flavonoids , Periodontitis , RANK Ligand , Animals , Rats , Flavonoids/pharmacology , Periodontitis/metabolism , Periodontitis/drug therapy , Periodontitis/pathology , RANK Ligand/metabolism , RANK Ligand/genetics , Male , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Fibroblasts/metabolism , Fibroblasts/drug effects , Osteoprotegerin/metabolism , Osteoprotegerin/genetics , Lipopolysaccharides , Gingiva/metabolism , Gingiva/drug effects , Tumor Necrosis Factor-alpha/metabolism , Cytokines/metabolism , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/genetics , Cells, Cultured , Rats, Sprague-Dawley
7.
Acta Odontol Scand ; 83: 238-248, 2024 May 03.
Article En | MEDLINE | ID: mdl-38700145

OBJECTIVE: The aim of this work was to explore the potential of polyphenol supplement consumption in enhancing the treatment of periodontitis and diabetes mellitus in both diabetic animals and humans. MATERIALS AND METHODS: A comprehensive search across eight databases (MEDLINE, EBSCO, Taylor & Francis, PRIMO, Web of Science, Wiley Online Library, ScienceDirect, and SAGE Journals) and two registers (ClinicalTrials.gov and Cochrane Library Trials) was conducted. Methodological quality assessment employed the Cochrane Collaboration Risk of Bias Assessment Tool for randomised controlled trials and the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias Tool for experimental animal studies. RESULTS: Ten articles meeting inclusion criteria were identified. Three clinical studies demonstrated significant reductions in probing depth (PD) and clinical attachment loss (CAL). Ginger supplementation showed a decrease in CAL (-0.57 ± 0.50 vs. -0.14 ± 0.35, p = 0.003) and PD (-0.52 ± 0.51 vs. -0.19 ± 0.51, p = 0.04), while resveratrol supplementation exhibited a reduction in PD (-1.1 ± 0.58 vs. -0.6 ± 0.47, p < 0.001). Additionally, cranberry juice supplementation led to a decrease in PD (-0.56 ± 0.03, p < 0.001). However, there was no significant improvement in inflammation status. Although polyphenol supplementation did not impact fasting blood glucose levels, it did result in improved insulin resistance (3.66 ± 0.97 vs. 4.49 ± 1.56, p = 0.045). In diabetic animals, six studies reported a significant reduction (p < 0.05) in bone loss along with marked improvements in inflammation status. CONCLUSIONS: Despite the promising results observed in the included studies, the overall evidence supporting the positive effects of polyphenols on periodontal and diabetes mellitus status, along with their anti-inflammatory properties, remains inadequate.


Periodontitis , Polyphenols , Polyphenols/administration & dosage , Polyphenols/therapeutic use , Periodontitis/drug therapy , Periodontitis/complications , Humans , Animals , Diabetes Mellitus/drug therapy , Dietary Supplements
8.
Biosens Bioelectron ; 259: 116404, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38772248

Periodontitis, a chronic disease, can result in irreversible tooth loss and diminished quality of life, highlighting the significance of timely periodontitis monitoring and treatment. Meanwhile, hydrogen sulfide (H2S) in saliva, produced by pathogenic bacteria of periodontitis, is an important marker for periodontitis monitoring. However, the easy volatility and chemical instability of the molecule pose challenges to oral H2S sensing. Here, we report a wearable hydrogel-based radio frequency (RF) sensor capable of in situ H2S detection and antibacterial treatment. The RF sensor comprises an agarose hydrogel containing conjugated silver nanoparticles-chlorhexidine (AG-AgNPs-CHL hydrogel) integrated with split-ring resonators. Adhered to a tooth, the hydrogel-based RF sensor enables wireless transmission of sensing signals to a mobile terminal and a concurrent release of the broad-spectrum antibacterial agent chlorhexidine without complex circuits. With the selective binding of the AgNPs to the sulfidion, the RF sensor demonstrates good sensitivity, a wide detection range (2-30 µM), and a low limit of detection (1.2 µM). Compared with standard H2S measurement, the wireless H2S sensor can distinguish periodontitis patients from healthy individuals in saliva sample tests. The hydrogel-based wearable sensor will benefit patients with periodontitis by detecting disease-related biomarkers for practical oral health management.


Anti-Bacterial Agents , Biosensing Techniques , Hydrogels , Hydrogen Sulfide , Metal Nanoparticles , Periodontitis , Radio Waves , Saliva , Silver , Humans , Hydrogen Sulfide/analysis , Periodontitis/microbiology , Periodontitis/drug therapy , Silver/chemistry , Biosensing Techniques/methods , Hydrogels/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Saliva/chemistry , Saliva/microbiology , Metal Nanoparticles/chemistry , Chlorhexidine , Wearable Electronic Devices , Limit of Detection
9.
J Nanobiotechnology ; 22(1): 287, 2024 May 26.
Article En | MEDLINE | ID: mdl-38797862

Periodontitis is a prevalent chronic inflammatory disease, which leads to gradual degradation of alveolar bone. The challenges persist in achieving effective alveolar bone repair due to the unique bacterial microenvironment's impact on immune responses. This study explores a novel approach utilizing Metal-Organic Frameworks (MOFs) (comprising magnesium and gallic acid) for promoting bone regeneration in periodontitis, which focuses on the physiological roles of magnesium ions in bone repair and gallic acid's antioxidant and immunomodulatory properties. However, the dynamic oral environment and irregular periodontal pockets pose challenges for sustained drug delivery. A smart responsive hydrogel system, integrating Carboxymethyl Chitosan (CMCS), Dextran (DEX) and 4-formylphenylboronic acid (4-FPBA) was designed to address this problem. The injectable self-healing hydrogel forms a dual-crosslinked network, incorporating the MOF and rendering its on-demand release sensitive to reactive oxygen species (ROS) levels and pH levels of periodontitis. We seek to analyze the hydrogel's synergistic effects with MOFs in antibacterial functions, immunomodulation and promotion of bone regeneration in periodontitis. In vivo and in vitro experiment validated the system's efficacy in inhibiting inflammation-related genes and proteins expression to foster periodontal bone regeneration. This dynamic hydrogel system with MOFs, shows promise as a potential therapeutic avenue for addressing the challenges in bone regeneration in periodontitis.


Bone Regeneration , Chitosan , Drug Delivery Systems , Hydrogels , Metal-Organic Frameworks , Periodontitis , Periodontitis/drug therapy , Hydrogels/chemistry , Bone Regeneration/drug effects , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Animals , Chitosan/chemistry , Chitosan/analogs & derivatives , Mice , Drug Delivery Systems/methods , Dextrans/chemistry , Male , Reactive Oxygen Species/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Delayed-Action Preparations/chemistry , Humans
10.
Clin Exp Dent Res ; 10(3): e908, 2024 Jun.
Article En | MEDLINE | ID: mdl-38798052

OBJECTIVE: Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1-2-wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) and ß-tricalcium phosphate (ß-TCP). MATERIALS AND METHODS: At the time of postscaling/root planing reevaluation, a 34-year-old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6-mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh-PDGF-BB with ß-TCP, without the use of a membrane. RESULTS: At the 1-year follow-up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re-entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21. CONCLUSION: These results demonstrate the efficacy of rh-PDGF-BB with ß-TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone.


Becaplermin , Calcium Phosphates , Guided Tissue Regeneration, Periodontal , Humans , Male , Calcium Phosphates/therapeutic use , Adult , Becaplermin/therapeutic use , Guided Tissue Regeneration, Periodontal/methods , Recombinant Proteins/therapeutic use , Recombinant Proteins/administration & dosage , Alveolar Bone Loss/surgery , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/pathology , Periodontitis/surgery , Periodontitis/drug therapy , Proto-Oncogene Proteins c-sis/therapeutic use , Bone Regeneration/drug effects , Esthetics, Dental
11.
Int Immunopharmacol ; 135: 112299, 2024 Jun 30.
Article En | MEDLINE | ID: mdl-38776853

OBJECTIVE: Periodontitis is a chronic infectious disease, characterized by loss of alveolar bone and supporting tissues. Cistanche deserticola(Cd), a local medicinal herb in Xinjiang, possesses favorable biological characteristics and potential applications. Our aim is to investigate the remodeling properties of Cd extract and elucidate the specific mechanisms underlying its therapeutic effects on periodontitis, by employing a combination of basic experimental and network pharmacology approaches. METHODS: Firstly, UHPLC-QTOF-MS analysis was conducted on Cd extract to identify its main components, with several compounds were identified by standard. Subsequently, in vitro studies were performed using the Cd extract on MC3T3-E1 cells. Cell proliferation viability was assessed using CCK-8 and apoptosis assays, while ALP and ARS staining and quantitative experiments, qRT-PCR, and Western blot assays were employed to evaluate the osteogenic differentiation capability. Network pharmacology analysis was then carried out using the identified compounds to establish a database of Cd components and targets, along with a database of periodontitis. The intersection of these databases revealed the network relationship between Cd components-mapped genes-signaling pathways. KEGG/GO pathway analysis of the targets was performed to filter potential enriched pathways. PPI/CytoHubba protein interaction network analysis was utilized to identify hub genes. Molecular docking and molecular dynamics simulations were employed to analyze the docking and interaction between core gene and Cd components. RESULTS: We detected 38 major components in the Cd extract, with Echinacoside, Acteoside, Tubuloside A, and Cistanoside A undergoing standard substance verification. In vitro studies indicated that the Cd, at concentrations below 100 µg/ mL, did not affect cell proliferation and inhibited apoptosis. Osteogenesis assays demonstrated that Cd at concentrations of 1 µg/ mL, 10 µg/ mL, and 100 µg/ mL significantly promoted the osteogenic differentiation ability of MC3T3-E1 cells. It also notably upregulated the mRNA and protein levels of Alp, Bmp2, Runx2, and Opn, and the optimal concentration was 10 µg/mL. Network pharmacology results revealed the network relationship between Cd's components, crossed targets and signaling pathways. Combined with KEGG/GO pathway analysis and PPI/CytoHubba protein interaction network analysis. The key pathway and hub genes of Cd regulating periodontitis are both related to hypoxia pathway and HIF-1α. Molecular docking results showed a strong binding affinity between Cd compounds and hub genes, and molecular dynamics simulation results indicated the stability of the complexes formed between HIF-1α and several Cd compounds. CONCLUSION: Cistanche deserticola exhibits a notable capacity to promote bone regeneration, and its mechanism of action in regulating periodontitis is associated with the hypoxia signaling pathway. HIF-1α may serve as a potential core gene. Future research will focus on exploring the mechanism of Cd in intervene periodontitis and promoting bone remodeling in hypoxic environment.


Bone Remodeling , Cistanche , Network Pharmacology , Osteogenesis , Periodontitis , Cistanche/chemistry , Animals , Mice , Periodontitis/drug therapy , Periodontitis/metabolism , Periodontitis/microbiology , Bone Remodeling/drug effects , Osteogenesis/drug effects , Cell Proliferation/drug effects , Molecular Dynamics Simulation , Protein Interaction Maps , Plant Extracts/pharmacology , Plant Extracts/chemistry , Molecular Docking Simulation , Osteoblasts/drug effects , Osteoblasts/metabolism , Signal Transduction/drug effects , Cell Differentiation/drug effects , Apoptosis/drug effects , Cell Line
12.
ACS Nano ; 18(22): 14312-14326, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38767151

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.


Anti-Bacterial Agents , Bone Regeneration , Chitosan , Copper , Fusobacterium nucleatum , Nanoparticles , Periodontitis , Chitosan/chemistry , Chitosan/pharmacology , Periodontitis/drug therapy , Periodontitis/microbiology , Periodontitis/therapy , Periodontitis/pathology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bone Regeneration/drug effects , Rats , Copper/chemistry , Copper/pharmacology , Fusobacterium nucleatum/drug effects , Nanoparticles/chemistry , Rats, Sprague-Dawley , Male , Sulfates/chemistry , Sulfates/pharmacology , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Microbial Sensitivity Tests
13.
PeerJ ; 12: e17252, 2024.
Article En | MEDLINE | ID: mdl-38708345

Background: Periodontitis is a chronic infectious disease, characterized by an exacerbated inflammatory response and a progressive loss of the supporting tissues of the teeth. Porphyromonas gingivalis is a key etiologic agent in periodontitis. Cystatin C is an antimicrobial salivary peptide that inhibits the growth of P. gingivalis. This study aimed to evaluate the antimicrobial activity of this peptide and its effect on cytokine production, nitric oxide (NO) release, reactive oxygen species (ROS) production, and programmed cell death in human macrophages infected with P. gingivalis. Methods: Monocyte-derived macrophages generated from peripheral blood were infected with P. gingivalis (MOI 1:10) and stimulated with cystatin C (2.75 µg/ml) for 24 h. The intracellular localization of P. gingivalis and cystatin C was determined by immunofluorescence and transmission electron microscopy (TEM). The intracellular antimicrobial activity of cystatin C in macrophages was assessed by counting Colony Forming Units (CFU). ELISA assay was performed to assess inflammatory (TNFα, IL-1ß) and anti-inflammatory (IL-10) cytokines. The production of nitrites and ROS was analyzed by Griess reaction and incubation with 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), respectively. Programmed cell death was assessed with the TUNEL assay, Annexin-V, and caspase activity was also determined. Results: Our results showed that cystatin C inhibits the extracellular growth of P. gingivalis. In addition, this peptide is internalized in the infected macrophage, decreases the intracellular bacterial load, and reduces the production of inflammatory cytokines and NO. Interestingly, peptide treatment increased ROS production and substantially decreased bacterial-induced macrophage apoptosis. Conclusions: Cystatin C has antimicrobial and immuno-regulatory activity in macrophages infected with P. gingivalis. These findings highlight the importance of understanding the properties of cystatin C for its possible therapeutic use against oral infections such as periodontitis.


Cystatin C , Macrophages , Nitric Oxide , Porphyromonas gingivalis , Reactive Oxygen Species , Porphyromonas gingivalis/immunology , Humans , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Macrophages/microbiology , Cystatin C/metabolism , Reactive Oxygen Species/metabolism , Nitric Oxide/metabolism , Cytokines/metabolism , Periodontitis/microbiology , Periodontitis/immunology , Periodontitis/drug therapy , Periodontitis/pathology , Apoptosis/drug effects
14.
J Nanobiotechnology ; 22(1): 181, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38622641

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.


Boronic Acids , Curcumin , Dental Plaque , Glycols , Multifunctional Nanoparticles , Nanoparticles , Periodontitis , Humans , Curcumin/pharmacology , Reactive Oxygen Species , Esters , Periodontitis/drug therapy , Hyaluronic Acid/pharmacology
15.
Front Immunol ; 15: 1374900, 2024.
Article En | MEDLINE | ID: mdl-38605968

Introduction: Cells expressing taste signaling elements in non-gustatory tissues have been described as solitary chemosensory cells (SCCs) or tuft cells. These "taste-like" cells play a critical role in the maintenance of tissue homeostasis. Although the expression of SCC markers and taste signaling constituents has been identified in mouse gingivae, their role in periodontal homeostasis is still unclear. Methods: Public RNA sequencing datasets were re-analyzed and further validated with RT-PCR/qRT-PCR and immunofluorescent staining to explore the expression of TAS2Rs and downstream signaling constituents in mouse gingival fibroblasts (MGFs). The specific action of salicin on MGFs via Tas2r143 was validated with RNA silence, heterologous expression of taste receptor/Gα-gustducin and calcium imaging. The anti-inflammatory effects of salicin against LPS-induced MGFs were investigated in cell cultures, and were further validated with a ligature-induced periodontitis mouse model using Ga-gustducin-null (Gnat3-/-) mice. Results: The expression of Tas2r143, Gnat3, Plcb2, and TrpM5 was detected in MGFs. Moreover, salicin could activate Tas2r143, elicited taste signaling and thus inhibited LPS-induced chemokines expression (CXCL1, CXCL2, and CXCL5) in MGFs. Consistently, salicin-treatment inhibited periodontal bone loss, inflammatory/chemotactic factors expression, and neutrophil infiltration in periodontitis mice, while these effects were abolished in Gnat3-/- mice. Discussion: Gingival fibroblasts play a critical role in the maintenance of periodontal homeostasis via "SCC-like" activity. Salicin can activate Tas2r143-mediated bitter taste signaling and thus alleviate periodontitis in mouse, indicating a promising approach to the resolution of periodontal inflammation via stimulating the "SCC-like" function of gingival fibroblasts.


Benzyl Alcohols , Fibroblasts , Glucosides , Periodontitis , Transducin , Animals , Mice , Fibroblasts/metabolism , Lipopolysaccharides , Periodontitis/drug therapy , Periodontitis/metabolism
16.
Int Immunopharmacol ; 133: 112094, 2024 May 30.
Article En | MEDLINE | ID: mdl-38652969

Periodontitis is a bacteria-induced inflammatory disease that damages the tissues supporting the teeth, gums, periodontal ligaments, and alveolar bone. Conventional treatments such as surgical procedures, anti-inflammatory drugs, and antibiotics, are somewhat effective; however, these may lead to discomfort and adverse events, thereby affecting patient outcomes. Therefore, this study aimed to find an effective method to prevent the onset of periodontal disease and explore the specific mechanisms of their action.The impact of thiostrepton on Porphyromonas gingivalis and periodontal ligament stem cells was evaluated in an inflammatory microenvironment. In vivo experiments were performed using a mouse periodontitis model to assess the effectiveness of locally applied thiostrepton combined with a silk fibroin hydrogel in impeding periodontitis progression. Thiostrepton exhibited significant antimicrobial effects against Porphyromonas gingivalis and anti-inflammatory properties by regulating the MAPK pathway through DUSP2. Locally applied thiostrepton effectively impeded the progression of periodontitis and reduced tissue damage. Thiostrepton treatment is a promising and tolerable preventive strategy for periodontitis, offering antimicrobial and anti-inflammatory benefits. These findings suggest the potential of thiostrepton as a valuable addition to periodontitis management, warranting further research and clinical exploration to improve patient outcomes.


Anti-Bacterial Agents , Anti-Inflammatory Agents , Periodontitis , Porphyromonas gingivalis , Animals , Porphyromonas gingivalis/drug effects , Periodontitis/drug therapy , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Humans , MAP Kinase Signaling System/drug effects , Periodontal Ligament/drug effects , Periodontal Ligament/pathology , Disease Models, Animal , Mice, Inbred C57BL , Stem Cells/drug effects , Male , Periodontium/drug effects , Periodontium/microbiology , Periodontium/pathology
17.
BMC Oral Health ; 24(1): 510, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38689229

BACKGROUND: Periodontitis is a chronic osteolytic inflammatory disease, where anti-inflammatory intervention is critical for restricting periodontal damage and regenerating alveolar bone. Ropinirole, a dopamine D2 receptor agonist, has previously shown therapeutic potential for periodontitis but the underlying mechanism is still unclear. METHODS: Human gingival fibroblasts (HGFs) treated with LPS were considered to mimic periodontitis in vitro. The dosage of Ropinirole was selected through the cell viability of HGFs evaluation. The protective effects of Ropinirole on HGFs were evaluated by detecting cell viability, cell apoptosis, and pro-inflammatory factor levels. The molecular docking between NAT10 and Ropinirole was performed. The interaction relationship between NAT10 and KLF6 was verified by ac4C Acetylated RNA Immunoprecipitation followed by qPCR (acRIP-qPCR) and dual-luciferase reporter assay. RESULTS: Ropinirole alleviates LPS-induced damage of HGFs by promoting cell viability, inhibiting cell apoptosis and the levels of IL-1ß, IL-18, and TNF-α. Overexpression of NAT10 weakens the effects of Ropinirole on protecting HGFs. Meanwhile, NAT10-mediated ac4C RNA acetylation promotes KLF6 mRNA stability. Upregulation of KLF6 reversed the effects of NAT10 inhibition on HGFs. CONCLUSIONS: Taken together, Ropinirole protected HGFs through inhibiting the NAT10 ac4C RNA acetylation to decrease the KLF6 mRNA stability from LPS injury. The discovery of this pharmacological and molecular mechanism of Ropinirole further strengthens its therapeutic potential for periodontitis.


Fibroblasts , Indoles , Kruppel-Like Factor 6 , N-Terminal Acetyltransferases , Periodontitis , Humans , Acetylation/drug effects , Apoptosis/drug effects , Cell Survival/drug effects , Cells, Cultured , Fibroblasts/drug effects , Fibroblasts/metabolism , Gingiva/drug effects , Gingiva/metabolism , Indoles/pharmacology , Indoles/therapeutic use , Kruppel-Like Factor 6/metabolism , Lipopolysaccharides , Molecular Docking Simulation , Periodontitis/drug therapy , Periodontitis/metabolism , N-Terminal Acetyltransferases/antagonists & inhibitors
18.
J Nanobiotechnology ; 22(1): 207, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664778

Several studies suggest that oral pathogenic biofilms cause persistent oral infections. Among these is periodontitis, a prevalent condition brought on by plaque biofilm. It can even result in tooth loss. Furthermore, the accumulation of germs around a dental implant may lead to peri-implantitis, which damages the surrounding bone and gum tissue. Furthermore, bacterial biofilm contamination on the implant causes soft tissue irritation and adjacent bone resorption, severely compromising dental health. On decontaminated implant surfaces, however, re-osseointegration cannot be induced by standard biofilm removal techniques such as mechanical cleaning and antiseptic treatment. A family of nanoparticles known as nanozymes (NZs) comprise highly catalytically active multivalent metal components. The most often employed NZs with antibacterial activity are those that have peroxidase (POD) activity, among other types of NZs. Since NZs are less expensive, more easily produced, and more stable than natural enzymes, they hold great promise for use in various applications, including treating microbial infections. NZs have significantly contributed to studying implant success rates and periodontal health maintenance in periodontics and implantology. An extensive analysis of the research on various NZs and their applications in managing oral health conditions, including dental caries, dental pulp disorders, oral ulcers, peri-implantitis, and bacterial infections of the mouth. To combat bacteria, this review concentrates on NZs that imitate the activity of enzymes in implantology and periodontology. With a view to the future, there are several ways that NZs might be used to treat dental disorders antibacterially.


Anti-Bacterial Agents , Biofilms , Dental Implants , Peri-Implantitis , Periodontitis , Peri-Implantitis/drug therapy , Peri-Implantitis/microbiology , Humans , Periodontitis/drug therapy , Periodontitis/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Biofilms/drug effects , Dental Implants/microbiology , Animals , Nanoparticles/chemistry , Bacteria/drug effects
19.
Int Immunopharmacol ; 132: 111984, 2024 May 10.
Article En | MEDLINE | ID: mdl-38565043

Periodontitis is a chronic inflammatory disease with the destruction of supporting periodontal tissue. This study evaluated the role of insulin-like growth factor 2 (IGF2) in periodontitis by inhibiting the polarization of M1 macrophages via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway. IGF2 was enriched in the gingival tissue of murine periodontitis model identified by RNA sequencing. IGF2 application alleviated the expression of pro-inflammatory factors and promoted osteogenesis and the expression of related genes and proteins in a dose-dependent manner in periodontitis. The result of micro-CT verified this finding. Both in vivo and in vitro results revealed that IGF2 decreased the polarization of M1 macrophages and pro-inflammatory factors by immunofluorescence staining, flow cytometry, western blotting and RT-PCR. IGF2 application promoted the osteogenic ability of periodontal ligament fibroblasts (PDLFs) indirectly via its inhibition of M1 polarization evaluated by alkaline phosphatase and alizarin red staining. Then, the cGAS/STING pathway was upregulated in periodontitis and macrophages challenged by LPS, the inhibition of which led to downregulation of M1 polarization. Furthermore, IGF2 could downregulate cGAS, STING and the phosphorylation of P65. Collectively, our study indicates IGF2 can regulate the polarization of M1 macrophages via the cGAS/STING pathway and highlights the promising future of IGF2 as a therapeutic treatment for periodontitis.


Insulin-Like Growth Factor II , Macrophages , Membrane Proteins , Nucleotidyltransferases , Periodontitis , Animals , Humans , Male , Mice , Bone Regeneration/drug effects , Cells, Cultured , Disease Models, Animal , Fibroblasts/drug effects , Fibroblasts/metabolism , Insulin-Like Growth Factor II/metabolism , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice, Inbred C57BL , Nucleotidyltransferases/metabolism , Osteogenesis/drug effects , Periodontal Ligament/metabolism , Periodontal Ligament/cytology , Periodontal Ligament/pathology , Periodontitis/immunology , Periodontitis/metabolism , Periodontitis/drug therapy , Signal Transduction
20.
ACS Appl Bio Mater ; 7(5): 2993-3004, 2024 May 20.
Article En | MEDLINE | ID: mdl-38593411

Bacterial biofilms play a central role in the development and progression of periodontitis, a chronic inflammatory condition that affects the oral cavity. One solution to current treatment constraints is using nitric oxide (NO)─with inherent antimicrobial properties. In this study, an antimicrobial coating is developed from the NO donor S-nitroso-N-acetylpenicillamine (SNAP) embedded within polyethylene glycol (PEG) to prevent periodontitis. The SNAP-PEG coating design enabled a controlled NO release, achieving tunable NO levels for more than 24 h. Testing the SNAP-PEG composite on dental floss showed its effectiveness as a uniform and bioactive coating. The coating exhibited antibacterial properties against Streptococcus mutans and Escherichia coli, with inhibition zones measuring up to 7.50 ± 0.28 and 14.80 ± 0.46 mm2, respectively. Furthermore, SNAP-PEG coating materials were found to be stable when stored at room temperature, with 93.65% of SNAP remaining after 28 d. The coatings were biocompatible against HGF and hFOB 1.19 cells through a 24 h controlled release study. This study presents a facile method to utilize controlled NO release with dental antimicrobial coatings comprising SNAP-PEG. This coating can be easily applied to various substrates, providing a user-friendly approach for targeted self-care in managing gingival infections associated with periodontitis.


Anti-Bacterial Agents , Coated Materials, Biocompatible , Escherichia coli , Materials Testing , Nitric Oxide , Streptococcus mutans , Streptococcus mutans/drug effects , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Escherichia coli/drug effects , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Microbial Sensitivity Tests , Particle Size , Biofilms/drug effects , S-Nitroso-N-Acetylpenicillamine/chemistry , S-Nitroso-N-Acetylpenicillamine/pharmacology , Surface Properties , Periodontitis/drug therapy , Periodontitis/microbiology , Gingiva/cytology
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