Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1270 - 1270

Published: Oct. 18, 2024

Periodontitis affects up to 40% of adults over 60 years old and is a consequence gingivitis. characterized by chronic inflammation, periodontal damage, alveolar bone resorption. The nuclear factor erythroid 2-related 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays key role in periodontitis modulating redox balance inflammation the periodontium. However, NRF2 expression decreased gingival tissues patients with while oxidative stress significantly increased this pathology. Oxidative lipopolysaccharide (LPS) produced gram-negative bacteria favor production inflammatory causing favoring bone. In review, we analyzed current literature regarding natural synthetic compounds NRF2/KEAP1 vitro vivo models order evaluate new potential treatments that can improve outcome disease.

Language: Английский

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Multifunctionalized and Dual‐Crosslinked Hydrogel Promotes Inflammation Resolution and Bone Regeneration via NLRP3 Inhibition in Periodontitis

Small Structures, Journal Year: 2024, Volume and Issue: 5(3)

Published: Feb. 5, 2024

Alveolar bone resorption caused by bacteria‐induced periodontitis remains challenging due to sustained inflammation. Periodontal pathogens like Porphyromonas gingivalis launch the primed signal of NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome in macrophages; consequent overproduction proinflammatory cytokines and reactive oxygen species (ROS) leads tissue destruction. This provides potential targets for a new therapeutic strategy. Herein, multifunctionalized dual‐crosslinked hydrogel pGM/cPL@NI with NLRP3 inhibitor MCC950 loaded is prepared. Driven strategic functionalization gelatin methacryloyl ε ‐poly‐lysine phenylboronic acid catechol, respectively, containing dynamic photo‐crosslinking networks demonstrates superior mechanical strength stimuli‐responsive behavior, as well overwhelmed performance bacteria killing ROS scavenging. Crucially, restores compromised osteogenesis specifically suppressing cytokine cascade triggered activation promoting anti‐inflammatory polarization macrophages. Collectively, presents robust an effective “cocktail therapy” combining antibacterial, antioxidant, inflammation resolution, regenerative functions. The present study reveals underlying mechanism bacterial‐immune‐regeneration extended approach periodontal engineering.

Language: Английский

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Correlation between Inflammasomes and Microbiota in Peri-Implantitis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 961 - 961

Published: Jan. 12, 2024

The activation of inflammasomes is thought to induce the inflammatory process around dental implants. No information available on correlation between microbiota and in clinical samples from patients suffering peri-implantitis. For this cross-sectional study, 30 biofilm were obtained 19 undergoing surgical treatment for peri-implantitis because presence bleeding probing, probing depth higher than 6 mm, radiographic bone loss 3 mm. Then, soft tissue implant also collected. relative abundance bacteria alpha-diversity indexes calculated after analyzing 16S rRNA gene using next-generation sequencing. soft-tissue processed evaluation NLRP3 AIM2 as well caspase-1 IL-1β. (mean (SD)) specific species indicated that most abundant Porphyromonas gingivalis (10.95 (14.17)%), Fusobacterium vincentii (10.93 (13.18)%), endodontalis (5.89 (7.23)%), Prevotella oris (3.88 (4.94)%), Treponema denticola (2.91 (3.19)%), Tannerella forsythia (2.84 (4.15)%). Several correlations found immunohistochemical detection IL-1β, both epithelium lamina propria. A network analysis an important cluster variables formed by propria AIM2, caspase-1, IL-1β with dentalis, tannerae, forsythia, or Selenomonas timonae. Thus, it could be concluded their downstream effectors interleukin-1β can significantly associated bacteria.

Language: Английский

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Interleukin‐37 ameliorates periodontitis development by inhibiting NLRP3 inflammasome activation and modulating M1/M2 macrophage polarization

Journal of Periodontal Research, Journal Year: 2023, Volume and Issue: 59(1), P. 128 - 139

Published: Nov. 10, 2023

Abstract Objective Our study was designed to explore the role of IL‐37 in M1/M2 macrophage polarization imbalance pathogenesis periodontitis. Background Periodontitis is a chronic progressive inflammatory disease featured by gingival inflammation and alveolar bone resorption. Recent research has revealed that regulating viable method ameliorate periodontal inflammation. an anti‐inflammatory cytokine, which been reported inhibit innate adaptive immunity. Methods For vitro experiment, mouse RAW264.7 cells were pretreated with 0.1 ng/mL recombinant human IL‐37. M1 M2 polarizations induced 100 LPS 20 IL‐4, respectively. The expression (iNOS, TNF‐α, IL‐6) (CD206, Arg1, IL‐10) phenotype markers detected RT‐qPCR, western blotting, immunofluorescence staining. vivo experimental periodontitis models established sterile silk ligation (5–0) around bilateral maxillary second molar mice for 1 week. H&E staining used show resorption root cementum dentin. Alveolar loss evaluated through micro‐CT analysis. iNOS CD206 tissues assessed immunohistochemistry NLRP3 inflammasome activation confirmed blotting. Results pretreatment reduced iNOS, IL‐6 LPS‐treated but increased CD206, IL‐10 IL‐4‐treated cells. LPS‐induced upregulation NLRP3, GSDMD, cleaved‐IL‐1β, cleaved‐caspase‐1 antagonized treatment. In addition, administration ameliorated dentin models. prominently decreased iNOS+ cell population CD206+ mice. enhancement offset administration. Conclusion prevents progression suppressing mediating polarization.

Language: Английский

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The effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis induced in mice

Clinical Oral Investigations, Journal Year: 2024, Volume and Issue: 28(5)

Published: April 30, 2024

Language: Английский

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DDIT3/CHOP promotes LPS/ATP-induced pyroptosis in osteoblasts via mitophagy inhibition

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(4), P. 119712 - 119712

Published: March 22, 2024

Language: Английский

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Probiotics as an adjunctive therapy in periodontitis treatment—reality or illusion—a clinical perspective

npj Biofilms and Microbiomes, Journal Year: 2024, Volume and Issue: 10(1)

Published: Dec. 16, 2024

Periodontitis, a prevalent oral health issue, involves various microorganisms and clinical effects. This review examines probiotics as adjunctive therapy for periodontitis by analyzing forty studies. Findings showed mixed results due to differences in study design, probiotic types, parameters; however, improved outcomes severe cases. Caution is advised when interpreting these results, longer follow-up periods reveal variability potential regression

Language: Английский

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Periodontitis and Alzheimer’s Disease: Is There a Connection?

Oral, Journal Year: 2024, Volume and Issue: 4(1), P. 61 - 73

Published: Jan. 22, 2024

The oral health/systemic health connection has been an area of research interest that increased dramatically during the 1990s. Periodontal disease associated with a number systemic conditions, including cardiovascular disease, diabetes, pre-term low-birth-weight infants, respiratory rheumatoid arthritis, cancer, and Alzheimer’s disease. Inflammation is obvious link connects periodontal these but this association casual or causal? We will address biologic plausibility, evidence from human studies, animal therapeutic interventions as we review current understanding between periodontitis

Language: Английский

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Salivary Biomarkers of Inflammasome Activation in Unstable Periodontitis: A Case–Control Study

European Journal of Dentistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract The objective of this study was to investigate the complex network inflammasome-related biomarkers (NOD-like receptor thermal protein domain associated 3 [NLRP3], caspase-1, interleukin [IL]-1β, IL-18, and IL-37) in unstable periodontitis by examining salivary concentrations these specific correlating them with periodontal parameters. design an observational case–control study. A sample collected from periodontally healthy patients (n = 40) 40). Full-mouth clinical parameters were recorded (plaque index, bleeding on probing, pocket depth, attachment loss). Enzyme-linked immunosorbent assay analyzed NLRP3, IL-1β, IL-37 levels. normality data tested using Shapiro–Wilk test. Mean, standard deviation, percentages used for description. An independent t-test, Mann–Whitney U test, chi-square test compare two groups a p-value < 0.05. Spearman's correlation analysis conducted examine relationships between variables. In saliva samples, IL-18 highest group (p 0.005), while 0.005). There significant 0.012) negative weak (−0.395) 0.003) moderate (−0.455) group. (0.031) positive (0.342) found 0.001) (−0.508) NLRP3 inflammasomes their cytokines (caspase-1, IL-18) significantly promote inflammation tissue destruction. contrast, acts as anti-inflammatory cytokine, inhibiting activity inflammasome reducing excessive inflammation. This interplay highlights potential targeting enhancing therapeutic approach treatment disease.

Language: Английский

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Injectable pH-Responsive Hydrogel Adapted to Gingival Crevicular Fluid Microenvironment for Periodontitis Therapy

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: May 18, 2025

Periodontitis is a prevalent chronic inflammatory disease that results in the progressive destruction of periodontal tissues and even tooth loss. Although scaling commonly used clinical treatment, it often fails to adequately solve underlying inflammation. Rutin, natural flavonoid with demonstrated anti-inflammatory properties, shows therapeutic potential for periodontitis but suffers from hydrophobicity-induced poor bioavailability. Unlike conventional pH-responsive systems targeting acidic inflammation microenvironments, gingival crevicular fluid (GCF) progressing undergoes pathological shift neutral alkaline pH. To address this specificity, we developed an alkaline-responsive dynamic hydrogel through stepwise sulfhydryl click reaction between four-arm poly(ethylene glycol) (PEG)-thiol alkyne crosslinkers, enabling efficient encapsulation bioactive rutin within matrix. Benefiting labile thioacetate bond, pH-triggered release response elevated alkalinity GCF periodontitis. As expected, resulting notably suppressed expression factors differentiation osteoclasts. Moreover, effectively rescued improved proliferative activity collagen formation ability ligament cells under conditions. assess its efficacy vivo, mouse model was established. The confirmed rutin-loaded significantly response, attenuated alveolar bone resorption, promoted reconstruction soft tissues. Further studies revealed effects on were associated NLRP3 inflammasome modulation.

Language: Английский

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