Pharmaceutics
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2023
·Vol. 15
·期 10
·2503
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IF 5.4
Yuchen Zhou,Jie Liu,Peng Xue,Jianjun Zhang
GSK2606414 is a new, effective, highly selective PERK inhibitor with adenosine-triphosphate-competitive characteristics. It can inhibit endoplasmic reticulum stress and has the possibility of treating periodontitis. However, owing to its strong hydrophobicity and side effects, highly efficient pharmaceutical formulations are urgently needed to improve the bioavailability and therapeutic efficacy of GSK2606414 in the treatment of periodontitis. Herein, a novel local GSK2606414 delivery system was developed by synthesizing GSK2606414 nanoparticles (NanoGSK) and further loading NanoGSK into a collagenase-responsive hydrogel. The drug release results showed that the drug-loaded hydrogels had outstanding enzymatic responsive drug release profiles under the local microenvironment of periodontitis. Furthermore, in vitro studies showed that the drug-loaded hydrogel exhibited good cellular uptake and did not affect the growth and proliferation of normal cells, while the drug-loaded hydrogel significantly improved the osteogenic differentiation of inflammatory cells. In the evaluations of periodontal tissue repair, the drug-loaded hydrogels showed a great effect on inflammation inhibition, as well as alveolar bone regeneration. Therefore, this work introduces a promising strategy for the clinical treatment of periodontitis.Keywords:GSK2606414;nanoparticles;PERK;hydrogel;periodontitis
研究领域:
药学
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牙科材料
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组织工程
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Xin Huang,Hong Shen,Zirui Li,Tingting Fu,Xin Wei,Sainan Qiu
The purpose of the present study was to evaluate the effect of isochlorogenic acid A (IAA) on periodontitis and explore its potential mechanism. A ligature/LPS procedure was employed to induce periodontitis in rats. LPS-induced HPDLF was used as the in vitro model. Bioinformatic analyses indicated that angiotensin-converting enzyme (ACE) might be the target of IAA in periodontitis. PGK1/STAT1 might be the related molecules of ACE. Treatment with IAA inhibited inflammatory cytokines, inflammatory molecule transcriptions in gingival tissues and HPDLFs. MicroCT, H&E, TRAP and Runx2 staining showed that IAA relieved periodontitis. Immunofluorescence observation and WB revealed that IAA inhibited ACE/PGK1/STAT1 in dental papilla, parodontium, gingival tissues and HPDLFs. IAA suppressed glycolysis, mitochondrial fission, oxidative stress and promoted oxidative phosphorylation, mitochondrial fusion. The application of the ACE-overexpression plasmid, PGK1 SiRNA, the ACE inhibitor captopril, the PGK1 inhibitor NG52 suggested that ACE and PGK1 were involved in IAA-mediated anti-inflammatory response. Molecular docking, molecular dynamics, DARTS and CETSA indicated that IAA might combine with ACE. It was also found that MYC governed ACE transcription. The Y195 residue of PGK1 was conservative and critical for the combination between PGK1 and ACE. ACE and PGK1 were also upregulated in gingival tissues of periodontitis patients. In conclusion, IAA ameliorated periodontitis by inhibiting inflammation via ACE/PGK1/STAT1 signaling.
研究领域:
药理学
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口腔医学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Jing Zhang,Zishuo Fang,Heng Dong,Yu Liu,Zhenyu Chu,Yongbin Mou,Wanqin Jin
In clinical settings, saliva has been established as a straightforward, noninvasive medium for diagnosing periodontitis. However, the precise diagnosis is often hampered by the absence of a specialized analyzer capable of detecting low concentrations of biomarkers typically found in saliva. In this study, we present a noninvasive, on-site screen-printed biomicrochip specifically engineered for the precise and sensitive quantification of lactate concentrations in saliva, a critical biomarker in the diagnosis of periodontitis. The microchip is constructed using a nanostructured ink formulation that includes MnFe@N-doped carbon nanotubes (MnFe@N-CNTs). These MnFe@N-CNTs exhibit a high degree of graphitization and low electrical resistance, significantly augmenting the electrocatalytic efficiency of the enzymatic reaction of lactate. This results in doubled sensitivity and a detection limit that surpasses those of the current advanced salivary assay methods. Remarkably, within just 30 s, the biomicrochip can quantitatively and precisely measure lactate concentrations in the saliva of 10 patients, which provides valuable insights into the severity of their periodontitis. This biosensor holds excellent potential for large-scale production and could broaden the scope of biomarker recognition, paving the way for the analysis of a wider range of oral diseases.
研究领域:
生物医学工程
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临床诊断
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材料科学
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产品关联
DOI
PubMed
高影响因子
Materials Horizons
·
2025
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IF 10.7
Jin Zhang,Lingzhuang Meng,Yinan Jia,Jianshu Li,Xinyuan Xu,Xin Xu
Periodontitis, a chronic inflammatory disease triggered by dental plaque, often presents challenges in management, particularly in severe cases where mechanical debridement alone may be insufficient. As a result, adjunctive therapies, particularly localized drug delivery systems with both antimicrobial and anti-inflammatory properties, are essential to enhance the efficacy of periodontitis management. In this study, we developed a multifunctional hydrogel by incorporating a salicylic acid–choline deep eutectic solvent (DES) into a chitosan/β-glycerol phosphate sodium (CS/GP) hydrogel matrix for the treatment of periodontitis. The DES-CS/GP hydrogel demonstrated favorable physicochemical properties, including gelation and injectability, making it highly suitable for application in the oral cavity. The hydrogel effectively inhibited the growth of key periodontal pathogens, Porphyromonas gingivalis and Fusobacterium nucleatum, and significantly downregulated the expression of pro-inflammatory cytokines TNF-α and IL-1β in vitro. Cytocompatibility assessments showed over 80% cell viability in human gingival fibroblasts, human gingival epithelial cells, and human oral keratinocytes over 5 days treated with DES-CS/GP, with fluorescence microscopy confirming robust cytoskeletal integrity. Furthermore, the hydrogel enhanced permeability through gingival tissues in vitro. In a rat model of periodontitis, the hydrogel significantly mitigated bone loss, reduced bacterial loads of P. g, and suppressed TNF-α and IL-1β expression in gingival tissues. These findings underscore the hydrogel's potential as a safe and effective adjunctive therapy for periodontitis, offering a combination of antimicrobial, anti-inflammatory, and tissue-permeating properties with high biosafety and ease of application.
研究领域:
口腔医学
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药剂学
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生物材料学
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DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Qian Wu,Tian Deng,Juan Cheng,Yujie Yang,Yulan Wang,Yin Xiao,Yufeng Zhang
Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport “bridge” (P–Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.
研究领域:
口腔医学
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材料科学
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生物医学工程
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DOI
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4815
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IF 3.267
Minmin Sun,Yaoting Ji,Zhen Li,Rourong Chen,Shuhui Zhou,Chang Liu,Minquan Du
Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 onPorphyromonas gingivalisLPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 amelioratedPorphyromonas gingivalisLPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.Keywords:anti-inflammatory agents;chronic periodontitis;ginsenoside;lipopolysaccharides
研究领域:
药理学
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牙科
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Zhen Huang,Yi Yu,Xiao-Liang Lin,Ting Zhang,Jin-Lian Huang,Lei Xiao,Ming Liang,Yu-Fei Wang,Jin Qi
Ethnopharmacological relevance Periodontal disease is a complex inflammatory disease that seriously affects peoples’ lives. Scutellaria radix (SR) is traditionally used as a folk medicine to clear away heat and dampness, purge fire and detoxification. Although it has been extensively used as a medicinal plant to treat a variety of inflammatory illnesses, the efficacy and active ingredient for topical administration in the treatment of periodontitis is unknown. Aim of study The aim of this study was to screen and validate the active ingredients in SR for the prevention and treatment of periodontitis. Materials and methods A ligature-induced periodontitis in rats was used to investigate the efficacy of topical administration of SR for the treatment of periodontitis, and the active fraction was screened after separation of the aqueous extract of SR into fractions of different polarities using a lipopolysaccharide (LPS)-induced cell model. Chromatographic fingerprints were established for 18 batches of SR by high performance liquid chromatography. The potential active components were screened using spectral effect relationship analysis and the target cell extraction method. Results SR has good efficacy in the topical treatment of periodontitis, according to animal experiments. Five active ingredients were screened out and their anti-inflammatory activity was confirmed in vitro . Conclusion The main active compounds in the treatment of periodontitis via topical administration of SR were found and this provides an experimental basis for further studies on the pharmacodynamic material basis of SR, as well as reference for the comprehensive evaluation of SR quality and the development of substitute resources.
研究领域:
药理学
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牙医学
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民族药理学
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化学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Zhisong Mai,Yuying Mai,Xianxian Huang,Shipeng Ning,Hongbing Liao
Background Periodontitis, one of the most common oral diseases caused by bacterial infection which affects gums, periodontal ligament and alveolar bone, is a leading cause of tooth loss in adults. Current clinical treatments, such as scaling or antibiotics, often result in incomplete biofilm removal or can contribute to drug resistance.Methods To address these limitations, a nanozyme comprising platinum, copper, and selenium was developed, which was then incorporated into a thermoresponsive hydrogel.Results When applied to periodontal pockets and exposed to 808 nm laser irradiation, the hydrogel became soft, dissolving to release the nanozyme. This nanozyme demonstrated superoxide dismutase (SOD)-like and catalase (CAT)-like activity, reducing excess reactive oxygen species (ROS) while displaying strong antibacterial and anti-inflammatory effects.Conclusion This photothermal nanozyme hydrogel showed excellent biocompatibility and has the potential to overcome the challenges of current periodontitis treatments.
研究领域:
口腔医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2023
·
IF 5.5
Meng Yan,Wen Liang,Lan Du,Rongjuan Guo,Yu Cao,Sheng Ni,Yuan Zhong,Kun Zhang,Kai Qu,Xian Qin,Liang Chen,Wei Wu
Aim: This study focused on treating periodontitis with bacterial infection and local over accumulation of reactive oxygen species. Materials & methods: Polydopamine nanoparticles (PDA NPs) were exploited as efficient carriers for encapsulated metronidazole (MNZ). The therapeutic efficacy and biocompatibility of PDA@MNZ NPs were investigated through both in vitro and in vivo studies. Results: The nanodrug PDA@MNZ NPs were successfully fabricated, with well-defined physicochemical characteristics. In vitro, the PDA@MNZ NPs effectively eliminated intracellular reactive oxygen species and inhibited the growth of Porphyromonas gingivalis. Moreover, the PDA@MNZ NPs exhibited synergistic therapy for periodontitisin in vivo. Conclusion: PDA@MNZ NPs were confirmed with exceptional antimicrobial and antioxidant functions, offering a promising avenue for synergistic therapy in periodontitis.Tweetable abstractClick to tweetA nanotherapeutic composed of dopamine nanoparticles loaded with metronidazole exhibited antimicrobial and antioxidative activities, presenting a safe and effective approach to periodontitis.
研究领域:
药剂学
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口腔医学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
·
2023
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IF 10.8
Rourong Chen,Yaoting Ji,Ting Li,Boxuan Zhao,Haiying Guo,Zijun Wang,Hantao Yao,Zicheng Zhang,Chang Liu,Minquan Du
Periodontitis is caused by oral flora imbalance, which leads to immune imbalance. Porphyromonas gingivalis is a keystone pathogen in periodontitis, causing the blooming of inflammophilic microbes, and becoming dormant to resist antibiotics. Targeted interventions are needed to destroy this pathogen and collapse its inflammophilic flora. Therefore, a targeting nanoagent antibody-conjugated liposomal drug carrier with ginsenoside Rh2 (A-L-R) was developed for pleiotropic benefits. A-L-R showed high quality in high-performance liquid chromatography (HPLC), Fourier transform infrared (FTIR), and transmission electron microscope (TEM) detection. Only P. gingivalis was influenced by A-L-R, as shown by live/dead cell staining and a series of antimicrobial effects assays. With fluorescence in situ hybridization (FISH) staining and in propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR), the clearance of P. gingivalis by A-L-R was more than for other groups, and only the proportion of P. gingivalis was reduced by A-L-R in monospecies culture. Moreover, in a periodontitis model, A-L-R targeted P. gingivalis with high efficiency and low toxicity, maintaining homeostasis with a relatively stable oral microflora. This targeting nanomedicine offers new strategies for periodontitis therapy, providing a foundation for the prevention and treatment of periodontitis.
研究领域:
医学
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微生物学
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药剂学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Yuyao Li,Pei Wang,Yifan Liu,Xuefei Wu,Guangning Long,Yi Chen,Jiyan Wang,Fei Tong,Xiaolei Wang
Periodontitis, a chronic inflammatory oral disease resulting from plaque biofilms, affects about 743 million individuals worldwide. However, the efficacy of current treatments is hampered by challenges in delivering antibiotics to recalcitrant oral biofilms and bacterial resistance, thereby impeding successful treatment of infectious diseases. To address the issues, an antibacterial photothermal material was designed, comprising a spherical structure of zinc oxide (ZnO) wrapped with triiron tetraoxide (Fe3O4). The outer layer of the material adsorbed epsilon-polylysine (EPL) by electrostatic action, ultimately leading to the fabrication of Fe3O4/ZnO/EPL nanoparticles (FZE NPs). The Fe3O4 core endowed the nanoparticles with efficient photothermal properties, facilitating the dispersion of dense biofilms, which dramatically promoted the adsorption and penetration of ZnO and EPL into the biofilms to effectively kill bacteria in biofilms in vitro with enhanced sterilization ability. Additionally, upon dissolution in aqueous media, EPL acts as a positively charged antimicrobial peptide that adsorbs onto the surface of negatively charged bacterial membranes, thereby effectively modulating inflammatory responses. In order to ascertain the efficacy of FZE NPs, an investigation was conducted into their antimicrobial effects against the periodontitis-associated pathogen Porphyromonas gingivalis (P. gingivalis) in vitro. Furthermore, the antiperiodontitis potential of FZE NPs was evaluated in Sprague–Dawley (SD) rats of ligamentous periodontitis. In addition, toxicity evaluations indicated that the material had an acceptable biosafety profile in vitro and in vivo. In summary, the nanospheres (FZE NPs) represent a promising therapeutic strategy for the treatment of periodontitis.
研究领域:
材料科学
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口腔医学
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感染性疾病研究
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产品关联
DOI
PubMed
高影响因子
DENTAL MATERIALS
·
2019
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IF 4.44
Manlin Qi,Xue Li,Xiaolin Sun,Chunyan Li,Franklin R. Tay,Michael D. Weir,Biao Dong,Yanmin Zhou,Lin Wang,Hockin H.K. Xu
Objective Periodontal tissue destruction and tooth loss are increasingly a worldwide problem as the population ages. Periodontitis is caused by bacterial infection and biofilm plaque buildup. Therefore, the objectives of this study were to: (1) develop a near-infrared light (NIR)-triggered core-shell nanostructure of upconversion nanoparticles and TiO 2 (UCNPs@TiO 2 ), and (2) investigate its inhibitory effects via antibacterial photodynamic therapy (aPDT) against periodontitis-related pathogens. Methods The core β-NaYF 4 :Yb 3+ ,Tm 3+ were synthesized via thermal decomposition and further modified with the TiO 2 shell via a hydrothermal method. The core-shell structure and the upconversion fluorescence-induced aPDT treatment via 980 nm laser were studied. Three periodontitis-related pathogens Streptococcus sanguinis ( S. sanguinis ), Porphyromonas gingivalis ( P. gingivalis ) and Fusobacterium nucleatum ( F. nucleatum ) were investigated. The killing activity against planktonic bacteria was detected by a time-kill assay. Single species 4-day biofilms on dentin were tested by live/dead staining, colony-forming units (CFU), and metabolic activity. Results The hexagonal shaped UCNPs@TiO 2 had an average diameter of 39.7 nm. UCNPs@TiO 2 nanoparticles had positively charged (+12.4 mV) surface and were biocompatible and non-cytotoxic. Under the excitation of NIR light (980 nm), the core NaYF 4 :Yb 3+ ,Tm 3+ UCNPs could emit intense ultraviolet (UV) light, which further triggered the aPDT function of the shell TiO 2 via energy transfer, thereby realizing the remarkable antibacterial effects against planktons and biofilms of periodontitis-associated pathogens. NIR-triggered UCNPs@TiO 2 achieved much greater reduction in biofilms than control (p < 0.05). Biofilm CFU was reduced by 3–4 orders of magnitude via NIR-triggered aPDT, which is significantly greater than that of negative control and commercial aPDT control groups. The killing efficacy of UCNPs@TiO 2 -based aPDT against the three species was ranked to be: S. sanguinis < F. nucleatum = P. gingivalis . Metabolic activities of biofilms were also greatly reduced via NIR-triggered aPDT (p < 0.05). Significance Upconversion fluorescence-based aPDT achieved strong inhibiting effects against all three species of periodontitis-related pathogens. This novel nanotechnology demonstrated a high promise to inhibit periodontitis, with exciting potential to combat other oral infectious diseases such as deep endodontic infections.
研究领域:
口腔医学
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纳米生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）