Frontiers in Cellular and Infection Microbiology
·
2023
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IF 5.7
Sun Hanyu,Li Pugeng,Kong Qingci,Deng Feilong,Yu Xiaolin
Zoledronic acid (ZA), one of the commonly used bisphosphonates, is mainly used for bone-metabolic diseases. Studies proved that ZA has adverse effects on oral soft tissues. As the first line of innate immunity, the gingival epithelium could be infected by periodontal pathogens, which is a key process of the initiation of periodontal diseases. Yet, how ZA affects the periodontal pathogens infecting the epithelial barrier remains unclear. This study aimed to investigate the influences of ZA on the process of Porphyromonas gingivalis (P. gingivalis) infecting the gingival epithelial barrier via in-vitro and in-vivo experiments. In the in-vitro experiments, under the condition of different concentrations of ZA (0, 1, 10, and 100 μM), P. gingivalis was used to infect human gingival epithelial cells (HGECs). The infections were detected by transmission electron microscope and confocal laser scanning microscope. Besides, the internalization assay was applied to quantify the P. gingivalis, which infected the HGECs, in the different groups. To evaluate the expression levels of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, by infected HGECs, real-time quantitative reverse transcription-polymerase chain reactions were applied. In the in-vivo experiments, rats were given ZA solution (ZA group) or saline (control group) by tail intravenous injection for 8 weeks. Subsequently, we put ligatures around the maxillary second molars of all the rats and inoculated P. gingivalis to the gingiva every other day from day 1 to day 13. The rats were sacrificed on days 3, 7, and 14 for micro-CT and histological analyses. The in-vitro results manifested that the quantity of P. gingivalis that had infected HGECs increased with the ZA concentrations. Pro-inflammatory cytokines expression by HGECs were significantly increased by 100 μM ZA. In the in-vivo study, compared to the control group, more P. gingivalis was detected in the superficial layer of gingival epithelium in the ZA group. Besides, ZA significantly increased the expression level of IL-1β on day 14 and IL-6 on days 7 and 14 in gingival tissues. These findings suggest that the oral epithelial tissues of patients who receive high-dose ZA treatment may be more susceptible to periodontal infections, resulting in severe inflammatory conditions.
研究领域:
牙科学
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药理学
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免疫学
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微生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Stem Cells International
·
2021
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IF 5.443
Yuxin Zhao,Bobo Cai,Weijun Zhu,Jue Shi,Yu Wang,Misi Si
Mesenchymal stem cells (MSCs) have been considered to be a future treatment option for periodontitis due to their excellent regenerative capability. However, it is still a challenge to protect MSCs’ biological properties from multiple bacterial toxins in local inflammatory environment. The present study is aimed at investigating the treatment effect of interleukin-1 receptor antagonist (IL-1ra) on cell proliferation, migration, and osteogenic differentiation of gingival-derived mesenchymal stem cells (GMSCs) under an inflammatory microenvironment induced by Porphyromonas gingivalis lipopolysaccharides (P. gingivalis-LPS). GMSCs derived from Sprague-Dawley (SD) rats’ free gingival tissues were treated with P. gingivalis-LPS (10 μg/mL) to create in vitro inflammatory environment. Different concentrations of IL-1ra (0.01-1 μg/mL) were used to antagonize the negative effect of LPS. Cell behaviors including proliferation, cloning formation unit (CFU), cell migration, osteogenic differentiation, mineral deposition, and cytokine production were assessed to investigate the protection effect of IL-1ra on GMSCs under inflammation. The toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway activated by LPS was evaluated by real-time quantitative polymerase chain reaction (RT-PCR) and western blot. In response to P. gingivalis-LPS treatment, cell numbers, cloning formation rate, cell migration rate, proinflammatory cytokine production, and osteogenic differentiation-associated protein/mRNA expressions as well as mineralized nodules were suppressed in a time-dependent manner. These negative effects were effectively attenuated by IL-1ra administration in a time- and dose-dependent manner. In addition, mRNA expressions of TLR4 and IkBα decreased dramatically when IL-1ra was added into LPS-induced medium. IL-1ra also reversed the LPS-induced TLR4/NF-κB activation as indicated by western blot. The present study revealed that IL-1ra decreased inflammatory cytokine production in a supernatant, so as to protect GMSCs’ osteogenesis capacity and other biological properties under P. gingivalis-LPS-induced inflammatory environment. This might be explained by IL-1ra downregulating TLR4-mediated NF-κB signaling pathway activation.
研究领域:
牙科科学
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干细胞生物学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2025
·Vol. 25
·期 1
·449
·
IF 3.4
Yuan Yue,Sun Jinlong,Raka Rifat Nowshin,Liu Zixuan,Zhang Zhongwei,Xiao Junsong,Wu Hua
Background Severe periodontitis has impacted upwards of 1 billion people worldwide, posing a public health challenge. Porphyromonas gingivalis ( P. gingivalis ) is a keystone pathogen implicated in periodontal dysbiosis and disease progression. Lemongrass essential oil (LEO), extracted from Cymbopogon citratus (DC.) Stapf, has shown clinical benefits in periodontitis management, yet its mechanisms remain poorly understood. Methods Antibacterial and bactericidal activities of LEO against P. gingivalis were evaluated, along with its effects on heme uptake and storage, early biofilm-related phenotypes, mature biofilm development, and transcriptional regulation of virulence-associated genes. Docking simulations were performed to predict interactions between metabolites identified via GC-MS and virulence-related proteins. LEO’s effects on oxidative stress, inflammatory cytokine secretion, and ferroptosis-related gene expression were also evaluated in LPS-induced RAW 264.7 macrophages. Results The antibacterial efficacy of LEO against P. gingivalis was evidenced by a 51.10 ± 2.17 mm inhibition zone, along with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 34.06 and 68.13 µg/mL, respectively. Growth curve analysis showed sustained suppression over 30 h. At 1/4 − 1/2 MIC, LEO inhibited P. gingivalis hemagglutination, hemolysis ( p < 0.05), and heme accumulation. Moreover, biofilm formation was significantly reduced by over 85% at 1/2 MIC though suppression of autoaggregation and hydrophobicity ( p < 0.05). Molecular docking analysis predicted that α -citral (46.41%) and neral (31.58%), the major metabolites of LEO, may act as potential bioactive metabolites. In addition, LEO significantly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), notably decreasing TNF-α secretion to 0.82× and 0.66× (MIC and MBC, respectively) relative to the LPS group ( p < 0.05). It also alleviated oxidative stress through slc7a11 upregulation and subsequent glutathione synthesis, leading to restoration of the GSH/GSSG ratio and a reduction in ROS and MDA levels ( p < 0.05). Moreover, LEO downregulated Tfrc expression and decreased Fe²⁺ accumulation ( p < 0.05), suggesting its potential role in restoring iron homeostasis and suppressing ferroptosis-associated markers, such as Ptgs2 . These effects highlight the multifunctional regulatory capacity of LEO during P. gingivalis -LPS-induced inflammatory stress. Conclusion LEO demonstrated multitarget inhibitory effects by attenuating P. gingivalis virulence and regulating macrophage oxidative and iron homeostasis. These findings support its potential as a natural adjunctive or preventive agent in periodontitis therapy.
研究领域:
微生物学
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口腔生物学
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植物药理学
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分子生物学
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传染病学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Hanan Al-Fakeh,Hasan M. Sharhan,Zheng Nan Nan,Cao Hongjuan,Wu Lin
MAO of Ti–2.5Ag yields micro-porous TiO₂ with enhanced roughness and hydrophilicity. • MAO porous structure sustains sub-cytotoxic Ag⁺ multiphasic release over 7 days. • MAO + Ag surface reduces P. gingivalis biofilm despite enhanced hydrophilicity. • Protein leakage confirms Ag⁺–SH membrane disruption as the bactericidal mechanism. • Ti–2.5Ag + MAO offers dual infection resistance with osseointegration-safe surface. Titanium implants remain susceptible to bacterial colonization by Porphyromonas gingivalis , a keystone pathogen in peri-implantitis, and although silver (Ag) incorporation and micro-arc oxidation (MAO) have each been explored individually, their combined effect on low-silver titanium alloys against anaerobic oral pathogens remains poorly characterized. This study fabricated CP-Ti, Ti–2.5Ag (Ti+Ag), and MAO-treated Ti–2.5Ag (Ti+Ag+MAO) surfaces and evaluated their physicochemical properties and antibacterial performance against P. gingivalis over seven days. MAO generated a micro-porous TiO₂ oxide layer (32.6% porosity) incorporating phosphorus and silicon, significantly increasing roughness Ra = 0.0846 µm; p < 0.01) and hydrophilicity (contact angle: 36.33°–41.34°; p < 0.05) versus CP-Ti. Cumulative Ag⁺ release from Ti + Ag + MAO reached 0.844 ppb by day 7, approximately twice that of Ti + Ag (0.399 ppb; p < 0.05), following a multiphasic release profile. Against P. gingivalis , Ti + Ag + MAO achieved adherent bacterial inhibition exceeding 91% by day 7 (versus 73% for Ti+Ag), with dead-cell percentages rising from 57.56% to 76.25% (p < 0.001 vs. both comparators). Crystal violet and protein leakage assays confirmed sustained anti-biofilm activity and progressive membrane disruption (p < 0.01–0.001), consistent with the observed Ag⁺ release kinetics. These findings demonstrate that MAO synergistically amplifies the antibacterial efficacy of Ti–2.5Ag through combined anti-adhesive and sustained ion-release-mediated mechanisms, establishing Ti + Ag + MAO as a promising multifunctional strategy for reducing peri-implant infections.
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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
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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