ABSTRACT
Periodontitis is a widely prevalent oral disease around the world characterized by the disruption of the periodontal ligament and the subsequent development of periodontal pockets, as well as the loss of alveolar bone, and may eventually lead to tooth loss. This research aims to assess the suppressive impact of Eupatilin, a flavone obtained from Artemisia argyi, on osteoclastogenesis in vitro and periodontitis in vivo. We found that Eupatilin can efficiently obstruct the differentiation of Raw264.7 and bone marrow-derived macrophages (BMDMs) induced by RANKL, leading to the formation of mature osteoclasts. Consistently, bone slice resorption assay showed that Eupatilin significantly inhibited osteoclast-mediated bone resorption in a dose-dependent manner. Eupatilin also downregulated the expression of osteoclast-specific genes and proteins in Raw264.7 and BMDMs. RNA sequencing showed that Eupatilin notably downregulated the expression of Siglec-15. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified significantly enriched pathways in DEGs, including MAPK signaling pathway. And further mechanistic investigations confirmed that Eupatilin repressed MAPKs/NF-κBsignaling pathways. It was found that Siglec-15 overexpression reversed the inhibitory impact of Eupatilin on the differentiation of osteoclasts. Furthermore, activating MAPK signaling pathway reversed the downregulation of Siglec-15 and the inhibition of osteoclastogenesis by Eupatilin. To sum up, Eupatilin reduced the expression of Siglec-15 by suppressing MAPK signaling pathway, ultimately leading to the inhibition of osteoclastogenesis. Meanwhile, Eupatilin suppressed the alveolar bone resorption caused by experimentalperiodontitis in vivo. Eupatilin exhibits potential therapeutic effects in the treatment of periodontitis, rendering it a promising pharmaceutical agent.
Subject(s)
Alveolar Bone Loss , Flavonoids , Osteoclasts , Osteogenesis , Periodontitis , Animals , Mice , Osteogenesis/drug effects , RAW 264.7 Cells , Flavonoids/pharmacology , Flavonoids/therapeutic use , Alveolar Bone Loss/drug therapy , Osteoclasts/drug effects , Periodontitis/drug therapy , Mice, Inbred C57BL , Cell Differentiation/drug effects , Male , Macrophages/drug effects , MAP Kinase Signaling System/drug effects , Signal Transduction/drug effects , Artemisia/chemistry , RANK Ligand/metabolismABSTRACT
As bone-resorbing cells rich in mitochondria, osteoclasts require high iron uptake to promote mitochondrial biogenesis and maintain a high-energy metabolic state for active bone resorption. Given that abnormal osteoclast formation and activation leads to imbalanced bone remodeling and osteolytic bone loss, osteoclasts may be crucial targets for treating osteolytic diseases such as periodontitis. Isobavachin (IBA), a natural flavonoid compound, has been confirmed to be an inhibitor of receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs). However, its effects on periodontitis-induced bone loss and the potential mechanism of its anti-osteoclastogenesis effect remain unclear. Our study demonstrated that IBA suppressed RANKL-induced osteoclastogenesis in BMMs and RAW264.7 cells and inhibited osteoclast-mediated bone resorption in vitro. Transcriptomic analysis indicated that iron homeostasis and reactive oxygen species (ROS) metabolic process were enriched among the differentially expressed genes following IBA treatment. IBA exerted its anti-osteoclastogenesis effect by inhibiting iron accumulation in osteoclasts. Mechanistically, IBA attenuated iron accumulation in RANKL-induced osteoclasts by inhibiting the mitogen-activated protein kinase (MAPK) pathway to upregulate ferroportin1 (Fpn1) expression and promote Fpn1-mediated intracellular iron efflux. We also found that IBA inhibited mitochondrial biogenesis and function, and reduced RANKL-induced ROS generation in osteoclasts. Furthermore, IBA attenuated periodontitis-induced bone loss by reducing osteoclastogenesis in vivo. Overall, these results suggest that IBA may serve as a promising therapeutic strategy for bone diseases characterized by osteoclastic bone resorption.
Subject(s)
Iron , Mice, Inbred C57BL , Mitochondria , Organelle Biogenesis , Osteoclasts , Periodontitis , Animals , Mice , Iron/metabolism , RAW 264.7 Cells , Periodontitis/drug therapy , Periodontitis/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Osteogenesis/drug effects , Male , Bone Resorption/metabolism , Bone Resorption/drug therapy , Bone Resorption/prevention & control , Bone Resorption/etiology , Alveolar Bone Loss/metabolism , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/prevention & control , Alveolar Bone Loss/etiology , Alveolar Bone Loss/pathologyABSTRACT
The healing of large bone defects remains a significant challenge in clinical practice. Accelerating both angiogenesis and osteogenesis can promote effective bone healing. In the natural healing process, angiogenesis precedes osteogenesis, providing a blood supply that supports the subsequent progression of osteogenesis. Developing a biomimetic scaffold that mimics the in vivo environment and promotes the proper sequence of vascularization followed by ossification is crucial for successful bone regeneration. In this study, a novel injectable dual-drug programmed releasing chitosan nanofibrous microsphere-based poly(D, l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,l-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel is fabricated by incorporating vascular endothelial growth factor (VEGF) and microspheres loaded with dental pulp stem cells-derived exosomes (DPSCs-Exo). Rapid release of VEGF promotes the swift initiation of angiogenesis, while DPSCs-Exo release ensures persistent osteogenesis. Our results demonstrate that chitosan microsphere-based PLGA-PEG-PLGA hydrogel significantly promotes angiogenesis in human umbilical vascular endothelial cells and enhances the osteogenic differentiation of pre-osteoblasts. Furthermore, in vivo transplantation of this injectable chitosan microsphere-based PLGA-PEG-PLGA hydrogel into calvarial bone defects markedly promotes bone formation. Overall, our study provides a promising approach for improving bone regeneration by temporally replicating the behavior of angiogenesis and osteogenesis.
Subject(s)
Chitosan , Exosomes , Nanofibers , Humans , Osteogenesis , Vascular Endothelial Growth Factor A/pharmacology , Chitosan/pharmacology , Microspheres , Endothelial Cells , Bone Regeneration , Biocompatible Materials/pharmacology , Hydrogels/pharmacologyABSTRACT
BACKGROUND AND PURPOSE: Inflammatory disorders have been found to induce bone loss through sustained and persistent activation of osteoclast differentiation, leading to heightened bone resorption. The current pharmacological interventions for combating bone loss to harbor adverse effects or contraindications. There is a pressing need to identify drugs with fewer side effects. EXPERIMENTAL APPROACH: The effect and underlying mechanism of sulforaphene (LFS) on osteoclast differentiation were illustrated in vitro and in vivo with RANKL-induced Raw264.7 cell line osteoclastogenesis and lipopolysaccharide (LPS)-induced bone erosion model. KEY RESULTS: In this study, LFS has been shown to effectively impede the formation of mature osteoclasts induced from both Raw264.7 cell line and bone marrow macrophages (BMMs), mainly at the early stage. Further mechanistic investigations uncovered that LFS suppressed AKT phosphorylation. SC-79, a potent AKT activator, was found to reverse the inhibitory impact of LFS on osteoclast differentiation. Moreover, transcriptome sequencing analysis revealed that treatment with LFS led to a significant upregulation in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant-related genes. Then it's validated that LFS could promote NRF2 expression and nuclear translocation, as well as effectively resist oxidative stress. NRF2 knockdown reversed the suppression effect of LFS on osteoclast differentiation. In vivo experiments provide convincing evidence that LFS is protective against LPS-induced inflammatory osteolysis. CONCLUSION AND IMPLICATIONS: These well-grounded and promising findings suggest LFS as a promising agent to addressing oxidative-stress related diseases and bone loss disorders.
Subject(s)
Bone Resorption , Osteogenesis , Humans , Lipopolysaccharides/pharmacology , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Cell Differentiation , Osteoclasts/metabolism , Signal Transduction , Bone Resorption/chemically induced , Bone Resorption/drug therapy , Bone Resorption/genetics , RANK Ligand/genetics , RANK Ligand/pharmacology , NF-kappa B/metabolismABSTRACT
BACKGROUND: Streptococcus, Bifidobacteria, Lactobacillus and Actinomyces are acidogenic aciduria that may be associated with root caries (RC). The aim of the study was to analyze Streptococcus mutans (S. mutans), Streptococcus sobrinus (S. sobrinus), Bifidobacterium spp., Lactobacillus spp. and Actinomyces naeslundii (A. naeslundii) in the saliva of nursing home elderly, to assess the correlation between bacterial composition and RC for five putative catiogenic organisms. METHODS: In this study, we collected 43 saliva samples and divided into two groups: the root caries group (RCG, n = 21) and the caries-free group (CFG, n = 22). Bacterial DNA was extracted from the saliva samples. The presence and abundance of the five microorganisms were detected by Quantitative real-time PCR (qPCR). Spearman correlation test was performed to evaluate the relationship between the numbers of root decayed filled surfaces (RDFS) and root caries index (RCI) and salivary levels of the bacteria. RESULTS: The salivary levels of S. mutans, S. sobrinus, Bifidobacterium spp. and Lactobacillus spp. were significantly higher in RCG than in CFG (p < 0.05). RDFS and RCI (RDFS/RCI) were positively associated with salivary levels of S. mutans, S. sobrinus and Bifidobacterium spp. (r = 0.658/0.635, r = 0.465/0.420 and r = 0.407/0.406, respectively). No significant differences in presence and amounts of A. naeslundii was observed between the two groups (p > 0.05). CONCLUSION: S. mutans, S. sobrinus and Bifidobacterium spp. in saliva appear to be associated with RC in the elderly. Taken together, the findings indicate that specific salivary bacteria may be involved in the progression of RC.
Subject(s)
Dental Caries , Root Caries , Humans , Aged , Root Caries/microbiology , Streptococcus mutans , Streptococcus sobrinus , Dental Caries/microbiology , Saliva/microbiology , Nursing HomesABSTRACT
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.
Subject(s)
Periodontitis , Porphyromonas gingivalis , Humans , Porphyromonas gingivalis/genetics , In Situ Hybridization, Fluorescence , Periodontitis/drug therapy , Periodontitis/microbiology , Periodontitis/prevention & control , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , HomeostasisABSTRACT
BACKGROUND: In peri-implantitis, Porphyromonas gingivalis and macrophage play important roles. The aim of this study was to detect the attenuating effect of an anti-diabetic drug sitagliptin on Porphyromonas gingivalis virulence and inflammatory response in macrophage on titanium discs. MATERIALS AND METHODS: Porphyromonas gingivalis and macrophage were cultured on titanium discs. Antibacterial and antibiofilm activities of sitagliptin were assessed and the morphology of Porphyromonas gingivalis was observed by SEM. Bacterial early adhesion, aggregation, hemolysis and Porphyromonas gingivalis virulence factors mRNA expression were assessed to preliminarily investigate the mechanisms of action. Flow cytometry assay, qRT-PCR assay and ELISA were used to assess the anti-inflammatory effect of sitagliptin on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophage. RESULTS: The present study demonstrated the inhibiting effect of sitagliptin on the growth, biofilm and virulence factors of Porphyromonas gingivalis and the protective effect on the Porphyromonas gingivalis lipopolysaccharide-induced polarization in macrophage. And we also confirmed the anti-inflammatory effect of sitagliptin on the secretion of inflammation-related factors in macrophage. CONCLUSIONS: Sitagliptin possesses the attenuating effect on Porphyromonas gingivalis virulence and inflammatory response in Porphyromonas gingivalis lipopolysaccharide-stimulated macrophage on titanium.
Subject(s)
Porphyromonas gingivalis , Titanium , Titanium/pharmacology , Virulence , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Macrophages , Virulence Factors/metabolism , Anti-Inflammatory Agents/pharmacologyABSTRACT
Caries are chronic infections in which the cariogenic biofilm plays a critical role in disease occurrence and progression. Photodynamic therapy (PDT) is a new effective treatment that is receiving wide attention in the antibacterial field, but it can lead to the upregulation of heat shock proteins (HSPs), which enhances bacterial resistance. Herein, we incorporated HSP inhibitors with PDT to evaluate the effect on Streptococcus mutans, Streptococcus sobrinus, and Streptococcus sanguinis under planktonic conditions and on cariogenic biofilms. Additionally, a model of caries was established in 2-week-old rats, and anticaries properties were evaluated by Keyes' scoring. Importantly, the combination of HSP inhibitors and PDT had outstanding efficiency in inhibiting the growth of tested Streptococcus strains and the formation of either monomicrobial or multispecies biofilms in vitro. In addition, the quantity of colonized streptococci and the severity of carious lesions were also distinctly suppressed in vivo. Overall, the synergistic application of HSP inhibitors and PDT has promising potential in the prevention and treatment of dental caries. IMPORTANCE Effective therapies for the prevention and control of caries are urgently needed. Cariogenic streptococci play a key role in the occurrence and progression of caries. Recently, photodynamic therapy has been demonstrated to have good antibacterial efficiency, but it can cause a heat shock response in bacteria, which may weaken its practical effects. We indicate here an effective therapeutic strategy of combining heat shock protein inhibitors and photodynamic therapy, which shows excellent inhibition toward three dominant streptococci related to caries and suppression of carious progression in a rat model. Further development for clinical application is promising.
Subject(s)
Dental Caries , Photochemotherapy , Rats , Animals , Dental Caries/drug therapy , Dental Caries/prevention & control , Dental Caries Susceptibility , Streptococcus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic useABSTRACT
OBJECTIVES: To analyse the characteristics of the oral microbiomes and expected to find biomarkers about Alzheimer's disease (AD). SUBJECTS AND METHODS: AD patients (n = 26) and cognitive intact people (n = 26) were examined for cognition, depression, oral health and collected saliva and gingival crevicular fluid (GCF) in the morning. Full-length 16S rRNA gene was amplified and sequencing was performed using the PacBio platform. RESULTS: The predominant bacterium of salivary microbiome and periodontal microbiome from AD patients was Streptococcus oralis and Porphyromonas gingivalis, respectively. With respect to ß diversity analysis, there was a significance difference in periodontal microbiome between AD patients and cognitively intact subjects. The relative abundance of Veillonella parvula significantly increased in oral microbiomes from AD patients. Interestingly, the dominant species were different between early-onset AD and late-onset AD patients. Moreover, the predominant species were changed as the clinical severity of AD. Furthermore, the correlation analysis revealed that V. parvula was associated with AD in both saliva and GCF and that P. gingivalis was associated with AD only in GCF. CONCLUSIONS: In this study, the microbiome community of oral microbes was altered in AD patients and periodontal microbiome was sensitive to cognition changes. Moreover, V. parvula and P. gingivalis were associated with AD.
Subject(s)
Alzheimer Disease , Microbiota , Humans , RNA, Ribosomal, 16S/genetics , Porphyromonas gingivalis , Microbiota/genetics , Cognition , Gingival Crevicular Fluid , Saliva/microbiologyABSTRACT
OBJECTIVE: The objective of the study was to determine the anti-osteoclastogenic potential of ginsenoside Rb3 for the treatment of periodontitis. METHODS: The anti-osteoclastogenic effect was determined using RANKL-induced RAW264.7 cells and murine bone marrow-derived macrophages followed by TRAP and phalloidin staining. Expression of osteoclastogenesis-related genes and proteins were examined by qPCR and WB. Activation of signaling pathways was detected by WB and IHC techniques. Experimental periodontitis rat model was built up by gingival injections of P. gingivalis LPS. After 21 days of Rb3 treatment, rats were sacrificed for micro-CT, IHC, H&E, and TRAP staining analyses. RESULTS: Rb3 dramatically inhibits RANKL-induced osteoclastogenesis. Nfatc1, Mmp9, Ctsk, Acp5 mRNA, and MMP9, CTSK proteins were dose-dependently downregulated by Rb3 pretreatment. WB results revealed that Rb3 suppressed activations of p38 MAPK, ERK, and p65 NF-κB, and the inhibition of ERK was most pronounced. Consistently, IHC analysis revealed that p-ERK was highly expressed in alveolar bone surface, blood vessels, odontoblasts, and gingival epithelia, which were notably suppressed by Rb3 treatment. H&E staining and micro-CT analyses showed that Rb3 significantly attenuated gingivitis and alveolar bone resorption in rats. CONCLUSION: Rb3 inhibits RANKL-induced osteoclastogenesis and attenuates P. gingivalis LPS-induced gingivitis and alveolar bone resorption in rats via ERK/NF-κB signaling pathway.
Subject(s)
Bone Resorption , Gingivitis , Periodontitis , Rats , Mice , Animals , NF-kappa B/metabolism , Osteogenesis , Matrix Metalloproteinase 9/metabolism , Osteoclasts/metabolism , Lipopolysaccharides/pharmacology , Signal Transduction , Gingivitis/metabolism , Periodontitis/metabolism , RANK Ligand/metabolism , Cell DifferentiationABSTRACT
Signal transducer and activator of transcription 3 (STAT3), a cytokine-responsive transcription factor, is known to play a role in immunity and bone remodeling. However, whether and how STAT3 impacts macrophage NLR family pyrin domain containing 3 (NLRP3) inflammasome activation associated with inflammatory bone loss remains unknown. Here, STAT3 signaling is hyperactivated in macrophages in the context of both non-sterile and sterile inflammatory osteolysis, and this was highly correlated with the cleaved interleukin-1ß (IL-1ß) expression pattern. Strikingly, pharmacological inhibition of STAT3 markedly blocks macrophage NLRP3 inflammasome activation in vitro, thereby relieving inflammatory macrophage-amplified osteoclast formation and bone-resorptive activity. Mechanistically, STAT3 inhibition in macrophages triggers PTEN-induced kinase 1 (PINK1)-dependent mitophagy that eliminates dysfunctional mitochondria, reverses mitochondrial membrane potential collapse, and inhibits mitochondrial reactive oxygen species release, thus inactivating the NLRP3 inflammasome. In vivo, STAT3 inhibition effectively protects mice from both infection-induced periapical lesions and aseptic titanium particle-mediated calvarial bone erosion with potent induction of PINK1 and downregulation of inflammasome activation, macrophage infiltration, and osteoclast formation. This study reveals the regulatory role of the STAT3/mitophagy axis at the osteo-immune interface and highlights a potential therapeutic intervention to prevent inflammatory bone loss. © 2022 American Society for Bone and Mineral Research (ASBMR).
Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Mice , Inflammasomes/metabolism , Macrophages/metabolism , Mitophagy/physiology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Protein Kinases/metabolism , Reactive Oxygen Species/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
The oral microbiome, associated with both oral disease and systemic disease, is in dynamic status along the whole life, and many factors including maternal microbiomes could impact the oral microbiome. While fewer studies have been conducted to study the characteristics of the oral microbiome in neonates and the associated maternal factors. Hence, we collected the microbiome of 15 mother-infant pairs across multiple body sites from birth up to 4âdays postpartum and used high-throughput sequencing to characterize the microbiomes in mothers and their neonates. The oral microbiome in the neonates changed obviously during the 4âdays after birth. Many bacteria originating from the vagina, skin, and environment disappeared in oral cavity over time, such as Prevotella bivia and Prevotella jejuni. Meanwhile, Staphylococcus epidermidis RP62A phage SP-beta, predominate bacterium in maternal skin microbiome and Streptococcus unclassified, main bacterium in vaginal microbiome, obviously increased in neonatal oral microbiome as time went on. Interestingly, as time progressed, the composition of the oral microbiome in the neonates was more similar to that of the milk microbiome in their mothers. Moreover, we found that the changes in the predominant bacteria in the neonates were in line with those in the neonates exposed to the environment. Together, these data described the sharp dynamics of the oral microbiome in neonates and the importance of maternal efforts in the development of the neonatal microbiome.
ABSTRACT
BACKGROUND: The ex vivo study is to compare the root canal preparation outcomes achieved by five nickel-titanium single-file instrumentation systems (M3-L, Reciproc Blue, V-Taper 2H, WaveOne Gold, XP-endo Shaper) in severely curved molar root canals. METHODS: A total of 60 root canals were selected from extracted human molar teeth with curvatures ranging from 25° to 50° and divided into five groups based on the instrumentation system employed (n = 12). Before and after root canal preparation, a Micro-CT scan was taken, and pre- and post-operative data were analyzed to evaluate the following parameters: volume increment of root canals (VI), untouched root canal areas (UTA), and canal transportation (CT). Apically extruded debris (AD) was collected during preparation. After that, all samples were separated into two parts and examined respectively by scanning electron microscope (SEM) to assess cleaning ability. Data were statistically analyzed with ANOVA (UTA, AD, VI) or Kruskal-Wallis test (CT, SEM-score), the level of significance was set at α = 0.05. RESULTS: There were no significant differences between the five systems regarding the AD, VI, and UTA parameters (P > 0.05). In terms of CT, no significant difference was noted at the straight section of canal and apical levels, while XP-endo Shaper showed less canal transportation than M3-L at the level of curved vertex (P < 0.05), and the centering ability of V-Taper 2H was significantly better than WaveOne Gold at the initial point of bending (P < 0.05). Debris and smear layers were present on the canal walls of all specimens, the apical thirds of the canal presented higher SEM scores than the coronal thirds in all groups (P < 0.05). Reciproc Blue and XP-endo Shaper showed fewer smear scores than WaveOne Gold in the apical thirds (P < 0.01 and P < 0.05, respectively), and no statistical difference was found between other groups in the middle and coronal thirds. CONCLUSION: The five single-file systems evaluated performed equally in apically debris extrusion, dentin removal, and untouched root canal areas, while XP-endo Shaper and V-Taper 2H resulted in less canal transportation compared to M3-L and WaveOne Gold. Regarding cleaning ability, Reciproc Blue and XP-endo Shaper were associated with less smear layer than WaveOne Gold in the apical thirds.
Subject(s)
Dental Instruments , Dental Pulp Cavity , Molar , Root Canal Preparation , Smear Layer , Humans , Dental Pulp Cavity/diagnostic imaging , Dental Pulp Cavity/surgery , Equipment Design/standards , Molar/diagnostic imaging , Molar/pathology , Molar/surgery , Root Canal Preparation/instrumentation , Root Canal Preparation/methods , Tooth Root/diagnostic imaging , X-Ray Microtomography , Dental Instruments/standardsABSTRACT
Bacteria residing within biofilms are more resistant to drugs than planktonic bacteria. They can thus play a significant role in the onset of chronic infections. Dispersion of biofilms is a promising avenue for the treatment of biofilm-associated diseases, such as dental caries. In this review, we summarize strategies for dispersion of cariogenic biofilms, including biofilm environment, signaling pathways, biological therapies, and nanovehicle-based adjuvant strategies. The mechanisms behind these strategies have been discussed from the components of oral biofilm. In the future, these strategies may provide great opportunities for the clinical treatment of dental diseases. Graphical Abstract.
ABSTRACT
In the original publication [...].
ABSTRACT
Periodontitis is a worldwide oral disease induced by the interaction of subgingival bacteria and host response and is characterized by local inflammation, bone resorption, and tooth loss. Ginsenoside Rd (Rd) is a biologically active component derived from Panax ginseng and has been demonstrated to exert antibacterial and anti-inflammatory activities. This study aims to investigate the inhibitory efficiency of Rd towards Porphyromonas gingivalis (P. gingivalis), periodontal inflammatory response, and osteoclastogenesis in vitro and to further validate the results in a mouse periodontitis model, thus, evaluate the potential effects of Rd on the control and prevention of periodontitis. According to the results, Rd exerted excellent antibacterial activities against planktonic P. gingivalis, along with attenuating P. gingivalis virulence and inhibiting its biofilms. Meanwhile, the inflammatory cytokine production and osteoclastogenesis were remarkably inhibited by Rd both in vitro and in vivo. Furthermore, Rd efficiently ameliorated the subgingival P. gingivalis abundance and suppressed the alveolar bone resorption in vivo as well. In conclusion, Rd has the potential to be developed as a promising medication in the control and prevention of periodontitis.
Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/microbiology , Alveolar Bone Loss/prevention & control , Animals , Anti-Bacterial Agents , Disease Models, Animal , Ginsenosides , Inflammation/drug therapy , Mice , Periodontitis/drug therapy , Periodontitis/microbiology , VirulenceABSTRACT
Early childhood caries (ECC) is a public healthcare concern that greatly reduces the quality of life of young children. As a leading factor of ECC, cariogenic biofilms are composed of acidogenic/aciduric pathogens and extracellular polysaccharides (EPSs), creating an acidic and protected microenvironment. Antimicrobial photodynamic therapy (aPDT) is a noninvasive, painless, and efficient therapeutic approach that is suitable for treating ECC. However, due to the hyperfine structure of cariogenic biofilms, most photosensitizers (PSs) could not access and penetrate deeply in biofilms, which dramatically hamper their efficiency in the clinic. Herein, bioresponsive nanoparticle loaded with chlorin e6 (MPP-Ce6) is developed, which largely increases the penetration depth (by over 75%) and retention (by over 100%) of PS in the biofilm compared with free Ce6. Furthermore, MPP-Ce6-mediated aPDT not only kills the bacteria in preformed biofilms but also inhibits multispecies biofilm formation. A rampant caries model is established to mimic ECC in vivo, where the population of cariogenic bacteria is decreased to 10% after MPP-Ce6-mediated aPDT. Importantly, the number and severity of carious lesions are efficiently reduced via Keyes' scoring and micro-CT analysis. This simple but effective strategy can serve as a promising approach for daily oral hygiene in preventing ECC.
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Reports on alterations in the oral mycobiome of HIV-infected patients are still limited. This study was designed to compare the salivary mycobiome between 30 human immunodeficiency virus (HIV) infections and 30 healthy controls and explore the effect of antiretroviral therapy (ART) administration on the oral mycobiome of HIV infections. Results showed that the diversity and richness of salivary mycobiome in HIV-infected individuals were higher than those of controls (P < 0.05). After ART, the diversity and richness of salivary mycobiome in HIV-infected patients were reduced significantly (P < 0.05). Candida, Mortierella, Malassezia, Simplicillium, and Penicillium were significantly enriched in the HIV group and dramatically decreased after ART. While the relative abundance of Verticillium, Issatchenkia, and Alternaria significantly increased in patients with HIV after ART. Correlation analysis revealed that Mortierella, Malassezia, Simplicillium, and Chaetomium were positively correlated with viral load (VL), whereas Thyrostroma and Archaeorhizomyces were negatively related to VL and positively related to CD4+ T-cell counts. All results showed that HIV infection and ART administration affected the composition of salivary mycobiome communities. Furthermore, differences of salivary mycobiome in HIV infections after ART were complex and might mirror the immune state of the body.
Subject(s)
HIV Infections , Malassezia , Mycobiome , HIV , HIV Infections/complications , HIV Infections/drug therapy , Humans , Viral LoadABSTRACT
Background: Since the outbreak of Coronavirus disease 2019 (COVID-19), the government of China adopted many measures which changed people's lifestyle including oral health-related lifestyle to control the transmission. The aim of this study was to investigate oral health status, oral healthcare behaviors, and parental attitudes toward oral healthcare among school-age children in Wuhan during the COVID-19 outbreak and what the status would be when the outbreak is under control. Methods: This study was an online cross-sectional survey facing elementary school students in Wuhan. The questionnaire was completed by children's parents or other family members. The information on demographic data, oral health status, oral healthcare behaviors, and parental attitudes toward oral healthcare was collected at the end of school closure. The chi-square test was used to test the association of different questionnaire items. Results: A total of 18,383 subjects aged 6-13 years with complete data were included in this investigation, and 44.2% of them suffered pain or discomfort related to teeth and gums during the epidemic. While there might be an increasing need and concern of oral healthcare during the outbreak and even when the outbreak was controlled, the worry of infection made it difficult for people to meet their demands of dental attendance. Conclusion: The risk of cross-infection during the treatment had a negative influence on parental attitudes toward dental attendance. Effective measures should be taken to meet people's demands of dental attendance.