ABSTRACT
Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.
Subject(s)
Bone Regeneration , Collagen , Mesenchymal Stem Cells , Nanowires , Osteogenesis , Tissue Scaffolds , Zinc Oxide , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Nanowires/chemistry , Bone Regeneration/drug effects , Tissue Scaffolds/chemistry , Humans , Collagen/chemistry , Mesenchymal Stem Cells/cytology , Osteogenesis/drug effects , Animals , Porphyromonas gingivalis/drug effects , Cell Differentiation/drug effects , Streptococcus mutans/physiology , Streptococcus mutans/drug effects , Cell Proliferation/drug effectsABSTRACT
Titanium implants are subject to bacterial adhesion and peri-implantitis induction, and biosurfactants bring a new alternative to the fight against infections. This work aimed to produce and characterize the biosurfactant from Bacillus subtilis ATCC 19,659, its anti-adhesion and antimicrobial activity, and cell viability. Anti-adhesion studies were carried out against Streptococcus sanguinis, Staphylococcus aureus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Proteus mirabilis as the minimum inhibitory concentration and the minimum bactericidal concentration. Cell viability was measured against osteoblast and fibroblast cells. The biosurfactant was classified as lipopeptide, with critical micelle concentration at 40 µg mL- 1, and made the titanium surface less hydrophobic. The anti-adhesion effect was observed for Staphylococcus aureus and Streptococcus sanguinis with 54% growth inhibition and presented a minimum inhibitory concentration of 15.7 µg mL- 1 for Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans. The lipopeptide had no cytotoxic effect and demonstrated high potential application against bacterial biofilms.
Subject(s)
Bacterial Adhesion , Biofilms , Dental Implants , Lipopeptides , Microbial Sensitivity Tests , Titanium , Titanium/pharmacology , Titanium/chemistry , Biofilms/drug effects , Biofilms/growth & development , Bacterial Adhesion/drug effects , Dental Implants/microbiology , Lipopeptides/pharmacology , Humans , Anti-Bacterial Agents/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Bacillus subtilis/drug effects , Porphyromonas gingivalis/drug effects , Porphyromonas gingivalis/physiology , Porphyromonas gingivalis/growth & development , Aggregatibacter actinomycetemcomitans/drug effects , Surface Properties , Fibroblasts/drug effects , Fusobacterium nucleatum/drug effects , Cell Survival/drug effects , Osteoblasts/drug effects , Surface-Active Agents/pharmacologyABSTRACT
BACKGROUND: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. METHODS: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. RESULTS: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. CONCLUSION: This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.
Subject(s)
Cell Proliferation , Curcumin , Fibroblasts , Keratinocytes , Porphyromonas gingivalis , Streptococcus mutans , Curcumin/pharmacology , Curcumin/therapeutic use , Humans , Keratinocytes/drug effects , Fibroblasts/drug effects , Porphyromonas gingivalis/drug effects , Cell Proliferation/drug effects , Streptococcus mutans/drug effects , Cell Line , Wound Healing/drug effects , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Candida albicans/drug effects , Lipopolysaccharides , In Vitro Techniques , Periodontal Ligament/cytology , Periodontal Ligament/drug effects , Gels , Inflammation/drug therapy , Apoptosis/drug effects , Stomatitis/drug therapy , Cell Adhesion/drug effectsABSTRACT
AIMS: This study aimed to investigate the antibacterial and anti-inflammatory effects of the antimicrobial peptide Microcin C7 for Porphyromonas gingivalis-associated diseases. METHODS AND RESULTS: Reverse-phase high-performance liquid chromatography revealed that Microcin C7 could remain 25.5% at 12 h in saliva. At a concentration of <10 mg ml-1, Microcin C7 showed better cytocompatibility, as revealed by a hemolysis test and a subchronic systemic toxicity test. Moreover, the minimum inhibitory concentration and minimum bactericidal concentration of Microcin C7 were analyzed using a broth microdilution method, bacterial growth curve, scanning electron microscopy, and confocal laser microscopy and determined to be 0.16 and 5 mg ml-1, respectively. Finally, in a rat model, 5 mg ml-1 Microcin C7 showed better performance in decreasing the expression of inflammatory factors (IL-1ß, IL-6, IL-8, and TNF-α) and alveolar bone resorption than other concentrations. CONCLUSIONS: Microcin C7 demonstrated favorable biocompatibility, antibacterial activity, and anti-inflammatory effect, and could decrease the alveolar bone resorption in a rat model, indicating the promising potential for clinical translation and application on P. gingivalis-associated diseases.
Subject(s)
Anti-Bacterial Agents , Bacteriocins , Microbial Sensitivity Tests , Porphyromonas gingivalis , Animals , Porphyromonas gingivalis/drug effects , Porphyromonas gingivalis/growth & development , Rats , Bacteriocins/pharmacology , Anti-Bacterial Agents/pharmacology , Bacteroidaceae Infections/drug therapy , Bacteroidaceae Infections/microbiology , Antimicrobial Peptides/pharmacology , Male , Rats, Sprague-Dawley , Anti-Inflammatory Agents/pharmacology , Disease Models, Animal , Alveolar Bone Loss/prevention & control , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/microbiologyABSTRACT
Controlling and reducing plaque formation plays a pivotal role in preventing and treating periodontal disease, often utilizing antibacterial drugs to enhance therapeutic outcomes. Mesoporous silica nanoparticles (MSN), an FDA-approved inorganic nanomaterial, possess robust physical and chemical properties, such as adjustable pore size and pore capacity, easy surface modification, and high biosafety. Numerous studies have exploited MSN to regulate drug release and facilitate targeted delivery. This study aimed to synthesize an MSN-tetracycline (MSN-TC) complex and investigate its inhibitory potential on Porphyromonas gingivalis (P. gingivalis)-induced bone resorption. The antibacterial efficacy of MSN-TC was evaluated through bacterial culture experiments. A P. gingivalis-induced bone resorption model was constructed by subcutaneously injecting P. gingivalis around the cranial bone of rats. Micro-computed tomography was employed to assess the inhibitory impact of MSN and MSN-TC on bone resorption. Furthermore, the influence of MSN and MSN-TC on osteoclast differentiation was examined in vitro. The MSN exhibited optimal pore size and particle dimensions for effective loading and gradual release of TC. MSN-TC demonstrated significant bacteriostatic activity against P. gingivalis. MSN-TC-treated rats showed significantly reduced cranial bone tissue destruction compared to MSN or TC-treated rats. Additionally, both MSN and MSN-TC exhibited inhibitory effects on the receptor activator of nuclear factor kappa-Β ligand-mediated osteoclast differentiation. The MSN-TC complex synthesized in this study demonstrated dual efficacy by exerting antibacterial effects on P. gingivalis and by resisting osteoclast differentiation, thereby mitigating bone resorption induced by P. gingivalis.
Subject(s)
Anti-Bacterial Agents , Bone Resorption , Nanoparticles , Porphyromonas gingivalis , Silicon Dioxide , Porphyromonas gingivalis/drug effects , Animals , Silicon Dioxide/chemistry , Bone Resorption/prevention & control , Rats , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Porosity , Osteoclasts/drug effects , Rats, Sprague-Dawley , Drug Delivery Systems , Male , Tetracycline/pharmacology , Tetracycline/chemistry , Tetracycline/administration & dosage , X-Ray Microtomography , Bacteroidaceae Infections/drug therapy , Bacteroidaceae Infections/microbiology , MiceABSTRACT
Periodontitis is a chronic inflammatory disease resulting from the dysbiosis of periodontal bacteria and the host's immune response, leading to tissue degradation and sustained inflammation. Traditional treatments, such as mechanical debridement and antimicrobial agents, often fail to fully eradicate pathogenic bacteria, especially in deep periodontal pockets. Consequently, the need for novel therapeutic approaches has increased the interest in bioactive natural extracts, such as that of Opuntia ficus-indica, known for its anti-inflammatory, antioxidant, and antimicrobial properties. This study investigates the encapsulation of Opuntia ficus-indica extract in OFI-loaded chitosan nanoparticles (OFI-NPs) via ionotropic gelation using a microfluidic system, allowing precise control over nanoparticle characteristics and enhancing protection against enzymatic degradation. To achieve localized and sustained release in periodontal pockets, a thermo-responsive hydrogel comprising hyaluronic acid and Pluronic F127 (OFI@tgels) was developed. The transition of OFI@tgels from a solution at low temperatures to a solid at body temperature enables prolonged drug release at inflammation sites. The in vitro application of the optimized formulation eradicated biofilms of S. mutans, P. aeruginosa (PAO1), and P. gingivalis over 36 h and disrupted extracellular polymeric substance formation. Additionally, OFI@tgel modulated immune responses by inhibiting M1 macrophage polarization and promoting a shift to the M2 phenotype. These findings suggest that OFI@tgel is a promising alternative treatment for periodontitis, effectively reducing biofilm formation and modulating the immune response.
Subject(s)
Chitosan , Hydrogels , Nanoparticles , Opuntia , Periodontitis , Plant Extracts , Chitosan/chemistry , Opuntia/chemistry , Nanoparticles/chemistry , Periodontitis/drug therapy , Periodontitis/microbiology , Periodontitis/therapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Hydrogels/chemistry , Animals , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Streptococcus mutans/drug effects , Humans , Biofilms/drug effects , Porphyromonas gingivalis/drug effects , Drug Liberation , Drug Carriers/chemistry , Poloxamer/chemistry , Pseudomonas aeruginosa/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistryABSTRACT
Periodontitis presents significant treatment challenges due to its complexity and potential complications. In response, an in situ forming gel (ISG) loaded with moxifloxacin HCl (Mx) and cellulose acetate butyrate (CAB) was developed for targeted periodontitis therapy. Mx-loaded 10-45% CAB-based ISGs were developed, and their physicochemical properties such as rheology, viscosity, contact angle, gel morphology and gel formation, interface interaction were investigated. Moreover, the formulation performance studies including drug release and kinetics, in vitro degradation, and antimicrobial activities were also evaluated. The Mx-loaded ISGs containing 25-45% CAB demonstrated rapid matrix formation in both macroscopic and microscopic examinations and presented plastic deformation matrix. Tracking with sodium fluorescein and Nile red fluorescence probes indicated delayed solvent movement owing to CAB matrix formation. Adequate CAB content sustained Mx release for one week, following Peppas-Sahlin model and indicating a predominantly Fickian diffusion mechanism. Higher CAB content likely contributed to a denser matrix structure, leading to a slower in vitro degradation rate. Synchrotron radiation X-ray tomographic and SEM imaging provided insights into the CAB matrix structure and porous network formation. These ISG formulations effectively inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, and Porphyromonas gingivalis. The Mx-loaded 40% CAB-based ISG shows promise as a dosage form for treating periodontitis. Further clinical trials are necessary to ensure the safety of this new ISG formulation, despite existing safety data for other medicinal uses of CAB. HIGHLIGHTS: Moxifloxacin HCl-loaded 10-45% cellulose acetate butyrate (CAB)-based in situ forming gels (ISG) were developed. They were evaluated for physicochemical properties, drug release, in vitro degradation, and antimicrobial activities. ISGs with 25-45% CAB showed swift matrix formation and plastic deformation Adequate CAB content sustained Mx release with Fickian diffusion mechanism They promise for periodontitis treatment because of effective inhibition of related pathogens.
Subject(s)
Cellulose , Drug Liberation , Gels , Moxifloxacin , Periodontitis , Cellulose/analogs & derivatives , Cellulose/chemistry , Periodontitis/drug therapy , Periodontitis/microbiology , Moxifloxacin/pharmacology , Moxifloxacin/administration & dosage , Candida albicans/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Viscosity , Chemistry, Pharmaceutical/methods , Microbial Sensitivity Tests/methods , Porphyromonas gingivalis/drug effectsABSTRACT
OBJECTIVE: To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial. RESULTS: The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC < 1.56% (v/v) and the MBC < 3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24 h, and 7 d post-mouthwash (P < 0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P < 0.01). CONCLUSIONS: The combination of ε-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe. TRIAL REGISTRATION: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).
Subject(s)
Dental Plaque , Halitosis , Mouthwashes , Polylysine , Humans , Halitosis/prevention & control , Halitosis/drug therapy , Halitosis/microbiology , Mouthwashes/therapeutic use , Dental Plaque/microbiology , Dental Plaque/prevention & control , Double-Blind Method , Male , Female , Polylysine/therapeutic use , Adult , Microbial Sensitivity Tests , Young Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Porphyromonas gingivalis/drug effects , Fusobacterium nucleatum/drug effects , Fibroblasts/drug effects , Peptides/therapeutic use , Peptides/pharmacology , Aggregatibacter actinomycetemcomitans/drug effects , Streptococcus mutans/drug effectsABSTRACT
BACKGROUND: There is insufficient clinical and microbiological evidence to support the use of diode laser and air-polishing with erythritol as supplements to scaling and root planning(SRP). The aim of the current study is to evaluate the clinical and microbiologic efficacy of erythritol subgingival air polishing and diode laser in treatment of periodontitis. METHODS: The study encompassed twenty-four individuals seeking periodontal therapy and diagnosed with stage I and stage II periodontitis. Eight patients simply underwent SRP. Eight more patients had SRP followed by erythritol subgingival air polishing, and eight patients had SRP followed by diode laser application. At baseline and six weeks, clinical periodontal parameters were measured, including Plaque Index (PI), Gingival Index (GI), periodontal Probing Depth (PPD), and Clinical Attachment Level (CAL). The bacterial count of Aggregatibacter actinomycetemcomitans(A.A), Porphyromonas gingivalis (P.G) was evaluated at different points of time. RESULTS: The microbiological assessment revealed significant differences in the count of A.A. between the laser and erythritol groups immediately after treatment, indicating a potential impact on microbial levels. However, the microbial levels showed fluctuations over the subsequent weeks, without statistically significant differences. Plaque indices significantly decreased post-treatment in all groups, with no significant inter-group differences. Gingival indices decreased, and the laser group showed lower values than erythritol and control groups. PPD and CAL decreased significantly across all groups, with the laser group exhibiting the lowest values. CONCLUSION: The supplementary use of diode laser and erythritol air polishing, alongside SRP, represents an expedited periodontal treatment modality. This approach leads to a reduction in bacteria and improvement in periodontal health. TRIAL REGISTRATION: This clinical trial was registered on Clinical Trials.gov (Registration ID: NCT06209554) and released on 08/01/2024.
Subject(s)
Aggregatibacter actinomycetemcomitans , Bacterial Load , Dental Plaque Index , Dental Scaling , Erythritol , Lasers, Semiconductor , Periodontal Index , Porphyromonas gingivalis , Root Planing , Adult , Female , Humans , Male , Middle Aged , Aggregatibacter actinomycetemcomitans/isolation & purification , Aggregatibacter actinomycetemcomitans/drug effects , Air Abrasion, Dental/methods , Bacterial Load/drug effects , Dental Scaling/methods , Erythritol/therapeutic use , Follow-Up Studies , Lasers, Semiconductor/therapeutic use , Periodontal Attachment Loss/therapy , Periodontal Attachment Loss/microbiology , Periodontal Pocket/therapy , Periodontal Pocket/microbiology , Periodontitis/microbiology , Periodontitis/therapy , Periodontitis/drug therapy , Porphyromonas gingivalis/isolation & purification , Porphyromonas gingivalis/drug effects , Root Planing/methods , Treatment OutcomeABSTRACT
OBJECTIVES: The present study aimed to assess and compare the effect of Morus alba and chlorhexidine gel as an adjunct to scaling and root planing (SRP) in treating stage II periodontitis. METHODS: A single-blind, randomized controlled trial was conducted on 180 patients with stage II periodontitis who received full-mouth SRP. They were randomly assigned to receive chlorhexidine digluconate (CHX) gel, Morus alba (MA) and placebo gel for Groups A, B and C, respectively, at the baseline, 15 days and 30 days. Plaque index (PI), Gingival index (GI), periodontal pocket depth (PPD) and quantitative analysis (culture) of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia were assessed at baseline and 45 days. Analysis of variance was used to compare the significant difference in PI, GI, PPD and microbiological parameters between the three groups after the intervention, followed by post hoc Mann-Whitney U and Tukey's HSD test for clinical and microbiological parameters, respectively. RESULTS: Intergroup comparison of the PI, GI and microbiological parameters between the MA and CHX groups at the end of 45 days did not show a statistically significant difference (p > 0.05), whereas a statistically significant difference was observed for PPD between MA and CHX groups with the mean difference of 0.18 mm (p = 0.002). CONCLUSION: Morus alba gel was found to be effective in decreasing PPD. However, there was no difference between Morus alba and chlorhexidine gel as an adjunct to SRP in treating stage II periodontitis.
Subject(s)
Chlorhexidine , Dental Scaling , Gels , Morus , Root Planing , Humans , Chlorhexidine/therapeutic use , Chlorhexidine/analogs & derivatives , Male , Female , Single-Blind Method , Adult , Root Planing/methods , Dental Scaling/methods , Middle Aged , Periodontal Index , Dental Plaque Index , Porphyromonas gingivalis/drug effects , Porphyromonas gingivalis/isolation & purification , Anti-Infective Agents, Local/therapeutic use , Treatment Outcome , Periodontitis/microbiology , Periodontitis/therapy , Periodontitis/drug therapy , Aggregatibacter actinomycetemcomitans/drug effects , Tannerella forsythia , Plant Extracts/therapeutic use , Combined Modality TherapyABSTRACT
OBJECTIVES: The aim of this study was to evaluate the potential protective effect of Chromobacterium violaceum and violacein against periodontitis, in experimental models. MATERIALS AND METHODS: A double-blind experimental study on the exposure to C. violaceum or violacein in experimentally ligature-induced periodontitis, as preventive factors against alveolar bone loss by periodontitis. Bone resorption was assessed by morphometry. Antibacterial potential of violacein was assessed in an in vitro assay. Its cytotoxicity and genotoxicity were evaluated using the Ames test and SOS Chromotest assay, respectively. RESULTS: The potential of C. violaceum to prevent/limit bone resorption by periodontitis was confirmed. Daily exposure to 106 cells/ml in water intake since birth and only during the first 30 days of life significantly reduced bone loss from periodontitis in teeth with ligature. Violacein extracted from C. violaceum was efficient in inhibiting or limiting bone resorption and had a bactericidal effect against Porphyromonas gingivalis in the in vitro assay. CONCLUSIONS: We conclude that C. violaceum and violacein have the potential to prevent or limit the progression of periodontal diseases, in an experimental model. CLINICAL RELEVANCE: The effect of an environmental microorganism with potential action against bone loss in animal models with ligature-induced periodontitis represents the possibility of understanding the etiopathogenesis of periodontal diseases in populations exposed to C. violaceum and the possibility of new probiotics and antimicrobials. This would imply new preventive and therapeutic possibilities.
Subject(s)
Alveolar Bone Loss , Anti-Bacterial Agents , Periodontitis , Animals , Alveolar Bone Loss/prevention & control , Alveolar Bone Loss/etiology , Anti-Bacterial Agents/administration & dosage , Disease Models, Animal , Periodontitis/drug therapy , Periodontitis/prevention & control , Periodontitis/complications , Indoles/administration & dosage , Double-Blind Method , Porphyromonas gingivalis/drug effectsABSTRACT
Epidemiological studies reveal significant associations between periodontitis and oral cancer. However, knowledge about the contribution of periodontal pathogens to oral cancer and potential regulatory mechanisms involved is limited. Previously, we showed that nisin, a bacteriocin and commonly used food preservative, reduced oral cancer tumorigenesis and extended the life expectancy in tumor-bearing mice. In addition, nisin has antimicrobial effects on key periodontal pathogens. Thus, the purpose of this study was to test the hypothesis that key periodontal pathogens (Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum) promote oral cancer via specific host-bacterial interactions, and that bacteriocin/nisin therapy may modulate these responses. All three periodontal pathogens enhanced oral squamous cell carcinoma (OSCC) cell migration, invasion, tumorsphere formation, and tumorigenesis in vivo, without significantly affecting cell proliferation or apoptosis. In contrast, oral commensal bacteria did not affect OSCC cell migration. Pathogen-enhanced OSCC cell migration was mediated via integrin alpha V and FAK activation, since stably blocking alpha V or FAK expression abrogated these effects. Nisin inhibited these pathogen-mediated processes. Further, Treponema denticola induced TLR2 and 4 and MyD88 expression. Stable suppression of MyD88 significantly inhibited Treponema denticola-induced FAK activation and abrogated pathogen-induced migration. Together, these data demonstrate that periodontal pathogens contribute to a highly aggressive cancer phenotype via crosstalk between TLR/MyD88 and integrin/FAK signaling. Nisin can modulate these pathogen-mediated effects, and thus has therapeutic potential as an antimicrobial and anti-tumorigenic agent.
Subject(s)
Bacteroidaceae Infections/drug therapy , Carcinoma, Squamous Cell/drug therapy , Mouth Neoplasms/drug therapy , Periodontitis/drug therapy , Porphyromonas gingivalis/drug effects , Probiotics/pharmacology , Animals , Apoptosis , Bacteroidaceae Infections/metabolism , Bacteroidaceae Infections/microbiology , Bacteroidaceae Infections/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Cell Movement , Cell Proliferation , Focal Adhesion Kinase 1/genetics , Focal Adhesion Kinase 1/metabolism , Humans , Integrins/genetics , Integrins/metabolism , Mice , Mice, Nude , Mouth Neoplasms/metabolism , Mouth Neoplasms/microbiology , Mouth Neoplasms/pathology , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Periodontitis/metabolism , Periodontitis/microbiology , Periodontitis/pathology , Porphyromonas gingivalis/pathogenicity , Toll-Like Receptor 2/genetics , Toll-Like Receptor 2/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Alzheimer's disease (AD) is a progressive neurological illness that causes dementia mainly in the elderly. The challenging obstacles related to AD has freaked global healthcare system to encourage scientists in developing novel therapeutic startegies to overcome with the fatal disease. The current treatment therapy of AD provides only symptomatic relief and to some extent disease-modifying effects. The current approach for AD treatment involves designing of cholinergic inhibitors, Aß disaggregation inducing agents, tau inhibitors and several antioxidants. Hence, extensive research on AD therapy urgently requires a deep understanding of its pathophysiology and exploration of various chemical scaffolds to design and develop a potential drug candidate for the treatment. Various issues linked between disease and therapy need to be considered such as BBB penetration capability, clinical failure and multifaceted pathophisiology requires a proper attention to develop a lead candidate. This review article covers all probable mechanisms including one of the recent areas for investigation i.e., lipid dyshomeostasis, pathogenic involvement of P. gingivalis and neurovascular dysfunction, recently reported molecules and drugs under clinical investigations and approved by FDA for AD treatment. Our summarized information on AD will attract the researchers to understand and explore current status and structural modifications of the recently reported heterocyclic derivatives in drug development for AD therapy.
Subject(s)
Alzheimer Disease/drug therapy , Anti-Bacterial Agents/pharmacology , Heterocyclic Compounds/pharmacology , Neuroprotective Agents/pharmacology , Porphyromonas gingivalis/drug effects , Alzheimer Disease/metabolism , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/chemistry , Humans , Microbial Sensitivity Tests , Molecular Structure , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistryABSTRACT
The ethanol extracts of 155 different foodstuffs containing medicinal plants were investigated for their biofilm eradication activities against pathogenic bacteria. A combined method of a colorimetric microbial viability assay based on reduction of a tetrazolium salt (WST-8) and a biofilm formation technique on the 96-pins of a microtiter plate lid was used to screen the biofilm eradication activities of foodstuffs. The ethanol extracts of licorice (Glycyrrhiza glabra) showed potent biofilm eradication activities against Streptococcus mutans, Staphylococcus aureus, and Porphyromonas gingivalis. Among the antimicrobial constituents in licorice, glabridin had the most potent eradication activities against microbial biofilms. The minimum biofilm eradication concentration of glabridin was 25-50 µg/ml. Furthermore, the combination of glabridin with É-poly-L-lysine, a food additive, could result in broad biofilm eradication activities towards a wide variety of bacteria associated with infection, including Escherichia coli and Pseudomonas aeruginosa.
Subject(s)
Biofilms/drug effects , Flavonoids/pharmacology , Glycyrrhiza/chemistry , Isoflavones/pharmacology , Phenols/pharmacology , Plant Extracts/pharmacology , Polylysine/pharmacology , Anti-Bacterial Agents/pharmacology , Ethanol , Food Additives , Microbial Sensitivity Tests , Microbial Viability/drug effects , Porphyromonas gingivalis/drug effects , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Streptococcus mutans/drug effectsABSTRACT
Dental pulp and periapical diseases are common conditions in stomatology, caused by various pathogenic microorganisms. Antimicrobial peptides, as new antibiotics, offer promising applications in the irrigation and disinfection medicaments for root canals.One patient with chronic periapical periodontitis was selected to extract the clinical pathogenic bacteria. Porphyromonas gingivalis (Pg) (ATCC 33,277), Streptococcus mutans (Sm) (ATCC 25,175), and Prevotella intermedius (Pi) (ATCC 25,611) were used as test strains. The effects of plantaricin (Pln) 149 on the biofilm formation and growth in infected root canals were evaluated by RT-PCR, laser confocal scanning microscopy, and bacterial diversity analysis. In addition, the cytotoxicity of Pln 149 (100 µg/mL) to human dental pulp stem cells (hDPSCs) was assessed using an MTT assay. Pln 149 exhibited significant inhibitory effects on Pg Sm and Pi (P < 0.05), with significant differences in the biofilm images of the laser confocal scanning microscope (P < 0.05). There were no significant differences in hDPSCs viability or proliferation between the Pln 149 and control groups. Considering the excellent antimicrobial effects and low cytotoxicity, we suggest that Pln 149 might be a promising option for root canal irrigation solutions.
Subject(s)
Anti-Bacterial Agents , Bacteriocins , Dental Pulp Cavity , Root Canal Irrigants , Root Canal Preparation , Humans , Anti-Bacterial Agents/pharmacology , Dental Pulp Cavity/microbiology , Root Canal Irrigants/chemistry , Root Canal Irrigants/pharmacology , Sodium Hypochlorite/pharmacology , Bacteriocins/pharmacology , Porphyromonas gingivalis/drug effects , Porphyromonas gingivalis/isolation & purification , Streptococcus mutans/drug effects , Streptococcus mutans/isolation & purification , Prevotella/drug effects , Prevotella/isolation & purificationABSTRACT
Periodontitis is a common inflammatory disease that affects the teeth-supporting tissue and causes bone and tooth loss. Moreover, in a worldwide population, periodontal disease is often associated with cardiovascular diseases. Emerging studies have reported that one of the major pathogens related to periodontitis is Porphyromonas gingivalis (P. gingivalis), which triggers the inflammatory intracellular cascade. Here, we hypothesized a possible protective effect of ascorbic acid (AA) in the restoration of the physiological molecular pathway after exposure to lipopolysaccharide derived from P. gingivalis (LPS-G). In particular, human gingiva-derived mesenchymal stem cells (hGMSCs) and endothelial-differentiated hGMSCs (e-hGMSCs) exposed to LPS-G showed upregulation of p300 and downregulation of DNA methyltransferase 1 (DNMT1), proteins associated with DNA methylation and histone acetylation. The co-treatment of AA and LPS-G showed a physiological expression of p300 and DNMT1 in hGMSCs and e-hGMSCs. Moreover, the inflammatory process triggered by LPS-G was demonstrated by evaluation of reactive oxygen species (ROS) and their intracellular localization. AA exposure re-established the physiological ROS levels. Despite the limitations of in vitro study, these findings collectively expand our knowledge regarding the molecular pathways involved in periodontal disease, and suggest the involvement of epigenetic modifications in the development of periodontitis.
Subject(s)
Ascorbic Acid/pharmacology , Endothelial Cells/drug effects , Mesenchymal Stem Cells/drug effects , Porphyromonas gingivalis/drug effects , Protective Agents/pharmacology , Ascorbic Acid/chemistry , Endothelial Cells/metabolism , Epigenesis, Genetic/drug effects , Humans , Mesenchymal Stem Cells/metabolism , Porphyromonas gingivalis/metabolism , Protective Agents/chemistryABSTRACT
We successfully fabricated the hydrogenated TiO2 nanotubes/Ti foil (H-TNTs/f-Ti) composite via one-step anodization and two-step annealing. H-TNTs/f-Ti composite had a higher visible light-induced photoelectric response and more hydroxyl functional groups compared with Ti foil and unmodified TiO2 nanotubes/Ti foil composite, which contributed to limiting the proliferation of Streptococcus mutans and Porphyromonas gingivalis, promoting the proliferation of MC3T3-E1 cell on the hydroxylated surface, and improving the biocompatibility with osteogenic cells. Our study provides a simple and effective method for significantly improving dental implant efficacy.
Subject(s)
Anti-Bacterial Agents , Cell Proliferation , Nanotubes/chemistry , Titanium , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cell Line , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Hydrogenation , Mice , Osteoblasts/drug effects , Photolysis , Porphyromonas gingivalis/drug effects , Streptococcus mutans/drug effects , Titanium/chemistry , Titanium/pharmacologyABSTRACT
This study aims to investigate the effect of antimicrobial photodynamic therapy (a-PDT) using a novel combination of sinoporphyrin sodium (DVDMS) and light-emitting diode (LED) with a wavelength of 390-400 nm on Porphyromonas gingivalis in vitro. Absorption spectrum of DVDMS was determined by spectrometer for selecting suitable wavelength light source. The uptake of DVDMS by P. gingivalis was evaluated according to fluorescence intensity detected by a spectrometer. Then effects of DVDMS alone, 390-400 nm LED alone, and photodynamic therapy produced by 10, 20, 40, and 80 µg/mL DVDMS and 390-400 nm LED on the suspension of P. gingivalis were evaluated by counting the number of colony forming units (CFU) after incubation. In the experiment, the LED illumination time was 30, 60, 90, 120, 180, 240, and 360 s, respectively, and the corresponding energy density was 1, 2, 3, 4, 6, 8, and 12 J/cm2, respectively. According to the absorption spectrum of DVDMS, the 390-400-nm light emitted by the LED was selected as the light source. The fluorescence intensity of DVDMS on P. gingivalis increased significantly at 5 min, and with the extension of time, it decreased at 30 min. DVDMS alone did not produce a significant toxicity on P. gingivalis compared with PBS (p = 0.979). While 390-400 nm LED alone had a certain bactericidal effect on P. gingivalis, the bactericidal effect was more obvious as the light dose increased (p < 0.001). The effect of a-PDT produced by 20, 40, and 80 µg/mL DVDMS and 390-400 nm LED were significantly better than that of 390-400 nm LED alone (p < 0.05). Both DVDMS concentration and light dose could enchance the bactericidal effect. The strongest photo-killing effect was generated by 80 µg/mL DVDMS with 360 s illumination (energy density is 12 J/cm2), and the log reduction of bacteria was 5.69 ± 1.70. a-PDT using the combination of DVDMS with 390-400 nm LED shows promise as a new treatment modality for pathogens elimination in periodontal therapy.
Subject(s)
Anti-Bacterial Agents/pharmacology , Photochemotherapy , Porphyrins/pharmacology , Porphyromonas gingivalis/drug effects , Porphyromonas gingivalis/radiation effects , Adsorption , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/toxicity , Dose-Response Relationship, Radiation , FluorescenceABSTRACT
Antimicrobial peptides (AMPs) have been an attractive alternative to traditional antibiotics. However, considerable efforts are needed to further enhance their antimicrobial effects and stability against bacterial degradation. Tetrahedral framework nucleic acids (tFNAs), a new class of three-dimensional nanostructures, have been utilized as a delivery vehicle. In this study, tFNAs were combined for the first time with an antimicrobial peptide GL13K, and the effects of the resultant complexes against Escherichia coli (sensitive to GL13K) and Porphyromonas gingivalis (capable of degrading GL13K) were investigated. tFNA-based delivery enhanced the effects of GL13K against E. coli. The tFNA vehicle both increased bacterial uptake and promoted membrane destabilization. Moreover, it enhanced the effects of GL13K against P. gingivalis by protecting the peptide against degradation in the protease-rich extracellular environment. Therefore, tFNA provides a delivery vehicle for AMPs targeting a broad range of disease.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Delivery Systems , Escherichia coli/drug effects , Nucleic Acids , Oligopeptides/pharmacology , Porphyromonas gingivalis/drug effectsABSTRACT
AIMS: To prepare a novel antimicrobial peptide Nal-P-113 loaded poly (ethylene glycol) combined chitosan nanoparticles (Nal-P-113-PEG-CSNPs) for root caries restorations to control the periodontitis related pathogens in periodontitis care. METHODS: Nanoparticles were prepared by simple polymerisation method and characterised using effective analytical methods (TEM, UV, etc.). The antimicrobial activity and biofilm formation of Nal-P-113-PEG-CSNPs was tested against periodontal bacterial pathogens by different in vitro methods. RESULTS: The size of Nal-P-113 loaded PEG-Chitosn nanoparticles was 216.2 ± 1.6 nm. The drug encapsulation efficiency (%EE (w/w) of Nal-P-113-PEG-CSNPs was found to be 89.33 ± 1.67% (w/w). The antimicrobial examination showed that prepared NPs have effectively inhibited the growth of Fusobacterium nucleatum, Streptococcus gordonii, and Porphyromonas gingivalis with the MIC of 23 µg/mL, 6 µg/mL and 31 µg/mL, respectively. CONCLUSIONS: The prepared antimicrobial peptide-loaded PEG-CSNPs provide excellent in vitro efficiency but, further studies are necessary to confirm its therapeutic efficacy on periodontitis care.