RESUMEN

Aim: The Insilco study uses deep learning algorithms to predict the protein-coding pg m RNA sequences. Material and methods: The NCBI GEO DATA SET GSE218606's GEO R tool discovered P.G's outer membrane vesicles' most differentially expressed mRNA. Genemania analyzed differentially expressed gene networks. Transcriptomics data were collected and labeled on P. gingivalis protein-coding mRNA sequence and pseudogene, lincRNA, and bidirectional promoter lincRNA. Orange, a machine learning tool, analyzed and predicted data after preprocessing. Naïve Bayes, neural networks, and gradient descent partition data into training and testing sets, yielding accurate results. Cross-validation, model accuracy, and ROC curve were evaluated after model validation. Results: Three models, Neural Networks, Naive Bayes, and Gradient Boosting, were evaluated using metrics like Area Under the Curve (AUC), Classification Accuracy (CA), F1 Score, Precision, Recall, and Specificity. Gradient Boosting achieved a balanced performance (AUC: 0.72, CA: 0.41, F1: 0.32) compared to Neural Networks (AUC: 0.721, CA: 0.391, F1: 0.314) and Naive Bayes (AUC: 0.701, CA: 0.172, F1: 0.114). While statistical tests revealed no significant differences between the models, Gradient Boosting exhibited a more balanced precision-recall relationship. Conclusion: In silico analysis using machine learning techniques successfully predicted protein-coding mRNA sequences within Porphyromonas gingivalis OMVs. Gradient Boosting outperformed other models (Neural Networks, Naive Bayes) by achieving a balanced performance across metrics like AUC, classification accuracy, and precision-recall, suggests its potential as a reliable tool for protein-coding mRNA prediction in P. gingivalis OMVs.

RESUMEN

Porphyromonas gingivalis uses a variety of mechanisms to actively interact with and promote the hydrolysis of red blood cells (RBCs) to obtain iron in the form of heme. In this study, we investigated the function of lipoprotein PG1881 which was previously shown to be up-regulated during subsurface growth and selectively enriched on outer membrane vesicles (OMVs). Our results show that wildtype strain W83 formed large aggregates encompassing RBCs whereas the PG1881 deletion mutant remained predominately as individual cells. Using a PG1881 antibody, immunofluorescence revealed that the wildtype strain's aggregation to RBCs involves an extracellular matrix enriched with PG1881. Our findings discover that RBCs elicit cell aggregation and matrix formation by P. gingivalis and that this process is promoted by an OMV-specific lipoprotein. We propose this strategy is advantageous for nutrient acquisition as well as dissemination from the oral cavity and survival of this periodontal pathogen.

RESUMEN

Bone regeneration plays a pivotal role in periodontal tissue repair. With advancements in biotechnology materials, the utilization of nanotechnology offers a reliable platform for bone restoration in periodontitis. In this study, we successfully established a long-term bacterial infection model using Porphyromonas gingivalis (P. gingivalis) with MOI = 50. CCK-8 and ROS immunofluorescence results demonstrated that the combined effect of Mg2+ and AS-IV significantly enhanced cell proliferation and effectively suppressed the inflammatory response during bacterial infection. Alkaline phosphatase and alizarin red staining revealed that the synergistic action of Mg2+ and AS-IV notably promoted osteogenic differentiation of MC3T3-E1 cells under P. gingivalis-infected conditions. Considering the properties of these two biomaterials, we fabricated polycaprolactone (PCL) artificial periosteum loaded with MgO and AS-IV using an electrostatic spinning technique. The findings indicated that PCL/MgO/AS-IV artificial periosteum exhibited excellent biocompatibility and hydrophilicity, thereby substantially enhancing cellular adhesion to its surface as well as augmenting cellular value-added rate. Moreover, efficient drug release from the PCL/MgO/AS-IV artificial bone membrane conferred remarkable antimicrobial activity along with in vitro osteogenic potentiality. The in vivo experiments conducted on animals further substantiated the exceptional properties exhibited by PCL/MgO/AS-IV artificial periosteum in bone defect repair. Additionally, it was observed that PCL/MgO/AS-IV artificial periosteum could modulate EphB4-EphrinB2 signaling to enhance osteogenic differentiation under P.gingivalis-infected conditions.This exciting outcome suggests that PCL/MgO/AS-IV artificial periosteum holds great promise as a biomaterial for treating periodontal bone loss.

RESUMEN

Porphyromonas gingivalis is the primary microbe in the "periodontal red complex" bacteria (PRCB) along with Tannerella forsythia and Treponema denticola, which are linked to periodontal disease (PD). These pathogens are also implicated in various systemic disorders, but their association with the incidence of gastrointestinal (GI) cancer is less explored. A systematic review followed by a meta-analysis was conducted as per standard guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2022) to find this association between GI cancers and PRCB after a literature search for full-text papers in the English language (between 2010 and 2023) in databases (Cochrane Library, PubMed, and Web of Science) with suitable keywords using the Boolean search strategy. Data extraction involved titles, abstracts, and full texts retrieved and scored by the modified Newcastle-Ottawa Scale. The data were analyzed by the Review Manager (RevMan 5.2, Cochrane Collaboration, Denmark). Standard Cochran Q test and I2 statistics (for heterogeneity) and a random effects model (pooled OR with 95% CI) were applied to report results. P. gingivalis among the PRCB was linked to GI cancers (OR: 2.16; 95% CI: 1.34-3.47). T. forsythia and T. denticola did not show meaningful associations as per existing evidence for GI cancers.

RESUMEN

OBJECTIVE: This study aimed to evaluate the impact of silver nanoparticles (AgNPs) synthesized from propolis on the formation of Porphyromonas gingivalis biofilms. MATERIAL AND METHODS: AgNPs were synthesized from propolis, and their inhibitory effect on P. gingivalis biofilm formation was assessed. Different concentrations of AgNPs (0.1%, 0.3%, and 0.5%) were tested to determine the dose-dependent antibacterial activity. RESULTS: The results of this study indicated that AgNPs exhibited an inhibitory effect on P. gingivalis biofilm formation. The antibacterial activity of AgNPs was dose-dependent, with concentrations of 0.1%, 0.3%, and 0.5% showing effectiveness. Notably, the concentration of 0.5% demonstrated the most significant anti-biofilm formation activity. CONCLUSION: The results of this study suggest that AgNPs synthesized from propolis have potential as an effective option for enhancing periodontal treatment outcomes. The inhibitory effect of AgNPs on P. gingivalis biofilm formation highlights their potential as alternative antimicrobial agents in the management of periodontal diseases.

Asunto(s)

Antibacterianos , Biopelículas , Nanopartículas del Metal , Porphyromonas gingivalis , Plata , Porphyromonas gingivalis/efectos de los fármacos , Biopelículas/efectos de los fármacos , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Tecnología Química Verde , Própolis/farmacología , Própolis/química , Pruebas de Sensibilidad Microbiana , Relación Dosis-Respuesta a Droga , Humanos

RESUMEN

Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis' virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.

RESUMEN

Porphyromonas gingivalis (Pg), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against P. gingivalis (W83) and Pg-derived lipopolysaccharide (Pg-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells. IEC-6 (ATCC, CRL-1592) cells were pretreated with or without CNM (100 µM), in the presence or absence of P. gingivalis (strain W83, 109 MOI) or Pg-LPS (1, 10, and 100 µg/mL), respectively, between 0-72 h time points by adopting a co-culture method. Intestinal barrier function, cytokine secretion, and intestinal oxidative stress protein markers were analyzed. P. gingivalis or Pg-LPS significantly (p < 0.05) increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels expressing oxidative stress damage. Pg-LPS, as well as Pg alone, induces inflammatory cytokines via TLR-4 signaling. Furthermore, infection reduced Nrf2 and NAD(P)H quinone dehydrogenase 1 (NQO1). Interestingly, inducible nitric oxide synthase (iNOS) protein expression significantly (p < 0.05) increased with Pg-LPS or Pg infection, with elevated levels of nitric oxide (NO). CNM treatment suppressed both Pg- and Pg-LPS-induced intestinal oxidative stress damage by reducing ROS, MDA, and NO production. Furthermore, CNM treatment significantly upregulated the expression of tight junction proteins via increasing the phosphorylation levels of PI3K/Akt/Nrf2 suppressing inflammatory cytokines. CNM protected against Pg infection-induced intestinal epithelial barrier dysfunction by activating the PI3K/Akt-mediated Nrf2 signaling pathway in IEC-6 cells.

Asunto(s)

Acroleína , Mucosa Intestinal , Factor 2 Relacionado con NF-E2 , Óxido Nítrico , Fosfatidilinositol 3-Quinasas , Porphyromonas gingivalis , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismo , Acroleína/análogos & derivados , Acroleína/farmacología , Animales , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Porphyromonas gingivalis/patogenicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Óxido Nítrico/metabolismo , Línea Celular , Lipopolisacáridos , Estrés Oxidativo/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Citocinas/metabolismo

RESUMEN

Chronic periodontitis (CP), an inflammatory disease of periodontal tissues driven by a dysbiotic subgingival bacterial biofilm, is also associated with several systemic diseases, including rheumatoid arthritis (RA). Porphyromonas gingivalis, one of the bacterial species implicated in CP as a keystone pathogen produces peptidyl arginine deiminase (PPAD) that citrullinates C-terminal arginine residues in proteins and peptides. Autoimmunity to citrullinated epitopes is crucial in RA, hence PPAD activity is considered a possible mechanistic link between CP and RA. Here we determined the PPAD enzymatic activity produced by clinical isolates of P. gingivalis, sequenced the ppad gene, and correlated the results with clinical determinants of CP in patients from whom the bacteria were isolated. The analysis revealed variations in PPAD activity and genetic diversity of the ppad gene in clinical P. gingivalis isolates. Interestingly, the severity of CP was correlated with a higher level of PPAD activity that was associated with the presence of a triple mutation (G231N, E232T, N235D) in PPAD in comparison to W83 and ATCC 33277 type strains. The relation between mutations and enhanced activity was verified by directed mutagenesis which showed that all three amino acid residue substitutions must be introduced into PPAD expressed by the type strains to obtain the super-active enzyme. Cumulatively, these results may lead to the development of novel prognostic tools to assess the progress of CP in the context of associated RA by analyzing the ppad genotype in CP patients infected with P. gingivalis.

Asunto(s)

Periodontitis Crónica , Porphyromonas gingivalis , Humanos , Desiminasas de la Arginina Proteica/genética , Desiminasas de la Arginina Proteica/metabolismo , Péptidos , Periodoncio/metabolismo , Periodontitis Crónica/genética

RESUMEN

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.

Asunto(s)

Pérdida de Hueso Alveolar , Curcumina , Compuestos Organometálicos , Periodontitis , Piridinas , Ratas , Animales , Curcumina/farmacología , Curcumina/uso terapéutico , Hidrogeles/uso terapéutico , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Periodontitis/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/metabolismo , Porphyromonas gingivalis

RESUMEN

The low oxygen environment of the periodontal pocket favors pathogenic anaerobes' growth, biofilm formation, and quick recurrence after periodontal treatment. In contrast, oxygen is detrimental to anaerobes, such as Porphyromonas gingivalis (P. gingivalis), since they lack a complete anti-oxidation mechanism to detoxify the oxygen challenge. Therefore, consistently feeding pathogenic anaerobes with abundant oxygen would be an effective strategy to combat them. Here, we reported injectable oxygen-generating hydrogels as oxygen mediators to alleviate the local anaerobic environment and eliminate periodontal pathogens. Gelatin methacrylate (GelMA) hydrogels loaded with calcium peroxide (CPO) possessed excellent injectability and exhibited burst releases of oxygen within 24 h with a 40 % oxygen tension peak. CPO-GelMA hydrogels with CPO concentrations of 5, 10, and 15 % reduced 60, 99, and 89.9 % viable P. gingivalis, respectively. Five percentage CPO-GelMA hydrogel downregulated gingipain and fimA gene expression in P. gingivalis without resistance development. Moreover, the CPO-GelMA hydrogels remarkably prevented biofilm formation and eradicated both monospecies and multispecies bacterial biofilms. In conclusion, CPO-GelMA hydrogels exert remarkable antimicrobial and antibiofilm effects on subgingival biofilms, providing a promising strategy for periodontal treatment.

Asunto(s)

Gelatina , Hidrogeles , Peróxidos , Hidrogeles/farmacología , Gelatina/farmacología , Metacrilatos/farmacología , Oxígeno , Biopelículas

RESUMEN

BACKGROUND: Arg-gingipain A (rgpA) and Arg-gingipain B (rgpB) are crucial virulence factors associated with Porphyromonas gingivalis (P. gingivalis) and have been recognized as promising targets for antibacterial vaccines. Although vaccines containing rgpA have shown efficacy, the incorporation of rgpB, which lacks the haemagglutinin adhesin (HA) domain, diminishes the vaccine's effectiveness. This study aims to assess the immunogenicity of the functional HA domain of rgpA in mouse periodontitis models. METHODS: A total of 24 mice were randomly divided into four groups, each receiving different immune injections: group A received phosphate-buffered saline (PBS) as an empty control; group B received pVAX1 as a negative control (NC); group C received pVAX1-HA; and group D received pVAX1-rgpA. The mice were subjected to intramuscular injections every two weeks for a total of three administrations. Prior to each immunization, blood samples were collected for antibody detection under isoflurane anesthesia. Following the final immunization, periodontitis was induced two weeks later by using sutures soaked in a P. gingivalis solution. The mice were euthanized after an additional two-week period. To assess the safety of the procedure, major organs were examined through hematoxylin-eosin (HE) staining. Subsequently, the levels of IgG, IgG1, and IgG2a in the serum were quantified via enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of inflammatory factors in the gingiva, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-α), was determined using quantitative real-time reverse transcript PCR (qRT-PCR). The extent of bone loss in periodontal tissues was evaluated using micro-computed tomography (micro-CT) and HE staining. RESULTS: HE staining of the organs confirmed the absence of vaccine-induced toxicity in vivo. After the second immunization, both the rgpA and HA groups displayed significantly higher specific IgG titers in comparison to the NC and PBS groups (p < 0.05). Furthermore, the rgpA and HA groups exhibited a noteworthy predominance of IgG1 antibodies after three immunization doses, while there was a noticeable reduction in IgG2a levels observed following ligation with P. gingivalis sutures, as opposed to the NC and PBS groups (p < 0.05). Additionally, both the HA and rgpA groups showed a significant decrease in the expression of inflammatory factors such as IL-6, IL-1ß, and TNF-α, as well as a reduction in bone loss around periodontitis-affected teeth, when compared to the NC and PBS groups (p < 0.05). CONCLUSIONS: The results of this study demonstrate that the rgpA-engineered/functionalized HA gene vaccine is capable of eliciting a potent prophylactic immune response against P. gingivalis-induced periodontitis, effectively serving as an immunogenic and protective agent in vivo.

Asunto(s)

Periodontitis , Vacunas de ADN , Ratones , Animales , Cisteína-Endopeptidasas Gingipaínas , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Vacunas de ADN/uso terapéutico , Porphyromonas gingivalis/genética , Interleucina-6 , Factor de Necrosis Tumoral alfa , Microtomografía por Rayos X , Adhesinas Bacterianas , Vacunación , Periodontitis/prevención & control , Inmunoglobulina G

RESUMEN

Periodontal disease is a risk factor for head and neck squamous cell carcinoma (HNSCC), and Porphyromonas gingivalis, a major periodontal pathogen, has been identified as a specific and potentially independent microbial factor that increases the risk of cancer mortality. Gene expression in HNSCC due to P. gingivalis infection and how changes in gene expression affect the prognosis of HNSCC patients are not clarified. When P. gingivalis was cultured with HNSCC cells, it efficiently adhered to these cells and enhanced their invasive ability. A transcriptome analysis of P. gingivalis -infected HNSCC cells showed that genes related to migration, including CCL20, CITED2, CTGF, C8orf44-SGK3, DUSP10, EGR3, FUZ, HBEGF, IL1B, IL24, JUN, PLAU, PTGS2, P2RY1, SEMA7A, SGK1 and SIX2, were highly up- or down-regulated. The expression of up-regulated genes was examined using the expression data of HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database, and the expression of 5 genes, including PLAU, was found to be higher in cancer tissue than in solid normal tissue. An analysis of protein-protein interactions revealed that these 5 genes formed a dense network. A Cox regression analysis showed that high PLAU expression levels were associated with a poor prognosis in patients with TCGA-HNSCC. Furthermore, the prognostic impact correlated with tumour size and the presence or absence of lymph node metastasis. Collectively, these results suggest the potential of PLAU as a molecular prognostic marker in HNSCC patients. Further in vivo and in vitro studies are needed to verify the findings of this study.

Asunto(s)

Neoplasias de Cabeza y Cuello , Proteínas de la Membrana , Porphyromonas gingivalis , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Biomarcadores de Tumor/genética , Fosfatasas de Especificidad Dual/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/microbiología , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética , Porphyromonas gingivalis/aislamiento & purificación , Pronóstico , Proteínas Represoras/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/microbiología , Transactivadores/genética , Proteínas de la Membrana/genética

RESUMEN

OBJECTIVE: Disruption of the gingival epithelial barrier is often mediated by aging or the pathogen Porphyromonas gingivalis. This study examined the combined effects of aging and P. gingivalis exposure on gingival epithelial barrier molecules. METHODS: In vitro experiments involved treating young- and senescence-induced primary human gingival epithelial progenitor cells (HGEPp) with P. gingivalis lipopolysaccharide (LPS). Transepithelial electrical resistance (TER) and paracellular permeability were measured. In vivo, male C57BL/6J mice aged 10 (young) and 80 (old) weeks were divided into four groups: young, old, young with P. gingivalis (Pg-Young) inoculation, and old with P. gingivalis (Pg-Old) inoculation. P. gingivalis was inoculated orally thrice a week for 5 weeks. The mice were sacrificed 30 days after the last inoculation, and samples were collected for further procedures. The junctional molecules (Claudin-1, Claudin-2, E-cadherin, and Connexin) were analyzed for mRNA expression using qRT-PCR and protein production using western blotting and immunohistochemistry. The alveolar bone loss and inflammatory cytokine levels in gingival tissues were also assessed. RESULTS: LPS-treated senescent cells exhibited a pronounced reduction in TER, increased permeability to albumin protein, significant upregulation of Claudin-1 and Claudin-2, and significant downregulation of E-cadherin and Connexin. Furthermore, the Pg-Old group showed identical results with aging in addition to an increase in alveolar bone loss, significantly higher than that in the other groups. CONCLUSION: In conclusion, the host susceptibility to periodontal pathogens increases with age through changes in the gingival epithelial barrier molecules.

Asunto(s)

Pérdida de Hueso Alveolar , Porphyromonas gingivalis , Masculino , Humanos , Animales , Ratones , Porphyromonas gingivalis/metabolismo , Claudina-1/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Claudina-2/metabolismo , Ratones Endogámicos C57BL , Cadherinas/metabolismo , Envejecimiento , Conexinas/metabolismo

RESUMEN

BACKGROUND: Cementoblasts on the tooth-root surface are responsible for cementum formation (cementogenesis) and sensitive to Porphyromonas gingivalis stimulation. We have previously proved transcription factor CXXC-type zinc finger protein 5 (CXXC5) participates in cementogenesis. Here, we aimed to elucidate the mechanism in which CXXC5 regulates P. gingivalis-inhibited cementogenesis from the perspective of mitochondrial biogenesis. METHODS: In vivo, periapical lesions were induced in mouse mandibular first molars by pulp exposure, and P. gingivalis was applied into the root canals. In vitro, a cementoblast cell line (OCCM-30) was induced cementogenesis and submitted for RNA sequencing. These cells were co-cultured with P. gingivalis and examined for osteogenic ability and mitochondrial biogenesis. Cells with stable CXXC5 overexpression were constructed by lentivirus transduction, and PGC-1α (central inducer of mitochondrial biogenesis) was down-regulated by siRNA transfection. RESULTS: Periapical lesions were enlarged, and PGC-1α expression was reduced by P. gingivalis treatment. Upon apical inflammation, Cxxc5 expression decreased with Il-6 upregulation. RNA sequencing showed enhanced expression of osteogenic markers, Cxxc5, and mitochondrial biogenesis markers during cementogenesis. P. gingivalis suppressed osteogenic capacities, mitochondrial biogenesis markers, mitochondrial (mt)DNA copy number, and cellular ATP content of cementoblasts, whereas CXXC5 overexpression rescued these effects. PGC-1α knockdown dramatically impaired cementoblast differentiation, confirming the role of mitochondrial biogenesis on cementogenesis. CONCLUSIONS: CXXC5 is a P. gingivalis-sensitive transcription factor that positively regulates cementogenesis by influencing PGC-1α-dependent mitochondrial biogenesis. Video Abstract.

Asunto(s)

Cementogénesis , Mitocondrias , Biogénesis de Organelos , Animales , Ratones , Línea Celular , Cementogénesis/genética , Cementogénesis/fisiología , ADN Mitocondrial/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Factores de Transcripción/metabolismo , Mitocondrias/metabolismo

RESUMEN

BACKGROUND: The relationship between the major periodontal bacteria, Porphyromonas gingivalis, and the pathogenesis of IgA nephropathy (IgAN)-particularly with respect to galactose-deficient IgA1 (Gd-IgA1)-has not been fully elucidated. METHODS: Saliva samples from 30 IgAN patients and 44 patients with chronic kidney disease (CKD) were subjected to analysis of P. gingivalis status via polymerase chain reaction using a set of P. gingivalis-specific primers. The associations between P. gingivalis presence and clinical parameters, including plasma Gd-IgA1, were analyzed in each group. RESULTS: Compared with the CKD group, the IgAN group demonstrated significantly higher plasma Gd-IgA1 levels (p < 0.05). Compared with the P. gingivalis-negative subgroup, the P. gingivalis-positive subgroup exhibited significantly higher plasma Gd-IgA1 levels in both IgAN and CKD patients (p < 0.05). Additionally, among IgAN patients, the P. gingivalis-positive subgroup displayed significantly higher plasma Gd-IgA1 and urine protein levels, compared with the P. gingivalis-negative subgroup (p < 0.05). With respect to renal biopsy findings, the frequencies of segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis were significantly greater in the P. gingivalis-positive subgroup than in the P. gingivalis-negative subgroup, according to the Oxford classification of IgAN (p < 0.05). CONCLUSION: Our findings suggest an association between the presence of P. gingivalis in the oral cavity and the pathogenesis of IgAN, mediated by increased levels of Gd-IgA1.

Asunto(s)

Glomerulonefritis por IGA , Insuficiencia Renal Crónica , Humanos , Glomerulonefritis por IGA/patología , Porphyromonas gingivalis/metabolismo , Galactosa/metabolismo , Inmunoglobulina A/metabolismo , Boca

RESUMEN

We found that GroEL in Porphyromonas gingivalis accelerated tumor growth and increased mortality in tumor-bearing mice; GroEL promoted proangiogenic function, which may be the reason for promoting tumor growth. To understand the regulatory mechanisms by which GroEL increases the proangiogenic function of endothelial progenitor cells (EPCs), we explored in this study. In EPCs, MTT assay, wound-healing assay, and tube formation assay were performed to analyze its activity. Western blot and immunoprecipitation were used to study the protein expression along with next-generation sequencing for miRNA expression. Finally, a murine tumorigenesis animal model was used to confirm the results of in vitro. The results indicated that thrombomodulin (TM) direct interacts with PI3 K/Akt to inhibit the activation of signaling pathways. When the expression of TM is decreased by GroEL stimulation, molecules in the PI3 K/Akt signaling axis are released and activated, resulting in increased migration and tube formation of EPCs. In addition, GroEL inhibits TM mRNA expression by activating miR-1248, miR-1291, and miR-5701. Losing the functions of miR-1248, miR-1291, and miR-5701 can effectively alleviate the GroEL-induced decrease in TM protein levels and inhibit the proangiogenic abilities of EPCs. These results were also confirmed in animal experiments. In conclusion, the intracellular domain of the TM of EPCs plays a negative regulatory role in the proangiogenic capabilities of EPCs, mainly through direct interaction between TM and PI3 K/Akt to inhibit the activation of signaling pathways. The effects of GroEL on tumor growth can be reduced by inhibiting the proangiogenic properties of EPCs through the inhibition of the expression of specific miRNAs.

Asunto(s)

Células Progenitoras Endoteliales , MicroARNs , Neoplasias , Ratones , Animales , MicroARNs/genética , MicroARNs/metabolismo , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/patología , Porphyromonas gingivalis/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Trombomodulina/genética , Trombomodulina/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Neovascularización Fisiológica/fisiología

RESUMEN

Doenças periodontais e síndrome metabólica estão relacionadas a condições multifatoriais complicadas. No entanto, a relação ainda não é evidente. A insuficiência de estrogênio pode estar correlacionada a essa condição, possivelmente causada pela remoção dos ovários e infecção por Porphyromonas gingivalis (P. gingivalis). Este estudo teve como objetivo avaliar o efeito da disfunção ovariana causada pela ovariectomia e infecção por P. gingivalis no desenvolvimento da síndrome metabólica. Este foi um estudo experimental de laboratório utilizando ratos fêmeas da linhagem Sprague Dawley. Os modelos animais foram divididos em quatro grupos: controle, ovariectomia (OVX), ovariectomia-periodontite (OPG) e periodontite (PG). O objetivo de cada tratamento em cada grupo foi obter disfunção ovariana. O grupo OVX foi submetido à cirurgia de remoção dos ovários; no grupo PG foi realizada a indução de P. gingivalis; e no grupo OPG foi feita uma combinação de ovariectomia e indução de P. gingivalis. O sangue foi coletado e observado nos dias 0, 3, 7, 14, 21 e 28. A amostra de sangue foi examinada para ácido úrico, colesterol, glicose e estrogênio. Os dados coletados foram todos examinados estatisticamente. Todos os grupos de tratamento apresentaram peso corporal e observações bioquímicas sanguíneas significativamente maiores do que o grupo controle, exceto o colesterol total (p<0,05). Além disso, a maioria das variáveis apresentou uma correlação entre os grupos com o peso corporal e indicadores bioquímicos sanguíneos, exceto o nível de ácido úrico no sangue (R>0,5). A síndrome metabólica foi desencadeada pela disfunção ovariana causada pela infecção por P. gingivalis após a ovariectomia. Ambos apresentaram o mesmo risco. Mesmo a indução por P. gingivalis piorou a síndrome metabólica no grupo de modelos animais que foram submetidos à ovariectomia.(AU)

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Periodontal diseases and metabolic syndrome are related to complicated multifactorial conditions. However, the relationship is not yet evident. Estrogen insufficiency might correlate to this condition, possibly caused by ovarian removal and Porphyromonas gingivalis (P. gingivalis) infection. This study aimed to evaluate the effect of ovarian dysfunction caused by ovariectomy and P. gingivalis infection to metabolic syndrome development. This study was an experimental laboratory study using female rats Sprague Dawley Strain. Animal models were divided into four groups: control, ovariectomy (OVX), ovariectomy-periodontitis (OPG), and periodontitis (PG). The purpose of every treatment in each group was to induce ovarian dysfunction. The OVX group was undertaken ovaries removal surgery. PG was performed P. gingivalis induction. Therefore OPG was a combination of ovariectomy and P. gingivalis induction. Blood was drawn and observed on days 0, 3, 7, 14, 21, and 28. The blood sample was examined for uric acid, cholesterol, glucose and estrogen. The collected data were all statistically examined. All treatment groups presented body weight and blood biochemical observation significantly higher than the control group, except total cholesterol (p<0.05). Moreover, most variables presented a correlation between groups to body weight and biochemical blood indicators, except blood uric acid level (R>0.5). The metabolic syndrome was triggered by ovarian dysfunction brought on by P. gingivalis infection after ovariectomy. They both took the same risk. Even P. gingivalis induction made metabolic syndrome in the group of animal models which underwent ovariectomy worse (AU)

Asunto(s)

Animales , Ratas , Ovariectomía , Síndrome Metabólico , Estrógenos

RESUMEN

We have developed an aptamer that specifically binds to Porphyromonas gingivalis to reduce the cellular damage caused by P. gingivalis infection and applied it as a biosensor. P. gingivalis is one of the major pathogens causing destructive periodontal disease among the periodontal microorganisms constituting complex biofilms. Porphyromonas gingivalis G-protein (PGP) known to play an important role in the transmission of germs was used as a target protein for the screening of aptamer. The aptamer that has binds to the G-protein of P. gingivalis, was screened and developed through the Systemic Evolution of Ligands by Exponential Energy (SELEX) method. Modified-Western blot analysis was performed with the aptamer which consisted of 38 single-stranded DNA to confirm the selectivity. ELONA (enzyme linked oligonucleotide assay) used to confirm that the aptamer was sensitive to PGP even at low concentration of 1 µg/ml. For the rapid detection of P. gingivalis, we constructed a surface plasmon resonance biosensor with SPREETA using the PGP aptamer. It was confirmed that PGP could be detected as low concentration as at 0.1 pM, which is the minimum concentration of aptamer sensor within 5 min. Based on these results, we have constructed a SPREETA biosensor based on aptamer that can bind to P. gingivalis G-protein. It can be used as an infection diagnosis system to rapidly diagnose and analyze oral diseases caused by P. gingivalis.

Asunto(s)

Técnicas Biosensibles , Enfermedades Periodontales , Humanos , Porphyromonas gingivalis/genética , Proteínas de Unión al GTP , Oligonucleótidos

RESUMEN

Background: Although widely explored in medicine, limited evidence exists in the literature regarding the efficacy of Lawsonia inermis Linn (henna) in the dental field. Aim: This study aimed to investigate the antibacterial effect of henna on Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis in vitro. Methods: The agar well diffusion and broth microdilution methods were used to evaluate the antibacterial effect of henna extracts. Dimethyl sulfoxide was used to prepare the ethanol extract of henna, and distilled water was used to prepare the water extract. For both ethanol and water extracts, 4 different concentrations were prepared as 15, 30, 60, and 120 mg/mL. Results: It was determined that the water and ethanol extracts of the henna samples did not show an inhibition zone on P.gingivalis and A.actinomycetemcomitans. As a result of the evaluations made with the broth microdilution method, it was found that the ethanol extract had a higher inhibitory effect on both bacteria, and both extracts had more inhibitory effects against A.actinomycetemcomitans. Conclusion: To understand the effect of henna on periodontal pathogens, more comprehensive in vitro studies should be performed on henna samples at different concentrations and with different bases.

RESUMEN

Cell death is a natural consequence of infection. However, although the induction of cell death was solely thought to benefit the pathogen, compelling data now show that the activation of cell death pathways serves as a nuanced antimicrobial strategy that couples pathogen elimination with the generation of inflammatory cytokines and the priming of innate and adaptive cellular immunity. Following cell death, the phagocytic uptake of the infected dead cell by antigen-presenting cells and the subsequent lysosomal fusion of the apoptotic body containing the pathogen serve as an important antimicrobial mechanism that furthers the development of downstream adaptive immune responses. Despite the complexity of regulated cell death pathways, pathogens are highly adept at evading them. Here, we provide an overview of the remarkable diversity of cell death and efferocytic pathways and discuss illustrative examples of virulence strategies employed by pathogens, including oral pathogens, to counter their activation and persist within the host.