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1.
J Cell Mol Med ; 28(4)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38363001

RESUMO

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.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas de Membrana , Porphyromonas gingivalis , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/genética , Fosfatases de Especificidade Dupla/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/microbiologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Porphyromonas gingivalis/isolamento & purificação , Prognóstico , Proteínas Repressoras/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Transativadores/genética , Proteínas de Membrana/genética
2.
Cell Commun Signal ; 22(1): 4, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167023

RESUMO

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.


Assuntos
Cementogênese , Mitocôndrias , Biogênese de Organelas , Animais , Camundongos , Linhagem Celular , Cementogênese/genética , Cementogênese/fisiologia , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Fatores de Transcrição/metabolismo , Mitocôndrias/metabolismo
3.
Clin Exp Nephrol ; 28(3): 192-200, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37806974

RESUMO

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.


Assuntos
Glomerulonefrite por IGA , Insuficiência Renal Crônica , Humanos , Glomerulonefrite por IGA/patologia , Porphyromonas gingivalis/metabolismo , Galactose/metabolismo , Imunoglobulina A/metabolismo , Boca
4.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731952

RESUMO

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.


Assuntos
Acroleína , Mucosa Intestinal , Fator 2 Relacionado a NF-E2 , Óxido Nítrico , Fosfatidilinositol 3-Quinases , Porphyromonas gingivalis , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Acroleína/análogos & derivados , Acroleína/farmacologia , Animais , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Porphyromonas gingivalis/patogenicidade , Fosfatidilinositol 3-Quinases/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Óxido Nítrico/metabolismo , Linhagem Celular , Lipopolissacarídeos , Estresse Oxidativo/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Citocinas/metabolismo
5.
BMC Oral Health ; 24(1): 395, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549147

RESUMO

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.


Assuntos
Perda do Osso Alveolar , Curcumina , Compostos Organometálicos , Periodontite , Piridinas , Ratos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , Hidrogéis/uso terapêutico , Modelos Animais de Doenças , Ratos Sprague-Dawley , Periodontite/metabolismo , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/metabolismo , Porphyromonas gingivalis
6.
J Clin Periodontol ; 50(9): 1253-1263, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37381658

RESUMO

AIM: Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, increases the risk of systemic diseases. P. gingivalis infection is closely associated with alcoholic liver disease (ALD), but the underlying mechanism remains unclear. We aimed to investigate the role of P. gingivalis in the pathogenesis of ALD. MATERIALS AND METHODS: An ALD mouse model was established using a Lieber-DeCarli liquid diet, and C57BL/6 mice were treated with P. gingivalis to detect the pathological indicators of ALD. RESULTS: Oral administration of P. gingivalis exacerbated alcohol-induced alterations in the gut microbiota, leading to gut barrier dysfunction and inflammatory response and disruption of the T-helper 17 cell/T-regulatory cell ratio in the colon of ALD mice. Furthermore, P. gingivalis worsened liver inflammation in ALD mice by increasing the protein expression of toll-like receptor 4 (TLR4) and p65, increasing the mRNA expression of interleukins-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) and up-regulating the transforming growth factor-beta 1 (TGF-ß1) and galectin-3 (Gal-3) production. CONCLUSIONS: These results indicate that P. gingivalis accelerates the pathogenesis of ALD via the oral-gut-liver axis, necessitating a new treatment strategy for patients with ALD complicated by periodontitis.


Assuntos
Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Animais , Camundongos , Porphyromonas gingivalis , Microbioma Gastrointestinal/genética , Camundongos Endogâmicos C57BL , Imunidade
7.
Oral Dis ; 29(5): 2297-2309, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35509129

RESUMO

OBJECTIVE: It aims to explore the effect of dental follicle cells-derived small extracellular vesicles (D-sEVs) with or without lipopolysaccharides (LPS) pretreating on the pathogenicity of Porphyromonas gingivalis (P. gingivalis). METHODS: The antibacterial effects of D-sEV were evaluated by measuring the growth, biofilm formation, gingipains, and type IX secretion system (T9SS) expression of P. gingivalis. And the influence of D-sEV on P. gingivalis adhesion, invasion, cytotoxicity, and host immune response was examined in gingival epithelial cells (GECs). Then P. gingivalis treated with D-sEV was applied to investigate the pathogenicity in experimental periodontitis of mice. RESULTS: It showed that both D-sEV and P. gingivalis LPS-pretreated D-sEV (L-D-sEV) could target P. gingivalis, inhibit their growth and biofilm formation, and hinder the attachment and invasion in GECs, therefore remarkably decreasing P. gingivalis cytotoxicity and the expression of IL-1ß and IL-6 in GECs. In addition, they significantly reduced the expression of P. gingivalis virulence factors (gingipains and T9SS). In vivo, it showed that the bacteria in the gingiva were significantly decreased after sEV treatment. Meanwhile, less bone loss and fewer inflammatory cells infiltration and osteoclast formation in D-sEV and L-D-sEV groups. CONCLUSION: Both D-sEV and L-D-sEV were proven to inhibit the pathogenicity of P. gingivalis and thus prevented the development of periodontitis.


Assuntos
Vesículas Extracelulares , Periodontite , Animais , Camundongos , Porphyromonas gingivalis/metabolismo , Virulência , Cisteína Endopeptidases Gingipaínas/metabolismo , Lipopolissacarídeos/farmacologia , Saco Dentário , Periodontite/metabolismo , Gengiva
8.
Ann Hepatol ; 28(2): 100887, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36646168

RESUMO

INTRODUCTION AND OBJECTIVES: Recent translational research indicated a bidirectional relationship between NASH (non-alcoholic steatohepatitis) and periodontitis; however, few clinical cohorts have studied this in detail. Thus we investigated this assumed association in a well-defined cohort. MATERIALS AND METHODS: Data were generated prospectively for 132 patients (32 patients with NASH and 100 unselected, consecutively collected, anonymized controls from a local dental practice): detailed periodontal parameters, i.e., pocket-probing-depths (PPD), bleeding-on-probing (BOP), plaque-index, and utilization of dental care were assessed and correlated with relevant hepatic parameters (liver stiffness via fibroscan, AST, ALT, bilirubin, and MELD-score). Gingiva samples were tested for Porphyromonas gingvalis (P.g.) and Actinobacillus actinomyctemcomitans (A.a.) by PCR. RESULTS: 87.5% of NASH patients and 47% of controls suffered from moderate to severe periodontitis (p=0.01). Liver stiffness was significantly correlated with elevated PPD (p=0.02) and BOP (p=0.03). 34 % of the NASH patients did not make use of regular dental health care. In these patients, AST (p=0.04), MELD score (p<0.01), and liver stiffness (p=0.01) were significantly elevated compared to those who see a dentist regularly. The severity of NASH was not associated with the intraoral detection of P.g. and A.a. CONCLUSIONS: The present study suggests that NASH might be associated with periodontitis, irrespective of the intraoral presence of P.g. and A.a. Moreover, regular dental care utilization might mitigate the course of NASH, and patients should be reminded by their hepatologists of the importance of regular dental visits. Future studies should investigate the role of regular dental care and additional anti-inflammatory treatments of the oral cavity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Doenças Periodontais , Periodontite , Humanos , Prevalência , Porphyromonas gingivalis , Doenças Periodontais/diagnóstico , Doenças Periodontais/epidemiologia , Doenças Periodontais/complicações , Periodontite/diagnóstico , Periodontite/epidemiologia , Periodontite/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações
9.
Lasers Med Sci ; 38(1): 112, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37103664

RESUMO

Periodontal disease is one of the most common chronic diseases in the oral cavity that causes tooth loss. Root scaling and leveling cannot eliminate all periodontal pathogens, and the use of antibacterial agents or lasers can increase the efficiency of mechanical methods. The aim of this study was to evaluate and compare the antibacterial activity of cadmium telluride nanocrystals in combination with 940-nm laser diode. Cadmium telluride nanocrystals were prepared by a green route of synthesis in aqueous medium. The results of this study showed that cadmium telluride nanocrystals significantly inhibit the growth of P. gingivalis. The antibacterial property of this nanocrystal increases with increasing its concentration, laser diode 940-nm irradiation and with increasing the time. It was shown that the antibacterial activity of combination of 940-nm laser diode and cadmium telluride nanocrystals is greater than the effect of either alone and can have a similar effect with its long-term presence of microorganisms. This is very important because it is not possible to use these nanocrystals in the mouth and in the periodontal bag for a long time.


Assuntos
Nanopartículas , Doenças Periodontais , Humanos , Bactérias Anaeróbias , Antibacterianos/farmacologia , Doenças Periodontais/tratamento farmacológico , Lasers Semicondutores/uso terapêutico , Porphyromonas gingivalis
10.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674463

RESUMO

Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, is associated with neuroinflammation. Periodontal disease increases with age; 70.1% of adults 65 years and older have periodontal problems. However, the P. gingivalis- lipopolysaccharide (LPS)induced mitochondrial dysfunction in neurodegenerative diseases remains elusive. In this study, we investigated the possible role of P. gingivalis-LPS in mitochondrial dysfunction during neurodegeneration. We found that P. gingivalis-LPS treatment activated toll-like receptor (TLR) 4 signaling and upregulated the expression of Alzheimer's disease-related dementia and neuroinflammatory markers. Furthermore, the LPS treatment significantly exacerbated the production of reactive oxygen species and reduced the mitochondrial membrane potential. Our study highlighted the pivotal role of P. gingivalis-LPS in the repression of serum response factor (SRF) and its co-factor p49/STRAP that regulate the actin cytoskeleton. The LPS treatment repressed the genes involved in mitochondrial function and biogenesis. P. gingivalis-LPS negatively altered oxidative phosphorylation and glycolysis and reduced total adenosine triphosphate (ATP) production. Additionally, it specifically altered the mitochondrial functions in complexes I, II, and IV of the mitochondrial electron transport chain. Thus, it is conceivable that P. gingivalis-LPS causes mitochondrial dysfunction through oxidative stress and inflammatory events in neurodegenerative diseases.


Assuntos
Lipopolissacarídeos , Doenças Neuroinflamatórias , Humanos , Adulto , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Porphyromonas gingivalis/metabolismo , Estresse Oxidativo , Mitocôndrias/metabolismo
11.
Int J Mol Sci ; 24(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37047666

RESUMO

Immune cell pattern-recognition receptors such as Toll-like receptors (TLRs) play important roles in the regulation of host responses to periodontal pathogens. Our previous studies have demonstrated that immune regulatory B cells were activated by TLRs and alleviated periodontitis inflammation and bone loss. The purpose of this study is to determine the role of TLR9 signaling in the activation and IL-10 production of the primed-immune B cells in vitro. Wild-type (WT) and TLR9 knockout (TLR9KO) mice (C57BL/6 background, n = 5) were pre-immunized intraperitoneally with 1 × 108 formalin-fixed P. gingivalis and boosted once with 1 × 107 formalin-fixed P. gingivalis. Isolated splenocytes and purified B cells from each mouse were cultured with 1 × 108 formalin-fixed P. gingivalis for 48 h. Immunocytochemistry was performed to detect CD45+ IL-10+ cells. Levels of IL-10 expression and secretion in splenocytes and B cells were detected using qRT-PCR and ELISA, respectively. After stimulation with fixed P. gingivalis, the percentage of CD45+ IL-10+ B cells and the level of IL-10 expression were significantly increased (p < 0.01) in splenocytes and purified B cells isolated from WT mice. However, these changes were not observed in splenocytes and purified B cells from TLR9KO mice when the cells were treated with fixed P. gingivalis. The percentage of CD45+ IL-10+ B cells was significantly reduced in splenocytes and purified B cells from TLR9KO mice compared to those from WT mice when challenged with P. gingivalis. IL-10 expression in B cells from TLR9KO mice was significantly decreased compared to those from WT mice at both the mRNA and protein levels. Additionally, P. gingivalis-induced up-regulation of TNF-α mRNA expressions were consistently observed in B cells from both WT and TLR9KO mice. P. gingivalis-induced B10 activation and IL-10 production during adaptive responses by primed B cells requires TLR9 signaling and can be achieved independent of T-cell help.


Assuntos
Interleucina-10 , Receptor Toll-Like 9 , Animais , Camundongos , Células Cultivadas , Interleucina-10/genética , Interleucina-10/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Porphyromonas gingivalis , RNA Mensageiro/metabolismo , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/metabolismo , Linfócitos B/imunologia
12.
BMC Oral Health ; 23(1): 664, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710216

RESUMO

BACKGROUND: Periodontitis has emerged as a potential risk factor for chronic obstructive pulmonary disease (COPD). However, the precise mechanism through which periodontitis influences the progression of COPD requires further investigation. Ferroptosis is one of the crucial pathogenesis of COPD and recent researches suggested that periodontitis was associated with ferroptosis. Nonetheless, the relationship among periodontitis, COPD and ferroptosis remains unclear. This study aimed to elucidate whether periodontitis contributes to COPD exacerbation and to assess the potential impact of ferroptosis on periodontitis affecting COPD. METHODS: The severity of COPD was assessed using Hematoxylin and eosin (H&E) staining and lung function tests. Iron assays, malondialdehyde (MDA) measurement and RT-qPCR were used to investigate the potential involvement of ferroptosis in the impact of periodontitis on COPD. Co-cultures of periodontitis associated pathogen Phophyromonas gingivalis (P. gingivalis) and lung tissue cells were used to evaluate the effect of P. gingivalis on inducing the ferroptosis of lung tissue via RT-qPCR analysis. Clinical Bronchoalveolar Lavage Fluid (BALF) samples from COPD patients were collected to further validate the role of ferroptosis in periodontal pathogen-associated COPD. RESULTS: Periodontitis aggravated the COPD progression and the promotion was prolonged over time. For the first time, we demonstrated that periodontitis promoted the ferroptosis-associated iron accumulation, MDA contents and gene expressions in the COPD lung with a time-dependent manner. Moreover, periodontitis-associated pathogen P. gingivalis could promote the ferroptosis-associated gene expression in single lung tissue cell suspensions. Clinical BALF sample detection further indicated that ferroptosis played essential roles in the periodontal pathogen-associated COPD. CONCLUSION: Periodontitis could contribute to the exacerbation of COPD through up-regulating the ferroptosis in the lung tissue.


Assuntos
Ferroptose , Periodontite , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Amarelo de Eosina-(YS) , Ferro , Periodontite/complicações
13.
Medicina (Kaunas) ; 59(10)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37893496

RESUMO

Background and Objectives: Periodontitis is an inflammatory disease in the supporting tissues of the teeth caused by specific microorganisms or groups of microorganisms. P. gingivalis bacterium is the keystone pathogen in periodontitis, so even at low concentrations, it has a considerable influence on the oral community. Antimicrobials and antiplaque agents can be used as adjunctive therapy for periodontitis treatment. Konjac glucomannan (KGM), as a natural polysaccharide, has flavonoid (3,5-diacetyltambulin) and triterpenoids (ambylon) compounds that show antibacterial activity. This research aims to analyze the antibacterial activity of KGM on animal and in vitro periodontitis models. Materials and Methods: The animal study divided 48 mice into four groups (control, KGM, periodontitis, KGM + periodontitis). Mice were given an intervention substance by oral gavage from day 1 to day 14, periodontitis was induced on day 7, and decapitation was performed on day 14. Samples from the right maxillary jaw of mice were used for histological preparations and morphometrics analysis. In vitro studies were carried out by adding several concentrations of KGM (25, 50, and 100 µg/mL) into a planktonic P. gingivalis and P. gingivalis biofilm. Results: In the animal model, KGM could prevent alveolar bone loss in the periodontitis mice model, both in histologic and morphometrics assessments. In vitro, KGM had antibacterial activity against P. gingivalis with better bacteriostatic (15-23%) than bactericidal (11-20%) ability, proven by its ability to inhibit P. gingivalis proliferation. Conclusions: KGM can be considered to have the potential as an antibacterial agent to prevent periodontitis. The prevention of periodontitis may improve patient well-being and human quality of life.


Assuntos
Periodontite , Qualidade de Vida , Humanos , Animais , Camundongos , Periodontite/tratamento farmacológico , Modelos Animais de Doenças , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
14.
Niger J Clin Pract ; 26(5): 625-629, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37357480

RESUMO

Background: Essential oils (EOs) have a considerable amount of therapeutic and preventive effect in treating dental diseases due to their wider potential as antibacterial and anti-inflammatory agents. EOs like virgin coconut oil, eucalyptus oil, peppermint oil thyme oil, and clove oil, when used in combination, may further have enhanced antimicrobial effects. However, limited information exists on the synergistic effect of these oils when used in combination, especially on the primary periodontal pathogen Porphyromonas gingivalis. Aim: The current study aims to compare the antimicrobial efficacy of commercially available EO on the periodontal pathogen, P. gingivalis, in comparison to chlorhexidine (CHX). Materials and Methods: Antimicrobial efficacy of EO and CHX was assessed at various concentrations against the periodontal pathogen P. gingivalis, by evaluating the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results: P. gingivalis was seen to be sensitive at a MIC of 100 µg/ml and 50 µg/ml concentration of the EO, which is regarded as the MIC of EO against P. gingivalis and CHX effectively inhibited microbial growth at 0.4 µg/ml. Conclusion: A combination of EOs possesses a potent antibacterial activity against P. gingivalis, and the antibacterial efficacy increases with increasing concentration of EOs.


Assuntos
Anti-Infecciosos , Óleos Voláteis , Humanos , Clorexidina/farmacologia , Óleos Voláteis/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
15.
J Periodontal Res ; 57(5): 1056-1069, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35989621

RESUMO

BACKGROUND AND OBJECTIVES: The potential role of the transcription factor Differentiated embryo-chondrocyte 2 (Dec2) in the progression of inflammatory diseases such as periodontitis has been unclear. Here, the effect of Dec2 on the expression of RANKL and on osteoclastogenesis was determined. MATERIAL AND METHODS: Wild-type (WT) and Dec2 knockout (KO) mice as a model for periodontitis were used to assess alveolar bone resorption by microcomputed tomography (CT). Western blot, flow cytometry, quantitative real-time PCR, and immunohistochemical analyses were utilized to detect inflammation and osteoclasts. Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays examined the interaction between Dec2 and RANKL. RESULTS: Micro-CT showed that the alveolar bone resorption of Dec2KO mice was more severe than WT mice after treatment with P. gingivalis. Immunohistochemistry and Tartrate-resistant acid phosphatase staining showed active osteoclast differentiation in Dec2KO mice. There was an increase in CD11b+ F4/80+ and CD4+ RANKL+ T cells in Dec2KO mice treated with P. gingivalis. Moreover, inflammatory and immune markers were expressed at significantly higher levels in gingival mononuclear cells in Dec2KO mice. Furthermore, luciferase reporter and ChIP assays confirmed the direct binding of Dec2 protein to the RANKL gene. CONCLUSION: Dec2 has an immune regulation ability that modulates P. gingivalis-induced periodontitis via RANKL.


Assuntos
Perda do Osso Alveolar , Reabsorção Óssea , Periodontite , Fatores de Transcrição/metabolismo , Perda do Osso Alveolar/diagnóstico por imagem , Animais , Camundongos , Camundongos Knockout , Osteoclastos , Periodontite/diagnóstico por imagem , Periodontite/metabolismo , Ligante RANK/metabolismo , Microtomografia por Raio-X
16.
Oral Dis ; 28(8): 2258-2266, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34139032

RESUMO

OBJECTIVES: Epulis is considered to be a massive reactive lesion rather than a true neoplasia. AhR is thought to be associated with inflammation and development of neoplasms. Here, we aimed to observe the expression of AhR in fibrous epulis and explore its role and possible mechanism in the pathogenesis of epulis. MATERIALS AND METHODS: Epulis and normal gingival tissues were collected, and AhR expression was detected at the mRNA and protein levels by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. The expression levels of proinflammatory cytokines and apoptosis-related factor genes in human periodontal ligament cells (hPDLCs) and human gingival fibroblasts (hGFs) transfected with AhR short interfering RNA (siRNA) or negative control siRNA, upon stimulation with lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS), were then examined. Finally, the expression levels of the proinflammatory cytokines and apoptosis-related factor genes in the epulis tissues were observed by qPCR. RESULTS: AhR expression in fibrous epulis was significantly increased at both the mRNA and protein levels. The expression of proinflammatory cytokines and apoptosis-related factor genes in hPDLCs transfected with AhR siRNA was significantly decreased when stimulated with Pg-LPS. The same trends were observed for hGFs. The opposite trend was detected in the epulis tissues. CONCLUSION: AhR may be a key factor in fibrous epulis pathogenesis that acts by regulating the expression of BCL2 family genes and inflammatory factor-related genes.


Assuntos
Doenças da Gengiva , Receptores de Hidrocarboneto Arílico , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células Cultivadas , Citocinas/metabolismo , Fibroblastos , Gengiva/patologia , Doenças da Gengiva/patologia , Humanos , Lipopolissacarídeos/farmacologia , Porphyromonas gingivalis/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2 , RNA Mensageiro , RNA Interferente Pequeno/genética , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores Imunológicos
17.
Int J Mol Sci ; 23(7)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35408801

RESUMO

Periodontitis, a chronic inflammatory disease is caused by a bacterial biofilm, affecting all periodontal tissues and structures. This chronic disease seems to be associated with cancer since, in general, inflammation intensifies the risk for carcinoma development and progression. Interactions between periodontal pathogens and the host immune response induce the onset of periodontitis and are responsible for its progression, among them Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic rod, capable of expressing a variety of virulence factors that is considered a keystone pathogen in periodontal biofilms. The aim of this study was to investigate the genome-wide impact of P. gingivalis W83 membranes on RNA expression of oral squamous carcinoma cells by transcriptome analysis. Human squamous cell carcinoma cells (SCC-25) were infected for 4 and 24 h with extracts from P. gingivalis W83 membrane, harvested, and RNA was extracted. RNA sequencing was performed, and differential gene expression and enrichment were analyzed using GO, KEGG, and REACTOME. The results of transcriptome analysis were validated using quantitative real-time PCR with selected genes. Differential gene expression analysis resulted in the upregulation of 15 genes and downregulation of 1 gene after 4 h. After 24 h, 61 genes were upregulated and 278 downregulated. GO, KEGG, and REACTONE enrichment analysis revealed a strong metabolic transcriptomic response signature, demonstrating altered gene expressions after 4 h and 24 h that mainly belong to cell metabolic pathways and replication. Real-time PCR of selected genes belonging to immune response, signaling, and metabolism revealed upregulated expression of CCL20, CXCL8, NFkBIA, TNFAIP3, TRAF5, CYP1A1, and NOD2. This work sheds light on the RNA transcriptome of human oral squamous carcinoma cells following stimulation with P. gingivalis membranes and identifies a strong metabolic gene expression response to this periodontal pathogen. The data provide a base for future studies of molecular and cellular interactions between P. gingivalis and oral epithelium to elucidate the basic mechanisms of periodontitis and the development of cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Periodontite , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/microbiologia , Periodontite/microbiologia , Porphyromonas gingivalis , RNA
18.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36499141

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder involving the accumulation of alpha-synuclein (α-syn)/Lewy bodies in the brain and -enteric nervous system. The etiology of the disease is not well understood, but bacterial and viral infections may contribute to the pathogenesis of PD. It has been suggested that the gastrointestinal (GI) complications observed in PD patients may arise from bacterial dysbiosis, leading to curli/α-syn deposits in the enteric nervous system. Enteric bacteria secrete curli, a functional amyloid peptide involved in adhesion to surfaces, cell invasion, and biofilm formation. However, these bacterial amyloids can initiate additional α-syn deposits through immune system activation and cross-seeding. In this study, we investigate the humoral response against α-syn, curli peptides, and various bacterial and viral immunogen peptides in PD patients, and compare them with those in healthy controls (HCs). Polyclonal IgG antibodies (Abs) were detected against peptides derived from α-syn (α-syn100−114), curli (Curli133−141), Porphyromonas gingivalis Pg (RgpA800−812, Kpg328−339), Aggregatibacter actinomycetemcomitans (LtxA1429−445, LtxA264−80), Mycobacterium avium subsp. paratuberculosis (MAP3865c125−133, MAP1,4-a-gbp157−173 and MAP_402718−32), Epstein−Barr virus (EBNA1400−413, BOLF1305−320), and Herpes Simplex virus 1 (UI4222−36), as investigated by indirect ELISA of 51 serum samples from PD and 58 sex and age-matched HCs. Significant differences in OD (optical density) values and Abs positivity between PD patients and HCs were observed for Kpg (82.3% vs. 10.3%), followed by RgpA (60.7% vs. 24.1%), curli (51% vs. 22.4%), and UI42 (43.1% vs. 25.8%) in PD, compared to HCs sera (p < 0.001). No significant difference was found in the ODs obtained from other tested peptides in PD patients, compared to HCs. Significant positive correlations between OD values obtained by ELISA were observed for UI42 and curli (r = 0.811, p < 0.0001), Kpg and RgpA (r = 0.659, p < 0.0001), followed by LtxA1 and LtxA2 (r = 0.653, p < 0.0001). The correlation between the HY scale (Hoehn and Yahr Scale) and LtxA1 (r = 0.306, p < 0.028) and HY and Kpg (r = 0.290, p < 0.038) were significantly positive. This study reports a significantly increased humoral response against curli, Pg, and HSV-1 in PD patients, implying that they could be important factors in the pathogenesis of the disease. In addition, the high positive correlation between UI42 and curli may suggest the involvement of HSV-1 in GI dysbiosis. Therefore, the role of each individual pathogen and curli in PD needs to be further investigated.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 1 , Mycobacterium avium subsp. paratuberculosis , Doença de Parkinson , Animais , Humanos , alfa-Sinucleína/metabolismo , Amiloide/metabolismo , Anticorpos , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 4 , Doença de Parkinson/metabolismo , Peptídeos , Proteínas Virais
19.
Medicina (Kaunas) ; 58(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35454345

RESUMO

Background and Objective: There is increasing interest in preventing periodontitis using natural products. The purpose of this study was to investigate the effect of Colocasia antiquorum var. esculenta (CA) varnish on the oral microbiome and alveolar bone loss in a mouse periodontitis model. Materials and Methods: Antibacterial activity against Porphyromonas gingivalis (P. gingivalis) ATCC 53978 and cell cytotoxicity using CCK-8 on L929 cells were measured. Balb/c mice were assigned into five groups (negative control, positive control, CA in drinking water, varnish, and CA varnish). P. gingivalis was administered to the mice by oral gavage three times. After sacrifice, the oral microbiome and the levels of the inflammatory cytokine IL-1ß and matrix metalloproteinase-9 were analyzed. Alveolar bone loss was measured using micro-computed tomography. Results: CA extract showed an antibacterial effect against P. gingivalis (p < 0.05) and showed no cytotoxicity at that concentration (p > 0.05). Although alpha diversity of the oral microbiome did not statistically differ between the groups (p > 0.05), the relative abundance of dominant bacteria tended to be different between the groups. The inflammatory cytokine IL-1ß was reduced in the CA varnish group (p < 0.05), and no difference was observed in MMP-9 expression and alveolar bone loss (p > 0.05). Conclusions: CA varnish did not affect the overall microflora and exhibited an anti-inflammatory effect, suggesting that it is possibility a suitable candidate for improving periodontitis.


Assuntos
Perda do Osso Alveolar , Colocasia , Microbiota , Periodontite , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Animais , Antibacterianos , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Periodontite/tratamento farmacológico , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Porphyromonas gingivalis/metabolismo , Microtomografia por Raio-X
20.
Rheumatology (Oxford) ; 60(2): 658-666, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32594174

RESUMO

OBJECTIVES: To assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA. METHODS: In the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up. RESULTS: Of 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia. CONCLUSIONS: ACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.


Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Anticorpos Anti-Idiotípicos/sangue , Artrite/imunologia , Vigilância da População , Fator Reumatoide/sangue , Adulto , Artrite/sangue , Artrite/epidemiologia , Artrite Reumatoide , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos
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