• International Journal of Oral Biology
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• v.39 no.1
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• pp.15-22
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• 2014

Aggregatibacter actinomycetemcomitans is an important pathogen in the development of localized aggressive periodontitis. Lipopolysaccharide (LPS) is a virulent factor of periodontal pathogens that contributes to alveolar bone loss and connective tissue degradation in periodontal disease. Our present study was designed to investigate the cytokine expression and signaling pathways regulated by A. actinomycetemcomitans LPS (Aa LPS). Cytokine gene expression profiling in RAW 264.7 cells was performed by microarray analyses. The cytokine mRNA and protein levels and related signaling pathways induced by Aa LPS were measured by RT-PCR, ELISA and western blotting. Microarray results showed that Aa LPS strongly induced the expression of NF-${\kappa}B$, NF-${\kappa}B$-related genes, inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in RAW 264.7 cells. NF-${\kappa}B$ inhibitor pretreatment significantly reduced the levels of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA and protein. In addition, the Aa LPS-induced TNF-${\alpha}$ and IL-$1{\beta}$ expression was inhibited by p38/JNK MAP kinase inhibitor pretreatment. These results show that Aa LPS stimulates TNF-${\alpha}$ and IL-$1{\beta}$ expression through NF-${\kappa}B$ and p38/JNK activation in RAW 264.7 cells, suggesting the essential role of this pathway in the pathogenesis of localized aggressive periodontitis.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.217-223
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• 2016

Porphyromonas gingivalis, a foremost periodontal pathogen, has been known to cause periodontal diseases. Epidemiologic evidences have indicated the involvement of P. gingivalis in the development of cardiovascular diseases. In this study, we show that the P. gingivalis lipopolysaccharide increases the mRNA expression and protein secretion of interleukin-6 in vascular smooth muscle cells. We demonstrate that P. gingivalis LPS activates the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and Akt, which mediate the IL-6 expression in vascular smooth muscle cells. Also, P. gingivalis LPS stimulates the vascular smooth muscle cell migration, which is a critical step for the progression of atherosclerosis. Moreover, neutralization of the IL-6 function inhibits the migration of vascular smooth muscle cells induced by P. gingivalis LPS. Taken together, these results indicate that P. gingivalis LPS promotes the expression of IL-6, which in turn increases the migration of vascular smooth muscle cells.

• International Journal of Oral Biology
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• v.49 no.1
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• pp.1-9
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• 2024

Oral bacterial infections substantially affect the development of various periodontal diseases and oral cancers. However, the molecular mechanisms underlying the association between Fusobacterium nucleatum (F. nucleatum ), a major periodontitis (PT)-associated pathogen, and these diseases require extensive research. Previously, our RNA-sequencing analysis identified a few hundred differentially expressed genes in patients with PT and peri-implantitis (PI) than in healthy controls. Thus, in the present study using oral squamous cell carcinoma (OSCC) cells, we aimed to evaluate the effect of F. nucleatum infection on genes that are differentially regulated in patients with PT and PI. Human oral squamous cell carcinoma cell lines OSC-2O, HSC-4, and HN22 were used. These cells were infected with F. nucleatum at a multiplicity of infection of 100 for 3 hours at 37℃ in 5% CO₂. Gene expression was then measured using reverse-transcription polymerase chain reaction. Among 18 genes tested, the expression of CSF3, an inflammation-related cytokine, was increased by F. nucleatum infection. Additionally, F. nucleatum infection increased the phosphorylation of AKT, p38 MAPK, and JNK in OSC-20 cells. Treatment with p38 MAPK (SB202190) and JNK (SP600125) inhibitors reduced the enhanced CSF3 expression induced by F. nucleatum infection. Overall, this study demonstrated that F. nucleatum promotes CSF3 expression in OSCC cells through p38 MAPK and JNK signaling pathways, suggesting that p38 MAPK and JNK inhibitors may help treat F. nucleatum-related periodontal diseases by suppressing CSF3 expression.

• International Journal of Oral Biology
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• v.43 no.1
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• pp.37-42
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• 2018

It is noted that Streptococcus mutans (S. mutans) triggers dental caries establishment by two major factors: the synthesis of organic acids, which demineralize dental enamel, and the synthesis of glucans, which mediate the attachment of bacteria to the tooth surface. Therefore, it is noted that the development of a more effective, substantial and safe preventive agent that works against dental caries and periodontal disease is required at this time. For this reason, the present study was designed to investigate the effect of croton seed ethanol extracts on the growth, acid production, adhesion, and insoluble glucan synthesis of S. mutans. In this case, the ethanol extract of croton seed showed concentration dependent inhibitory activity against the growth, acid production and adhesion of S. mutans. Especially, it is important to note that it has produced significant inhibition at the concentration of 0.1 and 0.2 mg/ml as compared to the control group. Moreover, these results suggest that the application of croton seed extract may be considered to be a useful method for the prevention of dental caries.

• Korean Journal of Microbiology
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• v.55 no.1
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• pp.52-54
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• 2019

Dialister pneumosintes is a Gram-staining-negative, anaerobic, non-fermenting, and rod-shaped bacterium. D. pneumosintes is considered to be a periodontal pathogen. D. pneumosintes KCOM 1685 (= ChDC B414) was isolated from a human postoperative maxillary cyst lesion. In this report, we present the draft genome sequence of D. pneumosintes KCOM 1685.

• International Journal of Oral Biology
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• v.44 no.1
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• pp.20-26
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• 2019

Periodontal diseases have been associated with the development of cardiovascular diseases. Accumulating evidences have indicated that Porphyromonas gingivalis, a major periodontopathic pathogen, plays a critical role in the pathogenesis of atherosclerosis. In the present study, we demonstrated that P. gingivalis lipopolysaccharide (LPS) increases the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9) in rat vascular smooth muscle cells. We showed that the MMP-9 expression induced by P. gingivalis LPS is mediated by the activation of signal transducer and activator of transcription 3 (STAT3) in vascular smooth muscle cells. Furthermore, the inhibition of STAT3 activity reduced P. gingivalis LPS-induced migration of vascular smooth muscle cells. Overall, our findings indicate that P. gingivalis LPS stimulates the migration of vascular smooth muscle cells via STAT3-mediated MMP-9 expression.

• Restorative Dentistry and Endodontics
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• v.34 no.6
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• pp.537-550
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• 2009

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). To date, some periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) have been reported to be relevant to CVD. Porphyromonas endodontalis (P. endodontalis), which shares approximately 87% sequence homology with P. gingivalis, is mostly found within infected root canals. However, recent studies reveal that this pathogen also resides in the dental plaque or periodontal pocket in patients with periodontitis. It has been shown that P. endodontalis invades human coronary artery endothelial cells (HCAEC) and coronary artery smooth muscle cells (CASMC). To evaluate whether P. endodontalis can participate in the progression of atherosclerosis and CVD, we examined the changes in transcriptional gene expression profiles of HCAEC responding to invaion by P. endodontalis in this study. The following results were obtained. 1. Porphyromonas endodontalis was invasive of HCAEC. 2. According to the microarray analysis, there were 625 genes upregulated more than two-folds, while there were 154 genes downregulated by half. 3. Upregulated genes were relevant to inflammatory cytokines, apoptosis, coagulation and immune response. Enhanced expression of MMP-1 was also noticeable. 4. The transcription profiles of the 10 selected genes examined by real-time PCR agreed well with those observed in the microarray analysis. Thus, these results show that P. endodontalis presents the potential to trigger and augment atherosclerosis leading to CVD.

• Korean Journal of Microbiology
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• v.43 no.3
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• pp.227-231
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• 2007

Many of antimicrobial components used in the mouthwash have disadvantages such as coloring of periodontal tissue and homing sensation. To find the more biocompatible antimicrobial agent, we have screened the 2,125 kinds of natural plant extracts obtained from by the Plant Extract Bank (Daejeon, Korea). The antimicrobial activity was determined by spectrophotometric growth inhibition assay for the major dental pathogens. For the Porphyromonas gingivalis, 19 plant extracts had an antimicrobial activity, 17 plant extracts for the Prevotella intermedia, 45 plant extracts for the Haemophilus actinomycetemcomitans and 85 plant extracts for the Streptococcus mutans. Among these effective extracts, 8 kind of natural plant extracts had an antimicrobial activity for more than 3 species of dental pathogens. In our experiment, Cudrania tricuspidata, Morus bombycis and Mallotus japonicas have antibacterial effects on the all kinds of major dental pathogens. Therefore these plant extracts have a possibility to be a candidate for major antibacterial components in dental products.

• Journal of Periodontal and Implant Science
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• v.38 no.1
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• pp.31-40
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• 2008

Purpose: The probiotic effects of lactic acid bacteria have widely been researched in diverse human pathogens, but only a few effects are reported against oral pathogens. The antimicrobial effects of the Enterococcus faecium 7413 isolated from Korean infants on the 9 pathogen including 6 oral streptococci were investigated the clinical use of the antimicrobial peptide for oral microflora control. Materials and Methods: E. faecium 7413 was identified by morphological, biochemical tests and 16S rDNA sequence analysis. Inhibitory effects of culture supernatants were determined for their ability to grow on agar plate containing pathogenic bacteria. Result: The culture supernatant of Enterococcus faecium 7413 showed inhibitory effects on oral pathogens, namely Streptococcus pyogenes KCTC 3556, S. pneumoniae KCTC 5080, S. mutans ATCC 25175, S. anginosus ATCC 33397, S. constellatus KCTC 3268, S. intermedius ATCC 27823 and Shigella flexneri KCTC 2008. Whereas it did not affect the multiplication of E. coli strains, KCTC 1041 and ATCC 43894. Conclusion: The data obtained in this study could be useful for future development of effective probiotics allowing prevention for oral pathogens.

• Pediatric Infection and Vaccine
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• v.29 no.3
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• pp.173-178
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• 2022

Streptococcus intermedius is a small, non-motile, Gram-positive, non-sporeforming, and aerotolerant anaerobic coccus. It is a part of the normal microflora in the oral cavity and upper respiratory, gastrointestinal and female urogenital tracts. It is an opportunistic pathogen that causes serious infections in patients with immunocompromised states or cardiac diseases as a result of trauma or invasive procedures. We describe a case of septic arthritis of the hip caused by S. intermedius in an immunocompetent healthy 7-year-old boy without a history of periodontal disease or invasive procedures. He had hip joint pain three weeks ago, and the fever began on the day of the visit. He had been healthy and had not undergone any invasive procedures recently. Septic arthritis of the hip was indicated in the magnetic resonance imaging of the hip. S. intermedius was identified in the hip joint fluid aspiration and blood culture. He was successfully treated with surgical intervention and antibiotic therapy with ceftriaxone followed by amoxicillin for five weeks.