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The American Journal of Medicine Mar 2024We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in...
BACKGROUND
We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease.
METHODS
This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes.
RESULTS
There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable.
CONCLUSIONS
Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.
Topics: Humans; C-Reactive Protein; Interleukin-6; Inflammation; Periodontal Diseases; Immunoglobulins
PubMed: 37984772
DOI: 10.1016/j.amjmed.2023.11.001 -
Journal of Cancer Research and Clinical... Apr 2024Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC)....
PURPOSE
Periodontitis-associated bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are closely linked to the risk of oral squamous cell carcinoma (OSCC). Emerging studies have indicated that another common periodontal pathogen, Prevotella intermedia (P. intermedia), is enriched in OSCC and could affect the occurrence and progression of OSCC. Our aim is to determine the effects of P. intermedia on the progression of OSCC and the role of antibiotics in reversing these effects.
METHODS
In this study, a murine xenograft model of OSCC was established, and the mice were injected intratumorally with PBS (control group), P. intermedia (P.i group), or P. intermedia combined with an antibiotic cocktail administration (P.i + ABX group), respectively. The effects of P. intermedia and ABX administration on xenograft tumor growth, invasion, angiogenesis, and metastasis were investigated by tumor volume measurement and histopathological examination. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the changes in serum cytokine levels. Immunohistochemistry (IHC) was adopted to analyze the alterations in the levels of inflammatory cytokines and infiltrated immune cells in OSCC tissues of xenograft tumors. Transcriptome sequencing and analysis were conducted to determine differential expression genes among various groups.
RESULTS
Compared with the control treatment, P. intermedia treatment significantly promoted tumor growth, invasion, angiogenesis, and metastasis, markedly affected the levels of inflammatory cytokines, and markedly altered M2 macrophages and regulatory T cells (Tregs) infiltration in the tumor microenvironment. However, ABX administration clearly abolished these effects of P. intermedia. Transcriptome and immunohistochemical analyses revealed that P. intermedia infection increased the expression of interferon-stimulated gene 15 (ISG15). Correlation analysis indicated that the expression level of ISG15 was positively correlated with the Ki67 expression level, microvessel density, serum concentrations and tissue expression levels of inflammatory cytokines, and quantities of infiltrated M2 macrophages and Tregs. However, it is negatively correlated with the quantities of infiltrated CD4 and CD8 T cells.
CONCLUSION
In conclusion, intratumoral P. intermedia infection aggravated OSCC progression, which may be achieved through upregulation of ISG15. This study sheds new light on the possible pathogenic mechanism of intratumoral P. intermedia in OSCC progression, which could be a prospective target for OSCC prevention and treatment.
Topics: Animals; Mice; Cytokines; Humans; Mouth Neoplasms; Ubiquitins; Disease Progression; Up-Regulation; Prevotella intermedia; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays; Mice, Nude; Bacteroidaceae Infections; Cell Line, Tumor; Mice, Inbred BALB C; Carcinoma, Squamous Cell; Anti-Bacterial Agents
PubMed: 38644421
DOI: 10.1007/s00432-024-05730-5 -
International Journal of Molecular... Aug 2023Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with...
Periodontitis is a widespread chronic inflammatory disease caused by a changed dysbiotic oral microbiome. Although multiple species and risk factors are associated with periodontitis, has been identified as a keystone pathogen. The immune-modulatory function of is well characterized, but the mechanism by which this bacterium secretes peptidyl arginine deiminase (PPAD), a protein/peptide citrullinating enzyme, thus contributing to the infinite feed-forward loop of inflammation, is not fully understood. To determine the functional role of citrullination in periodontitis, neutrophils were stimulated by bearing wild-type PPAD and by a PPAD mutant strain lacking an active enzyme. Flow cytometry showed that PPAD contributed to prolonged neutrophil survival upon bacterial stimulation, accompanied by the secretion of aberrant IL-6 and TNF-α. To further assess the complex mechanism by which citrullination sustains a chronic inflammatory state, the ROS production and phagocytic activity of neutrophils were evaluated. Flow cytometry and colony formation assays showed that PPAD obstructs the resolution of inflammation by promoting neutrophil survival and the release of pro-inflammatory cytokines, while enhancing the resilience of the bacteria to phagocytosis.
Topics: Humans; Porphyromonas gingivalis; Protein-Arginine Deiminases; Inflammation; Periodontitis
PubMed: 37629104
DOI: 10.3390/ijms241612922 -
ACS Infectious Diseases Sep 2023Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However,...
Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that , , , , , , , , and were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including , , , , and to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; RNA, Ribosomal, 16S; Biomarkers; Head and Neck Neoplasms
PubMed: 37565768
DOI: 10.1021/acsinfecdis.3c00269 -
International Journal of Nanomedicine 2023Silver nanoparticles (AgNPs) possess excellent antibacterial effects on periodontal pathogens, but their clinical application is limited mainly due to their cytotoxicity...
OBJECTIVE
Silver nanoparticles (AgNPs) possess excellent antibacterial effects on periodontal pathogens, but their clinical application is limited mainly due to their cytotoxicity through inducing oxidative stress in human cells. Ebselen disrupts the reactive oxygen species (ROS) scavenging in bacteria and relieves oxidative stress in mammalian cells. This study aimed to assess the antibacterial and anti-inflammatory effects of AgNPs and ebselen as well as the protective effect of ebselen, to further provide the theoretical basis for their future application in periodontal treatment.
METHODS
The antibacterial and anti-biofilm effects of the synthesized AgNPs combined with ebselen were assessed on ( (), and () in planktonic condition and as biofilms. In addition, the intracellular bactericidal efficiency of AgNPs and ebselen was evaluated in -infected human gingival fibroblasts (HGFs). The cytotoxicity, intracellular ROS levels, and potential antioxidative enzymes were detected in HGFs treated with AgNPs and ebselen. Further, the anti-inflammatory effects were evaluated by in vitro and in vivo experiments.
RESULTS
The combination of AgNPs and ebselen showed excellent antibacterial effects against planktonic and and synergistic antibiofilm effects on all mono- and multi-species biofilms. In addition, ebselen significantly enhanced the intracellular bactericidal efficiency of AgNPs. Furthermore, ebselen combined with up to 20 μg/mL AgNPs showed no obvious cytotoxicity to HGFs. Evidently, ebselen alleviated the AgNPs-induced ROS by increasing the levels of glutathione and superoxide dismutase 2. Moreover, AgNPs and ebselen together declined the release of -stimulated inflammatory cytokines both in vitro and in vivo, and reduced alveolar bone resorption effectively.
CONCLUSION
AgNPs combined with ebselen would be an effective adjuvant for periodontal treatment owing to their synergistic antibacterial and anti-inflammatory effects.
Topics: Humans; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biofilms; Metal Nanoparticles; Porphyromonas gingivalis; Reactive Oxygen Species; Silver
PubMed: 38169981
DOI: 10.2147/IJN.S434579 -
PeerJ 2023Periodontal disease is associated with systemic conditions such as diabetes, arthritis, and cardiovascular disease, all diseases with large inflammatory components....
BACKGROUND
Periodontal disease is associated with systemic conditions such as diabetes, arthritis, and cardiovascular disease, all diseases with large inflammatory components. Some, but not all, reports show periopathogens and at higher levels orally in people with one of these chronic diseases and in people with more severe cases. These oral pathogens are thought to be positively associated with systemic inflammatory diseases through induction of oral inflammation that works to distort systemic inflammation or by directly inducing inflammation at distal sites in the body. This study aimed to determine if, among patients with severe periodontal disease, those with multi-morbidity (or many chronic diseases) showed higher levels of periodontal pathogens.
METHODS
A total of 201 adult subjects, including 84 with severe periodontal disease were recruited between 1/2017 and 6/2019 at a city dental clinic. Electronic charts supplied self-reported diseases and conditions which informed a morbidity index based on the number of chronic diseases and conditions present. Salivary composition was determined by 16S rRNA gene sequencing.
RESULTS
As expected, patients with severe periodontal disease showed higher levels of periodontal pathogens in their saliva. Also, those with severe periodontal disease showed higher levels of multiple chronic diseases (multimorbidity). An examination of the 84 patients with severe periodontal disease revealed some subjects despite being of advanced age were free or nearly free of systemic disease. Surprisingly, the salivary microbiota of the least healthy of these 84 subjects, defined here as those with maximal multimorbidity, showed significantly lower relative numbers of periodontal pathogens, including and , after controlling for active caries, tobacco usage, age, and gender. Analysis of a control group with none to moderate periodontal disease revealed no association of multimorbidity or numbers of medications used and specific oral bacteria, indicating the importance of severe periodontal disease as a variable of interest.
CONCLUSION
The hypothesis that periodontal disease patients with higher levels of multimorbidity would have higher levels of oral periodontal pathogens is false. Multimorbidity is associated with a reduced relative number of periodontal pathogens and
Topics: Adult; Humans; RNA, Ribosomal, 16S; Periodontal Diseases; Periodontitis; Porphyromonas gingivalis; Tannerella forsythia; Inflammation
PubMed: 37465146
DOI: 10.7717/peerj.15502 -
American Journal of Cancer Research 2023(), a Gram-negative oral anaerobe, was demonstrated to facilitate colonization and progression in colonic tumor, while the underlying mechanism still remains to be...
(), a Gram-negative oral anaerobe, was demonstrated to facilitate colonization and progression in colonic tumor, while the underlying mechanism still remains to be clarified. Here, we identified the proteome profile changed by infection in HCT116 cells through label-free quantitative proteomics, and found that deubiquitinase UCHL3 was a key protein that response for infection. By CCK8, colony formation, wound healing assays, and in vivo subcutaneous tumor mouse moudle, we proved that could promote the proliferation and migration of colon cancer, while the process was inhibited by UCHL3 knock down. Through IP-MS, we identified GNG12 as the UCHL3 interacting protein. The protein level of GNG12 was significantly reduced when knock out UCHL3. Thus we propose that GNG12 is a substrate protein of UCHL3. Furthermore, we demonstrated that overexpression of GNG12 could restore the tumor inhibition effect caused by UCHL3 knock down, and UCHL3-GNG12 axis promote colon cancer progression via the NF-κB signal pathway. Collectively, this study unveiled that infection up-regulated UCHL3 and stabilized its substrate protein GNG12 to activate the NF-κB signal pathway to promote colon cancer progression. Our study indicate that UCHL3 is a potential biomarker and therapeutic target for colon cancer which infected with .
PubMed: 38187053
DOI: No ID Found -
BMC Microbiology Jul 2023The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly...
BACKGROUND
The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion samples were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted tooth extraction patients. DNA was extracted, and 16S rRNA sequencing was performed to explore the characteristics and structure of the microbiome in the sinuses and dental regions of OS patients.
RESULTS
The alpha diversity of the oral and nasal microbiomes in OS patients was higher than that in controls. Principal coordinate analysis (PCoA) showed that oral samples clustered separately from nasal samples, and the beta diversity of oral and nasal samples in OS patients was higher than that in controls. The dominant phylum was Bacteroidetes in OS patients and Firmicutes in controls in both the oral and nasal cavity. The dominant genera in the oral microbiome and nasal microbiome of OS patients were similar, including Fusobacterium, Porphyromonas and Prevotella. Co-occurrence network analysis showed decreased microbial connectivity in the oral mucosa and nasal secretion samples of OS patients.
CONCLUSIONS
Odontogenic infection promotes structural and functional disorders of the nasal microbiome in OS. The interaction of dominant pathogens in the nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS.
Topics: Humans; Adult; RNA, Ribosomal, 16S; Sinusitis; Nose; Bacteroidetes; Firmicutes
PubMed: 37516855
DOI: 10.1186/s12866-023-02917-7 -
Infection, Genetics and Evolution :... Sep 2023To systematically investigate the prophages carrying in Porphyromonas gingivalis (P. gingivalis) strains, analyze potential antibiotic resistance genes (ARGs) and...
To systematically investigate the prophages carrying in Porphyromonas gingivalis (P. gingivalis) strains, analyze potential antibiotic resistance genes (ARGs) and virulence genes in these prophages. We collected 90 whole genome sequences of P. gingivalis from NCBI and utilized the Prophage Hunter online software to predict prophages; Comprehensive antibiotic research database (CARD) and virulence factors database (VFDB) were adopted to analyze the ARGs and virulence factors (VFs) carried by the prophages. Sixty-nine prophages were identified among 24/90 P. gingivalis strains, including 17 active prophages (18.9%) and 52 ambiguous prophages (57.8%). The proportion of prophages carried by each P. gingivalis genome ranged from 0.5% to 6.7%. A total of 188 antibiotic resistance genes belonging to 25 phenotypes and 46 different families with six mechanisms of antibiotic resistance were identified in the 17 active prophages. Three active prophages encoded 4 virulence genes belonging to type III and type VI secretion systems. The potential hosts of these virulence genes included Escherichia coli, Shigella sonnei, Salmonella typhi, and Klebsiella pneumoniae. In conclusion, 26.7% P. gingivalis strains carry prophages, while the proportion of prophage genes in the P. gingivalis genome is relatively low. In addition, approximately 39.7% of the P. gingivalis prophage genes have ARGs identified, mainly against streptogramin, peptides, and aminoglycosides. Only a few prophages carry virulence genes. Prophages may play an important role in the acquisition, dissemination of antibiotic resistance genes, and pathogenicity evolution in P. gingivalis.
Topics: Prophages; Genome, Bacterial; Porphyromonas gingivalis; Virulence Factors; Virulence; Escherichia coli; Anti-Bacterial Agents
PubMed: 37572952
DOI: 10.1016/j.meegid.2023.105489 -
Molecules (Basel, Switzerland) Feb 2024The use of natural compounds to prevent and treat infective diseases is increasing its importance, especially in the case of multidrug-resistant (MDR)... (Review)
Review
The use of natural compounds to prevent and treat infective diseases is increasing its importance, especially in the case of multidrug-resistant (MDR) microorganisms-mediated infections. The drug resistance phenomenon is today a global problem, so it is important to have available substances able to counteract MDR infections. (L.) Merr. & L.M. Perry (commonly called clove) is a spice characterized by several biological properties. Clove essential oil (EO) consists of numerous active molecules, being eugenol as the principal component; however, other compounds that synergize with each other are responsible for the biological properties of the EO. is traditionally used for bowel and stomach disorders, cold and flu, oral hygiene, tooth decay, and for its analgesic action. Its EO has shown antioxidant, antimicrobial, anti-inflammatory, neuro-protective, anti-stress, anticancer, and anti-nociceptive activities. This review aims to investigate the role of EO in the counteraction of MDR microorganisms responsible for human disorders, diseases, or infections, such as , , , , , , , , and . This study might orient clinical researchers on future therapeutic uses of EO in the prevention and treatment of infectious diseases.
Topics: Humans; Syzygium; Clove Oil; Oils, Volatile; Eugenol; Anti-Infective Agents
PubMed: 38474510
DOI: 10.3390/molecules29050999