Occult lymph node metastasis in the contralateral neck of oropharyngeal squamous cell carcinoma: a meta-analysis and literature review.

PURPOSE: The purpose of this study was to determine whether contralateral cervical lymph node dissection is needed in patients with oropharyngeal squamous cell carcinoma (OPSCC) with contralateral cervical cN0. METHODS: We searched the PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM) and Cochrane Library databases up to August 14, 2021 for studies examining the contralateral neck occult metastasis rate of patients with ipsilateral clinical neck-negative (cN0) OPSCC and the contralateral neck occult metastasis rate of patients with ipsilateral clinical neck-positive (cN1, cN2a, cN2b) OPSCC. This rate is used to determine whether patients with contralateral cN0 OPSCC need contralateral cervical lymph node dissection. RESULTS: A total of 14 articles, including 532 cases, were included in the analysis. When studying the rate of ipsilateral cervical occult metastasis in patients with ipsilateral cN0, 163 cases were included in 11 studies. The results showed that the rate of contralateral cervical occult lymph node metastasis in patients with ipsilateral cN0 was 0.6816% (95% CI 0.0000-4.4880 (P = 0.3005)). In the study of ipsilateral cN+ (cN1, cN2a, cN2b), a total of 369 cases of 10 articles were included in the analysis. The results showed that the rate of contralateral cervical occult lymph node metastasis in patients with ipsilateral cN+ was 11.4920% [95% CI 7.8944-15.5223 (P = 0.0000)]. CONCLUSION: For cancer treatment, the ultimate goal is to achieve the best control of cancer and the lowest complications. It seems unnecessary to intervene in the contralateral neck of patients with OPSCC with ipsilateral cN0. For OPSCC with ipsilateral cN+ , this index is a factor that cannot be ignored when making clinical decisions.

Comparative genomics and evolution of the amylase-binding proteins of oral streptococci.

BACKGROUND: Successful commensal bacteria have evolved to maintain colonization in challenging environments. The oral viridans streptococci are pioneer colonizers of dental plaque biofilm. Some of these bacteria have adapted to life in the oral cavity by binding salivary α-amylase, which hydrolyzes dietary starch, thus providing a source of nutrition. Oral streptococcal species bind α-amylase by expressing a variety of amylase-binding proteins (ABPs). Here we determine the genotypic basis of amylase binding where proteins of diverse size and function share a common phenotype. RESULTS: ABPs were detected in culture supernatants of 27 of 59 strains representing 13 oral Streptococcus species screened using the amylase-ligand binding assay. N-terminal sequences from ABPs of diverse size were obtained from 18 strains representing six oral streptococcal species. Genome sequencing and BLAST searches using N-terminal sequences, protein size, and key words identified the gene associated with each ABP. Among the sequenced ABPs, 14 matched amylase-binding protein A (AbpA), 6 matched amylase-binding protein B (AbpB), and 11 unique ABPs were identified as peptidoglycan-binding, glutamine ABC-type transporter, hypothetical, or choline-binding proteins. Alignment and phylogenetic analyses performed to ascertain evolutionary relationships revealed that ABPs cluster into at least six distinct, unrelated families (AbpA, AbpB, and four novel ABPs) with no phylogenetic evidence that one group evolved from another, and no single ancestral gene found within each group. AbpA-like sequences can be divided into five subgroups based on the N-terminal sequences. Comparative genomics focusing on the abpA gene locus provides evidence of horizontal gene transfer. CONCLUSION: The acquisition of an ABP by oral streptococci provides an interesting example of adaptive evolution.

Publisher Erratum to: The rationale and potential for using Lactobacillus in the management of periodontitis.

Due to a technical defect the following articles have been mistakenly published Open Access:The rationale and potential for using Lactobacillus in the management of periodontitis. J. Microbiol. 60, 355-363 (doi: https://doi.org/10.1007/s12275-022-1514-4 ).The copyright of these article changes to 'Copyright © 2022, Author(s) under the exclusive license with the Microbiological Society of Kore' with all rights reserved.

The rationale and potential for using Lactobacillus in the management of periodontitis.

Periodontitis refers to a wide range of the inflammatory conditions of supporting dental structures. For some patients with periodontitis, antibacterial agents are needed as an adjuvant to mechanical debridement treatments and oral hygiene maintenance. However, the widespread use of broad-spectrum antibiotics for the prophylaxis and treatment of periodontal infections results in the emergence of resistant pathogens. Therefore, probiotics have become markedly interesting to researchers as a potentially safe alternative to periodontal treatment and maintenance. Probiotics have been used in medicine for decades and extensively applied to the treatment of inflammatory diseases through the modulation of microbial synergy and other mechanisms. A growing amount of evidence has shown that using Lactobacillus strains for oral cavity maintenance could improve periodontal health. In this study, we reviewed studies showing proof of the inhibitory effects of Lactobacillus species on periodontal inflammation. We also explored the rationale and potential for using Lactobacillus species in the management of periodontitis.

Inflammatory response of gut, spleen, and liver in mice induced by orally administered Porphyromonas gingivalis.

Background: Periodontitis is a chronic multifactorial inflammatory disease. Porphyromonas gingivalis is a primary periopathogen in the initiation and development of periodontal disease. Evidence has shown that P. gingivalis is associated with systemic diseases, including IBD and fatty liver disease. Inflammatory response is a key feature of diseases related to this species. Methods: C57BL/6 mice were administered either PBS, or P. gingivalis. After 9 weeks, the inflammatory response in gut, spleen, and liver was analyzed. Results: The findings revealed significant disturbance of the intestinal microbiota and increased inflammatory factors in the gut of P. gingivalis-administered mice. Administrated P. gingivalis remarkably promoted the secretion of IRF-1 and activated the inflammatory pathway IFN-γ/STAT1 in the spleen. Histologically, mice treated with P. gingivalis exhibited hepatocyte damage and lipid deposition. The inflammatory factors IL-17a, IL-6, and ROR-γt were also upregulated in the liver of mice fed with P. gingivalis. Lee's index, spleen index, and liver index were also increased. Conclusion: These results suggest that administrated P. gingivalis evokes inflammation in gut, spleen, and liver, which might promote the progression of various systemic diseases.

Multifaceted Impacts of Periodontal Pathogens in Disorders of the Intestinal Barrier.

Periodontal disease, a common inflammatory disease, is considered a hazardous factor that contributes to the development of diseases of the digestive system as well as other systems. The bridge between periodontitis and systemic diseases is believed to be periodontal pathogens. The intestine, as part of the lower gastrointestinal tract, has a close connection with the oral cavity. Within the intestine, the intestinal barrier acts as a multifunctional system including microbial, mucous, physical and immune barrier. The intestinal barrier forms the body's first line of defense against external pathogens; its breakdown can lead to pathological changes in the gut and other organs or systems. Reports in the literature have described how oral periodontal pathogens and pathobiont-reactive immune cells can transmigrate to the intestinal mucosa, causing the destruction of intestinal barrier homeostasis. Such findings might lead to novel ideas for investigating the relationship between periodontal disease and other systemic diseases. This review summarizes studies on the effects of periodontal pathogens on the intestinal barrier, which might contribute to understanding the link between periodontitis and gastrointestinal diseases.

Fusobacterium nucleatum Interaction with Pseudomonas aeruginosa Induces Biofilm-Associated Antibiotic Tolerance via Fusobacterium Adhesin A.

Respiratory infections with Pseudomonas aeruginosa or Fusobacterium nucleatum are associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and failure in antibiotic treatment. However, the impact of these dual-species interactions on the severity of chronic obstructive pulmonary disease (COPD) and biofilm antibiotic susceptibility remains poorly understood. This study demonstrated that F. nucleatum frequently coexisted with P. aeruginosa in the respiratory tract, and the number of F. nucleatum was negatively correlated with the lung function of AECOPD patients. The coculture of P. aeruginosa and F. nucleatum promoted bacterial proliferation and induced antibiotic tolerance through the formation of a dense biofilm surrounded by excessive Pel and Psl polysaccharides. Moreover, Fusobacterium adhesin A (FadA), rather than F. nucleatum spent medium, induced antibiotic tolerance of the P. aeruginosa biofilm. These results indicate that F. nucleatum is a biomarker of lung function decline in AECOPD patients and interacts with P. aeruginosa in vitro to resist antibiotics via FadA, which would be a potential anti-infective target of these dual-species infection.

Virulence genes of Porphyromonas gingivalis W83 in chronic periodontitis.

OBJECTIVE: To identify virulence genes found in highly virulent strains of Porphyromonas gingivalis (P. gingivalis) among Chinese patients with chronic periodontitis and to evaluate the association of these virulence genes with clinical parameters and with periodontal tissue destruction. MATERIAL AND METHODS: Suppression subtractive hybridization was applied to acquire short gene fragments harbored only in virulent strains of P. gingivalis W83. Eighteen genes, which were present in P. gingivalis W83 but absent from P. gingivalis ATCC 33277, were labeled with Cy5 and used as probes in DNA microarray hybridization to analyze DNA of P. gingivalis isolated from chronic periodontitis patients. RESULTS: Spearman correlation analysis revealed 10 genes correlated with probing depth, clinical attachment loss, and tooth mobility (p<0.05). CONCLUSION: These genes may provide an important clue towards our understanding the mechanism of occurrence and the development of periodontal disease.

The harmonic scalpel versus electrocautery for parotidectomy: A meta - analysis.

OBJECTIVE: Parotidectomy is the most classic and unequivocal intervention for parotid neoplasm. The operative outcomes and postoperative complications of parotidectomy between harmonic scalpel and electrocautery gained more prominence in physician. In spite of much research work within the past years, there was an obvious lack of randomized controlled trial to resolve this question. Hence, a quantitative and qualitative meta-analysis was essential to evaluate the differences in these two types of hemostasis method. METHOD: The major electronic databases, including Pubmed, Embase, Cochrane library, Google Scholar, China National Knowledge Infrastructure and Chinese Scientific and Technological Journal databases were using the key words "electrocautery", "electrocoagulation", "harmonic scalpel", "ultrasonic scalpel", "ultrasonic dissector", "parotidectomy" and "parotid surgery". 9 articles were included in our systematic review and meta-analysis. The operative time, intraoperative blood loss, hospital stay, salivary fistula and transient facial nerve paralysis were the outcome measures. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to evaluate the effect size for categorical outcomes and mean differences (MDs) with 95% confidence intervals (CIs) for continuous outcomes. RESULTS: In our meta-analysis, there was a significant reduction in operation time [mean difference: -20.97; 95%CI=(-24.02,-17.92); P < 0.00001], intraoperative blood loss [mean difference: -20.75, 95%CI=(-22.32,-19.18); P < 0.00001], hospital stay [mean difference: -0.83; 95%CI=(-1.10,-0.57); P < 0.00001], salivary fistula [ORs: 0.30, 95%CI=(0.08,1.14)] and transient facial nerve paralysis [OR:0.33, 95%CI=(0.19,0.58),P = 0.0001] in harmonic scalpel group compared with electrocautery group. CONCLUSION: This meta-analysis indicated that compared with electrocautery, harmonic scalpel (HS)was transcendent in the aspects of operative time, intraoperative blood loss, hospital stay, salivary fistula and transient facial nerve paralysis. The harmonic scalpel, as an efficient and useful instrument, was advocated in parotidectomy.

Inflammatory responses of gingival epithelial cells stimulated with Porphyromonas gingivalis vesicles are inhibited by hop-associated polyphenols.

BACKGROUND: Periodontitis is induced by an imbalance between bacterial virulence and host defense ability. Porphyromonas gingivalis, a predominant periodontal pathogen, triggers a series of host inflammatory responses that aggravate the destruction of periodontium. Thus, anti-inflammatory reagents are considered desirable for effective periodontal therapy. In the present study, we examined the inhibitory effects of hop bract polyphenol (HBP) on cellular inflammatory responses induced by P. gingivalis membrane vesicles. METHODS: Immortalized human gingival epithelial cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP on mRNA expression of cyclooxygenase (COX)-2, interleukin (IL)-6 and -8, and matrix metalloproteinase (MMP)-1 and -3 were examined using real-time reverse transcription-polymerase chain reaction. RESULTS: HBP inhibited the mRNA expression of COX-2, IL-6 and -8, and MMP-1 and -3 in a dose-dependent manner, whereas epigallocatechin gallate (a control polyphenol) inhibited COX-2 mRNA expression only. Following further fractionation of HBP to identify the effective components, 2-[(2-methylpropanoyl)-phloroglucinol]1-O-beta-D-glucopyranoside (MPPG) was identified as a significant anti-inflammatory element that completely inhibited the inflammatory mRNA induction. Kaempferol 3-O-beta-glucopyranoside (astragalin) also was found to have anti-inflammatory effects. CONCLUSIONS: HBP is suggested to be a potent inhibitor of cellular inflammatory responses induced by P. gingivalis vesicles. Further, MPPG and astragalin, identified here as effective components of HBP, also may be useful for the prevention and/or attenuation of periodontitis.

Cervical lymph node metastases in salivary gland adenoid cystic carcinoma: a systematic review and meta-analysis.

BACKGROUND: The purpose of this research was to determine whether neck dissection is necessary for the adenoid cystic carcinoma (ACC) of head and neck. MATERIALS AND METHODS: This article screened the abstract and full-text papers that investigated salivary gland primary ACC of head and neck. Two independent reviewers searched for articles published before October 2017 in three databases (Web of Science, PubMed, and Ovid), having no limits in date and language. Statistical data were analyzed statistically by Review Manager 5.3. RESULTS: In total, 18 studies involving 2993 patients were included in the analysis. Of the 2993 patients, 473 patients had cervical lymph node metastasis, with a merge frequency of 16% (95% CI: 13-19). Among included articles, only 4 involved cervical lymph node occult metastases, with a merge frequency of 14% (95% CI: 9-20). There were 5 articles containing minor salivary glands (MiSGs) involving 370 patients of which 92 patients had cervical lymph node metastases and the merge frequency was 25% (95% CI: 11-38). Moreover, there were 4 studies on major salivary glands involving 904 patients of which 158 patients had cervical lymph node metastases and the merge frequency was 17% (95% CI: 15-20). CONCLUSION: Elective neck dissection is unnecessary for all patients with salivary gland ACC of head and neck. Moreover, compared with major salivary glands, MiSGs have a higher cervical lymph node metastases rate in ACC. The overall cervical lymph node metastases rate of MiSGs is 25%, which is enough to attract our attention. Therefore, we suggest that neck dissection might be applied to ACC of MiSGs.

Mitophagy Contributes to the Pathogenesis of Inflammatory Diseases.

Mitophagy is a metabolic process to remove excessive or damaged mitochondria in eukaryotic cells. It is well-known that mitochondria are one of the major sources of reactive oxygen species (ROS). Mitochondrial ROS and damage-associated molecular patterns (DAMPs) can activate inflammasomes to induce inflammatory responses. Once the activation is regulated improperly, excessive inflammation will bring about various tissue injuries, resulting in a series of diseases. However, the selective mitochondrial autophagy can specifically eliminate dysfunctional mitochondria to maintain mitochondrial homeostasis and protect against the hyperinflammation induced by ROS and DAMPs. Recent studies demonstrated that a variety of internal and external factors regulate several inflammatory diseases via altering the level of mitophagy. In this review, we summarize the latest research progress of mitophagy and focus on the inflammatory responses regulated by mitophagy, aiming to illuminate the role of mitophagy in inflammation and provide clues to the diagnosis and therapy of inflammatory diseases.

Efficacy of Adjunctive Bioactive Materials in the Treatment of Periodontal Intrabony Defects: A Systematic Review and Meta-Analysis.

OBJECTIVES: Lots of bioactive materials have been additionally applied for the treatment of periodontal intrabony defect. However, there is dearth of studies to systematically evaluate the supplementary role of them in periodontal regeneration. The goal of this meta-analysis is to evaluate the adjunctive effects of bioactive materials such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), enamel matrix derivative (EMD), and amnion membrane (AM) on the outcomes of bone grafting treatment for periodontal intrabony defects. METHODS: Articles published before December 2017 were searched electronically in three databases (PubMed, Embase, and Cochrane Central), with no date or language limits. Randomized controlled trials (RCTs) on the assessment of effectiveness of the four biomaterials in conjunction with demineralized freeze-dried bone allografts (DFDBA) in the treatment of periodontal intrabony defects were enrolled in this meta-analysis. Data were analyzed with STATA 12. RESULTS: Nine studies were included. PRF and PRP significantly improved pocket depth (PD) reduction and clinical attachment loss (CAL) gain. Only PRF exhibited a positive result in recession reduction (RecRed). Only PRP showed a statistically significant increase in bone fill. AM merely gained more CAL. EMD did not improve any clinical outcome. CONCLUSION: Our data suggest that PRF/PRP could be taken as a preferred adjunct to facilitate periodontal regeneration of intrabony defects.

Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis.

PURPOSE: The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis. MATERIALS AND METHODS: Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure) without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3. RESULTS: Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0-7.0). Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0-10.0). Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels. CONCLUSION: Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated level IIb, level IIb dissection could be avoided when the primary lesions were in early stages (T1 and T2), with the exception of tongue cancer. It is recommended to dissect level IIb tongue cancers without considering the stages of primary lesions and the lymph nodes status. It is also suggested that level IIb dissection should be performed in patients preoperatively or intraoperatively found with multilevel neck metastasis, especially level IIa metastasis.

Porphyromonas gingivalis modulates Pseudomonas aeruginosa-induced apoptosis of respiratory epithelial cells through the STAT3 signaling pathway.

Pseudomonas aeruginosa is an important opportunistic bacterial pathogen, causing infections of respiratory and other organ systems in immunocompromised hosts that may invade and proliferate in mucosal epithelial cells to induce apoptosis. Previous studies suggest that oral bacteria, especially gram-negative periodontal pathogens, may enhance P. aeruginosa invasion into respiratory epithelial cells to augment tissue destruction. In this study, we investigated the effect of the periodontopathogen Porphyromonas gingivalis on P. aeruginosa-induced epithelial cell apoptosis. P. gingivalis invasion transiently inhibited P. aeruginosa-induced apoptosis in respiratory epithelial cells via the signal transducer and activator of transcription 3 (STAT3) signaling pathway. The activated STAT3 up-regulated the downstream anti-apoptotic moleculars survivin and B-cell leukemia-2 (bcl-2). This process was accompanied by down-regulation of pro-apoptosis molecular Bcl-2-associated death promoter (bad) and caspase-3 activity inhibition. In addition, the activation of the STAT3 pathway was affected by P. gingivalis in a dose-dependent manner. Finally, co-invasion of P. aeruginosa and P. gingivalis led to greater cell death compared with P. aeruginosa challenge alone. These results suggest that regulation of P. aeruginosa-induced apoptosis by P. gingivalis contributes to the pathogenesis of respiratory disease. Interference with this process may provide a potential therapeutic strategy for the treatment and prevention of respiratory disease.

Identification of hop polyphenolic components which inhibit prostaglandin E2 production by gingival epithelial cells stimulated with periodontal pathogen.

Chronic marginal periodontitis is a destructive inflammatory disease caused by an imbalance between bacterial virulence and host defense ability, resulting in eventual tooth exfoliation. Porphyromonas gingivalis, a major periodontal pathogen, triggers a series of cellular inflammatory responses including the production of prostaglandin E2 (PGE2), which causes periodontal destruction; thus, anti-inflammatory reagents are considered beneficial for periodontal therapy. In the present study, we examined whether hop- and apple-derived polyphenols (HBP and ACT, respectively) inhibit PGE2 production by human gingival epithelial (HGE) cells stimulated with P. gingivalis components. HGE cells were stimulated with P. gingivalis membrane vesicles, and the effects of HBP, ACT and epigallocatechin gallate (EGCg) on PGE2 production by HGE cells were evaluated using an enzyme-linked immunosorbent assay. HBP and EGCg significantly inhibited PGE2 production, whereas ACT did not. By further fractionation steps of HBP to identify the effective components, 3 components of HBP, 2-[(2-methylpropanoyl)-phloroglucinol]1-O-beta-D-glucopyranoside (MPPG), quercetin 3-O-beta-D-glucopyranoside (isoquercitrin), and kaempferol 3-O-beta-glucopyranoside (astragalin), were found to be elements which significantly inhibited cellular PGE2 production. These results suggest that HBP is a potent inhibitor of cellular PGE2 production induced by P. gingivalis, and HBP may be useful for the prevention and attenuation of periodontitis.

[Porphyromonas gingivalis vesicle induced cellular inflammatory responses of gingival epithelial cells in vitro].

OBJECTIVE: To establish the model of cellular inflammatory responses of gingival epithelial cells in vitro induced by Porphyromonas gingivalis vesicle and to probe into the pathogenesis of Porphyromonas gingivalis in periodontitis. METHODS: The effect of Porphyromonas gingivalis vesicle on prostaglandin E(2) (PGE(2)) production of gingival epithelial cells was detected by ELISA and the effects of Porphyromonas gingivalis vesicle on cyclooxygenase-2 (COX-2), interleukin (IL)-6 and IL-8 mRNA expression in gingival epithelial cells were determined by Real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Porphyromonas gingivalis vesicle dose-dependently induced PGE(2) production and up-regulated COX-2, IL-6 and IL-8 mRNA expression in gingival epithelial cells significantly. CONCLUSIONS: Cellular inflammatory responses of gingival epithelial cells induced by Porphyromonas gingivalis vesicle may contribute to the initiation and progression of periodontitis.

[Effects of epidermal growth factor on calciumion and cAMP in the ductal cells of submandibular glands].

PURPOSE: To study the effects of EGF on Ca(2+) and cAMP in the ductal cells of rat SMG. METHODS: Fluorometric technique and radioimmunological technique were used to investigate the dynamic changes of Ca(2+) and cAMP in the ductal cells. The data were analysed statistically by t test. RESULTS: After an momently latent period, intercellular calcium increased rapidly, then began to decline. This period could last 5 minutes. After 3 minutes, cAMP showed a rapid decrease, and then increased slowly. Its concentration could restore 90 minutes later. CONCLUSION: EGF may regulate intercellular calcium and cAMP, which results in the proliferation of the ductal cells.