ResearchPad - oral-diseases https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Confocal Raman microscopy to identify bacteria in oral subgingival biofilm models]]> https://www.researchpad.co/article/elastic_article_7675 The study of oral disease progression, in relation to the accumulation of subgingival biofilm in gingivitis and periodontitis is limited, due to either the ability to monitor plaque in vitro. When compared, optical spectroscopic techniques offer advantages over traditional destructive or biofilm staining approaches, making it a suitable alternative for the analysis and continued development of three-dimensional structures. In this work, we have developed a confocal Raman spectroscopy analysis approach towards in vitro subgingival plaque models. The main objective of this study was to develop a method for differentiating multiple oral subgingival bacterial species in planktonic and biofilm conditions, using confocal Raman microscopy. Five common subgingival bacteria (Fusobacterium nucleatum, Streptococcus mutans, Veillonella dispar, Actinomyces naeslundii and Prevotella nigrescens) were used and differentiated using a 2-way orthogonal Partial Least Square with Discriminant Analysis (O2PLS-DA) for the collected spectral data. In addition to planktonic growth, mono-species biofilms cultured using the ‘Zürich Model’ were also analyzed. The developed method was successfully used to predict planktonic and mono-species biofilm species in a cross validation setup. The results show differences in the presence and absence of chemical bands within the Raman spectra. The O2PLS-DA model was able to successfully predict 100% of all tested planktonic samples and 90% of all mono-species biofilm samples. Using this approach we have shown that Confocal Raman microscopy can analyse and predict the identity of planktonic and mono-species biofilm species, thus enabling its potential as a technique to map oral multi-species biofilm models.

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<![CDATA[Specific clones of Trichomonas tenax are associated with periodontitis]]> https://www.researchpad.co/article/5c900d3bd5eed0c48407e3b6

Trichomonas tenax, an anaerobic protist difficult to cultivate with an unreliable molecular identification, has been suspected of involvement in periodontitis, a multifactorial inflammatory dental disease affecting the soft tissue and bone of periodontium. A cohort of 106 periodontitis patients classified by stages of severity and 85 healthy adult control patients was constituted. An efficient culture protocol, a new identification tool by real-time qPCR of T. tenax and a Multi-Locus Sequence Typing system (MLST) based on T. tenax NIH4 reference strain were created. Fifty-three strains of Trichomonas sp. were obtained from periodontal samples. 37/106 (34.90%) T. tenax from patients with periodontitis and 16/85 (18.80%°) T. tenax from control patients were detected by culture (p = 0.018). Sixty of the 191 samples were tested positive for T. tenax by qPCR, 24/85 (28%) controls and 36/106 (34%) periodontitis patients (p = 0.089). By combining both results, 45/106 (42.5%) patients were positive by culture and/or PCR, as compared to 24/85 (28.2%) controls (p = 0.042). A link was established between the carriage in patients of Trichomonas tenax and the severity of the disease. Genotyping demonstrates the presence of strain diversity with three major different clusters and a relation between disease strains and the periodontitis severity (p<0.05). More frequently detected in periodontal cases, T. tenax is likely to be related to the onset or/and evolution of periodontal diseases.

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<![CDATA[Reporting quality and spin in abstracts of randomized clinical trials of periodontal therapy and cardiovascular disease outcomes]]> https://www.researchpad.co/article/N5a52c97b-59d0-4564-8bd9-d8b1530b3570

Objective

Poor reporting in randomized clinical trial (RCT) abstracts reduces quality and misinforms readers. Spin, a biased presentation of findings, could frequently mislead clinicians to accept a clinical intervention despite non-significant primary outcome. Therefore, good reporting practices and absence of spin enhances research quality. We aim to assess the reporting quality and spin in abstracts of RCTs evaluating the effect of periodontal therapy on cardiovascular (CVD) outcomes.

Methods

PubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), and 17 trial registration platforms were searched. Cohort, non-randomized, non-English studies, and pediatric studies were excluded. RCT abstracts were reviewed by 2 authors using the CONSORT for abstracts and spin checklists for data extraction. Cohen’s Kappa statistic was used to assess inter-rater agreement. Data on the selected RCT publication metrics were collected. Descriptive analysis was performed with non-parametric methods. Correlation analysis between quality, spin and bibliometric parameters was conducted.

Results

24 RCTs were selected for CONSORT analysis and 14 fulfilled the criteria for spin analysis. Several important RCT elements per CONSORT were neglected in the abstract including description of the study population (100%), explicitly stated primary outcome (87%), methods of randomization and blinding (100%), trial registration (87%). No RCT examined true outcomes (CVD events). A significant fraction of the abstracts appeared with at least one form of spin in the results and conclusions (86%) and claimed some treatment benefit in spite of non-significant primary outcome (64%). High-quality reporting had a significant positive correlation with reporting of trial registration (p = 0.04) and funding (p = 0.009). Spinning showed marginal negative correlation with reporting quality (p = 0.059).

Conclusion

Poor adherence to the CONSORT guidelines and high levels of data spin were found in abstracts of RCTs exploring the effects of periodontal therapy on CVD outcomes. Our findings indicate that journal editors and reviewers should consider strict adherence to proper reporting guidelines to improve reporting quality and reduce waste.

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<![CDATA[Mixed evidence for the relationship between periodontitis and Alzheimer’s disease: A bidirectional Mendelian randomization study]]> https://www.researchpad.co/article/N89b89fe7-2f39-423b-9f5f-6e2e7b2736b5

Recent experimental studies indicated that a periodontitis-causing bacterium might be a causal factor for Alzheimer’s disease (AD). We applied a two-sample Mendelian randomization (MR) approach to examine the potential causal relationship between chronic periodontitis and AD bidirectionally in the population of European ancestry. We used publicly available data of genome-wide association studies (GWAS) on periodontitis and AD. Five single-nucleotide polymorphisms (SNPs) were used as instrumental variables for periodontitis. For the MR analysis of periodontitis on risk of AD, the causal odds ratio (OR) and 95% confidence interval (CI) were derived from the GWAS of periodontitis (4,924 cases vs. 7,301 controls) and from the GWAS of AD (21,982 cases vs. 41,944 controls). Seven non-overlapping SNPs from another latest GWAS of periodontitis was used to validate the above association. Twenty SNPs were used as instrumental variables for AD. For the MR analysis of liability to AD on risk of periodontitis, the causal OR was derived from the GWAS of AD including 30,344 cases and 52,427 controls and from the GWAS of periodontitis consisted of 12,289 cases and 22,326 controls. We employed multiple methods of MR. Using the five SNPs as instruments of periodontitis, there was suggestive evidence of genetically predicted periodontitis being associated with a higher risk of AD (OR 1.10, 95% CI 1.02 to 1.19, P = 0.02). However, this association was not verified using the seven independent SNPs (OR 0.97, 95% CI 0.87 to 1.08, P = 0.59). There was no association of genetically predicted AD with the risk of periodontitis (OR 1.00, 95% CI 0.96 to 1.04, P = 0.85). In summary, we did not find convincing evidence to support periodontitis being a causal factor for the development of AD. There was also limited evidence to suggest genetic liability to AD being associated with the risk of periodontitis.

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<![CDATA[Subgingival areas as potential reservoirs of different Candida spp in type 2 diabetes patients and healthy subjects]]> https://www.researchpad.co/article/5c40f77fd5eed0c48438628b

Objectives

The aim of this cross-sectional observational study was to compare the prevalence of different oral Candida spp. in patients with Type 2 Diabetes and chronic periodontitis in two oral sites: dorsal surface of the tongue and subgingival area. In order to determine subgingival areas as potential reservoirs of yeasts, this study aimed to find differences in the yeasts’ detection between the dorsum of the tongue, as the oral site most commonly inhabited with microorganisms, and subgingival samples. Additionally, potential predictors for the yeasts prevalence were determined.

Material and methods

Subjects (N = 146) were divided into four groups: group A- healthy individuals without periodontitis, group B- healthy individuals with chronic periodontitis, group C- Type 2 Diabetes patients with good glycoregulation and Chronic periodontitis and group D- Type 2 Diabetes patients with poor glycoregulation and Chronic periodontitis. Samples were obtained from the tongue by swabbing. Subgingival plaque samples were taken by paper points and periodontal curette. Isolation and identification of different Candida spp. was done using ChromAgar medium. In addition, germ-tube production and carbohydrate assimilation tests were performed.

Results

The prevalence of Candida spp. was higher in diabetics with poor glycoregulation. The most frequently isolated species was Candida albicans followed by Candida glabrata and Candida tropicalis. In 15.6% of cases, Candida spp. was present in the subgingival area while absent on the tongue. Multivariate regression model showed that HbA1c was Candida spp. predictor for both locations.

Conclusions

Our results confirmed that there are Candida spp. carriers among subjects with clinically healthy oral mucosa. Also, this study identified subgingival areas as potential reservoirs of these pathogenic species. Glycoregulation has been recognized as a positive predictor factor of Candida spp.

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<![CDATA[Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis]]> https://www.researchpad.co/article/5c2544f9d5eed0c48442bc3a

Chronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and TLR-4 mRNA exhibited an inverse correlation (r2 = 0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.

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<![CDATA[Genetic Variations in Key MicroRNA Processing Genes and Risk of Head and Neck Cancer: A Case-Control Study in Chinese Population]]> https://www.researchpad.co/article/5989da71ab0ee8fa60b94ca6

MicroRNAs (miRNAs) have been reported to play a key role in oncogenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the miRNA-mRNA interactions, hence promoting tumorigenesis. In the present study, we hypothesized that potentially functional polymorphisms in miRNA processing genes may contribute to head and neck cancer (HNC) susceptibility. To test this hypothesis, we genotyped three SNPs at miRNA binding sites of miRNA processing genes (rs1057035 in 3′UTR of DICER, rs3803012 in 3′UTR of RAN and rs10773771 in 3′UTR of HIWI) with a case-control study including 397 HNC cases and 900 controls matched by age and sex in Chinese. Although none of three SNPs was significantly associated with overall risk of HNC, rs1057035 in 3′UTR of DICER was associated with a significantly decreased risk of oral cancer (TC/CC vs. TT: adjusted OR  = 0.65, 95% CI  = 0.46–0.92). Furthermore, luciferase activity assay showed that rs1057035 variant C allele led to significantly lower expression levels as compared to the T allele, which may be due to the relatively high inhibition of hsa-miR-574-3p on DICER mRNA. These findings indicated that rs1057035 located at 3′UTR of DICER may contribute to the risk of oral cancer by affecting the binding of miRNAs to DICER. Large-scale and well-designed studies are warranted to validate our findings.

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<![CDATA[Role of Bcr1-Activated Genes Hwp1 and Hyr1 in Candida Albicans Oral Mucosal Biofilms and Neutrophil Evasion]]> https://www.researchpad.co/article/5989daa4ab0ee8fa60ba6f07

Candida albicans triggers recurrent infections of the oropharyngeal mucosa that result from biofilm growth. Prior studies have indicated that the transcription factor Bcr1 regulates biofilm formation in a catheter model, both in vitro and in vivo. We thus hypothesized that Bcr1 plays similar roles in the formation of oral mucosal biofilms and tested this hypothesis in a mouse model of oral infection. We found that a bcr1/bcr1 mutant did not form significant biofilm on the tongues of immunocompromised mice, in contrast to reference and reconstituted strains that formed pseudomembranes covering most of the tongue dorsal surface. Overexpression of HWP1, which specifies an epithelial adhesin that is under the transcriptional control of Bcr1, partly but significantly rescued the bcr1/bcr1 biofilm phenotype in vivo. Since HWP1 overexpression only partly reversed the biofilm phenotype, we investigated whether additional mechanisms, besides adhesin down-regulation, were responsible for the reduced virulence of this mutant. We discovered that the bcr1/bcr1 mutant was more susceptible to damage by human leukocytes when grown on plastic or on the surface of a human oral mucosa tissue analogue. Overexpression of HYR1, but not HWP1, significantly rescued this phenotype. Furthermore a hyr1/hyr1 mutant had significantly attenuated virulence in the mouse oral biofilm model of infection. These discoveries show that Bcr1 is critical for mucosal biofilm infection via regulation of epithelial cell adhesin and neutrophil function.

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<![CDATA[Identification and Characterization of Fusolisin, the Fusobacterium nucleatum Autotransporter Serine Protease]]> https://www.researchpad.co/article/5989d9ebab0ee8fa60b6c950

Fusobacterium nucleatum is an oral anaerobe associated with periodontal disease, adverse pregnancy outcomes and colorectal carcinoma. A serine endopeptidase of 61–65 kDa capable of damaging host tissue and of inactivating immune effectors was detected previously in F. nucleatum. Here we describe the identification of this serine protease, named fusolisin, in three oral F. nucleatum sub-species. Gel zymogram revealed fusobacterial proteolytic activity with molecular masses ranging from 55–101 kDa. All of the detected proteases were inhibited by the serine protease inhibitor PMSF. analysis revealed that all of the detected proteases are encoded by genes encoding an open reading frame (ORF) with a calculated mass of approximately 115 kDa. Bioinformatics analysis of the identified ORFs demonstrated that they consist of three domains characteristic of autotransporters of the type Va secretion system. Our results suggest that the F. nucleatum fusolisins are derived from a precursor of approximately 115 kDa. After crossing the cytoplasmic membrane and cleavage of the leader sequence, the C-terminal autotransporter domain of the remaining 96–113 kDa protein is embedded in the outer membrane and delivers the N-terminal S8 serine protease passenger domain to the outer cell surface. In most strains the N-terminal catalytic 55–65 kDa domain self cleaves and liberates itself from the autotransporter domain after its transfer across the outer cell membrane. In F. nucleatum ATCC 25586 this autocatalytic activity is less efficient resulting in a full length membrane-anchored serine protease. The mature serine protease was found to cleave after Thr, Gly, Ala and Leu residues at the P1 position. Growth of F. nucleatum in complex medium was inhibited when serine protease inhibitors were used. Additional experiments are needed to determine whether fusolisin might be used as a target for controlling fusobacterial infections.

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<![CDATA[Thrombospondin-1 Production Is Enhanced by Porphyromonas gingivalis Lipopolysaccharide in THP-1 Cells]]> https://www.researchpad.co/article/5989daa1ab0ee8fa60ba5fb1

Periodontitis is a chronic inflammatory disease caused by gram-negative anaerobic bacteria. Monocytes and macrophages stimulated by periodontopathic bacteria induce inflammatory mediators that cause tooth-supporting structure destruction and alveolar bone resorption. In this study, using a DNA microarray, we identified the enhanced gene expression of thrombospondin-1 (TSP-1) in human monocytic cells stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS). TSP-1 is a multifunctional extracellular matrix protein that is upregulated during the inflammatory process. Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis. TSP-1 is secreted from neutrophils, monocytes, and macrophages, which mediate immune responses at inflammatory regions. However, TSP-1 expression in periodontitis and the mechanisms underlying TSP-1 expression in human monocytic cells remain unknown. Here using real-time RT-PCR, we demonstrated that TSP-1 mRNA expression level was significantly upregulated in inflamed periodontitis gingival tissues and in P. gingivalis LPS-stimulated human monocytic cell line THP-1 cells. TSP-1 was expressed via Toll-like receptor (TLR) 2 and TLR4 pathways. In P. gingivalis LPS stimulation, TSP-1 expression was dependent upon TLR2 through the activation of NF-κB signaling. Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production. These results suggest that modulation of TSP-1 expression by P. gingivalis plays an important role in the progression and chronicity of periodontitis. It may also contribute a new target molecule for periodontal therapy.

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<![CDATA[Differential Impact of IL-10 Expression on Survival and Relapse between HPV16-Positive and -Negative Oral Squamous Cell Carcinomas]]> https://www.researchpad.co/article/5989da79ab0ee8fa60b97e01

Human papillomavirus (HPV) is a risk factor in a subset of oropharyngeal cancer; however, the contribution of HPV in the malignancy of oral squamous cell carcinomas (OSCC) is not fully understood in Taiwanese. Herein, 61 patients with no risk factors and 117 patients with one or more risk factors were enrolled in this study. HPV16/18 infection rate in non-smokers, non-drinkers and non-betel quid chewers was higher than their counterparts. The development of HPV-infected cancer has been shown to be associated with interleukin-10 (IL-10) expression. To this end, IL-10 mRNA expression in OSCC tumors was evaluated by real-time RT-PCR. Data showed that HPV-positive patients had higher IL-10 mRNA levels than in HPV-negative patients. Kaplan-Meier and Cox-regression analysis indicated that the prognostic significance of IL-10 mRNA on overall survival and relapse free survival was only observed in HPV-positive OSCC, but not in HPV-negative OSCC. Mechanistically, the elevation of IL-10 by E6 was responsible for increased colony formation and migration capability in OSCC cells. Therefore, we suggest that IL-10 induced by E6 promotes cell growth and migration capability and consequent poor survival and relapse in HPV-positive OSCC.

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<![CDATA[Simultaneous Assessment of Acidogenesis-Mitigation and Specific Bacterial Growth-Inhibition by Dentifrices]]> https://www.researchpad.co/article/5989da39ab0ee8fa60b8763a

Dentifrices can augment oral hygiene by inactivating bacteria and at sub-lethal concentrations may affect bacterial metabolism, potentially inhibiting acidogenesis, the main cause of caries. Reported herein is the development of a rapid method to simultaneously measure group-specific bactericidal and acidogenesis-mitigation effects of dentifrices on oral bacteria. Saliva was incubated aerobically and anaerobically in Tryptone Soya Broth, Wilkins-Chalgren Broth with mucin, or artificial saliva and was exposed to dentifrices containing triclosan/copolymer (TD); sodium fluoride (FD); stannous fluoride and zinc lactate (SFD1); or stannous fluoride, zinc lactate and stannous chloride (SFD2). Minimum inhibitory concentrations (MIC) were determined turbidometrically whilst group-specific minimum bactericidal concentrations (MBC) were assessed using growth media and conditions selective for total aerobes, total anaerobes, streptococci and Gram-negative anaerobes. Minimum acid neutralization concentration (MNC) was defined as the lowest concentration of dentifrice at which acidification was inhibited. Differences between MIC and MNC were calculated and normalized with respect to MIC to derive the combined inhibitory and neutralizing capacity (CINC), a cumulative measure of acidogenesis-mitigation and growth inhibition. The overall rank order for growth inhibition potency (MIC) under aerobic and anaerobic conditions was: TD> SFD2> SFD1> FD. Acidogenesis-mitigation (MNC) was ordered; TD> FD> SFD2> SFD1. CINC was ordered TD> FD> SFD2> SFD1 aerobically and TD> FD> SFD1> SFD2 anaerobically. With respect to group-specific bactericidal activity, TD generally exhibited the greatest potency, particularly against total aerobes, total anaerobes and streptococci. This approach enables the rapid simultaneous evaluation of acidity mitigation, growth inhibition and specific antimicrobial activity by dentifrices.

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<![CDATA[Inverse Association of Plasma IgG Antibody to Aggregatibacter actinomycetemcomitans and High C-Reactive Protein Levels in Patients with Metabolic Syndrome and Periodontitis]]> https://www.researchpad.co/article/5989da52ab0ee8fa60b8e31d

The association between clinically diagnosed periodontitis, a common chronic oral infection, and metabolic syndrome has been previously reported. The aim of this study was to investigate the association of plasma IgG levels against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, C-reactive protein, and periodontal status with metabolic syndrome. Plasma IgG levels and C-reactive protein were measured by enzyme-linked immunosorbent assay, and salivary levels of A. actinomycetemcomitans and P. gingivalis were determined by quantitative real-time polymerase chain reaction. Among 127 individuals aged 35–76 years, 57 participants had metabolic syndrome and severe periodontitis, 25 had metabolic syndrome and an absence of severe periodontitis, 17 healthy individuals had severe periodontitis, and 28 healthy individuals were without severe periodontitis. Patients with metabolic syndrome had reduced humoral immune response to A. actinomycetemcomitans (p = 0.008), regardless of their salivary levels or periodontitis status compared with healthy participants. The IgG antibody response to P. gingivalis, regardless of their salivary levels or participants’ health condition, was significantly higher in severe periodontitis patients (p<0.001). Plasma IgG titers for P. intermedia were inconsistent among metabolic syndrome or periodontal participants. Our results indicate that the presence of lower levels of IgG antibodies to A. actinomycetemcomitans (OR = 0.1; 95%CI 0.0–0.7), but not P. gingivalis, a severe periodontitis status (OR = 7.8; 95%CI 1.1–57.0), high C-reactive protein levels (OR = 9.4; 95%CI 1.0–88.2) and body mass index (OR = 3.0; 95%CI 1.7–5.2), are associated with the presence of metabolic syndrome. The role of the decreased IgG antibody response to A. actinomycetemcomitans, increased C-reactive protein levels on the association between periodontal disease and metabolic syndrome in a group of Thai patients is suggested.

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<![CDATA[Profiling of subgingival plaque biofilm microbiota in adolescents after completion of orthodontic therapy]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdb95f

Background

Fixed orthodontic treatment is the most common method for malocclusion but has the potential risk of periodontal complication with unclear outcomes of whether microbiologic and clinical changes could be reversible in adolescents after orthodontic therapy.

Methods

Twenty adolescents with orthodontic treatment were enrolled in the study as the case group at end of the therapy, while 19 periodontally healthy adolescents were involved in the control group. At baseline (T0), clinical parameters including gingival index, probing depth and sulcus bleeding index were tested, and subgingival plaque samples were collected from the lower incisors. The counts of A. actinomycetemcomitans, P. gingivalis, P. intermedia, T. forsythia and total bacteria were determined by real-time PCR. All parameters were reassessed after 1 month (T1) and 3 months (T2) in the case group and compared with that of the controls.

Results

At baseline (T0), clinical parameters (including GI, PD, SBI) of the test sites in the case group were significantly higher than that of the control group (P<0.05 or P<0.01). At 3 months (T2), no differences were noticed in GI and SBI between two groups. The prevalence and counts of periodontopathogens tend to be normal (P>0.05), while PD and the amount of P.intermedia were still significantly higher compared with that of the control group (P<0.05 or P<0.01).

Conclusion

After removal of appliances, the periodontal changes induced by orthodontic therapy are only partially reversible at 3 months after removal.

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<![CDATA[Targeting Serum Glucocorticoid-Regulated Kinase-1 in Squamous Cell Carcinoma of the Head and Neck: A Novel Modality of Local Control]]> https://www.researchpad.co/article/5989daf8ab0ee8fa60bc3a9a

Purpose

The inhibition of serum glucocorticoid-regulated kinase-1 (SGK-1) has been found to decrease growth of colon and prostate cancer cells. The purpose of this study is to evaluate the therapeutic effect of SGK-1 inhibition in head and neck squamous cell carcinoma (SCC).

Experimental Design

Human head and neck tumors (HTB41/43) were established in athymic mice. Growth rates between mice treated with vehicle (PBS) injection (group 1, n = 5), SGK-1 Inhibitor GSK 650394 (group 2, n = 6), systemic cisplatin (group 3, n = 6), and a combination of SGK-1 Inhibitor and cisplatin (group 4, n = 6) were compared using repeated measures one-way ANOVA with Newman-Keuls Multiple Comparison Test. Tumor cells were subsequently submitted to further analyses.

Results

At the end of the experiment mean tumor sizes were 122.33+/−105.86, 76.73+/−36.09, 94.52+/−75.92, and 25.76+/−14.89 mm2 (mean +/− SD) for groups 1 to 4. Groups 2 and 3 showed decreased tumor growth compared to controls (p<0.001). Group 4 displayed even greater growth suppression (p<0.0001). Importantly, group 4 fared better than group 3 (p<0.001). CD44 expression was reduced in group 2 (p<0.05), and to an even greater extent in groups 3 and 4 (p<0.0025). A trend towards reduction of HER 2 expression was noted in group 4.

Conclusions

SGK-1 inhibition suppresses tumor growth, and in combination with systemic cisplatin exceeds the effect of cisplatin alone. Decreased expression of CD44 and HER 2 implies depletion of tumor stem cells, and less tumorigenicity. SGK-1 inhibition represents a potential modality of local control for palliation in advanced cases.

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<![CDATA[Expression Profiling of CYP1B1 in Oral Squamous Cell Carcinoma: Counterintuitive Downregulation in Tumors]]> https://www.researchpad.co/article/5989d9f0ab0ee8fa60b6e452

Oral Squamous Cell Carcinoma (OSCC) has a very flagitious treatment regime. A prodrug approach is thought to aid in targeting chemotherapy. CYP1B1, a member of cytochrome P450 family, has been implicated in chemical carcinogenesis. There exists a general accordance that this protein is overexpressed in a variety of cancers, making it an ideal candidate for a prodrug therapy. The activation of the prodrug facilitated by CYP1B1 would enable the targeting of chemotherapy to tumor tissues in which CYP1B1 is specifically overexpressed as a result reducing the non-specific side effects that the current chemotherapy elicits. This study was aimed at validating the use of CYP1B1 as a target for the prodrug therapy in OSCC. The expression profile of CYP1B1 was analysed in a panel of 51 OSCC tumors, their corresponding normal tissues, an epithelial dysplasia lesion and its matched normal tissue by qRT-PCR, Western blotting and Immunohistochemistry. CYP1B1 was found to be downregulated in 77.78% (28/36) tumor tissues in comparison to their corresponding normal tissues as well as in the epithelial dysplasia lesion compared to its matched normal tissue at the transcriptional level, and in 92.86% (26/28) of tumor tissues at the protein level. This report therefore clearly demonstrates the downregulation of CYP1B1 at the transcriptional and translational levels in tumor tissues in comparison to their corresponding normal tissues. These observations indicate that caution should be observed as this therapy may not be applicable universally to all cancers and also suggest the possibility of a prophylactic therapy for oral cancer.

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<![CDATA[Annexin A10 in Human Oral Cancer: Biomarker for Tumoral Growth via G1/S Transition by Targeting MAPK Signaling Pathways]]> https://www.researchpad.co/article/5989d9d6ab0ee8fa60b65e5e

Background

Annexins are calcium and phospholipid binding proteins that form an evolutionary conserved multigene family. Considerable evidence indicates that annexin A10 (ANXA10) is involved in tumoral progression, although little is known about its role in human oral carcinogenesis. In this study, we investigated the involvement of ANXA10 in oral squamous cell carcinoma (OSCC).

Methodology/Principal Findings

ANXA10 mRNA and protein expressions were assessed by quantitative reverse transcriptase polymerase chain reaction and immunoblotting, and we conducted a proliferation assay and cell-cycle analysis in ANXA10 knockdown cells in vitro. We evaluated the correlation between the ANXA10 expression status in 100 primary OSCCs and the clinicopathological features by immunohistochemistry. ANXA10 mRNA and protein expression levels were up-regulated in all cellular lines examined (n = 7, p<0.05). ANXA10 knockdown cells showed that cellular proliferation decreased by inactivation of extracellular regulated kinase (ERK) (p<0.05), and cell-cycle arrest at the G1 phase resulted from up-regulation of cyclin-dependent kinase inhibitors. ANXA10 protein expression in primary OSCCs was also significantly greater than in normal counterparts (p<0.05), and higher expression was correlated with tumoral size (p = 0.027).

Conclusions/Significance

Our results proposed for the first time that ANXA10 is an indicator of cellular proliferation in OSCCs. Our results suggested that ANXA10 expression might indicate cellular proliferation and ANXA10 might be a potential therapeutic target for the development of new treatments for OSCCs.

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<![CDATA[Near Infrared Imaging of EGFR of Oral Squamous Cell Carcinoma in Mice Administered Arsenic Trioxide]]> https://www.researchpad.co/article/5989d9d6ab0ee8fa60b65d35

Background

The effectiveness of near-infrared imaging (NIR) interrogation of epidermal growth factor receptor (EGFR) expression as a sensitive biomarker of oral squamous cell carcinoma (OSCC) response to arsenic trioxide therapy was studied in mice.

Material and Methods

A431 OSCC in vitro were exposed to 0 µM, 0.5 µM, 2.5 µM, or 5 µM of As2O3 for 0 h, 24 h, 48 h and 72 h. Confocal microscopy and flow cytometry confirmed EGFR expression and demonstrated a sensitivity dose-related signal decline with As2O3 treatment. Next, mice with pharynx-implanted A431 cells received As2O3 i.p. every 48 h at 0.0, 0.5, 2.5, or 5 mg/kg/day (n = 6/group) from day 0 to 10. An intravenous NIR probe, EGF-Cy5.5, was injected at baseline and on days 4, 8, and 12 for dynamic NIR imaging. Tumor volume and body weights were measured three times weekly.

Results

In vitro, A431 EGFR expression was well appreciated in the controls and decreased (p<0.05) with increasing As2O3 dose and treatment duration. In vivo EGFR NIR tumor signal intensity decreased (p<0.05) in As2O3 treated groups versus controls from days 4 to 12, consistent with increasing dosage. Tumor volume diminished in a dose-related manner while body weight was unaffected. Immunohistochemical staining of excised tumors confirmed that EGFR expression was reduced by As2O3 treatment in a dose responsive pattern.

Conclusion

This study demonstrates for the first time that OSCC can be interrogated in vivo by NIR molecular imaging of the EGFR and that this biomarker is effective for the longitudinal assessment of OSCC response to As2O3 treatment.

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<![CDATA[Identifying Factors to Improve Oral Cancer Screening Uptake: A Qualitative Study]]> https://www.researchpad.co/article/5989db0aab0ee8fa60bc9d10

Aims

To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake.

Methods

Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week), irregular dental attenders living in economically deprived areas of Teesside.

Results

There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is ‘inaccessible’ on a physical and psychological level, costly, a ‘tooth specialist’ not a ‘mouth specialist’, and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer.

Conclusions

The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a “health” screening setting as opposed to a “dental” setting for such checks.

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<![CDATA[Rapid Maxillary Anterior Teeth Retraction En Masse by Bone Compression: A Canine Model]]> https://www.researchpad.co/article/5989da09ab0ee8fa60b76d05

Objective

The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time.

Method

Extraction of the maxillary canine and alveolar surgery were performed on twelve adult beagle dogs. After that, the custom-made tooth-borne distraction devices were placed on beagles' teeth. Nine of the dogs were applied compression at 0.5 mm/d for 12 days continuously. The other three received no force as the control group. The animals were killed in 1, 14, and 28 days after the end of the application of compression.

Results

The tissue responses were assessed by craniometric measurement as well as histological examination. Gross alterations were evident in the experimental group, characterized by anterior teeth crossbite. The average total movements of incisors within 12 days were 4.63±0.10 mm and the average anchorage losses were 1.25±0.12 mm. Considerable root resorption extending into the dentine could be observed 1 and 14 days after the compression. But after consolidation of 28 days, there were regenerated cementum on the dentine. There was no apparent change in the control group. No obvious tooth loosening, gingival necrosis, pulp degeneration, or other adverse complications appeared in any of the dogs.

Conclusions

This is the first experimental study for testing the technique of rapid anterior teeth retraction en masse aided by modified alveolar surgery. Despite a preliminary animal model study, the current findings pave the way for the potential clinical application that can accelerate orthodontic tooth movement without many adverse complications.

Clinical Relevance

It may become a novel method to shorten the clinical orthodontic treatment time in the future.

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