Effect of non-surgical periodontal therapy on salivary histone deacetylases expression: A prospective clinical study.

AIM: To evaluate the effect of non-surgical periodontal therapy (NSPT) on salivary histone deacetylases (HDACs) gene expression in patients with Stage III-IV periodontitis at baseline and at 3 and 6 months post NSPT treatment. MATERIALS AND METHODS: Twenty patients completed the study. Periodontitis (as well as the corresponding staging and grading) was diagnosed according to the 2017 World Workshop Classification. Clinical measures were recorded and whole unstimulated saliva was collected at baseline and at 3 and 6 months after NSPT. The expression of 11 HDACs was determined using reverse-transcription PCR, and the respective changes over time were evaluated. RESULTS: Six months after NSPT, significant improvements in all clinical periodontal parameters were observed, concomitant with significant up-regulation of HDAC2, 4, 6, 8, 9 and 11 expressions. Subgroup analyses of non-responders and responders revealed no significant differences in HDACs mRNA expression between groups at any time point. CONCLUSIONS: This prospective clinical study identified longitudinal changes in salivary HDACs expression in response to NSPT, which provides new insights into the epigenetic mechanisms underlying the pathobiology of periodontitis and creates avenues for the discovery of novel biomarkers.

TNF-α and OSX mRNA of Salivary Small Extracellular Vesicles in Periodontitis: A Pilot Study.

This cross-sectional pilot study explored extracellular vesicle (EV)-derived gene expression of markers for bone turnover and pro-inflammatory cytokines in periodontal disease. Whole unstimulated saliva was collected from 52 participants (18 healthy, 13 gingivitis, and 21 stages III/IV periodontitis), from which salivary small extracellular vesicles (sEVs) were enriched using the size-exclusion chromatography method, and characterized by morphology, EV-protein, and size distribution, using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), and Nanoparticle Tracking Analysis (NTA), respectively. Bone turnover markers and pro-inflammatory cytokines in salivary sEVs were evaluated using reverse transcription PCR. Salivary sEVs morphology, mode, size distribution, and particle concentration were comparable between healthy, gingivitis, and periodontitis patients. The CD9+ subpopulation was significantly higher in periodontitis-derived salivary sEVs compared with healthy. The detection of sEVs mRNA for osterix and tumor necrosis factor-alpha was significantly decreased and increased, respectively, in periodontitis compared with healthy controls, with good discriminatory power for periodontitis diagnosis (area under the curve >0.72). This pilot study demonstrated that salivary sEVs mRNAs may serve as a potential noninvasive biomarker source for periodontitis diagnosis.

Salivary histone deacetylase in periodontal disease: A cross-sectional pilot study.

OBJECTIVE: The objective of the study was to profile the expression level of histone deacetylase enzymes (HDACs) in human saliva in periodontal health, gingivitis and periodontitis. BACKGROUND: HDACs are epigenetic modulators and a group of enzymes that catalyse the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. HDACs have been detected in gingival tissues and may provide valuable insight into the periodontal inflammatory response. However, no studies have investigated the expression of HDACs in saliva from periodontitis-affected individuals and their capacity for periodontal diagnostics and screening. MATERIALS AND METHODS: Whole unstimulated saliva was collected from 53 participants (17 healthy, 14 gingivitis and 22 stages III/IV periodontitis). The expression of 11 HDACs in saliva samples was determined using RT-qPCR and diagnostic power was calculated using the receiver operating characteristic (ROC) curves and area under the ROC Curve (AUC). RESULTS: Relative to health, the expression of HDAC4, 8 and 10 was downregulated in gingivitis, and the expression of HDAC4, 6, 8 and 9 was downregulated in periodontitis. Increased HDAC1 and decreased HDAC9 expression were observed in periodontitis compared to gingivitis. Higher HDAC1 and lower HDAC6 and 9 expression was observed in periodontitis compared to non-periodontitis (combining health and gingivitis). Expression of HDAC3, 4, 8, 9 and 10 was significantly decreased in periodontal disease (combining gingivitis and periodontitis) compared to health. HDAC4 and 8 exhibited an excellent diagnostic capacity for distinguishing gingivitis and periodontal disease from health (AUC 0.79-0.86). HDAC9 showed an acceptable power in discriminating periodontitis from health, gingivitis and non-periodontitis (AUC 0.76-0.80). Salivary HDAC enzyme activity showed no significant difference among the groups. CONCLUSION: This pilot study has demonstrated the differential expression of HDACs in human saliva for the first time and identified HDAC4, 8 and 9 as potential biomarkers in periodontal diagnosis.

The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review.

Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with periodontitis management. This scoping review aims to evaluate current evidence of global and specific DNA methylation and histone modification in periodontitis and discuss the gaps and implications for future research and clinical practice. Methods: A scoping literature search of three electronic databases was performed in SCOPUS, MEDLINE (PubMed) and EMBASE. As epigenetics in periodontitis is an emerging research field, a scoping review was conducted to identify the extent of studies available and describe the overall context and applicability of these results. Results: Overall, 30 studies were evaluated, and the findings confirmed that epigenetic changes in periodontitis comprise specific modifications to DNA methylation patterns and histone proteins modification, which can either dampen or promote the inflammatory response to bacterial challenge. Conclusions: The plasticity of epigenetic modifications has implications for the future development of targeted epi-drugs and diagnostic tools in periodontitis. Such advances could be invaluable for the early detection and monitoring of susceptible individuals.

Controversies on the relationship between increased body mass index and treatment-resistant chronic constipation in children.

BACKGROUND: There are conflicting reports on the association between children with increased body mass index (BMI), and constipation. This retrospective chart review of two groups of children from a primary care clinic was designed to address the controversy. METHODS: Group-1: Charts of all children seen in a year for general pediatric care were reviewed for incidences of increased BMI (>85th percentile) and constipation as well as overweight recognition in the final diagnosis; Group-2: Children diagnosed with constipation at the same primary care setting for 5 years were identified by ICD-9 code. These charts were reviewed for prevalence of increased BMI and incidences of referral to subspecialty clinic. RESULTS: Group-1: Three hundred nineteen (33.4%) of the 955 children had increased BMI and 28 (2.93%) had constipation. The prevalence of constipation was not increased among children with increased BMI. Group-2: 24 of the 66 children with constipation were referred to the pediatric gastroenterology clinic. children with increased BMI were three times more likely to be referred (n = 20, p = 0.04). The two groups had a similar prevalence of children with increased BMI (Group 1 = 33.4%; Group 2 = 30.3%). CONCLUSION: In the general pediatric population, children with an increased BMI were not at an increased risk of developing constipation. However, children with increased BMI and constipation were three times more likely to be referred, presumably for treatment failure, to the pediatric gastroenterology clinic .Hence children with increased BMI were more likely to develop treatment resistant constipation.

Orthodontic mechanotherapies and their influence on external root resorption: A systematic review.

INTRODUCTION: This systematic review assesses the literature regarding the association between orthodontic tooth movement and external root resorption. By determining the evidence level supporting the association, the results could provide clinical evidence for minimizing the deleterious effect of orthodontic tooth movement. METHODS: Electronic databases, including MEDLINE, PubMed, Embase, Scopus, CINAHL, Cochrane Library, and LILACS, were searched up to February 2018, with hand searching of selected orthodontic journals undertaken to identify any preelectronic publications. Searches were undertaken with no restrictions on year, publication status, or language. Selection criteria included randomized controlled trials conducted with the use of fixed orthodontic appliances or sequential thermoplastic aligners on human patients. The quality of included studies was assessed with the use of the Cochrane Risk of Bias Tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Inter-rater agreement of the review authors was used for the inclusion of primary articles, risk of bias assessment, and evaluation of the quality of evidence (GRADE), and it was calculated with the use of the Cohen kappa statistic. RESULTS: A total of 654 articles were retrieved in the initial search. After the review process, 25 articles describing 24 individual trials met the inclusion criteria. Sample sizes ranged from 6 to 154 patients. Most articles were classified as having unclear risks of bias and very low to low quality of evidence. CONCLUSIONS: There is very low to low evidence for supporting positive associations between root resorption and increased force levels, force continuity, intrusive forces, and treatment duration. Moreover, by including a pause in treatment for patients experiencing root resorption, it may be possible for the clinician to reduce the severity of the condition. Of the included studies, the most common methodologic flaws include the absence of a control group, appropriate randomization strategy, and adequate examinations before and after treatment.