miRNAs as Epigenetic Biomarkers in the Study of the Bidirectional Relationship between Type 2 Diabetes Mellitus and Periodontitis: A Systematic Review.

The objective of this study is to analyze the miRNA expression of oral fluids such as gingival crevicular fluid (GCF) in patients with periodontitis and Type 2 diabetes mellitus, and how these epigenetic biomarkers can influence the bidirectional relationship of these two inflammatory diseases. This review was conducted following the PRISMA criteria. PubMed, Scopus, Cochrane Library, Embase, and Web of Science databases were searched for clinical studies conducted on humans investigating, through GCF miRNA expression, the relationship between periodontal diseases and type 2 diabetes mellitus. In addition, the etiopathogenic pathways of the studied miRNAs were analyzed using the DIANA MIR path tool. A total of 1436 references were identified in the initial literature search, and seven articles were finally included in this review. Most of the articles included in this review were case-control studies and examined the expression of miRNAs in patients with periodontitis with or without diabetes. Due to their characteristics, miRNAs appear to be the ideal biomarkers for improving the understanding and knowledge of the etiopathogenic pathways that link both diseases. Among all the studied miRNAs, miR-146a, miR-155, miR-200b, miR-223, and miR-203 showed strong involvement in inflammatory and metabolic pathways, making them potential good diagnostic and prognostic biomarkers.

MicroRNAs in Gingival Crevicular Fluid: An Observational Case-Control Study of Differential Expression in Periodontitis.

OBJECTIVES: microRNAs (miRNAs) present in the gingival crevicular fluid (GCF) of patients with chronic periodontitis may serve as biomarkers of periodontal disease. The aim of this study was to perform a miRNA-sequencing study of all miRNAs present in GCF, comparing miRNA expression level profiles between advanced chronic periodontitis (CP) patients and healthy subjects (HS). MATERIALS AND METHODS: GCF samples were collected from the single-rooted teeth of patients with severe CP (n = 11) and of HS (n = 12). miRNAs were isolated from GCF using an miRNeasy Serum/Plasma kit(Qiagen GmbH, Hilden, Germany). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression levels of miRNA candidates involved in periodontal pathogenesis. RESULTS: Of all the sequenced miRNAs, miR-199, miR-146a, miR-30a, and miR-338 were identified as best representing the CP patient samples. The validation study identified miR-199 as the most powerful biomarker used to define periodontitis. CONCLUSIONS: Upon sequencing all known miRNAs in GCF for the first time, we uncovered several potential biomarkers to define periodontitis. Identifying miRNAS in the GCF using high-throughput approaches will clarify the role of these molecules in periodontitis and provide biomarkers with potential applications.

MicroRNAs and periodontal disease: a qualitative systematic review of human studies.

PURPOSE: MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators that modulate gene expression and have been identified as biomarkers for several diseases, including cancer. This study aimed to systematically review the relationship between miRNAs and periodontal disease in humans, and to evaluate the potential of miRNAs as diagnostic and prognostic biomarkers of disease. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42020180683). The MEDLINE, Scopus, Cochrane Library, Embase, Web of Science, and SciELO databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs. Expression levels of miRNAs across the different groups were analysed using the collected data. RESULTS: A total of 1,299 references were identified in the initial literature search, and 23 articles were finally included in the review. The study designs were heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-146a. Most studies reported higher expression levels of miR-146a in patients with periodontitis than in healthy controls. In addition, many studies also focused on identifying target genes of the differentially expressed miRNAs that were significantly related to periodontal inflammation. CONCLUSIONS: The results of the studies that we analysed are promising, but diagnostic tests are needed to confirm the use of miRNAs as biomarkers to monitor and aid in the early diagnosis of periodontitis in clinical practice.

Role of cone-beam computed tomography (CBCT) in diagnosis and treatment planning of two-rooted maxillary lateral incisor with palatogingival groove. Case report.

BACKGROUND: The embryonic root groove is an anatomical abnormality that starts in the cingulum and extends longitudinally down the long axis root towards the apex. This developmental anomaly is more frequently reported in maxillary lateral incisors. Gu YC in 2011 established three types of radicular grooves depending on its severity. According to this classification, type III presents a greater diagnostic and therapeutic complexity. The prevalence of palatogingival grooves in maxillary lateral incisors ranges from 1.9 to 14%. This case report provides valuable information about the diagnosis and treatment plan of palatogingival grooves with Cone-beam computed tomography (CBCT) scan. CASE REPORT: The patient was referred to the University Dental Clinic of European University of Valencia, with recurrent abscesses at the upper right lateral incisor region for the last two years. Palpation and percussion tests were positive for tooth 1.2. There was no clinical history of caries or previous trauma. Periapical radiography showed periapical radiolucent lesions located, not only in the apical area of tooth 1.2, but also in tooth 1.3. Both teeth had previously been endodontically treated. Periodontal probing showed normal values. CBCT scan was perfomed in order to establish a definitive diagnosis and appropriate treatment plan. DISCUSSION: The complex anatomy of the palatal root groove requires detailed knowledge of the internal root morphology for endodontic treatment success. This complementary tool allows a more accurate image of hard tissue structures, such as palatal grooves and/or accessory roots, in comparison to conventional periapical radiography. The treatment plan of this primary periodontal lesion with secondary endodontic involvement was as follows: periapical surgery combined with root amputation and sealing with MTA, and guided bone regeneration. Key words:Palatal radicular groove, palatogingival groove, maxillary lateral incisor, cone-beam computed tomography, endodontic-periodontal lesion, guided bone regeneration.

Update of the therapeutic planning of irrigation and intracanal medication in root canal treatment. A literature review.

BACKGROUND: The success of endodontic treatment derives from the complete elimination of microorganisms capable of causing an intraradicular or extraradicular infection. To achieve a more effective eradication of these microorganisms, endodontic instrumentation must always be implemented with abundant irrigation, which has to achieve chemical, mechanical and biological effects. The irrigators most used today are NaOCl, CHX and EDTA, released into the ducts through different techniques such as syringe, manual agitation, positive or negative apical pressure, sonic or ultrasonic activation, PIPS and PDT. The objective of this review is to update the different irrigating solutions and intracanal disinfection drugs, as well as to establish an irrigation protocol in the endodontic treatment. MATERIAL AND METHODS: Systematic search of scientific articles in the databases PubMed, Medline and Google Scholar, with the following keywords Endodontic, Infection, Failure, Irrigation, Retreatment and Irrigation protocol. The exclusion criteria were "case report" articles and articles with a publication date prior to 2000. RESULTS: 48 articles that met the inclusion criteria were analyzed. Comparing the different articles it can be seen that the NaOCl is the "gold standard" in terms of immediate antimicrobial efficacy, followed by the CHX that has a long-term antibacterial effect. As an intra-conductive drug it is advisable to use the combination of Ca(OH)2 with CPMC. CONCLUSIONS: The most adequate irrigation protocol consists of using 2.5% NaOCl activated with ultrasound followed by a final wash with 7% MA or 0.2% CTR combined with 2% CHX. Key words:Endodontic failure, endodontic infection, enterococcus faecalis, endodontic retreatment, irrigation, sodium hipoclorite, irrigation protocol.

Epigenetics and periodontics: A systematic review

Background: Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of different variations in gene expression, providing this great advantage to the static measurement provided by genetic markers. The aim of this systematic review is to analyze the possible relationships between different epigenetic mechanisms and periodontal diseases, and to assess their potential use as biomarkers of periodontitis. Material and Methods: A systematic search was conducted in six databases using MeSH and non-MeSH terms. The review fulfilled PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-analysis). Results: 36 studies met the inclusion criteria. Due to the heterogeneity of the articles, it was not possible to conduct quantitative analysis. Regarding qualitative synthesis, however, it was found that epigenetic mechanisms may be used as biological markers of periodontal disease, as their dynamism and molecular stability makes them a valu-able diagnostic tool. Conclusions: Epigenetic markers alter gene expression, producing either silencing or over-expression of molecular transcription that respond to the demands of the cellular surroundings. Gingival crevicular fluid collection is a non-invasive and simple procedure, which makes it an ideal diagnostic medium for detection of both oral and systemic issues. Although further research is needed, this seems to be a promising field of research in the years to come

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miR-1226 detection in GCF as potential biomarker of chronic periodontitis: A pilot study

BACKGROUND: The study and identification of new biomarkers for periodontal disease, such as microRNAs (miR-NAs), may give us more information about the location and severity of the disease and will serve as a basis for treatment planning and disease-monitoring. miRNAs are a group of small RNAs which are involved in gene regulation by binding to their messenger RNA target (mRNA). In this pilot study, the procedure for purifying miRNAs from gingival crevicular fluid (GCF) was, for the first time, described. In addition, the concentration of miRNAs in GCF was analyzed and compared between patients with moderate or severe chronic periodontitis (CP) and healthy controls. MATERIAL AND METHODS: GCF samples were collected from single-rooted teeth of patients with moderate or severe CP (n=9) and of healthy individuals (n=9). miRNAs were isolated from GCF using miRNeasy Serum/Plasma kit (Qiagen, CA. USA). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression of a series of miRNAs candidates that are related to bone metabolism. The significance of differences in miRNA levels between both groups was determined using Mann-Whitney U test. RESULTS: The results from this pilot study indicate that miRNAs can be isolated from GCF. Six different miRNAs were analyzed (miR-671, miR-122, miR-1306, miR-27a, miR-223, miR-1226), but only miR-1226 showed statically significant differences between the CP group and healthy controls (p < 0.05). This miRNA was downregulated in patients with CP. CONCLUSIONS: Within the limitations of the present study, it may be concluded that miR-1226 can be a promising biomarker for periodontal disease, adding relevant information to common clinical parameters used for diagnosis and prognosis of periodontitis