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      Expression dynamics of microRNA-223/Ras-associated binding protein 12 axis in Stage III/Grade B periodontal disease: A case–control analysis

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          Abstract

          Background:

          The intricate interplay between periodontal polymicrobial flora and an altered immune response is the central cause of periodontal disease. Multiple cell death methods and their interactions, along with the associated signaling pathways, significantly impact the initiation and advancement of periodontitis. Our speculation revolves around the role of the miR-223/Ras-associated binding protein (RAB12) signaling axis in regulating autophagy-induced pyroptosis, contributing to the pathophysiology of periodontitis. Thus, this study aimed to investigate miR-223 and RAB12 expression patterns in Stage III/Grade B periodontal disease.

          Materials and Methods:

          The study included 50 healthy individuals and 50 patients diagnosed with Stage III/Grade B periodontal disease. Clinical parameters were cataloged for each participant. miRNA-223 underwent an in silico analysis to identify its potential target genes. Gingival crevicular fluid (GCF) samples were collected from the subjects for real-time polymerase chain reaction to evaluate the expression of both miR-223 and the RAB12 gene.

          Results:

          The miRTargetLink2.0 analysis highlighted the RAB12 gene as a prime target for miR-223. In periodontal disease patients, miR-223 and RAB12 gene expressions significantly increased (15.21 and 34.70-fold changes, respectively; P < 0.05). Receiver operating characteristic analysis suggested that miR-223 is a potential biomarker for periodontal disease, with 76% diagnostic accuracy and an area under the curve of 0.777 ( P < 0.01).

          Conclusion:

          MicroRNA-223 and its target gene RAB12 exhibit high expression levels in GCF samples from individuals with periodontal disease. This suggests modulation of autophagy and the signaling mechanism for pyroptotic cell death in periodontal tissues during pathogenesis. Consequently, the miR-223/RAB12 axis might represent a plausible link for periodontal disease.

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          Most cited references55

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores.

            Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and Asp275, respectively, to generate an N-terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1β. Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined.
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              PERIODONTAL DISEASE IN PREGNANCY. II. CORRELATION BETWEEN ORAL HYGIENE AND PERIODONTAL CONDTION.

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                Author and article information

                Journal
                J Indian Soc Periodontol
                J Indian Soc Periodontol
                JISP
                J Indian Soc Periodontol
                Journal of Indian Society of Periodontology
                Wolters Kluwer - Medknow (India )
                0972-124X
                0975-1580
                Jan-Feb 2024
                04 June 2024
                : 28
                : 1
                : 99-105
                Affiliations
                [1 ] Department of Periodontology, Thaimoogambigai Dental College and Hospital, M.G.R. Educational and Research Institute, Kattankulathur, Chennai, Tamil Nadu, India
                [2 ] Department of Periodontology, S.R.M. Dental College and Hospital, Kattankulathur, Chennai, Tamil Nadu, India
                [3 ] Department of Periodontology, Thaimoogambigai Dental College and Hospital, Kattankulathur, Chennai, Tamil Nadu, India
                [4 ] Former Assistant Professor, Department of Periodontology, SRM Dental College and Hospital, Kattankulathur, Chennai, Tamil Nadu, India
                Author notes
                Address for correspondence: Dr. Dhathri Priya Bandi, Department of Periodontology, Thaimoogambigai Dental College and Hospital, M.G.R. Educational and Research Institute, Chennai - 600 107, Tamil Nadu, India. E-mail: drdha3priya@ 123456gmail.com

                The work belongs to Department of Periodontology, Thaimoogambigai Dental College and Hospital, Dr. M.G.R Educational and Research Institute, Chennai, Tamil Nadu

                Article
                JISP-28-99
                10.4103/jisp.jisp_179_23
                11232797
                38988960
                5f797bf6-38e4-4a78-b3b6-75194c1cd069
                Copyright: © 2024 Indian Society of Periodontology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 07 April 2023
                : 03 April 2024
                : 08 April 2024
                Categories
                Original Article

                Dentistry
                autophagy,microrna,periodontitis,pyroptosis,ras-associated binding proteins
                Dentistry
                autophagy, microrna, periodontitis, pyroptosis, ras-associated binding proteins

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