UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

It is well known that necrotic cells are capable of promoting inflammation through releasing so-called endogenous \'danger signals\' that can promote activation of macrophages, dendritic cells, and other sentinel cells of the innate immune system. However, the identity of these endogenous proinflammatory molecules, also called damage-associated molecular patterns (DAMPs), has been debated since the \'danger model\' was first advanced 20 years ago. While a relatively large number of molecules have been proposed to act as DAMPs, little consensus has emerged concerning which of these represent the key activators of sterile inflammation. Here I argue that the canonical DAMPs have long been hiding in plain sight, in the form of members of the extended IL-1 cytokine family (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ). The latter cytokines possess all of the characteristics expected of endogenous DAMPs and initiate inflammation in a manner strikingly similar to that utilized by the other major category of inflammatory triggers, pathogen-associated molecular patterns (PAMPs). Furthermore, many PAMPs upregulate the expression of IL-1 family DAMPs, enabling robust synergy between these distinct classes of inflammatory triggers. Thus, multiple lines of evidence now suggest that IL-1 family cytokines represent the key initiators of necrosis-initiated sterile inflammation, as well as amplifiers of inflammation in response to infection-associated tissue injury.