MicroRNA: Dynamic Regulators of Macrophage Polarization and Plasticity.

The ability of a healthy immune system to clear the plethora of antigens it encounters incessantly relies on the enormous plasticity displayed by the comprising cell types. Macrophages (MΦs) are crucial member of the mononuclear phagocyte system (MPS) that constantly patrol the peripheral tissues and are actively recruited to the sites of injury and infection. In tissues, infiltrating monocytes replenish MΦ. Under the guidance of the local micro-milieu, MΦ can be activated to acquire specialized functional phenotypes. Similar to T cells, functional polarization of macrophage phenotype viz., inflammatory (M1) and reparative (M2) is proposed. Equipped with diverse toll-like receptors (TLRs), these cells of the innate arm of immunity recognize and phagocytize antigens and secrete cytokines that activate the adaptive arm of the immune system and perform key roles in wound repair. Dysregulation of MΦ plasticity has been associated with various diseases and infection. MicroRNAs (miRNAs) have emerged as critical regulators of transcriptome output. Their importance in maintaining health, and their contribution toward disease, encompasses virtually all aspects of human biology. Our understanding of miRNA-mediated regulation of MΦ plasticity and polarization can be utilized to modulate functional phenotypes to counter their role in the pathogenesis of numerous disease, including cancer, autoimmunity, periodontitis, etc. Here, we provide an overview of current knowledge regarding the role of miRNA in shaping MΦ polarization and plasticity through targeting of various pathways and genes. Identification of miRNA biomarkers of diagnostic/prognostic value and their therapeutic potential by delivery of miRNA mimics or inhibitors to dynamically alter gene expression profiles in vivo is highlighted.

microRNAs: Emerging players in oral cancers and inflammatory disorders.

Association of oral diseases and disorders with altered microRNA profiles is firmly recognized. These evidences support the potential use of microRNAs as therapeutic tools for diagnosis, prognosis, and treatment of various diseases. In this review, we highlight the association of altered microRNA signatures in oral cancers and oral inflammatory diseases. Advances in our ability to detect microRNAs in human sera and saliva further highlight their clinical value as potential biomarkers. We have discussed key mechanisms underlying microRNA dysregulation in pathological conditions. The use of microRNAs in diagnostics and their potential therapeutic value in the treatment of oral diseases are reviewed.

MiRNA-Target Interaction Reveals Cell-Specific Post-Transcriptional Regulation in Mammalian Cell Lines.

MicroRNAs are 18-22 nucleotides long, non-coding RNAs that bind transcripts with complementary sequences leading to either mRNA degradation or translational suppression. However, the inherent differences in preferred mode of miRNA regulation among cells of different origin have not been examined. In our previous transcriptome profiling studies, we observed that post-transcriptional regulation can differ substantially depending on the cell in context. Here we examined mechanistic differences in the regulation of a let-7a targeted (wild type) or resistant (mutant) engineered renilla transcript across various mammalian cell lines of diverse origin. Dual luciferase assays show that compared to mutant (mut), the reporter gene containing wild type (wt) let-7a binding sites was efficiently suppressed upon transfection in various cell lines. Importantly, the strength of miRNA regulation varied across the cell lines. Total RNA analysis demonstrates that wt renilla mRNA was expressed to similar or higher levels compared to mut suggesting that translation repression is a predominant mode of miRNA regulation. Nonetheless, transcript degradation was observed in some cell lines. Ago-2 immunoprecipitation show that miRNA repressed renilla mRNA are associated with functional mi-RISC (miRNA-RNA induced silencing complex). Given the immense potential of miRNA as a therapeutic option, these findings highlight the necessity to thoroughly examine the mode of mRNA regulation in order to achieve the beneficial effects in targeting cells.

Comparison of clinical periodontal status among habitual smokeless-tobacco users and cigarette smokers.

AIM: Investigating the comparative effect of cigarette smoking and smokeless-tobacco use on periodontal health. BACKGROUND: There is a dearth of studies comparing the effects of smoking and smokeless tobacco on periodontal health. Smokeless tobacco is emerging as a major public health hazard, but is often neglected as a risk factor by many clinicians. MATERIALS AND METHODS: A cross-sectional study of 286 subjects was conducted. The participants were divided into mutually exclusive groups (i.e. any subject who had the habit of both smoking as well as smokeless tobacco usage was excluded from the study), as follows: a smoking group (SG; n=121); a smokeless-tobacco group (ST; n=81); and a non-tobacco-consuming group (NT; n=84). Data were obtained using a questionnaire and by clinical examination. The Periodontal Disease Index (PDI) and Oral Hygiene Index-Simplified (OHI-S) were used to clinically evaluate the periodontal and dental health status of the subjects. Multivariate analysis was performed to identify statistical correlations. RESULTS: The Plaque Index was higher in the ST group than in the SG group and was statistically significantly higher in the ST group than in the NT group. Probing depth and gingival inflammation (components of the PDI) were also higher in the ST group than in the SG and NT groups, but this was not statistically significant. CONCLUSIONS: Within the limits of the study, and for this study population, the impact on the periodontium as a result of smokeless tobacco use appeared to be comparable with that of smoking tobacco. The results of this study affirm the need to consider smokeless tobacco as a possible contributory factor to periodontal disease, in addition to smoking, and to counsel patients accordingly. Further randomised clinical trials are necessary to validate the long-term impact of smokeless tobacco on periodontal disease.