OBJECTIVE: This systematic review and meta-analysis assess the effectiveness of salivary biomarkers in the diagnosis and prognosis of RA, examining current evidence and proposing avenues for future research.
METHODOLOGY: A literature review following PRISMA 2021 guidelines was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify studies from the past five years on salivary biomarkers in RA patients compared to healthy controls.
RESULT: The review focused on original research articles, and meta-analysis was performed on studies reporting standard deviation values for inflammatory markers such as IL-6, IL-8, MMP-8, and TNF-alpha. The meta-analysis included eleven studies with 394 RA patients and 255 healthy controls, evaluating IL-8, IL-6, MMP-8, and TNF-α as RA biomarkers. IL-8 showed a mean difference of 7.32 (CI: -5.48 to 20.13), not statistically significant, favouring controls. IL-6 had a CI of -0.09 (CI: -2.20 to 2.02) with high heterogeneity (I² = 98%), suggesting its potential as a diagnostic and prognostic biomarker. TNF-α and MMP-8 showed no significant differences (CIs: 4.54 and 2.71, respectively).
CONCLUSION: This systematic review and meta-analysis emphasize saliva's potential in identifying RA biomarkers, especially IL-6, which is associated with the disease's pathogenesis. However, significant evidence heterogeneity necessitates larger, multicentric studies for validation.
METHODS: 20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA.
RESULTS: There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system.
CONCLUSION: The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.
METHODS: Cells were pre-incubated with 32µM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined ex-vivo using a myograph.
RESULTS: 15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.
CONCLUSION: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.