Serum miR-210 and miR-155 expression levels as novel biomarkers for rheumatoid arthritis diagnosis.

BACKGROUND: MicroRNAs play a crucial role in the regulation of immune response. We hypothesised roles for serum miR-210 and miR-155 in the diagnosis of rheumatoid arthritis (RA) and relationships with the clinical and laboratory variables including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, tumour necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß). METHODS: MiR-210 and miR-155 levels were identified by real-time polymerase chain reaction (PCR). TNF-α and IL-1ß were measured by enzyme-linked immunosorbent assay and routine markers by standard techniques in 100 patients with RA and 100 individuals as healthy controls. Disease activity in the patients was assessed by DA-S28. RESULTS: MiR-210 was lower in RA compared to controls [median/IQR 0.96 (0.8-1.24) vs. 4 (1.28-3.93), p < 0.001]. miR-210 correlated inversely with clinical and laboratory variables including TNF-α and IL-1ß (both r = -0.96, p < 0.001). MiR-155 expression was increased in RA compared to controls [median/IQR 6 (3.5-8.1) vs. 1.0 (0.95-1.6), p < 0.001] and correlated with TNF-α and IL-1ß (both r = 0.94, p < 0.001). In multivariate analysis, miR-210 and miR-155 were both independent diagnostic markers for RA, and both were associated with RA disease activity. CONCLUSION: Serum miR-210 and miR-155 levels are independent diagnostic markers for RA, out-performing several routine indices and reflect disease activity. Thus, miR-210 and miR-155 might serve as non-invasive biomarkers for the diagnosis of RA.

Estrogens control inflammation in experimental colitis.

There is now a wealth of experimental evidence indicating that the deficit in endogenous estrogen facilitates the onset of inflammation that can be antagonized by estrogen replacement therapy. This work investigated the role of estrogen in the control of intestinal inflammation in a panel of colitis models, focusing on the morphological changes, the activity of mast cells, the expression of cytokines (IL-1beta, IL-6, and TNF-alpha), fibronectin and reactive oxygen species. Two hundred adult male rats were divided into 4 groups: colitis was induced in Group I and Group II but only the latter was treated with estrogen; Group III received estrogen only, and Group IV saline. Colitis was induced in 4 models using: iodoacetamide; iodoacetamide + enteropathogenic E. coli; 2, 4, 6-Trinitrobenzene sulfonic acid; and dextran sulfate sodium salt. Macroscopic and microscopic evaluations of abdominal structures as well as molecular analysis were made on days 7, 14, 28 and 56. There was a significant improvement in the health condition of the estrogen-treated rats: the inflammation scores were reduced by at least 10-15%, the number of mast cells in the colon decreased by 30%, fibronectin expression was only 50% and reactive oxygen species decreased by 30%. In addition, there was a significant decrease in TNF-alpha, IL-6 and IL-1beta expression by about 25%. In conclusion, there was an improvement in the inflammatory status in all estrogen-treated groups through the duration of the experiment at all-time points. In addition, there was less tissue necrosis as depicted by less fibronectin and a marked antioxidant effect.

Cyclooxygenase-2 169C>G and 8473T>C gene polymorphisms and prostaglandin E2 level in breast cancer: a case-control study.

AIMS: Cyclooxygenase 2 (COX-2) with the resulting prostaglandin E2 (PGE2) is linked to increased risk of human breast cancer (BC). The aim of this study was to determine COX-2 169C>G and 8473T>C gene polymorphisms and PGE2 level at various stages of BC clarifying the role of COX-2 gene polymorphism and PGE2 in relation to BC. METHODS: The study population comprised 160 women at different stages of BC and 150 gender- and age-matched healthy control subjects. Plasma PGE2 was measured by ELISA, the COX-2 gene polymorphisms were determined using PCR-RFLP. RESULTS: The variant alleles COX-2 169G and 8473C were significantly associated with BC susceptibility [OR=3.1, 95% CI (2.2-4.4), P<0.001 for 169C>G and OR=1.74, 95%CI (1.3-2.4), P=0.005 for 8473C]. However, both COX-2 gene polymorphisms were not associated with breast cancer stage. Plasma PGE2 levels were significantly increased in patients compared to the controls. In early and late stages of BC, there was a significant increase in the plasma PGE2 levels towards the presence of homozygous GG compared with homozygous CC (P<0.001) for 169 C>G, also towards the presence of CC than TT (P<0.001) for 8473T>C SNP. CONCLUSION: The 169C>G and 8473T>C polymorphisms of the COX-2 gene were associated with the BC in Egyptian women. Furthermore, individuals with COX-2 169GG and 8473CC genotypes showed significant increase in plasma PGE2 levels. PGE2 levels may serve as a predictor of poor prognosis in patients with BC.