Increase in the conductivity and work function of pyrosol indium tin oxide by infrared irradiation

ArticleTHIN SOLID FILMS. 484(1-2): 272-277 (2005)journal articl

Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in patients with rheumatoid arthritis

Objectives: MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity. Methods: Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays. Results: Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a. Conclusions: Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis

Glatiramer Acetate Treatment Normalizes Deregulated microRNA Expression in Relapsing Remitting Multiple Sclerosis

The expression of selected microRNAs (miRNAs) known to be involved in the regulation of immune responses was analyzed in 74 patients with relapsing remitting multiple sclerosis (RRMS) and 32 healthy controls. Four miRNAs (miR-326, miR-155, miR-146a, miR-142-3p) were aberrantly expressed in peripheral blood mononuclear cells from RRMS patients compared to controls. Although expression of these selected miRNAs did not differ between treatment-naïve (n = 36) and interferon-beta treated RRMS patients (n = 18), expression of miR-146a and miR-142-3p was significantly lower in glatiramer acetate (GA) treated RRMS patients (n = 20) suggesting that GA, at least in part, restores the expression of deregulated miRNAs in MS

Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis

Background: Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from "at-risk" to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from "at-risk" to RA. Methods: We performed global profiling of 754 miRNAs per patient on a matched serum sample cohort of 12 anti-cyclic citrullinated peptide (CCP) + "at-risk" individuals that progressed to RA. Each individual had a serum sample from baseline and at time of detection of synovitis, forming the matched element. Healthy controls were also studied. miRNAs with a fold difference/fold change of four in expression level met our primary criterion for selection as candidate miRNAs. Validation of the miRNAs of interest was conducted using custom miRNA array cards on matched samples (baseline and follow up) in 24 CCP+ individuals; 12 RA progressors and 12 RA non-progressors. Results: We report on the first study to use matched serum samples and a comprehensive miRNA array approach to identify in particular, three miRNAs (miR-22, miR-486-3p, and miR-382) associated with progression from systemic autoimmunity to RA inflammation. MiR-22 demonstrated significant fold difference between progressors and non-progressors indicating a potential biomarker role for at-risk individuals. Conclusions: This first study using a cohort with matched serum samples provides important mechanistic insights in the transition from systemic autoimmunity to inflammatory disease for future investigation, and with further evaluation, might also serve as a predictive biomarker

MiR-133a in Human Circulating Monocytes: A Potential Biomarker Associated with Postmenopausal Osteoporosis

Background: Osteoporosis mainly occurs in postmenopausal women, which is characterized by low bone mineral density (BMD) due to unbalanced bone resorption by osteoclasts and formation by osteoblasts. Circulating monocytes play important roles in osteoclastogenesis by acting as osteoclast precursors and secreting osteoclastogenic factors, such as IL-1, IL-6 and TNF-a. MicroRNAs (miRNAs) have been implicated as important biomarkers in various diseases. The present study aimed to find significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis. Methodology/Principal Findings: We used ABI TaqManH miRNA array followed by qRT-PCR validation in circulating monocytes to identify miRNA biomarkers in 10 high and 10 low BMD postmenopausal Caucasian women. MiR-133a was upregulated (P = 0.007) in the low compared with the high BMD groups in the array analyses, which was also validated by qRT-PCR (P = 0.044). We performed bioinformatic target gene analysis and found three potential osteoclast-related target genes, CXCL11, CXCR3 and SLC39A1. In addition, we performed Pearson correlation analyses between the expression levels of miR-133a and the three potential target genes in the 20 postmenopausal women. We did find negative correlations between miR-133a and all the three genes though not significant. Conclusions/Significance: This is the first in vivo miRNA expression analysis in human circulating monocytes to identif