Abstract We predicted miRNAs with regulatory impact on NFKB1 and TRAF6 gene expression and selected the miR-194-5p, miR-124-3p, miR-9-5p, and miR-340-5p and their target genes for expression analyses on CD14+ monocytes from rheumatoid arthritis (RA) patients and healthy controls. Additionally, we evaluated the influence of genes and miRNA expression on RA patients’ cytokine levels. No difference was observed in genes or miRNAs expression when compared to healthy controls and RA patients or clinical parameters. However, we found a significant difference between miR-194-5p and miR-9-5p levels (FC=-2.31; p=0.031; FC=-3.05;p=0.031, respectively) and non-prednisone users as compared to prednisone using patients. We conducted correlation analyses to identify the strength of the relationship between expression data and cytokine plasma levels. We observed a moderate positive correlation between miR-124-3p expression and IL-6 plasma levels (r=0.46; p=0.033). In addition, overexpression of miRNAs was concomitant to TRAF6 and NFKB1 genes as indicated by correlation analyses: TRAF6 and miR-194-5p (r=0.60;p<0.001) and miR-9-5p (r=0.63;p<0.001) and NFKB1 and miR-194-5p (r=0.72;p<0.001), miR-9-5p (r=0.72;p<0.001) and miR-340-5p (r=0.61;p<0.001). NFKB1 and TRAF6 genes and miRNAs monocyte expression do not appear to be related to RA but showed a significant difference in different groups of RA therapy. In addition, increased levels of miRNAs can be linked to concomitant overexpression of TRAF6 and NFKB1 in monocytes and act as its regulators. NFKB TRAF miR1945p, miR1945p miRp miR 194 5p, 5p p miR1243p, miR1243p 124 3p, 3p miR95p, miR95p 9 miR3405p 340 CD14 CD (RA Additionally parameters However FC=2.31 FC231 FC FC= 2.31 2 31 (FC=-2.31 p=0.031 p0031 0 031 FC=3.05p=0.031, FC305p0031 FCp 3.05 p=0.031, 3 05 FC=-3.05;p=0.031 respectively nonprednisone non IL6 IL 6 IL- r=0.46 r046 r 46 (r=0.46 p=0.033. p0033 p=0.033 . 033 p=0.033) addition r=0.60p<0.001 r060p0001 rp r=0.60 p<0.001 60 001 (r=0.60;p<0.001 r=0.63p<0.001 r063p0001 r=0.63 63 (r=0.63;p<0.001 r=0.72p<0.001, r072p0001 r=0.72 , 72 r=0.72p<0.001 (r=0.72;p<0.001 r=0.61p<0.001. r061p0001 r=0.61 61 (r=0.61;p<0.001) therapy regulators 19 12 34 CD1 FC=2.3 FC23 231 2.3 (FC=-2.3 p=0.03 p003 03 05p FC=3.05p=0.031 FC305p003 305 3.0 FC=-3.05;p=0.03 r=0.4 r04 4 (r=0.4 60p r=0.60p<0.00 r060p000 r060 r=0.6 p0001 p<0.00 00 (r=0.60;p<0.00 63p r=0.63p<0.00 r063p000 r063 (r=0.63;p<0.00 72p r072p000 r072 r=0.7 7 r=0.72p<0.00 (r=0.72;p<0.00 61p r=0.61p<0.001 r061p000 r061 (r=0.61;p<0.001 1 FC=2. FC2 23 2. (FC=-2. p=0.0 p00 FC=3.05p=0.03 FC305p00 30 3. FC=-3.05;p=0.0 r=0. r0 (r=0. r=0.60p<0.0 r060p00 r06 p000 p<0.0 (r=0.60;p<0.0 r=0.63p<0.0 r063p00 (r=0.63;p<0.0 r072p00 r07 r=0.72p<0.0 (r=0.72;p<0.0 r=0.61p<0.00 r061p00 (r=0.61;p<0.00 FC=2 (FC=-2 p=0. p0 FC=3.05p=0.0 FC305p0 FC=-3.05;p=0. r=0 (r=0 r=0.60p<0. r060p0 p<0. (r=0.60;p<0. r=0.63p<0. r063p0 (r=0.63;p<0. r072p0 r=0.72p<0. (r=0.72;p<0. r=0.61p<0.0 r061p0 (r=0.61;p<0.0 (FC=- p=0 FC=3.05p=0. FC305p FC=-3.05;p=0 r= (r= r=0.60p<0 r060p p<0 (r=0.60;p<0 r=0.63p<0 r063p (r=0.63;p<0 r072p r=0.72p<0 (r=0.72;p<0 r=0.61p<0. r061p (r=0.61;p<0. (FC= p= FC=3.05p=0 FC=-3.05;p= (r r=0.60p< p< (r=0.60;p< r=0.63p< (r=0.63;p< r=0.72p< (r=0.72;p< r=0.61p<0 (r=0.61;p<0 (FC FC=3.05p= FC=-3.05;p r=0.60p (r=0.60;p r=0.63p (r=0.63;p r=0.72p (r=0.72;p r=0.61p< (r=0.61;p< FC=3.05p r=0.61p (r=0.61;p

Abstract Turner syndrome (TS) is characterized by a set of clinical conditions, including autoimmune/inflammatory diseases and infectious conditions, that can compromise a patient’s quality of life. Here we assessed polymorphisms in CTLA-4 +49A/G (rs231775), PTPN22 +1858G/A (rs2476601), and MBL2 -550 (H/L) (rs11003125), -221(X/Y) (rs7096206) and exon 1 (A/O) in women from northeastern Brazil to determine whether polymorphisms within these key immune response genes confer differential susceptibility to clinical conditions in TS. A case-control genetic association study was performed, including 86 female TS patients and 179 healthy women. An association was observed for the A/G genotype of CTLA-4 +49A/G in TS patients (p=0.043, odds ratio [OR]=0.54). In addition, an association between the CTLA-4 G/G genotype and obesity was detected in TS patients (p=0.02, OR=6.04). Regarding, the -550(H/L) polymorphism in the MBL2 promoter, the frequency of the H/L genotype was significantly higher in the TS group than healthy controls (p=0.01, OR=1.96). The H/H genotype indicated a protective effect in TS patients (p=0.01, OR=0.23). No differences were observed in the distribution of -221(X/Y), MBL2 exon 1 variants, and PTPN22 +1858G/A in any assessed groups. CTLA-4 variants are potentially involved in obesity in this cohort of TS patients from northeastern Brazil.

Gliomas are the most common tumors in the central nervous system, the average survival time of patients with glioblastoma multiforme being about 1 year from diagnosis, in spite of harsh therapy. Aiming to study the transcriptional profiles displayed by glioma cells undergoing cisplatin treatment, gene expression analysis was performed by the cDNA microarray method. Cell survival and apoptosis induction following treatment were also evaluated. Drug concentrations of 12.5 to 300 μM caused a pronounced reduction in cell survival rates five days after treatment, whereas concentrations higher than 25 μM were effective in reducing the survival rates to ~1%. However, the maximum apoptosis frequency was 20.4% for 25 μM cisplatin in cells analyzed at 72 h, indicating that apoptosis is not the only kind of cell death induced by cisplatin. An analysis of gene expression revealed 67 significantly (FDR < 0.05) modulated genes: 29 of which down- and 38 up-regulated. These genes belong to several classes (metabolism, protein localization, cell proliferation, apoptosis, adhesion, stress response, cell cycle and DNA repair) that may represent several affected cell processes under the influence of cisplatin treatment. The expression pattern of three genes (RHOA, LIMK2 and TIMP2) was confirmed by the real time PCR method.

The velocardiofacial syndrome (VCFS), a condition associated with 22q11.2 deletions, is characterized by a typical facies, palatal anomalies, learning disabilities, behavioral disturbances and cardiac defects. We investigated the frequency of these chromosomal deletions in 16 individuals with VCFS features who presented no cardiac anomalies, one of the main characteristics of VCFS. Fluorescent in situ hybridization (FISH) with the N25 (D22S75; 22q11.2) probe revealed deletions in ten individuals (62%). Therefore, even in the absence of cardiac anomalies testing for the 22q11.2 microdeletions in individuals showing other clinical features of this syndrome is recommended.