MicroRNAs as Immune Regulators of Inflammation in Children with Epilepsy.

Epilepsy is a chronic clinical syndrome of brain function which is caused by abnormal discharge of neurons. MicroRNAs (miRNAs) are small non-coding RNAs which act post-transcriptionally to regulate negatively protein levels. They affect neuroinflammatory signaling, glial and neuronal structure and function, neurogenesis, cell death, and other processes linked to epileptogenesis. The aim of this study was to explore the possible role of miR-125a and miR-181a as regulators of inflammation in epilepsy through investigating their involvement in the pathogenesis of epilepsy, and their correlation with the levels of inflammatory cytokines. Thirthy pediatric patients with epilepsy and 20 healthy controls matched for age and sex were involved in the study. MiR-181a and miR-125a expression were evaluated in plasma of all subjects using qRT-PCR. In addition, plasma levels of inflammatory cytokines (IFN-γ and TNF-) were determined using ELISA. Our findings indicated significantly lower expression levels of miR-125a (P=0.001) and miR-181a (P=0.001) in epileptic patients in comparison with controls. In addition, the production of IFN-γ and TNF- was non-significantly higher in patients with epilepsy in comparison with the control group. Furthermore, there were no correlations between miR-125a and miR-181a with the inflammatory cytokines (IFN-γ and TNF-) in epileptic patients. MiR-125a and miR-181a could be involved in the pathogenesis of epilepsy and could serve as diagnostic biomarkers for pediatric patients with epilepsy.

Aberrant Expression of Immune-related MicroRNAs in Pediatric Patients with Asthma.

MicroRNAs (miRNAs) have been implicated as regulatory molecules that could play a considerable role in the pathogenesis of different diseases including asthma. This work aims at exploring the role of miR-146a and miR- 106b in the pathogenesis of asthma and their association with asthma severity, IgE, and inflammatory cytokines in asthmatic children. Thirty asthmatic children and twenty age-matched healthy children aged 4-17 years old were enrolled. Expression of plasma miR-146a and miR-106b was measured using quantitative real-time PCR. Plasma levels of interleukin-5 (IL-5) and interleukin-13 (IL-13) were assessed using ELISA. Lung functions were measured by Spirometry. MiR-146a and miR-106b were significantly over-expressed in asthmatic children compared to healthy children. A significant positive correlation between total IgE and both miR-146a and miR-106b was found while no significant correlation could be detected between these miRNAs and asthma severity in asthmatic children. Plasma levels of IL-5 and IL-13 were non-significantly higher in asthmatic children compared to healthy children, and there was no significant correlation between them and both miR-146a and miR-106b expressions in the asthmatic children. The aberrant expression of immune-related miRNAs (miR-146a and miR-106b) and inflammatory cytokines (IL-5 and IL-13) among asthmatic children suggest their probable role in asthma pathogenesis.

The relation between glutathione S-Transferase M1 null-genotype and cardiac problems in beta-thalassemia.

UNLABELLED: This work was carried out to investigate the role of Glutathione S-Transferase M1 (GSTM1) null genotype frequency in prognosis of ß-thalassemia, and to detect the correlation between GSTM1 null genotype and appearance of cardiac complications in ß-thalassemia. MATERIALS AND METHODS: The studied groups in the present work were divided to three groups (group I: 20 healthy subjects, group II: 56 ß-thalassemic patients and group III: 16 ß-thalassemic patients with cardiac complications were taken from group II). The measurement of human high sensitive C-reactive protein (hs-CRP) was performed using nephelometry. GSTM1 genotype was detected by Polymerase Chain Reaction (PCR) and cardiac complications were determined by using Echocardiography. RESULTS: A statistically significant increase in hs-CRP and interleukin-6 (IL-6) levels was found in ß-thalassemic patients with cardiac complications compared to normal subjects. Results showed no relation between GSTM1 null genotype frequency neither with ß-thalassemia nor with cardiac complications appearance, where the interaction between GSTM1 null genotype in ß-thalassemic patients with cardiac complications and healthy subjects were insignificant compared to subjects with GSTM1 non-null genotype. CONCLUSIONS: GSTM1 null genotype frequency has no role in ß-thalassemia or cardiac complications appearance.

Evaluation of Bax and Bak gene mutations and expression in breast cancer.

Genetic analyses have provided evidence to suggest that Bax and Bak are the essential genes for apoptosis in mammalians cells. This study aimed to search for biomarkers in breast cancer to be used as prognostic markers for the disease. The Bak and Bax genes expressions were analyzed in 23 breast cancer patients by RT-PCR technique. SSCP technique was used to detect the mobility of the abnormal fragment in Bak exon 4. PCR for Bax promoter was digested with Tau 1 restriction enzyme to identify a single polymorphism G(-248)A. The expression of Bak gene is related to several clinical factors of breast cancer. The analysis of Bax RNA showed 4 isoforms of Bax with different distributions in the normal and tumor tissues. These isoforms were Bax α , d, δ , and ζ . Exon 4 had a normal pattern in all cases of breast cancer. There was a statistically significant difference in the frequency distribution of the G(-248)A genotypes in the breast cancer tissues with grade 3+high, T2 stage, lobular +other, and PR -ve subgroups. In this study, Bak expression seems to lead to development of breast cancer and affects the disease progression. Also, Bax d and Bax δ could be used as risk factor and biomarker for breast cancer with the distribution of G284A.

TRAIL mRNA expression in peripheral blood mononuclear cells of Egyptian SLE patients.

Although the definite etiopathogenesis of systemic lupus erythematosus (SLE) remains unclear, many different mechanisms may contribute to its pathogenesis. Tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family with pro-apoptotic activity. The accumulation of apoptotic cell debris has been hypothesized to induce the autoimmune inflammation in SLE, and TRAIL may trigger this programmed cell death. We investigated TRAIL mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 60 SLE patients and 40 controls using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and we studied the association between the results and clinical and laboratory parameters of the patients. Expression levels of TRAIL mRNAs in SLE patients were significantly higher than in controls (p<0.001). A statistically significant association was detected between TRAIL mRNA expression and SLE activity (p=0.001).