Assessment of expression of calcium signaling related lncRNAs in epilepsy.

Calcium signaling is a metabolic pathway that is essential in neurons development and can be involved in the pathobiology of epilepsy. We assessed expression of three mRNA coding gene (SLC1A1, SLC25A12, and ATP2B2) and three related long non-coding RNAs (LINC01231:1, lnc-SLC25A12-8:1 and lnc-MTR-1:1) from this pathway in 39 patients with refractory epilepsy and 71 healthy controls. Expression of all genes except for lnc-SLC25A12 was higher in total epileptic cases compared with controls (P values = 0.0002, < 0.0001, < 0.0001, 0.049 and 0.0005 for SLC1A1, SLC25A12, LINC01231, ATP2B2 and lnc-MTR-1, respectively. When we separately compared expression of genes among males and females, SLC1A1, SLC25A12, LINC01231 and lnc-MTR-1 showed up-regulation in male cases compared with male controls. Moreover, expressions of SLC1A1 and SLC25A12 were higher in female cases compared with female controls. Remarkably, SLC25A12 was found to have the highest sensitivity value (= 1) for differentiation of epileptic cases from controls. Moreover, lnc-MTR-1 and lnc-SLC25A12 were sensitive markers for such purpose (sensitivity values = 0.89 and 0.87, respectively). The highest value belonged to LINC01231 with the value of 0.76. Taken together, this study demonstrates dysregulation of calcium-signaling related genes in epileptic patients and suggests these genes as potential biomarkers for epilepsy.

Assessment of expression of oxytocin-related lncRNAs in schizophrenia.

BACKGROUND: Schizophrenia is a neuropsychiatric disorder characterized by a variety of clinical manifestations. This disorder has a complex inheritance. Oxytocinegic system has been shown to be implicated in the pathophysiology of schizophrenia. This system can alter social cognition through direct interaction with dopaminergic signaling, facilitating brain-stimulation reward, reduction of defense mechanism and stress reactivity, and modulation of social information processing through enhancing the greatness of social incentives. Long non-coding RNAs (lncRNAs) can affect activity of oxytocinegic system, thus contributing in the etiology of this disorder. METHODS: We designed the current study to appraise dysregulation of nine oxytocin-associated mRNAs and lncRNAs in the venous blood of patients with schizophrenia. RESULTS: Expression of FOS was up-regulated in total patients compared with total control group (Expression ratio (95% CI)= 13.64 (5.46-34.05), adjusted P value<0.0001) and in female patients compared with female control group (Expression ratio (95% CI)=32.13 (5.81-176), adjusted P value<0.0001). Such pattern was also seen for Lnc-FOXF1 (Expression ratio (95% CI)= 6.41 (2.84-14.3), adjusted P value<0.0001 and Expression ratio (95% CI)= 14.41 (3.2-64.44), adjusted P value<0.0001, respectively). ITPR1 was down-regulated in total patients compared with total controls (Expression ratio (95% CI)= 0.22 (0.076-0.67), adjusted P value=0.0079). ROC curve analyses demonstrated that FOS had the best AUC value among other genes in differentiation between patients and controls (AUC=0.78). CONCLUSION: The above-mentioned results imply dysregulation of oxytocin-related genes in the circulatory blood of patients with schizophrenia.

Assessment of Expression of Regulatory T Cell Differentiation Genes in Autism Spectrum Disorder.

Dysfunction of regulatory T cells (Tregs) has been shown to affect the etiology of autism spectrum disorder (ASD). Differentiation of this group of T cells has been found to be regulated by a group of long non-coding RNAs (lncRNAs). In this study, we have examined the expression of five lncRNAs that regulate this process in the blood samples of ASD cases compared with controls. These lncRNAs were FOXP3 regulating long intergenic non-coding RNA (FLICR), MAF transcriptional regulator RNA (MAFTRR), NEST (IFNG-AS1), RNA component of mitochondrial RNA processing endoribonuclease (RMRP), and Th2 cytokine locus control region (TH2-LCR). Expression of RMRP was significantly lower in total ASD cases compared to controls [expression ratio (95% CI) = 0.11 (0.08-0.18), adjusted P-value < 0.0001]. This pattern was also detected in both men and women cases compared with corresponding controls [expression ratio (95% CI) = 0.15 (0.08-0.29) and 0.08 (0.03-0.2), respectively]. Likewise, expression of NEST was reduced in total cases and cases among men and women compared with corresponding controls [expression ratio (95% CI) = 0.2 (0.14-0.28); 0.22 (0.12-0.37); and 0.19 (0.09-0.43), respectively; adjusted P-value < 0.0001]. Lastly, FLICR was downregulated in total cases and cases among both boys and girls compared with matched controls [expression ratio (95% CI) = 0.1 (0.06-0.19); 0.19 (0.08-0.46); and 0.06 (0.01-0.21), respectively; adjusted P-value < 0.0001]. These three lncRNAs had appropriate diagnostic power for differentiation of ASD cases from controls. Cumulatively, our study supports dysregulation of Treg-related lncRNAs in patients with ASD and suggests these lncRNAs as proper peripheral markers for ASD.

Assessment of Treg-related lncRNAs in epilepsy.

Recent studies have shown dysregulation of several groups of long non-coding RNAs in the context of epilepsy. According to evidence regarding the role of regulatory T cells in this disorder, we examined expression levels of regulatory T cell-related lncRNAs, namely TH2-LCR, RMRP, IFNG-AS1 (NEST), MAFTRR and FLICR in the blood of epileptic cases compared with controls. Expression of RMRP was lower in patients with refractory epilepsy compared with controls [expression ratio (95% CI) = 0.32 (0.13-0.8), adjusted p-value = 0.0008]. Besides, its expression was lower in refractory patients vs. non-refractory patients [expression ratio (95% CI) = 0.2 (0.1-0.41), adjusted p-value < 0.0001]. Expression of TH2-LCR was lower in refractory patients vs. controls [expression ratio (95% CI) = 0.4 (0.17-0.93), adjusted p-value = 0.0044] and in refractory patients vs. non-refractory ones [Expression ratio = 0.28 (0.19-0.58), p-value < 0.0001]. Expression of NEST was higher in total patients [expression ratio (95% CI) = 2.48 (1.15-5.27), adjusted p-value = 0.0012] and in both groups of patients compared with controls. However, its expression was not different between refractory and non-refractory cases. Similarly, FLICR and MAFTRR were over-expressed in total cases and both groups of patients compared with controls, but their expressions were similar between refractory and non-refractory cases. MAFTRR could differentiate between total epileptic cases and controls with AUC value of 0.8. This lncRNA could separate refractory and non-refractory cases from healthy controls with AUC values of 0.73 and 0.88, respectively. This study provides evidence for deregulation of regulatory T cell-related lncRNAs in epilepsy and their potential role as diagnostic markers in this condition.

Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients.

Contribution of the renin-angiotensinogen system in the risk of COVID-19 and related complications have been assessed by several groups. However, the results are not consistent. We examined levels of ACE1 and ACE2 in the circulation of two groups of COVID-19 patients (ICU-admitted and general ward-admitted patients) compared with healthy controls. We also genotyped two polymorphisms in ACE1 gene (the ACE1-I/D polymorphism rs1799752 and rs4359) to appraise their association with expression levels of ACE1 and ACE2. Expression level of ACE1 was significantly higher in ICU patients compared with non-ICU patients (P value = 0.02). However, its expression was not significantly different between total COVID-19 patients and total controls (P value = 0.34). ACE2 expression was not different ether between two groups of COVID-19 patients (P value = 0.12) or between total COVID-19 patients and total controls (P value = 0.79). While distribution of rs1799752 and rs4359 alleles was similar between study groups, genotype frequencies of rs1799752 were differently distributed among total COVID-19 patients and controls (P value = 0.00001). Moreover, genotypes of the other polymorphism tended to be distinctively distributed among these two groups (P value = 0.06). In the total population of patients and controls, different ACE1 mRNA levels were observed among carriers of different rs1799752 genotypes; of note, ID genotype carriers showed a higher expression of ACE1 compared with II genotype carriers (P = 0.01). ACE1 polymorphisms might affect risk of COVID-19 and expression of ACE transcripts.