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Abstract Neuromyelitis optica spectrum disorder (NMOSD) is an immune-related demyelinating defect. Long non-coding RNAs (lncRNAs) might influence the pathobiology and progression of NMOSD. The current study assessed expression level of NEAT1, PANDAR, MEG3 and TUG1 lncRNAs in the peripheral blood of NMOSD patients compared with healthy individuals. All mentioned lncRNAs were shown to be over-expressed in total NMOSD cases, male NMOSD cases and female NMOSD cases compared with the matching control subgroups. MEG3 had the most robust over-expression in patients subgroups compared with normal subjects. There was no noteworthy difference in the expression of any of lncRNAs between female and male patients. MEG3 had an ideal performance in the differentiation of NMOSD cases from healthy persons (Sensitivity and specificity values = 100%). Other lncRNAs could also efficiently separate NMOSD cases from control subjects (AUC values = 0.97, 0.89 and 0.88 for PANDAR, NEAT1 and TUG1, respectively). Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD.

Abstract 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,

Abstract Bipolar disorder (BD) patients suffer from severe disability and premature death because of failure in prognosis, diagnosis, and treatment. Although neural mechanisms of bipolar have not been fully discovered, studies have shown long noncoding RNAs (lncRNAs) can play an important role in signaling pathways such as PI3K/AKT pathway. There has been little study on deregulated lncRNAs and the lncRNAs’ mode of action in the BD. Hence, we aimed to investigate the expression of PI3K/AKT pathway-related lncRNAs named TUG1, GAS5, and FOXD3-AS1 lncRNAs in the PMBC in 50 bipolar patients and 50 healthy controls. Our results showed that FOXD3-AS1 and GAS5 under-expressed significantly in bipolar patients compared to healthy controls (P = 0.0028 and P

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA with important roles in regulation of autophagy, neurite growth and morphogenesis. Polymorphisms within this gene have been associated with some neuropsychiatric conditions. In the current case-control study, we investigated associations between obsessive-compulsive disorder (OCD) and four single nucleotide polymorphism within this gene, namely rs12826786, rs4759314, rs1899663 and rs920778. There was significant difference in genotype distribution of rs920778 between OCD patients and normal controls (P value = 0.01). rs920778 was associated with risk of OCD in co-dominant model (TT versus CC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 0.66 (0.49–0.88), P value = 0.005 and OR (95 % CI) = 0.63 (0.44–0.91), P value = 0.014, respectively). This SNP was associated with OCD in dominant model (TT+TC versus CC) only in un-adjusted analysis (OR (95 % CI) = 0.52 (0.31–0.88), P value = 0.015). Finally, this SNP was associated with OCD in over-dominant model (CC+TT versus TC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 2.38 (1.33–4.25), P value = 0.003 and OR (95 % CI) = 2.78 (1.31–5.89), P value = 0.008, respectively). The current study shows possible impact of rs920778 on risk of OCD in Iranian population.

Abstract Schizophrenia (SCZ) is a severe mental disorder with an unknown pathophysiology. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been associated with synapse plasticity, learning, and memory, as well as neurodevelopment and neuroprotection. The importance of neurodevelopmental and neurotoxicity-related components in the pathophysiology of SCZ has been highlighted in research on the neurobiology of this disease. The purpose of this research is to investigate the significant expression of two variables, tristetraprolin (TTP) and miR-16, which are known to be regulators of BDNF expression. Fifty Iranian Azeri SCZ patients were enrolled, and fifty healthy volunteers were age- and gender-matched as controls. A quantitative polymerase chain reaction measured the expression levels of the TTP and miR-16 in the peripheral blood (PB) of SCZ patients and healthy people. TTP expression levels in patients were higher than in controls, regardless of gender or age (posterior beta = 1.532, adjusted P-value = 0.012). TTP and miR-16 expression levels were found to be significantly correlated in both SCZ patients and healthy controls (r = 0.701, P

Abstract Bipolar disorder (BD) is a mental disorder that leads to abnormal swings in mood, energy, activity level, attention, and the capability to accomplish daily tasks. Several long non-coding RNAs (lncRNAs) are dysregulated in BD patients. We have compared expression levels of five NF-κB-associated lncRNAs, namely ANRIL, CEBPA-DT, H19, NKILA and HNF1A-AS1 in blood samples of BD patients compared with controls. While ANRIL, CEBPA-DT and HNF1-AS1 were significantly under-expressed in BD patients compared with controls, NKILA levels were higher in patients versus controls. Among differentially expressed genes, HFN1A-AS1 exhibited the best diagnostic parameters in the separation of patients from controls (AUC ± SD = 0.86 ± 0.03, sensitivity = 0.82, specificity = 0.82, P value

Abstract Suppressor of cytokine signalling (SOCS) family comprises a group of proteins that impede JAK/STAT signalling, thus being involved in the pathogenesis of immune-related conditions. In the present work, we aimed at identification of the role of SOCS genes in the pathogenesis of periodontitis through evaluation of their expression levels both in the circulation and in the affected tissues of patients. Thus, we measured expression levels of SOCS1-3 and SOCS5 transcripts in the blood and gingival samples of patients with periodontitis in comparison with control samples obtained during dental crown lengthening. Expressions of SOCS1, SOCS2, SOCS3 and SOCS5 genes were similar between gingival tissues of patients and controls. However, our results demonstrated under-expression of SOCS1 in blood samples of patients compared with controls (Ratio of mean expression (RME) = 0.47, P value = 0.04). The same pattern was observed among female subjects (RME = 0.38, P value = 0.04). SOCS2 was down-regulated in blood samples of female patients compared with female controls (RME = 0.22, P value = 0.04). SOCS3 was also under-expressed in the circulation of total cases versus total controls (RME = 0.29, P value = 0.02) and in female patients compared with female controls (RME = 0.19, P value = 0.04). Expression of SOCS5 was not different between blood samples two study groups. SOCS2 had the best function in separation of affected tissues from unaffected ones (AUC = 0.66, sensitivity = 0.39, specificity = 0.83). SOCS3 was superior to other transcripts in differentiation of blood samples of patients from normal blood samples (AUC = 0.69, sensitivity = 0.81, specificity = 0.68). Combination of transcript levels of SOCS1, SOCS2, SOCS3 and SOCS5 genes enhanced the AUC values to 0.64 and 0.67 in tissue and blood specimens, respectively. Taken together, certain SOCS genes have been found to be dysregulated in the circulation of patients with periodontitis.

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.

Abstract Background Periodontitis is a chronic inflammatory disorder with a complex etiology. Long non-coding RNAs (lncRNAs) have been shown to affect pathoetiology of periodontitis. We aimed at identification of expression of five lncRNAs, namely Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 in the circulation and gingival tissues of these patients compared with healthy controls. Methods In a pilot case–control study, we compared expressions of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 lncRNAs between blood and tissue samples of patients with periodontitis and healthy controls using real time quantitative PCR technique. The present work was performed on samples got from 26 patients with periodontitis and 28 controls. Female/male ratio was 16/10 and 12/16 in cases and controls, respectively. Results There was no significant difference in the expressions of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 genes between affected and unaffected tissues. However, expressions of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 genes were significantly lower in the blood samples of patients when compared with control samples (Ratio of mean expression = 0.16, 0.14, 0.13, 0.10 and 0.14, respectively). Subsequently, we compared expressions of these lncRNAs between patients and controls in a sex-based manner. Expressions of Linc00667, FENDRR and DIRC3 genes were significantly lower in female patients compared with female controls (RME = 0.09, 0.07 and 0.10, respectively). Yet, there was no significant difference in expression of any of mentioned lncRNAs among male subgroups. Consistent with the similar levels of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 in tissue samples of patients and controls, none of them could separate these two sets of samples. However, AUC values for of Linc0116, Linc00667, CDK6-AS1, FENDRR and DIRC3 expression levels in blood samples were 0.66, 0.72, 0.70, 0.72, 0.70 and 0.68, respectively with FENDRR having the best sensitivity value. Conclusion Taken together, lncRNAs might be involved in the pathologic events in the circulation of patients with periodontitis.

Abstract Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) are inflammatory neuropathies with different clinical courses but similar underlying mechanisms. Long non-coding RNAs (lncRNAs) might affect pathogenesis of these conditions. In the current project, we have selected HULC, PVT1, MEG3, SPRY4-IT1, LINC-ROR and DSCAM-AS1 lncRNAs to appraise their transcript levels in the circulation of CIDP and GBS cases versus controls. Expression of HULC was higher in CIDP patients compared with healthy persons (Ratio of mean expression (RME) = 7.62, SE = 0.72, P

Periodontitis is a common oral disorder leading to tooth loss in both developed and developing regions of the world. This multifactorial condition is related to the abnormal activity of several molecular pathways, among them are oxytocin-related pathways. In this study, we enrolled 26 patients and 28 controls and assessed the expression of four oxytocin-related genes, namely, FOS, ITPR, RCAN1, and RGS2, in circulation and affected tissues of enrolled individuals using real-time PCR. Expression of FOS was downregulated in total periodontitis tissues compared with total control tissues [ratio of mean expression (RME) = 0.23, P-value = 0.03]. Expression of FOS was also lower in total blood samples of patients compared with total controls. Expression of ITPR was downregulated in total periodontitis tissues compared with total control tissues (RME = 0.16, P-value = 0.01). Moreover, the expression of ITPR was reduced in total blood samples of patients compared with controls (RME = 0.25, P-value = 0.03). Expression of RCAN1 was downregulated in total periodontitis tissues compared with total control tissues (RME = 0.17, P-value = 0.01). However, the expression of RCAN1 was not different in blood samples of affected vs. unaffected individuals. Finally, the expression of RGS2 was lower in total periodontitis tissues compared with total control tissues (RME = 0.24, P-value = 0.01) and in total blood samples of affected individuals compared with controls (RME = 0.42, P-value = 0.05). This study provides data about the association between expressions of oxytocin-related genes and the presence of periodontitis. Future studies are needed to unravel the mechanistic links and find the correlation between expressions of these genes and the pathological stage of periodontitis.

Alzheimer’s disease (AD) is a heterogeneous degenerative disorder of the brain that is on the rise worldwide. One of the critical processes that might be disturbed in AD is gene expression regulation. Tristetraprolin (TTP) and RC3H1 gene (ROQUIN) are two RNA-binding proteins (RBPs) that target AU-rich elements (AREs) and constitutive decay elements (CDEs), respectively. TTP and ROQUIN, members of the CCCH zinc-finger protein family, have been demonstrated to fine-tune numerous inflammatory factors. In addition, miR-16 has distinct characteristics and may influence the target mRNA through the ARE site. Interestingly, BDNF mRNA has ARE sites in the 3’ untranslated region (UTR) and can be targeted by regulatory factors, such as TTP and miR-16 on MRE sequences, forming BDNF/miR-16/TTP regulatory axis. A number of two microarray datasets were downloaded, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD and corresponding controls. R software was used to identify BDNF, TTP, ROQUIN, and miR-16 expression levels in temporal cortex (TC) tissue datasets. Q-PCR was also used to evaluate the expression of these regulatory factors and the expression of BDNF in the blood of 50 patients with AD and 50 controls. Bioinformatic evaluation showed that TTP and miR-16 overexpression might act as post-transcriptional regulatory factors to control BDNF expression in AD in TC samples. Instead, this expression pattern was not found in peripheral blood samples from patients with AD compared to normal controls. ROQUIN expression was increased in the peripheral blood of patients with AD. Hsa-miR-16-5p levels did not show significant differences in peripheral blood samples. Finally, it was shown that TTP and BDNF, based on evaluating the receiver operating characteristic (ROC), effectively identify patients with AD from healthy controls. This study could provide a new perspective on the molecular regulatory processes associated with AD pathogenic mechanisms linked to the BDNF growth factor, although further research is needed on the possible roles of these factors in AD.

Long non-coding RNAs (lncRNAs) have been demonstrated to in the pathophysiology of multiple sclerosis (MS). In order to appraise the role of T cell-related lncRNAs in this disorder, we assessed expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR in MS patients and healthy individuals. We detected significant difference in the expression of RMRP and FLICR between cases and controls. There were substantial correlations between expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR lncRNAs among patients, but not controls. The strongest correlations were found between RMRP and TH2-LCR, and between MAFTRR and RMRP with correlation coefficients of 0.69 and 0.59, respectively. ROC curve analysis revealed appropriate power of FLICR in differentiating between MS patients and healthy controls (AUC value = 0.84). Expression of NEST lncRNA was positively correlated with disease duration in MS patients, but negatively correlated with age at onset. In brief, we reported dysregulation of two T cell-related lncRNAs in MS patients and proposed FLICR as a putative marker for this disorder.

Abstract Background Coronavirus disease 2019 (COVID-19) has been shown to cause serious health problems among them is the Acute Respiratory Distress syndrome (ARDS). Vitamin D receptor (VDR) signaling possibly partakes in the pathophysiology of this devastating complication. Methods In the current project, we have appraised expression levels of VDR, CYP27B1 and a number of associated lncRNAs in the circulation of COVID-19 patients versus healthy subjects using real-time PCR method. Results Expression of SNHG6 was considerably lower in COVID-19 patients compared with control subjects (Ratio of mean expression (RME) = 0.22, P value = 7.04E-05) and in both female and male COVID-19 patients compared with sex-matched unaffected individuals (RME = 0.32, P value = 0.04 and RME = 0.16, P value = 0.000679683, respectively). However, its expression was similar among ICU-hospitalized and non-ICU patients. Similarly, expression of SNHG16 was lower in in COVID-19 patients compared with controls (RME = 0.20, P value = 5.94E-05) and in both female and male patients compared with sex-matched controls (RME = 0.32, P value = 0.04 and RME = 0.14, P value = 0.000496435, respectively) with no significant difference among ICU-hospitalized and non-ICU hospitalized patients. Expression of VDR was lower in COVID-19 patients compared with controls (RME = 0.42, P value = 0.04) and in male patients compared with male controls (RME = 0.27, P value = 0.02). Yet, expression of VDR was statistically similar between female subgroups and between ICU-hospitalized and non-ICU hospitalized patients. Expression levels CYP27B, Linc00511 and Linc00346 were similar among COVID-19 patients and healthy subjects or between their subgroups. Significant correlations have been detected between expression levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 lncRNAs both among COVID-19 patients and among healthy controls with the most significant ones being SNHG6 and SNHG16 (r = 0.74, P value = 3.26e-17 and r = 0.81, P = 1.54e-22, respectively). Conclusion Combination of transcript levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 could differentiate patients from controls with AUC = 0.76, sensitivity = 0.62 and specificity = 0.81. The current data potentiate SNHG6, SNHG16 and VDR as possible contributors in COVID-19 infection but not in the severity of ARDS.

Abstract Oxytocin is a neuropeptide released by the central nervous system. A number of studies have demonstrated the role of this neuropeptide in the pathogenesis of breast cancer. In the present project, we have identified mRNA coding genes and long non-coding RNAs (lncRNAs) that are associated with this pathway through an in-silico strategy, and measured their expression in a cohort of Iranian females affected with this type of malignancy. Expression levels of OXTR, FOS, ITPR1, RCAN1, CAMK2D, CACNA2D and lnc_ZFP161 were significantly down-regulated in breast cancer tissues compared with nearby non-cancerous tissues. On the other hand, expression of lnc_MTX2 was higher in breast cancer tissues compared with controls. Expression of lnc_TNS1 and lnc_FOXF1 were not different between these two kinds of samples. Expression of CACNA2D was associated with mitotic rate and PR status (P values = 3.02E−02 and 2.53E−02, respectively). Expression of other oxytocin-related genes was not associated with clinicopathological parameters. FOS and ITPR1 had the highest AUC value among the oxytocin-related genes. Combination of expression profiles of all oxytocin-related genes increased the AUC value to 0.75. However, the combinatorial sensitivity and specificity values were lower than some individual genes. In the breast cancer tissues, the most robust correlations have been detected between lnc_ZFP161/ lnc_FOXF1, CAMK2D/ lnc_ZFP161 and CAMK2D / lnc_FOXF1 (r = 0.86, 0.71 and 0.64 respectively). In the non-cancerous tissues, the strongest correlation was detected between lnc_FOXF1/lnc_MTX2 and lnc_ZFP161/CAMK2D respectively (r = 0.78 and 0.65). Taken together, oxytocin-associated genes have been dysregulated in breast cancer tissues. Moreover, the correlation ratio between these genes is connected with the existence of cancer.

The β-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer’s disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the BACE1 expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson’s disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.

Long non-coding RNAs (lncRNAs) have crucial roles in lncRNAs in periodontal development and disorders of this tissue. A number of lncRNAs especially those regulating immune responses contribute in the pathophysiology of periodontitis. In the current case-control study, we assessed expression levels of two immune response-related lncRNAs namely the antisense non-coding RNA in the INK4 locus (ANRIL) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in gingival tissues and blood samples of patients with periodontitis and healthy subjects. Expression of ANRIL was significantly lower in peripheral blood of patients compared with controls (Posterior Beta RE = -1.734, P value = 0.035). However, when diving study participants based on their gender, no significant difference was found between patients and sex-matched controls. Expression of this lncRNA was not different between periodontitis tissues and normal tissues. Expression of MALAT1 was not different between samples obtained from cases and controls. Tissue or blood expressions of ANRIL or MALAT1 were not correlated with age of either patients or controls. There were significant correlations between expression levels of ANRIL and MALAT1 in gingival tissues both in cases (r = 0.62, P

Parkinson’s disease (PD) has been shown to affect approximately 1% of the persons aged more than 65 years. This multifactorial disorder has been associated with abnormal function of NF-κB signals. In this research, we have evaluated expressions of NF-κB-related long non-coding RNAs in the circulation of PD patients compared with healthy controls. Expression of PACER was lower in total PD patients compared with healthy persons (Ratio of mean expressions (RME)=0.32, P value

Migraine is a complex neurological condition affecting a large proportion of persons. Dysregulation of several immune-related transcripts has been noted in migraineurs suggesting an immune-based background for this condition. We measured expression levels suppressor of cytokine signaling (SOCS) genes in the venous blood of migraineurs compared with controls. SOCS1 was down-regulated in patients without aura compared with controls [Ratio of mean expression (RME) = 0.08, P value < 0.001]. This pattern was also detected among female subgroups (RME = 0.06, P value = 0.010), but not among male subgroups (RME = 0.22, P value = 0.114). Expression of SOCS1 was significantly higher in patients with aura compared with those without aura (RME = 5.89, P value = 0.037). Meanwhile, expression of SOCS2 was lower in migraineurs with aura compared with controls (RME = 0.03, P value < 0.001). In addition, this gene was under-expressed in patients without aura compared with controls and in both sex-based subgroups of this group of patients (RME = 0.01, P value < 0.001 for all comparisons). However, its expression was higher in male patients with aura compared with those without aura (P value < 0.001). For SOCS3, we detected a lower level of expression in patients without aura compared with controls (RME = 0.07, P value < 0.001). However, the expression of SOCS3 was higher in patients with aura compared with those without aura (RME = 7.46, P value = 0.001). SOCS5 was down-regulated in patients without aura compared with controls (RME = 0.10, P value < 0.001). Expression of this gene was also lower in patients with aura compared with controls (RME = 0.03, P value < 0.001), and in male patients of this group compared with controls (RME = 0.03, P value = 0.004). On the other hand, expression of SOCS5 was higher in male patients with aura compared with sex-matched patients without aura (RME = 6.67, P value = 0.001). SOCS2 levels could appropriately differentiate migraineurs from healthy subjects. The current study suggests the role of SOCS genes in the pathoetiology of migraine.

Protein inhibitors of activated STAT (PIAS) are involved in the regulation of the JAK/STAT signaling pathway and have interactions with NF-κB, p73 and p53. These proteins regulate immune responses; therefore dysregulation in their expression leads to several immune-mediated disorders. In the present study, we examined expression of PIAS1-4 in peripheral blood of patients with acute/chronic inflammatory demyelinating polyradiculoneuropathy (AIDP/CIDP) compared with healthy subjects. We demonstrated down-regulation of all PIAS genes in both AIDP and CIDP cases compared with controls. Similarly, comparisons in gender-based groups revealed down-regulation of these gene0s in patients of each gender compared with gender-matched controls. There was no significant difference in expression of PIAS genes between AIDP and CIDP cases. Based on the area under the receiver operating characteristic curves, PIAS1-4 genes could distinguish between inflammatory demyelinating polyradiculoneuropathy and healthy status with accuracy values of 0.87, 0.87, 0.79 and 0.80, respectively. In differentiation between AIDP cases and healthy controls, these values were 0.92, 0.92, 0.83 and 0.86, respectively. Finally, PIAS1-4 genes could discriminate CIDP from healthy status with accuracy values of 0.82, 0.83, 0.75 and 0.75, respectively. The current study underscores the role of PIAS genes in the pathogenesis of inflammatory demyelinating polyradiculoneuropathy and their potential usage as biomarkers.

Background: Self-regulation learning (SRLS) and emotional intelligence constructs among youth considering effectiveness and enhancement of optimization and quality of life. Materials and Methods: The research sample composed of 200 students who studied at Iranian universities in 2016-17 academic year. SRLS and Goleman's emotional intelligence questionnaire were utilized in this research. Collected data was analyzed using Pearson’s correlation coefficient and multivariate regression technique. Results: Scores of goal setting and planning (p=0.009) and self-consequating (p=0.021) were higher among females, and those of support from teacher (p=0.014), notes review (p=0.001), and homework review (p=0.004) were higher among males. Furthermore, regarding emotional intelligence, scores of self-motivation (p=0.012) and social skills (p=0.008) were higher among males. Conclusion: Goal-setting and planning for these strategies help people organize materials more easily, and understand that, self-consequating includes learner’s judgement about his/her own capabilities, and this self-trust contributes to better implementation of his/her cognitive skills in his/her studies. Regarding the support from teacher, notes review and homework review among males, which fall within the scope of resource management strategies, by organizing learning environment, seeking support from parents and teacher, and adjusting efforts help the learner either eliminate or attenuate distraction, and the fact that others can help us. Furthermore, both note taking and note reading contribute to better recovery of information from memory. This strategy includes administrating or regulating one’s own and others’ emotions, appropriate adoption of those in human relationships, controlling instantaneous desires, and confronting opposite or negative emotions. Being composed of self-motivation and social skills, this strategy has higher levels among males.

Long non-coding RNAs (lncRNAs) have been shown to alter immune responses, thus contributing to the pathobiology of autoimmune conditions. We investigated the expression levels of ANRIL, PICART1, MALAT1, CCAT1, CCAT2, and CCHE1 lncRNAs in acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP). ANRIL, PICART1, MALAT1, CCAT1, CCAT2, and CCHE1 lncRNAs were significantly downregulated in individuals with both AIDP and CIDP compared with unaffected individuals. Gender-based comparisons also verified such downregulations in both male and female subjects compared with sex-matched unaffected controls for all lncRNAs. There was no significant difference in the expression of any of the lncRNAs between cases with AIDP and cases with CIDP. While the expression levels of ANRIL and PICART1 were significantly correlated in healthy subjects (r = 0.86, p = 8.5E-16), similar analysis in cases with AIDP and CIDP revealed no significant correlation. The most robust correlation among patients was detected between ANRIL and MALAT1 lncRNAs (r = 0.59, p = 3.52E-6). ANRIL, MALAT1, and PICART1 had the diagnostic power of 0.96, 0.94, and 0.92 in distinguishing between cases with CIDP and controls, respectively. A combination of all lncRNAs resulted in 0.95 diagnostic power with a sensitivity of 0.85 and specificity of 0.96 for this purpose. Diagnostic power values of these lncRNAs in differentiation between cases with AIDP and controls were 0.98, 0.95, and 0.93, respectively. The combinatorial diagnostic power reached 0.98 for differentiation between cases with AIDP and controls. The six-lncRNA panel could differentiate combined cases with AIDP and CIDP from controls with area under the curve (AUC), sensitivity, and specificity values of 0.97, 0.90, and 0.96, respectively. Collectively, the lncRNA panel is suggested as a sensitive and specific diagnostic panel for acquired immune-mediated polyneuropathies.

Phosphatase and tensin homolog (PTEN) gene encodes a tumor suppressor protein which is altered in several malignancies. This protein is a negative regulator of the PI3K/AKT signaling. Several transcription factors regulate the expression of PTEN in positive or negative directions. Moreover, numerous microRNAs (miRNAs) have functional interactions with PTEN and inhibit its expression. Suppression of PTEN can attenuate the response of cancer cells to chemotherapeutic agents. Based on the critical role of this tumor suppressor gene, the identification of negative regulators of its expression has practical significance particularly in the prevention and management of cancer. Meanwhile, the interaction between miRNAs and PTEN has functional consequences in non-malignant disorders including myocardial infarction, osteoporosis, cerebral ischemic stroke, and recurrent abortion. In the present review, we describe the role of miRNAs in the regulation of expression and activity of PTEN.

Periodontitis is a bacteria-related chronic immune-associated condition that destructs bone and connective tissues around teeth. With a high incidence rate, it is regarded as a condition that impose substantial health burden. About half of the variance in the severity of periodontitis is attributed to genetic factors. Long non-coding RNAs (lncRNAs) have crucial roles in the development of several disorders such as periodontitis. A number of studies have reported dysregulation of lncRNAs such as UCA1, ANRIL, FGD5-AS1, NEAT1, FAS-AS1, Linc-RAM and NKILA in gingival tissues or blood samples of patients with periodontitis in comparison with healthy subjects. Moreover, several single nucleotide polymorphisms within lncRNAs have been associated with the susceptibility to this disorder. In the current review, we discuss the most recent articles about the role of lncRNAs in the pathogenesis of periodontitis.

A number of recent studies have shown dysregulation of some long non-coding RNAs (lncRNAs) in affected tissues or peripheral blood of patients with periodontitis. In the current study, we investigated the role of TNF and HNRNPL related immunoregulatory (THRIL) and p50-associated COX-2 extragenic RNA (PACER) lncRNAs in periodontitis. We assessed expression of these lncRNAs in 30 affected tissue, 30 control tissue samples, 23 blood samples from patients and 18 blood samples from healthy controls. Expression of PACER was higher in total blood samples of patients compared with controls (Posterior beta of RE = 5.143, P value = 0.001). However, when assessing its expression in a gender-based manner, the difference in the expression of this lncRNA was significant only among male subgroups (Posterior beta of RE = 7.16, P value < 0.0001). Moreover, expression of PACER was significantly higher in female subjects compared with male subjects (Posterior beta of RE = 3.098, P value < 0.0001). There was no significant difference in tissue expression of PACER between study subgroups. Expression of THRIL was not significantly different between blood/tissue samples of cases and controls. However, expression of this lncRNA was higher in blood of female subjects compared with male subjects (Posterior beta of RE = 4.353, P value = 0.002). Tissue expression of THRIL was correlated with blood levels of this lncRNA (r = 0.33, P < 0.0001) and with the tissue levels of PACER (r = 0.3, P < 0.0001). Moreover, blood levels of these lncRNAs were correlated with each other (r = 0.34, P < 0.0001). However, there was no significant correlation between blood and tissue levels of PACER. Expression of these lncRNAs were not correlated with age either in males or in females. Taken together, we demonstrated a sex-based up-regulation of PACER in blood samples of patients with periodontitis which implies possible participation of this lncRNA in the pathobiology of periodontitis.

Background: Long non-coding RNAs (lncRNAs) are a group of functional transcripts that are not translated to proteins. Recent investigations have underscored their role in the pathogenesis of neurodevelopmental disorders.Methods: In the current investigation, we quantified expression levels of four lncRNAs (HOXA-AS2, SPRY4-IT1, MEG3, and LINC-ROR) in peripheral blood of epileptic patients and normal controls.Results: Expression of HOXA-AS2 was significantly higher in patients compared with controls (Posterior beta = 1.982, P = 0.001). We detected interaction effects of gender on expression of HOXA-AS2 (P = 0.012). Further analyses showed over-expression of HOXA-AS2 in male patients compared with male controls (P = 0.003), in spite of similar levels of expression between female cases and female controls (P = 0.77). Expression of SPRY4-IT1 was higher in total patients compared with total controls (Posterior beta = 1.27, P = 0.02). Such difference was only observed between male patients and male controls when dividing study participants based on their gender (P = 0.012). There was no significant difference in expression of MEG3 and LINC-ROR between patients and controls.Conclusion: Expression levels of all lncRNAs were correlated with each other with r values ranging from 0.61 to 0.76 (P < 0.0001). However, expressions of none of lncRNAs were correlated with age of study participants. The current data implies a putative role for two lncRNAs in the pathogenesis of epilepsy and warrants future functional studies to verify the observed association.

For downloading the full-text of this article please click here. Background and Objective: Decision making is of great importance in not only personal and social life but also organizational life. One of the most key factors influencing the decision making process is the value system as well as the beliefs and thoughts of decision-makers. Since the value system in Islam is fully comprehensiveness, in this research, the health managers’ decision-making process on the basis of the values and ethical principles from the Islamic point of view is examined. Method: ‘Content analysis’ is used in this study which falls into the category of non-experimental or descriptive research. The Islamic references and sources such as “Holy Quran”, “Nah al-balagha”, “Ghorar al-hekam & Dorar al-kalem”, “Al-kafi”, “Al-hayat” and also a number of related books and papers were investigated in this study. All ethical issues were observed in this research and the researchers declared no conflict of interests. Results: In this research, three general steps were taken for the health managers’ decision-making process based on the teachings of the Holy Quran, which included “decision-making”, “decision implementation” and “reliance on God”. In order to accurately explain the steps above, a number of distinct and interpretable indices, derived from three main sources of Islamic studies, namely the “Holy Qur'an”, “the Prophet's Sunnah”, and “the life-method of infallible Imams”, were extracted, explained and interpreted. Conclusion: Any health manager or any ordinary Muslim can use the Islamic factors extracted in this research beside the science of decision-making for the triple stages of decision-making in his decision-making process and finally can complete his decision-making process relying on Almighty Allah, with an indomitable spirit. This way, in addition to succeeding in decision making, he will feel the consent of the Almighty Creator in every single stage of decision-making. For downloading the full-text of this article please click here.

For downloading the full-text of this article please click here. Decision-making is of paramount importance in personal, social, and organizational life, influencing both personal and organizational affairs. Indeed, all human’s life is a chain of decisions made by him (1). In this regard, decision-making in major managements, particularly in health sector where lives of people as well as physical and spiritual health are involved, is of particular importance. For downloading the full-text of this article please click here.

Objective: Multiple sclerosis (MS) is a common disease of the central nervous system. This disease may be initiated by either vitamin deficiency or triggered by abnormality in CYP24A1 and vitamin D receptor. Materials and Methods: In this case-control study, the expression of genes encoding vitamin D receptor (VDR) and CYP24A1 in relapsing-remitting MS (RR-MS) patients was compared with normal individuals in the Iranian population. RNA from whole blood of 50 RR-MS patients (HLA-DRB1*15-negative and responders to interferonbeta with a normal vitamin D level) and 50 normal controls was extracted. The levels of CYP24A1 and VDR expression were measured using real-time quantitative polymerase chain reaction. Results: The RR-MS group had a significantly more than 2 times higher expression level of VDR than the normal group (P=0.04). On the other hand, there was a 0.89 times decrease in the expression level of CYP24A1 in RR-MS patients which was not statistically significant. There was no linear correlation between the risk of expanded disability status scale of Kurtzke (EDSS) and the expression level of either CYP24A1 or VDR. In addition, the expression level of CYP24A1 or VDR was not correlated with the duration of the disease. Conclusion: Up-regulation of VDR is likely to happen in RR-MS patients in the Iranian population. We did not observe a gene expression-phenotype correlation for CYP24A1 which may be due to limited statistical power as a result of the small sample size. Although the individuals taking part in this study had normal levels of vitamin D, the increase in VDR expression levels may perhaps be a response to a defect in vitamin D processing. Another possibility is that despite an increase in VDR expression level, factors such as micro-RNAs may result in their deactivation while an increase in VDR expression level can be seen as a compensatory response. Of course, further studies are required to identify the mechanism of action of vitamin D by analyzing genes involved in its signaling pathway, particularly VDR and CYP24A1.

Objective The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 locus) as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients. Materials and Methods In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms (SNPs) in 122 breast can- cer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). Results The TT genotype at rs1333045 was significantly over-represented among pa- tients (P=0.038) but did not remain significant after multiple-testing correction. In addi- tion, among all observed haplotypes (with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278), four haplotypes were shown to be associated with breast cancer risk. However, after multiple testing corrections, TCGA was the only haplotype which remained significant. Conclusion These results suggest that breast cancer risk is significantly associated with ANRIL variants. Future work analyzing the expression of different associated ANRIL haplotypes would further shed light on the role of ANRIL in this disease.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), in which axonal damage is a deteriorative factor. Brain-Derived Neurotrophic Factor (BDNF) is described as a neuronal-survival gene, also capable of exerting pleiotropic effects on the immune cells. Here, we aimed to investigate expression levels of BDNF and its antisense RNA, BDNF-AS, in Iranian MS patients. Our case-control study was based on collecting 50 whole blood samples of relapsing-remitting MS patients and 50 healthy controls. Then, expression analysis of BDNF and BDNF-AS was performed by Real-time quantitative PCR. We found a strong and positive correlation between BDNF and BDNF-AS in MS patients. This is while no significant difference in BDNF and BDNF-AS expression levels was seen between MS patients and controls (p>0.05). A significant and strong positive correlation was found between the expression levels of BDNF-AS and BDNF (r=0.785, p0.05). BDNF and BDNF-AS expression levels revealed insignificant discrepancies in patients and controls. We found a strong and positive correlation between BDNF and BDNF-AS in MS patients, which is, based on previous studies, a quit novel finding and can be further discussed by future works to unravel its possible application in MS. We suggest evaluation of different leukocytes subsets separately along with large cohort studies comprising a higher number of individuals from different ages to unravel the effects of other possible aspects.

Recently, Long noncoding RNAs (lncRNAs) have been described as regulatory factors for several biological mechanisms through regulating the gene expression. Among them the TNF and HNRNPL related immunoregulatory (THRIL) lncRNA may be involved in the pathogenesis of immune-related and inflammatory disease through controlling the expression of the tumor necrosis factor-alpha (TNF-α) expression. In this case-control study, we investigate the THRIL expression in blood 25 samples of de novo acute myeloid leukemia (AML) cases (10 females and 15 males, mean age±SD: 35.1±3.2 years) in comparison to 50 healthy age and sex matched controls (21 females and 29 males, mean age±SD: 34.9± 3.1) using real-time quantitative reverse transcription-PCR (qRT-PCR) in order to explore any association between THRIL and AML. Our results revealed that there was no significant difference in the expression level of THRIL lncRNA between AML patients and healthy individuals (p=0.2, 95% CI=-0.129-28.35). In addition, there was no significant association between male subgroup and THRIL expression as well as females (p=0.08, 95% CI=-0.197-19.251, p=0.4, 95% CI=-0.185-12.041, respectively). In comparison between control group and FAB classification subtypes of AML patients, there was not any significant association. In conclusion, our study showed that THRIL cannot be used as an informative biomarker for AML diagnosis, however, our results need to be clarify by evolution of more cases.

OBJECTIVE: Multiple myeloma (MM) is a B-cell malignancy characterized by the clonal proliferation of malignant plasma cells. According to results of some studies, it has been suggested that the HLA class 1 and 2 genes have susceptibility effects on MM. Studies of different populations have reported different HLA class 1 and 2 alleles that affect MM. In this study, we assessed the association of HLA class 1 and class 2 antigens with MM in Iranian patients METHODS: We performed a case-control genotyping study with 105 Iranian MM patients that were selected from the bone marrow transplantation department of Taleghani Hospital and 150 controls using single specific primerpolymerase chain reaction with the HLA-Ready Gene ABDR Kit. RESULTS: Our results demonstrated that 21% of patients versus 12% of controls and 11% of patients versus 3% of controls carried HLA-A*03 and HLA-B*18, respectively. The MM patients had a significant increase in the frequency of HLA-A*03 and HLA-B*18 alleles in comparison to control subjects (p=0.039, OR=2.057 and p=0.013, OR=3.567, respectively). CONCLUSION: Our findings suggested that the HLA-A*03 and HLA-B*18 alleles have significant susceptibility effects on MM in the Iranian population. However, compared to other populations, the above-mentioned alleles had different statuses. Since there are not many studies evaluating and calculating this association among ethnic groups, further studies among other populations are needed to explain the exact association of the HLA genes with MM.

The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients. Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls. Higher significant frequencies of the T allele and TT genotype for rs6897932 (C/T) were observed in patients comparing to controls (p=0.006). Higher frequencies of the T allele and the TT and TG genotypes and lower frequencies of the G allele and GG genotypes for rs201084372 (G/A) were found in patients comparing to controls (p

Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central nervous system that women are at a higher risk to acquire than men. Myxovirus resistance protein A (MxA) is used as a predictive marker of bioactivity of interferon-beta (IFN-β) therapy in MS patients. This study was undertaken in west of Iran to investigate gender differences in the expression level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-β therapy, compared with untreated normal individuals. The expression level of the MxA gene in RRMS samples were compared to untreated normal individuals using the extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and 50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15 negative and responded to IFN-β with a normal vitamin D level. The level of MxA gene expression was measured by quantitative RT-PCR. The levels of gene expression were decreased in RRMS patients compared with normal counterparts (p=0.025). This decrease was significant in females (p=0.009) compared to males (p>0.05). The level of expression varied across different female age-groups with no significant difference in women younger than 30 years, but a significant decrease in expression in women between 30 to 40 years or above 40 years of age was seen. There was neither linear correlation between the MxA expression level and risk of expanded disability status scale of Kurtzke (EDSS); nor were there any significant correlation between expression status of MxA and duration of the disease. In conclusion, the decrease in the level of MxA expression in MS patients treated with IFN-β when compared to normal individuals was significantly lower in females than males. This demonstrated a gender bias in the response to IFN-β therapy that will need to be confirmed and further investigated in more detail.

Objective: Multiple sclerosis (MS) is a chronic autoimmune disease due to demyelination of the central nervous system. It is believed that cytokines are involved in the pathogenesis of MS. The interleukin-2 (IL2) gene is powerful functional candidate that is involved in immune regulation and operation. In this study, for the first time, we investigated the effect of -475 A/T and -631 G/A IL2 polymorphisms on MS disease in Iranian patients.Materials and Methods: In this case-control study, 100 MS patients (mean age: 32.95 ± 6.51 years, age range: 20-42 years) selected according to McDonald criteria, and 100 ethnically, sex and age matched healthy controls (mean age: 29 ± 7.8 years, age range: 20-52 years) with no personal or family history of autoimmune diseases were studied. The restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method was applied to define different alleles and genotypes of IL2 promoter single nucleotide polymorphism -475 A/T as well as -631 G/A among individuals. χ2 was calculated and Fisher’s exact test was applied to analyze the obtained data. The value of p

Objective: Type 1 diabetes mellitus (T1D) is an autoimmune and multifactorial disorder. Subsequent analysis on human leukocyte antigen ( HLA) region shows that HLA-DRB1 and -DQB1 genes have the strongest association with T1D. In this study, for the first time, we investigated the influence of gender on the HLA-DRB1 and -DQB1 association with type 1 diabetes mellitus in Iranian patients in order to determine gender dependent HLA heterogeneity in Iranian T1D patients.Materials and Methods: In this case control study, the HLA-DRB1 and -DQB1 typing were performed on 105 Iranian T1D patients and 100 healthy controls. The data were evaluated by using Fisher exact test.Results: Our results indicate that DRB1*04:01, DQB1*03:02 alleles and DRB1*04:01-DQB1*03:02 haplotype were significantly more frequent in male T1D patients than females. Also, DRB1*03:01, DRB1*15:01, DQB1*06:01 alleles, DQB1*03:01/05:01 genotype, DRB1*03:01-DQB1*02:01 and DRB1*15:01-DQB1*06:01 haplotypes were significantly higher in female T1D group than males. Furthermore, our results showed that DRB1*04:01 and DQB1*03:02 alleles were significantly more frequent in male T1D patients 1-5 years old at onset than females with similar condition. The DRB1*03:01 allele and DRB1*03:01-DQB1*02:01 haplotype were significantly higher in female T1D patients 6-10 years old at onset than males with similar condition. The DRB1*15:01 allele and DRB1*15:01-DQB1*06:01 haplotype were significantly more frequent in female T1D patients 16-20 years old at onset than males with similar condition.Conclusion: Our findings suggest that gender has a significant influence on the distribution of HLA-DR and -DQ alleles, genotypes and haplotypes. Also, distribution of the HLA-DRB1 and -DQB1 alleles, genotypes and haplotypes vary based on the gender of T1D patients in different age at onset.

Multiple sclerosis (MS) is a chronic neuroinflammatory demyelinating disease of the central nervous system. The cytokine genes are involved in autoimmune diseases such as MS. In this study, we report the influence of −330 interleukin-2 (IL2) gene polymorphism on its plasma levels in a group of Iranian MS patients. In this study 100 MS patients and 100 ethnically, age, and sex matched healthy controls were selected from Medical Genetics Department of Sarem Women Hospital. Blood samples of all individuals were collected in EDTA tubes. The restriction fragment length polymorphism PCR (RFLP) method was applied to determine various alleles and genotypes in these individuals. Plasma concentration of IL2 was measured in all the samples using human IL2 kit. The frequency of −330 T/T IL2 genotype was higher in MS patients compared to normal individuals. Accordingly, the plasma levels of IL2 were significantly higher (P