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Acquired immune-mediated polyneuropathies are classified to some subtypes among them are acute and chronic inflammatory demyelinating polyradiculoneuropathies (AIDP and CIDP). These two conditions share some common signs and underlying mechanisms. Based on the roles of Suppressor of cytokine signaling ( SOCS ) genes in the modulation of immune system reactions, these genes might be involved in the pathogenesis of these conditions. We evaluated expression of SOCS1-3 and SOCS5 genes in the leukocytes of 32 cases of CIDP, 19 cases of AIDP and 40 age- and sex-matched controls using real time PCR method. The Bayesian regression model was used to estimate differences in mean values of genes expressions between cases and control group. Expression levels of SOCS1 and SOCS2 were significantly lower in male patients compared with controls. This sex-specific pattern was also observed for SOCS3 down-regulation. Based on the area under curve values in Receiver Operating Characteristics (ROC) curve, diagnostic powers of SOCS1 , SOCS2 , SOCS3 and SOCS5 genes in the mentioned disorder were 0.61, 0.73, 0.68 and 0.58, respectively. Expression of none of genes was correlated with age of enrolled cases. The current study shows evidences for participation of SOCS genes in the pathophysiology of acquired immune-mediated polyneuropathies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Taheri, Sangseifid, Shahani, Eftekharian, Arsang-Jang and Ghafouri-Fard.)

Multiple sclerosis (MS) is among the most common diseases affecting brain and spinal cord. MS progression is characterized by breakdown of blood brain barrier which leads to increased vascular permeability and angiogenesis. Consequently, vascular endothelial growth factor A (VEGF) and its receptors are considered to be important components of MS progression. VEGFA and fms-related tyrosine kinase 1 (FLT1) play important roles in various aspects of MS. In this study, we investigated the relationship between these genes and MS. For this purpose, the expression levels of VEGFA and FLT1 were measured in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy individuals using TaqMan quantitative real-time PCR. A significant upregulation of VEGFA expression was observed among MS patients compared with controls (p = 0.04). However, the difference in FLT1 gene expression between study groups was insignificant (p = 0.947). In addition, there was a significant positive correlation between VEGFA and FLT1 genes expressions (r = 0.769, p < 0.0001). In spite of the highly complex molecular mechanisms behind this, the findings imply participation of VEGFA in the pathogenesis of MS.

Epilepsy is a brain disorder with a global prevalence of 1%. It has been attributed to genetics and environmental factors. Despite efforts to identify the molecular pathology of epilepsy, the underlying mechanism is not understood yet. This study was carried out to compare GRIN2B, BDNF, and IL-1β gene expressions in 50 patients suffering from generalized epilepsy with tonic-colonic seizures and 50 age- and sex-matched healthy subjects using TaqMan Real-time PCR. Our results demonstrated significant upregulation of these genes in people with epilepsy compared with healthy subjects. We also found a positive correlation between GRIN2B and BDNF expression (r 2 =0.4619, p < 0.0001), BDNF and IL-1β expression (r 2  = 0.515, p < 0.0001), and GRIN2B and IL-1β gene expressions (r 2  = 0.666, p < 0.0001) which implies the possibility to estimate the expression level of these genes by assessment of expression of one of them. Considering the results of the previous animal studies which showed upregulation of these genes in brain tissues of epileptic animals, the expression levels of GRIN2B, BDNF, and IL-1β in blood samples might be related to their expression in brain samples. Future studies are needed to assess the role of these genes in the pathogenesis of epilepsy and evaluate whether altered expression of these genes along with imaging methods can facilitate subtyping the epilepsy.

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<0.0001).  A decreased level of mRNA expression for the membrane-bound IL-7Rα (mbIL-7Rα) and an increased level of mRNA for the soluble IL-7Rα (sIL-7Rα) were observed in patients versus controls (p=0.005 and p=0.002 respectively). A significant decreased level of mRNA expression for mbIL-7Rα (p=0.01) and an increased level of mRNA for sIL-7Rα (p=0.008) were observed in RRMS patients compared to healthy controls carrying the TT+CT genotypes. The higher levels of mRNA expression for the sIL-7Rα isoform in MS patients carrying the IL7R*TT genotype is a new finding not previously reported in studies on the genotype-induced effects of IL-7Rα expression in multiple sclerosis.

Background & Objective: Heat shock proteins (HSPs) have garnered significant interest as a potential host factor in COVID-19. By exerting control over HSP levels, the invading virus can effectively manipulate the destiny of host cells, capitalizing on their essential roles in cellular pathways and viral life cycles. Within this investigation, we present novel findings elucidating the variations in HSP27 protein and mRNA expression between patients exhibiting mild symptoms and those manifesting moderate-to-severe symptoms of COVID-19, juxtaposed against a control cohort. Materials & Methods: A total of 102 patient samples were included in the study, comprising 54 individuals with moderate-to-severe COVID-19 symptoms and 48 with mild symptoms. Additionally, 42 samples from healthy individuals constituted the control group. HSP27 protein levels were quantified using ELISA, while the transcript content was assessed using Real-Time PCR. Results: Our initial findings revealed a statistically significant reduction in serum HSP27 levels among patients displaying mild COVID-19 symptoms when compared to the control group (P< 0.05). Nonetheless, this disparity did not achieve statistical significance in patients with moderate-to-severe symptoms. In contrast, the transcriptomic profile of HSP27 exhibited striking similarity across all groups, including mild, moderate-to-severe, and controls (P= 0.25 and P= 0.56, respectively). Conclusion: The present study, to date, is the first to investigate HSP27 gene expression levels in COVID-19 patients. Conducting further studies on HSP27 is of considerable help to clarify the importance of this molecule in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

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 < 0.001 and r = 0.777, P < 0.001, respectively). Due to the increased expression of TTP in SCZ and the existence of a significant correlation between TTP and miR-16, which helps to act on target mRNAs with AU-rich elements, this mechanism can be considered an influencing factor in SCZ. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. SHISA7 (CKAMP59) has emerged as one of the most intriguing new members of the SHISA family, in that, unlike other CKAMP counterparts, it exhibits a direct function in inhibitory synaptic GABAAR regulation. We used bioinformatics and experimental methods in this research to explore competing endogenous RNA (ceRNA) regulation of BCAS4 and SHISA7 in tau pathogenesis and their capacity as peripheral biomarkers linked to an abnormal inflammatory response in AD. The Gene Expression Omnibus database included two microarray datasets, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD with different degrees of AD-associated neurofibrillary pathology in the temporal cortex (TC) tissue specimens and corresponding controls were downloaded from the Gene Expression Omnibus database. The limma package in the R software was used to identify differently expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) associated with AD-related neurofibrillary pathology. Additionally, we used the quantitative polymerase chain reaction technique to examine the expression of the BCAS4 / hsa-miR-185-5p / SHISA7 ceRNA axis in the peripheral blood (PB) of fifty AD patients and fifty control subjects. BCAS4 was shown to act as a ceRNA to control the SHISA7 expression throughout AD-associated neurofibrillary pathology in TC tissue specimens by sponging hsa-miR-185-5p , based on our bioinformatics study. Furthermore, in PB specimens from individuals suffering from AD and normal controls, we found no substantial differences in BCAS4 expression patterns. SHISA7 expression in AD patients' PB was found to be reduced, as was the case in the TC. On the other hand, we discovered reduced amounts of hsa-miR-185-5p in AD patients' PB samples compared to control subjects, unlike in TC tissue, where it had been demonstrated to be overexpressed. BCAS4 and SHISA7 expression levels showed a strong positive correlation, suggesting the presence of an interconnected network, most likely as a result of ceRNA regulation among PB specimens. The present study is the first evidence to highlight the expression of the BCAS4 / miR-185-5p / SHISA7 ceRNA axis in the brain and PB of AD patients, and offers a new viewpoint on molecular processes underlying AD pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Vitamin D has been vastly acknowledged as a neuroactive steroid controlling neurodevelopment. As it exerts its functions through activation of vitamin D receptor (VDR), several studies have assessed the role of VDR in brain function. More recently, a number of long non-coding RNAs (lncRNAs) have been recognized that alter expression of VDR. In the current study, we evaluated expression of four VDR-related lncRNAs (LINC00511, LINC00346, SNHG6 and SNHG16) in peripheral blood of 40 epileptic patients and 39 healthy subjects using quantitative real time PCR method. The relative expression levels of SNHG16 and LINC00511 were higher in epileptic patients compared with healthy subjects. For SNHG16, the difference was only significant between male patients and male controls, while LINC00511 had the opposite pattern. The results of Quantile regression model showed significant associations between SNHG6 and SNHG16 expressions and gender (P values of 0.027 and 0.009 respectively). Significant correlations were detected between expression levels of SNHG6 and SNHG16 (r = 0.32, P = 0.004), SNHG6 and LINC00346 (r = 0.37, P = 0.001), SNHG16 and LINC00346 (r = 0.30, P = 0.007) as well as SNHG16 and LINC00511 (r = 0.29, P = 0.009). Expression of LINC00346 was inversely correlated with vitamin D levels only in male epileptic patients (r = −0.58, P = 0.011). Expression of SNHG6 was correlated with vitamin D levels in male controls but no other subgroups (r = 0.51, P = 0.044). Based on the results of ROC curve analysis, SNHG16 had the diagnostic power of 0.86 in male subjects. Taken together, the current study provides evidences for dys-regulation of VDR-related lncRNAs in epileptic patients. The clinical significance of these finding should be explored in future studies. [ABSTRACT FROM AUTHOR]

The role of long non-coding RNAs (lncRNAs) in the pathogenesis of neurological disorders including schizophrenia has been highlighted by independent studies. In the present study, we compared peripheral blood expression of seven lncRNAs between schizophrenic patients and sex- and age-matched controls using quantitative real-time PCR technique. FAS-AS1, PVT1 and TUG1 were significantly down-regulated in schizophrenic patients compared with healthy individuals (P = 0.007, 0.003 and 0.001, respectively). The association between FAS-AS1 expression and schizophrenia was significant in male subjects aged more than 50 but not in other subgroups. GAS5, NEAT1 and OIP5-AS1 expressions were not significantly different between patients and controls (P = 0.523, 0.739 and 0.267, respectively). The associations between GAS5, NEAT1 and OIP5-AS1 expressions and schizophrenia were significant in female subjects but not in male subjects. THRIL was up-regulated in schizophrenic patients compared with healthy subjects. Based on the results of bootstraped median regression, and after controlling for the effects of age and sex, the difference in its expression between cases and controls was significant (P = 0.014), while the interaction between group and sex was not significant. The expression of lncRNAs was not correlated with age in any study subgroups. In addition, we found sex-based pairwise correlations between PVT1 expression and expression levels of OIP5-AS1, THRIL and NEAT1. We also demonstrated high sensitivity and specificity of GAS5 for diagnosis of schizophrenia in female patients. The current study provides further evidence for the participation of lncRNAs in the pathogenesis of schizophrenia. Future studies are needed to confirm the suitability of lncRNAs as peripheral biomarkers for this psychiatric disorder. [ABSTRACT FROM AUTHOR]

Objectives:Protein inhibitors of activated STAT (PIAS) are transcription co-regulator of the Janus kinase/signal transducer and activator of transcription signaling pathway as well as nuclear factor-κB family of transcription factors. Both of them are involved in cytokine release during inflammatory response. Patients and methods: Considering the role of cytokine imbalance in the pathogenesis of multiple sclerosis (MS), we compared blood expressions of PIAS1-4 genes in 48 interferon β(IFNβ)-treated MS patients with those of healthy subjects by means of real time PCR. Results: Although the expression levels of these genes were not significantly different between MS patients and healthy subjects, significant inverse correlations have been found between PIAS1 expression and age at disease onset. PIAS2 and PIAS3 expressions were inversely cor-related with Expanded Disability Status Scale (EDSS) in patients. Moreover, PIAS3 expression was correlated with disease duration in patients and with age in controls. In addition, PIAS4 expression was inversely correlated with EDSS and age at disease onset while it was positively correlated with disease duration. Conclusion: The present study provides evidences for altered expression of PIAS genes in IFNβ-treated MS patients compared with healthy subjects. However, future studies are needed for elaboration of their exact function in this disorder. [ABSTRACT FROM AUTHOR]

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, p<0.0001). Further, significant positive moderate correlations of BDNF and BDNF-AS with other lncRNAs (GSTT1-AS1 and IFNG-AS1) and genes (TNF and IFNG) were revealed (p<0.0001). Additionally, there was no correlation between the BDNF and BDNF-AS expressions and disease duration, age at onset, and Expanded Disability Status Scale of Kurtzke (EDSS) (p>0.05). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, immune-mediated, demyelinating disease of the central nervous system which disturbs cerebral vascular permeability. OBJECTIVE: Matrix metalloproteinase can increase capillary permeability and are involved in neurological diseases. METHODS: The study compared the expression level of MMP9 gene in RRMS samples with normal individuals in Iran. RNA from the buffy coat of 50 RRMS patients and 50 normal controls were extracted. All patients were HLA-DRB1*15 negative and were responders to interferon-beta with a normal vitamin D level. The level of MMP9 gene expression was measured using quantitative RT-PCR. RESULTS: The RRMS patients manifested a higher expression level of MMP9 than their normal counterparts (P = 0.02). Age-wise, there was no correlation between different age groups (> 30, 30-40, 40 <). In terms of sex, only the female patients manifested a statistically significant increase inMMP9 (p value =0.037). Besides, there was no linear correlation between MMP9 expression level and risk of Expanded Disability Status Scale of Kurtzke (EDSS); nor were there any significant correlation between expression status of MMP9 and duration of the disease. CONCLUSION: Up regulation of MMP9 gene expression would happen in RRMS IFN-B responders, but the level of increase in female patients is significantly more than males. [ABSTRACT FROM AUTHOR]

• We evaluated expression levels of GAS8 and GAS8-AS1 genes in RRMS patients compared with age- and sex-matched controls. • Expressions of both genes were significantly higher in total MS patients compared with controls. • GAS8-AS1 was higher in male patients in both age-based subgroups compared with the corresponding healthy subjects. • Expressions of both genes were inversely correlated with age of male study participants but no other subgroups. • GAS8-AS1 transcript levels had 99.6% accuracy in diagnosis of disease status in male. Expressions of the Growth arrest specific 8 (GAS8) and its naturally occurring anti-sense RNA (GAS8-AS1) have been assessed in tumoral tissues of different origins. However, their association with immune-related disorders has been poorly understood. In the current study, we evaluated expression levels of these genes in 50 relapsing-remitting multiple sclerosis (RRMS) patients compared with age- and sex-matched controls. Expressions of both genes were significantly higher in total MS patients compared with controls (P = 0.001 and P < 0.0001 respectively). The difference in GAS8 expression was also significant in total female patients and females aged less than 50 when compared with the corresponding control subjects (P = 0.002 and 0.006 respectively). GAS8-AS1 was higher in male patients in both age-based subgroups compared with the corresponding healthy subjects (P < 0.0001). Expressions of both genes were inversely correlated with age of male study participants but no other subgroups. GAS8-AS1 transcript levels had 99.6% accuracy in diagnosis of disease status in male subjects. The current study shows significance of GAS8 and GAS8-AS1 in the pathogenesis of MS and the putative role of GAS8-AS1 as a diagnostic biomarker in a subset of patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a complex inflammatory, autoimmune disease of the central nervous system (CNS). The disease pathogenesis is not well defined yet. Cytokines have an important role in inflammation as characteristic feature of the disease. Janus kinase/signal transducers and activators of transcriptions (JAK/STAT) family promote cytokine-mediated cell activation. Failure in the JAK/STAT signaling pathway is associated with the pathological outcome in MS. In this study, we compared the expression levels of STAT5a and STAT6 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group. We found that STAT5a expression was significantly down-regulated (p = .049), whereas STAT6 gene expression was significantly up-regulated (p = .046) in MS patients compared with controls. Moreover, there was significant correlation between the STAT6 gene expression and Kurtzke Expanded Disability Status Scale (EDSS) criterion. However, no significant correlation was demonstrated between the expression of STAT5a gene and clinical findings. Furthermore, there was not significant correlation between expression levels of STAT5a and STAT6 genes. Our findings suggest that STAT5a and STAT6 dysregulation may have a critical role in modification of immune responses leading to imbalance between Th2- and Th1-related cytokines. However, the mechanisms underlying it still remain to be elucidated. Future studies are needed to explore the role of STAT5a and STAT6 as prognostic biomarkers in research, design of experimental therapies or clinical settings of the MS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]