Expression Analysis of <Emphasis Type="Italic">CYFIP1</Emphasis> and <Emphasis Type="Italic">CAMKK2</Emphasis> Genes in the Blood of Epileptic and Schizophrenic Patients

Schizophrenia and epilepsy are two prevalent neurological disorders with high global burden to the society. Genome-wide studies have identified potential underlying causes for these neurological diseases. In the present case-control study, we have assessed expression of CYFIP1 and CAMKK2 genes in the blood samples of epileptic and schizophrenic patients compared with healthy subjects. A total of 180 subjects including 40 epileptic patients, 50 schizophrenic patients, and 90 healthy individuals participated in the study. Expression of the mentioned genes was measured using TaqMan real-time PCR. The results demonstrated a significant upregulation of CYFIP1 gene expression in epileptic patients (P?=?0.029). CAMKK2 was downregulated in female schizophrenic patients compared with female healthy individuals (P?=?0.048). These results may provide new insight into the pathogenesis of epilepsy and schizophrenia and suggest these genes as potential therapeutic targets for these neurological disorders. Future studies should evaluate these results in larger cohorts of patients.     

Association Study of <Emphasis Type="Italic">ANRIL</Emphasis> Genetic Variants and Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disorder of central nervous system with several genetic and environmental risk factors. Genes with regulatory roles on immune system have been implicated in its pathogenesis. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to control some aspects of immune response. Among them is antisense non-coding RNA in the INK4 locus (ANRIL) whose involvement in NF-κB signaling pathway has been highlighted. In the current study, we evaluated the association between rs1333045, rs4977574, rs1333048, and rs10757278 variants of ANRIL and MS risk in a population of 410 Iranian MS patients and 410 healthy subjects. There was no significant difference in allele and genotype frequencies between MS patients and healthy subjects. However, haplotype analysis (rs1333045, rs1333048, rs4977574, and rs10757278 respectively) demonstrated protective effect of CCGG and TAAA haplotypes against MS (P values of 0.043 and 0.0026 respectively). In addition, TAGG and CCGA haplotypes were significantly associated with MS risk in the studied population (P values of 0.0065 and 0.024 respectively). The present study reveals a possible role for ANRIL in the pathogenesis of MS.     

Beneficial effects of MnTBAP, a broad-spectrum reactive species scavenger, in rat renal ischemia/reperfusion injury

Background In recent years, several lines of evidence have implicated reactive species as contributors to renal ischemia/reperfusion injury (I/R). This study was designed to investigate the effect of Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a broad-spectrum reactive species scavenger, in the prevention of renal I/R injury. Methods Experiments were performed on rats anesthetized with pentobarbital. After tracheotomy, the right femoral artery was cannulated and the mean arterial pressure and heart rate were recorded. A midline laparatomy was performed, and the renal arteries were carefully separated from surrounding tissues. After surgery and a stabilization period (60 min), the animals were randomly assigned to four groups: sham-operated; sham+MnTBAP; I/R; I/R+MnTBAP. In I/R groups, the rats were subjected to bilateral renal artery occlusion for 40 min followed by 6 h reperfusion. Other groups underwent the surgery protocol but did not undergo renal artery occlusion, and were maintained under anesthesia for the duration of the experiment. Rats were administered either MnTBAP (10 mg kg⁻¹, i.v. bolus, 15 min prior to I/R) or saline. Renal function was assessed by plasma creatinine (Cr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) measurements. The fractional excretion of Na⁺ (FE_Na+) and urinary N-acetyl-β-D-glucosaminidase (NAG) activities were also measured. Renal section damage was evaluated by light microscopy, and oxidative stress status was evaluated by measurements of plasma and renal vitamin E levels. Results We found that MnTBAP significantly reduced the I/R-mediated increases in plasma Cr, BUN, AST, FE_Na+, and NAG and improved the renal tissue histology. Conclusion Our results showed that MnTBAP was effective in preventing the development of I/R-induced renal injury.     

The role of excitatory amino acid transporter 2 (EAAT2) in epilepsy and other neurological disorders

Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Excitatory amino acid transporters (EAATs) have important roles in the uptake of glutamate and termination of glutamatergic transmission. Up to now, five EAAT isoforms (EAAT1-5) have been identified in mammals. The main focus of this review is EAAT2. This protein has an important role in the pathoetiology of epilepsy. De novo dominant mutations, as well as inherited recessive mutation in this gene, have been associated with epilepsy. Moreover, dysregulation of this protein is implicated in a range of neurological diseases, namely amyotrophic lateral sclerosis, alzheimer’s disease, parkinson’s disease, schizophrenia, epilepsy, and autism. In this review, we summarize the role of EAAT2 in epilepsy and other neurological disorders, then provide an overview of the therapeutic modulation of this protein.

     

Association between human leucocyte antigen alleles and risk of stroke in Iranian population

Previous studies have demonstrated associations between human leucocyte antigen (HLA) and some types of ischaemic stroke. In the present study, we genotyped HLA‐A,‐B and ‐DRB1 alleles in 140 Iranian patients with history of ischaemic stroke and 140 age‐/sex‐matched healthy subjects. No significant difference has been found in the distribution of HLA‐A and B alleles between cases and controls. The DRB1*16 allele was significantly over‐represented in patient group compared with control group (Adjusted p value = 0.048). Other HLA‐DRB1 alleles were not associated with stroke risk. The HLA‐B*35,B*52 genotype was significantly more prevalent among patients compared with controls (Adjusted p value = 0.03, OR [95% CI] = 9.3 [1.3, 407.2]). Several HLA haplotypes were associated with risk of stroke in the assessed population. The current study provides further evidences for participation of HLA in conferring risk of ischaemic stroke.     

A review of recent advances in histopathological assessment of head and neck squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common non-cutaneous head and neck (H&N) malignancy. Referrals for suspected SCC are seen by oral and maxillofacial surgery (OMFS) surgeons and represent the bulk of 2-week wait referrals. The diagnosis and treatment of SCC is heavily influenced by national and international guidelines. The majority of research and funding is directed towards this condition. This has led to continuous changes to update these guidelines. However, there remain areas of controversy and conflicting evidence. This article summarises articles pertinent to pathologists between 2016 and 2018 published in the leading British OMFS journal. A total of 22 published articles relating to the histopathology of non-cutaneous H&N SCC were selected.     

Expression Analysis of lncRNAs in Refractory and Non-Refractory Epileptic Patients

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the pathogenesis of neuropsychiatric disorders such as epilepsy. In the current study, we evaluated expression of eight lncRNAs in 80 epileptic patients (40 refractory and 40 non-refractory ones) and 40 normal individual using quantitative real-time PCR. Bayesian regression model showed significant higher expression of UCA1 in both refractory and non-refractory groups compared with controls (posterior beta of relative expression (RE) =?2.03, P value?=?0.003, and posterior beta of RE?=?4.05, P value?<?0.0001, respectively). Besides, expression of UCA1 was higher in non-refractory patients compared with refractory ones (posterior beta of RE?=?2.008, P value?=?0.019). When repeating statistical analyses in a gender-based manner, differences in expression of UCA1 were significant in all subgroup analyses except for male non-refractory vs. refractory subgroups analysis. Expression levels of NKILA and ANRIL were higher in both refractory and non-refractory groups compared with controls (posterior beta of RE?=?1.565, P value?=?0.018, and posterior beta of RE?=?1.902, P value?=?0.006 for NKILA; posterior beta of RE?=?1.304, P value?<?0.0001, and posterior beta of RE?=?1.603, P value?=?0.019 for ANRIL, respectively). However, expression levels of these two lncRNAs were not different between refractory and non-refractory groups. Gender-based analysis for these two lncRNAs revealed similar results except for lack of difference in ANRIL expression between male refractory group and controls. Expression of THRIL was significantly lower in both refractory and non-refractory groups compared with controls (posterior beta of RE?=???0.842, P value?=?0.044 and posterior beta of RE?=???1.969, P value?<?0.0001, respectively). Furthermore, expression of this lncRNA was lower in non-refractory patients compared with refractory ones (posterior beta of RE?=???1.129, P value?=?0.002). However, no significant difference was detected between non-refractory and refractory patients either in males or females. The interactions between gender and relative expressions of PACER, DILC, and MALAT1 were significant, so the results were assessed in gender-based manner. In females, expression of DILC was higher in non-refractory patients compared with refractory ones (posterior beta of RE?=?0.959, P value?=?0.044). Expression of MALAT1 was lower in female non-refractory patients compared with controls and in female non-refractory patients compared with refractory ones (posterior beta of RE?=???1.35, P value?=?0.002, and posterior beta of RE?=???0.942, P value?=?0.045, respectively). Finally, expression of PACER was higher in refractory patients vs. controls and non-refractory patients vs. controls in both male and female subgroups. However, comparison between non-refractory and refractory patients revealed significant results only among females. Expression of none of the assessed lncRNAs was correlated with age of study participants. There were robust correlations between expression levels of lncRNAs. The most robust correlations were detected between UCA1 and PACER (r?=?0.84, P?<?0.0001) and between UCA1 and ANRIL (r?=?0.75, P?<?0.0001). Taken together, our study demonstrated dysregulation of lncRNAs in peripheral blood of epileptic patients and potentiated them as biomarkers for this neurologic condition.