Downregulation of Cancer-Associated lncRNAs in Peripheral Blood of Multiple Sclerosis Patients.

Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of immune-related disorders including multiple sclerosis (MS). Based on the role of these transcripts in the regulation of immune response, peripheral levels of lncRNAs can reflect the level of immune activation. In the present study, we quantified expression of four lncRNAs namely SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 in venous blood of MS patients and controls using quantitative real-time PCR method. Relative expressions of SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 were significantly lower in female MS patients compared with female healthy subjects. For MEG3, this pattern of expression was also observed in male subjects. However, for other lncRNAs, no significant difference was detected between male patients and male controls. Expression of HOXA-AS2 was correlated with progression index (r = 0.36, P < 0.001). Besides, there was a significant correlation between expression of this lncRNA and expression of LINC-ROR in MS patients (r = 0.44, P < 0.0001). There was no other correlation between expression of lncRNAs and clinical data in MS patients. In control group, expressions of none of lncRNAs were correlated with age of persons. Notably, significant correlations were demonstrated between expression levels of all lncRNAs in healthy subjects with r values ranging from 0.23 to 0.42. The current investigation shows dysregulation of lncRNAs in MS patients in a sex-specific manner and warrants further studies to unravel the clinical and therapeutic implications of such dysregulation.

Identification of HLA-A/B/DRB1 alleles in Iranian patients with Fanconi anemia.

Fanconi anemia includes a number of clinically and genetically diverse disorders all of them being associated with genomic instability. Some previous studies reported higher frequencies of certain HLA alleles in patients with Fanconi anemia. In the current study, we genotyped HLA-A/B/DRB1 alleles in 40 Iranian patients with Fanconi anemia. We also genotyped these alleles in the same number of Iranian sex-matched healthy individuals. The frequency of DRB1*11 was significantly higher in patients compared with controls (OR (95% CI) = 2.143 [1.05, 4.46], P value = 0.036). On the other hand, the frequencies of DRB1*13 and B*13 were lower in patients compared with controls (OR (95% CI) = 0.134 [0.02, 0.55], P value = 0.003 and OR (95% CI) = 0.13 [0.01, 0.89], P value = 0.035, respectively). Assessment of genetic divergence using Fstat test showed complete divergence in HLA-A, -B, -DRB1 alleles and haplotypes between patients and controls. The current study provides evidences for different distribution of HLA alleles between patients with Fanconi anemia and healthy subjects.

ANRIL Variants Are Associated with Risk of Neuropsychiatric Conditions.

The antisense non-coding RNA in the INK4 locus (ANRIL) is a long non-coding RNA (lncRNA) whose contribution in several human disorders has been verified. In the current projects, we genotyped two single nucleotide polymorphisms (SNPs) in this lncRNA (rs1333045 and rs1333048) in a population of Iranian patients with bipolar disorder (BP), major depressive disorder (MDD), and methamphetamine addiction. The rs1333045 was associated with methamphetamine addiction in recessive and multiplicative models (OR (95% CI) = 1.867 (1.211-2.877), adjusted p value = 8.75E-03 and OR (95% CI) = 1.415 (1.089-1.839), adjusted p value = 1.87E-02 respectively). The rs1333048 was associated with methamphetamine addiction in co-dominant model (A/A vs. C/C: OR (95% CI) = 0.195 (0.114-0.336), adjusted p value = 2.44E-09) and in other inheritance models. The rs1333045 was not associated with risk of BP I in any inheritance model. However, the rs1333048 was associated with BP I in co-dominant model (A/A vs. C/C: OR (95% CI) = 0.499 (0.286-0.870), adjusted p value = 2.53E-07) and in other inheritance models. In BP II cohort, we detected significant associations between both SNPs and risk of disorder in all inheritance models. In co-dominant model, these associations were detected just between homozygotes (T/T vs. C/C (rs1333045); A/A vs. C/C and (rs1333048)). The rs1333045 was associated with MDD in recessive model (OR (95% CI) = 2.221 (1.173-4.207), adjusted p value = 0.026). The rs1333048 was associated with MDDs in dominant, recessive, and multiplicative models. The selected SNPs were not in linkage disequilibrium (D' statistic = 0.23, r2 = 0.05). Haplotype analyses have shown that T A haplotype block (rs1333045 and rs1333048 respectively) significantly decreases risk of addiction, BP I, BP II, and MDD. Besides, the C C haplotype decreases risk of addiction, BP II and MDD. Finally, the T C haplotype increases risk of BP I, BP II, and MDD. Based on the above-mentioned data, the selected ANRIL SNPs or other SNPs in linkage disequilibrium with them might confer risk of neuropsychiatric disorders. Taken together, ANRIL can be regarded as a risk locus for these conditions.

Association between HLA alleles and risk of celiac disease in Iranian patients.

Celiac disease (CD) is a common autoimmune disease that is manifested by inflammation of the small intestine and varying extra intestinal symptoms, also considered to be associated with human HLA-DQ genes. In this study, 40 patients of CD and 40 healthy control samples were genotyped for HLA-DQB1 and 14 patients of CD and 14 healthy control samples were genotyped for HLA-DQA1genes using the SSP-PCR technique and a commercial kit.The DQA1*05 allele had the highest frequency among the patient group (42.86%). The frequency of this allele was 28.57% in healthy controls, and there was no statistically significant difference in this case (p= 0.771).The DQB1*02 allele was the most common in patients (33.75%) followed by the DQB1*03 allele (31.25%).The difference in frequency of the HLA-DQB1*02 allele in the patient and control groups was statistically significant (P= 0.0002, OR = 4.72). The remarkable differences in the distribution of HLA-DQ2 in Iranian patients compared to controls and relative risks signified the role of these alleles in the development of CD in Iranian patients and confirmed the likelihood of using HLA-DQ typing in the substantiation of the disease.

IFNG/IFNG-AS1 expression level balance: implications for autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different epidemiological, genetic, epigenetic, and environmental factors. Although its etiology is not fully understood, immune dysfunction is implicated in this disease. Recently, a large number of genes encoding long noncoding RNAs (lncRNAs) were discovered which act as positive or negative regulators of neighboring target genes. The lncRNA, Interferon gamma-antisense RNA (IFNG-AS1), regulates expression levels of the Interferon gamma (IFNG) gene. In the present study, we investigated expression of IFNG and IFNG-AS1 in 50 children with ASD (15 females and 35 males, mean age: 6 ± 1.4 years) and 50 healthy controls (14 females and 36 males, mean age: 6 ± 1.74 years) by real time PCR technique. The results showed significant up-regulation of IFNG and down-regulation of IFNG-AS1 expression in children with ASD compared to controls (Fold change = 1.5, P < 0.0001; Fold change = -0.143, P = 0.013, respectively). The IFNG expression level increase was more pronounced in male ASD children (Fold change = 1.621; p < 0.0001). Our data reveal a functional disruption in the interactive network of IFNG/IFNG-AS1 regulation, which could be a contributing factor in the chronic inflammatory aspect of ASD. Our findings can help understanding the underlying contributors to ASD pathogenesis and find novel treatment options for children with ASD.

Expression Levels of lncRNAs in the Patients with the Renal Transplant Rejection.

PURPOSE: Long non-coding RNAs (lncRNAs) include a vast portion of human transcripts. They exert regulatory roles in immune responses and participate in diverse biological functions. Recent studies indicated dysregulation of lncRNAs in the process of transplant rejection. In the current study, we aimed at identification of the expression of five lncRNAs (OIP5-AS1, FAS-AS1, TUG1, NEAT1 and PANDAR) in association with the process of transplant rejection. MATERIAL AND METHODS: We assessed expression of these lncRNAs in the peripheral blood of 61 kidney transplant receivers including 29 transplant rejected patients and 32 transplant non-rejected patients using real time PCR technique. RESULTS: Expression of FAS-AS1 was significantly higher in rejected group compared to non-rejected group in males, however, differences between case and control groups were insignificant among females. For other lncRNAs no significant differences were detected between two study groups. Quantile regression model showed that patients' gender was an important parameter in determination of FAS-AS1 expression (Beta=-9.46, t=-2.82, P=0.007) but not for other lncRNAs expressions. Significant pairwise correlations were detected between expression levels of lncRNAs in a disease related manner. CONCLUSION: Based on the higher expression of FAS-AS1 in patients with transplant rejection, this lncRNA might be associated with the pathogenesis of renal transplant rejection.

Epilepsy Is Associated With Dysregulation of Long Non-coding RNAs in the Peripheral Blood.

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.

Sex-specific up-regulation of lncRNAs in peripheral blood of patients with schizophrenia.

Schizophrenia as a common disabling psychiatric disorder has been associated with dysregulation of several genes and pathways among them are those being regulated by long non-coding RNAs (lncRNAs). Based on the acknowledged roles of lncRNAs in neurodevelopment, in the current study, we assessed expression of six lncRNAs namely HOXA-AS2, Linc-ROR, MALAT1, MEG3, SPRY4-IT1 and UCA1 in peripheral blood of 60 patients with schizophrenia and 60 healthy subjects. HOXA-AS2, Linc-ROR, MEG3, SPRY4-IT1 and UCA1 levels were significantly higher in total patients compared with total controls. However, when evaluating expression of genes in sex-based subgroups, the differences in the expression of these lncRNAs were significant only among females. Assessment of partial correlation between expression of lncRNAs and age of study participants after controlling the effect of sex, revealed significant correlations for HOXA-AS2, MALAT1 and UCA1 in both patients and controls. Besides, expressions of Linc-ROR and SPRY4-IT1 were correlated with age only in patients. Significant pairwise correlations were recognized between expression levels of lncRNAs in both patients with schizophrenia and controls. Based on the area under curve (AUC) values, SPRY4-IT1 had the best performance in differentiation of female patients with schizophrenia from female controls (AUC = 0.85, P < 0.0001). Combination of Linc-ROR, MEG3, SPRY4-IT1 and UCA1 expression levels could differentiate female patients with 95.2% sensitivity, 76.9% specificity and diagnostic power of 0.88 (P < 0.0001). The current study suggests the presence of a sex-based dysregulation of lncRNAs in patients with schizophrenia and their possible application as diagnostic biomarkers.

The Expression of CCAT2, UCA1, PANDA and GHET1 Long Non-coding RNAs in Lung Cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been considered to be prospective biomarkers for diagnosing lung cancer due to the fundamental roles they hold in the regulating several cancer-related pathways. METHODS: Using the quantitative real-time polymerase chain reaction method, we evaluated the expression of CCAT2, UCA1, PANDA and GHET1 lncRNAs in 32 lung cancer tissue samples and their corresponding adjacent non-cancerous tissues (ANCTs) from lung cancer patients admitted to the Labbafi-Nejad Hospital from 2015 to 2016. RESULTS: No significant differences were found in the expression of lncRNAs within the tumoral and non-tumoral tissue samples. Bayesian Multilevel analysis showed no association between the expression of lncRNAs and the patient's tumor node metastasis (TNM) stage following adjustments for age. Spearman correlation analysis revealed an inverse correlation between the expression of PANDA in tumoral tissues and age. Additionally, the difference in CCAT2 expression among the tumoral and non-tumoral tissues was inversely correlated with patients' age. Significant pairwise correlations were found between the expression of lncRNAs in both the tumoral and non-tumoral tissues. CONCLUSION: Despite the findings supporting a role for the lncRNAs, CCAT2, UCA1, PANDA and GHET1 in the pathogenesis of lung cancer, our data suggests no relationship for expression of these lncRNAs in lung cancer, questioning their potential as lung cancer biomarkers.

Peripheral expression of long non-coding RNAs in bipolar patients.

BACKGROUND: Long non-coding RNAs (lncRNAs) have established roles in the pathogenesis of diverse human disorders including neuropsychiatric disorders. METHODS: In the current study, we evaluated expression levels of six apoptosis-related lncRNAs (CCAT2, TUG1, PANDA, NEAT1, FAS-AS1 and OIP5-AS1) in the peripheral blood of bipolar disorder (BD) patients and healthy subjects to assess their contribution in the pathogenesis of BD. RESULTS: CCAT2, TUG1 and PANDA were up-regulated in total BD patients compared with total healthy subjects (P values = 0.006, <0.001 and 0.004 respectively) while OIP5-AS1 was down-regulated (P = 0.001). When expression levels of these genes were compared between patients and sex-matched healthy subjects, CCAT2 and TUG1 expression levels were only different in male subgroups; while PANDA expression was different in both male and female subgroups compared with the corresponding control subgroups. Transcript levels of lncRNAs were not correlated with any of demographic or clinical parameters of BD patients or controls after adjustment for gender. Pairwise correlations between expression levels of lncRNAs followed a disease-dependent manner. Based on receiver operating characteristic curves, among the assessed lncRNAs TUG1 had the highest diagnostic power in BD. Combination of transcript levels of CCAT2, TUG1, PANDA and OIP5-AS1 improved both sensitivity and specificity resulting in diagnostic power of 0.96. CONCLUSION: Our data demonstrated a possible role of certain lncRNAs in the pathogenesis of BD and potentiated them as diagnostic markers in this disorder.

GRM7 polymorphisms and risk of schizophrenia in Iranian population.

The role of metabotropic glutamate receptors in the pathogenesis of schizophrenia or response to antipsychotic treatment has been proposed previously. The aim of the current study was to investigate the associations between two intronic variants within GRM7 gene (rs6782011 and rs779867) and schizophrenia in Iranian population. These two single nucleotide polymorphisms (SNPs) were genotyped in 273 schizophrenic patients and 300 age and sex-matched normal controls. The frequency of A allele of the rs779867 was significantly lower in the schizophrenic patients compared with healthy subjects (OR (95% CI) = 0.71 (0.56-0.89), adjusted P value = 0.008). This SNP was associated with schizophrenia in co-dominant and dominant models (adjusted P values of 0.03 and 0.02 respectively). However, there was no difference in allele and genotype frequencies of the rs6782011 SNP between cases and controls. Consequently, the results of current study further highlight the participation of GRM7 in the pathogenesis of schizophrenia.

Aberrant Expression of Long Non-coding RNAs in Peripheral Blood of Autistic Patients.

Long non-coding RNAs (lncRNAs) constitute a large proportion of human transcriptome and are involved in fundamental aspects of neurodevelopment. In the present study, we evaluated expression levels of three lncRNAs, namely, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), p21-associated ncRNA DNA damage-activated (PANDA), and taurine-upregulated gene 1 (TUG1), in peripheral blood of autism spectrum disorder (ASD) patients compared with those in healthy subjects. We found a significant upregulation of NEAT1 and TUG1 in ASD patients. In addition, relative expressions of the pairs of lncRNAs were significantly correlated in both patients and healthy subjects. However, expressions of these lncRNAs were not correlated with age of study participants. The present study provides further evidences for dysregulation of lncRNAs in ASD patients.

Interleukin (IL)-8 polymorphisms contribute in suicide behavior.

Previous studies have highlighted the role of immune dysregulation in suicide behavior. Interleukin (IL)-8 is a chemokine with neuroprotective effects whose lower serum concentrations have been detected in individuals committed suicide. In the present study, we genotyped three single nucleotide polymorphisms (SNPs) within IL-8 gene (rs4073, rs2227306 and rs1126647) in 229 individuals who attempted suicide with soft suicide methods, 235 suicide victims and 290 individuals without any history of psychiatric disorders or suicide attempt. The T allele of rs4073 was significantly over-represented in suicide attempt group compared with both control and completed suicide groups (adjusted P values of 8.3E-7 and 9.8E-8 respectively). This SNP was associated with suicide attempt in both dominant and co-dominant models (P values of 6.2E-9 and 4.3 E-8 respectively). The genotype and allele frequencies of other SNPs were not significantly different among the three study groups. The T C A haplotype (rs4073, rs2227306 and rs1126647 respectively) were significantly less prevalent in completed suicide group compared with suicide attempt group (OR (95% CI) = 0.63 (0.46-0.86), adjusted P value = 0.03). Besides, the A T A haplotype has significant lower frequency in individuals who attempted soft suicide compared with controls (OR (95% CI) = 0.44 (0.26-0.75), adjusted P value = 0.02). However, this haplotype was significantly more prevalent in individuals attempted hard methods compared with those attempted soft methods (OR (95% CI) = 2.21 (1.26-3.87), adjusted P value = 0.04). The present study provided further evidence for the role of IL-8 in suicide behavior.

Application of the speckle-based phase retrieval method in reconstructing two unknown interfering wavefronts.

We numerically demonstrate a novel method to simultaneously reconstruct two unknown interfering wavefronts. The speckle-based phase retrieval technique is applied to derive the interference field. The derived interference field along with the phase-shifting concept is used for calculating the interfering wavefronts. Our results show the success of this method even under noisy conditions.

Detection and characterization of an optical vortex by the branch point potential method: analytical and simulation results.

Singularities are discontinuities in optical wavefronts that can be produced by turbulence effects. Since the presence of singularities in a wavefront severely degrades the adaptive optics correction performance, their detection is very important. The gradient of the wavefront phase, as measured by the Shack-Hartmann wavefront sensor in the presence of singularities, can be considered as the sum of the rotational and irrotational parts. The rotational part of the phase gradient originating from the phase singularities can be considered as a potential based on Helmholtz-Hodge decomposition. The potential at the singularities positions appears as peaks and valleys of the potential depending on the positive or negative charges of singularities. In this article, the detection of phase singularities based on the branch point potential (BPP) method is investigated. The irrotational part of the gradient produces a background potential where singularities positions appear as local extremum of the potential. With our method, the irrotational part of the gradient is eliminated and the value of peaks and valleys is increased. In addition, in this method, the potential value characterizes the optical singularities. Here, analytical and simulation results for the detection of general forms of the singularity are presented. Our simulations show the performance of singularities detection in noisy conditions.

Reconstruction of two interfering wavefronts using Zernike polynomials and stochastic parallel gradient descent algorithm.

We numerically and experimentally demonstrate an iterative method to simultaneously reconstruct two unknown interfering wavefronts. A three-dimensional interference pattern is analyzed and then Zernike polynomials and the stochastic parallel gradient descent algorithm are used to expand and calculate wavefronts.

Application of the transport of intensity equation in determination of nonlinear refractive index.

We investigate the determination of nonlinear refractive index n(2), based on solving the transport of intensity equation (TIE) in conjunction with a pump-probe technique. As the pump and probe beams propagate through a sample, the pump-induced refractive index variations in the sample change the phase distribution of the probe beam. Using two recorded probe intensities in TIE, this phase change is derived, and so the nonlinear refractive index n(2) is obtained. The influence of some characteristics of the pump beam and noise on the accuracy of determining n(2) is also investigated. The simulation results show that the proposed method has a good capability for determining the nonlinear refractive index of materials.

Very low resistance ZnS/Ag/ZnS/Ag/ZnS nano-multilayer anode for organic light emitting diodes applications.

In this paper, design and simulation of conductive nanometric multilayer systems are discussed and optimum thickness of Ag and ZnS layers are calculated to reach simultaneously to high transmittance and low sheet resistance. The conductive transparent ZnS/Ag/ZnS/Ag/ZnS (ZAZAZ) nanometric multilayer systems are deposited on glass substrates at room temperature by a thermal evaporation method. The electrical, optical, and structural properties of these multilayers, such as sheet resistance, optical transmittance, and the root-mean-square surface roughness are obtained. High quality nanometric multilayer systems with sheet resistance of 2.7 Ω/sq and the optical transmittance of ~75.5% are obtained for the ZAZAZ system. Organic light emitting diodes (OLEDs) were fabricated and tested on the ZAZAZ anode. The ZAZAZ multilayer anode based OLED shows the performance comparable to that of the indium-tin oxide anode based OLED.

Theoretical and experimental investigation of generating pulsed Bessel-Gauss beams by using an axicon-based resonator.

Nondiffracting Bessel-Gauss beams are assumed as the superposition of infinite numbers of Gaussian beams whose wave vectors lie on a cone. Based on such a description, different methods are suggested to generate these fields. In this paper, we followed an active scheme to generate these beams. By introducing an axicon-based resonator, we designed the appropriate resonator, studied its resonance modes, and analyzed the beam propagation outside the resonator. Experimentally, we succeeded to obtain Bessel-Gauss beams of the first kind and zero order. We also investigated the changes in effective parameters on the output beam, both theoretically and experimentally.

Generation of pulsed Bessel-Gauss beams using passive axicon-theoretical and experimental studies.

We studied the conditions for generating passive Bessel-Gauss beams by using an axicon. We designed an appropriate Gaussian resonator and extracted a quasi-fundamental Gaussian mode from a pulsed Nd:YAG laser pumped by a Xenon flash lamp and measured its parameters, such as propagation factor, divergence angle, and Rayleigh range. Then we generated passive Bessel-Gauss beams using an axicon and investigated their propagation properties, theoretically and experimentally. For example, for the axicon of 1°, the output energy and the Rayleigh range of the generated Bessel-Gauss beams were measured to be 58 mJ and 229.3 mm, respectively. We compared these properties with our results of the Gaussian mode. Finally, by using axicons with different apex angles, and also by changing the beam spot size on the axicon, we generated Bessel-Gauss beams and studied their properties theoretically and experimentally.