Assessment of expression of calcium signaling related lncRNAs in epilepsy.

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

Assessment of expression of oxytocin-related lncRNAs in schizophrenia.

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

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

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

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

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

Assessment of Treg-related lncRNAs in epilepsy.

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

Assessment of Expression of SOCS Genes in Acquired Immune-Mediated Polyneuropathies.

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.

Identification of oxytocin-related lncRNAs and assessment of their expression in breast cancer.

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.

Assessment of the role of non-coding RNAs in the pathophysiology of Parkinson's disease.

Parkinson's disease (PD) is the second main neurodegenerative disease causing motor abnormalities in the middle-aged and old individuals. In some cases, cognitive dysfunction also occurs. The clinical signs of PD are bradykinesia, rigidity and resting tremor. As these signs might be detected in other neurological conditions such as multiple systems atrophy and corticobasal degeneration, it is necessary to find specific and sensitive markers for this disorder. Non-coding RNAs are implicated in the different PD-associated features such as α-synuclein expression and Lewy body construction, mitochondrial dysfunction, apoptosis, neuroinflammation and defects in glial cell-derived neurotrophic factor. Several researches have confirmed dysregulation of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in brain tissues, plasma exosomes and leukocytes of affected individuals or animal models of PD. A number of these transcripts directly regulate the neurodegenerative process in PD. In the current study, we review the current data about dysregulation of ncRNAs and the role of their genomic variants in the pathogenesis of PD.

In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples.

Mitogen-activated protein kinase (MAP kinase) pathways participate in regulation of several cellular processes involved in breast carcinogenesis. A number of non-coding RNAs including both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate or being regulated by MAPKs. We performed an in-silico method for identification of MAPKs with high number of interactions with miRNAs and lncRNAs. Bioinformatics approaches revealed that MAPK14 ranked first among MAPKs. Subsequently, we identified miRNAs and lncRNAs that were predicted to be associated with MAPK14. Finally, we selected four lncRNAs with higher predicted scores (NORAD, HCG11, ZNRD1ASP and TTN-AS1) and assessed their expression in 80 breast cancer tissues and their adjacent non-cancerous tissues (ANCTs). Expressions of HCG11 and ZNRD1ASP were lower in tumoral tissues compared with ANCTs (P values < 0.0001). However, expression levels of MAPK14 and NORAD were not significantly different between breast cancer tissues and ANCTs. A significant association was detected between expression of HCG11 and estrogen receptor (ER) status in a way that tumors with up-regulation of this lncRNA were mostly ER negative (P value = 0.04). Expressions of ZNRD1ASP and HCG11 were associated with menopause age and breast feeding duration respectively (P values = 0.02 and 0.04 respectively). There was a trend towards association between ZNRD1ASP expression and patients' age of cancer diagnosis. Finally, we detected a trend toward association between expression of NORAD and history of hormone replacement therapy (P value = 0.06). Expression of MAPK14 was significantly higher in grade 1 tumors compared with grade 2 tumors (P value = 0.02). Consequently, the current study provides evidences for association between lncRNA expressions and reproductive factors or tumor features.

Assessment of IL-38 Levels in Patients with Acquired Immune-Mediated Polyneuropathies.

Acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP) are two types of immune-mediated neuropathies in which abnormal cellular or humoral immune responses have been observed. Although dysregulation of several cytokines has been detected in these disorders, expression of interleukin 38 (IL-38) has not yet been assessed in AIDP and CIDP. In the current study, we evaluated serum concentrations of this member of the IL-1 family of cytokines in 24 patients with CIDP, 13 patients with AIDP and 27 healthy subjects. We detected higher levels of IL-38 in CIDP patients compared with controls. When assessing study subgroups based on gender, there were no significant differences in IL-38 levels among the three female subgroups (P = 0.14). However, the difference among male subgroups was significant (P = 0.010). A Tukey test showed significant differences between male CIDP patients and male controls (P = 0.014). Considering the proposed anti-inflammatory role of IL-38, higher levels of this cytokine in CIDP might reflect the presence of a compensatory mechanism to reduce inflammatory processes in these patients. Further longitudinal assessment of this cytokine is need to test this hypothesis.

Assessment of Association between NINJ2 Polymorphisms and Suicide Attempts in an Iranian Population.

Suicidal behavior as a psychological problem with high public health burden is associated with a number of genetically determined risk factors. In the current study, we investigated the association between two polymorphisms within the NINJ2 gene and risk of suicide in an Iranian population. The study included 295 individuals who attempted suicide with soft suicide methods, 234 suicide victims and 410 normal controls. The rs11833579 SNP was associated with death from suicide in a codominant model in that the AG genotype decreased the risk of death from suicide compared with the GG genotype (OR (95% CI) = 0.49 (0.34-0.71), adjusted P value = 4e-04). This SNP was also associated with death from suicide in dominant (AG + AA versus GG: OR (95% CI) = 0.63 (0.46-0.87), adjusted P value = 0.011) and overdominant (AG versus GG + AA: OR (95% CI) = 0.49 (0.35-0.69), adjusted P value < 0.0001) models. In addition, this SNP was associated with soft suicide attempts in a codominant model (AG versus AA + GG: OR (95% CI) = 0.7 (0.5-0.98), adjusted P value = 0.02). The rs3806263 SNP was associated with death from suicide in allelic (A versus G: OR (95% CI) = 1.48 (1.17-1.88), adjusted P value = 0.002), codominant (AA versus GG: OR (95% CI) = 3.14 (1.89-5.21), adjusted P value < 0.0001), recessive (AA versus GG + AG: OR (95% CI) = 3.47 (2.15-5.61), adjusted P value < 0.0001), overdominant (AG versus AA + GG: OR (95% CI) = 0.62 (0.45-0.87), adjusted P value = 0.0092) and log-additive models (OR (95% CI) = 1.45 (1.15-1.83), adjusted P value = 0.0034). When comparing allele/genotype frequencies of this SNP between suicide victims and soft suicide attempters, significant associations were found in allelic, codominant, recessive and log-additive models. The AG haplotype (rs11833579 and rs3806263, respectively) was significantly less prevalent among suicide victims compared with controls (OR (95% CI) = 0.37 (0.26-0.52), adjusted P value < 0.0001). This haplotype was also less prevalent among suicide victims vs. soft suicide attempters (OR (95% CI) = 0.43 (0.31-0.61), adjusted P value < 0.0001). The GA haplotype (rs11833579 and rs3806263, respectively) was less frequent among suicide victims compared with controls (OR (95% CI) = 0.63 (0.45-0.89), adjusted P value = 0.0156). Finally, the AA haplotype was more prevalent among suicide victims compared with both controls (OR (95% CI) = 2.37 (1.56-3.6), adjusted P value = 0.0002) and soft suicide attempters (OR (95% CI) = 1.92 (1.32-2.78), adjusted P value = 0.0012). Thus, these two SNPs might be regarded as genetic determinants of suicide risk in Iranian populations. Further studies in different populations are needed to verify these results.

Assessment of expression profile of microRNAs in multiple sclerosis patients treated with fingolimod.

Fingolimod is an immunotherapeutic drug approved in certain countries as first-line therapy for relapsing-remitting multiple sclerosis (RRMS). The drug has been shown to alter the expression of several coding and non-coding genes. In the current study, we assessed the expression of miR-506-3p, miR-217, miR-381-3p, miR-1827, miR-449a and miR-655-3p in peripheral blood of patients with RRMS undergoing treatment with fingolimod compared with healthy controls. We also compared the expression of these miRNAs between fingolimod responders and non-responders to determine their relevance with regard to response to fingolimod. Expression of miR-381-3p was significantly higher in responders than in controls (RE difference = 3.903, P = 0.005), while expression of miR-655-3p was significantly lower in both responders and non-responders compared with controls (RE difference = -1.03, P = 0.014; RE difference = -1.41, P < 0.0001, respectively). No difference was found in the expression of other miRNAs between study subgroups. In addition, there was no significant difference in the expression of any miRNA between responders and non-responders. Although there were significant pairwise correlations between expression levels of all of the assessed miRNAs in controls, MS patients exhibited differences in correlation patterns. Expression of miR-381-3p was correlated with age in responders. However, expression of other miRNAs did not correlate with age in any study subgroup. The current study indicates a possible role for miR-655-3p and miR-381-3p in the pathogenesis of MS or possible effects of fingolimod on the expression of these miRNAs. Future studies are needed to verify these results in larger patient populations.

Expression assessment of a panel of long non-coding RNAs in gastric malignancy.

BACKGROUND: Long non-coding RNAs (lncRNAs) have several important functions in the regulation of cell homeostasis and cell fate. Consequently, abnormal transcription of lncRNAs has been correlated with malignant transformation of cells. These human transcripts have been shown to participate in the progression of gastric cancer. METHODS: In the current project, we evaluated expression of a panel of lncRNAs including HULC, MALAT1, FAS-AS1, GAS5, PVT1, OIP5-AS1 and THRIL in 30 gastric cancer tissues and paired adjacent non-cancerous tissues (ANCTs) using quantitative real-time PCR. RESULTS: HULC, OIP5-AS1 and THRIL transcription quantities were significantly lower in gastric tumors compared to ANCTs (P values = .02, 0.02 and 0.007, respectively). Relative transcription quantities of HULC, MALAT1, OIP5-AS1, PVT1, FAS-AS1 and THRIL were associated with the site of the primary tumor (P values = .002, 0.003, 0.002, 0.002, 0.002, and 0.001, respectively). Moreover, relative expression levels of PVT1 were associated with history of smoking (P value = .04). Correlations were identified between transcript quantities of these lncRNAs in both tumor samples and ANCTs. Receiver operating characteristic curve assessment demonstrated that THRIL had the highest diagnostic power among the mentioned lncRNAs (area under curve (AUC) = 0.72, P value = .001). HULC and OIP5-AS1 ranked afterwards (AUC values of 0.69 and 0.68; P values = .005 and 0.007, respectively). CONCLUSION: The current investigation underscores the dysregulation of these transcripts in gastric cancer specimens and suggests a number of these transcripts for further assessments of their suitability as cancer biomarkers.

Assessment of Apoptosis Pathway in Peripheral Blood of Autistic Patients.

Autism spectrum disorder (ASD) includes a number of severe neurodevelopmental disorders known by defects in social interaction, impaired verbal and non-verbal interactions, and stereotypic activities and limited interests. Dysregulation of apoptotic pathways have been demonstrated in brain tissues of affected individuals. In the present study, we evaluated expression levels of apoptosis-related genes and miRNAs in peripheral blood of ASD patients compared with healthy subjects. Transcript levels of BCL2, CASP8, and hsa-29c-3p were significantly lower in total ASD patients compared with total normal children (P values = 0.003, 0.002, and 0.01 respectively). When sex of study participants was considered in the analysis, the difference in transcript levels of these genes was significant only in male subjects. Peripheral expression of BCL2 and hsa-29c-3p had 100% sensitivity 92% specificity in ASD diagnosis. The diagnostic power of combination of transcript levels of these genes was estimated to be 78% based on the calculated AUC value. The present study provides evidences for dysregulation of apoptotic pathways in peripheral blood of ASD patients and suggests certain apoptosis-related genes as biomarkers in this regard.

Assessment of SGO1 and SGO1-AS1 contribution in breast cancer.

Shugoshin-like protein 1 (SGO1) participated in the proper progression of mitosis. This fundamental role has indicated the importance of this gene in the pathogenesis of cancer as a disorder of mitotic cell division. A previous high throughput study of long non-coding RNAs (lncRNAs) expression in lung cancer has identified aberrant expression of SGO1-antisense 1 (SGO1-AS1) in these specimens. In the current study, we quantified expression of SGO1 and SGO1-AS1 in 39 breast cancer tissues and their paired adjacent non-cancerous tissues (ANCTs). Expression of SGO1-AS1 was considerably decreased in tumoral tissues compared with ANCTs (expression ratio = 0.49, P value = 0.03). However, we could not identify significant difference in expression of SGO1 between these two sets of specimens (expression ratio = 2.9, P value = 0.2). Transcript quantities of SGO1-AS1 were associated with age at disease onset (P= 0.01). Expression of either gene was associated with hormone receptors status or clinical features such as grade and stage. There was an inverse correlation between expressions of genes in both sets of samples. Finally, transcript amounts of SGO1-AS1 could distinguish these two sets of samples with accuracy of 63% (P value = 0.03). Our results imply significance of SGO1-AS1 in breast cancer and necessitate conduction of mechanistic studies to find the molecular pathways in this regard.

Assessment of the expression pattern of mTOR-associated lncRNAs and their genomic variants in the patients with breast cancer.

The mechanistic target of rapamycin (mTOR) is a fundamental component of a signaling pathway that is involved in the pathogenesis of breast cancer via different mechanisms. This pathway is functionally linked with a number of small nucleolar RNA host genes (SNHGs). In the present project, we have searched for the expression quantitative trait loci (eQTLs) within SNHGs that are possibly involved in the pathogenesis of breast cancer. Following this in silico step, we have assessed expression levels of mTOR and four SNHGs in malignant and nonmalignant samples obtained from 80 patients with breast cancer. We also genotyped rs4615861 of SNHG3 and rs3087978 of SNHG5 in the peripheral blood of patients. SNHG12 expression was not detected in any of the assessed malignant or nonmalignant tissues. So this gene was excluded from further steps. Expression of mTOR and other three long noncoding RNAs (lncRNAs) were significantly increased in the malignant tissues compared with the nonmalignant tissues. When classifying patients into down-/upregulation categorized based on the transcript levels of each gene in malignant tissue versus nonmalignant tissues, we noticed associations between expression of SNHG1 and stage (p = 0.03), expression of SNHG5 and grade (p = 0.05), as well as between expression of SNHG3 and history of oral contraceptive use (p = 0.04). We also detected higher levels of SNHG3 expression in estrogen receptor/progesterone receptor (ER/PR) negative tumors compared with the ER/PR positive tumors (p = 0.003 and p = 0.01, respectively). Moreover, there was a trend toward higher expression of this lncRNA in HER2-positive tumors compared with the HER2-negative ones (p = 0.07). Combination of transcript levels of all genes could differentiate malignant tissues from nonmalignant tissues with the diagnostic power of 69% (p = 0.0001). The rs3087978 was associated with the expression of mTOR in malignant tissues in a way that TT and TG genotypes were associated with the higher and lower levels of expressions, respectively (p = 0.01). The current study underscores the significance of SNHGs in the pathogenesis of breast cancer.

Assessment of expression of RELN signaling pathway in multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Nearly 85% of MS patients are recognized with relapsing-remitting MS (RRMS), a typical clinical course of disease which is distinguished by several episodes of relapses, separated by remissions of neurological impairment. Failure of repair mechanisms is a main factor in progression of neurological dysfunction in MS. Several lines of evidence suggest that Reelin (RELN) signaling pathway can contribute in the regulation of repair mechanisms in MS patients. In the present study, we assessed expression levels of RELN and Disabled-1 (DAB1), two key genes in RELN signaling pathway, in peripheral blood of 50 RRMS patients and 50 matched healthy subjects. RELN was significantly down-regulated in total MS patients, and total female patients compared with the matched controls. However, no statistically significant difference was found in DAB1 mRNA expression between MS patients and controls. Furthermore, considerable correlations were detected between expression levels of RELN and DAB1 in the patients group. There were no significant correlations between expression levels of genes and EDSS, disease duration or age at onset. Our study provides evidences for the role of RELN signaling pathway in the pathogenesis of MS. Further studies are required to clarify the exact clinical significance of this pathway in MS patients.

Clinical assessment of depth sensor based pose estimation algorithms for technology supervised rehabilitation applications.

Encouraging rehabilitation by the use of technology in the home can be a cost-effective strategy, particularly if consumer-level equipment can be used. We present a clinical qualitative and quantitative analysis of the pose estimation algorithms of a typical consumer unit (Xbox One Kinect), to assess its suitability for technology supervised rehabilitation and guide development of future pose estimation algorithms for rehabilitation applications. We focused the analysis on upper-body stroke rehabilitation as a challenging use case. We found that the algorithms require improved joint tracking, especially for the shoulder, elbow and wrist joints, and exploiting temporal information for tracking when there is full or partial occlusion in the depth data.

DSCAM-AS1 up-regulation in invasive ductal carcinoma of breast and assessment of its potential as a diagnostic biomarker.

BACKGROUND: The long non-coding RNA (lncRNA) DSCAM-AS1 has been demonstrated to participate in the pathogenesis of breast cancer and tamoxifen resistance. OBJECTIVE: To evaluate expression profile of DSCAM-AS1 in invasive ductal carcinoma of breast and its suitability as a biomarker for diagnosis of breast cancer. METHODS: We evaluated expression of DSCAM-AS1 in 108 breast tissues including tumoral and adjacent non-cancerous tissues (ANCTs) by means of quantitative real time PCR. RESULTS: DSCAM-AS1 was up-regulated in tumoral tissues compared with ANCTs (Fold change = 2.86, P = 0.011). Its expression was significantly higher in patients aged less than 55 compared with older patients (P = 0.02). However, its expression levels had not a good performance as a diagnostic biomarker for breast cancer. CONCLUSIONS: The significant up-regulation of DSCAM-AS1 in tumoral tissues compared with ANCTs provides further evidences for participation of this lncRNA in the pathogenesis of breast cancer.

Assessment of expression of interferon γ (IFN-G) gene and its antisense (IFNG-AS1) in breast cancer.

BACKGROUND: The role of long non-coding RNAs has been extensively appreciated in the contexts of cancer. Interferon γ-antisense RNA1 (IFNG-AS1) is an lncRNA located near to IFN-γ-encoding (IFNG) gene and regulates expression of IFNG in Th1 cells. METHODS: In the present study, we evaluated expression of IFNG and IFNG-AS1 in 108 breast samples including tumoral tissues and their adjacent non-cancerous tissues (ANCTs) using real-time PCR. IFNG-AS1 was significantly upregulated in tumoral tissues compared with ANCTs (expression ratio = 2.23, P = 0.03). RESULTS: Although the expression of IFNG was higher in tumoral tissues compared with ANCTs (relative expression = 1.89), it did not reach the level of significance (P = 0.07). IFNG expression was significantly higher in HER2-negative tumoral tissues compared with HER2-positive ones (P = 0.01) and in grade 1 samples compared with grade 2 ones (P = 0.03). No other significant difference was found in expressions of genes between other groups. CONCLUSION: Significant strong correlations were detected between expression of IFNG and IFNG-AS1 in both tumoral tissues and ANCTs. The present study provides evidences for participation of IFNG and IFNG-AS1 in the pathogenesis of breast cancer and warrants future studies to elaborate the underlying mechanism.