Neurotrophin growth factors and their receptors as promising blood biomarkers for Alzheimer's Disease: a gene expression analysis study.

BACKGROUND: Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions. METHODS AND RESULTS: The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls. The mRNA expression levels of neurotrophin growth factors and their receptors were measured using quantitative PCR. A Bayesian regression model was used in the research to assess the relationship between gene expression levels and demographic characteristics such as age and gender. The correlations between variables were analyzed using Spearman correlation coefficients, and the diagnostic potential was assessed using a Receiver Operating Characteristic curve. NTRK2, TrkA, TrkC, and BDNF expression levels were found to be considerably lower (p-value < 0.05) in the blood samples of AD patients compared to the control group. The expression of BDNF exhibited the most substantial decrease in comparison to other neurotrophin growth factors. Correlation analysis indicates a statistically significant positive association between the genes. The ROC analysis showed that BDNF exhibited the greatest Area Under the Curve (AUC) value of 0.76, accompanied by a sensitivity of 70% and specificity of 66%. TrkC, TrkA, and NTRK2 demonstrated considerable diagnostic potential in distinguishing between cases and controls. CONCLUSION: The observed decrease in the expression levels of NTRK2, TrkA, TrkC, and BDNF in AD patients, along with the identified associations between specific genes and their diagnostic capacity, indicate that these expressions have the potential to function as biomarkers for the diagnosis and treatment of AD.

Expression analysis of inhibitory B7 family members in Alzheimer's disease.

Alzheimer's disease (AD) is a global health problem due to its complexity, which frequently makes the development of treatment methods extremely difficult. Therefore, new methodologies are necessary to investigate the pathophysiology of AD and to treat AD. The interaction of immune modulation and neurodegeneration has added new dimensions in current knowledge of AD etiology and offers an attractive opportunity for the discovery of novel biomarkers and therapies. Using quantitative polymerase chain reaction, we compared the expression levels of inhibitory B7 family members (B7-1, B7-2, B7-H1, B7-DC, B7-H3, B7-H4, B7-H5, B7-H7, and ILDR2), as immune regulators, in the peripheral blood of late-onset AD (LOAD) patients (n = 50) and healthy individuals (n = 50). The levels of B7-2, B7-H4, ILDR2, and B7-DC expression were significantly higher in-patient blood samples than in control blood samples. Furthermore, we discovered a substantial positive correlation between all gene expression levels. In addition, the current study indicated that ILDR2, B7-H4, B7-2, and B7-DC might serve as diagnostic biomarkers to identify LOAD patients from healthy persons. The present work provides additional evidence for the significance of inhibitory B7 family members to the etiology of LOAD.

Expression analysis of IFNAR1 and TYK2 transcripts in COVID-19 patients.

As a member of JAK family of non-receptor tyrosine kinases, TYK2 has a crucial role in regulation of immune responses. This protein has a crucial role in constant expression of IFNAR1 on surface of cells and initiation of type I IFN signaling. In the current study, we measured expression of IFNAR1 and TYK2 levels in venous blood samples of COVID-19 patients and matched controls. TYK2 was significantly down-regulated in male patients compared with male controls (RME = 0.34, P value = 0.03). Though, levels of TYK2 were not different between female cases and female controls, or between ICU-admitted and non-ICU-admitted cases. Expression of IFNAR1 was not different either between COVID-19 cases and controls or between patients required ICU admission and non-ICU-admitted cases. However, none of these transcripts can properly diffrentiate COVID-19 cases from controls or separate patients based on disease severity. The current study proposes down-regulation of TYK2 as a molecular mechanism for incapacity of SARS-CoV-2 in induction of a competent IFN response.

Expression analysis of vitamin D receptor and its related long non-coding RNAs in peripheral blood of patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurological condition that is associated with abnormal expression of several transcripts. Vitamin D receptor (VDR) is a possible participant in the pathogenesis of PD. METHODS AND RESULTS: In the present research project, we evaluated expressions of VDR and three functionally associated long non-coding RNAs with this signaling, namely SNHG6, SNHG16 and LINC00346 in PD patients versus normal controls. Level of SNHG6 transcripts was lower in total patients in comparison with total controls (Expression ratio (95% CI) 0.44 (0.17-1.08)) and in male patients compared with male controls (Expression ratio (95% CI) 0.29 (0.13-0.65)). On the other hand, expression of VDR was higher in total patients compared with total controls (Expression ratio (95% CI) 10.86 (4.37-26.72)) and in male patients compared with male controls (Expression ratio (95% CI) 22.16 (6.23-78.8)). There was no significant difference in expression of SNHG16 and LINC00346 between PD patients and controls. Amounts of SNHG6 and VDR transcripts could differentiate total PD patients from total controls with AUC values of 0.66 and 0.86, respectively. CONCLUSIONS: Cumulatively, the results of the present investigation imply dysregulation of VDR signaling in PD and necessitate conduction of further functional studies.

Assessing the expression of two post-transcriptional BDNF regulators, TTP and miR-16 in the peripheral blood of patients with Schizophrenia.

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.

Expression of BDNF-Associated lncRNAs in Parkinson's disease.

Decreased level of neurotrophic factor brain-derived neurotrophic factor (BDNF) has been supposed to participate in the pathoetiology of Parkinson's disease (PD). However, the underlying mechanisms of its dysregulation and the functional network between this factor and other transcripts have not been elucidated. In the current study, we measured expressions of BDNF, and four related long non-coding RNAs, namely BDNF-AS, MIR137HG, MIAT and PNKY in blood of PD patients and normal controls to find their expression levels in these patients and propose a possible mechanism for dysregulation of BDNF in PD patients. Notably, we detected down-regulation of all transcripts in the circulation of PD patients compared with controls. There was no significant difference in expression of either gene between male and female PD patients or patients receiving L-Dopa versus those receiving other drugs. Expression of none of genes was correlated with age, disease duration, disease stage, MMSE or UPDRS. Dynamic principal component analysis showed that expression levels of these genes almost clearly separated samples collected from healthy controls and PD patients into their respective groups. This suggests that the observed lncRNAs differences are associated with the pathophysiology of PD, and these lncRNAs might constitute an important biomarker signature for PD.

Phosphatidylinositol 3-kinase signaling inhibitors for treatment of multiple myeloma: From small molecules to microRNAs.

Multiple myeloma is one of the most hard-to-treat cancers among blood malignancies due to the high rate of drug resistance and relapse. The researchers are trying to find more effective drugs for treatment of the disease. Hence, the use of drugs targeting signaling pathways has become a powerful weapon. Overactivation of phosphatidylinositol 3-kinase signaling pathways is frequently observed in multiple myeloma cancer cells, which increases survival, proliferation, and even drug resistance in such cells. In recent years, drugs that inhibit the mediators involved in this biological pathway have shown promising results in the treatment of multiple myeloma. In the present study, we aimed to introduce phosphatidylinositol 3-kinase signaling inhibitors which include small molecules, herbal compounds, and microRNAs.

Altered expression of SOCS genes periodontitis.

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

Evaluation of expression of VDR-associated lncRNAs in COVID-19 patients.

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

Expression analysis of cytokine transcripts in inflammatory demyelinating polyradiculoneuropathy.

Inflammatory demyelinating polyradiculoneuropathies are a group of peripheral nerve system disorders in which immune reactions are dysregulated. Cytokines have noticeable roles in the regulation of these responses. We compared transcript levels of nine cytokine coding genes namely IL-1B, IL-2, IL-4, IL-6, IL-8, IL-17A, IFN-G, TGF-B and TNF-A in the peripheral blood of patients with acute and chronic kinds of this condition (AIDP and CIDP) and healthy persons. Expression of IL-17A was significantly lower in female AIDP cases compared with female controls (Expression Ratio = 0.02, P value = 0.02). Expression of this cytokine was higher in female CIDP cases compared with female AIDP cases (Expression ratio = 65.69, P value = 0.02). Moreover, expression of IL-6 tended to be diminished in female AIDP cases compared with normal females (Expression Ratio = 0.06, P value = 0.05). Expression of TGF-B was lower in female AIDP cases compared with female controls (Expression Ratio = 0.06, P value = 0.01). Transcript amounts of IL-1B were lower in whole CIDP cases compared with whole controls and in female AIDP cases compared with female controls (Expression Ratios = 0.09 and 0.00; P values = 0.04 and 0.01, respectively). Expression of this gene was considerably increased in female CIDP cases compared with female AIDP cases (Expression Ratio = 764.10, P value = 0.02). Finally, expression of this gene was lower in total cases compared with total controls (Expression ratio = 0.19, P value = 0.03). Diagnostic power of IL-4 was estimated to be 0.7 in differentiating between CIDP cases and controls. IL-1B had the diagnostic power of 0.72 in distinguishing between ADP cases and controls. Finally, TNF-A had the diagnostic power of 0.71 in differentiating between AIDP cases and CIDP cases. The current results suggest the possible role of these cytokines in the pathogenesis of inflammatory demyelinating polyradiculoneuropathies.

Abnormal expression of NF-κB-related transcripts in blood of patients with inflammatory peripheral nerve disorders.

The NF-κB family includes some transcription factors which have important functions in the regulation of immune responses, therefore participating in the pathophysiology of inflammatory conditions such as peripheral neuropathies. We have quantified expression of a number of NF-κB-related transcripts in patients with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) versus healthy subjects. These transcripts have been previously shown to be functionally related with this family of transcription factors. Expressions of ATG5, DICER-AS1, PACER, DILC, NKILA and ADINR have been increased in both CIDP and GBS patients compared with controls. However, expression of ATG5 was not different between female CIDP cases and female controls. Moreover, expression of PACER was not different between male GBS cases and male controls. Expression levels of CHAST and CEBPA were not different between patients and controls. Expression of none of the assessed genes was different between GBS and CIDP cases. Significant correlations have been revealed between expression amounts of NF-κB-related transcripts both among CIDP/ GBS patients and among controls except for NKILA/ATG5, ADINR/ATG5 and PACER/ATG5 and DICER-AS1/ATG5 pairs among controls whose expression levels have not been correlated. In the patient group, CEBPA/PACER, CHAST/PACER and CHAST/DICER-AS1 pairs had the most robust correlations (r = 0.94). Among controls, NKILA/ADINR pair had the most strong correlation (r = 0.78). ADINR and DICER-AS1 levels could differentiate CIDP cases from controls with 100% sensitivity and specificity. In differentiation of GBS cases from controls, these two transcripts had the AUC values of 0.99 and 1. Combination transcript levels of NF-κB-related transcripts similarly detects CIDP and GBS cases from healthy controls with 100% sensitivity and specificity. Therefore, NF-κB-related transcripts are possibly involved in the pathophysiology of inflammatory peripheral nerve disorders and can be used as diagnostic markers for these conditions.

Dysregulation of lncRNAs in circulation of patients with periodontitis: results of a pilot study.

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

Blood and tissue levels of lncRNAs in periodontitis.

Periodontitis is a complex disorder that affects a large number of human beings from different ethnic groups. This condition has been associated with dysregulation of a number of genes, among them are long noncoding RNAs (lncRNAs). In the current study, we assessed the expression of four lncRNAs (BDNF-AS, MIAT, MIR137HG, and PNKY) as well as BDNF in the peripheral blood and gingival tissues obtained from patients with periodontitis and healthy subjects. The expression of BDNF was significantly lower in blood samples of male patients with periodontitis compared with male controls (posterior ß of RE = -4.754, p = .048). However, there was no significant difference in the expression of BDNF in tissue samples from the cases and controls. The expression of BDNF-AS was significantly lower in the tissue samples of patients compared with control tissue samples (posterior ß of RE = -2.151, p = .019). Such an expression difference was detected between male subgroups as well (posterior ß of RE = -3.679, p = .009). However, expression of this lncRNA was not different in blood samples obtained from patients compared with healthy subjects. The expression of PNKY was significantly higher in tissue samples obtained from female patients compared with sex-matched controls (posterior ß of RE = 6.23, p = .037). Blood levels of this lncRNA were not different between cases and controls. There was no significant difference either in the tissue expression or in blood expression of MIR137HG or MIAT between cases and controls. The current study indicates the putative role of BDNF, BDNF-AS, and PNKY in the pathophysiology of periodontitis and potentiates these genes as candidates for functional studies.

Upregulation of VEGF-A and correlation between VEGF-A and FLT-1 expressions in Iranian multiple sclerosis patients.

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.

Association study of a single nucleotide polymorphism in brain cytoplasmic 200 long-noncoding RNA and psychiatric disorders.

The Brain cytoplasmic 200 RNA (BC200 RNA) is neuron-specific lncRNA with putative roles in normal aging and in the pathogenesis of Alzheimer's disease. Its role in the neuron plasticity has also been documented. In the current study, we genotyped a single nucleotide polymorphism (SNP) within this lncRNA (rs4404327) in a population of Iranian patients with diverse neuropsychiatric conditions including substance addiction (n = 315), attention deficit hyperactive disorder (ADHD) (n = 53), bipolar 1 (BP1) (n = 131), bipolar 2 (BP2) (n = 68), major depressive disorder (MDD) (n = 56) and schizophrenia (SCZ) (n = 177) as well as age-/ sex-matched healthy controls. This SNP was associated with ADHD in co-dominant model (C/T vs. C/C) (OR (95% CI) = 3.7 (1.96-10), P value = 0.000193), dominant model (C/T + T/T vs. C/C) (OR (95% CI) = 4.43(2.02-9.72), P value = 1.37E-04) and multiplicative model (C vs. T) (OR (95% CI) = 3.20(1.64-6.25), P value = 4.316269E-04). Moreover, this SNP was associated with risk of BP1 in dominant model (OR (95% CI) = 1.67(1.08-2.62), P value = 0.02) and multiplicative model (OR (95% CI) = 1.51 (1.04-2.21), P value = 0.028). After correction for multiple comparisons (6 cohorts × 4 models), associations remained significant in ADHD but not in BP1. No other significant association was detected. The current project showed association between a certain SNP within BC200 RNA and ADHD. Further studies are required to assess these associations in larger cohorts of patients and find the underlying mechanism for this observation.

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.

Integrative analysis of OIP5-AS1/HUR1 to discover new potential biomarkers and therapeutic targets in multiple sclerosis.

Multiple sclerosis (MS) is a devastating autoimmune disease of the central nervous system associated with demyelination and axonal injury. This study was designed to find potential lncRNAs and their targets that are associated with the molecular basis of MS pathogenesis. In this study, peripheral blood samples were obtained from 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls. lncRNAs and their target were selected for validation using TaqMan Real-Time PCR. Interactions were studied based on approaches that used to investigation biological functions and signaling pathways affected by differentially expressed messenger RNAs (mRNAs). The results of this study indicate an increase in the expression of HUR1 (p = 0.0001), CPSF7 (p = 0.02), and reduction of CSTF2 expression (p = 0.04). Also, an increase in the expression of OIP5-AS1 (p = 0.01) was observed in men less than 30 years old. We performed a comparative analysis of the long noncoding RNAs (lncRNAs), and then we ranked them as candidate biomarkers according to a decreasing area under the receiver operating characteristic (ROC) curve (AUC) and plotted the results. Dysregulation of lncRNA expression has been linked to diseases. Further studies on the HUR1 gene can be used as diagnostic tools for the identification of high-risk individuals in families with a history of disease before, during, and even after treatment. Our data uncovered the expression profiles of lncRNAs and mRNAs in MS patients, which will help delineate the molecular mechanisms in MS pathogenesis. However, further studies need to determine the precise role of these genes in the pathological process in MS.

PIAS genes as disease markers in bipolar disorder.

The protein inhibitors of activated STAT (PIAS) are involved in regulation of many transcription factors and signaling pathways that contribute to the pathogenesis of bipolar disease (BD). In the current study, we evaluated the expression of four PIAS genes (PIAS1-4) in peripheral blood of BD patients and healthy subjects to explore their contribution in the pathogenesis of BD and their suitability as peripheral biomarkers for this disorder. All PIAS genes were significantly upregulated in total BD patients compared with total controls. The sex-based analysis confirmed upregulation of PIAS1-4 genes in male BD patients compared with male controls (P < 0.001). However, PIAS1 was significantly downregulated in female patients compared with female controls (P = 0.02). Expression levels of other PIAS genes were not significantly different between female patients and female controls. There were no significant correlations between expression levels of PIAS genes and any of the clinical data of study participants after adjustment of the effects of the sex. On the basis of the area under the curve (AUC) values in receiver operating characteristic curves, PIAS4 had the best performance in the differentiation of disease status between study participants (AUC = 0.81). PIAS3 and PIAS4 genes had the best sensitivity and specificity values, respectively. Combination of expression levels of four genes resulted in the improvement of diagnostic power (AUC = 0.82). The current data implies the role of PIAS genes in the pathogenesis of BD and denotes their suitability as peripheral markers for this disorder.

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.

Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients.

Multiple sclerosis (MS) is a progressive chronic autoimmune-mediated disease. Recently, long non-coding RNAs (lncRNAs) are characterized to participate in the adjustment of immune responses. Here, we evaluated the expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs and their targets (TNF and IFNG, respectively) in Iranian MS patients.In this case-control study, 50 relapsing-remitting MS patients and 50 healthy subjects were recruited. Expressions of GSTT1-AS1 and IFNG-AS1 lncRNAs, as well as TNF and IFNG genes, were assessed in their peripheral blood samples by SYBR Green-based Real-time quantitative PCR.Expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs were both significantly downregulated (p values 0.032 and 0.013, respectively). On the other hand, the expression of TNF and IFNG showed increased levels, however, did not reach statistical significance after our analysis (p > 0.05). Spearman correlation analysis showed that GSTT1-AS1 had a significant positive moderate correlation with IFNG-AS1 (r = 0.541, p < 0.0001), IFNG (r = 0.329, p = 0.001), and TNF (r = 0.204, p = 0.041). Also, IFNG-AS1 revealed the same correlation with IFNG (r = 0.475, p < 0.0001) as well as TNF (r = 0.399, p < 0.0001). Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder. Larger sample size and further investigation assays could shed light on the underlying mechanisms in this area of science.