Abnormal pattern of vitamin D receptor-associated genes and lncRNAs in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a multifactorial condition. Several signaling pathways affect development of this disorder. With the purpose of exploring the role of vitamin D receptor (VDR) signaling in this disorder, we measured expression of selected mRNA coding genes and long non-coding RNAs (lncRNAs) in this pathway in patients versus normal subjects. METHODS: We measured expression of VDR-associated lncRNAs and mRNAs (SNHG6, MALAT1, Linc00511, Linc00346, VDR and CYP27B1) in the peripheral blood of BD patients vs. healthy individuals. RESULTS: Expression of SNHG6 was significantly higher in cases vs. controls (Posterior beta = 1.29, P value < 0.0001. Subgroup analysis by sex revealed significant results in both subgroups (P value < 0.0001 and P value = 0.023 for males and females, respectively). Expression of CYP27B1 was up-regulated in cases vs. controls (Posterior beta = 0.415, P < 0.0001). Such pattern was also detected among males (P < 0.0001), but not females (P = 0.419). Similarly, MALAT1 and Linc00346 were up-regulated in total cases vs. controls (Posterior beta = 0.694, P < 0.0001 and Posterior beta = 0.4, P = 0.012, respectively) and in male cases compared with male controls (Posterior beta = 0.712, P < 0.0001 and Posterior beta = 0.41, P value = 0.038, respectively). Expression of VDR was up-regulated in total cases compared with controls (Posterior beta = 0.683, P value = 0.001). Finally, expression of Linc00511 was not different between groups. MALAT1, SNHG6, CYP27B1, VDR and Linc00346 had AUC values of 0.95, 0.94, 0.91, 0.85 and 0.83 in differentiation of male patients from controls, respectively. CONCLUSION: The current study suggests VDR-associated genes as possible markers for BD.

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.

Downregulation of miR-185 is a common pathogenic event in 22q11.2 deletion syndrome-related and idiopathic schizophrenia.

Schizophrenia (SCZ) is known as a complicated mental disease with an unknown etiology. The microdeletion of 22q11.2 is the most potent genetic risk factor. Researchers are still trying to find which genes in the deletion region are linked to SCZ. MIR185, encoding microRNA (miR)-185, is present in the minimal 1.5 megabase deletion. Nonetheless, the miR-185 expression profile and its corresponding target genes in animal models and patients with 22q11.2 deletion syndrome (22q11.2DS) imply that more study is required about miR-185 and its corresponding downstream pathways within idiopathic SCZ. The expression of hsa-miR-185-5p and its corresponding target gene, shisa family member 7 (SHISA7), sometimes called CKAMP59, were evaluated in the peripheral blood (PB) samples of Iranian Azeri patients with idiopathic SCZ and healthy subjects, matched by gender and age as control groups by quantitative polymerase chain reaction (qPCR). Fifty SCZ patients (male/female: 22/28, age (mean ± standard deviation (SD)): 35.9 ± 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean ± SD): 34.7 ± 5.4) were enrolled. The expression of hsa-miR-185-5p in the PB samples from subjects with idiopathic SCZ was substantially lower than in that of control groups (posterior beta = -0.985, adjusted P-value < 0.0001). There was also a difference within the expression profile between female and male subgroups (posterior beta = -0.86, adjusted P-value = 0.046 and posterior beta = -1.015, adjusted P-value = 0.004, in turn). Nevertheless, no significant difference was present in the expression level of CKAMP59 between PB samples from patients and control groups (adjusted P-value > 0.999). The analysis of the receiver operating characteristic (ROC) curve suggested that hsa-miR-185-5p may correctly distinguish subjects with idiopathic SCZ from healthy people (the area under curve (AUC) value: 0.722). Furthermore, there was a strong positive correlation between the expression pattern of the abovementioned genes in patients with SCZ and healthy subjects (r = 0.870, P < 0.001 and r = 0.812, P < 0.001, respectively), indicating that this miR works as an enhancer. More research is needed to determine if the hsa-miR-185-5p has an enhancer activity. In summary, this is the first research to highlight the expression of the miR-185 and CKAMP59 genes in the PB from subjects with idiopathic SCZ. Our findings suggest that gene expression alterations mediated by miR-185 may play a role in the pathogenesis of idiopathic and 22q11.2DS SCZ. It is worth noting that, despite a substantial and clear relationship between CKAMP59 and hsa-miR-185-5p, indicating an interactive network, their involvement in the development of SCZ should be reconsidered based on the whole blood sample since the changed expression level of CKAMP59 was not significant. Further research with greater sample sizes and particular leukocyte subsets can greatly make these results stronger.

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study.

OBJECTIVES: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). MATERIALS AND METHODS: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. RESULTS: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. CONCLUSION: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended.

Study rationale and design of a study of EMPAgliflozin's effects in patients with type 2 diabetes mellitus and Coronary ARtery disease: the EMPA-CARD randomized controlled trial.

BACKGROUND: Recent trials have revealed that sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are effective against hyperglycemia and also reduce micro- and macro-vascular complications in patients with type 2 diabetes mellitus (T2DM). Most of the beneficial cardiovascular effects have been investigated in patients with heart failure and coronary artery disease (CAD). Yet, few human studies have been conducted to investigate the molecular mechanisms underlying these clinically beneficial effects in patients with CAD. Accordingly, the EMPA-CARD trial was designed to focus on the molecular effects of empagliflozin in patients with T2DM and CAD. METHODS: In this multicenter, triple-blind randomized controlled trial, patients with documented known T2DM and CAD will be recruited. They will be randomized on a 1:1 ratio and assigned into two groups of empagliflozin 10 mg/daily and placebo. The primary endpoint is the effect of empagliflozin on changes of plasma interleukin 6 (IL-6) after 26 weeks of treatment. The secondary endpoints will consist of changes in other inflammatory biomarkers (Interleukin 1-beta and high-sensitive C-reactive protein), markers of oxidative stress, platelet function, and glycemic status. DISCUSSION: The EMPA-CARD trial mainly tests the hypothesis that SGLT2 inhibition by empagliflozin may improve inflammatory status measured as reduction in inflammatory biomarkers in patients with T2DM and CAD. The results will provide information about the underlying mechanisms of SGLT2 inhibition that mediate the beneficial effects of this medication on clinical outcomes. TRIAL REGISTRATION: Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Temporal trend analysis of stroke and salt intake: a 15-year population-based study.

Objectives: The aim of this study was to evaluate temporal trends of salt intake with stroke incidence, stroke subtypes, and blood pressure in an adult population.Methods: Data were extracted from Isfahan Salt Study. The stroke incidence rate, average salt intake, systolic and diastolic blood pressure in adults, aged over 18 years were considered from 2000 to 2014. The Average Annual Percent Changes (AAPC), parallelism, and the coincidence of trends were estimated, using a permutation test.Results: The trend of salt intake was increased from 2010 to 2014 (AAPC = +1.59, P-value = 0.004). The trend of the stroke incidence rate was nonlinear with two change points in 2003 and 2009. The overall stroke incidence rate increased by 6.65% per year (95% CI: 1.66, 11.8, P-value = 0.015). The temporal trend changes of stroke incidence rate were steeper in patients who aged 40-45 and over 50 years (+6 to +11.5%) than in patients who aged 19-40 and 45-50 (range: -3.3% to 0). The parallelism hypothesis of longitudinal changes between salt intake and ischemic stroke was accepted in patients, aged <50 years (P-value = 0.871).Conclusions: The average salt intake and its cone-shaped variance over 15 years of the study, indicated that salt intake reduction programs and policies were effective to stop associating intake increase until 2007, however, associated intake was increased since that time, which necessitates performing preventive programs. More importantly, the trend of salt intake and ischemic stroke was similar in patients who aged <50 years, regardless of considering their blood pressure.

MEG3 lncRNA is over-expressed in autism spectrum disorder.

Long non-coding RNAs (lncRNAs) comprise a group of regulatory transcripts which partake in the biological processes leading to development of neuropsychiatric disorders such as autism spectrum disorder (ASD). We measured circulatory levels of MEG3, GAS5, CYTOR, UCA1 lncRNAs and CRYBG3 gene in children with ASD and controls. Expression of MEG3 was remarkably higher in children with ASD when compared with controls (Posterior Beta = 2.919, SE = 0.51, P value < 0.0001). This difference was significant among male subgroups (Posterior Beta = 2.913, SE = 0.56, P value < 0.0001) as well as female subgroups (95% CrI for Beta = [0.29, 2.4], SE = 0.53, P value < 0.0001). Expression levels of other lncRNAs or CRYBG3 were not different between children with ASD and controls. Among children with ASD, the most robust correlations were found between GAS5/CYTOR, CYTOR/UCA1 and GAS5/UCA1 with correlation coefficients of 0.83, 0.83 and 0.73, respectively. Among controls, GAS5/UCA1, MEG3/UCA1 and GAS5/MEG3 pairs had the highest correlation coefficients (0.89, 0.84 and 0.80, respectively). ROC curve analysis revealed that MEG3 can distinguish children with ASD from controls with diagnostic power of 0.792 (P value < 0.0001). This value was higher among male subgroups (AUC = 0.84, P value < 0.0001) compared with female subgroups (AUC = 0.727, P value = 0.0727). The current research highlights the role of MEG3 in ASD and provides clues for depiction of an lncRNA network with possible contribution in the pathogenesis of ASD.

Altered expression of lncRNAs in autism spectrum disorder.

Long non-coding RNAs (lncRNAs) have been recognized as an important epigenetic factor in the evolution of neuropsychiatric conditions. We have selected five lncRNAs (DISC2, PRKAR2A-AS1, LOC105375675, LRRC2-AS1, and LOC101928237) to measure their expression in blood samples of children with autism spectrum disorder (ASD) versus children with normal development. Expressions of DISC2, PRKAR2A-AS1 and LOC101928237 have been enhanced in ASD cases compared with healthy children (Posterior Beta = 2.508, P value<0.0001; Posterior Beta = 2.793, P value = 0.014 and Posterior Beta = 1.646, P value <0.0001, respectively). On the other hand, expression of LRRC2-AS1 has been lower in ASD patients compared with controls (Posterior Beta = -3.781, P value<0.0001). Remarkably, expression of DISC2 and PRKAR2A-AS1 have been lower in girls compared with boys (Posterior Beta = -0.982, P value<0.0001 and Posterior Beta = -0.135, P value<0.0001, respectively). In addition, expression of DISC2 has been lower in ASD cases aged more than 6 compared with those aged less than 6 years (Posterior Beta = -0.876, P value = 0.003). DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 had the area under curve (AUC) values of 0.76, 0.90, 0.92, and 0.79 in distinguishing between ASD and healthy children. Expression levels of none of DISC2, LOC101928237, LOC105375675, LRRC2-AS1, and PRKAR2A-AS1 were correlated with age of ASD cases or healthy controls. A significant correlation was detected between expressions of DISC2 and PRKAR2A-AS1. There were inverse correlations between the following pairs of lncRNAs: DISC2/LRRC2-AS1, DISC2/LOC101928237, LRRC2-AS1/PRKAR2A-AS1, LOC101928237/LRRC2-AS1, and LOC101928237 /LOC105375675. We conclude that DISC2, LOC101928237, LRRC2-AS1, and PRKAR2A-AS1 might be used as potential markers for this condition.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

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.

Expression analysis of NF-κB interacting long noncoding RNAs in breast cancer.

The nuclear factor-κB (NF-κB) has a prominent role in development of breast cancer and response of patients to conventional therapies. Several factors regulate the activity of this transcription factor. In the current investigation, we compared expression levels of five long non-coding RNAs (lncRNAs) with putative interactions with NF-κB namely CHAST, ADINR, DICER1-AS1, HNF1A-AS1 and NKILA between 78 breast cancer tissues and their paired adjacent non-cancerous tissues (ANCTs). We also assessed expression levels of ATG5 and CEBPA mRNA coding genes that are functionally linked with NF-κB signaling in these two sets of samples. All assessed genes except for NKILA were significantly down-regulated in tumoral tissues compared with ANCTs. Expression of NKILA was not significantly different between tumoral tissues and ANCTs. Expression levels of CEBPA and HNF1A-AS were significantly associated with cancer stage (P values of 0.03 and 0.02 respectively). Expression levels of ATG5 tended to be associated with mitotic rate (P = .05). The association between expression levels of ATG5 and tumor size was also significant (P = .02). Expression of CHAST was significantly associated with PR status (P = .04) and tended to be associated with ER status (P = .05). Finally, expression of NKILA was significantly associated with first pregnancy age (P = .01). No other significant association was detected between expression levels of assessed genes and clinical parameters. Expression levels of mentioned genes were significantly correlated with each other. The most significant correlations were found between CHAST and ADINR (correlation coefficients of 0.78 and 0.69 in tumoral tissues and ANCTs respectively). Based on the area under curve (AUC) values, DICER1-AS and CEBPA had the best performance in differentiation of tumoral tissues from ANCTs (AUC values of 0.92 and 0.90 respectively. Combination of transcript quantities of six genes could differentiate these two sets of samples with 92.3% sensitivity, 91% specificity and diagnostic power of 95%. The current project highlights dysregulation of NF-κB-associated genes in breast cancer tissues and suggests them as potential diagnostic markers in breast cancer.

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.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.

Expression of long non-coding RNAs (lncRNAs) has been dysregulated in non-small cell lung cancer tissues.

BACKGROUND: Non-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard. METHODS: In the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs). RESULTS: NEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs. CONCLUSIONS: The observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.

Expression Pattern of Long Non-coding RNAs in Schizophrenic Patients.

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

Sex-based dimorphisms in expression of BDNF and BACE1 in bipolar patients.

Bipolar disorder (BD) is a chronic, serious mental disorder distinguished by repeated episodes of mania and depression. Previous studies have demonstrated dysregulation of a number of transcripts in brain tissue or peripheral blood of BD patients. In the present study, we compared expression of two protein coding genes (brain-derived neurotrophic factor (BDNF) and beta-secretase 1 (BACE1)) and their natural occurring anti-sense (AS) RNAs (BDNF-AS and BACE1-AS) in peripheral blood of 50 BD patients (mean age ±â€¯standard deviation (SD) = 36.5 ±â€¯9.32) and 50 healthy subjects (mean age ±â€¯SD = 33.62 ±â€¯8.59). BDNF and BACE1 were significantly up-regulated in peripheral blood of total BD patients compared with total healthy subjects (Expression ratio = 2.2, P value = 0.003; Expression ratio = 2.2, P value = 0.002 respectively). However, comparison of their levels in sex-based subgroups showed their up-regulations only in male patients compared with male health subjects (Expression ratio = 2.48, P value = 0.006; Expression ratio = 2.1, P value = 0.01). No significant differences were found in expressions of BDNF-AS and BACE1-AS between BD and health subjects. We detected a significant correlation between BDNF expression and age at disease onset in BD group after adjustment of the effects of sex (R = 0.26, P value = 0.03). Moreover, there were trends toward correlations between BDNF expression and disease duration in BD group and between BDNF expression and age in health subjects (P values = 0.05). Combination of BDNF, BDNF-AS and BACE1 expression levels could differentiate BD patients from healthy subjects with 68% sensitivity and 82% specificity (area under curve = 0.72, P value = 0.0001). The current study suggests a sex-based dimorphic pattern in expression of BDNF and BACE1. Moreover, our results imply that expression pattern of these genes could be diagnostic markers in BD. Future studies are needed to assess this speculation in larger patient samples.

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.

Temporal Trend of Non-Invasive Method Capacity for Early Detection of Metabolic Syndrome in Children and Adolescents: A Bayesian Multilevel Analysis of Pseudo-Panel Data.

BACKGROUND: The aim of this study was to examine the ability of Noninvasive methods to early predictions of metabolic syndrome (MetS) among children and adolescents from 2003 to 2016. METHODS: This was a repeated cross-sectional study based on 24,409 Iranian children and adolescents. The variables included anthropometric measures, serum lipid profiles, hypertension, and MetS. The receiver operating characteristic regression and Bayesian multilevel modeling conducted on data to comparison the power of anthropometric measures to early prediction of cardiometabolic risk factors. RESULTS: The tri-ponderal body shape index (TBSI) in females and waist circumference (WC) percentile in males yielded a greater ability to predict lipid profiles and hypertension than the rest of anthropometric factors. The TBSI (ß = 6.24, 95% credible interval [95% Crl] 3.9-8.7) followed by the WC percentile (ß = 4.43, 95% Crl 3.5-5.4) were considered the better predictors of MetS compared with the body mass index (BMI), tri-ponderal mass index (TMI), WC, waist-to-height ratio, and WC to height5 in adolescents. The TBSI with Youden index J (JI) = 0.85 was significantly more accurate than the BMI (JI = 0.73), and TMI (JI = 0.7) for classifying individuals with MetS and in healthy groups. The predictability of early MetS was consistent for both TBSI and WC components throughout the study period. CONCLUSIONS: The TBSI including, both BMI and WC components, predicts MetS and cardiometabolic risk factors more accurately than BMI or WC alone in females. The TBSI ability was higher than other anthropometric factors for screening MetS and cardiometabolic risk factors among adolescents.

Hepatocellular carcinoma up-regulated long non-coding RNA: a putative marker in multiple sclerosis.

Highly up-regulated in liver cancer (HULC) is a cancer-associated long non-coding RNA (lncRNA) which may regulate expression of other genes by working as a competing RNA for microRNAs. In the current study, we assessed transcript levels of this lncRNA in peripheral blood of multiple sclerosis (MS) patients and healthy persons to evaluate its possible role in the pathogenesis of this inflammatory disease and its diagnostic power. The results of Multilevel Bayesian showed no significant difference between cases and controls (P = 0.002, 95% confidence interval (CI) = [3.08, 13.3]). However, based on the results of Quantile regression, there was a significant difference in HULC expression between cases and controls after controlling the effects of sex and age (P = 0.002, 95% CI = [3.08, 13.3]) which shows different trends in males and females. HULC expression was inversely correlated with age of male subjects but not female subjects. HULC transcript levels had 91.1% accuracy in diagnosis of MS disease (Specificity: 80%, Sensitivity: 86.6%). The diagnostic power of HULC was higher in male subjects aged less than 50 years (AUC = 0.923, Specificity: 80%, Sensitivity: 100%). The present study shows the possibility of application of transcript levels of HULC as diagnostic marker in MS disease. However, future studies with larger sample sizes are necessary to validate our results.

Expression analysis of vitamin D receptor-associated lncRNAs in epileptic patients.

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