Publications by authors named "Shahram Arsang-Jang"

80 Publications

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.

BMC Cardiovasc Disord 2021 Jun 30;21(1):318. Epub 2021 Jun 30.

Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

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.
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http://dx.doi.org/10.1186/s12872-021-02131-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242278PMC
June 2021

Down-regulation of a panel of immune-related lncRNAs in breast cancer.

Pathol Res Pract 2021 Jun 22;224:153534. Epub 2021 Jun 22.

Department of Surgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Breast cancer is a common neoplasm among women. This type of cancer is among malignancies in which role of long non-coding RNAs (lncRNAs) has been extensively explored. Some recently recognized lncRNAs have been less investigated in this neoplastic condition. LncRNAs that regulate tumor immunity are among those contributing in the pathogenesis of cancer. In the present expression assay, we compared expressions of nine immune-related lncRNAs namely lnc-MICAL3-2 (AC016027.1), lnc-DDX31 (AL445645.1), LINC01063, LINC02381, ENST0000615051 (AC083809.1), AC009237.14 (lnc-TRIM43B-1), ENST0000603791, LINC1234 and AC008760.1 between breast cancer samples and their paired non-cancerous samples. Expression levels of lnc-MICAL3-2, lnc-DDX31, LINC01063, LINC02381, ENST0000615051 and lnc-TRIM43B-1 were significantly decreased in breast cancer samples compared with paired control tissues (Posterior mean difference= -2.774, -2.012, -2.012, -2.015, -0.884 and -2.872; P values= 0.019, 0.0001, 0.0001, 0.0001, 0.032 and 0.0001, respectively). Expression levels of these lncRNAs have been associated with a number of clinical characteristics of breast cancer patients. Lnc-TRIM43B-1 had the highest performance in distinguishing between tumoral and non-tumoral tissues (AUC=0.82, Sensitivity=76%, Specificity=73.24%). As these lncRNAs could differentiate tumor samples from control samples, they might be regarded as putative tissue markers for breast cancer.
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http://dx.doi.org/10.1016/j.prp.2021.153534DOI Listing
June 2021

Expression Analysis of VDR-Related LncRNAs in Autism Spectrum Disorder.

J Mol Neurosci 2021 Jul 14;71(7):1403-1409. Epub 2021 Jun 14.

Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Vitamin D receptor (VDR) signaling has been reported to affect neurodevelopment, thus participating in the risk of autism spectrum disorder (ASD). We have measured expression amounts of VDR, CYP27B1, and two related long non-coding RNAs, namely SNHG6 and LINC00511, in the circulation of ASD patients compared with normal controls. Expression of CYP27B1 was remarkably higher in ASD cases compared with controls (posterior beta = 2.38, SE = 0.46, adjusted P value < 0.0001, 95% credible interval (CrI) for beta = [1.49, 3.27]). Level of SNHG6 was lower in ASD cases compared with controls (posterior beta = - 0.791, SE = 0.24, adjusted P value = 0.029, 95% CrI for beta = [- 1.27, - 0.33]). Expression levels of VDR and LINC00511 were similar between ASD cases and controls (P values = 0.97 and 0.46, respectively). Expressions of VDR, CYP27B1, SNHG6, and LINC00511 were not correlated with age of children. However, significant correlations were perceived between expressions of CYP27B1 and LINC00511 (r = 0.47, P < 0.0001), VDR and CYP27B1 (r = 0.42, P < 0.0001), and VDR and SNHG6 (r = 0.32, P < 0.0001). Therefore, these results imply dysregulation of a number of VDR-related genes in ASD patients.
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http://dx.doi.org/10.1007/s12031-021-01858-yDOI Listing
July 2021

MEG3 lncRNA is over-expressed in autism spectrum disorder.

Metab Brain Dis 2021 Jun 11. Epub 2021 Jun 11.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s11011-021-00764-xDOI Listing
June 2021

The Ability of the Framingham Steatosis Index (FSI) to Predict Non-alcoholic Fatty Liver Disease (NAFLD): A Cohort Study.

Clin Res Hepatol Gastroenterol 2021 Mar 9;45(6):101567. Epub 2021 Mar 9.

Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals.

Methods: Our study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor.

Results: The odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009-2010 to 2016-2017 were 4.909 (4.243-5.681) and 2.453 (2.024-2.972), respectively (P<0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95% CI: 0.8314-0.8527) and 0.7093 (95% CI: 0.6863-0.7322), respectively.

Conclusion: The FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD.
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http://dx.doi.org/10.1016/j.clinre.2020.10.011DOI Listing
March 2021

Altered expression of lncRNAs in autism spectrum disorder.

Metab Brain Dis 2021 06 15;36(5):983-990. Epub 2021 Feb 15.

Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s11011-021-00681-zDOI Listing
June 2021

Expression of BDNF-Associated lncRNAs in Treatment-Resistant Schizophrenia Patients.

J Mol Neurosci 2021 Jan 5. Epub 2021 Jan 5.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) play a decisive role in the development of the central nervous system and modulation, differentiation, and function of neurons. Thus, any abnormal pattern of expression of these transcripts might alter normal development leading to neuropsychiatric disorders. In this regard, transcripts of brain-derived neurotrophic factor (BDNF) and four BDNF-associated lncRNAs (BDNF-AS, MIR137HG, MIAT, and PNKY) were evaluated in the peripheral blood of schizophrenia (SCZ) patients as well as normal subjects. The results indicated that the relative expression (RE) of PNKY was higher in SCZ patients as compared with controls (posterior beta of RE = 2.605, P value = 0.006) and in female patients compared with female controls (posterior beta of RE = 2.831, P value < 0.0001). BDNF expression was also higher in SCZ patients when compared with controls (posterior beta of RE = 0.64, P value < 0.036). Finally, a correlation was detected between the disease status and gender in terms of BDNF-AS expression (P value = 0.026). An inverse correlation was also found between levels of PNKY and age in the control group (r = - 0.30, P value < 0.0001). Expressions of BDNF and all lncRNAs were correlated with each other in both patients and controls. PNKY had the best diagnostic power among all assessed genes in the identification of disease status (area under curve = 0.78). BDNF, BDNF-AS, MIR137HG, and MIAT genes could discriminate SCZ patients from normal subjects with diagnostic power of 71%, 72%, 67%, and 68%, respectively. The current investigation suggests the possibility of the application of transcript levels of lncRNAs as an SCZ diagnostic marker. However, it warrants further studies in larger sample sizes.
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http://dx.doi.org/10.1007/s12031-020-01772-9DOI Listing
January 2021

Differential Expression of Cytokine-Coding Genes among Migraine Patients with and without Aura and Normal Subjects.

J Mol Neurosci 2021 Jun 12;71(6):1197-1204. Epub 2020 Nov 12.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Migraine is a prevalent disorder in humans and represents one of the top 10 causes of years lived with disability. Several genetic and environmental factors are involved in the pathobiology of migraine. A number of studies have underscored the role of dysregulated immune reactions. We compared the expression levels IL-2, IL-4, CXCL8, IL-17, IFN-γ, TGF-β and TNF-α cytokines in blood specimens of patients with migraine and those of healthy persons to identify any possible dysregulation in their expression and to propose mechanisms for this disorder. Expression of INF-γ was suggestively higher in migraine cases than in healthy individuals (posterior beta = 0.35, adjusted P value = 0.017). In addition, expression of this cytokine was lower in female subjects than in male subjects (posterior beta = -0.712, adjusted P value = 0.012). Expression of IL-4, TGF-β and TNF-α was also higher in cases compared with controls (posterior beta = 1.34, adjusted P value = 0.04; posterior beta = 0.849, adjusted P value = 0.036; posterior beta = 0.451, adjusted P value = 0.042, respectively). On the other hand, CXCL8 expression was lower in migraine cases than in controls (posterior beta = -0.78, adjusted P value = 0.039). Expression levels of IL-1B, IL-17 and IL-2 were not meaningfully different between cases and controls. The current study highlights the dysregulation of cytokine-coding genes in the blood of patients with migraine.
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http://dx.doi.org/10.1007/s12031-020-01745-yDOI Listing
June 2021

Expression analysis of and in multiple sclerosis patients versus healthy subjects.

Nucleosides Nucleotides Nucleic Acids 2021 9;40(2):157-165. Epub 2020 Nov 9.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: Recent investigations which have aimed at unraveling the etiology of multiple sclerosis (MS), have underscored the role of mitochondria in this disorder. gene codes a serine/threonine kinase that protects mitochondria and maintains its normal function.

Methods: In the current project, we quantified expression levels of and a long non-coding RNA which is transcribed antisense to this gene () in the peripheral blood of MS patients versus normal persons.

Results: Peripheral expression of was remarkably higher in MS patients compared with healthy individuals. A significant difference in level was also recognized in male patients compared with male controls. But, the difference was not remarkable between female subgroups. Expression of was not different between MS patients and healthy persons. Univariate analysis showed significant differences in age, disease duration, progression index and age at disease onset between males and females (P values of 0.041, 0.001, <0.0001 and 0.007 respectively). There was a trend toward correlation between expression levels of and (r = 0.26, P = 0.074). However, expressions of either genes were correlated with any of the demographic or clinical features.

Conclusion: Based on the altered expression of in the peripheral blood of MS patients, might be a putative culpript in the pathogenesis of MS. We recommend conduction of additional studies to unravel the mechanism of partake in the MS.
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http://dx.doi.org/10.1080/15257770.2020.1844229DOI Listing
June 2021

Expression of NF-κB associated lncRNAs in schizophrenia.

Sci Rep 2020 10 22;10(1):18105. Epub 2020 Oct 22.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

NF-κB signaling pathway has important roles in the regulation of growth and development of nervous system. This pathway has also been shown to participate in the pathogenesis of schizophrenia. Meanwhile, activity of NF-κB signaling pathway is regulated by several factors including non-coding RNAs (lncRNAs). In the current study, we evaluated expression of nine NF-κB-related lncRNAs namely DILC, ANRIL, PACER, CHAST, ADINR, DICER1-AS1, HNF1A-AS1, H19 and NKILA as well as two mRNA coding genes namely ATG5 and CEBPA in the peripheral blood of patients with schizophrenia compared with matched healthy subjects. Expressions of these genes were assessed by real time PCR technique. Expression of PACER was lower in patients with schizophrenia compared with controls (Posterior beta = - 0.684, P value = 0.049). On the other hand, expressions of CHAST, CEBPA, H19, HNF1A-AS1 and DICER1-AS1 were higher in patients compared with controls (Posterior beta = 0.39, P value = 0.005; Posterior beta = 0.844, P value < 0.0001; Posterior beta = 0.467, P value < 0.0001; Posterior beta = 1.107, P value = 0.005; Posterior beta = 0.176, P value = 0.044, respectively). We also appraised the diagnostic power of transcript quantities of CHAST, CEBPA, DICER1-AS1, H19 and HNF1A-AS1 in distinguishing between patients with schizophrenia and controls through depicting ROC curves. Based on the area under curve (AUC) values, CEBPA had the best diagnostic power (AUC = 0.948, P < 0.0001), followed by H19 (AUC = 0.815, P < 0.0001). Taken together, our study demonstrated dysregulation of NF-κB-related lncRNAs and genes in the peripheral blood of patients with schizophrenia and their potential as peripheral markers for this psychiatric condition.
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http://dx.doi.org/10.1038/s41598-020-75333-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581809PMC
October 2020

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

J Stroke Cerebrovasc Dis 2020 Dec 16;29(12):105321. Epub 2020 Sep 16.

Westchester Medical Center Health Network, Director of Neurocritical Care and Emergency Neurological Services, Valhalla, NY, USA; Westchester Medical Center Health Network, New York Medical College, Valhalla, NY, USA.

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.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494258PMC
December 2020

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Hum Antibodies 2021 ;29(1):49-54

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.
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http://dx.doi.org/10.3233/HAB-200428DOI Listing
April 2021

Environmental and ecological factors of stomach cancer incidence and mortality: a systematic review study on ecological studies.

Rev Environ Health 2020 Nov 19;35(4):443-452. Epub 2020 Jul 19.

Health Promotion Research Center, Faculty of Health, Zahedan University of Medical Sciences, Zahedan, Iran.

Objectives: Stomach cancer (SC) is one of the most common and deadly types of cancer. It is the third leading cause of cancer deaths worldwide. The effect of environmental and ecological factors in SC have been assessed in some studies. Thus, we aimed to synthesize the environmental and ecological factors of SC incidence and mortality.

Content: In this systematic review study, the scientific databases, including Web of Science, Scopus and PubMed, were searched from inception to November 2019 for all primary articles written in English by using relevant Medical Subject Heading (Mesh) terms. Two independent authors conducted the screening process to decide on the eligibility and inclusion of the articles in the study. The third author acted as an arbiter to resolve any disagreements.

Summary And Outlook: A total of 157 potentially relevant articles were identified from the initial search 38 of which met the eligibility criteria; finally, 34 articles were included in the systematic review. The results revealed that soil arsenic exposure, coal and other opencast mining installations, living near incinerators and installations for the recovery or disposal of hazardous waste, installations for the production of cement, lime, plaster, and magnesium oxide, proximity to a metal industry sources, dietary iron, ingested asbestos, farming, arsenic in soil, altitude, organochlorines and environmental exposure to cadmium and lead have positive associations with SC incidence or death. Most of the ecological and environmental factors such as living near the mineral industries, the disposal of hazardous waste, metal industry sources and environmental exposure to cadmium and lead are positively related to SC mortality and incidence. However, solar UV-B, heat index and dietary zinc can be taken into account as protective factors against SC mortality and incidence.
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http://dx.doi.org/10.1515/reveh-2020-0022DOI Listing
November 2020

Correlations between COVID-19 and burden of dementia: An ecological study and review of literature.

J Neurol Sci 2020 09 4;416:117013. Epub 2020 Jul 4.

Department of Neurology and Stroke Unit, San Camillo de' Lellis General District Hospital, Rieti, Italy; Neurological Section, Neuro-epidemiology Unit, SMDN-Centre for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Sulmona, L'Aquila, Italy. Electronic address:

Introduction: Current evidence on the association between COVID-19 and dementia is sparse. This study aims to investigate the associations between COVID-19 caseload and the burden of dementia.

Methods: We gathered data regarding burden of dementia (disability-adjusted life years [DALYs] per 100,000), life expectancy, and healthy life expectancy (HALE) from the Global Burden of Disease (GBD) 2017 study. We obtained COVID-19 data from Our World in Data database. We analyzed the association of COVID-19 cases and deaths with the burden of dementia using Spearman's rank correlation coefficient.

Results: Globally, we found significant positive (p < .001) correlations between life expectancy (r = 0.60), HALE (r = 0.58), and dementia DALYs (r = 0.46) with COVID-19 caseloads. Likewise, we found similar correlations between life expectancy (r = 0.60), HALE (r = 0.58) and dementia DALYs (r = 0.54) with COVID-19 mortality.

Conclusion: Health policymakers should clarify a targeted model of disease surveillance in order to reduce the dual burden of dementia and COVID-19.
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http://dx.doi.org/10.1016/j.jns.2020.117013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334961PMC
September 2020

The Prevalence of Renal Scars Among Infants Under One Year Old With a First UTI With or Without VUR in Qom, Iran, 2017.

Iran J Kidney Dis 2020 07;14(4):308-311

faculty member of Sabzevar University of Medical Sciences.

Renal scarring with reflux develops renal nephropathy. The risk is higher when it is associated with urinary tract infection (UTI). Hence, we investigated the prevalence of renal scars among children under one-year-old with the first UTI in Qom, Iran. We conducted this retrospective study on 140 infants divided in two reflux (n = 70) and non-reflux (n = 70) groups. Participant's records had been analyzed by descriptive and analytic statistics. The prevalence of renal scar was 32.12% among all 140 infants. The prevalence of renal scars among children with and without reflux, was 33 (47.1%), and 12 (17.1%) out of 70 (P < .001); respectively. The rate of renal defects increased with higher grades of reflux. We found that the rate of renal scar is high in Qom. Therefore, we recommend screening susceptible children in order to prevent renal damage.
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July 2020

Dysregulation of NF-κB-Associated lncRNAs in Multiple Sclerosis Patients.

J Mol Neurosci 2021 Jan 29;71(1):80-88. Epub 2020 Jun 29.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of several complex disorders such as immune-related disorders. Multiple sclerosis (MS) as an inflammatory disorder of the central nervous system has been associated with aberrant expression of several lncRNAs. In the current study, we assessed expression of NF-κB-, autophagy-, and obesity-associated lncRNAs/genes and two inflammatory cytokines in the peripheral blood of MS patients and healthy controls. LNC-MKI67IP was down-regulated in total MS patients compared with total controls (P value < 0.0001). However, when comparing its expression in a gender-based manner, no significant difference was found between patients and controls. Expression of HNF1A-AS1 was significantly lower in total MS patients and patients of both sexes when compared with the matched controls (P value < 0.0001; P value = 0.03; P value = 0.004, respectively). Expression of LINC00305 had a similar pattern to HNF1A-AS1 (P value < 0.0001; P value = 0.005; P value < 0.0001, respectively). Expressions of other assessed NF-κB associated lncRNAs were not different between cases and controls. Expression of IL-1B was significantly lower in total MS patients compared with total controls (P value < 0.0001). Such decreased expression was detected in female patients compared with female controls as well (P value < 0.0001). Expression of IL-6 was not different between cases and controls. Expression of CEBPA was higher in total MS patients compared with controls (P value = 0.047). However, when dividing study participants into male and female subgroups, no significant difference was detected between cases and gender-matched controls. There were no significant difference in the expression of any assessed autophagy-associated lncRNAs between cases and controls. ATG5, CEBPA, HNF1A-AS1, IL-1B, LINC00305, and LNC-MKI67IP could differentiate disease status with diagnostic power values of 0.781, 0.582, 0.744, 0.76, 0.926, and 0.703, respectively. Expression levels of ADINR and CHAST were correlated with age of MS patients and disease duration, respectively (r = 0.33, P < 0.0001; r = 0.34, P < 0.0001, respectively). The present study highlighted the role of a number lncRNAs in the pathogenesis of MS and supported the previous data regarding aberrant expression of these transcripts in this immune-related disorder.
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http://dx.doi.org/10.1007/s12031-020-01628-2DOI Listing
January 2021

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

J Mol Neurosci 2020 Oct 23;70(10):1533-1540. Epub 2020 Jun 23.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of immune-related disorders including multiple sclerosis (MS). Based on the role of these transcripts in the regulation of immune response, peripheral levels of lncRNAs can reflect the level of immune activation. In the present study, we quantified expression of four lncRNAs namely SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 in venous blood of MS patients and controls using quantitative real-time PCR method. Relative expressions of SPRY4-IT1, HOXA-AS2, LINC-ROR, and MEG3 were significantly lower in female MS patients compared with female healthy subjects. For MEG3, this pattern of expression was also observed in male subjects. However, for other lncRNAs, no significant difference was detected between male patients and male controls. Expression of HOXA-AS2 was correlated with progression index (r = 0.36, P < 0.001). Besides, there was a significant correlation between expression of this lncRNA and expression of LINC-ROR in MS patients (r = 0.44, P < 0.0001). There was no other correlation between expression of lncRNAs and clinical data in MS patients. In control group, expressions of none of lncRNAs were correlated with age of persons. Notably, significant correlations were demonstrated between expression levels of all lncRNAs in healthy subjects with r values ranging from 0.23 to 0.42. The current investigation shows dysregulation of lncRNAs in MS patients in a sex-specific manner and warrants further studies to unravel the clinical and therapeutic implications of such dysregulation.
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http://dx.doi.org/10.1007/s12031-020-01646-0DOI Listing
October 2020

Sex-specific up-regulation of () lncRNA in periodontitis.

Heliyon 2020 May 13;6(5):e03897. Epub 2020 May 13.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

A number of recent studies have shown dysregulation of some long non-coding RNAs (lncRNAs) in affected tissues or peripheral blood of patients with periodontitis. In the current study, we investigated the role of () and () lncRNAs in periodontitis. We assessed expression of these lncRNAs in 30 affected tissue, 30 control tissue samples, 23 blood samples from patients and 18 blood samples from healthy controls. Expression of was higher in total blood samples of patients compared with controls (Posterior beta of RE = 5.143, P value = 0.001). However, when assessing its expression in a gender-based manner, the difference in the expression of this lncRNA was significant only among male subgroups (Posterior beta of RE = 7.16, P value < 0.0001). Moreover, expression of was significantly higher in female subjects compared with male subjects (Posterior beta of RE = 3.098, P value < 0.0001). There was no significant difference in tissue expression of between study subgroups. Expression of was not significantly different between blood/tissue samples of cases and controls. However, expression of this lncRNA was higher in blood of female subjects compared with male subjects (Posterior beta of RE = 4.353, P value = 0.002). Tissue expression of was correlated with blood levels of this lncRNA (r = 0.33, P < 0.0001) and with the tissue levels of (r = 0.3, P < 0.0001). Moreover, blood levels of these lncRNAs were correlated with each other (r = 0.34, P < 0.0001). However, there was no significant correlation between blood and tissue levels of . Expression of these lncRNAs were not correlated with age either in males or in females. Taken together, we demonstrated a sex-based up-regulation of in blood samples of patients with periodontitis which implies possible participation of this lncRNA in the pathobiology of periodontitis.
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http://dx.doi.org/10.1016/j.heliyon.2020.e03897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226669PMC
May 2020

Blood and tissue levels of lncRNAs in periodontitis.

J Cell Physiol 2020 12 5;235(12):9568-9576. Epub 2020 May 5.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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 β 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 β of RE = -2.151, p = .019). Such an expression difference was detected between male subgroups as well (posterior β 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 β 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.
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http://dx.doi.org/10.1002/jcp.29764DOI Listing
December 2020

The lncRNA is down-regulated in peripheral blood of patients with periodontitis.

Noncoding RNA Res 2020 Jun 17;5(2):60-66. Epub 2020 Apr 17.

Department of Periodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have crucial roles in lncRNAs in periodontal development and disorders of this tissue. A number of lncRNAs especially those regulating immune responses contribute in the pathophysiology of periodontitis. In the current case-control study, we assessed expression levels of two immune response-related lncRNAs namely the antisense non-coding RNA in the INK4 locus () and metastasis-associated lung adenocarcinoma transcript 1 () in gingival tissues and blood samples of patients with periodontitis and healthy subjects. Expression of was significantly lower in peripheral blood of patients compared with controls (Posterior Beta RE = -1.734, P value = 0.035). However, when diving study participants based on their gender, no significant difference was found between patients and sex-matched controls. Expression of this lncRNA was not different between periodontitis tissues and normal tissues. Expression of was not different between samples obtained from cases and controls. Tissue or blood expressions of or were not correlated with age of either patients or controls. There were significant correlations between expression levels of and in gingival tissues both in cases (r = 0.62, P < 0.0001) and in controls (r = 0.37, P < 0.0001). However, blood levels of these lncRNAs were not correlated with each other either in cases or in controls. Most notably, there was no significant correlation between expression levels of these lncRNAs in gingival tissues and in the blood of study participants. The current study indicates dysregulation of in the peripheral blood of patients with periodontitis in spite of its normal levels in gingival tissues which might reflect disturbance in systemic immune responses in these patients.
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http://dx.doi.org/10.1016/j.ncrna.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182695PMC
June 2020

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

Hum Antibodies 2020 ;28(3):221-226

Pediatric Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Fanconi anemia includes a number of clinically and genetically diverse disorders all of them being associated with genomic instability. Some previous studies reported higher frequencies of certain HLA alleles in patients with Fanconi anemia. In the current study, we genotyped HLA-A/B/DRB1 alleles in 40 Iranian patients with Fanconi anemia. We also genotyped these alleles in the same number of Iranian sex-matched healthy individuals. The frequency of DRB1*11 was significantly higher in patients compared with controls (OR (95% CI) = 2.143 [1.05, 4.46], P value = 0.036). On the other hand, the frequencies of DRB1*13 and B*13 were lower in patients compared with controls (OR (95% CI) = 0.134 [0.02, 0.55], P value = 0.003 and OR (95% CI) = 0.13 [0.01, 0.89], P value = 0.035, respectively). Assessment of genetic divergence using Fstat test showed complete divergence in HLA-A, -B, -DRB1 alleles and haplotypes between patients and controls. The current study provides evidences for different distribution of HLA alleles between patients with Fanconi anemia and healthy subjects.
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http://dx.doi.org/10.3233/HAB-200410DOI Listing
January 2020

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

J Mol Neurosci 2020 Aug 25;70(8):1274-1281. Epub 2020 Mar 25.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s12031-020-01537-4DOI Listing
August 2020

Evaluation of Expression of STAT Genes in Immune-Mediated Polyneuropathies.

J Mol Neurosci 2020 Jun;70(6):945-952

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Immune-mediated polyneuropathies are acquired conditions that can be categorized to acute and chronic forms based on the disease course. Although the basic mechanism of these conditions has not been clarified yet, genes that regulate immune responses are putative contributors in their development. In the current study, we assessed expression of signal transducer and activator of transcription (STAT)1-3 and STAT5a genes in peripheral blood of 51 patients and 40 healthy subjects. Expression of STAT1 was higher in female patients compared with female controls (Posterior Beta = 3.622, P = 0.044). The gender*group interaction was significant for this gene which indicates different direction of association in males and females. Expressions of other STAT genes were not different between cases and controls. The diagnostic power of STAT1 in female subjects was estimated to be 0.72 with sensitivity of 68.75% and specificity of 84.62%. There was no significant correlation either between expression of different STAT genes or between their expression and age of study participants. The current study potentiates STAT1 as a putative factor in the pathophysiology of acquired immune-mediated polyneuropathies in females and suggests conduction of further functional studies to elaborate the molecular mechanism of this contribution.
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http://dx.doi.org/10.1007/s12031-020-01494-yDOI Listing
June 2020

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

Neurol Sci 2020 Jun 11;41(6):1459-1465. Epub 2020 Jan 11.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, PO Box 1985717443, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s10072-019-04234-2DOI Listing
June 2020

Expression analysis of inflammatory response-associated genes in coronary artery disease.

Arch Physiol Biochem 2020 Jan 8:1-7. Epub 2020 Jan 8.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Coronary artery disease (CAD) is among prominent causes of death throughout the world. Inflammatory processes participate in the pathogenesis of this disorder. In the current case-control study, we compared expression levels of three inflammation-associated genes namely (), and between CAD patients and matched healthy subjects. , and were significantly down-regulated in CAD patients compared with controls ( values of <.0001, .023 and <.0001, respectively). When evaluating study participants based on their gender, the differences in expression levels of and were significant in both male and female patients compared with the matched controls. However, was only down-regulated in female patients compared with female controls. Taken together, our study revealed dysregulation of inflammation-associated genes in the peripheral blood of CAD patients and supported the previously suggested role of inflammation in the pathogenesis of CAD.
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http://dx.doi.org/10.1080/13813455.2019.1708953DOI Listing
January 2020

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

J Mol Neurosci 2020 May 3;70(5):689-698. Epub 2020 Jan 3.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the pathogenesis of neuropsychiatric disorders such as epilepsy. In the current study, we evaluated expression of eight lncRNAs in 80 epileptic patients (40 refractory and 40 non-refractory ones) and 40 normal individual using quantitative real-time PCR. Bayesian regression model showed significant higher expression of UCA1 in both refractory and non-refractory groups compared with controls (posterior beta of relative expression (RE) = 2.03, P value = 0.003, and posterior beta of RE = 4.05, P value < 0.0001, respectively). Besides, expression of UCA1 was higher in non-refractory patients compared with refractory ones (posterior beta of RE = 2.008, P value = 0.019). When repeating statistical analyses in a gender-based manner, differences in expression of UCA1 were significant in all subgroup analyses except for male non-refractory vs. refractory subgroups analysis. Expression levels of NKILA and ANRIL were higher in both refractory and non-refractory groups compared with controls (posterior beta of RE = 1.565, P value = 0.018, and posterior beta of RE = 1.902, P value = 0.006 for NKILA; posterior beta of RE = 1.304, P value < 0.0001, and posterior beta of RE = 1.603, P value = 0.019 for ANRIL, respectively). However, expression levels of these two lncRNAs were not different between refractory and non-refractory groups. Gender-based analysis for these two lncRNAs revealed similar results except for lack of difference in ANRIL expression between male refractory group and controls. Expression of THRIL was significantly lower in both refractory and non-refractory groups compared with controls (posterior beta of RE = - 0.842, P value = 0.044 and posterior beta of RE = - 1.969, P value < 0.0001, respectively). Furthermore, expression of this lncRNA was lower in non-refractory patients compared with refractory ones (posterior beta of RE = - 1.129, P value = 0.002). However, no significant difference was detected between non-refractory and refractory patients either in males or females. The interactions between gender and relative expressions of PACER, DILC, and MALAT1 were significant, so the results were assessed in gender-based manner. In females, expression of DILC was higher in non-refractory patients compared with refractory ones (posterior beta of RE = 0.959, P value = 0.044). Expression of MALAT1 was lower in female non-refractory patients compared with controls and in female non-refractory patients compared with refractory ones (posterior beta of RE = - 1.35, P value = 0.002, and posterior beta of RE = - 0.942, P value = 0.045, respectively). Finally, expression of PACER was higher in refractory patients vs. controls and non-refractory patients vs. controls in both male and female subgroups. However, comparison between non-refractory and refractory patients revealed significant results only among females. Expression of none of the assessed lncRNAs was correlated with age of study participants. There were robust correlations between expression levels of lncRNAs. The most robust correlations were detected between UCA1 and PACER (r = 0.84, P < 0.0001) and between UCA1 and ANRIL (r = 0.75, P < 0.0001). Taken together, our study demonstrated dysregulation of lncRNAs in peripheral blood of epileptic patients and potentiated them as biomarkers for this neurologic condition.
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http://dx.doi.org/10.1007/s12031-019-01477-8DOI Listing
May 2020

Downregulation of Protein Inhibitor of Activated STAT (PIAS) 1 Is Possibly Involved in the Process of Allograft Rejection.

Transplant Proc 2020 Jan - Feb;52(1):414-418. Epub 2019 Dec 20.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Protein inhibitors of activated STAT (PIAS) proteins are regarded as negative regulators of cytokine-signaling and potent immunosuppressive proteins. However, their role in the process of organ transplant rejection has not been elucidated.

Methods: In the current study, we compared transcript levels of PIAS1 to 4 in the peripheral blood of renal transplant recipients who experienced transplant rejection with those having normal transplant functions. Expression of PIAS1 was significantly higher in nonrejected group compared with the rejected group among male recipients; however, differences were insignificant among female recipients. Expressions of other PIAS genes were not different between study groups. Significant pairwise correlations were found between expression levels of PIAS genes in all study subgroups. The current investigation highlights the role of PIAS1 downregulation in the evolution of graft rejection and potentiates this gene as a predictive marker for transplant fate.
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http://dx.doi.org/10.1016/j.transproceed.2019.10.006DOI Listing
July 2020

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

Exp Mol Pathol 2020 02 14;112:104359. Epub 2019 Dec 14.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yexmp.2019.104359DOI Listing
February 2020

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

Urol J 2019 12 24;16(6):572-577. Epub 2019 Dec 24.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: Long non-coding RNAs (lncRNAs) include a vast portion of human transcripts. They exert regulatory roles in immune responses and participate in diverse biological functions. Recent studies indicated dysregulation of lncRNAs in the process of transplant rejection. In the current study, we aimed at identification of the expression of five lncRNAs (OIP5-AS1, FAS-AS1, TUG1, NEAT1 and PANDAR) in association with the process of transplant rejection.

Material And Methods: We assessed expression of these lncRNAs in the peripheral blood of 61 kidney transplant receivers including 29 transplant rejected patients and 32 transplant non-rejected patients using real time PCR technique.

Results: Expression of FAS-AS1 was significantly higher in rejected group compared to non-rejected group in males, however, differences between case and control groups were insignificant among females. For other lncRNAs no significant differences were detected between two study groups. Quantile regression model showed that patients' gender was an important parameter in determination of FAS-AS1 expression (Beta=-9.46, t=-2.82, P=0.007) but not for other lncRNAs expressions. Significant pairwise correlations were detected between expression levels of lncRNAs in a disease related manner.

Conclusion: Based on the higher expression of FAS-AS1 in patients with transplant rejection, this lncRNA might be associated with the pathogenesis of renal transplant rejection.
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http://dx.doi.org/10.22037/uj.v0i0.5456DOI Listing
December 2019

Dysregulation of autophagy-related lncRNAs in peripheral blood of coronary artery disease patients.

Eur J Pharmacol 2020 Jan 10;867:172852. Epub 2019 Dec 10.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Coronary artery disease (CAD) as a major cause of death has been associated with dysregulation of several processes among them is autophagy. In the current study, we assessed expression of autophagy related gene 5 (ATG5) and three ATG5-associated long non-coding RNAs (lncRNAs Chast, HULC and DICER1-AS1) in the peripheral blood of patients with premature CAD and healthy subjects. Expression levels of ATG5, Chast, HULC and DICER1-AS1 were significantly lower in peripheral blood of CAD cases compared with healthy subjects. Receiver Operating Characteristic (ROC) curve analysis showed that HULC and DICER1-AS1 can properly differentiate CAD patients from healthy subjects (area under curve (AUC) values of 0.90 and 0.87, respectively). Expression levels of ATG5 and Chast were inversely correlated with FBS levels (r = -0.41, P < 0.0001 and r = -0.38, P < 0.0001 respectively) but no other biochemical factors. Expression of DICER1-AS1 was inversely correlated with FBS (r = -0.54, P < 0.0001), TG (r = -0.29, P < 0.0001) and TG/HDL ratio (r = -0.27, P < 0.0001). Expression of HULC was inversely correlated with age (r = -0.24, P < 0.0001), FBS (r = -0.62, P < 0.0001) and TG (r = -0.31, P < 0.0001). There were significant pairwise correlations between expression levels of all genes. The most robust correlations were detected ATG5 and Chast (r = 0.81, P < 0.0001) and between DICER1-AS1 and HULC (r = 0.75, P < 0.0001). The current study further verified associations between dysregulation of autophagy and CAD. Moreover, our results indicate appropriateness of two autophagy-related lncRNAs for differentiation of CAD status.
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http://dx.doi.org/10.1016/j.ejphar.2019.172852DOI Listing
January 2020
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