Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients.

OBJECTIVE: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. METHODS: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. RESULTS: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. CONCLUSION: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Investigation of highly cited publications related to vaccines against COVID-19: current state and future predictions.

BACKGROUND: Since the date of declaring the COVID-19 outbreak a pandemic by the World Health Organization (March 11, 2020), vaccine studies have been initiated. In this article, we aimed to investigate highly cited articles on vaccines and guide researchers for future studies. MATERIAL AND METHODS: Publications with 6 or more citations (highly cited publications) were extracted from Web of Science (WoS) database. These publications were investigated according to the number of citations, language, publication year, WoS categories, publication types, organizations involved, authors, countries and research areas. Additionally, top 20 articles were investigated in detail. RESULTS: A total of 126 publications were determined. When WoS categories were investigated, 18 pertained to immunology (14.2 %), 17 to biochemistry (13.4 %) and 17 to multidisciplinary sciences (13.4 %). There were three types of publications, namely 80 original articles (63.4 %), 46 reviews (36.5 %) and 11 early access publications (8.7 %). Top universities were Harvard University (n=9, 7.1 %), Chinese Academy of Medical Sciences (n=7, 5.5 %) and University of California system (n=7, 5.5 %). Top authors were Qin CF with 4 articles (3.1 %), Wang L with 4 articles (3.1 %) and Baric RS with 3 articles (2.3 %). Top journals with the highest number of publications were Journal of Biomolecular Structure Dynamics (n=8, 6.3 %), Nature (n=8, 6.3 %) and Science (n=6, 4.7 %). Top countries were the United States of America (USA) with 45 articles (35.7 %), People's Republic of China with 44 articles (34.9 %), and India with 15 articles (11.9 %). Research areas of the publications were science technology other topics (n=21, 16.6 %), immunology (n=18, 14.2 %) and pharmacology (n=18, 14.2 %). CONCLUSION: Vaccine studies play a pivotal role in the warfare against COVID-19. Our results revealed that under the leadership of the USA, China and India, the number of scientists focusing on vaccines is increasing and gratifying results are obtained from vaccine studies (Tab. 3, Ref. 40).

MicroRNA dysregulation in manic and euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BPD) is a major psychiatric disorder with an unclear pathophysiology. Peripheral blood samples are easily drawn, making them are good candidates for diagnosing diseases. MicroRNAs are small non-coding RNA transcripts that regulate gene expression by binding to the 3'- UTR of mRNAs and directing their degradation. The aim of this study was to use blood plasma to investigate microRNA dysregulations in bipolar manic and euthymic patients. SUBJECTS AND METHODS: Blood samples were collected from 58 patients with bipolar I disorder (19 manic, 39 euthymic) and 51 healthy controls. RESULTS: Four microRNAs (miR-29a-3p, p = 0.035; miR-106b-5p, p = 0.014; miR-107, p = 0.011; and miR-125a-3p, p = 0.014) were upregulated in the entire bipolar group, compared to the healthy controls. Seven microRNAs (miR-9-5p, p = 0.032; miR-29a-3p, p = 0.001; miR-106a-5p, p = 0.034; miR-106b-5p, p = 0.003; miR-107, p < 0.001; miR-125a-3p, p = 0.016; and miR-125b-5p, p = 0.004) were more upregulated in bipolar manic patients compared to the healthy controls, and two microRNAs (miR-106a-5p, p = 0.013, and miR-107, p = 0.021) showed statistically significant upregulation in the manic patients compared to the euthymic patients. CONCLUSIONS: Our results showed greater miRNA dysregulation in the manic patients than in the euthymic patients. Two microRNAs could be more selective for bipolar manic episodes. Future studies should include depressive patients along with euthymic and manic patients.

Report of a rare case of severe allergic reaction due to nasal myiasis and a brief review of the literature in Turkey.

Myiasis is defined as infestation of a mammal by fly larvae. It may occur on either living tissues (primary myiasis) or dead tissues (secondary myiasis). In this report, we present a patient with myiasis with an extremely rare clinical manifestation and severe allergic reaction, and we review the literature in order to reveal the current status. A 20-year-old female patient was admitted to our emergency department due to rush on face, cough and shortness of breath. The maggot came out of her nose was identified as Oestrus ovis. With a diagnosis of severe allergic reaction due to myiasis, she was treated diphenhidramine, prednisone and inhale albuterol in the emergency department. After treatment and further investigation, she was discharged with full recovery. Myiasis is a rare cause for severe allergic reaction in patients with definite diagnosis. Immediate diagnosis and treatment are milestones in preventing bad outcomes.

Genetic Predisposition to Unexplained Recurrent Pregnancy Loss: Killer Cell Immunoglobulin-Like Receptor Gene Polymorphisms as Potential Biomarkers.

AIM: The aim of this study was to investigate the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and unexplained recurrent pregnancy loss (URPL). MATERIALS AND METHODS: This study included 70 URPL patients with a history of two or more miscarriages and 70 healthy multiparous women as a control group. KIR genotyping was performed in all subjects for the KIRs 2DL1-4 and 2DS1-5 genes using polymerase chain reaction with sequence-specific primers. RESULTS: There was a significant relationship between the KIR genotypes and URPL. We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype was not detected in either the case or control group. Gene-gene interactions for all genes were statistically significant. The KIR Bx genotype was found primarily in the case group, and at a higher frequency when compared with the control group. There was a significant relationship between the URPL cases and Bx haplotypes. CONCLUSION: We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype of the KIR gene, however, was not detected in either the case or control group. The observations reported herein on KIR genotyping offer a new avenue for innovations in biomarker research concerning URPL and other complex obstetrics diseases.

The role of certain gene polymorphisms involved in the apoptotic pathways in polycythemia vera and essential thrombocytosis.

BACKGROUND: Polycythemia vera (PV) and essential thrombocytosis (ET) are hematological disorders characterized by excessive production of mature and functional blood cells. These cellular disorders are thought to be associated with impaired apoptosis, which is one of the major cellular death mechanisms in hematopoietic cells. OBJECTIVES: In this study, our objective was to examine the association between potential polymorphisms of the Bcl 2, Bax, Fas and Fas Ligand genes involved in apoptosis and the occurrence of PV and ET. MATERIAL AND METHODS: A total of 93 patients diagnosed with PV (n = 38) or ET (n = 55) at the Department of Hematology were included in this study, and 93 healthy individuals served as controls. DNA isolation was performed in blood samples obtained from both groups of subjects to determine the Bcl 2, Bax, Fas, and Fas L genotypes using the real-time PCR method. RESULTS: No statistically significant differences between controls and patients were found in terms of Fas -670 G > A (rs1800682), Fas -1377 G > A (rs2234767), Fas L IVS2 -124 A > G (rs5030772), Bax -248 G > A (rs4645878) and Bcl 2 -938 C > A (rs2279115) polymorphisms, genotypes, and allele frequency (p > 0.05). CONCLUSIONS: The results show that polymorphisms in the Bcl 2, Bax, Fas, and Fas Ligand genes involved in the apoptotic pathways may not play a role in the pathogenesis of PV and ET.

Regulating the Regulators in Attention-Deficit/Hyperactivity Disorder: A Genetic Association Study of microRNA Biogenesis Pathways.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent complex psychiatric disorders in children as well as adults. ADHD impacts not only the affected individuals but also their families and social and professional networks. The clinical and diagnostic criteria for ADHD remain imprecise, in part, due to lack of robust biomarkers. ADHD comprises multiple subsets of diseases that present a shared set of downstream clinical findings, while displaying extensive molecular heterogeneity. This calls for innovation in diagnostic strategies that can help establish an ADHD diagnosis unequivocally as well as guiding precision medicine in this common mental health disorder. No study has examined, to the best of our knowledge, the upstream regulation of miRNAs that impact the downstream final ADHD phenotype. The latter focus on putative genetic biomarkers that regulate the regulators and can be tested empirically, for example, through genetic association analyses of the biogenesis pathways for miRNAs that impact the ADHD phenotype. Hence, we report here polymorphic variation in 10 miRNA biogenesis pathway candidate genes, including RNASEN, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, and GEMIN4, in a large sample from the Eastern Mediterranean region (N = 355; 191 cases and 164 controls). We found that AGO1 rs595961 was significantly associated with ADHD susceptibility (p < 0.05). While polymorphic variation in other miRNA biogenesis pathway genes did not display a significant association in the present sample, the observations reported herein on miRNA biogenesis variation offer a new avenue of research for innovation in biomarker discovery concerning ADHD and other complex psychiatric diseases with major global health burden.

Radiation therapy for biliary tract tumors: the joint experience of three centers.

BACKGROUND/AIM: This study presents the joint experience of three centers in the treatment of patients with biliary tract tumors with radiation therapy (RT). MATERIALS AND METHODS: The records of 27 patients were retrospectively reviewed. All of the patients who had undergone surgical resection received postoperative adjuvant RT, whereas all of the patients who had not undergone a surgical resection received RT with palliative intent. Twenty patients with adequate performance status were treated with RT and chemotherapy, while the remaining seven patients were treated with RT alone. RESULTS: Follow-up ranged from 1 to 44 months. Local control was not achieved in 10 out of 11 patients who had received RT with palliative intent. Systemic failure was observed in eight patients at 5 to 16 months. Fifteen patients died due to disease-related causes at 1 to 22 months. At 2 years, overall survival was 33% and disease-free survival was 19%. A surgical resection with curative intent predicted improved local failure-free survival and improved disease-free survival. CONCLUSION: Since local recurrence is still the leading cause of failure following postoperative RT and the outcome following palliative RT is far from satisfactory, the indications, the target volume, and the doses for RT should be reconsidered.

Investigation of Dysregulation of Several MicroRNAs in Peripheral Blood of Schizophrenia Patients.

OBJECTIVE: The prevalence of schizophrenia is 1%, and it is a debilitating disorder that often results in a shortened lifespan. Peripheral blood samples are good candidates to investigate because they can be easily drawn, and they are widely studied in psychiatric disorders. MicroRNAs are small non-coding RNA transcripts. They regulate the expression of genes by binding to the 3'-untranslated region (UTR) of mRNAs and pointing them to degrade. In this study, we aimed to investigate the expression of miR-9-5p, miR-29a-3p, miR-106-5p, miR-106b-5p, miR-107, miR-125a-3p, and miR-125b-3p in schizophrenia patients and healthy controls. METHODS: We collected blood samples from 16 patients with schizophrenia and 16 healthy controls. MicroRNAs were measured with reverse transcriptase polymerase chain reaction. RESULTS: Schizophrenia patients showed statistically significant upregulation of five microRNAs: miR9-5p (p=0.002), miR29a-3p (p＜0.001), miR106b-5p (p=0.002), miR125a-3p (p＜0.001), and miR125b-3p (p=0.018). CONCLUSION: Our results increased the value of the miR106 and miR29 families as potentially and consistently dysregulated in psychiatric disorders. Our results should be considered preliminary, and they need confirmation in future studies with larger sample sizes.

White matter alterations related to attention-deficit hyperactivity disorder and COMT val(158)met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus).

INTRODUCTION: In this article, the COMT gene val(158)met polymorphism and attention-deficit hyperactivity disorder (ADHD)-related differences in diffusion-tensor-imaging-measured white matter (WM) structure in children with ADHD and controls were investigated. PATIENTS AND METHODS: A total of 71 children diagnosed with ADHD and 24 controls aged 8-15 years were recruited. Using diffusion tensor imaging, COMT polymorphism and ADHD-related WM alterations were investigated, and any interaction effect between the COMT polymorphism and ADHD was also examined. The effects of age, sex, and estimated total IQ were controlled by multivariate analysis of covariance (MANCOVA). RESULTS: First, an interaction between the COMT val(158)met polymorphism and ADHD in the right (R) cingulum (cingulate gyrus) (CGC) was found. According to this, valine (val) homozygote ADHD-diagnosed children had significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the R-CGC than ADHD-diagnosed methionine (met) carriers, and val homozygote controls had higher FA and lower RD in the R-CGC than val homozygote ADHD patients. Second, met carriers had higher FA and axial diffusivity in the left (L)-uncinate fasciculus and lower RD in the L-posterior corona radiata and L-posterior thalamic radiation (include optic radiation) than the val homozygotes, independent of ADHD diagnosis. Third, children with ADHD had lower FA in the L-CGC and R-retrolenticular part of the internal capsule than the controls, independent of the COMT polymorphism. CONCLUSION: Significant differences reported here may be evidence that the COMT gene val(158)met polymorphism variants, as well as ADHD, could affect brain development. ADHD and the COMT polymorphism might be interactively affecting WM development in the R-CGC to alter the WM connectivity in children with val homozygote ADHD.

The Effect of Single Dose Methylphenidate on Neurometabolites according to COMT Gene Val158Met Polymorphism in the Patient with Attention Deficit Hyperactivity Disorder: A Study Using Magnetic Resonance Spectroscopy.

OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Thus, the present study aimed to determine the effects of a single dose of methylphenidate (Mph) on neurometabolite levels according to polymorphisms of the catechol-O-methyltransferase (COMT) gene. METHODS: This study evaluated the neurometabolite levels including N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) of ADHD patients, before and after treatment with Mph (10 mg) according to the presence of COMT polymorphisms. The spectra were obtained from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), cerebellum, and striatum. RESULTS: The NAA levels of the val/val and val genotype carriers (val/val and val/met genotypes) increased in the DLPFC and ACC, respectively, following Mph treatment. The NAA/Cr ratio was lower in the DLPFC of val carriers than in the met/met genotype carriers prior to Mph administration. The Cho levels of the val/met genotype and val carriers increased in the striatum following Mph treatment. Following Mph treatment, the Cr levels of the met/met genotype carriers were higher than those of the val/met genotype and val carriers. Additionally, after Mph treatment, there was a significant increase in Cr levels in the DLPFC of the met/met genotype carriers but a significant decrease in such levels in the striatum of val/val genotype carriers. CONCLUSION: These findings suggest that polymorphisms of the COMT gene can account for individual differences in neurochemical responses to Mph among ADHD patients. Therefore, further studies are needed to fully characterize the effects of the Val158met polymorphism of the COMT gene on treatment outcomes in patients with ADHD.

LACK OF ASSOCIATIONS BETWEEN CLU AND PICALM GENE POLYMORPHISMS AND ALZHEIMER'S DISEASE IN A TURKISH POPULATION.

BACKGROUND AND PURPOSE: To investigate the association between the rs11136000 single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458 and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene and Alzheimer's disease (AD) in a Turkish population, and to determine whether there are any relationships between the CLU and the PICALM genotypes and behavioral and psychological symptoms of dementia (BPSD) in the Turkish population. METHODS: One-hundred and twelve AD patients and 106 controls were included in this study. BPSD were evaluated by the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene were genotyped by Real-Time PCR. Genotype distributions were assessed for the groups of patients and controls, for the patient groups with and without each BPSD, and "No BPSD" and "BPSD". RESULTS: The CLU and the PICALM genotypes were similar in the AD and control subjects, and the groups with and without each BPSD. There were also no significant differences between the "No BPSD" and the "BPSD" groups for the PICALM genotypes, but even without a statistical significance, it is notable that none of the "No BPSD" patients had genotype pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU-rs11136000-TT had higher mean score of BEHAVE-AD. CONCLUSION: This study claims that investigated SNPs are not genetic risk factors for AD in a Turkish population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not related to development of BPSD, but the rs11136000 of CLU SNP might be related to development of BPSD in AD female Turkish subpopulation.

MicroRNA Expression Analysis in Patients with Primary Myelofibrosis, Polycythemia vera and Essential Thrombocythemia.

MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in cell differentiation, proliferation and apoptosis and thus regulate haematopoietic stem cells and committed progenitor cells. We analyzed expressions of miRNAs associated with hematopoietic transformation of myeloid, erythroid and megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221, mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22), polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT-PCR testing was negative for BCR-ABL1 fusion gene in all the patients. Mir155 was expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV patients (p < 0.05) and higher in ET and PMF patients compared to control group. Mir223 expression was higher in ET and PMF group than control group (p > 0.05). Mir451 levels were lower in all three groups compared to control group (p < 0.05). There was no difference in expression levels of mir181a between groups. JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA expressions. This study holds promise for the future application of these molecules for differential diagnosis and as therapeutic targets in Philadelphia chromosome negative myeloproliferative neoplasms.

Microribonucleic acid dysregulations in children and adolescents with obsessive-compulsive disorder.

AIM: Obsessive-compulsive disorder (OCD) is a disorder characterized by the presence of obsessions and/or compulsions. Although disorder etiology and pathogenesis remains unknown, several theories about OCD development have been proposed, and many researchers believe that it is caused by both genetic and environmental factors. In the current study, our aim was to investigate miRNA levels in OCD. METHODS: In the current study, we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p, and miR155a-5p levels in child and adolescent OCD patients. The research sample consisted of a group of 23 OCD patients and 40 healthy volunteer controls. RESULTS: There was no significant difference in age and sex between the two groups (P>0.05). The levels of miR22-3p, miR24-3p, miR106b-5p, miR125b-5p, and miR155a-5p were significantly increased in the OCD subjects (P≤0.05). There were no statistically significant differences in miR18a-5p or miR107 levels between groups (P≥0.05). CONCLUSION: There could be a close relationship between levels of circulating miRNAs and OCD. If we could understand how the signaling pathways arranged by miRNAs impact on central nervous system development, function, and pathology, this understanding could improve our knowledge about OCD etiology and treatment.

Lack of association of DRD3 and CNR1 polymorphisms with premenstrual dysphoric disorders.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized with physical and affective symptoms during the luteal phase of susceptible women. OBJECTIVE: The aim of this study was to investigate the association of Dopamine D3 receptor (DRD3) polymorphism, and Cannabinoid receptor Type 1 (CNR1) polymorphism with PMDD. MATERIALS AND METHODS: Fifty one participants with documented PMDD according to the DSM IV criteria and 51 healthy controls were included in this cross sectional study. Symptom severity was measured with daily self-rating, monthly premenstrual assessment forms and psychiatric interviews. The genotyping of DRD3 receptor and Cannabinoid type 1 receptors were performed using Taqmanfluorogenic assay method. RESULTS: Distribution of DRD3 and CNR1 polymorphism was not different between patients and controls. CONCLUSION: These findings do not support a major role of DRD3, and CNR1 polymorphisms in contributing to susceptibility to premenstrual dysphoric disorder.

Effects of 2.4 GHz radiofrequency radiation emitted from Wi-Fi equipment on microRNA expression in brain tissue.

PURPOSE: MicroRNAs (miRNA) play a paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. However, their interaction with radiofrequencies is still unknown. The aim of this study was to investigate the long-term effects of radiofrequency radiation emitted from a Wireless Fidelity (Wi-Fi) system on some of the miRNA in brain tissue. MATERIALS AND METHODS: The study was carried out on 16 Wistar Albino adult male rats by dividing them into two groups such as sham (n = 8) and exposure (n = 8). Rats in the exposure group were exposed to 2.4 GHz radiofrequency (RF) radiation for 24 hours a day for 12 months (one year). The same procedure was applied to the rats in the sham group except the Wi-Fi system was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. miR-9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p in brain were investigated in detail. RESULTS: The results revealed that long-term exposure of 2.4 GHz Wi-Fi radiation can alter expression of some of the miRNAs such as miR-106b-5p (adj p* = 0.010) and miR-107 (adj p* = 0.005). We observed that mir 107 expression is 3.3 times and miR- 106b-5p expression is 3.65 times lower in the exposure group than in the control group. However, miR-9-5p, miR-29a-3p and miR-125a-3p levels in brain were not altered. CONCLUSION: Long-term exposure of 2.4 GHz RF may lead to adverse effects such as neurodegenerative diseases originated from the alteration of some miRNA expression and more studies should be devoted to the effects of RF radiation on miRNA expression levels.

Folate metabolism gene polymorphisms and risk for down syndrome offspring in Turkish women.

AIMS: Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Six common polymorphisms in folate-metabolizing genes were analayzed to determine possible risk factors for a child to be born having DS (DS mothers); these samples were taken from 47 Turkish mothers having DS children (case group) and 49 control mothers. Investigated polymorphisms include methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), A1298C (rs1801131), methionine synthase reductase (MTRR) A66G (rs1801394), methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A (rs2236225), reduced folate carrier (RFC1) A80G (rs1051266), and cystathionine ß-synthase (CBS) 844ins68. RESULTS: The frequency of the MTHFR 677C allele in DS mothers (79.8%) was significantly higher than in controls (66.3%), with a 0.499-fold increased risk of having a DS offspring (p=0.038 and 95% confidence interval [CI], 0.259-0.961). Mothers with the MTHFD1 1958A allele had a 1.880-fold increased risk of having a child with DS (p=0.031 and 95% CI, 1.060-3.335). No significant association was found for the other polymorphic variants in this study. Gene-gene interactions were not statistically significant. CONCLUSION: Polymorphic variants of the enzymes involved in folate metabolism may play an important role in determining the susceptibility of having a DS offspring. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in future studies.

Long term and excessive use of 900 MHz radiofrequency radiation alter microRNA expression in brain.

PURPOSE: We still do not have any information on the interaction between radiofrequency radiation (RF) and miRNA, which play paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. The purpose of this study was to bridge this gap by investigating effects of long-term 900 MHz mobile phone exposure on some of the miRNA in brain tissue. MATERIALS AND METHODS: The study was carried out on 14 Wistar Albino adult male rats by dividing them into two groups: Sham (n = 7) and exposure (n = 7). Rats in the exposure group were exposed to 900 MHz RF radiation for 3 h per day (7 days a week) for 12 months (one year). The same procedure was applied to the rats in the sham group except the generator was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. rno-miR-9-5p, rno-miR-29a-3p, rno-miR-106b-5p, rno-miR-107 and rno-miR-125a-3p in brain were investigated in detail. RESULTS: Results revealed that long-term exposure of 900 MHz RF radiation only decreased rno-miR107 (adjP* = 0.045) value where the whole body (rms) SAR value was 0.0369 W/kg. However, our results indicated that other microRNA evaluated in this study was not altered by 900 MHz RF radiation. CONCLUSION: 900 MHz RF radiation can alter some of the miRNA, which, in turn, may lead to adverse effects. Therefore, further studies should be performed.

Evaluation of several micro RNA (miRNA) levels in children and adolescents with attention deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood disorders, although disorders etiology and pathogenesis remains unknown, several theories about ADHD development have been proposed and many researchers believe that it is caused by both genetic and environmental factors. In this study we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p and miR155a-5p levels in child and adolescent ADHD patients. The research sample consisted a group of 52 ADHD patients, and 52 healthy volunteer controls. There was no significant difference in age and sex between the two groups (p>0.05). miRNA 18a-5p, 22-3p, 24-3p, 106b-5p and 107 levels were statistically significantly decreased in ADHD patients(p<0.05). miRNA 155a-5p levels were increased in patients group (p<0.05). The positive predictive value (PPV) and negative predictive value of miR107 was estimated for the cutoff point of 0.4480. PPV was 70% and NPV was 86.5% for the taken cut off point. There could be a close relationship between levels of circulating miRNAs and ADHD. If we could understand how the signaling pathways arranged by miRNAs, impact on CNS development, function and pathology this can improve our knowledge about ADHD etiology and treatment.