Erythropoietin decreases apoptosis induced by 6-hydroxydopamine in PC12 cells

Aim: In the present study, we investigated whether Erythropoietin (Epo) has a protective effect against cytotoxicity and apoptotic cell death induced by 6-hydroxydopamine (6-OHDA) in PC12 cell line cultures. Material and Methods: Epo exerted significant protective effect against 6-OHDA-induced cell injury and apoptosis as confirmed by lactate dehydrogenase cytotoxicity assay, anti-single strand DNA immunostaining and annexin-V staining. Results: Epo significantly decreased 6-OHDA-induced DP5 pro-apoptotic protein mRNA expression and increased bcl-XL anti-apoptotic protein mRNA expression. Any effect of Epo on CREB transcription factor phosphorylation was not observed. Conclusion: These results suggest that Epo exerts neuroprotective effect against 6-OHDA-induced cell death at least partially via the differential regulation of the expression of genes involved in the apoptotic process

Folate Metabolism Gene Polymorphisms and Risk for Down Syndrome Offspring in Turkish Women

Erdal, Mehmet Emin/0000-0002-6191-2930; Soylemez, Fatma/0000-0002-1939-8691; yildirim, didem derici/0000-0001-7709-6133; derici, didem/0000-0001-7709-6133; Ay, Mustafa Ertan/0000-0002-6152-7450;WOS: 000352344400006PubMed: 25671679Aims: 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 beta-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.Mersin University of Scientific FoundationMersin University [BAP-TF TTB 2009-2]This study was supported by the Mersin University of Scientific Foundation (BAP-TF TTB 2009-2). Ethics committee consent was obtained from the Local Ethics Committee of Mersin University. The authors thank all those who participated in the study, the IZEM Rehabilitation Center, particularly all the personnel at the IZEM and Metin Ugur Sarikaya Rehabilitation Center in Mersin

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  \u3c 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