Evaluation of Depression and its Related Factors Among Female Students in Fasa, Iran

Background: We aimed to determine frequency of depression among female adolescent students and its related factors in Fasa, Iran.Methods: In a cross-sectional study, female high school students were evaluated. Depression, mental disorder and family’s relative peace were measured using standard scales.Results: A total of 516 students were evaluated in which 157 (30.4%) students did not suffer any type of depression. The mean depression score of students had significant relationship with history of an addicted family member (P < 0.001), family relative peace (P < 0.001), history of any mental-psychological disorder in family (P < 0.001) and parents’ educational level (P = 0.03).Conclusion: The prevalence of depression was high in female students and was associated with variables such as drug-addicted family member, relative peace and history of mental-psychological disorders in the family

Knockdown of BACE1-AS Nonprotein-Coding Transcript Modulates Beta-Amyloid-Related Hippocampal Neurogenesis

Background. Alzheimer's disease (AD) is a devastating neurological disorder and the main cause of dementia in the elderly population worldwide. Adult neurogenesis appears to be upregulated very early in AD pathogenesis in response to some specific aggregates of beta-amyloid (Aβ) peptides, exhausting the neuronal stem cell pools in the brain. Previously, we characterized a conserved nonprotein-coding antisense transcript for β-secretase-1 (BACE1), a critical enzyme in AD pathophysiology. We showed that the BACE1-antisense transcript (BACE1-AS) is markedly upregulated in brain samples from AD patients and promotes the stability of the (sense) BACE1 transcript. In the current paper, we examine the relationship between BACE1, BACE1-AS, adult neurogenesis markers, and amyloid plaque formation in amyloid precursor protein (APP) transgenic mice (Tg-19959) of various ages. Results. Consistent with previous publications in other APP overexpressing mouse models, we found adult neurogenesis markers to be noticeably upregulated in Tg-19959 mice very early in the development of the disease. Knockdown of either one of BACE1 or BACE1-AS transcripts by continuous infusion of locked nucleic acid- (LNA-) modified siRNAs into the third ventricle over the period of two weeks caused concordant downregulation of both transcripts in Tg-19959 mice. Downregulation of BACE1 mRNA was followed by reduction of BACE1 protein and insoluble Aβ. Modulation of BACE1 and BACE1-AS transcripts also altered oligomeric Aβ aggregation pattern, which was in turn associated with an increase in neurogenesis markers at the RNA and protein level. Conclusion. We found alterations in the RNA and protein concentrations of several adult neurogenesis markers, as well as non-protein-coding BACE1-AS transcripts, in parallel with the course of β-amyloid synthesis and aggregation in the brain of Tg15999 mice. In addition, by knocking down BACE1 or BACE1-AS (thereby reducing Aβ production and plaque deposition), we were able to modulate expression of these neurogenesis markers. Our findings suggest a distortion of adult neurogenesis that is associated with Aβ production very early in amyloid pathogenesis. We believe that these alterations, at the molecular level, could prove useful as novel therapeutic targets and/or as early biomarkers of AD

A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome

Several genome-wide transcriptomics efforts have shown that a large percentage of the mammalian genome is transcribed into RNAs, however, only a small percentage (1–2%) of these RNAs is translated into proteins. Currently there is an intense interest in characterizing the function of the different classes of noncoding RNAs and their relevance to human disease. Using genomic approaches we discovered FMR4, a primate-specific noncoding RNA transcript (2.4 kb) that resides upstream and likely shares a bidirectional promoter with FMR1. FMR4 is a product of RNA polymerase II and has a similar half-life to FMR1. The CGG expansion in the 5′ UTR of FMR1 appears to affect transcription in both directions as we found FMR4, similar to FMR1, to be silenced in fragile X patients and up-regulated in premutation carriers. Knockdown of FMR4 by several siRNAs did not affect FMR1 expression, nor vice versa, suggesting that FMR4 is not a direct regulatory transcript for FMR1. However, FMR4 markedly affected human cell proliferation in vitro; siRNAs knockdown of FMR4 resulted in alterations in the cell cycle and increased apoptosis, while the overexpression of FMR4 caused an increase in cell proliferation. Collectively, our results demonstrate an antiapoptotic function of FMR4 and provide evidence that a well-studied genomic locus can show unexpected functional complexity. It cannot be excluded that altered FMR4 expression might contribute to aspects of the clinical presentation of fragile X syndrome and/or related disorders

Evidence for natural antisense transcript-mediated inhibition of microRNA function

MicroRNAs (miRNAs) have the potential to regulate diverse sets of mRNA targets. In addition, mammalian genomes contain numerous natural antisense transcripts, most of which appear to be non-protein-coding RNAs (ncRNAs). We have recently identified and characterized a highly conserved non-coding antisense transcript for beta-secretase-1 (BACE1), a critical enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript is markedly up-regulated in brain samples from Alzheimer's disease patients and promotes the stability of the (sense) BACE1 transcript. We report here that BACE1-antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed, miR-485-5p and BACE1-antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA. We observed opposing effects of BACE1-antisense and miR-485-5p on BACE1 protein in vitro and showed that Locked Nucleic Acid-antimiR mediated knockdown of miR-485-5p as well as BACE1-antisense over-expression can prevent the miRNA-induced BACE1 suppression. We found that the expression of BACE1-antisense as well as miR-485-5p are dysregulated in RNA samples from Alzheimer's disease subjects compared to control individuals. Our data demonstrate an interface between two distinct groups of regulatory RNAs in the computation of BACE1 gene expression. Moreover, bioinformatics analyses revealed a theoretical basis for many other potential interactions between natural antisense transcripts and miRNAs at the binding sites of the latter

Association of Food Allergies, Cow’s Milk Allergy, and Asthma With Pediatric Inflammatory Bowel Disease

There are controversies on the association of childhood allergic diseases with inflammatory bowel diseases (IBD). The aim of this study was to examine the association between food allergy, cow’s milk allergy (CMA), and asthma with pediatric IBD in Iranian population. This case-control study was conducted on 200 individuals less than 18-year-old (100 with IBD and 100 as control group). Medical records, clinical presentation, and laboratory and para-clinical findings related to food allergy, CMA, and asthma were reviewed for all participants in both groups and were recorded. Among 100 children with IBD, 40 had Crohn's disease, and 60 had ulcerative colitis. The frequency of food allergy, cow's milk allergy, and asthma in children with IBD was significantly higher than the control group (P<0.001). Asthma in children with Crohn's disease was significantly more prevalent than children with ulcerative colitis (P=0.008). Food allergy (OR: 22.1, 95% CI: 5.1-95.05, P<0.001), CMA (OR: 15, 95% CI: 3-67, P<0.001), and asthma (OR: 10, 95% CI: 3-37.05, P<0.001) were significantly associated with increased risk of IBD in children. Food allergy, CMA in infancy and asthma are more prevalent in children with different subtypes of IBD. The diagnosis of these risk factors is associated with increased risk of Crohn's disease and ulcerative colitis

Comparing Oral Route Paraffin Oil versus Rectal Route for Disimpaction in Children with Chronic Constipation; a Randomized Control Trial

Objective: Functional constipation is a common and challenging problem in pediatrics. Fecal disimpaction prior to maintenance therapy is recommended to ensure successful treatment. The aim of this study was to compare the efficacy and patient's compliance of the two methods of paraffin oil administration (oral and rectal route) with the purpose of disimpaction in treatment of children with functional constipation. Methods: A total of 80 children (49 males and 31 females) aged 1-12 years, with functional constipation according to Rome III criteria, whose rectal examination confirmed fecal impaction were divided into two groups randomly. Group I received 3 ml/kg/day paraffin oil orally and group II received 3ml/kg/day paraffin oil rectally during 3 consequent days. Successful treatment was defined as no detectable fecal impaction in rectal examination after at most 72 hours. Patient compliance and family satisfaction also was evaluated using a scored questionnaire. Findings: Response to the treatment in both groups was with 92.5% and 82.5% in group I and II, respectively. So, there was no significant difference between the two methods of therapy. Family satisfying and compliance were obviously more achieved in group 1 (87.5% vs 57.5%) than in Group 2 (P<0.001). No parents in group I complained about type of treatment while 12.5% of parents in group II were unsatisfied with the mode of paraffin oil administration. The most common side effect of paraffin oil in both groups was anal oil seepage (27.5%). Nausea and abdominal pain were more common side effects in group 1 and 2 respectively. Conclusion: It seems that using paraffin oil per oral route in comparison with rectal route could be a preferred option for disimpaction in children causing less anxiety to the family

The The Effect of Time-Dependence of 10 Hz Electromagnetic Field on Spatial Learning and Memory in Rats: A 10 Hz Electromagnetic Field Improves Spatial Memory

Introduction: In everyday life, electrical devices are the primary sources of extremely low-frequency electromagnetic fields (ELF-EMF), and the human body may be a great conductor of these fields. We chose alpha band power, especially at 10 Hz frequency, due to its prior beneficial role in memory. The purpose was to clarify whether there is a relationship between ELF-EMF exposure and cognitive deficits in rats, clinical signs, behavioral analysis, and the impact of ELF-EMF during different times of exposure on neuroplasticity via the expression of BDNF.Methods: Forty adult male rats were selected randomly. The rats were exposed to ELF-EMF (10 Hz, 4 mT) for 7 days and 30 days, one hour daily. The expression of BDNF proteins in the hippocampus was evaluated after sacrificing animals to assess learning and memory function. The body weight of rats in the long-term exposed group differed significantly (P&lt;0.05). The level of BDNF mRNA in the hippocampus was found by the RT-PCR method.Results: Our findings indicate that exposure to ELF-EMF affects spatial learning and memory and can improve memory, especially with long-term exposure. In addition, we discovered a significant difference in the long-term exposed group (P&lt;0.05), where radiation for 30 days resulted in a substantial rise in BDNF levels.Conclusion: After prolonged exposure, male rats spent more time and traveled a greater percentage of their distance in the target quadrant, demonstrating that long-term exposure improves spatial memory and that 10 Hz might be safe

Screening for Small-Molecule Modulators of Long Noncoding RNA-Protein Interactions Using AlphaScreen

Long non-protein coding RNAs (lncRNAs) are an important class of molecules that help orchestrate key cellular events. Although their functional roles in cells are not well understood, thousands of lncRNAs and a number of possible mechanisms by which they act have been reported. LncRNAs can exert their regulatory function in cells by interacting with epigenetic enzymes. In this study, we developed a tool to study lncRNA-protein interactions for high-throughput screening of small-molecule modulators using AlphaScreen technology. We tested the interaction of two lncRNAs: brain-derived neurotrophic factor antisense (BDNF-AS) and Hox transcript antisense RNA (HOTAIR), with Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase against a phytochemical library, to look for small-molecule inhibitors that can alter the expression of downstream target genes. We identified ellipticine, a compound that up-regulates BDNF transcription. Our study shows the feasibility of using high-throughput screening to identify modulators of lncRNA-protein interactions and paves the road for targeting lncRNAs that are dysregulated in human disorders using small-molecule therapies

Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report

Abstract Background Osteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance. Case Presentation Here we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A > G, IVS7-2A > G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation. Conclusions Our study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations