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1.
Int J Biol Macromol ; 261(Pt 2): 129714, 2024 Mar.
Article En | MEDLINE | ID: mdl-38286377

MicroRNAs (miRNAs), a class of non-coding RNAs, are utilized as biomarkers for a wide range of disorders. Circulating miRNAs are proposed as potential markers in the clinical identification of heart failure (HF). However, identifying miRNA biomarkers in HF requires identification of robust endogenous control miRNAs for normalization in differential expression analysis. Hence, this study aimed to identify circulating miRNAs that can be utilized as endogenous controls in HF. We evaluated the expression of eight miRNAs, which were previously reported as endogenous controls in different pathological conditions. Total RNA, including miRNA, was extracted from the serum samples of 30 HF patients (15 HFrEF and 15 HFpEF) and their matched controls (n = 15). We used quantitative PCR to determine the miRNA expression. The stability of the selected endogenous miRNAs was assessed and compared using a standard set of criteria with the RefFinder software. Six of the eight miRNAs analyzed showed consistent expression among all sample groups. Stability analysis ranked hsa-let-7i-5p, hsa-miR-148b-3p, and hsa-miR-484 as the most stable miRNAs, indicating their potential as reliable endogenous controls.


Heart Failure , MicroRNAs , Humans , Heart Failure/genetics , Stroke Volume , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers , Software
2.
Curr Pharm Des ; 25(41): 4368-4378, 2019.
Article En | MEDLINE | ID: mdl-31692427

BACKGROUND: Efforts to unravel the extensive impact of the non-coding elements of the human genome on cell homeostasis and pathological processes have gained momentum over the last couple of decades. miRNAs refer to short, often 18-25 nucleotides long, non-coding RNA molecules which can regulate gene expression. Each miRNA can regulate several mRNAs. METHODS: This article reviews the literature on the roles of miRNAs in autism. RESULTS: Considering the fact that ~ 1% of the human DNA encodes different families of miRNAs, their overall impact as critical regulators of gene expression in the mammalian brain should be immense. Though the autism spectrum disorders (ASDs) are predominantly genetic in nature and several candidate genes are already identified, the highly heterogeneous and multifactorial nature of the disorder makes it difficult to identify common genetic risk factors. Several studies have suggested that the environmental factors may interact with the genetic factors to increase the risk. miRNAs could possibly be one of those factors which explain this link between genetics and the environment. CONCLUSION: In the present review, we have summarized our current knowledge on miRNAs and their complex roles in ASD, and also on their therapeutic applications.


Autism Spectrum Disorder/genetics , MicroRNAs/genetics , Animals , Brain , Gene Expression Regulation , Humans
3.
Adv Clin Chem ; 90: 81-132, 2019.
Article En | MEDLINE | ID: mdl-31122612

Ever since their discovery, the telomeres and the telomerase have been topics of intensive research, first as a mechanism of cellular aging and later as an indicator of health and diseases in humans. By protecting the chromosome ends, the telomeres play a vital role in preserving the information in our genome. Telomeres shorten with age and the rate of telomere erosion provides insight into the proliferation history of cells. The pace of telomere attrition is known to increase at the onset of several pathological conditions. Telomere shortening has been emerging as a potential contributor in the pathogenesis of several neurological disorders including autism spectrum disorders (ASD), schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD) and depression. The rate of telomere attrition in the brain is slower than that of other tissues owing to the low rate of cell proliferation in brain. Telomere maintenance is crucial for the functioning of stem cells in brain. Taking together the studies on telomere attrition in various neurological disorders, an association between telomere shortening and disease status has been demonstrated in schizophrenia, AD and depression, in spite of a few negative reports. But, studies in ASD and PD have failed to produce conclusive results. The cause-effect relationship between TL and neurological disorders is yet to be elucidated. The factors responsible for telomere erosion, which have also been implicated in the pathogenesis of neurological disorders, need to be explored in detail. Telomerase activation is now being considered as a potential therapeutic strategy for neurological disorders.


Nervous System Diseases/genetics , Telomere/genetics , Telomere/metabolism , Animals , Blotting, Southern , Humans , In Situ Hybridization, Fluorescence , Polymerase Chain Reaction
4.
Article En | MEDLINE | ID: mdl-25194460

Epidemiological studies suggest that perinatal complications, particularly hypoxia-related ones, increase the risk of schizophrenia. Recent genetic studies of the disorder have identified several putative susceptibility genes, some of which are known to be regulated by hypoxia. It can be postulated therefore that birth complications that cause hypoxia in the fetal brain may be associated with a dysregulation in the expression of some of the schizophrenia candidate genes. To test this, we used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Caesarean section birth, and examined the expression of mRNA of five of the putative susceptibility genes (NRG1, ErbB4, AKT1, COMT and BDNF) by real-time quantitative PCR in the medial prefrontal cortex (mPFC) and the hippocampus at 6 and 12 weeks after birth. The expression of NRG1 mRNA was significantly decreased in the mPFC, but not in the hippocampus, at 6 and 12 weeks after birth. In addition, a significant increase in COMT mRNA expression was observed in the mPFC at 12 weeks. The alteration in mRNA levels of NRG1 and COMT was not associated with a change in their protein levels. These results suggest that perinatal asphyxia may lead to disturbances in the PFC, which in turn may exert a long-lasting influence on the expression of specific genes, such as NRG1 and COMT. Our results also suggest that translational interruption may occur in this model of perinatal asphyxia.


Asphyxia/pathology , Catechol O-Methyltransferase/metabolism , Gene Expression Regulation/physiology , Neuregulin-1/metabolism , Prefrontal Cortex/metabolism , Age Factors , Analysis of Variance , Animals , Asphyxia/metabolism , Catechol O-Methyltransferase/genetics , Female , Male , Neuregulin-1/genetics , Pregnancy , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley
5.
Mol Autism ; 3(1): 11, 2012 Oct 30.
Article En | MEDLINE | ID: mdl-23110844

BACKGROUND: Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients. METHODS: We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features. RESULTS: Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function. CONCLUSIONS: Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities.

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