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Huntington's disease (HD) is caused by an expansion of CAG trinucleotide repeat in the HTT gene; the exact pathogenesis of HD currently remains unclear. One of the promising directions in the study of HDs is to determine the molecular mechanism underlying the development and role of microRNAs (miRNAs). This study aimed to identify the profile of miRNAs in an HD human cell line model as diagnostic biomarkers for HD. To study HD, the human SH-SY5Y HD cell model is based on the expression of two different forms: pEGFP-Q23 and pEGFP-Q74 of HTT. The expression of Htt protein was confirmed using aggregation assays combined with immunofluorescence and Western blotting methods. miRNA levels were measured in SH-SY5Y neuronal cell model samples stably expressing Q23 and Q74 using the extraction-free HTG EdgeSeq protocol. A total of 2083 miRNAs were detected, and 354 (top 18 miRNAs) miRNAs were significantly differentially expressed (DE) (p < 0.05) in Q23 and Q74 cell lines. A majority of the miRNAs were downregulated in the HD cell model. Moreover, we revealed that six DE miRNAs target seven genes (ATN1, GEMIN4, EFNA5, CSMD2, CREBBP, ATXN1, and B3GNT) that play important roles in neurodegenerative disorders and showed significant expression differences in mutant Htt (Q74) when compared to wild-type Htt (Q23) using RT-qPCR (p < 0.05 and 0.01). We demonstrated the most important DE miRNA-mRNA profiles, interaction binding sites, and their related pathways in HD using experimental and bioinformatics methods. This will allow the development of novel diagnostic strategies and provide alternative therapeutic routes for treating HD.
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The increase in industrialization has led to an exponential increase in heavy metal (HM) soil contamination, which poses a serious threat to public health and ecosystem stability. This review emphasizes the urgent need to develop innovative technologies for the environmental remediation of intensive anthropogenic pollution. Phytoremediation is a sustainable and cost-effective approach for the detoxification of contaminated soils using various plant species. This review discusses in detail the basic principles of phytoremediation and emphasizes its ecological advantages over other methods for cleaning contaminated areas and its technical viability. Much attention has been given to the selection of hyperaccumulator plants for phytoremediation that can grow on heavy metal-contaminated soils, and the biochemical mechanisms that allow these plants to isolate, detoxify, and accumulate heavy metals are discussed in detail. The novelty of our study lies in reviewing the mechanisms of plant-microorganism interactions that greatly enhance the efficiency of phytoremediation as well as in discussing genetic modifications that could revolutionize the cleanup of contaminated soils. Moreover, this manuscript discusses potential applications of phytoremediation beyond soil detoxification, including its role in bioenergy production and biodiversity restoration in degraded habitats. This review concludes by listing the serious problems that result from anthropogenic environmental pollution that future generations still need to overcome and suggests promising research directions in which the integration of nano- and biotechnology will play an important role in enhancing the effectiveness of phytoremediation. These contributions are critical for environmental scientists, policy makers, and practitioners seeking to utilize phytoremediation to maintain the ecological stability of the environment and its restoration.
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Raman spectroscopy (RS), a powerful analytical technique, has gained increasing recognition and utility in the fields of biomedical and biological research. Raman spectroscopic analyses find extensive application in the field of medicine and are employed for intricate research endeavors and diagnostic purposes. Consequently, it enjoys broad utilization within the realm of biological research, facilitating the identification of cellular classifications, metabolite profiling within the cellular milieu, and the assessment of pigment constituents within microalgae. This article also explores the multifaceted role of RS in these domains, highlighting its distinct advantages, acknowledging its limitations, and proposing strategies for enhancement.
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Análise Espectral Raman , Análise Espectral Raman/métodosRESUMO
The variability of nucleotide repeats is considered one of the causes of diseases, but their biological function is not understood. In recent years, the interaction of miRNAs and piRNAs with the mRNAs of genes responsible for developing neurodegenerative and oncological diseases and diabetes have been actively studied. We explored candidate genes with nucleotide repeats to predict associations with miRNAs and piRNAs. The parameters of miRNAs and piRNA binding sites with mRNAs of human genes having nucleotide repeats were determined using the MirTarget program. This program defines the start of the initiation of miRNA and piRNA binding to mRNAs, the localization of miRNA and piRNA binding sites in the 5'-untranslated region (5'UTR), coding sequence (CDS) and 3'-untranslated region (3'UTR); the free energy of binding; and the schemes of nucleotide interactions of miRNAs and piRNAs with mRNAs. The characteristics of miRNAs and piRNA binding sites with mRNAs of 73 human genes were determined. The 5'UTR, 3'UTR and CDS of the mRNAs of genes are involved in the development of neurodegenerative, oncological and diabetes diseases with GU, AC dinucleotide and CCG, CAG, GCC, CGG, CGC trinucleotide repeats. The associations of miRNAs, piRNAs and candidate target genes could be recommended for developing methods for diagnosing diseases, including neurodegenerative diseases, oncological diseases and diabetes.
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MicroRNAs , Regiões 3' não Traduzidas/genética , Regiões 5' não Traduzidas , Biologia Computacional/métodos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Nucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Repetições de TrinucleotídeosRESUMO
There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington's disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Doenças Neurodegenerativas , Doenças Priônicas , Vesículas Extracelulares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/terapia , Doenças Priônicas/metabolismoRESUMO
BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. At present, there is a need to search for new, accurate, reliable, minimally invasive and cheap biomarkers in addition to existing methods for the diagnosis and prognosis of BC. The main goal of this study was to test the diagnostic value of six circulating miRNAs in Kazakh women. MATERIALS AND METHODS: TaqMan-based miRNA profiling was conducted using plasma specimens from 35 BC women patients and 33 healthy women samples (control group). RESULTS: The level of all seven miRNAs (including endogenous control) normalized by synthetic cel-miR-39 were significantly elevated in the group of BC patients. Normalization using miR-222-3p as endogenous control reduced differences in level of miRNAs between groups; as a result, only three miRNAs were significantly upregulated in the group of BC patients-miR-145-5p (P = 6.5e-12), miR-191-5p (P = 3.7e-10) and miR-21-5p (P = 0.0034). Moreover, ROC analysis showed that the use of miR-145-5p and miR-191-5p, both individually (AUC = 0.931 and 0.904, respectively) or in combination (AUC = 0.984), allows to accurately differentiate BC patients from healthy individuals. CONCLUSIONS: Two plasma miRNAs-miR-145-5p and miR-191-5p-are potential biomarkers for diagnosis of BC in the Kazakh population. The findings need to be further substantiated using a more representative sample.