Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3630 - 3630

Published: March 24, 2024

The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and role in disease. Targeting ncRNAs, including microRNAs (miRNAs) long (lncRNAs), an attractive approach for treating various diseases, such cardiovascular disease cancer. This seminar discusses the current status ncRNAs therapeutic different pathological conditions. Regarding miRNA-based drugs, this has made significant progress preclinical clinical testing where limitations conventional pharmacotherapy are evident. challenges specificity, delivery, tolerability, will be discussed. New approaches improve success explored. Furthermore, it extensively potential development targeted therapies Finally, document reports on recent advances identifying characterizing microRNAs, manipulating them, translating them into applications. It also addresses perspectives towards application.

Language: Английский

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Next RNA Therapeutics: The Mine of Non-Coding

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7471 - 7471

Published: July 5, 2022

The growing knowledge on several classes of non-coding RNAs (ncRNAs) and their different functional roles has aroused great interest in the scientific community. Beyond Central Dogma Biology, it is clearly known that not all code for protein products, they exert a broader repertoire biological functions. As described this review, ncRNAs participate gene expression regulation both at transcriptional post-transcriptional levels represent critical elements driving controlling pathophysiological processes multicellular organisms. For reason, recent years, boost was given to ncRNA-based strategies with potential therapeutic abilities, nowadays, use RNA molecules experimentally validated actually exploited clinics counteract diseases. In we summarize principal ncRNA are potentially implied disease onset progression, which already used or under clinical trials, highlighting advantages need targeted strategy design. Furthermore, discuss benefits limits therapeutics ongoing development delivery limit off-target effects increase translational application.

Language: Английский

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miR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 212, P. 111818 - 111818

Published: April 27, 2023

Language: Английский

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Cardiac tissue engineering for myocardial infarction treatment

European Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 185, P. 106439 - 106439

Published: March 30, 2023

Myocardial infarction is one of the major causes morbidity and mortality worldwide. Current treatments can relieve symptoms myocardial ischemia but cannot repair necrotic tissue. Novel therapeutic strategies based on cellular therapy, extracellular vesicles, non-coding RNAs growth factors have been designed to restore cardiac function while inducing cardiomyocyte cycle re-entry, ensuring angiogenesis cardioprotection, preventing ventricular remodeling. However, they face low stability, cell engraftment issues or enzymatic degradation in vivo, it thus essential combine them with biomaterial-based delivery systems. Microcarriers, nanocarriers, patches injectable hydrogels yielded promising results preclinical studies, some which are currently being tested clinical trials. In this review, we cover recent advances made acellular therapies used for after MI. We present current trends tissue engineering related use microcarriers, as systems biologics. Finally, discuss most crucial aspects that should be addressed order advance towards translation approaches.

Language: Английский

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Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1341 - 1341

Published: May 8, 2023

Reactive oxygen species (ROS) are radical intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds buffering capacity antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC shifts vascular system into a pro-coagulative, proinflammatory state, thereby increasing risk developing cardiovascular (CV) diseases metabolic disorders. Studies have turned to investigation microRNA treatment for CV factors, post-transcription regulators known co-regulate ROS. In this review, we will discuss ROS pathways generation, normal physiology ROS-induced dysfunction, current knowledge common disorders their connection stress. Therapeutic strategies based on microRNAs response microRNA’s regulatory roles controlling also be explored. It is gain an in-depth comprehension mechanisms generating how manipulating enzymatic byproducts can protect function from prevent development

Language: Английский

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Mitigating off‐target effects of small RNAs: conventional approaches, network theory and artificial intelligence

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Three types of highly promising small RNA therapeutics, namely, interfering RNAs (siRNAs), microRNAs (miRNAs) and the subtype antisense oligonucleotides (ASOs), offer advantages over small-molecule drugs. These can target any gene product, opening up new avenues effective safe therapeutic approaches for a wide range diseases. In preclinical research, synthetic play an essential role in investigation physiological pathological pathways as silencers specific genes, facilitating discovery validation drug targets different conditions. Off-target effects RNAs, however, could make it difficult to interpret experimental results phase may contribute adverse events therapeutics. Out two major off-target we focused on hybridization-dependent, especially miRNA-like effects. Our main aim was discuss several approaches, including sequence design, chemical modifications prediction, reduce hybridization-dependent that should be considered even at early development therapy. Because there is no standard way predicting effects, this review provides overview all state-of-the-art computational methods proposes such possible inclusion network theory artificial intelligence (AI) prediction workflows. Case studies concise survey validating silico predictions are also presented. results, minimize hopefully avoid off-target-related

Language: Английский

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Oxidative Stress, Endothelial Dysfunction, and N-Acetylcysteine in Type 2 Diabetes Mellitus

Antioxidants and Redox Signaling, Journal Year: 2024, Volume and Issue: 40(16-18), P. 968 - 989

Published: March 18, 2024

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Endothelial dysfunction is closely associated with development progression CVDs. Patients diabetes mellitus (DM) especially type 2 DM (T2DM) exhibit a significant endothelial cell (EC) substantially increased risk for

Language: Английский

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A Novel Machine Learning-Based Prediction Method for Early Detection and Diagnosis of Congenital Heart Disease Using ECG Signal Processing

Technologies, Journal Year: 2024, Volume and Issue: 12(1), P. 4 - 4

Published: Jan. 2, 2024

Congenital heart disease (CHD) represents a multifaceted medical condition that requires early detection and diagnosis for effective management, given its diverse presentations subtle symptoms manifest from birth. This research article introduces groundbreaking healthcare application, the Machine Learning-based Heart Disease Prediction Method (ML-CHDPM), tailored to address these challenges expedite timely identification classification of CHD in pregnant women. The ML-CHDPM model leverages state-of-the-art machine learning techniques categorize cases, taking into account pertinent clinical demographic factors. Trained on comprehensive dataset, captures intricate patterns relationships, resulting precise predictions classifications. evaluation model’s performance encompasses sensitivity, specificity, accuracy, area under receiver operating characteristic curve. Remarkably, findings underscore ML-CHDPM’s superiority across six pivotal metrics: precision, recall, false positive rate (FPR), negative (FNR). method achieves an average accuracy 94.28%, precision 87.54%, recall 96.25%, specificity 91.74%, FPR 8.26%, FNR 3.75%. These outcomes distinctly demonstrate effectiveness reliably predicting classifying cases. marks significant stride toward diagnosis, harnessing advanced within realm ECG signal processing, specifically

Language: Английский

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Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 2, 2024

Abstract Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, contraction, making them valuable long-term repair. In this study, we find downregulated miR-199a-5p expression MI. Intramyocardial injection into the infarcted region male rats revealed its dual protective effects on heart. Specifically, targets AGTR1, diminishing early oxidative damage post-myocardial infarction, MARK4, which influences contractility enhances cardiac function. To deliver efficiently specifically to ischemic tissue, use CSTSMLKAC peptide construct P-MSN/miR199a-5p nanoparticles. Intravenous administration these nanoparticles reduces injury protects Our findings demonstrate effectiveness repairing through enhanced contraction anti-apoptosis. miR199a-5p holds significant therapeutic potential repair infarction.

Language: Английский

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Inferring single-cell and spatial microRNA activity from transcriptomics data

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 18, 2025

Abstract The activity of miRNA varies across different cell populations and systems, as part the mechanisms that distinguish types roles in living organisms human health disease. Typically, regulation drives changes composition levels protein-coding RNA lncRNA, with targets being down-regulated when miRNAs are active. term “miRNA activity" is used to refer this transcriptional effect miRNAs. This study introduces miTEA-HiRes, a method designed facilitate evaluation at high resolution. applies single-cell transcriptomics, type-specific populations, spatial transcriptomics data. By comparing conditions, differential inferred. For instance, miTEA-HiRes analysis peripheral blood mononuclear cells Multiple Sclerosis patients control groups revealed miR-20a-5p others, consistent literature on underexpression Sclerosis. We also show miR-519a-3p specific populations.

Language: Английский

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