Identifying Novel Drug Targets for Calcific Aortic Valve Disease through Mendelian Randomization

Atherosclerosis, Journal Year: 2025, Volume and Issue: unknown, P. 119110 - 119110

Published: Jan. 1, 2025

Language: Английский

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Recent advances of PIWI‐interacting RNA in cardiovascular diseases

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(8)

Published: July 31, 2024

Abstract Background The relationship between noncoding RNAs (ncRNAs) and human diseases has been a hot topic of research, but the study ncRNAs in cardiovascular (CVDs) is still its infancy. PIWI‐interacting RNA (piRNA), small ncRNA that binds to PIWI protein maintain genome stability by silencing transposons, was widely studied germ lines stem cells. In recent years, piRNA shown be involved key events multiple CVDs through various epigenetic modifications, revealing potential value as new biomarker or therapeutic target. Conclusion This review explores origin, degradation, function, mechanism important role CVDs, promising targets were summarized. provide strategy for treatment lay theoretical foundation future research. Key points can used target biomaker CVDs. influences apoptosis, inflammation angiogenesis regulating modificaions. Critical knowledge gaps remain unifying nomenclature PIWI‐independent function.

Language: Английский

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Calcific aortic stenosis: omics-based target discovery and therapy development

European Heart Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Calcific aortic valve disease (CAVD) resulting in stenosis (AS) is the most common form of valvular heart disease, affecting 2% those over age 65. Those who develop symptomatic severe AS have an average further lifespan <2 years without replacement, and three-quarters these patients will failure, undergo or die within 5 years. There are no approved pharmaceutical therapies for AS, due primarily to a limited understanding molecular mechanisms that direct CAVD progression complex haemodynamic environment. Here, advances efforts understand pathogenesis identify putative drug targets derived from recent multi-omics studies [including (epi)genomics, transcriptomics, proteomics, metabolomics] blood tissues reviewed. The explosion single-cell omics-based pathobiological potential discovery insights gained application omics this area primary focus. Lastly, translation knowledge pathobiology into clinical addressed, with particular emphasis on treatment regimens consider sex-specific, renal, lipid-mediated contributors CAVD, ongoing Phase I/II/III trials aimed at prevention/treatment described.

Language: Английский

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Recent advances in the regulatory and non-coding RNA biology of osteogenic differentiation: biological functions and significance for bone healing

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 6, 2025

Injuries associated with contemporary life, such as automobile crashes and sports injuries, can lead to large numbers of traumatic neuromuscular injuries that are intimately bone fractures. Regulatory non-coding RNAs play essential roles in multiple cellular processes, including osteogenic differentiation healing. In this review, we discuss the most recent advances our understanding regulatory RNA biology stem, stromal progenitor cells. We focused on circular RNAs, small nucleolar PIWI-interacting comprehensively summarized their biological functions well discussed significance for healing tissue regeneration.

Language: Английский

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MARCH5 ameliorates aortic valve calcification via RACGAP1-DRP1 pathway associated mitochondrial quality control

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 119911 - 119911

Published: Jan. 1, 2025

Language: Английский

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piR-38,736 promotes gastric cancer cell proliferation by downregulating SMAD4 expression

Journal of Molecular Histology, Journal Year: 2025, Volume and Issue: 56(2)

Published: April 1, 2025

PIWI-interacting RNAs (piRNAs) play an important role in cancer development and progression. Although recent studies had advanced our understanding of the functions various piRNAs cancer, specific piR-38736 gastric remained poorly understood. This study aimed to investigate clinical significance underlying mechanisms cancer. found that was significantly upregulated cells tissues. Positive expression closely correlated with larger tumor size medium poor differentiation. Survival analysis revealed patients positive shorter survival times compared those negative expression. Knockdown markedly inhibited cell proliferation growth Furthermore, directly bind 3' untranslated region (UTR) SMAD4 mRNA, resulting significant downregulation at both mRNA protein levels upon overexpression piR-38,736. In conclusion, these findings indicate piR-38,736 promotes by downregulating may serve as a prognostic biomarker potential therapeutic target for Further are required fully elucidate explore its implications management.

Language: Английский

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Stem-Cell Derived Exosomal microRNAs as Biomarkers and Therapeutics for Pediatric Cardiovascular Disease

Current Treatment Options in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 9, 2025

In recent years, several pre-clinical studies have demonstrated the therapeutic potential of stem cell-derived exosomes in treatment cardiovascular disease (CVD). Here, we evaluate their as biomarkers for detection and monitoring CVD, with a particular focus on pediatric heart disease. Exosomes isolated from cell sources, including mesenchymal cells (MSCs) pluripotent (PSCs), benefit function, inflammatory responses, angiogenesis injured diseased hearts. These carry variety cargo, such proteins, lipids, nucleic acids. However, majority contain non-coding RNA molecules. Review existing literature RNAs relationship to CVD suggests that containing microRNAs (miRNAs) can serve promising due presence circulation, ease isolation, potential. are especially screening diagnostic tools early congenital

Language: Английский

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PiRNAs, PiRNA‐Like, and PIWI Proteins in Somatic Cells: From Genetic Regulation to Disease Mechanisms

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2025, Volume and Issue: 16(2)

Published: March 1, 2025

ABSTRACT PIWI‐interacting RNAs (piRNAs) are small non‐coding RNA molecules that were originally described as responsible for binding to PIWI proteins silence transposons in the germline genome. Here we discuss their controversial influence regulating gene expression human somatic cells. Although functions cells remain controversial, current research has focused on potential contribution diseases including cancers and cardiovascular (CVDs). These directly interact with form piRNA‐induced silencing complexes (piRISC). regulate not only long (lncRNAs) but also mRNAs 3′ untranslated region. The controversy occurs because all of reports demonstrate a direct interaction between whether these established have activities. Therefore, importance physiology pathology continues controversial. challenges limitations need be addressed order establish harness ncRNAs clinical applications. In this review, distinguish those examples been shown function from appear based ability bind (piRNA‐like)

Language: Английский

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Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 11, 2024

Vascular calcification (VC) arises from the accumulation of calcium salts in intimal or tunica media layer aorta, contributing to higher risk cardiovascular events and mortality. Despite this, mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity hypertension neointimal hyperplasia. In this study, we sought investigate role mechanism VC. The expression was measured calcified VSMCs aortas, well patients. Loss- gain-of-function experiments were evaluated roles pathogenesis. transcription activation detected using mass spectrometry. found levels both patients with coronary calcification. Loss-of-function revealed key regulator by facilitating osteogenic transformation VSMCs. Mechanistically, promoted de-ubiquitination stability BMP-2 via inhibiting E3 ligase SYTL4, interaction potentiated signaling induced phosphorylation Smad, followed HDAC4 nuclear exclusion. dissociation RUNX2 elicited acetylation subsequent translocation, leading upregulation OPN, critical player From small library natural compounds, identified Curculigoside Chebulagic acid reduced development binding nesfatin-1. Eventually, designed spectrometry-based DNA-protein screening identify STAT3 mediated context Overall, our study demonstrates enhances thereby stabilizing downstream SMAD1/5/9 HDAC4. This cascade leads transcriptional MSX2, These insights position potential therapeutic target preventing treating VC, advancing understanding molecular underlying condition.

Language: Английский

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Somatic piRNA and PIWI-mediated post-transcriptional gene regulation in stem cells and disease

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Dec. 9, 2024

PIWI-interacting RNAs (piRNAs) are small non-coding that bind to the PIWI subclass of Argonaute protein family and essential for maintaining germline integrity. Initially discovered in

Language: Английский

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