The correlation between gut microbiome and atrial fibrillation: pathophysiology and therapeutic perspectives

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Nov. 7, 2023

Regulation of gut microbiota and its impact on human health is the theme intensive research. The incidence prevalence atrial fibrillation (AF) are continuously escalating as global population ages chronic disease survival rates increase; however, mechanisms not entirely clarified. It gaining awareness that alterations in assembly, structure, dynamics intimately engaged AF progression. Owing to advancements next-generation sequencing technologies computational strategies, researchers can explore novel linkages with genomes, transcriptomes, proteomes, metabolomes through parallel meta-omics approaches, rendering a panoramic view culture-independent microbial investigation. In this review, we summarized evidence for bidirectional correlation between microbiome. Furthermore, proposed concept "gut-immune-heart" axis addressed direct indirect causal roots microbiome AF. intricate relationship was unveiled generate innovative microbiota-based preventive therapeutic interventions, which shed light definite direction future experiments.

Language: Английский

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Ferroptosis in organ fibrosis: From mechanisms to therapeutic medicines

Journal of Translational Internal Medicine, Journal Year: 2024, Volume and Issue: 12(1), P. 22 - 34

Published: Feb. 1, 2024

Abstract Fibrosis occurs in many organs, and its sustained progress can lead to organ destruction malfunction. Although numerous studies on fibrosis have been carried out, underlying mechanism is largely unknown, no ideal treatment currently available. Ferroptosis an iron-dependent process of programmed cell death that characterized by lipid peroxidation. In the past decade, a growing body evidence demonstrated association between ferroptosis fibrotic diseases, while targeting may serve as potential therapeutic strategy. This review highlights recent advances crosstalk fibrosis, discusses ferroptosis-targeted approaches against are being explored.

Language: Английский

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The crosstalk between exosomes and ferroptosis: a review

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 9, 2024

Abstract Exosomes are a subtype of extracellular vesicles composed bioactive molecules, including nucleic acids, proteins, and lipids. generated by the fusion intracellular multivesicular bodies (MVBs) with cell membrane subsequently released into space to participate in intercellular communication diverse biological processes within target cells. As crucial mediator, exosomes have been implicated regulating ferroptosis—an iron-dependent programmed death characterized lipid peroxide accumulation induced reactive oxygen species. The involvement iron, lipid, amino acid metabolism contributes their regulatory role specific mechanisms underlying how modulate ferroptosis, which remains incompletely understood, some related studies still preliminary. Therefore, targeting regulation ferroptosis holds promise for future clinical treatment strategies across various diseases. This review aims provide insights pathophysiology governing interaction between implications disease development serve as reference further research.

Language: Английский

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M2 macrophage‑derived exosomes alleviate KCa3.1 channel expression in rapidly paced HL‑1 myocytes via the NF‑κB (p65)/STAT3 signaling pathway

Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(4)

Published: Feb. 8, 2024

The present study was designed to explore the role of M2 macrophage‑derived exosomes (M2‑exos) on KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL‑1 myocytes. macrophages and M2‑exos were isolated identified. MicroRNA (miR)‑146a‑5p levels quantified reverse transcription‑quantitative PCR (RT‑qPCR). myocytes randomly divided into six groups: Control group, pacing + coculture group (pacing cells cocultured with M2‑exos), mimic‑miR‑146a‑5p NC‑miR‑146a‑5p pyrrolidine dithiocarbamate (PDTC; special blocker NF‑κB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT‑qPCR immunohistochemistry performed study. A whole‑cell clamp also applied record current density action potential duration (APD) each results revealed that miR‑146a‑5p highly expressed both M2‑exos. Pacing led shorter APD, an increased higher protein KCa3.1, phosphorylated (p‑)NF‑κB p65, p‑STAT3 IL‑1β compared control M2‑exos, miR‑146a‑5p‑mimic PDTC reduced expression p‑NF‑κB resulting longer APD cells. In conclusion, their cargo, which comprised miR‑146a‑5p, decreased secretion via NF‑κB/STAT3 pathway, limiting caused by rapid pacing.

Language: Английский

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The Regulation of Ferroptosis by Noncoding RNAs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13336 - 13336

Published: Aug. 28, 2023

As a novel form of regulated cell death, ferroptosis is characterized by intracellular iron and lipid peroxide accumulation, which different from other death forms morphologically, biochemically, immunologically. Ferroptosis metabolism, antioxidant defense systems as well various transcription factors related signal pathways. Emerging evidence has highlighted that associated with many physiological pathological processes, including cancer, neurodegeneration diseases, cardiovascular ischemia/reperfusion injury. Noncoding RNAs are group functional RNA molecules not translated into proteins, can regulate gene expression in manners. An increasing number studies have shown noncoding RNAs, especially miRNAs, lncRNAs, circRNAs, interfere the progression modulating ferroptosis-related genes or proteins directly indirectly. In this review, we summarize basic mechanisms regulations focus on recent mechanism for types ncRNAs to conditions, will deepen our understanding regulation provide new insights employing ferroptosis-associated therapeutic strategies.

Language: Английский

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Noncoding RNAs as Key Regulators for Cardiac Development and Cardiovascular Diseases

Journal of Cardiovascular Development and Disease, Journal Year: 2023, Volume and Issue: 10(4), P. 166 - 166

Published: April 12, 2023

Noncoding RNAs (ncRNAs) play fundamental roles in cardiac development and cardiovascular diseases (CVDs), which are a major cause of morbidity mortality. With advances RNA sequencing technology, the focus recent research has transitioned from studies specific candidates to whole transcriptome analyses. Thanks these types studies, new ncRNAs have been identified for their implication CVDs. In this review, we briefly describe classification into microRNAs, long ncRNAs, circular RNAs. We then discuss critical CVDs by citing most up-to-date articles. More specifically, summarize formation heart tube morphogenesis, mesoderm specification, embryonic cardiomyocytes progenitor cells. also highlight that recently emerged as key regulators focusing on six them. believe review concisely addresses perhaps not all but certainly aspects current progress ncRNA Thus, would be beneficial readers obtain picture mechanisms action

Language: Английский

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Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

Cardiology, Journal Year: 2024, Volume and Issue: 149(4), P. 357 - 368

Published: Jan. 1, 2024

<b><i>Introduction:</i></b> Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are AF, but many senior individuals do not develop AF despite having multiple factors. This finding suggests that other may be involved in onset. study aimed to identify upregulated genes the peripheral blood and left atrium of patients AF. These serve as potential biomarkers predict onset its complications. <b><i>Methods:</i></b> Gene expression data were analyzed from (<i>n</i> = 3) atrial samples 15) sinus rhythm. We evaluated significant identified using <i>p</i> value analysis weighted average difference confirm their rankings. created figures for GeneMANIA performed functional Cytoscape3.10.1. Hub bottleneck based on degree betweenness centrality. used reference (RefEx) organs which extracted expressed. Heatmaps ontology term evaluation further elucidate biological functions genes. <b><i>Results:</i></b> 12 (<i>CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1</i>, <i>BNIP3L</i>, <i>PABPC1</i>, <i>YBX3</i>, <i>S100A6</i>) both gene Cytoscape. The variety pathways, including lysosomal function lipid sphingolipid catabolism. Next, we investigated whether systemically expressed or had high organ specificity. Finally, RefEx was analyze levels various tissues. Four genes, <i>FTL, S100A6</i>, highly normal heart tissue. heatmap. Our findings suggest this study, especially lysosome-related (<i>FTL</i> <i>ASAH1</i>), pathogenesis. <b><i>Conclusion:</i></b> Lysosome-related important understand pathophysiology AF-related future studies.

Language: Английский

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Non-coding RNA and arrhythmias: expression, function, and molecular mechanism

EP Europace, Journal Year: 2023, Volume and Issue: 25(4), P. 1296 - 1308

Published: March 7, 2023

Abstract Arrhythmias are a class of cardiac dysfunction characterized by heart rate disturbances and rhythm abnormalities, which associated with substantial morbidity mortality. Due to the limited understanding pathological mechanism, current antiarrhythmic drugs invasive therapies on arrhythmias lack sufficient efficacy always accompanied potential adverse effects. Non-coding RNAs (including microRNAs, long non-coding RNAs, circular other small RNAs) have been demonstrated be involved in occurrence development various diseases including arrhythmias, opens new prospect for exploring mechanism developing therapeutic targets. Therefore, this review, we aimed provide an overview expression ncRNAs their roles arrhythmia’s pathophysiology, arrhythmias. As atrial fibrillation (AF) is most common arrhythmia clinical practice studies mainly focus it, review primarily discussed about AF. It was expected that may basis better mechanistic role facilitate mechanic-based

Language: Английский

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Ferroptosis in cardiovascular diseases: role and mechanism

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 15, 2023

Abstract In multicellular organisms, regulatory cell death is a crucial aspect of growth and development. Ferroptosis, which was postulated roughly ten years ago, mode that differs from apoptosis, autophagy, pyrodeath. This distinct pattern triggered by an imbalance between oxidants antioxidants strongly associated with the metabolism iron, lipids, amino acids, glutathione. A growing body research has implicated ferroptosis in incidence progression many organ traumas degenerative diseases. Recently, gained attention as mechanism underlying initiation development variety cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiomyopathy, arrhythmia, chemotherapy, Corona Virus-2-induced cardiac injury. Pharmacological therapies inhibit have great potential for management disorders. review discusses prevalence mechanisms ferroptosis, effect on immune system, significance therapeutic value regulating heart

Language: Английский

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Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

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

Published: Feb. 7, 2024

Ferroptosis, an iron-dependent form of programmed cell death, introduces a novel perspective on cellular demise. This study investigates the regulatory network exosomal non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, in ferroptosis modulation. The primary goal is to examine pathological roles ferroptosis-related ncRNAs, particularly ischemic reperfusion injuries. research reveals intricate molecular interactions governing interplay between ncRNAs ferroptosis, elucidating their diverse different non-malignant contexts. Attention given impact diseases, cardiac, cerebral, liver, kidney injuries, as well lung, wound, neuronal Beyond theoretical exploration, provides insights into potential therapeutic applications, emphasizing significance mesenchymal stem cells (MSCs)-derived exosomes. Findings underscore pivotal role MSC-derived modulating responses related regulation, introducing cutting-edge dimension. recognition emphasizes importance exosomes crucial mediators with broad implications. Insights unveil promising avenues for targeted interventions, capitalizing providing comprehensive foundation future strategies.

Language: Английский

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