Kaempferol: Paving the path for advanced treatments in aging-related diseases

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 188, P. 112389 - 112389

Published: March 8, 2024

Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, flavonoid found in several plants, has emerged as promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, pharmacokinetics, highlights its potential therapeutic utility against underpinned by distinctive structure, which confers antioxidative anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) modulates crucial cellular pathways, thereby combating oxidative stress inflammation, hallmarks low toxicity wide margins, demonstrated preclinical clinical studies, further substantiate potential. Compelling evidence supports substantial addressing ARDs through mechanisms, notably anti-inflammatory, antioxidant, anti-apoptotic actions. exhibits versatile neuroprotective effect modulating various proinflammatory signaling including NF-kB, p38MAPK, AKT, β-catenin cascade. Additionally, it hinders formation aggregation beta-amyloid protein regulates brain-derived neurotrophic factors. In terms anticancer potential, kaempferol acts diverse inducing apoptosis, arresting cell cycle at G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, affecting phosphoinositide 3-kinase/protein kinase B pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, conducting trials to translate these findings into applications.

Language: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

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Disrupting pathologic phase transitions in neurodegeneration

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(13)

Published: July 2, 2023

Solid-like protein deposits found in aged and diseased human brains have revealed a relationship between insoluble accumulations the resulting deficits neurologic function. Clinically diverse neurodegenerative diseases, including Alzheimer's disease, Parkinson's frontotemporal lobar degeneration, amyotrophic lateral sclerosis, exhibit unique disease-specific biochemical signatures abnormal depositions that often correlate with disease pathogenesis. Recent evidence indicates many pathologic proteins assemble into liquid-like phases through highly coordinated process of liquid-liquid phase separation. Over last decade, biomolecular transitions emerged as fundamental mechanism cellular organization. Liquid-like condensates organize functionally related biomolecules within cell, neuropathology-associated reside these dynamic structures. Thus, examining enhances our understanding molecular mechanisms mediating toxicity across diseases. This Review explores known contributing to aberrant focusing on tau TDP-43 proteinopathies outlining potential therapeutic strategies regulate events.

Language: Английский

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Regulation and roles of RNA modifications in aging‐related diseases

Aging Cell, Journal Year: 2022, Volume and Issue: 21(7)

Published: June 19, 2022

With the aging of global population, accumulating interest is focused on manipulating fundamental aging-related signaling pathways to delay physiological process and eventually slow or prevent appearance severity multiple diseases. Recently, emerging evidence has shown that RNA modifications, which were historically considered infrastructural features cellular RNAs, are dynamically regulated across most species in cells thereby critically involved major biological processes, including senescence aging. In this review, we summarize current knowledge about modifications provide a catalog different species, mRNAs, miRNAs, lncRNA, tRNAs, rRNAs. Most importantly, focus regulation roles these diseases, neurodegenerative cardiovascular cataracts, osteoporosis, fertility decline. This would be an important step toward better understanding mechanisms facilitating development novel diagnostics therapeutics for

Language: Английский

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Multimodal Omics Approaches to Aging and Age-Related Diseases

Phenomics, Journal Year: 2024, Volume and Issue: 4(1), P. 56 - 71

Published: Feb. 1, 2024

Language: Английский

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Current insights into transcriptional role(s) for the nutraceutical Withania somnifera in inflammation and aging

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: May 3, 2024

The health-beneficial effects of nutraceuticals in various diseases have received enhanced attention recent years. Aging is a continuous process wherein physiological activity an individual declines over time and characterized by indefinite hallmarks which contribute toward aging-related comorbidities include many neurodegenerative diseases, cardiac problems, diabetes, bone-degeneration, cancer. Cellular senescence homeostatic biological that has important function driving aging. Currently, growing body evidence substantiates the connection between epigenetic modifications aging process, along with diseases. These are now being recognized as promising targets for emerging therapeutic interventions. Considering almost all processes modulated RNAs, numerous RNA-binding proteins been found to be linked age-related complexities. studies shed light on ability nutraceutical Withania somnifera (Ashwagandha) influence RNA expression, stability, processing, offering insights into its mechanisms action. By targeting RNA-related pathways, may exhibit ameliorating age-associated molecular changes, gene expression signaling networks. This review summarizes potential role modulating RNA-level changes associated aging, encompassing both vitro vivo studies. Taken together, putative role(s) modulation key RNAs will provide understanding facilitate development preventive strategies employing healthy

Language: Английский

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The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11830 - 11830

Published: Oct. 5, 2022

Metals are common toxic environmental pollutants. Acute or chronic exposure to metal pollutants causes severe adverse health effects in animals and humans, such as developmental retardation, abnormal metabolism, disorders of cardiovascular, neurologic, respiratory, reproductive, urologic systems. Moreover, several metals (arsenic, cadmium, chromium, nickel) classified potent Group I carcinogens cause various types cancer humans. Although the toxicity carcinogenicity well recognized, underlying mechanisms have not been clearly defined. The epitranscriptome includes all kinds chemical modifications forms RNA molecules inside a cell. Recent progresses demonstrating reversible pattern their roles physiology pathogenesis represent breakthrough field biology function study. epitranscriptomic study is now an exciting emerging toxicology research. While few studies conducted so far determine pollutants, they offer novel insights for understanding carcinogenesis. goal this review discuss recent on propose some thoughts future field.

Language: Английский

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Contribution of A-to-I RNA editing, M6A RNA Methylation, and Alternative Splicing to physiological brain aging and neurodegenerative diseases

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 212, P. 111807 - 111807

Published: April 5, 2023

Aging is a physiological and progressive phenomenon in all organisms' life cycle, characterized by the accumulation of degenerative processes triggered several alterations within molecular pathways. These changes compromise cell fate, resulting loss functions tissues throughout body, including brain. Physiological brain aging has been linked to structural functional alterations, as well an increased risk neurodegenerative diseases. Post-transcriptional RNA modifications modulate mRNA coding properties, stability, translatability, expanding capacity genome, are involved cellular processes. Among post-transcriptional modifications, A-to-I editing, m6A Methylation Alternative Splicing play critical role phases neuronal cycle their mechanisms action significantly contribute neurodegeneration. Here we review our current understanding contribution Methylation, process

Language: Английский

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Ashwagandha’s Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes—A Review

Nutrients, Journal Year: 2024, Volume and Issue: 16(15), P. 2481 - 2481

Published: July 31, 2024

, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial effects. This review examines impact Ashwagandha on vascular endothelium, inflammation, lipid metabolism, cardiovascular outcomes. Studies extracts exhibit an anti-angiogenic effect by inhibiting endothelial growth factor (VEGF)-induced capillary sprouting formation lowering mean density microvessels. Furthermore, results numerous highlight anti-inflammatory role extract, action plant causes a decrease in expression pro-inflammatory cytokines. Interestingly, withanolides, present root, ability inhibit differentiation preadipocytes into adipocytes. Research also proved

Language: Английский

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Analysis of human brain RNA-seq data reveals combined effects of 4 types of RNA modifications and 18 types of programmed cell death on Alzheimer’s disease

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 3, 2025

Language: Английский

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