Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 10, 2023

Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt

Language: Английский

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Novel Insights into the Molecular Mechanisms of Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13434 - 13434

Published: Aug. 30, 2023

Atherosclerosis is one of the most fatal diseases in world. The associated thickening arterial wall and its background consequences make it a very composite disease entity with many mechanisms that lead to creation. It an active process, scientists from various branches are engaged research, including molecular biologists, cardiologists, immunologists. This review summarizes available information on pathophysiological implications atherosclerosis, focusing endothelium dysfunction, inflammatory factors, aging, uric acid, vitamin D, miRNA expression as recent evidence interactions cellular elements. Analyzing new discoveries for underlying causes this condition assists general research improve understanding mechanism pathophysiology thus prevention cardiovascular diseases.

Language: Английский

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Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 21, 2024

Hypertension, a multifaceted cardiovascular disorder influenced by genetic, epigenetic, and environmental factors, poses significant risk for the development of coronary artery disease (CAD) in individuals with type 2 diabetes mellitus (T2DM). Epigenetic alterations, particularly histone modifications, DNA methylation, microRNAs, play pivotal role unraveling complex molecular underpinnings blood pressure regulation. This review emphasizes crucial interplay between epigenetic attributes hypertension, shedding light on prominence both globally at gene-specific level, essential hypertension. Additionally, including acetylation emerge as markers linked to Furthermore, microRNAs exert regulatory influence homeostasis, targeting key genes within aldosterone renin-angiotensin pathways. Understanding intricate crosstalk genetics epigenetics hypertension is pertinent context its interaction T2DM, where serves notable factor CAD. These findings not only contribute comprehensive elucidation but also offer promising avenues innovative strategies prevention treatment complications, especially T2DM.

Language: Английский

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Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 378 - 378

Published: March 5, 2025

Endothelial dysfunction is the main initiating factor in atherosclerosis. Through mechanotransduction, shear stress regulates endothelial cell function both homeostatic and diseased states. Accumulating evidence reveals that epigenetic changes play critical roles etiology of cardiovascular diseases, including The metabolic regulation epigenetics has emerged as an important control gene expression states, but to best our knowledge, this connection remains largely unexplored In review, we (1) summarize how (or flow) (dys)function; (2) explore alterations occur endothelium response disturbed flow; (3) review metabolism under different conditions; (4) suggest mechanisms which may link altered epigenome by modulations metabolite availability. We believe plays role reprogramming could pave way for novel metabolism-based therapeutic strategies.

Language: Английский

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Epigenetic regulation of stress

Progress in brain research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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DNA methylation patterns and predictive models for metabolic disease risk in offspring of gestational diabetes mellitus

Diabetology & Metabolic Syndrome, Journal Year: 2025, Volume and Issue: 17(1)

Published: May 2, 2025

Gestational diabetes mellitus (GDM) is a common pregnancy complication with far-reaching implications for maternal and offspring health, strongly tied to epigenetic modifications, particularly DNA methylation. However, the precise molecular mechanisms by which GDM increases long-term metabolic disease risk in remain insufficiently understood. We integrated multiple publicly available whole-genome methylation datasets focusing on neonates born mothers GDM. Using differentially methylated positions (DMPs) identified these datasets, we developed machine learning model predict GDM-associated changes, then validated its performance clinical target cohort. In public DMPs corresponding genes involved glucose homeostasis insulin sensitivity, marked enrichment signaling, AMPK activation, adipocytokine signaling pathways. The predictive exhibited strong data (AUC = 0.89) moderate cohort 0.82). Although CpG sites PPARG INS displayed similar trends both small validation did not yield statistically significant differences. By integrating robust targeted cohort, this study provides comprehensive profile of GDM-exposed offspring. Owing limited sample size lack statistical significance, definitive conclusions cannot yet be drawn; however, observed directional consistency suggests promising avenues future research. Larger more diverse cohorts are warranted confirm preliminary findings, clarify their implications, enhance early assessment disorders children mothers.

Language: Английский

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Epigenetic Regulation in Myocardial Fibroblasts and Its Impact on Cardiovascular Diseases

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(10), P. 1353 - 1353

Published: Oct. 10, 2024

Myocardial fibroblasts play a crucial role in heart structure and function. In recent years, significant progress has been made understanding the epigenetic regulation of myocardial fibroblasts, which is essential for cardiac development, homeostasis, disease progression. healthy hearts, (CFs) synthesizing extracellular matrix (ECM) when dormant state. However, under pathological environmental stress, CFs transform into activated known as myofibroblasts. These myofibroblasts produce an excess ECM, promotes fibrosis. Although multiple molecular mechanisms are associated with CF activation dysfunction, emerging evidence highlights involvement this process. Epigenetics refers to heritable changes gene expression that occur without altering DNA sequence. have emerged key regulators fibroblast This review focuses on advancements emphasizes impact modifications activation. Furthermore, we present perspectives prospects future research their implications fibroblasts.

Language: Английский

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Biological disturbance of MiR-425 and its application prospects in cardiovascular diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: May 9, 2025

MiR-425 is a biological molecule that has potential applications in cardiovascular diseases. It can regulate functions by combining with LncRNAs, binding proteins, and changing the differentiation of immune cells. also role as biomarker disease. In diseases, it clinical significance reducing inflammation heart repair, inducing angiogenesis, improving prediction atherosclerosis, cardiac fibrosis, regulating atrial natriuretic peptide to affect function. Target gene KEGG enrichment analysis are mentioned.

Language: Английский

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The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3866 - 3866

Published: March 30, 2024

For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications childbirth. Thus, many females did not reach age menopause (45–50 years age) and it is mainly past several hundred that has been extended >75 primarily public health advances, medical interventions, antibiotics, nutrition. Therefore, underlying biological mechanisms responsible disease risk following must have evolved during complex processes leading Homo sapiens serve functions pre-menopausal state. Furthermore, as a primary function survival species effective reproduction, likely most advantages having such post-menopausal risks relate reproduction ability address environmental stresses. This opinion/perspective will be discussed context how could enhance with improved offspring, perhaps why are preserved. Not all exhibit this set diseases, those who do develop diseases conditions. The state operate unified complex, but independent variables, potential some overlap. there would heterogeneity if factors essential reproductive also concept sets reversible epigenetic changes associated puberty, pregnancy, lactation offered explain observations regarding distribution conditions their roles reproduction. While involvement an system dynamic “modification-demodification-remodification” paradigm contributing hypothesis at point, validation lead better understanding commonalities may future interventions control after menopause.

Language: Английский

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“Bet hedging” against climate change in developing and adult animals: roles for stochastic gene expression, phenotypic plasticity, epigenetic inheritance and adaptation

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 6, 2023

Animals from embryos to adults experiencing stress climate change have numerous mechanisms available for enhancing their long-term survival. In this review we consider these options, and how viable they are in a world increasingly extreme weather associated with change. A deeply understood mechanism involves natural selection, leading evolution of new adaptations that help cope stochastic events While potentially effective at staving off environmental challenges, such typically occur very slowly incrementally over evolutionary time. Consequently, adaptation through selection is most instances regarded as too slow aid survival rapidly changing environments, especially when considering the nature Alternative operating much shorter time frame than involve rapid creation alternate phenotypes within life cycle or few generations. Stochastic gene expression creates multiple same genotype even absence cues. contrast, other phenotype externally driven by clues include well-understood developmental phenotypic plasticity (variation, flexibility), which can enable rapid, within-generation changes. Increasingly appreciated epigenetic influences during development changes also immediately be widespread throughout population, rather confined individuals case favorable mutations. Such epigenetically-induced arise response stressors generation across generations just “sunsetted” stressor dissipates, providing some capability withstand emerging Importantly, resulting not necessarily mutually exclusive, allowing classic “bet hedging”. Thus, appearance single population provides optimal future environment. This enhances Finally, end recommendations physiological experiments, recommending particular experiments investigating flexibility adopt more realistic protocols reflect weather.

Language: Английский

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