The sirtuin family in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 29, 2022

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, involved numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles members SIRT family health disease conditions. Notably, this protein plays a variety important cellular biology such as inflammation, metabolism, oxidative stress, apoptosis, etc., thus, it is considered potential therapeutic target for different kinds pathologies including cancer, cardiovascular disease, respiratory other Moreover, identification modulators exploring functions these prompted increased efforts discover new small molecules, which can modify activity. Furthermore, several randomized controlled trials indicated that interventions might affect expression human samples, supplementation diverse impact on physiological function participants. In review, we introduce history structure family, discuss molecular mechanisms elaborate regulatory SIRTs summarize inhibitors activators, review related clinical studies.

Language: Английский

---

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

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

Published: March 2, 2023

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism others. The term ‘epigenetics’ was firstly proposed 1942 with the development technologies, exploration epigenetics made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, noncoding RNA (ncRNA), which exert different effects on diseases. Genetic non-genetic factors, ageing, diet, exercise, interact jointly affect formation phenotype. Understanding could be applied diagnosing treating diseases clinic, biomarkers, drugs, editing. In this review, we introduce brief history well milestone events since proposal ‘epigenetics’. Moreover, summarise research methods general mechanisms modulation. Furthermore, interaction between genetic or factors. Finally, clinical trials applications

Language: Английский

---

Targeting epigenetic regulators to overcome drug resistance in cancers

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

Published: Feb. 17, 2023

Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic mechanisms, DNA methylation, histone modification, non-coding RNA have been well studied. Increasing evidence has shown that aberrant regulations contribute to tumor resistance. Therefore, targeting regulators represents an effective strategy reverse drug In this review, we summarize roles addition, as essential factors modifications, demethylases mediate or genomic modifications. Herein, comprehensively describe functions demethylase family including lysine-specific family, Jumonji C-domain-containing arginine fully discuss their regulatory mechanisms related therapeutic strategies, small-molecule inhibitors small interfering overcome resistance, are also described.

Language: Английский

---

Hallmarks of cardiovascular ageing

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(11), P. 754 - 777

Published: May 16, 2023

Language: Английский

---

mRNA vaccines in disease prevention and treatment

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

Published: Sept. 20, 2023

Abstract mRNA vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases, thanks largely although not totally to their extraordinary performance recent years against worldwide plague COVID-19. The huge superiority regarding efficacy, safety, large-scale manufacture encourages pharmaceutical industries biotechnology companies expand application a diverse array despite nonnegligible problems design, fabrication, mode administration. This review delves into technical underpinnings vaccines, covering synthesis, delivery, adjuvant technologies. Moreover, this presents systematic retrospective analysis logical well-organized manner, shedding light on representative employed various diseases. scope extends across infectious cancers, immunological tissue damages, rare showcasing versatility potential therapeutic areas. Furthermore, engages prospective discussion current challenge direction for advancement utilization vaccines. Overall, comprehensive serves valuable resource researchers, clinicians, industry professionals, providing understanding aspects, historical context, future prospects fight

Language: Английский

---

Vascular remodelling in cardiovascular diseases: hypertension, oxidation, and inflammation

Clinical Science, Journal Year: 2024, Volume and Issue: 138(13), P. 817 - 850

Published: June 26, 2024

Abstract Optimal vascular structure and function are essential for maintaining the physiological functions of cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular molecular composition. These result from multiple risk factors may be compensatory adaptations to sustain blood function. They occur diverse pathologies, hypertension heart failure atherosclerosis. Dynamic endothelium, fibroblasts, smooth muscle cells, pericytes or other wall cells underlie remodelling. In addition, immune macrophages lymphocytes, infiltrate vessels initiate inflammatory signalling. contribute a dynamic interplay between cell proliferation, apoptosis, migration, inflammation, extracellular matrix reorganisation, all critical mechanisms Molecular pathways underlying these processes include growth (e.g., endothelial factor platelet-derived factor), cytokines interleukin-1β tumour necrosis factor-α), reactive oxygen species, signalling pathways, such as Rho/ROCK, MAPK, TGF-β/Smad, related nitric oxide superoxide biology. MicroRNAs long noncoding RNAs crucial epigenetic regulators gene expression We evaluate potential therapeutic targeting clinical translational perspective. summary, remodelling, coordinated modification function, is disease pathology.

Language: Английский

---

Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 16, 2024

Abstract Histone post-translational modifications (HPTMs), as one of the core mechanisms epigenetic regulation, are garnering increasing attention due to their close association with onset and progression diseases potential targeted therapeutic agents. Advances in high-throughput molecular tools abundance bioinformatics data have led discovery novel HPTMs which similarly affect gene expression, metabolism, chromatin structure. Furthermore, a growing body research has demonstrated that histone also play crucial roles development various diseases, including cancers, cardiovascular infectious psychiatric disorders, reproductive system diseases. This review defines nine modifications: lactylation, citrullination, crotonylation, succinylation, SUMOylation, propionylation, butyrylation, 2-hydroxyisobutyrylation, 2-hydroxybutyrylation. It comprehensively introduces modification processes these HPTMs, transcription, replication, DNA repair recombination, structure, well involvement promoting occurrence clinical applications targets biomarkers. Moreover, this provides detailed overview HPTM inhibitors targeting emerging strategies treatment multiple while offering insights into future prospects challenges. Additionally, we briefly introduce techniques field research.

Language: Английский

---

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(7), P. 3027 - 3048

Published: March 12, 2024

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis increased in the endothelium atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated lactate, can regulate gene expression and participate disease regulation. However, whether histone lactylation involved atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced increasing lactate-dependent H3 lysine 18 (H3K18la) vitro vivo, as well atherosclerotic patients' arteries. Mechanistically, chaperone ASF1A was first identified cofactor P300, which precisely regulated enrichment H3K18la at promoter SNAI1, thereby activating SNAI1 transcription promoting EndMT. We found deletion inhibited EndMT improved endothelial dysfunction. Functional analysis based on ApoeKOAsf1aECKO mice model confirmed involvement endothelium-specific deficiency alleviated development. Inhibition pharmacologic inhibition advanced PROTAC attenuated H3K18la, transcription, This study illustrates precise crosstalk between metabolism epigenetics via P300/ASF1A molecular complex during atherogenesis, provides emerging therapies for

Language: Английский

---

Metabolic and epigenetic regulation of macrophage polarization in atherosclerosis: molecular mechanisms and targeted therapies

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107588 - 107588

Published: Jan. 7, 2025

Atherosclerosis, a multifactorial progressive inflammatory disease, is the common pathology underlying cardiovascular and cerebrovascular diseases. The macrophage plasticity involved in pathogenesis of atherosclerosis. With advance metabolomics epigenetics, metabolites/metabolic epigenetic modification such as DNA methylation, histone noncoding RNA, play crucial role polarization progression Herein, we provide comprehensive review essential metabolic regulation, well crosstalk between two regulating We also highlight potential therapeutic strategies via modifications for atherosclerosis, offer recommendations to our knowledge roles metabolic-epigenetic context Fundamental studies that elucidate mechanisms by which regulation influence atherosclerosis will pave way novel approaches.

Language: Английский

---

Blockade of IL-6 signaling alleviates atherosclerosis in Tet2-deficient clonal hematopoiesis

Nature Cardiovascular Research, Journal Year: 2023, Volume and Issue: 2(6), P. 572 - 586

Published: June 8, 2023

Language: Английский

---