BACKGROUND: Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during cardiac remodeling. METHODS: NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation and sequencing, thiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), and ribosome sequencing (Ribo-seq) were employed to elucidate the role of ac4C-modified posttranscriptional regulation in cardiac remodeling. Additionally, functional experiments involving the overexpression or knockdown of NAT10 were conducted in mice models challenged with Ang II (angiotensin II) and transverse aortic constriction. RESULTS: NAT10 expression and RNA ac4C levels were increased in in vitro and in vivo cardiac remodeling models, as well as in patients with cardiac hypertrophy. Silencing and inhibiting NAT10 attenuated Ang II-induced cardiomyocyte hypertrophy and cardiofibroblast activation. Next-generation sequencing revealed ac4C changes in both mice and humans with cardiac hypertrophy were associated with changes in global mRNA abundance, stability, and translation efficiency. Mechanistically, NAT10 could enhance the stability and translation efficiency of CD47 and ROCK2 transcripts by upregulating their mRNA ac4C modification, thereby resulting in an increase in their protein expression during cardiac remodeling. Furthermore, the administration of Remodelin, a NAT10 inhibitor, has been shown to prevent cardiac functional impairments in mice subjected to transverse aortic constriction by suppressing cardiac fibrosis, hypertrophy, and inflammatory responses, while also regulating the expression levels of CD47 and ROCK2 (Rho associated coiled-coil containing protein kinase 2). CONCLUSIONS: Therefore, our data suggest that modulating epitranscriptomic processes, such as ac4C acetylation through NAT10, may be a promising therapeutic target against cardiac remodeling.

Retinopathy of prematurity (ROP), which is characterized by retinal neovascularization (RNV), is a major cause of neonatal blindness. The primary treatment for ROP is anti-vascular endothelial growth factor (VEGF) therapy, which is costly and can rapidly lead to desensitization. Celastrol, a bioactive compound extracted from Tripterygium wilfordii Hook F. (“Thunder of God Vine”), has been shown to exert anticancer and anti-inflammatory effects. However, whether celastrol has antiangiogenic activity and can suppress inflammation to inhibit ROP progression is unclear. This was investigated in the present study in vitro as well as in vivo using a mouse model of oxygen-induced retinopathy (OIR). Our results showed that celastrol treatment reduced neovascular and avascular areas in the retina and inhibited microglia activation and inflammation in OIR mice. Celastrol also inhibited proliferation, migration, and tube formation in cultured human retinal microvascular endothelial cells, and reversed the activation of the microRNA (miR)-17-5p/hypoxia-inducible factor (HIF)-1α/VEGF pathway in the retina of OIR mice. These results indicate that celastrol alleviates pathologic RNV in the retina by protecting neuroglia and suppressing inflammation via inhibition of miR-17-5p/HIF-1α/VEGF signaling, and thus has therapeutic potential for the prevention and treatment of ROP. Abbreviations: BSA, bovine serum albumin; COX2, cyclooxygenase 2; ECM, endothelial cell medium; FBS, fetal bovine serum; HDAC, histone deacetylase; HIF-1, hypoxia-inducible factor 1; HRMEC, human retinal microvascular endothelial cell; Hsp70, heat shock protein; IB4, isolectin B4; ICAM-1, intercellular adhesion molecule 1; IL-1β/6, interleukin 1 beta/6; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein 1; miRNA, microRNA; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-kappa B; OIR, oxygen-induced retinopathy; PBS, phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; PI3K, phosphatidylinositol-3-kinase; qRT-PCR, quantitative real-time PCR; RNV, retinal neovascularization; ROP, retinopathy of prematurity; RTCA, real-time cell analyzer; RVO, retinal vaso-obliteration; TNF-α, tumor necrosis factor alpha; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.

Aims: Epigenetics has significantly evolved and emerged as important players in the pathogenesis of neurodegenerative diseases. However, a scientometric synthesis of such changes over time is currently lacking.Methods: We conducted a comprehensive search of the Web of Science Core Collection from inception until November 5, 2022, using appropriate keywords. Our primary objective was to employ scientometric analysis to depict changes in keywords over time and to assess the structure and credibility of clusters. Additionally, we examined the network of research (countries, institutions, and authors) using CiteSpace and VOSviewer.Results: We identified 25 clusters with well-structured networks (Q = 0.82) and highly credible clustering (S = 0.91) from 16,181 articles published between 1999 and 2022. Our findings are as follows: (a) the literature and research interest concerning the epigenetics of neurodegenerative diseases are continuously growing; (b) the three most productive countries are the USA, China, and Germany; (c) international collaborative relationships exist, alongside small, isolated collaboration networks of individual institutions.Conclusion: The number and impact of global publications on the epigenetics of neurodegenerative diseases have expanded rapidly over the past 20 years. This review provides valuable guidelines for researchers interested in neurodegenerative diseases research.

Background: Cardiovascular disease (CVD) remains a major health killer worldwide, and the role of epigenetic regulation in CVD has been widely studied in recent decades. Herein, we perform a bibliometric study to decipher how research topics in this field have evolved during the past 2 decades. Results: Publications on epigenetics in CVD produced during the period 2000–2022 were retrieved from the Web of Science Core Collection (WoSCC). We utilized Bibliometrix to build a science map of the publications and applied VOSviewer and CiteSpace to assess co-authorship, co-citation, co-occurrence, and bibliographic coupling. In total, 27,762 publications were included for bibliometric analysis. The yearly amount of publications experienced exponential growth. The top 3 most influential countries were China, the United States, and Germany, while the most cited institutions were Nanjing Medical University, Harbin Medical University, and Shanghai Jiao Tong University. Four major research trends were identified: (a) epigenetic mechanisms of CVD; (b) epigenetics-based therapies for CVD; (c) epigenetic profiles of specific CVDs; and (d) epigenetic biomarkers for CVD diagnosis/prediction. The latest and most important research topics, including “nlrp3 inflammasome”, “myocardial injury”, and “reperfusion injury”, were determined by detecting citation bursts of co-occurring keywords. The most cited reference was a review of the current knowledge about how miRNAs recognize target genes and modulate their expression and function. Conclusions: The number and impact of global publications on epigenetics in CVD have expanded rapidly over time. Our findings may provide insights into the epigenetic basis of CVD pathogenesis, diagnosis, and treatment.

Context: The results of detection assays for the same specimen are usually quite different in different laboratories or when tested with different detection systems.Objective: This study was designed to investigate the value of applying sigma metrics derived from different standards for allowable total error (TEa) in evaluating the analytical quality of tumor marker assays.Methods: Assays were evaluated for these six tumor markers: total prostate‐specific antigen (tPSA), carcinoembryonic antigen (CEA), alpha‐fetoprotein (AFP), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 153 (CA153). Sigma values were calculated for two concentrations of quality control products to assess differences in quality of tumor marker assays. Improvement measures were recommended according to the quality goal index, and appropriate quality control rules were selected according to the sigma value.Results: The sigma value was highest using the higher biological variation‐derived “appropriate” TEa standard: it was sigma ≥6 or higher in 16.7% of tumor markers. Sigma was below 6 for all tumor markers using the other three TEa. CEA, AFP, CA199, CA125, and CA153 required improved precision. The marker tPSA required improve precision and accuracy. According to sigma values by using China's external quality assessment standards, CEA, AFP, CA125, and CA153 require 1_3s/2_2s/R_4s/4_1s multirules for internal quality control, CA199 requires use of 1_3s/2_2s/R_4s/4_1s/8_x multirules, and tPSA requires maximum quality control rules.Conclusion: Six Sigma is useful for evaluating performance of tumor markers assays and has important application value in the quality control of these assays.

Background: Cardiac fibrosis is a hallmark of various end-stage cardiovascular diseases (CVDs) and a potent contributor to adverse cardiovascular events. During the past decades, extensive publications on this topic have emerged worldwide, while a bibliometric analysis of the current status and research trends is still lacking.Methods: We retrieved relevant 13,446 articles on cardiac fibrosis published between 1989 and 2022 from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks.Results: We identified four major research trends: (1) pathophysiological mechanisms; (2) treatment strategies; (3) cardiac fibrosis and related CVDs; (4) early diagnostic methods. The most recent and important research themes such as left ventricular dysfunction, transgenic mice, and matrix metalloproteinase were generated by burst analysis of keywords. The reference with the most citations was a contemporary review summarizing the role of cardiac fibroblasts and fibrogenic molecules in promoting fibrogenesis following myocardial injury. The top 3 most influential countries were the United States, China, and Germany, while the most cited institution was Shanghai Jiao Tong University, followed by Nanjing Medical University and Capital Medical University.Conclusions: The number and impact of global publications on cardiac fibrosis has expanded rapidly over the past 30 years. These results are in favor of paving the way for future research on the pathogenesis, diagnosis, and treatment of cardiac fibrosis.