Xiaosong Yang

Objective Cardiovascular diseases (CVDs) are major public health problems that threaten the lives and health of individuals. The article has reviewed recent progresses about ferroptosis and ferroptosis-related intervention approaches for the treatment of CVDs and provided more references and strategies for targeting ferroptosis to prevent and treat CVDs. Methods A comprehensive review was conducted using the literature researches. Results and discussion Many ferroptosis-targeted compounds and ferroptosis-related genes may be prospective targets for treating CVDs and our review provides a solid foundation for further studies about the detailed pathological mechanisms of CVDs. Conclusion There are challenges and limitations about the translation of ferroptosis-targeted potential therapies from experimental research to clinical practice. It warrants further exploration to pursure safer and more effective ferroptosis-targeted thereapeutic approaches for CVDs. Graphical Abstract

Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Here we discover that histone methyltransferase suppressor of variegation 4–20 homolog 2 ( Suv420h2) expression parallels that of Ucp1 in brown and beige adipocytes and that Suv420h2 knockdown significantly reduces — whereas Suv420h2 overexpression significantly increases — Ucp1 levels in brown adipocytes. Suv420h2 knockout (H2KO) mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study shows that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 ( 4e-bp1 ) promoter, leading to downregulated expression of 4e-bp1 , a negative regulator of the translation initiation complex. This in turn upregulates PGC1α protein levels, and this upregulation is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.

Evidence from clinical research and animal studies indicates that inflammation is an important factor in the occurrence and development of cardiovascular disease (CVD). Emerging evidence shows that nucleic acids serve as crucial pathogen-associated molecular patterns (PAMPs) or non-infectious damage-associated molecular patterns (DAMPs), are released and then recognized by pattern recognition receptors (PRRs), which activates immunological signaling pathways for host defense. Mechanistically, the released nucleic acids activate cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING) to promote type I interferons (IFNs) production, which play an important regulatory function during the initiation of an innate immune response to various diseases, including CVD. This pathway represents an essential defense regulatory mechanism in an organism’s innate immune system. In this review, we outline the overall profile of cGAS-STING signaling, summarize the latest findings on nucleic acid release and trafficking, and discuss their potential role in CVD. This review also sheds light on potential directions for future investigations on CVD.

Clinical and epidemiological research shows that people with diabetes mellitus frequently experience diabetic cognitive impairment. Schisandrin A (SchA), one of the lignans found in the dried fruit of Schisandra chinensis, has a variety of pharmacological effects on immune system control, apoptosis suppression, anti-oxidation and anti-inflammation. The goal of the current investigation was to clarify the probable neuro-protective effects of SchA against streptozotocin-induced diabetes deficiencies of the spatial learning and memory in rats. The outcomes show that SchA therapy effectively improved impaired glucose tolerance, fasting blood glucose level and serum insulin level in diabetic rats. Additionally, in the Morris water maze test, diabetic rats showed deficits in spatial learning and memory that were ameliorated by SchA treatment. Moreover, giving diabetic rats SchA reduced damage to the hippocampus structure and increased the production of synaptic proteins. Further research revealed that SchA therapy reduced diabetic-induced hippocampus neuron damage and the generation of Aβ, as demonstrated by the upregulated phosphorylation levels of insulin signaling pathway connected proteins and by the decreased expression levels of inflammatory-related factors. Collectively, these results suggested that SchA could improve diabetes-related impairments in spatial learning and memory, presumably by reducing inflammatory responses and regulating the insulin signaling system.

Purpose MicroRNAs (miRNAs) have been reported to play pivotal role in drugs-induced cardiotoxicity act as biomarkes, diagnostic tools and endogenous repressors of gene expression by lowering mRNA stability and interfering with mRNA translation. However, the effect of miRNAs on doxorubicin-induced cardiotoxicity still not clear. In the present study, we identified several key candidate miRNAs involving doxorubicin (DOX)-induced cardiotoxicity in rat myocardial tissues and adult rat cardiomyocytes from the Gene Expression Omnibus (GEO) database via integrated bioinformatics analysis, and the possible effect of miR-143 in the protection of DOX-induced cardiotoxicity by phosphocreatine was subsequently investigated in vivo and in vitro. Methods GSE36239 miRNA expression profiles of DOX-induced cardiotoxicity in rat myocardial tissues and adult rat cardiomyocytes (ARC) were extracted fromGEO datasets. |log₂FC| > 1 and P < 0.05 were set as screening criteria, miRNAs expressed in myocardial tissues or ARC were selected as different expression miRNA (DEMs), and subsequently the key miRNAs were obtained from candidate DEMs between myocardial tissues and ARC with Venny 2.1 software. Target genes of miR-143 were predicted with Targetscan and miRBase in the species of homo sapiens, and candidate genes were obtained with Venny 2.1. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were carried out. Final, the expression and potential role of miR-143 were verified in DOX-induced cardiotoxicity of rat and cardiomyocytes H9c2. Results A total 24 DEMs were captured , including 15 up-regulated and 9 down-regulated genes in rat myocardial tissues and 42 DEMs were discovered, including 13 up-regulated and 29 down-regulated in ARC. Ultimately, 6 DEMs were determined in rat myocardial tissues and ARC by venny 2.1 software. 46 target genes of miR-143, one of the 6 DEMs, were captured from the predict results of Targetscan and miRBase with venny 2.1. The target genes were notably enriched in biological processes (BP) such as cell proliferation and migration. KEGG pathway analysis showed the target genes were enriched in HIF-1 and PI3K-Akt signaling pathway, which closely related to the oxidative stress and cardiomyocytes apoptosis. Further, western blot and RT-PCR results showed DOX-induced oxidative stress down-regulated the expression of miR-143 and Nrf2, SOD and BCL2, and up-regulated Bax and Cleaved caspase 3, while they could been reversed by the intervention of phosphocreatine (PCr) or N-acetyl-L-cystine (NAC) in DOX-induced cardiotoxicity in vivo and in vitro.Conclusion Our data showed that DOX-induced oxidative stress could decrease the expression of miR-143, promote apoptosis of cardiomyocytes, while PCr or NAC mediated antioxidation could reverse the expression down-regulation of miR-143, alleviated apoptosis in DOX-induced cardiotoxicity. Our findings elucidated the regulatory network involving miR-143 in DOX-induced cardiotoxicity, and might unveiled a potential biomarker and molecular mechanisms, which could be helpful to the diagnosis and treatment of DOX-induced cardiotoxicity.