Fetal lung development is a crucial and complex process that lays the groundwork for postnatal respiratory health. However, disruptions in this delicate developmental journey can lead to fetal lung development disorders, impacting neonatal outcomes and potentially influencing health outcomes well into adulthood. Recent research has shed light on the intriguing association between fetal lung development disorders and the development of adult diseases. Understanding these links can provide valuable insights into the developmental origins of health and disease, paving the way for targeted preventive measures and clinical interventions. This review article aims to comprehensively explore the association of fetal lung development disorders with adult diseases. We delve into the stages of fetal lung development, examining key factors influencing fetal lung maturation. Subsequently, we investigate specific fetal lung development disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), and other abnormalities. Furthermore, we explore the potential mechanisms underlying these associations, considering the role of epigenetic modifications, transgenerational effects, and intrauterine environmental factors. Additionally, we examine the epidemiological evidence and clinical findings linking fetal lung development disorders to adult respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other respiratory ailments. This review provides valuable insights for healthcare professionals and researchers, guiding future investigations and shaping strategies for preventive interventions and long-term care.

[This corrects the article DOI: 10.3389/fonc.2023.1093063.].

RNA methylation modifications are closely linked to tumor development, migration, invasion and responses to various therapies. Recent studies have shown notable advancements regarding the roles of RNA methylation in tumor immunotherapy, the tumor microenvironment and metabolic reprogramming. However, research on the association between tumor chemoresistance and N6‑methyladenosine (m6A) methyltransferases in specific cancer types is still scarce. Colorectal cancer (CRC) is among the most common gastrointestinal cancers worldwide. Conventional chemotherapy remains the predominant treatment modality for CRC and chemotherapy resistance is the primary cause of treatment failure. The expression levels of m6A methyltransferases, including methyltransferase‑like 3 (METTL3), METTL14 and METTL16, in CRC tissue samples are associated with patients\' clinical outcomes and chemotherapy efficacy. Natural pharmaceutical ingredients, such as quercetin, have the potential to act as METTL3 inhibitors to combat chemotherapy resistance in patients with CRC. The present review discussed the various roles of different types of key RNA methylation enzymes in the development of CRC, focusing on the mechanisms associated with chemotherapy resistance. The progress in the development of certain inhibitors is also listed. The potential of using natural remedies to develop antitumor medications that target m6A methylation is also outlined.

The mechanisms of immune dysfunction in alcohol-associated liver disease (ALD) have garnered growing research interest in recent times. Alcohol-mediated immune dysfunction has been implicated as a potential cause of ALD-associated microbial infection and inflammatory response. The immune microenvironment of an organism is essentially a complex network of interactions between immune cells, cytokines, extracellular matrix, and other immune-related molecules. This microenvironment is highly adaptive and responsive to environmental cues. Epigenetic reprogramming of the immune microenvironment has recently emerged as a key driver of ALD progression, particularly in the context of endotoxin tolerance and immune disorders. Although epigenetic modifications are known to play an important role in the regulation of the immune microenvironment in ALD, the specific mechanisms and molecular processes by which this regulation is achieved are yet to be fully understood. This paper aims to provide an overview of the current knowledge on the effects of alcohol consumption on epigenetics, with special focus on summarizing the data on the epigenetic regulatory mechanisms involved in the effects of alcohol consumption on the immune microenvironment. In addition, this paper aims to present a review of the epigenetic modifications involved in different forms of ALD. This review is expected to offer new perspectives for the diagnosis, treatment, monitoring, and prognostic assessment of ALD from an epigenetic perspective.

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies, with high incidence and mortality. As the majority of HCC patients are diagnosed at an advanced stage and die of recurrence and metastasis, its pathology and new biomarkers are needed. Circular RNAs (circRNAs) are a large subclass of long non-coding RNAs (lncRNAs) with covalently closed loop structures and abundant, conserved, stable, tissue-specific expression in mammalian cells. CircRNAs exert multiple functions in HCC initiation, growth and progression, serving as promising biomarkers for diagnosis, prognosis and therapeutic targets for this disease. This review briefly describes the biogenesis and biological functions of circRNAs and elucidates the roles of circRNAs in the development and progression of HCC, especially regarding epithelial-mesenchymal transition (EMT), drug resistance and interactions with epigenetic modifications. In addition, this review highlights the implications of circRNAs as potential biomarkers and therapeutic targets for HCC. We hope to provide novel insight into the roles of circRNAs in HCC.

Fruit softening that occurs during fruit ripening and postharvest storage determines the fruit quality, shelf life and commercial value and makes fruits more attractive for seed dispersal. In addition, over-softening results in fruit eventual decay, render fruit susceptible to invasion by opportunistic pathogens. Many studies have been conducted to reveal how fruit softens and how to control softening. However, softening is a complex and delicate life process, including physiological, biochemical and metabolic changes, which are closely related to each other and are affected by environmental conditions such as temperature, humidity and light. In this review, the current knowledge regarding fruit softening mechanisms is summarized from cell wall metabolism (cell wall structure changes and cell-wall-degrading enzymes), plant hormones (ETH, ABA, IAA and BR et al.), transcription factors (MADS-Box, AP2/ERF, NAC, MYB and BZR) and epigenetics (DNA methylation, histone demethylation and histone acetylation) and a diagram of the regulatory relationship between these factors is provided. It will provide reference for the cultivation of anti-softening fruits.

Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD‑1)/programmed death ligand 1 (PD‑L1) axis have achieved marked and durable efficacy in patients with different solid tumors and have improved their survival. However, the presence of primary or acquired resistance to immune checkpoint blockades results in only a small fraction of patients benefiting from the treatment. An increasing number of preclinical studies have reported that PD‑L1 expression in tumor cells is involved in a number of epigenetic changes, including histone modifications, non‑coding RNA regulation and DNA methylation. In addition, multiple epigenetic targeting drugs have been demonstrated to directly or indirectly interfere with PD‑L1 expression in various cancer models. This provides opportunities to better characterize the regulatory mechanisms of PD‑L1 expression and explore novel therapeutic strategies to improve immunosuppressant response rates and overcome drug resistance. The present review focuses on the latest findings and evidence on the epigenetic mechanism regulating PD‑L1 expression and discusses the biological and clinical implications of this regulatory mechanism in solid tumors. A rational combination of epigenetic regulation and PD‑1/PD‑L1 axis blockade may improve the prognosis of patients with solid tumors.

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.
When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Atherosclerosis is a chronic inflammatory disease characterized by extensive remodeling of medium and large-sized arteries. Inward remodeling (=lumen shrinkage) of the vascular walls is the underlying cause for ischemia in target organs. Therefore, inward remodeling can be considered the predominant feature of atherosclerotic pathology. Outward remodeling (=lumen enlargement) is a physiological response compensating for lumen shrinkage caused by neointimal hyperplasia, but as a pathological response to changes in blood flow, outward remodeling leads to substantial arterial wall thinning. Thinned vascular walls are prone to rupture, and subsequent thrombus formation accounts for the majority of acute cardiovascular events. Pathological remodeling is driven by inflammatory cells which induce vascular smooth muscle cells to switch from quiescent to a proliferative and migratory phenotype. After decades of intensive research, the molecular mechanisms of arterial remodeling are starting to unfold. In this mini-review, we summarize the current knowledge of the epigenetic and transcriptional regulation of vascular smooth muscle cell phenotype switching from the contractile to the synthetic phenotype involved in arterial remodeling and discuss potential therapeutic options.

The DNA methyltransferase family contains a conserved set of DNA-modifying enzymatic proteins. They are responsible for epigenetic gene modulation, such as transcriptional silencing, transcription activation, and post-transcriptional modulation. Recent research has revealed that the canonical DNA methyltransferases (DNMTs) biological roles go beyond their traditional functions of establishing and maintaining DNA methylation patterns. Although a complete DNA methylation toolkit is absent in most insect orders, recent evidence indicates the de novo DNA methylation and maintenance function remain conserved. Studies using various molecular approaches provided evidence that DNMTs are multi-functional proteins. However, still in-depth studies on their biological role lack due to the least studied area in insects. Here, we review the DNA methylation toolkit of insects, focusing on recent research on various insect orders, which exhibit DNA methylation at different levels, and for which DNMTs functional studies have become available in recent years. We survey research on the potential roles of DNMTs in the regulation of gene transcription in insect species. DNMTs participate in different physiological processes by interacting with other epigenetic factors. Future studies on insect\'s DNMTs will benefit to understand developmental processes, responses to various stimuli, and adaptability of insects to different environmental conditions.