Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, as it affects up to 30 % of adults in Western countries. Moreover, NAFLD is also considered an independent risk factor for cardiovascular diseases. Insulin resistance and inflammation have been identified as key factors in the pathophysiology of NAFLD. Although the mechanisms associated with the development of NAFLD remain to be fully elucidated, a complex interaction between adipokines and cytokines appear to play a crucial role in the development of this condition. Adiponectin is the most common adipokine known to be inversely linked with insulin resistance, lipid accumulation, inflammation and NAFLD. Consequently, the focus has been on the use of new therapies that may enhance hepatic expression of adiponectin downstream targets or increase the serum levels of adiponectin in the treatment NAFLD. While currently used therapies show limited efficacy in this aspect, accumulating evidence suggest that various dietary polyphenols may stimulate adiponectin levels, offering potential protection against the development of insulin resistance, inflammation and NAFLD as well as associated conditions of metabolic syndrome. As such, this review provides a better understanding of the role polyphenols play in modulating adiponectin signaling to protect against NAFLD. A brief discussion on the regulation of adiponectin during disease pathophysiology is also covered to underscore the potential protective effects of polyphenols against NAFLD. Some of the prominent polyphenols described in the manuscript include aspalathin, berberine, catechins, chlorogenic acid, curcumin, genistein, piperine, quercetin, and resveratrol.

A breakthrough in oncology research was the discovery of doxorubicin (Dox) in the 1960’s. Unlike other chemotherapy drugs, Dox was determined to have a greater therapeutic index. Since its discovery, Dox has, in part, contributed to the 5–10-year survival increase in cancer patient outcomes. Unfortunately, despite its efficacy, both in adult and pediatric cancers, the clinical significance of Dox is tainted by its adverse side effects, which usually manifest as cardiotoxicity. The issue stems from Dox’s lack of specificity which prevents it from accurately distinguishing between cancer cells and healthy cell lines, like cardiomyocytes. In addition, the high binding affinity of Dox to topoisomerases, which are abundantly found in cancer and cardiac cells in different isoforms, potentiates DNA damage. In both cell lines, Dox induces cytotoxicity by stimulating the production of pro-oxidants whilst inhibiting antioxidant enzymatic activity. Given that the cardiac muscle has an inherently low antioxidant capacity makes it susceptible to oxidative damage thereby, allowing the accumulation of Dox within the myocardium. Subsequently, Dox drives the activation of cell death pathways, such as ferroptosis, necroptosis and apoptosis by triggering numerous cellular responses that have been implicated in diseases. To date, the exact mechanism by which Dox induces the cardiotoxicity remains an aspect of much interest in cardio-oncology research. Hence, the current review summarizes the proposed mechanisms that are associated with the onset and progression of DIC.

Although numerous studies have demonstrated the biological and multifaceted nature of dimethyl sulfoxide (DMSO) across different in vitro models, the direct effect of “non-toxic” low DMSO doses on cardiac and cancer cells has not been clearly explored. In the present study, H9c2 cardiomyoblasts and MCF-7 breast cancer cells were treated with varying concentrations of DMSO (0.001–3.7%) for 6 days. Here, DMSO doses < 0.5% enhanced the cardiomyoblasts respiratory control ratio and cellular viability relative to the control cells. However, 3.7% DMSO exposure enhanced the rate of apoptosis, which was driven by mitochondrial dysfunction and oxidative stress in the cardiomyoblasts. Additionally, in the cancer cells, DMSO (≥0.009) led to a reduction in the cell’s maximal respiratory capacity and ATP-linked respiration and turnover. As a result, the reduced bioenergetics accelerated ROS production whilst increasing early and late apoptosis in these cells. Surprisingly, 0.001% DMSO exposure led to a significant increase in the cancer cells proliferative activity. The latter, therefore, suggests that the use of DMSO, as a solvent or therapeutic compound, should be applied with caution in the cancer cells. Paradoxically, in the cardiomyoblasts, the application of DMSO (≤0.5%) demonstrated no cytotoxic or overt therapeutic benefits.

Obesity rates continue to rise in an unprecedented manner in what could be the most rapid population‐scale shift in human phenotype ever to occur. Increased consumption of unhealthy, calorie‐dense foods, coupled with sedentary lifestyles, is the main factor contributing to a positive energy balance and the development of obesity. Leptin and insulin are key hormones implicated in pathogenesis of this disorder and are crucial for controlling whole‐body energy homeostasis. Their respective function is mediated by the counterbalance of anorexigenic and orexigenic neurons located within the hypothalamic arcuate nucleus. Dysregulation of leptin and insulin signaling pathways within this brain region may contribute not only to the development of obesity, but also systemically affect the peripheral organs, thereby manifesting as metabolic diseases. Although the exact mechanisms detailing how these hypothalamic nuclei contribute to disease pathology are still unclear, increasing evidence suggests that altered DNA methylation may be involved. This review evaluates animal studies that have demonstrated diet‐induced DNA methylation changes in genes that regulate energy homeostasis within the arcuate nucleus, and elucidates possible mechanisms causing hypothalamic leptin and insulin resistance leading to the development of obesity and metabolic diseases.

Non-communicable diseases (NCDs) are the leading cause of death worldwide, with cardiovascular disease (CVD) accounting for half of all NCD-related deaths. The biological onset of CVD may occur long before the development of clinical symptoms, hence the urgent need to understand the molecular alterations underpinning CVD, which would facilitate intervention strategies to prevent or delay the onset of the disease. There is evidence to suggest that CVD develops through a complex interplay between genetic, lifestyle, and environmental factors. Epigenetic modifications, including DNA methylation, serve as proxies linking genetics and the environment to phenotypes and diseases. In the past decade, a growing list of studies has implicated DNA methylation in the early events of CVD pathogenesis. In this regard, screening for these epigenetic marks in asymptomatic individuals may assist in the early detection of CVD and serve to predict the response to therapeutic interventions. This review discusses the current literature on the relationship between blood-based DNA methylation alterations and CVD in humans. We highlight a set of differentially methylated genes that show promise as candidates for diagnostic and prognostic CVD biomarkers, which should be prioritized and replicated in future studies across additional populations. Finally, we discuss key limitations in DNA methylation studies, including genetic diversity, interpatient variability, cellular heterogeneity, study confounders, different methodological approaches used to isolate and measure DNA methylation, sample sizes, and cross-sectional study design.

Chronic hyperglycaemia is a major risk factor for diabetes-induced cardiovascular dysfunction. In a hyperglycaemic state, excess production of reactive oxygen species (ROS), coupled with decreased levels of glutathione, contribute to increased lipid peroxidation and subsequent myocardial apoptosis. N-acetylcysteine (NAC) is a thiol-containing antioxidant known to protect against hyperglycaemic-induced oxidative stress by promoting the production of glutathione. While the role of NAC against oxidative stress-related cardiac dysfunction has been documented, to date data is lacking on its beneficial effect when used with glucose lowering therapies, such as metformin (MET). Thus, the aim of the study was to better understand the cardioprotective effect of NAC plus MET against hyperglycaemia-induced cardiac damage in an H9c2 cardiomyoblast model. H9c2 cardiomyoblasts were exposed to chronic high glucose concentrations for 24 h. Thereafter, cells were treated with MET, NAC or a combination of MET and NAC for an additional 24 h. The combination treatment mitigated high glucose-induced oxidative stress by improving metabolic activity i.e. ATP activity, glucose uptake (GU) and reducing lipid accumulation. The combination treatment was as effective as MET in diminishing oxidative stress, lipid peroxidation and apoptosis. We observed that the combination treatment prevented hyperglycaemic-induced cardiac damage by increasing GLUT4 expression and mitigating lipid accumulation via phosphorylation of both AMPK and AKT, while decreasing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), as well as protein kinase C (PKC), a known activator of insulin receptor substrate-1 (IRS-1), via phosphorylation at Ser307. On this basis, the current results support the notion that the combination of NAC and MET can shield the diabetic heart against impaired glucose utilization and therefore its long-term protective effect warrants further investigation.