Iron deficiency anaemia is a widespread global nutritional disorder, affecting almost a quarter of the global population and contributing to impaired cognitive development, adverse pregnancy outcomes, and weakened immune function. Despite its prevalence, oral iron supplementation remains problematic due to the poor solubility and low bioavailability of ferric supplements, coupled with the frequently experienced gastrointestinal side effects associated with ferrous iron salt supplements. Hemin, a chloride-ligated ferric analogue of heme, presents a potentially safer alternative. However, its poor solubility at neutral pH limits its practical application in oral supplementation. Here, we aimed to develop a novel formulation for hemin using electrospun polyvinylpyrrolidone (PVP) nanofibres, as a platform to enhance the aqueous solubility of hemin and thereby improve its bioavailability. Hemin at various concentrations was successfully encapsulated within PVP nanofibres. The nanofibres were characterised for their morphology, physicochemical properties, encapsulation efficiency and dissolution properties. Notably, the nanofibres dissolved rapidly in phosphate-buffered saline (pH 7.4), forming hemin-PVP nanoparticles (10-80 nm in diameter) and larger aggregates (200-2000 nm in diameter) that maintained hemin in a soluble form. This approach achieved a total solubilised hemin concentration of 273 µM, representing an approximately 200-fold enhancement in solubility. These findings highlight the potential of electrospun hemin-PVP nanofibres as a promising component of an oral iron supplement, offering enhanced solubility and the potential of improved bioavailability for cellular uptake.

The neuronal ceroid lipofuscinoses (NCLs) are mostly seen as diseases affecting the central nervous system, but there is accumulating evidence that they have co-morbidities outside the brain. One of these co-morbidities is a decline in cardiac function. This is becoming increasingly recognised in teenagers and adolescents with juvenile CLN3, but it may also occur in individuals with other NCLs. The purpose of this review is to summarise the current knowledge of the structural and functional changes found in the hearts of animal models and people diagnosed with NCL. In addition, we present evidence of structural changes that were observed in a systematic comparison of the cardiomyocytes from CLN3^Δex7/8 mice.

The pulmonary vein, which returns oxygenated blood to the left atrium, is ensheathed by a population of unique, myocyte-like cells called pulmonary vein sleeve cells (PVCs). These cells autonomously generate action potentials that propagate into the left atrial chamber and cause arrhythmias resulting in atrial fibrillation; the most common, often sustained, form of cardiac arrhythmia. In mice, PVCs extend along the pulmonary vein into the lungs, and are accessible in a lung slice preparation. We exploited this model to study how aberrant Ca²⁺ signaling alters the ability of PVC networks to follow electrical pacing. Cellular responses were investigated using real-time 2-photon imaging of lung slices loaded with a Ca²⁺-sensitive fluorescent indicator (Ca²⁺ measurements) and phase contrast microscopy (contraction measurements). PVCs displayed global Ca²⁺ signals and coordinated contraction in response to electrical field stimulation (EFS). The effects of EFS relied on both Ca²⁺ influx and Ca²⁺ release, and could be inhibited by nifedipine, ryanodine or caffeine. Moreover, PVCs had a high propensity to show spontaneous Ca²⁺ signals that arose via stochastic activation of ryanodine receptors (RyRs). The ability of electrical pacing to entrain Ca²⁺ signals and contractile responses was dramatically influenced by inherent spontaneous Ca²⁺ activity. In PVCs with relatively low spontaneous Ca²⁺ activity (1.5 Hz), electrical pacing was less effective; PVCs became unpaced, only partially-paced or displayed alternans. Because spontaneous Ca²⁺ activity varied between cells, neighboring PVCs often had different responses to electrical pacing. Our data indicate that the ability of PVCs to respond to electrical stimulation depends on their intrinsic Ca²⁺ cycling properties. Heterogeneous spontaneous Ca²⁺ activity arising from stochastic RyR opening can disengage them from sinus rhythm and lead to autonomous, pro-arrhythmic activity.

Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies would be beneficial. Recently, it has become apparent that epicardial adipose tissue plays an important role in normal and pathological cardiac function, and it is now the focus of considerable research. Epicardial adipose tissue can be studied by imaging of various kinds, and these approaches have yielded much useful information. However, at a molecular level, it is more difficult to study as it is relatively scarce in animal models and, for practical and ethical reasons, not always available in sufficient quantities from patients. What is needed is a robust model system in which the interactions between epicardial adipocytes and cardiac myocytes can be studied, and physiologically relevant manipulations performed. There are drawbacks to conventional culture methods, not least the difficulty of culturing both cardiac myocytes and adipocytes, each of which has special requirements. We discuss the benefits of a three‐dimensional co‐culture model in which in vivo interactions can be replicated.Linked Articles: This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc

Much effort is focussed on understanding the structural and functional changes in the heart that underlie age-dependent deterioration of cardiac performance. Longitudinal studies, using aged animals, have pinpointed changes occurring to the contractile myocytes within the heart. However, whilst longitudinal studies are important, other experimental approaches are being advanced that can recapitulate the phenotypic changes seen during ageing. This study investigated the induction of an ageing cardiomyocyte phenotypic change by incubation of cells with hydroxyurea for several days ex vivo. Hydroxyurea incubation has been demonstrated to phenocopy age- and senescence-induced changes in neurons, but its utility for ageing studies with cardiac cells has not been examined. Incubation of neonatal rat ventricular myocytes with hydroxyurea for up to 7 days replicated specific aspects of cardiac ageing including reduced systolic calcium responses, increased alternans and a lesser ability of the cells to follow electrical pacing. Additional functional and structural changes were observed within the myocytes that pointed to ageing-like remodelling, including lipofuscin granule accumulation, reduced mitochondrial membrane potential, increased production of reactive oxygen species, and altered ultrastructure, such as mitochondria with disrupted cristae and disorganised myofibres. These data highlight the utility of alternative approaches for exploring cellular ageing whilst avoiding the costs and co-morbid factors that can affect longitudinal studies.