Consumption of flavonoid-rich nutraceuticals has been associated with a reduction in coronary events. The present study analyzed the effects of cocoa flavonols on myocardial injury following acute coronary ischemia-reperfusion (I/R). A commercially available cocoa extract was identified by chromatographic mass spectrometry. Nineteen different phenolic compounds were identified and 250 mg of flavan-3-ols (procyanidin) were isolated in 1 g of extract. Oral administration of cocoa extract in incremental doses from 5 mg/kg up to 25 mg/kg daily for 15 days in Sprague Dawley rats (n = 30) produced a corresponding increase of blood serum polyphenols and become constant after 15 mg/kg. Consequently, the selected dose (15 mg/kg) of cocoa extract was administered orally daily for 15 days in a treated group (n = 10) and an untreated group served as control (n = 10). Both groups underwent surgical occlusion of the left anterior descending coronary artery and reperfusion. Cocoa extract treatment significantly reversed membrane peroxidation, nitro-oxidative stress, and decreased inflammatory markers (IL-6 and NF-kB) caused by myocardial I/R injury and enhanced activation of both p-Akt and p-Erk1/2. Daily administration of cocoa extract in rats is protective against myocardial I/R injury and attenuate nitro-oxidative stress, inflammation, and mitigates myocardial apoptosis.

Nuclear receptors (NRs), are a wide family of ligand-regulated transcription factors sharing a common modular structure composed by an N-terminal domain and a ligand-binding domain connected by a short hinge linker to a DNA-binding domain. NRs are involved in many physiological processes, including metabolism, reproduction and development. Most of them respond to small lipophilic ligands, such as steroids, retinoids, and phospholipids, which act as conformational switches. Some NRs are still “orphan” and the search for their ligands is still ongoing. Upon DNA binding, NRs can act both as transcriptional activators or repressors of their target genes. Theoretically, the possibility to modulate NRs activity with small molecules makes them ideal therapeutic targets, although the complexity of their signaling makes drug design challenging. In this review, we discuss the role of NRs in erythropoiesis, in both homeostatic and stress conditions. This knowledge is important in view of modulating red blood cells production in disease conditions, such as anemias, and for the expansion of erythroid cells in culture for research purposes and for reaching the long-term goal of cultured blood for transfusion.

progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery, REP+ cells were observed in the intimal 24 hours post-operation, which significantly enhanced neointimal lesions at 2 weeks. This increased neointimal lesion was rescued by pre-treatment of Sca-1+ cells with leptin antagonist CYT-566. In addition, when wild-type Sca-1+ progenitor cells were delivered to the adventitia of the injured artery in leptin receptor deficient mice, a significant increased neointimal formation was observed at 2 weeks, indicating crucial roles of leptin receptor and Sca-1+ progenitor cells in vascular remodelling. Conclusions-Levels of leptin in both the vessel wall and the circulation are upregulated after vessel injury, leading to the migration of Sca-1+ progenitor cells that enhances neointimal formation. Background and purpose Ischaemic Heart Diseases (IHD) are the most common cause of morbidity and mortality. Incidence and prevalence are continuously growing. There is an escalating risk for revascularisation or resuscitation in patients with IHD. Recently, it has been reported that a sphingosine 1-phosphate receptor agonist play an anti-apoptotic and anti-inflammatory role in the ischemia-reperfusion injury. Objectives The aim of our study is to investigate the cardioprotective effects of sphingosine 1-phosphate receptor agonist fingolimod (FTY720) on global ischemia-reperfusion injury related to the cardiac surgery. Methods In our experimental study, global ischemia-reperfusion was achieved by cardiopulmonary bypass by cardioplegic arrest on ventilated male Sprague-Dawley rats (300-350 g). The global ischaemic period lasted 10 min in the cardioplegic arrest while reperfusion times were maintained for 60 min and 24 hours. ECG monitoring was done using AD instrument and using Millar catheter, heart rate, systolic and diastolic pressures were recorded and mean arterial pressure was calculated. The statistical significance was considered at P 0.05. Results The myocardial protection was observed in the group treated with Fingolimod as compared to control groups. Reduced frequency of apoptotic cells and inflammatory mediators were found in the treated group. The level of adenylates was preserved in the treated group as compared to controls (94%, 61% respectively)(p0.001). Reactive Oxygen Species (ROS) were attenuated in the fingolimod-treated group. Fingolimod treatment improved systolic and diastolic ventricular pressures and contractility strength (p0.005). Conclusions The intravenous administration of fingolimod in global ischemia-reperfusion was cardioprotective. Fingolimod cardioprotection appears to be mediated through preservation of high energy phosphates, reduction in oxidative stress, inhibition of apoptosis and inflammation leading to improved cardiac functions. 168

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