The poor water solubility of natural antioxidants restricts their bioavailability and therapeutic use. We aimed to develop a new phytosome formulation with active compounds from extracts of ginger (GINex) and rosehips (ROSAex) designed to increase their bioavailability, antioxidant and anti-inflammatory properties. The phytosomes (PHYTOGINROSA-PGR) were prepared from freeze-dried GINex, ROSAex and phosphatidylcholine (PC) in different mass ratios using the thin-layer hydration method. PGR was characterized for structure, size, zeta potential, and encapsulation efficiency. Results showed that PGR comprises several different populations of particles, their size increasing with ROSAex concentration, having a zeta potential of ~-21mV. The encapsulation efficiency of 6-gingerol and β-carotene was >80%. ³¹P NMR spectra showed that the shielding effect of the phosphorus atom in PC is proportional to the amount of ROSAex in PGR. PGR with a mass ratio GINex:ROSAex:PC-0.5:0.5:1 had the most effective antioxidant and anti-inflammatory effects in cultured human enterocytes. PGR-0.5:0.5:1 bioavailability and biodistribution were assessed in C57Bl/6J mice, and their antioxidant and anti-inflammatory effects were evaluated after administration by gavage to C57Bl/6J mice prior to LPS-induced systemic inflammation. Compared to extracts, PGR induced a 2.6-fold increase in 6-gingerol levels in plasma and over 40% in the liver and kidneys, in parallel with a 65% decrease in the stomach. PGR treatment of mice with systemic inflammation increased the sera antioxidant enzymes paraoxonase-1 and superoxide dismutase-2 and decreased the proinflammatory TNFα and IL-1β levels in the liver and small intestine. No toxicity was induced by PGR either in vitro or in vivo. In conclusion, the phytosome formulation of GINex and ROSAex we developed resulted in stable complexes for oral administration with increased bioavailability, antioxidant and anti-inflammatory potential of their active compounds.

Coronary artery disease (CAD) is a leading cause of mortality worldwide. In this study, we aimed to assess the potential of plasma long non-coding RNAs (lncRNAs) LIPCAR and MALAT1 and microRNAs (miRNAs) miR-142-3p and miR-155-5p to discriminate unstable CAD patients from stable ones. 23 stable angina (SA), 21 unstable angina (UA), and 50 ST-segment elevation myocardial infarction (STEMI) patients were enrolled; their plasma was collected. ncRNA plasma levels were evaluated using RT-qPCR. All measured ncRNA levels were significantly increased in UA patients’ plasma compared to SA patients’ plasma and in STEMI-with major adverse cardiovascular event (MACE) patients’ plasma vs. STEMI-without MACE patients’ plasma. ROC analysis showed that increased levels of LIPCAR and MALAT1 were associated with UA, and the prognostic model improved with the addition of miR-155-5p levels. The assessed lncRNAs discriminated between hyperglycemic (HG) and normoglycemic (NG) UA patients, and they were associated with MACE incidence in STEMI patients; this prediction was improved by the addition of miR-142-3p levels to the ROC multivariate model. We propose LIPCAR and MALAT1 as effective diagnostic markers for vulnerable CAD, their association with HG in UA patients, and as robust predictors for unfavorable evolution of STEMI patients.

Metabolic disorders (MDs), including dyslipidemia, non-alcoholic fatty liver disease, diabetes mellitus, obesity and cardiovascular diseases are a significant threat to human health, despite the many therapies developed for their treatment. Different classes of bioactive compounds, such as polyphenols, flavonoids, alkaloids, and triterpenes have shown therapeutic potential in ameliorating various disorders. Most of these compounds present low bioavailability when administered orally, being rapidly metabolized in the digestive tract and liver which makes their metabolites less effective. Moreover, some of the bioactive compounds cannot fully exert their beneficial properties due to the low solubility and complex chemical structure which impede the passive diffusion through the intestinal cell membranes. To overcome these limitations, an innovative delivery system of phytosomes was developed. This review aims to highlight the scientific evidence proving the enhanced therapeutic benefits of the bioactive compounds formulated in phytosomes compared to the free compounds. The existing knowledge concerning the phytosomes’ preparation, their characterization and bioavailability as well as the commercially available phytosomes with therapeutic potential to alleviate MDs are concisely depicted. This review brings arguments to encourage the use of phytosome formulation to diminish risk factors inducing MDs, or to treat the already installed diseases as complementary therapy to allopathic medication.

Acute ST elevation myocardial infarction (STEMI) remains a leading cause of morbidity and mortality worldwide despite continuous advances in diagnostic, prognostic and therapeutic methods. Myocardial work (MW) indices and miRNAs have both emerged as potential prognostic markers in acute coronary syndromes in recent years. In this study we aim to assess the prognostic role of myocardial work indices and of a group of miRNAs in young patients with STEMI. We enrolled 50 young patients (<55 years) with STEMI who underwent primary PCI and 10 healthy age-matched controls. We performed standard 2D and 3D echocardiography; we also calculated left ventricular global longitudinal strain (GLS) and the derived myocardial work indices. Using RT-PCR we determined the plasmatic levels of six miRNAs: miR-223-3p, miR-142-3p, miR-146a-5p, miR-125a-5p, miR-486-5p and miR-155-5p. We assessed the occurrence of major adverse cardiac events (MACE) at up to one year after STEMI. Out of 50 patients, 18% experienced MACE at the one-year follow-up. In a Cox univariate logistic regression analysis, myocardial work indices were all significantly associated with MACE. The ROC analysis showed that GWI, GCW and GWE as a group have a better predictive value for MACE than each separately (AUC 0.951, p = 0.000). Patients with higher miRNAs values at baseline (miR-223-3p, miR-142-3p and miR-146a-5p) appear to have a higher probability of developing adverse events at 12 months of follow-up. ROC curves outlined for each variable confirmed their good predictive value (AUC = 0.832, p = 0.002 for miR-223-3p; AUC = 0.732, p = 0.031 for miR-142-3p and AUC = 0.848, p = 0.001 for miR-146a-5p); the group of three miRNAs also proved to have a better predictive value for MACE together than separately (AUC = 0.862). Moreover, adding each of the miRNAs (miR-233, miR-142-3p and miR-146a-5p) or all together over the myocardial work indices in the regression models improved their prognostic value. In conclusion, both myocardial work indices (GWI, GCW and GWE) and three miRNAs (miR-223-3p, miR-142-3p and miR-146a-5p) have the potential to be used as prognostic markers for adverse events after acute myocardial infarction. The combination of miRNAs and MW indices (measured at baseline) rather than each separately has very good predictive value for MACE in young STEMI patients (C-statistic 0.977).

RNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the cellular machinery, both A-to-I and C-to-U editing change the nucleotide sequence of the RNA. Editing events in coding sequences have the potential to change the amino acid sequence of proteins, whereas editing events in noncoding RNAs can, for example, affect microRNA target binding. With advancing RNA sequencing technology, more RNA editing events are being discovered, studied, and reported. However, RNA editing events are still often overlooked or discarded as sequence read quality defects. With this position paper, we aim to provide guidelines and recommendations for the detection, validation, and follow-up experiments to study RNA editing, taking examples from the fields of cardiovascular and brain disease. We discuss all steps, from sample collection, storage, and preparation, to different strategies for RNA sequencing and editing-sensitive data analysis strategies, to validation and follow-up experiments, as well as potential pitfalls and gaps in the available technologies. This paper may be used as an experimental guideline for RNA editing studies in any disease context.