Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge.

Perchlorate is regarded as an emerging persistent inorganic contaminant. It is widely known that perchlorate is an endocrine disruptor as it competitively inhibits iodide transport in the thyroid gland. As drinking water is the major source of human exposure to perchlorate, its occurrence in commercially available bottled waters purchased in different regions of Italy was investigated. Perchlorate was measured using the rapid, sensitive, and selective LC-ESI-MS/MS (liquid chromatography-electrospray tandem mass spectrometry) method by multiple reaction monitoring (MRM) of the transition 98.8→82.8, which corresponds to the loss of one oxygen atom in the perchlorate ion (ClO₄⁻→ClO₃⁻). The chlorine isotope ratio (³⁵Cl/³⁷Cl) was used as a confirmation tool. The limit of quantification (LOQ) for this method was 5 ng/L, and the recovery ranged from 94% to 108%. Perchlorate was detected in 44 of the 62 drinking waters tested, with concentrations ranging from <5 to 75 ng/L. These values are similar in magnitude to those reported in drinking water from the USA and do not pose an immediate health concern.

(1) Background: almond peels are rich in polyphenols such as catechin and epicatechin, which are important anti-free-radical agents, anti-inflammatory compounds, and capable of breaking down cholesterol plaques. This work aims to evaluate the biological and technological activity of a “green” dry aqueous extract from Sicilian almond peels, a waste product of the food industry, and to develop healthy nutraceuticals with natural ingredients. Eudraguard^® Natural is a natural coating polymer chosen to develop atomized formulations that improve the technological properties of the extract. (2) Methods: the antioxidant and free radical scavenger activity of the extract was rated using different methods (DPPH assay, ABTS, ORAC, NO). The metalloproteinases of the extracts (MMP-2 and MMP-9), the enhanced inhibition of the final glycation products, and the effects of the compounds on cell viability were also tested. All pure materials and formulations were characterized using UV, HPLC, FTIR, DSC, and SEM methods. (3) Results: almond peel extract showed appreciable antioxidant and free radical activity with a stronger NO inhibition effect, strong activity on MMP-2, and good antiglycative effects. In light of this, a food supplement with added health value was formulated. Eudraguard^® Natural acted as a swelling substrate by improving extract solubility and dissolution/release (4) Conclusions: almond peel extract has significant antioxidant activity and MMP/AGE inhibition effects, resulting in an optimal candidate to formulate safe microsystems with potential antimetabolic activity. Eudraguard^® Natural is capable of obtaining spray-dried microsystems with an improvement in the extract‘s biological and technological characteristics. It also protects the dry extract from degradation and oxidation, prolonging the shelf life of the final product.

In recent years, epidemiological studies have identified a relationship between diet and cerebro–cardiovascular disease (CVD). In this regard, there is a promising dietary group for cardiovascular protection are polyphenols, especially anthocyanins. Vascular reactivity studies were performed using Healthberry 865^® and constituent single anthocyanins to characterize vasomotor responses; immunofluorescence analysis with dichlorofluorescein diacetate and dihydroethidium were used to evaluate nitric oxide and oxidative stress; lucigenin assay was used to measure NADPH oxidase activity; and gel electrophoresis and immunoblotting were used to dissect the molecular mechanisms involved. We demonstrated that Healthberry 865^® exerts an important vasorelaxant effect of resistance artery functions in mice. Its action is mediated by nitric oxide release through the intracellular signaling PI3K/Akt. Moreover, behind its capability of modulating vascular tone, it also exerts an important antioxidant effect though the modulation of the NADPH oxidase enzyme. Interestingly, its cardiovascular properties are mediated by the selective action of different anthocyanins. Finally, the exposure of human dysfunctional vessels to Healthberry 865^® significantly reduces oxidative stress and improves NO bioavailability. Although further investigations are needed, our data demonstrate the direct role of Healthberry 865^® on the modulation of vasculature, both on the vasorelaxation and on oxidative stress; thus, supporting the concept that a pure mixture of anthocyanins could be helpful in preventing the onset of vascular dysfunction associated with the development of CVD.

A new series of tetrasubstituted pyrrole derivatives (TSPs) was synthesized based on a previously developed hypothesis on their ability to mimic hydrophobic protein motifs. The resulting new TSPs were endowed with a significant toxicity against human epithelial melanoma A375 cells, showing IC₅₀ values ranging from 10 to 27 μM, consistent with the IC₅₀ value of the reference compound nutlin-3a (IC₅₀ = 15 μM). In particular, compound 10a (IC₅₀ = 10 μM) resulted as both the most soluble and active among the previous and present TSPs. The biological investigation evidenced that the anticancer activity is related to the activation of apoptotic cell-death pathways, supporting our rational design based on the ability of TSPs to interfere with PPI involved in the cell cycle regulation of cancer cells and, in particular, the p53 pathway. A reinvestigation of the TSP pharmacophore by using DFT calculations showed that the three aromatic substituents on the pyrrole core are able to mimic the hydrophobic side chains of the hot-spot residues of parallel and antiparallel coiled coil structures suggesting a possible molecular mechanism of action. A structure–activity relationship (SAR) analysis which includes solubility studies allows us to rationalize the role of the different substituents on the pyrrole core.