Transcriptional deregulation of genes encoding for H(2)S-producing enzymes is present in uraemia. Although the specificity of the method employed for H(2)S detection is low, the finding that H(2)S is decreased is complemented by the lower sulphhaemoglobin levels. Potential implications of this study relate to the pathogenesis of the uraemic syndrome manifestations, such as hypertension and atherosclerosis.

H2S is the third endogenous gaseous mediator, after nitric oxide and carbon monoxide, possessing pleiotropic effects, including cytoprotection and anti-inflammatory action. We analyzed, in an in vitro model entailing monocyte adhesion to an endothelial monolayer, the changes induced by H2S on various potential targets, including cytokines, chemokines, and proteases, playing a crucial role in inflammation and cell adhesion. Results show that H2S prevents the increase in monocyte adhesion induced by tumor necrosis factor-α (TNF-α). Under these conditions, downregulation of monocyte chemoattractant protein-1 (MCP-1), chemokine C-C motif receptor 2, and increase of cluster of differentiation 36 could be detected in monocytes. In endothelial cells, H2 S treatment reduces the increase in MCP-1, inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, and of a disintegrin and metalloproteinase metallopeptidase domain 17 (ADAM17), both at the gene expression and protein levels. Cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase, the major H2S forming enzymes, are downregulated in endothelial cells. In addition, H2S significantly reduces activation of ADAM17 by PMA in endothelial cells, with consequent reduction of both ADAM17-dependent TNF-α ectodomain shedding and MCP-1 release. In conclusion, H2S is able to prevent endothelial activation by hampering endothelial activation, triggered by TNF-α. The mechanism of this protective effect is mainly mediated by down-modulation of ADAM17-dependent TNF-converting enzyme (TACE) activity with consequent inhibition of soluble TNF-α shedding and its relevant MCP-1 release in the medium. These results are discussed in the light of the potential protective role of H2S in pro-inflammatory and pro-atherogenic processes, such as chronic renal failure.

Food plays a central role in health, especially through consumption of plant-derived foods. Functional foods, supplements, and nutraceuticals are increasingly entering the market to respond to consumer demand for healthy products. They are foods, supplements, and ingredients which offer health benefits beyond the standard nutritional value. Some benefits are associated with phenolic compounds and phytochemicals with antioxidant properties. An olive pâté (OP) was added with antioxidants derived from olive mill wastewater (OMWW) to obtain a functional product rich in phenolic compounds. The olive pâté is produced from the ground olive pericarp, which shows an excellent natural antioxidant content. The OMWW is a waste product from oil processing, which is also rich in phenolic compounds. The result was a product rich in trans-resveratrol, OH tyrosol, and tyrosol in concentrations such as satisfying the European community’s claims regarding the possible antioxidant action on plasma lipids with excellent shelf-life stability. The total phenolic content was assayed by a colorimetric method, the antioxidant activity by the ABTS [(2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] test, the phenolic profile by Q Exactive Orbitrap LC-MS/MS. The shelf-life stability was confirmed by yeast, molds, and total microbial count, pH, and water activity determinations, and the best pasteurization parameters were determined. The palatability was judged as excellent.

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function.

Heart failure (HF) represents the end-stage condition of several structural and functional cardiovascular diseases, characterized by reduced myocardial pump function and increased pressure load. The dysregulation of neurohormonal systems, especially the hyperactivity of the cardiac adrenergic nervous system (ANS), constitutes a hallmark of HF and exerts a pivotal role in its progression. Indeed, it negatively affects patients’ prognosis, being associated with high morbidity and mortality rates, with a tremendous burden on global healthcare systems. To date, all the techniques proposed to assess the cardiac sympathetic nervous system are burdened by intrinsic limits that hinder their implementation in clinical practice. Several biomarkers related to ANS activity, which may potentially support the clinical management of such a complex syndrome, are slow to be implemented in the routine practice for several limitations due to their assessment and clinical impact. Lymphocyte G-protein-coupled Receptor Kinase 2 (GRK2) levels reflect myocardial β-adrenergic receptor function in HF and have been shown to add independent prognostic information related to ANS overdrive. In the present manuscript, we provide an overview of the techniques currently available to evaluate cardiac ANS in HF and future perspectives in this field of relevant scientific and clinical interest.