Thyroid Hormones and Antioxidant Systems: Focus on Oxidative Stress in Cardiovascular and Pulmonary Diseases

In previous works we demonstrated an inverse correlation between plasma Coenzyme Q₁₀ (CoQ₁₀) and thyroid hormones; in fact, CoQ₁₀ levels in hyperthyroid patients were found among the lowest detected in human diseases. On the contrary, CoQ₁₀ is elevated in hypothyroid subjects, also in subclinical conditions, suggesting the usefulness of this index in assessing metabolic status in thyroid disorders. A Low-T3 syndrome is a condition observed in several chronic diseases: it is considered an adaptation mechanism, where there is a reduction in pro-hormone T4 conversion. Low T3-Syndrome is not usually considered to be corrected with replacement therapy. We review the role of thyroid hormones in regulation of antioxidant systems, also presenting data on total antioxidant capacity and Coenzyme Q₁₀. Published studies suggest that oxidative stress could be involved in the clinical course of different heart diseases; our data could support the rationale of replacement therapy in low-T3 conditions.     

Why Our Patients Like Daily Hemodialysis

The option of daily hemodialysis (HD) was discussed in November 1998 with a group of 35 HD patients on home or self‐care/limited‐care HD in a single, freestanding unit. After the meeting, 3 patients on home HD chose to switch to daily HD. The clinical success of the first patient and the immediate followers was one of the main reasons for further extension of this experience. At the time of this writing (February 2000), 10 patients were on a daily HD program (8 at home and 2 in a self‐care/limited‐care center) and one was in training for home daily HD. One further patient who tried 1 month of daily HD dropped out for logistic reasons. On daily HD, patients are dialyzed 2 – 3 hours/day, 6 days/ week, with blood flow of 270 – 300 mL/min, on bicarbonate dialysate with individually determined levels of Na and K. The schedule is flexible and a switch to 3 – 4 dialyses/week is occasionally allowed for working needs or for vacation. In addition to the well‐known clinical advantages (better well‐being, blood pressure control, nutrition, etc.), some patients preferred daily HD because of easier organization of daily activities, including work schedule. Patients initially feared frequent needle punctures and excessive burden on partners, but those concerns proved to be less a problem than anticipated. All current patients are willing to continue daily HD; only a nursing shortage limits further extension of the program in the self‐care/limited‐care center.     

A Food-Grade Method for Enhancing the Levels of Low Molecular Weight Proanthocyanidins with Potentially High Intestinal Bioavailability

Proanthocyanidins (PACs) are a group of bioactive molecules found in a variety of plants and foods. Their bioavailability depends on their molecular size, with monomers and dimers being more bioavailable than those that have a higher polymerization degree. This study aimed to develop a method to convert high-molecular-weight PACs to low-molecular-weight ones in a grape seed extract (GSE) from Vitis vinifera L. Therefore, GSE was subjected to alkaline treatment (ATGSE), and its difference in chemical composition, compared to GSE, was evaluated using a molecular networking (MN) approach based on results obtained from HPLC-ESI HRMS/MS characterization analysis. The network analysis mainly noted the PAC cluster with about 142 PAC compounds identified. In particular, the obtained results showed a higher content of monomeric and dimeric PACs in ATGSE compared to GSE, with 58% and 49% monomers and 31% and 24% dimers, respectively. Conversely, trimeric (9%), polymeric (4%), and galloylated PACs (14%) were more abundant in GSE than in ATGSE (6%, 1%, and 4%, respectively). Moreover, in vitro antioxidant and anti-inflammatory activities were investigated, showing the high beneficial potential of both extracts. In conclusion, ATGSE could represent an innovative natural matrix rich in bioavailable and bioaccessible PACs for nutraceutical applications with potential beneficial properties.     

Profound Modification of Fatty Acid Profile and Endocannabinoid-Related Mediators in PPARα Agonist Fenofibrate-Treated Mice

Fenofibrate (FBR), an oral medication used to treat dyslipidemia, is a ligand of the peroxisome proliferator-activated receptor α (PPARα), a nuclear receptor that regulates the expression of metabolic genes able to control lipid metabolism and food intake. PPARα natural ligands include fatty acids (FA) and FA derivatives such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), known to have anti-inflammatory and anorexigenic activities, respectively. We investigated changes in the FA profile and FA derivatives by HPLC and LC-MS in male C57BL/6J mice fed a standard diet with or without 0.2% fenofibrate (0.2% FBR) for 21 days. Induction of PPARα by 0.2% FBR reduced weight gain, food intake, feed efficiency, and liver lipids and induced a profound change in FA metabolism mediated by parallel enhanced mitochondrial and peroxisomal β-oxidation. The former effects led to a steep reduction of essential FA, particularly 18:3n3, with a consequent decrease of the n3-highly unsaturated fatty acids (HUFA) score; the latter effect led to an increase of 16:1n7 and 18:1n9, suggesting enhanced hepatic de novo lipogenesis with increased levels of hepatic PEA and OEA, which may activate a positive feedback and further sustain reductions of body weight, hepatic lipids and feed efficiency.     

Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis

Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic cleavage. Recently it has been the topic of investigation in several types of cancer. In this study, we conducted a systematic review and meta-analysis to investigate its implication in different types of cancer. Our results suggest that irisin expression is decreased in cancer patients, thus it can be used as a valid biomarker for the diagnosis of several types of cancer. In addition, our results indicate that irisin may have an important role in tumor progression and metastasis since it is involved in multiple signaling pathways that promote cell proliferation and migration.     

The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L

Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro³]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non-natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non-natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure–activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.     

Second Order Fully Semi-Lagrangian Discretizations of Advection-Diffusion-Reaction Systems

Journal of Scientific Computing - We analyse numerically the periodic problem and the initial boundary value problem of the Korteweg-de Vries equation and the Drindfeld–Sokolov–Wilson...     

Functional Validation of Glutamine synthetase and Glutamate synthase Genes in Durum Wheat near Isogenic Lines with QTL for High GPC

Durum wheat (Triticum turgidum L. ssp. durum) is a minor crop grown on about 17 million hectares of land worldwide. Several grain characteristics determine semolina’s high end-use quality, such as grain protein content (GPC) which is directly related to the final products’ nutritional and technological values. GPC improvement could be pursued by considering a candidate gene approach. The glutamine synthetase (GS)/glutamate synthase (GOGAT) cycle represents a bottleneck in the first step of nitrogen assimilation. QTL for GPC have been located on all chromosomes, and several major ones have been reported on 2A and 2B chromosomes, where GS2 and Fd-GOGAT genes have been mapped. A useful and efficient method to validate a putative QTL is the constitution of near-isogenic lines (NILs) by using the marker found to be associated to that QTL. Here, we present the development of two distinct sets of heterogeneous inbred family (HIF)- based NILs segregating for GS2 and Fd-GOGAT genes obtained from heterozygous lines at those loci, as well as their genotypic and phenotypic characterizations. The results allow the validation of the previously identified GPC QTL on 2A and 2B chromosomes, along with the role of these key genes in GPC control.