Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, and other organoleptic characteristics, as well as contributing to important nutritional aspects. Beyond these characteristics, due to their biochemical properties and characteristics, they can be considered bioactive compounds. Several interesting studies have demonstrated their biological activity in different cellular and physiological processes in high-order organisms including humans. The flavonoid molecular structure confers the capability of reacting with and neutralizing reactive oxygen species (ROS), behaving as scavengers in all processes generating this class of molecules, such as UV irradiation, a process widely present in plant physiology. Importantly, the recent scientific literature has demonstrated that flavonoids, in human physiology, are active compounds acting not only as scavengers but also with the important role of counteracting the inflammation process. Among the wide variety of flavonoid molecules, significant results have been shown by investigating the role of the flavones luteolin and luteolin-7-O-glucoside (LUT-7G). For these compounds, experimental results demonstrated an interesting anti-inflammatory action, both in vitro and in vivo, in the interaction with JAK/STAT3, NF-κB, and other pathways described in this review. We also describe the effects in metabolic pathways connected with inflammation, such as cellular glycolysis, diabetes, lipid peroxidation, and effects in cancer cells. Moreover, the inhibition of inflammatory pathway in endothelial tissue, as well as the NLRP3 inflammasome assembly, demonstrates a key role in the progression of such phenomena. Since these micronutrient molecules can be obtained from food, their biochemical properties open new perspectives with respect to the long-term health status of healthy individuals, as well as their use as a coadjutant treatment in specific diseases.

Flavonoids display a broad range of structures and are responsible for the major organoleptic characteristics of plant-derived foods and beverages. Recent data showed their activity, and in particular of luteolin-7-O-glucoside (LUT-7G), in reduction of oxidative stress and inflammatory mechanisms in different physiological systems. In this paper, we tried to elucidate how LUT-7G could exert both antioxidant and anti-inflammatory effects in endothelial cells cultured in vitro. Here, we showed that LUT-7G is able to inhibit the STAT3 pathway, to have an antiproliferative action, and an important antioxidant property in HUVEC cells. These properties are exerted by the flavone in endothelial through the transcriptional repression of a number of inflammatory cytokines and their receptors, and by the inhibition of ROS generation. ROS and STAT3 activation has been correlated with the production of oxysterols and other hydroxylated fatty acids, and they have been recognized important as players of atherogenesis and cardiocirculatory system diseases. The analysis of the general production pathway of these hydroxylated species, showed a strong decrease of cholesterol hydroxylated species such as 7-alpha-hydroxicholesterol, 7-beta-hydroxicholesterol by the treatment with LUT-7G. This confirms the anti-inflammatory properties of LUT-7G also in the endothelial district, showing for the first time the molecular pathway that verify previous postulated cardiovascular benefits of this flavone.

Dyslipidemia and abnormal phospholipid metabolism are frequent in uremic patients and increase their risk of cardiovascular disease (CVD): ω-3 polyunsaturated fatty acids (PUFAs) may reduce this risk in the general population. In this study we compared the plasma and erythrocyte cell membrane composition of PUFAs in a group of Caucasian hemodialysis (HD) patients and in a control group of healthy subjects and evaluated the erythrocyte/cell membrane fatty acid ratio as a marker of the dietary intake of phospholipids. The relationship between ω-3 and ω-6 fatty acids and the possible differences in PUFAs concentrations were also investigated. After obtaining a fully informed consent, a total of ninety-nine HD patients and 160 non uremic control subjects from “Tor Vergata” University Hospital were enrolled into the study. None of them took antioxidant drugs or dietary supplements for at least 90 days prior to the observation. Blood samples were analysed by gas-chromatographic coupled to a mass spectrometric detector. The daily intake of total calories, proteins, lipids and carbohydrates is significantly lower in HD patients than in controls (p < 0.001). Most plasma and erythrocyte PUFA were also reduced significantly in HD patients (p < 0.001). Our results suggest that many classes of PUFAs are lacking in HD patients, due to the removal of nutrients during the dialysis and to persistent malnutrition. A dietary treatment addressed to increase plasma ω-3 PUFAs and to optimize ω-6/ω-3 ratio may exert a protective action and reduce the risk of CVD in HD patient.

Background: Ataxia-telangiectasia (AT) is a rare hereditary genetic disease caused by one of more than 500 mutations in the ataxia-telangiectasia mutated gene (ATM). AT is characterized by cerebellar ataxia, telangiectasia of blood vessels, immunodeficiency with frequent lung infections, susceptibility to cancer, and sensitivity to ionizing radiation. A correct immunophenotyping of lymphocytes is necessary to identify the cause of the immunodeficiency. Methods: We evaluated a patient (female, 15 years) with AT by estimation of antibody titers, characterization of peripheral B- and T-cell subsets and investigation of proliferation response of B- and T-cells undergoing specific stimulation with PHA, CD3/CD28, and R848/CD40L. A healthy volunteer was used as a control. Results: The patient showed a heterozygous mutation in the ATM gene (c.5932G>T[p.E1978X]/c.7788+3A>G). Interestingly, despite a very low level of class-switched memory B-cells normal levels of serum immunoglobulins and antibody titers to viral and bacterial antigens could be observed. Furthermore, the analysis revealed an increase in total numbers of T-cells, caused by an extraordinarily high amount of γ/δ T-cells (CD3+CD4–CD8) (>75% of T-cells). Remaining CD4+/CD8+T-cells were decreased, naïve cells and recent thymic emigrants (RTEs) were strongly deficient. Subsequently, the proliferation activity of T-cells was strongly impaired, in contrast to normal B-cell proliferation both compared to the healthy control. Conclusions: Initial lymphocyte immunophenotyping suggested a defect in T- and B-cell differentiation, but normal humoral antibody titers and B-cell proliferation were inconsistent with this suspicion. Therefore, the results revealed an underlying T-cell defect and low levels of class-switched B-cells results from the lacking assistance from T-cells.

Over the last years, incretin receptor agonists—including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide—have dramatically improved the management of type 2 diabetes, overweight and obesity. However, as the use of incretin receptor agonists continues to increase worldwide, micronutrient deficiencies—including iron deficiency—have emerged as newly recognized adverse effects of these drugs. The present article aims to discuss recent preliminary observational evidence on the potential relationship between incretin receptor agonist-based therapies and the development of iron deficiency and iron deficiency anemia (IDA), as well as the potential mechanisms by which incretin receptor agonists may affect iron homeostasis. Potential mechanisms and factors underlying the development of iron deficiency and IDA in patients treated with incretin receptor agonist-based therapies include inadequate dietary iron intake (due to incretin receptor agonist-mediated reduction in food intake and/or gastrointestinal adverse effects of incretin receptor agonists), low dietary variety, monotonous diets, and changes in food preferences, as well as impairment of intestinal iron absorption (due to delayed gastric emptying, reduced small intestinal motility and/or decreased gastric acid secretion caused by incretin receptor agonists). Moreover, vitamin B2 (riboflavin) deficiency and changes in gut microbiota composition are hypothetical mechanisms that may partly explain iron deficiency in patients treated with incretin receptor agonists, although these hypotheses require confirmation through mechanistic studies. Even though iron deficiency and IDA currently appear to be uncommon adverse effects of incretin receptor agonist-based therapies, clinicians should be aware of the possibility of their occurrence to ensure appropriate prevention and management of these nutritional complications. Nevertheless, future prospective studies are certainly needed to better establish the causal relationship between the initiation of incretin receptor agonist-based therapies and the development of iron deficiency/IDA, as well as the exact mechanisms underlying the potential development of these nutritional complications in patients treated with incretin receptor agonists. Meanwhile, the prescription of incretin receptor agonists should not be unjustifiably restricted by the possible and modest risk of iron deficiency and IDA in patients with one or more approved indications for therapeutic use of these agents. Since no established guidelines currently exist for the prevention and management of iron deficiency and IDA in patients treated with incretin receptor agonists, we herein propose practical strategies to address these possible nutritional complications of incretin receptor agonist-based therapies. These proposed strategies should only be regarded as practical clinical approaches deriving from the existing recommendations for the prevention and management of iron deficiency and IDA, although their cost-effectiveness for the prevention and management of incretin receptor agonist-associated iron deficiency/IDA should be appropriately assessed in future clinical trials.