Free radicals and antioxidants in food and in vivo: What they do and how they work

A wide variety of oxygen free radicals and other reactive oxygen species can be formed in the human body and in food systems. Transition metal ions accelerate free‐radical damage. Antioxidant defenses, both enzymic and nonenzymic, protect the body against oxidative damage, but they are not 100% efficient, and so free‐radical damage must be constantly repaired. Nonenzymatic antioxidants are frequently added to foods to prevent lipid peroxidation. Several lipid antioxidants can exert prooxidant effects toward other molecules under certain circumstances, and so antioxidants for food and therapeutic use must be characterized carefully. Methods of measuring oxidative damage and trapping free radicals in vivo are briefly discussed. Such methods are essential in checking proposals that increased intake of food‐derived antioxidants (such as antioxidant vitamins) would be beneficial to humans.     

Bioprotectives and probiotics for dry sausages

The microbial stability of dry sausages is determined by the combination and timing of different factors referred to as the hurdle-concept. However, the hurdles present in dry sausage are not sufficient to prevent the survival of Listeria monocytogenes or enterohemorrhagic Escherichia coli O157:H7. Recently bioprotective lactic acid bacteria, which in addition to the production of antimicrobial lactic acid, have been found to contribute to the safety of the dry sausage by producing antimicrobial peptide, i.e. bacteriocins and other low-molecular-mass compounds. Furthermore, the possibilities to use probotics in dry sausage manufacturing process has been addressed recently. As one possible mode of action for probiotics is the production of antimicrobial compounds, lactic acid bacteria may act as both probiotic and bioprotective culture as well as fermenting agent in meat product, such as dry sausage.     

Resveratrol-like Compounds as SIRT1 Activators

The sirtuin 1 (SIRT1) activator resveratrol has emerged as a promising candidate for the prevention of vascular oxidative stress, which is a trigger for endothelial dysfunction. However, its clinical use is limited by low oral bioavailability. In this work, we have applied a previously developed computational protocol to identify the most promising derivatives from our in-house chemical library of resveratrol derivatives. The most promising compounds in terms of SIRT1 activation and oral bioavailability, predicted in silico, were evaluated for their ability to activate the isolated SIRT1 enzyme. Then, we assessed the antioxidant effects of the most effective derivative, compound 3d, in human umbilical vein endothelial cells (HUVECs) injured with H₂O₂ 100 µM. The SIRT1 activator 3d significantly preserved cell viability and prevented an intracellular reactive oxygen species increase in HUVECs exposed to the oxidative stimulus. Such effects were partially reduced in the presence of a sirtuin inhibitor, sirtinol, confirming the potential role of sirtuins in the activity of resveratrol and its derivatives. Although 3d appeared less effective than resveratrol in activating the isolated enzyme, the effects exhibited by both compounds in HUVECs were almost superimposable, suggesting a higher ability of 3d to cross cell membranes and activate the intracellular target SIRT1.     

Impact of CFTR Modulators on the Impaired Function of Phagocytes in Cystic Fibrosis Lung Disease

Cystic fibrosis (CF), the most common genetically inherited disease in Caucasian populations, is a multi-systemic life-threatening autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In 2012, the arrival of CFTR modulators (potentiators, correctors, amplifiers, stabilizers, and read-through agents) revolutionized the therapeutic approach to CF. In this review, we examined the physiopathological mechanism of chronic dysregulated innate immune response in the lungs of CF patients with pulmonary involvement with particular reference to phagocytes, critically analyzing the role of CFTR modulators in influencing and eventually restoring their function. Our literature review highlighted that the role of CFTR in the lungs is crucial not only for the epithelial function but also for host defense, with particular reference to phagocytes. In macrophages and neutrophils, the CFTR dysfunction compromises both the intricate process of phagocytosis and the mechanisms of initiation and control of inflammation which then reverberates on the epithelial environment already burdened by the chronic colonization of pathogens leading to irreversible tissue damage. In this context, investigating the impact of CFTR modulators on phagocytic functions is therefore crucial not only for explaining the underlying mechanisms of pleiotropic effects of these molecules but also to better understand the physiopathological basis of this disease, still partly unexplored, and to develop new complementary or alternative therapeutic approaches.     

Stem Cell Therapy for Sequestration of Traumatic Brain Injury-Induced Inflammation

Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disabilities in the world. TBI is a signature disease for soldiers and veterans, but also affects civilians, including adults and children. Following TBI, the brain resident and immune cells turn into a “reactive” state, characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Other injuries to the brain, including radiation exposure, may trigger TBI-like pathology, characterized by inflammation. Currently there are no treatments to prevent or reverse the deleterious consequences of brain trauma. The recognition that TBI predisposes stem cell alterations suggests that stem cell-based therapies stand as a potential treatment for TBI. Here, we discuss the inflamed brain after TBI and radiation injury. We further review the status of stem cells in the inflamed brain and the applications of cell therapy in sequestering inflammation in TBI.     

Distinct Longitudinal Changes in Immunoglobulin G N-Glycosylation Associate with Therapy Response in Chronic Inflammatory Diseases

Immunosuppressants and biologicals are widely used therapeutics for various chronic inflammatory diseases (CID). To gain more detailed insight into their downstream effects, we examined their impact on serum immunoglobulin G (IgG) glycosylation. We analyzed IgG subclass-specific fragment crystallizable (Fc) N-glycosylation in patients suffering from various CID using the LC-MS approach. Firstly, we compared IgG Fc N-glycosylation between 128 CID patients and 204 healthy controls. Our results replicated previously observed CID-related decrease in IgG Fc galactosylation (adjusted p-value range 1.70 × 10⁻²–5.95 × 10⁻²²) and sialylation (adjusted p-value range 1.85 × 10⁻²–1.71 × 10⁻¹⁸). Secondly, to assess changes in IgG Fc N-glycosylation associated with therapy and remission status, we compared 139 CID patients receiving either azathioprine, infliximab, or vedolizumab therapy. We observed an increase in IgG Fc galactosylation (adjusted p-value range 1.98 × 10⁻²–1.30 × 10⁻¹⁵) and sialylation (adjusted p-value range 3.28 × 10⁻⁶–4.34 × 10⁻¹⁸) during the treatment. Furthermore, patients who reached remission displayed increased Fc galactosylation levels (p-value range 2.25 × 10⁻²–5.44 × 10⁻³) in comparison to patients with active disease. In conclusion, the alterations in IgG Fc glycosylation and the fact these changes are even more pronounced in patients who achieved remission, suggest modulation of IgG inflammatory potential associated with CID therapy.     

Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development

Changes in mitochondrial function were studied in perfused liver from rats aged 24-365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage.