Luciano Cominacini

In this study, we first focused on measuring H₂S and oxidative stress as indicators of in-hospital mortality observed within 24 h from admission in hospitalized non-survivor and survivor patients affected by COVID-19. Then, we analyzed whether N-acetylcysteine (NAC) can increase H₂S and GSH concentrations in different cell lines. H₂S levels were significantly increased in all COVID-19 patients (both survivors and non-survivors) compared to non-COVID-19 subjects (p = 0.0016), but non-survivors showed significantly lower H₂S plasma levels than survivors (p = 0.008). Oxidative stress measured as circulating malondialdehyde (MDA) resulted in lower levels in non-COVID-19 subjects than in the two COVID-19 patient groups (p = 0.03). However, non-survivors had significantly higher plasma MDA than survivors (p = 0.0001). A Kaplan–Meier curve for H₂S indicates a markedly reduced survival probability in COVID-19 patients with lower H₂S levels (log-rank p = 0.004). NAC activity significantly reduced reactive oxygen species and lipid peroxidation induced by tert-butyl hydroperoxide in cultured cells (p from 2S (p < 0.01) and GSH (p < 0.01). These findings indicate the important prognostic role of H₂S in COVID-19 patients at hospital admission and that NAC might be helpful in all clinical situations characterized by low levels of H₂S.

The olive oil-production sector engages with the environment on multiple levels, and the valorization of olive pomace (OP) has emerged as a key strategy to improve the entire system’s sustainability. Numerous studies have investigated the biological effects of OP phenolic fraction for nutraceutical applications, highlighting its antioxidant properties. This study aimed to assess the effect of an OP extract (OPE) and its phenolic content on ferroptosis induced by RAS-selective lethal 3 (RSL3), an inhibitor of glutathione peroxidase 4. After characterization of OPE phenolic composition, its antioxidant properties were confirmed through the Fenton reaction assay. Subsequently, we examined the effect of OPE on ter-butyl hydroperoxide-induced ROS generation and lipid peroxidation in TPH-1 and HIECs cells and found that OPE reduced ROS and lipid peroxidation. RSL3 decreased the number of vital cells, which was associated with an elevation in ROS and lipid peroxidation, and a reduction in GSH. Interestingly, all these detrimental effects were reversed by OPE. Furthermore, OPE was also found to significantly increase GSH and the GSH/GSSG ratio per se. In conclusion, the fact that OPE decreases ROS and lipid peroxidation induced by RSL3 and augments GSH and cell viability suggests that OPE has potential as a ferroptosis inhibitor.

This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia and acute respiratory failure. The median time from the onset of COVID-19 symptoms to hospital admission was lower in non-survivors than survivors (p < 0.05). Respiratory failure, expressed as the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen (P/F), was more severe in non-survivors than survivors (p < 0.0001). Comorbidities were similar in both groups. Among biochemical parameters and cytokines, eGFR and interleukin (IL)-1β were found to be significantly lower (p < 0.05), while LDH, IL-10, and IL-8 were significantly higher in non-survivors than in survivors (p < 0.0005, p < 0.05 and p < 0.005, respectively). Among other parameters, LDH values distribution showed the most significant difference between study groups (p < 0.0001). LASSO feature selection combined with Cox proportional hazards and logistic regression models was applied to identify features distinguishing between survivors and non-survivors. Both approaches highlighted LDH as the strongest predictor, with IL-22 and creatinine emerging in the Cox model, while IL-10, eGFR, and creatinine were influential in the logistic model (AUC = 0.744 for Cox, 0.723 for logistic regression). In a similar manner, we applied linear regression for predicting LDH levels, identifying the P/F ratio as the top predictor, followed by IL-10 and eGFR (NRMSE = 0.128). Collectively, these findings underscore LDH’s critical role in mortality prediction, with P/F and IL-10 as key determinants of LDH increases in this Italian COVID-19 cohort.

Chronic diseases and cancer are worldwide health problems which result in death and disability for millions of people

Cardiovascular diseases (CVDs) are the principal cause of disease burden and death worldwide. Ferroptosis is a new form of regulated cell death mainly characterized by altered iron metabolism, increased polyunsaturated fatty acid peroxidation by reactive oxygen species, depletion of glutathione and inactivation of glutathione peroxidase 4. Recently, a series of studies have indicated that ferroptosis is involved in the death of cardiac and vascular cells and has a key impact on the mechanisms leading to CVDs such as ischemic heart disease, ischemia/reperfusion injury, cardiomyopathies, and heart failure. In this article, we reviewed the molecular mechanism of ferroptosis and the current understanding of the pathophysiological role of ferroptosis in ischemic heart disease and in some cardiomyopathies. Moreover, the comprehension of the machinery governing ferroptosis in vascular cells and cardiomyocytes may provide new insights into preventive and therapeutic strategies in CVDs.

Moderate wine consumption has been associated with several benefits to human health due to its high polyphenol content. In this study, we investigated whether polyphenols contained in a particular red wine, rich in polyphenols, can pass the cell membrane and switch the oxidant/antioxidant balance toward an antioxidant pattern of THP-1 cells and human cardiomyocytes through a gene regulatory system. First, we identified which metabolite polyphenols present in red wine extract cross cell membranes and may be responsible for antioxidant effects. The results showed that the wine metabolites in treated cells belonged mainly to stilbenes, flavan-3-ols derivatives, and flavonoids. Other metabolites present in cells were not typical wine metabolites. Then, we found that red wine extract dose-dependently lowered reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBHP) up to 50 ± 7% in both cell lines (p < 0.01). Furthermore, wine extract increased nuclear Nrf2 of about 35 ± 5% in both cell lines (p < 0.01) and counteracted its reduction induced by TBHP (p < 0.01). The rise in Nrf2 was paralleled by the increase in hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit gene expression (both mRNA and protein) (p < 0.01). These results could help explain the healthful activity of wine polyphenols within cells.

Oxidative stress (OS) is an imbalance between the formation of reactive oxygen and nitrogen species and antioxidant defenses

Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.

Over the last few decades, many efforts have been put into fields that explore the potential benefits of antioxidants, especially with regards to aging, cancer, cardiovascular diseases, and neurodegenerative diseases

The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Here, we review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress (OS) and inflammation. Furthermore, we analyze the potential role of antioxidant and anti-inflammatory therapies to prevent severe complications. OS has a potential key role in the COVID-19 pathogenesis by triggering the NOD-like receptor family pyrin domain containing 3 inflammasome and nuclear factor-kB (NF-kB). While exposure to many pro-oxidants usually induces nuclear factor erythroid 2 p45-related factor2 (NRF2) activation and upregulation of antioxidant related elements expression, respiratory viral infections often inhibit NRF2 and/or activate NF-kB pathways, resulting in inflammation and oxidative injury. Hence, the use of radical scavengers like N-acetylcysteine and vitamin C, as well as of steroids and inflammasome inhibitors, has been proposed. The NRF2 pathway has been shown to be suppressed in severe SARS-CoV-2 patients. Pharmacological NRF2 inducers have been reported to inhibit SARS-CoV-2 replication, the inflammatory response, and transmembrane protease serine 2 activation, which for the entry of SARS-CoV-2 into the host cells through the angiotensin converting enzyme 2 receptor. Thus, NRF2 activation may represent a potential path out of the woods in COVID-19 pandemic.