Nowadays, it is known that oxidative stress plays at least two roles within the cell, the generation of cellular damage and the involvement in several signaling pathways in its balanced normal state. So far, a substantial amount of time and effort has been expended in the search for a clear link between cardiovascular disease (CVD) and the effects of oxidative stress. Here, we present an overview of the different sources and types of reactive oxygen species in CVD, highlight the relationship between CVD and oxidative stress and discuss the most prominent molecules that play an important role in CVD pathophysiology. Details are given regarding common pharmacological treatments used for cardiovascular distress and how some of them are acting upon ROS-related pathways and molecules. Novel therapies, recently proposed ROS biomarkers, as well as future challenges in the field are addressed. It is apparent that the search for a better understanding of how ROS are contributing to the pathophysiology of CVD is far from over, and new approaches and more suitable biomarkers are needed for the latter to be accomplished.

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.

Utilization of contrast media to visualize vasculature structures in the setting of cardiovascular disorders (CVD) can lead to acute kidney injury, referred to as contrast-induced nephropathy (CIN). CIN can potentiate mortality and hospitalization in aged individuals, patients with CVD, nephropathy, enhancing kidney damage, and cardiac events. Preventing CIN by identifying risk factors is important. The underlying mechanisms of CIN pathology are unclear, but the key factors include direct cytotoxicity, oxidative stress, vascular and endothelial dysfunction and inflammatory processes. Reactive Oxygen Species and inflammatory mediators have been proposed as key factors influencing the development of CIN and CVD, and the elucidation of the interplay between the mechanisms evoked by them may provide a better understanding of the signaling processes happening in these conditions, thereby potentially enabling early identification, prevention and characterization of novel drug targets.

Background Inflammation during pregnancy may aggravate iron deficiency by increasing serum hepcidin and reducing iron absorption. This could restrict iron transfer to the fetus, increasing risk for infant iron deficiency and its adverse effects. Objectives To assess whether iron bioavailability and/or iron transfer to the fetus is impaired in overweight/obese (OW) women with adiposity-related inflammation, compared to normal weight (NW), pregnant women. Design In this prospective study, we followed NW (n = 43) and OW (n = 40) pregnant women who were receiving iron supplements from the 14th gestational week to term and followed their infants to age six months. We administered 57Fe and 58Fe in test meals mid-2nd and mid-3rd trimester, and measured tracer kinetics throughout pregnancy and infancy. Results 38 NW and 36 OW completed the study to pregnancy week 36 and 30 NW and 27 OW mother infant pairs completed the study to six months postpartum. Both groups had comparable iron status, hemoglobin and serum hepcidin throughout pregnancy. Compared to the NW, the OW pregnant women had: 1) 43% lower fractional iron absorption in the 3rd trimester (P = 0.033) with median (IQR) 23.9 (11.4–35.7) and 13.5 (10.8–19.5) %; and 2) 17% lower maternal-fetal iron transfer from the first tracer (P = 0.051) with median (IQR) 4.8 (4.2–5.4) and 4.0 (3.6–4.6) %. Compared to the infants born to NW, infants born to OW had lower body iron stores (BIS) with median (IQR) 7.7 (6.3–8.8) and 6.6 (4.6–9.2) mg/kg body weight at age six months (P = 0.024). Prepregnancy BMI was a negative predictors of maternal-fetal iron transfer (β = –0.339, SE = 0.144, P = 0.025) and infant BIS (β = –0.237, SE = 0.026, P = 0.001). Conclusions Compared to NW, OW pregnant women fail to upregulate iron absorption in late pregnancy, transfer less iron to their fetus, and their infants have lower BIS. These impairments are associated with inflammation independent of serum hepcidin. The study was registered at clinicaltrials.gov (NCT02747316).

Although hepcidin synthesis is stimulated by inflammation and inhibited by iron deficiency, the strength of their opposing effects on serum hepcidin in humans remain unclear. It was recently shown that an inflammatory stimulus in anemic women did not increase serum hepcidin or decrease iron absorption. The enhancing effect of ascorbic acid on iron absorption may not be effective during inflammation, because of increased serum hepcidin. Our study aim was to test whether reducing inflammation in iron-depleted overweight women with low-grade inflammation would lower serum hepcidin and improve iron absorption with and without ascorbic acid, compared to normal-weight women without inflammation. Before and after 14d of anti-inflammatory treatment (3x600mg ibuprofen daily) in overweight and normal-weight women (n=36; age 19-46 y), we measured serum hepcidin and fractional iron absorption (erythrocyte iron incorporation) from 57Fe- and 58Fe-labeled test meals with and without ascorbic acid. There were significant group effects on interleukin (IL)-6, C-reactive protein, serum ferritin, and SHep (for all, p<0.05). There was a significant treatment effect on SHep (p<0.05): in overweight women, treatment decreased IL-6 by ≍30% and SHep by ≍45%. However, there were no significant treatment or group effects on FIA. Body iron stores were a significant positive predictor of SHep before and after treatment (p<0.001), but IL-6 was not. Reducing chronic inflammation in overweight women halved SHep but did not affect iron absorption with or without ascorbic acid, and the main predictor of iron absorption was body iron stores.

To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses.One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.

Background: The correlate(s) of protection against SARS-CoV-2 remain incompletely de-fined. Additional information regarding the combinations of antibody and T cell-mediated immunity which can protect against (re)infection are needed. Methods: We conducted a population-based, longitudinal cohort study including 1044 individuals of varying SARS-CoV-2 vaccination and infection statuses. We assessed Spike (S)- and Nucleocapsid (N)-IgG and wildtype, delta, and omicron neutralizing antibodies. In a subset of 328 individuals, we evaluated S, Membrane (M) and N-specific T cells. 3 months later, we reassessed antibody (n=964) and T cell (n=141) responses and evaluated factors associated with protection from (re)infection. Results: At study start, >98% of participants were S-IgG seropositive. N-IgG and M/N-T cell responses increased over time, indicating viral (re)exposure, despite existing S-IgG. Com-pared to N-IgG, M/N-T cells were a more sensitive measure of viral exposure. N-IgG titers in the top 33% of participants, omicron neutralizing antibodies in the top 25%, and S-specific T cell responses were all associated with reduced likelihood of (re)infection over time. Conclusions: Population-level SARS-CoV-2 immunity is S-IgG-dominated, but heterogenous. M/N T cell responses can distinguish previous infection from vaccination, and monitoring a combination of N-IgG, omicron neutralizing antibodies and S-T cell responses may help estimate protection against SARS-CoV-2 (re)infection.

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