Giovanni Vanni Frajese

Endothelial cell dysfunction plays a key role in the pathogenesis of severe and critical COVID-19, leading to a multi-systemic inflammatory disease, and results from the direct interaction of the SARS-CoV-2 Spike proteins with endothelial cells. COVID-19 RNA vaccines encode a recombinant SARS-CoV-2 Spike protein which undergoes systemic biodistribution. No information is however so far available on the direct effects of COVID-19 RNA vaccines on human endothelial cells. In the present study, we exposed cultured human umbilical venous endothelial cells (HUVEC) to the COVID-19 RNA vaccine Spikevax ^TM (Moderna, Inc.), and thereafter we measured the expression of the Spike protein, of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as the attachment of human leukocytes to HUVEC layers. We also assessed the effects of Spikevax ^TM on HUVEC viability. Exposure of HUVEC to the COVID-19 RNA vaccine Spikevax ^TM resulted in effective cell transfection, and subsequent production of the Spike protein, which was expressed in the cells and secreted in the culture medium. Spike protein production was accompanied by increased gene expression of IL-6 and TNF-α and of ICAM-1 and VCAM-1, as well as by increased attachment of leukocytes to HUVEC monolayers. Exposure to the COVID-19 RNA vaccine Spikevax ^TM did not affect HUVEC viability. Our results provide a mechanistic explanation to post-COVID-19 RNA vaccination pathologies resulting from endothelial dysfunction, such as during atherosclerosis, autoimmune inflammation, and systemic inflammatory conditions.

The spread of COVID-19 led to an extremely high number of deaths in Italy in 2020 with respect to previous years. Because the total number of deaths may depend on both the population structure and the mortality rate by age groups, a detailed overview of the Italian pandemic situation is here provided by following two main lines of inquiry: (i) checking for similarities and differences among mortality rates per age groups before and during the COVID-19 spread; (ii) analyzing the responsiveness of the Italian population structure to different mortality rates. Real-based evidence led us to conduct analyses for two groups associated with different population stages of life, referred to as younghood and adulthood periods. We focus on the Italian pandemic from February 2020 to March 2021. Our study helps to understand why elders dramatically impacted the total number of deaths. In addition, it reveals how badly the 2020 Italian population structure would have reacted to mortality rates already faced in the past. Finally, politicians, scientists, and journalists’ statements and other ways of communicating information about COVID-19 are questioned in the light of scientific data available at that time.

Electrochemical reduced water (ERW) has been proposed to have beneficial effects on human health due to its rich content of H₂ and the presence of platinum nanoparticles with antioxidant effects. Many studies have demonstrated that ERW scavenging properties are able to reduce the damage caused by oxidative stress in different experimental models. Although few in vivo studies have been reported, it has been demonstrated that ERW may display anticancer effects by induction of tumor cells apoptosis and reduction of both angiogenesis and inflammation. In this study, we show that ERW treatment of MCF‐7, MDA‐MB‐453, and mouse (TUBO) breast cancer cells inhibited cell survival in a time‐dependent fashion. ERW decreased ErbB2/neu expression and impaired pERK1/ERK2 and AKT phosphorylation in breast cancer cells. In addition, ERW treatment induced apoptosis of breast cancer cell lines independently of the status of p53 and ER and PR receptors. Our in vivo results showed that ERW treatment of transgenic BALB‐neuT mice delayed the development of mammary tumors compared to the control. In addition, ERW induced a significant prolongation of tumor‐free survival and a reduction in tumor multiplicity. Overall, these results suggest a potential beneficial role of ERW in inhibiting cancer cells growth.

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least "typical" PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.