No abstract

Sex differences in adaptive and innate immune responses have been shown to occur and anecdotal reports suggest that vaccine efficacy and safety may be sex-dependent. We investigated the influence of sex on the efficacy of COVID-19 vaccines through a systematic review and meta-analysis of clinical trials on COVID-19 vaccines. The safety profile of COVID-19 vaccines was also investigated. A systematic review included eligible articles published in three databases and three websites. A meta-analysis of available data, stratified by sex, was conducted. Statistical analysis was performed using the Hartung–Knapp–Sidik–Jonkman method, as well as influence and heterogeneity analysis. Pooled analysis showed significantly higher efficacy, measured as the rate of new COVID-19 cases, in men compared to women in the vaccine group (OR = 0.67, 95% CI 0.48–0.94). No sex differences were found in the rate of new cases in the control group (OR = 0.92, 95% CI 0.78–1.09). Safety profiles derived from pharmacovigilance reports appear to indicate increased toxicity in women. In conclusion, evidence of a potential role of sex in COVID-19 vaccine efficacy was described. It strengthens the need to include sex as a core variable in the clinical trial design of COVID-19 vaccines.

Resveratrol (3,5, is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.properties of resveratrol are, however, marked by a pharmacokinetic profile and by an unfavorable oral bioavailability, which requires a thorough analysis. To date, to the best of our knowledge, scientific papers and reviews summarizing multiple characteristics of resveratrol, its pharmacokinetic, pharmacodynamic profiles and potential drug interaction in oncology are lacking in literature. Therefore, this review aimed to describe the potential use of resveratrol in cancer management presenting the main biochemical pathways involved, issues and potential uses in cancer patients. Moreover, the involvement of resveratrol in cardioncology, its potential use for risk reduction of myocardial ischemia, myocarditis, cardiac hypertrophy as well as heart failure are also discussed. To endorse this review, we made a comprehensive search on PubMed, Web of Science and SciFinder. The search terms were "resveratrol" combined with "cardioncology" or "cancer" or "drug-food" or "cardiology" or "pharmacokinetic" or "pharmacodynamic". Physico-Chemical and Pharmacokinetic Properties of ResveratrolResveratrol is a low molecular weight phyto-polyphenol of 228 Da that appears as an off-white powder with lipophilic properties (octanol/water partition coefficient, log Kow = 3.1). Its melting point is between 253 and 255 • C, and its solubility in water is very low (3 mg/100 mL) [8]. The ethylene bridge due to a limited degree of freedom generates two geometric isomers: cis-resveratrol and trans-resveratrol ( Figure 1) [5]. These isoforms co-exist in resveratrol extracts even if a greater biological activity and stability are attributed to trans-resveratrol. Comparing to the geometric isomers, the nearly planar structure of trans-resveratrol is less flexible than the non-planar structure of cis-resveratrol, but it possesses a lower repulsive energy that ensures it, albeit small, higher stability. Isomerization of trans-resveratrol to cis-resveratrol occurs via molecule breakdown when trans-resveratrol is exposed to UV radiation at a wavelength of 254 or 366 nm, to high pH conditions or in plants during fermentation processes [5,9]. In analyzing some physical-chemical aspects of resveratrol, Zupancic et al. showed how trans-resveratrol is rapidly degradable in high-pH solutions. In par...