Cocoa Consumption Decreases Oxidative Stress, Proinflammatory Mediators and Lipid Peroxidation in Healthy Subjects: A Randomized Placebo-Controlled Dose-Response Clinical Trial.

INTRODUCTION: Cocoa flavonoids have been described to reduce the cardiovascular risk. Nevertheless, the involved mechanisms should be clarified and the dose-effect relation has never been evaluated. AIM: To investigate the dose-dependent effects of cocoa flavonoids on markers of endothelial and platelet activation and oxidative stress. METHODS: According to a randomized, double-blind, controlled, cross-over design, 20 healthy nonsmokers were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. RESULTS: Compared with flavonoid-free cocoa control, cocoa reduced sICAM-1 mean values [from 1190.2 to 1123.0; 906.3; 741.7 and 625.6 pg/mL (p = 0.0198 and p = 0.0016, for 500 and 800 mg respectively], sCD40L mean values [from 218.8 to 210.2; 165.5; 134.5 and 128.4 pg/mL (p = 0.023 and p = 0.013, for 500 and 800 mg respectively] and 8-isoprostanes F2 mean values [from 4703.9 to 4670.7; 2000.1; 2098.4 and 2052.3 pg/mL (p = 0.025; p = 0.034 and p = 0.029, for 200, 500 and 800 mg respectively)]. CONCLUSIONS: In our study we observed that short-term cocoa consumption improved proinflammatory mediators, lipid peroxidation and oxidative stress with a significant effect for higher dosages of flavonoids. Our findings suggest cocoa might be a valid tool for dietary intervention in prevention of atherosclerosis.

Electrocardiographic Abnormalities in Hospitalized Patients with COVID-19 and the Associations with Clinical Outcome.

The cardiovascular (CV) system can often be affected during SARS-CoV-2 infection and several acute manifestations, such as myocardial infarction, pericarditis, myocarditis and arrhythmias have been described. We provide a retrospective overview of electrocardiographic (ECG) features and their relationship with clinical outcomes in a cohort of patients admitted to our COVID-19 Unit between November 2020 and May 2021. Resting standard 12-lead ECGs were performed in all patients at admission and in those recovering from SARS-CoV-2 infection also at discharge. Clinical and serological records alongside ECG measurements were retrospectively evaluated and statistical analysis was performed to identify relationships between variables. A total of 123 patients (44% females) with a mean age of 73.9 years were enrolled. Ninety-five (77%) patients recovered from SARS-CoV-2 infection and were discharged while 28 (23%) died in hospital. Almost 90% of patients displayed at least one CV risk factor and 41 (33%) patients had at least one previous CV event. We observed that heart rate, corrected QT interval dispersion (QTcd) and inverted T waves are independently associated with in-hospital death and inverted T waves show the strongest association. This association remained significant even after correcting for the number of CV risk factors at baseline and for the type of CV risk factor at baseline. Our study demonstrated that some ECG abnormalities at admission are independently associated with in-hospital death regardless of pre-existing CV risk factors. These findings may be of particular relevance in clinical settings with limited access to advanced techniques, such as cardiac magnetic resonance and could help improve the outcomes of patients with cardiac involvement related to SARS-CoV-2 infection.

Acute and Long Term Effects of a Nutraceutical Combination on Lipid Profile, Glucose Metabolism and Vascular Function in Patients with Dyslipidaemia with and Without Cigarette Smoking.

INTRODUCTION: Lifestyle changes present a fundamental role in cardiovascular prevention. Nutraceuticals also supplementing diet could help in controlling the cardiometabolic risk. AIM: (1) to evaluate acute effects of a combination of nutraceuticals (cNUT) on vascular function, BP, metabolism in dyslipidaemic patients before and after smoking; (2) to evaluate 12 weeks effects of the cNUT on lipid profile, insulin resistance and vascular function in patients with hypercholesterolemia not on statins. METHODS: After 14 d run-in period, 33 patients assumed a cNUT [patented formula containing: berberine (531.25 mg), red yeast rice powder (220 mg, 3.3 mg monacolin K) and leaf extract of Morus alba (200 mg) (LopiGLIK®, Akademy Pharma)]. To evaluate acute effects, cNUT or cNUT + smoking (in smoking subjects) on the morning of the first day of the study and then 26 patients prolonged 12 weeks effects. RESULTS: In non smokers, cNUT improved FMD (p = 0.041 for treatment). In smokers, FMD decreased after smoking, this was counteracted by intake of cNUT. In smokers, DBP increased after smoking a cigarette (p = 0.042 for treatment), counteracted by the cNUT intake. In non smokers, thermogenesis was increased after cNUT administration (p < 0.0001 for treatment). After 12 weeks of cNUT, FMD significantly increased (p < 0.05) and SBP (p = 0.04), total cholesterol and LDL cholesterol (p = 0.03) decreased. CONCLUSIONS: Our study suggests benefits of cNUT on cardiovascular prevention in hypercolesterolemic patients, non statin treated, that goes beyond the cholesterol and insulin resistance reduction protecting the subject from negative effects induced by smoking too.

Anti-Inflammatory and Anti-Nociceptive Effects of Cocoa: A Review on Future Perspectives in Treatment of Pain.

Cocoa has been reported to have medicinal properties. It contains a wide range of phytochemicals, including polyphenols, which have been shown to exert anti-inflammatory and antioxidant actions, and also to have a positive effect on pain. Other components of cocoa might be able to positively influence pain perception through various mechanisms. Despite encouraging results from preclinical studies, there is a lack of evidence of antinociceptive effects of cocoa from clinical trials in humans. Further research is needed to better identify the active principles in cocoa, to understand the underlying mechanisms of action, and to establish efficacy in humans.

GMP-grade platelet lysate enhances proliferation and migration of tenon fibroblasts.

Tenon's fibroblasts (TFs), widely employed as in vitro model for many ophthalmological studies, are routinely cultured with FBS. Platelet Lysate (PL), a hemoderivate enriched with growth factors and cytokines has been largely tested in several clinical applications and as substitute of FBS in culture. Here, we investigate whether PL can exert biological effects on TF populations similarly to other cell types. Results show that PL significantly enhances cell proliferation and migration vs. FBS, without influencing cell size/granularity. Upregulation of EGF, VEGF, KDR, MMP2-9, FAK mRNA levels also occurs and phosphorylation of AKT but not of ERK1/2 is significantly enhanced. The inhibition of the PI3kinase/AKT pathway with the specific inhibitor wortmannin, decreases PL-induced cell migration but not proliferation. Condition supernatants containing PL show increased bioavailability of Nitric Oxide and reduced levels of 8-Iso-PGF2-alpha, correlating with cell proliferation and migration. Pro-angiogenic/inflammatory soluble factors (GRO, Angiogenin, EGF, I-309, PARC) are exclusively or greater expressed in media containing PL than FBS. GMP-grade PL preparations positively influence in vitro biological effects of TFs representing a suitable and safer alternative to FBS.

KlHsl1 is a component of glycerol response pathways in the milk yeast Kluyveromyces lactis.

In Saccharomyces cerevisiae, HSL1 (NIK1) encodes a serine-threonine protein kinase involved in cell cycle control and morphogenesis. Deletion of its putative orthologue in Kluyveromyces lactis, KlHSL1, gives rise to sensitivity to the respiratory inhibitor antimycin A (AA). Resistance to AA on glucose (Rag+ phenotype) is associated with genes (RAG) required for glucose metabolism/glycolysis. To understand the relationship between RAG and KlHSL1, rag and Klhsl1Δ mutant strains were investigated. The analysis showed that all the mutants contained a phosphorylated form of Hog1 and displayed an inability to synthesize/accumulate glycerol as a compatible solute. In addition, rag mutants also showed alterations in both cell wall and membrane fatty acids. The pleiotropic defects of these strains indicate that a common pathway regulates glucose utilization and stress response mechanisms, suggesting impaired adaptation of the plasma membrane/cell wall during the respiratory-fermentative transition. KlHsl1 could be the link between these adaptive pathways and the morphogenetic checkpoint.