Disruption of mitochondrial membrane potential by ferulenol and restoration by propolis extract: Antiapoptotic role of propolis

This paper reports an investigation of the ability of propolis extract (a resinous substance collected by honeybees from various plant sources) to restore the collapse of mitochondrial membrane potential induced by ferulenol, a sesquiterpene prenylated coumarin derivative isolated from the plant Ferula vesceritensis . We show that ferulenol was able to induce the permeability transition pore (PTP) opening. This effect is caused by the interaction of the compound with the mitochondrial respiratory chain, more particularly by the fall of membrane potential and the inhibition of complex II. We have previously demonstrated that this inhibition results from a limitation of electron transfers involved in the respiratory chain and initiated by the reduction of ubiquinone. We hypothesized that the protective effect of propolis could be due to a direct action on mitochondrial functions. So we have investigated in vitro the mitochondrial effects of Algerian propolis using rat liver mitochondria, by analysing their effects on membrane potential, mitochondrial respiration and mitochondrial swelling. We show that propolis extract was able to restore the fall of mitochondrial membrane potential. Taken together these data reveal that propolis extract may be an interesting inhibitor of PTP and provide an additional mechanism by which the natural product propolis extract may restore the mitochondrial membrane potential and to prevent apoptotic process

Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study

International audienc

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup