Exercise effects on cardiovascular disease: from basic aspects to clinical evidence.

Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, and all-cause mortality. Although exact details regarding the ideal doses of ET, including resistance and, especially, aerobic ET, as well as the potential adverse effects of extreme levels of ET, continue to be investigated, there is no question that most of the world's population have insufficient levels of PA/ET, and many also have lower than ideal levels of CRF. Therefore, assessment and promotion of PA, ET, and efforts to improve levels of CRF should be integrated into all health professionals' practices worldwide. In this state-of-the-art review, we discuss the exercise effects on many areas related to CVD, from basic aspects to clinical practice.

Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity.

Ferulic acid, a bacterial metabolite of anthocyanins, seems likely to be a primary mediator of the health benefits associated with anthocyanin-rich diets, and has long been employed in Chinese cardiovascular medicine. In rodent studies, it has exerted wide-ranging antioxidant and anti-inflammatory effects, the molecular basis of which remains rather obscure. However, recent studies indicate that physiologically relevant concentrations of ferulic acid can boost expression of Sirt1 at mRNA and protein levels in a range of tissues. Sirt1, a class III deacetylase, functions to detect a paucity of oxidisable substrate, and in response works in various ways to promote cellular survival and healthful longevity. Sirt1 promotes 'cell cleansing' and cell survival by boosting autophagy, mitophagy, mitochondrial biogenesis, phase 2 induction of antioxidant enzymes via Nrf2, and DNA repair-while inhibiting NF-kB-driven inflammation, apoptosis, and cellular senescence, and boosting endothelial expression of the protective transcription factor kruppel-like factor 2. A deficit of the latter appears to mediate the endothelial toxicity of the SARS-CoV-2 spike protein. Ferulic acid also enhances the activation of AMP-activated kinase (AMPK) by increasing expression and activity of its activating kinase LKB1-whereas AMPK in turn amplifies Sirt1 activity by promoting induction of nicotinamide phosphoribosyltranferase, rate-limiting for generation of Sirt1's obligate substrate NAD+. Curiously, AMPK acts by independent mechanisms to potentiate many of the effects mediated by Sirt1. Hence, it is proposed that ferulic acid may exert complementary or synergistic health-promoting effects when used in conjunction with clinically useful AMPK activators, such as the nutraceutical berberine. Additional nutraceuticals which might have potential for amplifying certain protective effects of ferulic acid/berberine are also discussed.

Magnesium and Vitamin D Deficiency as a Potential Cause of Immune Dysfunction, Cytokine Storm and Disseminated Intravascular Coagulation in covid-19 patients.

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immune system has been known for decades, the benefits of magnesium has only recently been elucidated. Indeed, magnesium is important for activating vitamin D and has a protective role against oxidative stress. Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation. Furthermore, magnesium deficient animals and humans have depressed immune responses, which, when supplemented with magnesium, a partial or near full reversal of the immunodeficiency occurs. Moreover, intracellular free magnesium levels in natural killer cells and CD8 killer T cells regulates their cytotoxicity. Considering that magnesium and vitamin D are important for immune function and cellular resilience, a deficiency in either may contribute to cytokine storm in the novel coronavirus 2019 (COVID-19) infection.

Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond.

Inflammasomes are intracellular protein complexes that form in response to a variety of stress signals and that serve to catalyze the proteolytic conversion of pro-interleukin-1ß and pro-interleukin-18 to active interleukin-1ß and interleukin-18, central mediators of the inflammatory response; inflammasomes can also promote a type of cell death known as pyroptosis. The NLRP3 inflammasome has received the most study and plays an important pathogenic role in a vast range of pathologies associated with inflammation-including atherosclerosis, myocardial infarction, the complications of diabetes, neurological and autoimmune disorders, dry macular degeneration, gout, and the cytokine storm phase of COVID-19. A consideration of the molecular biology underlying inflammasome priming and activation enables the prediction that a range of nutraceuticals may have clinical potential for suppressing inflammasome activity-antioxidants including phycocyanobilin, phase 2 inducers, melatonin, and N-acetylcysteine, the AMPK activator berberine, glucosamine, zinc, and various nutraceuticals that support generation of hydrogen sulfide. Complex nutraceuticals or functional foods featuring a number of these agents may find utility in the prevention and control of a wide range of medical disorders.

Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

Inflammasomes are intracellular protein complexes that form in response to a variety of stress signals and that serve to catalyze the proteolytic conversion of pro-interleukin-1βand pro-interleukin-18 to active interleukin-1βand interleukin-18, central mediators of the inflammatory response;inflammasomes can also promote a type of cell death known as pyroptosis. The NLRP3 inflammasome has received the most study and plays an important pathogenic role in a vast range of pathologies associated with inflammation—including atherosclerosis, myocardial infarction, the complications of diabetes, neurological and autoimmune disorders, dry macular degeneration, gout, and the cytokine storm phase of COVID-19. A consideration of the molecular biology underlying inflammasome priming and activation enables the prediction that a range of nutraceuticals may have clinical potential for suppressing inflammasome activity—antioxidants including phycocyanobilin, phase 2 inducers, melatonin, and N-acetylcysteine, the AMPK activator berberine, glucosamine, zinc, and various nutraceuticals that support generation of hydrogen sulfide. Complex nutraceuticals or functional foods featuring a number of these agents may find utility in the prevention and control of a wide range of medical disorders.

Takotsubo Syndrome: Cardiotoxic Stress in the COVID Era.

Takotsubo syndrome (TTS), also known as stress cardiomyopathy and broken heart syndrome, is a neurocardiac condition that is among the most dramatic manifestations of psychosomatic disorders. This paper is based on a systematic review of TTS and stress cardiomyopathy using a PubMed literature search. Typically, an episode of severe emotional or physical stress precipitates regions of left ventricular hypokinesis or akinesis, which are not aligned with a coronary artery distribution and are out of proportion to the modest troponin leak. A classic patient with TTS is described; one who had chest pain and dyspnea while watching an anxiety-provoking evening news program on the coronavirus disease 2019 (COVID-19) pandemic. An increase in the incidence of TTS appears to be a consequence of the COVID-19 pandemic, with the TTS incidence rising 4.5-fold during the COVID-19 pandemic even in individuals without severe acute respiratory syndrome coronavirus 2 infection. Takotsubo syndrome is often mistaken for acute coronary syndrome because they both typically present with chest pain, electrocardiographic changes suggesting myocardial injury/ischemia, and troponin elevations. Recent studies report that the prognosis for TTS is similar to that for acute myocardial infarction. This review is an update on the mechanisms underlying TTS, its diagnosis, and its optimal management.