The renin–angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE–Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling.

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential.

The search for new drugs with the potential to ensure therapeutic success in the treatment of cardiovascular diseases has become an essential pathway to follow for health organizations and committees around the world. In June 2021, the World Health Organization listed cardiovascular diseases as one of the main causes of death worldwide, representing 32% of them. The most common is coronary artery disease, which causes the death of cardiomyocytes, the cells responsible for cardiac contractility, through ischemia and subsequent reperfusion, which leads to heart failure in the medium and short term. Metformin is one of the most-used drugs for the control of diabetes, which has shown effects beyond the control of hyperglycemia. Some of these effects are mediated by the regulation of cellular energy metabolism, inhibiting apoptosis, reduction of cell death through regulation of autophagy and reduction of mitochondrial dysfunction with further reduction of oxidative stress. This suggests that metformin may attenuate left ventricular dysfunction induced by myocardial ischemia; preclinical and clinical trials have shown promising results, particularly in the setting of acute myocardial infarction. This is a review of the molecular and pharmacological mechanisms of the cardioprotective effects of metformin during myocardial ischemia-reperfusion injury.

Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such as myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such as cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy. Moreover, cardiomyocytes are unable to regenerate; thus, lost cells are replaced with fibrotic tissue, with a potentially severe impact on myocardial function. Several therapeutic agents and strategies to reduce cardiomyocyte damage are currently available. This manuscript reviews the state of the art regarding novel cardioprotective endogenous peptides, such as neuregulin-1, angiotensin-(1-9), growth/differentiation factor-11, growth/differentiation factor- 15 and insulin-like growth factor-1. We discuss their protective effects and therapeutic potential in cardiovascular diseases and the current challenges to harnessing their full cardioprotective power. We also explore targeting of exosomes as a cardioprotective approach along with the therapeutic potential of cardiac regeneration strategies. Further advances associated with these molecules and cardioprotective approaches may provide more effective therapies to attenuate or prevent cardiomyocyte death, thereby preserving the myocardium.

CONTEXT: Genotyping of single nucleotide polymorphism (SNP C/T-13910) located upstream of the lactase gene is used to determine adult-type hypolactasia/lactase persistence in North-European Caucasian subjects. The applicability of this polymorphism has been studied by comparing it with the standard diagnostic methods in different populations. OBJECTIVE: To compare the lactose hydrogen breath test with the genetic test in a sample of the Colombian Caribbean population. METHODS: Lactose hydrogen breath test and genotyping of SNP C/T-13910 were applied to 128 healthy individuals (mean age 35 ± 1). A positive lactose hydrogen breath test was indicative of hypolactasia. Genotyping was done using polymerase chain reaction/restriction fragment length polymorphism. The kappa index was used to establish agreement between the two methods. RESULTS: Seventy-six subjects (59%) were lactose-maldigesters (hypolactasia) and 52 subjects (41%) were lactose-digesters (lactase persistence). The frequencies of the CC, CT and TT genotypes were 80%, 20% and 0%, respectively. Genotyping had 97% sensitivity and 46% specificity. The kappa index = 0.473 indicates moderate agreement between the genotyping of SNP C/T-13910 and the lactose hydrogen breath test. CONCLUSION: The moderate agreement indicates that the genotyping of the SNP C/T-13910 is not applicable to determine adult-type hypolactasia/lactase persistence in the population participating in this study.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin–angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin–angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin–angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin–angiotensin system.