Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.

Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.

Biological parameters and estimation of the vectorial capacity of two subspecies of Triatoma protracta (Uhler) and their laboratory hybrids in Mexico.

Chagas disease is one of the most important vector-borne diseases in Latin America. Studying the biological parameters of each vector species or subspecies contributes to our understanding of their epidemiologic importance. The aim of our study was to compare the biological parameters and start to estimate the vectorial capacity of Triatoma protracta protracta Ryckman, T. p. nahuatlae Ryckman, and their laboratory hybrids. Specifically, we estimated nine biological parameters to increase knowledge about the potential role of triatomine hybrids in the transmission of T. cruzi to reservoir hosts. Nine biological parameters related to the lifecycle, feeding and defecation patterns, number of females, fecundity, and egg eclosion rates in cohorts of T. p. protracta, T. p. nahuatlae, and their hybrids were evaluated and compared. Eight parameters (exception: number of laid eggs) indicated that T. p. nahuatlae was a potentially effective vector of T. cruzi. Our results showed that the hybrid cohorts had better fitness and could potentially have higher vectorial capacity than the parental cohorts. The outstanding characteristics of the hybrids found in our study could lead to an increase in the epidemiologic risks caused by transmission of T. cruzi to humans.