RESUMO
One of the most relevant and differentiating aspects provided by the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure is the retraction of the historical stepped and vertical pharmacological treatment scheme for heart failure with reduced ejection fraction (HFrEF). Subsequently, it was replaced by an updated algorithm that places four therapeutic families in the same initial horizontal step with an equally high degree of recommendation (class I). In this context, these four pillars, which have demonstrated a significant reduction in mortality and hospitalizations in patients with HFrEF, include (1) angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin II receptor-neprilysin inhibitors (ARNi), (2) beta blockers, (3) mineralocorticoid receptor antagonists (MRA) and (4) sodium-glucose cotransporter 2 inhibitors (SGLT2is) as the main novelty. This manuscript reviews the current therapeutic algorithm with a special focus on the therapeutic value of adding an MRA (still underused in both clinical trials and real world), changing an ACEi/ARB for an ARNi and incorporating an SGLT2i in patients with HFrEF. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.
RESUMO
RESUMEN El ARN de interferencia (ARNi) es un mecanismo evolutivamente conservado en la mayoría de las células eucariotas que permite silenciar genes mediante la degradación de ARN mensajero (ARNm) y la supresión de la síntesis de proteínas. En plantas, las moléculas de ARNi están involucradas en mecanismos de defensa contra patógenos y transposones, en la respuesta adaptativa al estrés, y en la expresión de genes relacionados con su crecimiento. El ARNi se considera una herramienta biotecnológica eficaz para silenciar la expresión de genes de microorganismos fitopatógenos, esto permite el diseño de bioplaguicidas ambientalmente seguros con una afinidad y selectividad, en muchos casos superior a la de los plaguicidas químicos. En esta revisión se señalan los últimos avances en la aplicación del ARNi en el contexto agrícola y su efectividad en el control biológico de fitopatógenos e insectos plaga. Asimismo, se presentan diversos ensayos experimentales cuyos resultados pueden ser la base para futuros bioproductos, además de algunos ejemplos disponibles en el mercado. Por último, se abordan aspectos de bioseguridad y consideraciones regulatorias necesarias para la aceptación y uso de esta tecnología a nivel global.
ABSTRACT RNA interference (RNAi) is an evolutionarily conserved mechanism in most eukaryotic cells that allows genes to be silenced by degradation of messenger RNA (mRNA) and suppression of protein synthesis. In plants, RNAi molecules are involved in defense mechanisms against pathogens and transposons, in the adaptive response to stress, and in the expression of genes related to their growth. RNAi is an effective biotechnological tool to silence the expression of specific genes which are essential for the survival of phytopathogenic microorganisms, thus allowing the design of environmentally safe biopesticides with affinity and selectivity, in many cases greater than chemical pesticides. This review describes the latest advances in the application of RNAi in the agricultural context and its effectiveness in the biological control of phytopathogens and pest insects. Likewise, various experimental trials are presented, the results of which may be the basis for future bioproducts, as well as some examples available on the market. Finally, biosafety aspects and regulatory considerations necessary for the acceptance and use of this technology at a global level are presented.