Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer

Acetate metabolism is an important metabolic pathway in many cancers and is controlled by acetyl-CoA synthetase 2 (ACSS2), an enzyme that catalyzes the conversion of acetate to acetyl-CoA. While the metabolic role of ACSS2 in cancer is well described, the consequences of blocking tumor acetate metabolism on the tumor microenvironment and antitumor immunity are unknown. We demonstrate that blocking ACSS2, switches cancer cells from acetate consumers to producers of acetate thereby freeing acetate for tumor-infiltrating lymphocytes to use as a fuel source. We show that acetate supplementation metabolically bolsters T-cell effector functions and proliferation. Targeting ACSS2 with CRISPR-Cas9 guides or a small-molecule inhibitor promotes an antitumor immune response and enhances the efficacy of chemotherapy in preclinical breast cancer models. We propose a paradigm for targeting acetate metabolism in cancer in which inhibition of ACSS2 dually acts to impair tumor cell metabolism and potentiate antitumor immunity

Talleres presenciales y virtuales dirigidos a personas mayores: Resignificando hábitos alimenticios; ¡Vamos a crear! Taller de activación cognitiva y estimulación; Me nutro, Me cuido y Me Quiero; Yo y mis Emociones

En este documento se encontrará la información del desarrollo del PAP de Ciudades Globales Amigables con las Personas Mayores en el área metropolitana de Guadalajara correspondiente al periodo escolar de Verano 2022. El objetivo general del PAP que se identificó al inicio de la asignatura con ayuda de todos los integrantes del equipo fue prevenir el deterioro de la calidad de vida que experimentan las personas mayores a través de talleres intergeneracionales que promuevan hábitos saludables con relación a la salud física, social, mental y emocional encaminados a fortalecer su autonomía y autoaceptación. Este proyecto tiene distintos temas por abordar para diseñar, desarrollar y evaluar proyectos que generen alternativas para mejorar las condiciones de vida de las personas mayores que habitan en el AMG en cuanto a el autocuidado, la nutrición, la sociabilización y recreación, las emociones, la estimulación cognitiva, el hábitat, espacio público y espacio privado, comunidad en línea y hospitalidad en servicios. Para el logro del objetivo, se desarrollaron cuatro ejes distintos relacionados con la motricidad, las emociones y la nutrición, en donde cada uno trabajó en la elaboración de talleres diseñados para cuatro sesiones en la presencialidad en el Centro tapatío de atención al Adulto Mayor y en el Centro de Desarrollo Comunitario Reyes Heroles de DIF Guadalajara; una en modalidad virtual a través de WhatsApp y una más a través de Zoom para personas mayores que forman parte de los grupos del DIF Guadalajara, Tlaquepaque, Zapopan y Tlajomulco de Zúñiga.ITESO, A.C

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)