RESUMEN
Breast cancer brain metastases (BCBM) are a significant cause of mortality and are incurable. Thus, identifying BCBM targets that reduce morbidity and mortality is critical. BCBM upregulate Stearoyl-CoA Desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, suggesting a potential metabolic vulnerability of BCBM. In this study, we tested the effect of a brain-penetrant clinical-stage inhibitor of SCD (SCDi), on breast cancer cells and mouse models of BCBM. Lipidomics, qPCR, and western blot were used to study the in vitro effects of SCDi. Single-cell RNA sequencing was used to explore the effects of SCDi on cancer and immune cells in a BCBM mouse model. Pharmacological inhibition of SCD markedly reshaped the lipidome of breast cancer cells and resulted in endoplasmic reticulum stress, DNA damage, loss of DNA damage repair, and cytotoxicity. Importantly, SCDi alone or combined with a PARP inhibitor prolonged the survival of BCBM-bearing mice. When tested in a syngeneic mouse model of BCBM, scRNAseq revealed that pharmacological inhibition of SCD enhanced antigen presentation by dendritic cells, was associated with a higher interferon signaling, increased the infiltration of cytotoxic T cells, and decreased the proportion of exhausted T cells and regulatory T cells in the tumor microenvironment (TME). Additionally, pharmacological inhibition of SCD decreased engagement of immunosuppressive pathways, including the PD-1:PD-L1/PD-L2 and PVR/TIGIT axes. These findings suggest that SCD inhibition could be an effective strategy to intrinsically reduce tumor growth and reprogram anti-tumor immunity in the brain microenvironment to treat BCBM.
RESUMEN
RESUMEN Fundamento: El dormir adecuadamente es una necesidad fisiológica de primer orden. Cuestiones tan cotidianas como la carga académica, tareas domésticas, o el trabajo nocturno, contribuyen a que algunos se priven de las horas de sueño recomendadas, y ello trae consecuencias para la salud, el estado anímico, y la inteligencia emocional. Objetivo: describir la relación entre la somnolencia diurna y la inteligencia emocional en estudiantes universitarios. Métodos: estudio descriptivo, correlacional, con 140 alumnos del sexto al décimo ciclo de la carrera de Terapia Física y Rehabilitación, en la Universidad Norbert Wiener, Lima, Perú. Se aplicó la escala de somnolencia de Epworth para evaluar la somnolencia diurna, y la Trait Meta Mood Scale para inteligencia emocional. Mediante la prueba estadística Rho de Spearman, se evaluó la correlación entre variables. Resultados: la edad media de los estudiantes fue 25,73 ± 4,2 años, y un promedio de horas de sueño de 5,86±1,28. El valor medio de somnolencia diurna fue 9,95±3,6; esta fue ligera en la mayoría de los casos (69,65 %). La inteligencia emocional presentó un valor medio de 78,66±13,08, y fue el factor reparación el de mayor puntuación (28,36±5,63), seguido de la claridad (25,91±5,58) y la atención (24,38±5,50). Se observó una correlación negativa débil entre la somnolencia diurna y la inteligencia emocional (p= 0,058). Conclusión: la somnolencia diurna tiene consecuencias en el comportamiento de las reacciones comprendidas por la inteligencia emocional. Los estudiantes universitarios de Terapia Física y Rehabilitación analizados se caracterizan fundamentalmente por presentar somnolencia diurna ligera e inteligencia emocional adecuada.
ABSTRACT Foundation: Adequate sleep is a physiological necessity of the first order. Issues as daily as academic load, housework, or night work, contribute to some depriving themselves of recommended sleep hours, and this brings consequences for health, mood, and emotional intelligence. Objective: to describe the relationship between daytime sleepiness and emotional intelligence in university students. Methods: descriptive, correlational study, with 140 students from the sixth to the tenth cycle of the Physical Therapy and Rehabilitation degree, at Norbert Wiener University, Lima, Peru. Epworth's sleepiness scale was applied to assess daytime sleepiness, and the Trait Meta Mood Scale for emotional intelligence. By means of Spearman's Rho statistical test, the correlation between variables was evaluated. Results: the students´ average age was 25.73 ± 4.2 years, and an average time hours of sleep was 5.86 ± 1.28 hours. The mean value of daytime sleepiness was 9.95 ± 3.6; This was mild in most cases (69.65%). Emotional intelligence had an average value of 78.66 ± 13.08, and the repair factor was the highest score (28.36 ± 5.63), followed by clarity (25.91 ± 5.58) and attention (24.38 ± 5.50). A weak negative correlation was observed between daytime sleepiness and emotional intelligence (p = 0.058). Conclusion: daytime sleepiness has consequences on the behavior of reactions comprised by emotional intelligence. The analyzed University Physical Therapy and Rehabilitation students are mainly characterized by mild daytime sleepiness and adequate emotional intelligence.