RESUMEN
Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1ß maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5'-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1ß and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.
Asunto(s)
Artritis Gotosa , Proteína Relacionada con la Hormona Paratiroidea , Fragmentos de Péptidos , Ratones , Animales , Artritis Gotosa/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Regulación hacia Arriba , Lipopolisacáridos/efectos adversos , Ácido Úrico , Inflamación/metabolismo , Adenosina Trifosfato , Caspasas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
Abstract Introduction Premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD) may be neuropsychologically understood as impairments of executive functions (EF), since these are related to the regulation of complex behavior and cognition. Objective To test the utility of self-report of EF versus performance-based measures, for the understanding of PMS/PMDD, and to analyze interactive effects between symptoms of these pathologies and EF on daily-life functionality. Method Mexican women were recruited through non-probabilistic procedures. The Premenstrual Symptoms Screening Tool (PSST) was used to determine severity of symptoms and functional impairment in daily-life activities, and the Behavioral Rating Inventory of Executive Functions-Adults (BRIEF-A) (short Spanish-translated version) adapted to collect information on EF during luteal versus follicular phases. Performance was evaluated with Stroop, Trail Making Test and Letter-Number Sequencing. Results A total of 157 were analyzed. Three groups were formed: No diagnosis ( n = 78); PMS ( n = 67) and PMDD ( n = 12). Between-group differences were observed for both BRIEF-A-Luteal and BRIEF-A-Follicular. Bivariate correlations between these measures and the PSST were found, with double the magnitude relative to BRIEF-A-Luteal. Only two indicators of performance-based measures were weakly associated to the PSST. The regression model showed high multicollinearity between self-reported EF and PMS/PMDD symptoms, and no interaction was found. Discussion and conclusion Self-report probed a better association than based-performance tests for the assessment of EF in PMS/PMDD. EF deficits and PMS/PMDD symptoms, particularly during luteal phase, may be as closely link as to allow for the consideration of these diagnoses as partial forms of dysexecutive syndrome.
Resumen Introducción El síndrome premenstrual/trastorno disfórico premenstrual (SPM/TDPM) pueden entenderse neuropsicológicamente como alteraciones de las funciones ejecutivas (FE), ya que éstas permiten la regulación del comportamiento complejo y la cognición. Objetivo Evaluar la utilidad del autorreporte de las FE versus pruebas de desempeño para comprender el SPM/TDPM, y analizar los efectos interactivos entre los síntomas de estas patologías y las FE sobre el funcionamiento diario. Método Mujeres mexicanas fueron reclutadas por medio de procedimientos no probabilísticos. El Instrumento de Detección de Síntomas Premenstruales (PSST) se utilizó para determinar la gravedad de los síntomas y el deterioro funcional en las actividades de la vida diaria, y el Inventario de Evaluación Conductual de la Función Ejecutiva-Adultos (BRIEF-A) (versión breve traducida al español) para recopilar información sobre EF durante las fases lútea versus folicular. Se emplearon también las pruebas de desempeño: Stroop, Trail Making Test y Secuencia de Letras y Números. Resultados Se analizó un total de 157 participantes. Se formaron tres grupos: sin diagnóstico ( n = 78); SPM ( n = 67) y TDPM ( n = 12). Se observaron diferencias entre los grupos para BRIEF-A-Lútea y BRIEF-A-Folicular. Se encontraron correlaciones bivariadas entre estas medidas y el PSST, con el doble de magnitud en relación con BRIEF-A-Lútea. Solo dos indicadores de medidas basadas en el desempeño mostraron una asociación débil con el PSST. El modelo de regresión mostró alta multicolinealidad entre el autorreporte de FE y SPM/TDPM, y no se encontró la interacción esperada. Discusión y conclusión El autorreporte mostró una mejor asociación que las pruebas de rendimiento para la evaluación de FE en SPM/TDPM. Los déficits de EF y los síntomas de SPM/TDPM, particularmente durante la fase lútea, pueden estar tan estrechamente vinculados como para permitir la consideración de estos diagnósticos como formas parciales de síndrome disejecutivo.