Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles.

Liver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one-directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs-derived conditioned medium (CM) was harvested from different time intervals (Day 0-2: CM-D2 and Day 5-7: CM-D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM-D2 significantly induced the inflammatory phenotype in KCs, but not CM-D7. Neither CM-D2 nor CM-D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs-derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV-depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll-like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.

Protective effect of metformin against palmitate-induced hepatic cell death.

Lipotoxicity causes hepatic cell death and therefore plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metformin, a first-line anti-diabetic drug, has shown a potential protective effect against NAFLD. However, the underlying mechanism is still not clear. In this study, we aim to understand the molecular mechanism of the protective effect of metformin in NAFLD, focusing on lipotoxicity. Cell death was studied in HepG2 cells and primary rat hepatocytes exposed to palmitate and metformin. Metformin ameliorated palmitate-induced necrosis and apoptosis (decreased caspase-3/7 activity by 52% and 57% respectively) in HepG2 cells. Metformin also reduced palmitate-induced necrosis in primary rat hepatocytes (P < 0.05). The protective effect of metformin is not due to reducing intracellular lipid content or activation of AMPK signaling pathways. Metformin and a low concentration (0.1 µmol/L) of rotenone showed moderate inhibition on mitochondrial respiration indicated by reduced basal and maximal mitochondrial respiration and proton leak in HepG2 cells. Moreover, metformin and rotenone (0.1 µmol/L) preserved mitochondrial membrane potential in both HepG2 cells and primary rat hepatocytes. In addition, metformin and rotenone (0.1 µmol/L) also reduces reactive oxygen species (ROS) production and increase superoxide dismutase 2 (SOD2) expression. Our results establish that metformin AMPK-independently protects against palmitate-induced hepatic cell death by moderate inhibition of the mitochondrial respiratory chain, recovering mitochondrial function, decreasing cellular ROS production, and inducing SOD2 expression, indicating that metformin may have beneficial actions beyond its glucose-lowering effect and also suggests that mitochondrial complex І may be a therapeutic target in NAFLD.

Cumplimiento de estándares de calidad en la atención del parto institucional y nivel de satisfacción de usuarias / Meeting standards of quality care and institutional delivery

Objetivos: Determinar la correlación entre el nivel de satisfacción de usuarias y el nivel de cumplimiento de índices estandarizados de atención del parto en 58 establecimientos de salud del Perú. Materiales y Métodos: Se realizó un estudio transversal y comparativo aplicado a una población de 21 departamentos del Perú realizada en forma aleatoria (37 hospitales y 21 centros de salud cabeceras de red. Se utilizaron dos instrumentos: Encuesta de satisfacción a puérperas usuarias de los establecimientos de salud y la lista de chequeo para la medición de procesos de calidad de atención en servicios materno perinatales. Para el análisis de los datos se realizó un análisis bivariado y se utilizó el coeficiente de correlación de Spearman. Resultados: El Coeficiente de Correlación de Spearman entre el "Grado de satisfacción de la puérpera usuaria de los servicios de atención de parto" y el "Porcentaje de cumplimiento del manejo estandarizado de atención del parto" resultó de 0.027, lo que revela la no existencia de relación directa entre dichas variables. Conclusiones: En el presente trabajo se demuestra la falta de correlación entre el nivel de satisfacción de usuarias y el nivel de cumplimiento de índices estandarizados de atención del parto en los Centros Hospitalarios.

Objectives: To determine the correlation between the level of users satisfaction and the fulfillment level of attention childbirth standardized indexes in Peru Health establishments. Methods: A cross-sectional and comparative study was made applied to a population of 58 Health Establishments in 21 departments of Peru made in random form. Two instruments were used: One for the survey of satisfaction to puerperal users and another for the fullfielment attention quality processes measurement in maternal perinatal services. For the analysis of the data a bivaried analysis was made and the Spearman's Correlation Coefficient was used. Results: The Spearman Correlation Coefficient between the principal variables was from 0,027. Conclusions: This work demonstrates the lack of correlation between the users satisfaction level and the level of standardized childbirth attention fulfillment in Health Centers.