RESUMEN
Preeclampsia is associated with the insufficient invasion of trophoblasts. NF-κB is a transcription factor in almost all mammalian cells and has been validated to be upregulated in the maternal circulation and placenta of women with preeclampsia. MiR-518a-5p is also overexpressed in pre-eclamptic placenta. The present study was designed to explore whether NF-κB can transcriptionally activate miR-518a-5p and investigate the influences of miR-518a-5p on the viability, apoptosis, migration, and invasion of HTR8/SVneo trophoblast. In situ hybridization and real time polymerase chain reaction were used to reveal miR-518a-5p expression in placenta tissues and HTR8/SVneo cells, respectively. Cell migration and invasion were detected using Transwell inserts. Our findings indicated that NF-κB p52, p50, and p65 can bind to miR-518a-5p gene promoter. MiR-518a-5p further influences the levels of p50 and p65 but not p52. HTR8/SVneo cell viability and apoptosis were not influenced by miR-518a-5p. However, miR-518a-5p represses the migratory/invasive capacities of HTR8/SVneo cell and decreased gelatinolytic activity of MMP2 and MMP9, which was reversed by an NF-κB inhibitor. To sum up, miR-518a-5p is induced by NF-κB and represses trophoblast cell migration and invasion by the NF-κB pathway.
Asunto(s)
MicroARNs , Preeclampsia , Embarazo , Animales , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Trofoblastos/metabolismo , FN-kappa B/metabolismo , Preeclampsia/genética , Línea Celular , Movimiento Celular/genética , Proliferación Celular , Mamíferos/genéticaRESUMEN
Sodium dehydroacetate (Na-DHA) is widely used as an antibacterial and preservative additive in food and cosmetics. Previously, we reported that repeated oral administration of Na-DHA induces coagulation disorders, and inhibited liver vitamin K epoxide reductase complex subunit 1 (VKORC1) and VKORC1-like protein 1 (VKORC1L1) in rats. However, the effects of Na-DHA on coagulation factors in rat hepatocytes and the mechanism of VKORC1 and VKORC1L1 signaling in that process are unclear. Here, we constructed stable Vkorc1 and Vkorc1l1 overexpressing cell lines using lentiviruses and transfected small interfering RNAs into buffalo rat liver BRL3A cells for Vkorc1 and Vkorc1l1 overexpression and silencing, respectively. After treatment with 5 mmol/L Na-DHA for 24 h, VKORC1 and VKORC1L1 expression levels were detected by real-time PCR and western blotting. Vitamin K (VK) and factor IX (FIX) contents were detected using enzyme linked immunosorbent assays. We observed that Na-DHA inhibited VKORC1 and VKORC1L1 expression levels and reduced VK and FIX levels in rat hepatocytes. Overexpression or silencing of Vkorc1 and Vkorc1l1 increased or decreased, respectively, the production and secretion of VK and FIX in rat hepatocytes, and alleviated or aggravated the inhibitory effects of Na-DHA on VKORC1 and VKORC1L1 expression levels. Taken together, the results indicated that both VKORC1 and VKORC1L1 signaling play regulatory roles in the effects of Na-DHA on coagulation factors in rat hepatocytes.
Asunto(s)
Hepatocitos , Vitamina K , Ratas , Animales , Vitamina K Epóxido Reductasas/genética , Vitamina K Epóxido Reductasas/metabolismo , Vitamina K/metabolismo , Hepatocitos/metabolismo , Factores de Coagulación SanguíneaRESUMEN
SUMMARY OBJECTIVE To study factors affecting the liver regeneration after hepatectomy METHODS With 3D reconstitution technology, liver regeneration ability of 117 patients was analysed, and relative factors were studied. RESULTS There was no statistically difference between the volume of simulated liver resection and the actual liver resection. All livers had different degrees of regeneration after surgery. Age, gender and blood indicators had no impact on liver regeneration, while surgery time, intraoperative blood loss, blood flow blocking time and different ways of liver resection had a significant impact on liver regeneration; In addition, the patients' own pathological status, including, hepatitis and liver fibrosis all had a significant impact on liver regeneration. CONCLUSION 3D reconstitution model is a good model to calculate liver volume. Age, gender, blood indicators and biochemistry indicators have no impact on liver regeneration, but surgery indicators and patients' own pathological status have influence on liver regeneration.
RESUMO OBJETIVO Estudar os fatores que afetam a regeneração hepática após hepatectomia. MÉTODOS A capacidade de regeneração hepática de 117 pacientes foi analisada com a tecnologia de reconstituição 3D e foram estudados os fatores relacionados. RESULTADOS Não houve diferença estatística significante entre o volume de ressecção hepática simulada e a ressecção atual. Todos os fígados apresentaram diferentes graus de regeneração após cirurgia. Idade, gênero e indicadores sanguíneos não tiveram impacto na regeneração hepática, enquanto que tempo de cirurgia, perda sanguínea intraoperatória, tempo de bloqueio do fluxo sanguíneo e diferentes formas de ressecção mostraram impacto significante na regeneração do órgão. Além disso, condições patológicas dos pacientes, incluindo hepatite e fibrose hepática, tiveram impacto significante na regeneração hepática. CONCLUSÃO O modelo de reconstituição 3D é um bom modelo para calcular o volume do fígado. Idade, gênero, indicadores sanguíneos e bioquímicos não tiveram impacto na regeneração hepática, mas indicadores operatórios e condição patológica dos pacientes mostraram influência na regeneração do órgão.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/cirugía , Hepatectomía/rehabilitación , Neoplasias Hepáticas/cirugía , Regeneración Hepática/fisiología , Tamaño de los Órganos , Factores de Riesgo , Análisis de Varianza , Pérdida de Sangre Quirúrgica , Resultado del Tratamiento , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/rehabilitación , Imagenología Tridimensional , Carga Tumoral , Tempo Operativo , Hepatitis/patología , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/rehabilitación , Persona de Mediana Edad , Modelos AnatómicosRESUMEN
OBJECTIVE: To study factors affecting the liver regeneration after hepatectomy. METHODS: With 3D reconstitution technology, liver regeneration ability of 117 patients was analysed, and relative factors were studied. RESULTS: There was no statistically difference between the volume of simulated liver resection and the actual liver resection. All livers had different degrees of regeneration after surgery. Age, gender and blood indicators had no impact on liver regeneration, while surgery time, intraoperative blood loss, blood flow blocking time and different ways of liver resection had a significant impact on liver regeneration; In addition, the patients' own pathological status, including, hepatitis and liver fibrosis all had a significant impact on liver regeneration. CONCLUSION: 3D reconstitution model is a good model to calculate liver volume. Age, gender, blood indicators and biochemistry indicators have no impact on liver regeneration, but surgery indicators and patients' own pathological status have influence on liver regeneration.