Amyloid precursor protein regulates 5-fluorouracil resistance in human hepatocellular carcinoma cells by inhibiting the mitochondrial apoptotic pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality globally. It accounts for the majority of primary liver cancer cases. Amyloid precursor protein (APP), a cell membrane protein, plays a vital role in the pathogenesis of Alzheimer's disease, and has been found to be implicated in tumor growth and metastasis. Therefore, to understand the relationship between APP and 5-fluorouracil (5-FU) resistance in liver cancer, Cell Counting Kit-8, apoptosis and cell cycle assays, western blotting, and reverse transcription-quantitative polymerase chain reaction (qPCR) analysis were performed. The results demonstrated that APP expression in Bel7402-5-FU cells was significantly up-regulated, as compared with that in Bel7402 cells. Through successful construction of APP-silenced (siAPP) and overexpressed (OE) Bel7402 cell lines, data revealed that the Bel7402-APP751-OE cell line was insensitive, while the Bel7402-siAPP cell line was sensitive to 5-FU in comparison to the matched control group. Furthermore, APP overexpression decreased, while APP silencing increased 5-FU-induced apoptosis in Bel7402 cells. Mechanistically, APP overexpression and silencing can regulate the mitochondrial apoptotic pathway and the expression of apoptotic suppressor genes (B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl)). Taken together, these results preliminarily revealed that APP overexpression contributes to the resistance of liver cancer cells to 5-FU, providing a new perspective for drug resistance.

Anestesia, demencias y enfermedad de Alzheimer: ¿coincidencia o certeza? / Anesthesia, dementia and Alzheimer's disease: coincidence or certainty?

Existe creciente evidencia derivada de modelos experimentales in vitro, cultivos celulares y modelos animales que sugiere el efecto de la anestesia sobre la degeneración neuronal y una interacción entre la cirugía, la anestesia y la neuropatología denominada Alzheimer. También existe la firme creencia de que los ancianos corren el riesgo de sufrir deterioro cognitivo transitorio, aunque también puede ser persistente, después de haber sido sometidos a una cirugía mayor, y ese deterioro puede estar asociado a muerte o debilidad. En este trabajo revisamos brevemente los fundamentos básicos de la enfermedad de Alzheimer y su interacción con la anestesia general, y los pocos datos clínicos en humanos que han sido utilizados para proponer una posible asociación entre la anestesia general y las demencias.