RESUMEN
BACKGROUND: Hypertension and its associated dysfunction of the blood-brain barrier (BBB) are considered to contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), as an important vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension, but also causes BBB leakage, cSVD and its related cognitive impair. Hyperoside (Hyp), a flavone glycoside, has antioxidant, antiphlogistic and anti-apoptosis effects. In this study, we investigate the protection of Hyp on apoptosis of bEnd.3 cells and BBB disruption in vitro induced by Ang II. METHODS: We used bEnd.3 cells to imitate a BBB monolayer model and explored the protection of Hyp on Ang II-induced BBB leakage. The apoptotic activity was assessed by TUNEL staining and flow cytometry. The expression of apoptosis pathway related proteins, tight junction proteins and transcytosis related proteins were detected by western blot assay. The BBB model permeability was detected through measuring the flux of sodium fluorescein (Na-F). RESULTS: We found that Hyp can not only effectively inhibit the apoptosis of bEnd.3 induced by Ang II, but also protect the structural soundness and functional integrity of BBB model by affecting the expression levels of junctional adhesion molecule A (JAM-A), Claudin-5, zonula occludens-1 (ZO-1), Caveolin-1 (Cav-1) and major facilitator superfamily domain-containing protein 2a (Mfsd2a). CONCLUSION: Hyp might be a potent compound for preventing Ang II-induced BBB disruption.
Asunto(s)
Barrera Hematoencefálica , Hipertensión , Angiotensina II/metabolismo , Angiotensina II/farmacología , Animales , Apoptosis , Barrera Hematoencefálica/metabolismo , Humanos , Hipertensión/metabolismo , Ratones , Quercetina/análogos & derivadosRESUMEN
Infantile hemangioma (IH) is one of the most common vascular tumors that occurs during childhood, but its pathogenesis is currently not completely understood. Even though lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays vital roles in tumorigenesis of malignant tumors, its roles in IH remain unclear. Therefore, we evaluate the function of lncRNA NEAT1 in IH. Reverse transcription-quantitative PCR indicated that IH tissues exhibited high expression levels of NEAT1 and hypoxiainducible factor 1α (HIF1α), and low expression levels of the microRNA (miR)33a5p. Small interfering RNAmediated depletion of NEAT1 suppressed hemangioma endothelial cell (HemEC) proliferation, migration and invasion. The data suggested that NEAT1 positively regulated HIF1α expression by sponging miR33a5p in HemECs. miR33a5p overexpression or HIF1α silencing also acted to suppress HemEC proliferation, migration and invasion. Furthermore, the results indicated that the NEAT1/miR33a5p/HIF1α axis regulated the NFκB signaling pathway. Collectively, the results revealed that depletion of lncRNA NEAT1 suppressed the tumorigenesis of IH by competitively binding miR33a5p and thereby stimulating the HIF1α/NFκB signaling pathway.
Asunto(s)
Hemangioma/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regiones no Traducidas 3' , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lactante , Masculino , FN-kappa B/metabolismo , ARN Largo no Codificante/antagonistas & inhibidores , ARN Interferente Pequeño/farmacología , Transducción de Señal/efectos de los fármacos , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To evaluate whether neutrophil-lymphocyte ratio(NLR) predicts risk of recurrence in patients with advanced colon cancer undergoing curative resection followed by adjuvant chemotherapy. METHODS: A total of 149 patients with advanced colon cancer undergoing curative resection followed by adjuvant chemotherapy(FOLFOX6 protocol) were included. NLR was calculated preoperatively and before chemotherapy. The changes in NLR and the predictive value of NLR for prognosis were analyzed. RESULTS: The NLR of 149 patients was 2.8±1.5. NLR of 3.5 was identified according to the ROC curve. NLR<3.5 and NLR≥3.5 were classified as low and high NLR group, respectively. The 5-year recurrence-free survival(RFS) of patients with high preoperative NLR(n=22) was significantly worse than that of those with low preoperative NLR(n=127)(50.9% vs. 76.4%, P=0.025). The difference of 5-year RFS between high pre-chemotherapy NLR group(n=34) and low pre-chemotherapy NLR group(n=115) was statistically significant(50.1% vs. 71.4%, P=0.032). The 5-year RFS was 79.5% in patients with low preoperative NLR converting to high pre-chemotherapy NLR(n=16), similar to the group with high pre-chemotherapy group(P=0.077). The 5-year RFS was 17.7% in patients with high preoperative NLR reverting to low pre-chemotherapy NLR(n=12), similar to the group with low pre-chemotherapy group(P=0.978). There was significant difference in 5-year RFS between the postoperatively elevated group and postoperatively decreased group(P=0.036). CONCLUSION: An elevated blood NLR may be a biomarker of poor RFS in patients with advanced colon cancer after curative resection and chemotherapy.