RESUMEN
We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3ß(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.
Asunto(s)
Apoptosis/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/tratamiento farmacológico , Sitoesteroles/farmacología , Animales , Encéfalo/citología , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Glucosa/metabolismo , Glucógeno Sintasa Quinasa 3/biosíntesis , Glucógeno Sintasa Quinasa 3 beta , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/biosíntesis , Oxígeno/metabolismo , Podofilotoxina/análogos & derivados , Podofilotoxina/farmacología , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores de Somatomedina/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/biosíntesisRESUMEN
PURPOSE: the study aimed to compare the quality of life (QOL) and radiotherapy complications among Chinese nasopharyngeal carcinoma (NPC) patients at different 3-dimensional conformal radiotherapy (3DCRT) stages adjusting for other variables. METHODS: 511 NPC patients at different 3DCRT stages were enrolled. They were interviewed regarding SF-36, complications and socio-demographic variables and cancer- or treatment- related variables. Analysis of covariance (ANCOVA) based on SF-36, complications scores as dependent variables, 3DCRT stages as independent variables, and other variables as covariate were established. RESULTS: The influencing factors of PCS included 3DCRT stages and age group. The influencing factors of MCS included 3DCRT stages and income. Most QOL scores of NPC patients were significantly associated with 3DCRT stage, after accounting for other variables. QOL scores of the patients receiving 3DCRT were the lowest, QOL scores of people after 3DCRT gradually increased. PCS scores of people greater than 5 years after 3DCRT was improved to or even better than the level before 3DCRT. The complications with significantly different scores of patients at different 3DCRT status included xerostomia, throat ache, hypogeusia, caries, hearing loss, snuffles. CONCLUSIONS: Clinicians should pay more attention to older NPC patients and patients with lower income. When patients receive 3DCRT, measures should be taken to reduce radiation injury to improve the patients' QOL.