RESUMEN
Lethal lipid peroxidation caused by reactive oxygen species occurs in different types of programmed cell death, especially in ferroptosis. Ferroptosis inducers, which serve as small-molecule probes, can provide insight into the mechanism of ferroptosis and facilitate drug discovery. The classical ferroptosis inducers indirectly lead to lipid peroxidation; thus, it is difficult to explore lipid regulation during the ferroptotic process. In this study, we designed two quinazolinone-based lipophilic probes BODIQPy-TPA and QPy-TPA, which proved to directly induce lipid peroxidation by light irradiation in vitro. The probe BODIQPy-TPA, which was mainly distributed in the endoplasmic reticulum (ER), specifically triggered ferroptosis in B16 and HepG2 cells upon light irradiation. As a comparison, the probe QPy-TPA, which was mainly distributed in lipid droplets (LDs), induced cell death by a nonferroptotic pathway. Further lipidomic analysis revealed that these two probes caused different patterns of lipid regulation and lipid peroxidation, suggesting that ferroptosis might activate distinct lipid regulation.
Asunto(s)
Ferroptosis , Muerte Celular , Apoptosis , Peroxidación de Lípido , Retículo Endoplásmico , LípidosRESUMEN
:To explore the value of quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging ï¼DCE-MRIï¼ in pathological classification of uterine leiomyoma and its correlation with Ki-67 protein expression. Thirty five patients with uterine leiomyoma confirmed by operation and pathology at Shaoxing People's Hospital from October 2015 to September 2017 were analyzed retrospectivelyï¼including 15 cases of ordinary typeï¼8 cases of cellular type and 12 cases of degenerative type. All patients were examined by pelvic DCE-MRI before operationï¼and the histogram parameters ï¼medianï¼meanï¼skewnessï¼kurtosisï¼energyï¼entropyï¼ of various quantitative perfusion parametersï¼including volume transport constant ï¼Kï¼ï¼rate constant ï¼Kï¼ï¼extravascular extracellular space distribute volume per unit tissue volume ï¼Vï¼ï¼blood plasma volume per unit volume of tissue ï¼Vï¼ were calculatedï¼and the efficacy of different parameters in pathological classification of uterine leiomyoma was evaluated by ROC curve. The expression of Ki-67 protein in uterine leiomyoma was detected by immunohistochemical methodï¼and the correlation between histogram parameters and Ki-67 protein expression was analyzed by Pearson and Spearman correlation analysis. The median and mean values of Kï¼Kï¼V and V in the cellular group were higher than those in the degenerative group and the ordinary groupï¼<0.05 or <0.01ï¼ï¼while the skewness of Vï¼the skewness and kurtosis of K in the cellular group were lower than those in the ordinary group ï¼all <0.05ï¼. The entropy of K in the cellular group was higher than that in the degenerative group and the ordinary group ï¼all < 0.05ï¼. The entropy of V in the cellular group was higher than that in the ordinary group ï¼<0.01ï¼. The medianï¼meanï¼skewness of Kï¼median and mean of Kï¼median and mean of Vï¼medianï¼meanï¼energy and entropy of V were correlated with Ki-67 expressionï¼all <0.05ï¼. The results of ROC curve analysis showed that the median threshold of K was 0.994/minï¼the sensitivity and specificity for the diagnosis of cellular uterine leiomyoma were 100.0% and 77.8% respectivelyï¼and the area under the ROC curve was 0.949. When the mean threshold of K was 1.170/minï¼the sensitivity and specificity for diagnosing cellular uterine leiomyoma were 100.0% and 77.8% respectivelyï¼and the area under the ROC curve was 0.958. The area under the ROC curve of K ï¼entropyï¼ï¼K ï¼medianï¼meanï¼ï¼V ï¼medianï¼meanï¼entropyï¼ in the diagnosis of cellular uterine leiomyoma were 0.755-0.907. :DCE-MRI quantitative perfusion histogram parameters have high diagnostic value in differentiating pathological types of uterine leiomyomaï¼especially for cellular uterine leiomyoma.