ABSTRACT
Objective:To investigate the predictive value of neutrophil to lymphocyte ratio (NLR) for hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS).Methods:Consecutive patients with AIS without performing intravenous thrombolysis and mechanical thrombectomy admitted to the Cerebrovascular Disease Treatment Center, the Affiliated Brain Hospital of Nanjing Medical University from December 2015 to December 2020 were enrolled. The clinical, imaging and laboratory examination data were collected. HT was defined as the first imaging examination of AIS patients without finding bleeding signs, but the imaging reexamination after hospitalization found intracranial hemorrhage. Multivariate logistic regression analysis was used to determine the independent correlation between NLR and HT. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of NLR for HT. Results:A total of 805 patients with AIS were included. The median age was 67 years (interquartile range, 63-71 years), the median National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-9), the median NLR was 3.84 (interquartile range, 2.66-5.30). Seventy-ywo patients (8.9%) had HT. There were significant differences in age, baseline systolic blood pressure, baseline NIHSS score, time from onset to admission, time from onset to blood collection, time from onset to imaging reexamination, NLR, atrial fibrillation, history of previous stroke and transient ischemic attack and stroke etiology between the HT group and the non-HT group (all P<0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for HT in patients with AIS after adjusting for confounding factors (odds ratio 1.355, 95% confidence interval 1.099-1.672; P=0.005). The ROC curve analysis showed that the area under the curve of NLR predicting HT was 0.852, and the optimal cut-off value was 4.75. Its sensitivity and specificity of predicting HT were 88.3% and 71.8% respectively. Conclusion:High NLR is an independent risk factor for HT in patients with AIS during hospitalization, and had better predictive value for HT risk.
ABSTRACT
Objective:To investigate the relationship between YES-related protein 1(YAP1)and prostate-specific antigen(PSA)in human castration-resistant prostate cancer(CRPC), and explore the regulation mechanism of YAP1 on PSA.Methods:The luciferase reporter gene was used to detect the activity change of the PSA gene promoter region after the over expression of YAP1 in LNCaP and C4-2 cells.The effect of over expression of YAP1 gene on PSA protein in different prostate cancer cell lines was detected by Western blot(WB)method, and the effect of YAP1 silencing on PSA protein in C4-2 cells was observed.The Q-PCR method was used to further verify the expression change of PSA mRNA affected by YAP1 gene over expressed in C4-2 cells.Meanwhile, WB was used to explore the effect of YAP1 on androgen receptor(AR)in C4-2 cells.Results:After over expression YAP1 in CRPC, the luciferase experiment showed that the average C4-2 cell ratio of experimental group to control group was 3.17815892(>2 times, P<0.001). After Q-PCR detection of all over-expressed YAP1 gene fragments, the measured PSA mRNA values in the experimental groups were 2.306667, 1.553333333, 2.613333333, and 2.673333333, respectively, which were higher than those in the control group(1 time, P<0.001), indicating that the PSA expression was significantly increased.WB analysis showed that after C4-2 cells over expressed YAP1, the AR band was significantly enhanced in the experimental group compared with the control group, suggesting that the AR protein expression in the nucleus was significantly increased in the YAP1 over expression group. Conclusions:YAP1 might positively regulate the PSA expression in CRPC and have an ability to promote AR translocation into the nucleus.
ABSTRACT
Objective:To investigate the effect of exosomes (Exo) secreted by brain vascular endothelial cell bEnd.3 after ischemic preconditioning (IPC) on neurons suffering from oxygen and glucose deprivation (OGD).Methods:bEnd.3 was exposed to OGD for 3 h to simulate IPC in vivo. After 48 h of reoxygenation, the Exo (IPC Exo) in the conditioned medium were extracted and identified by Western blot and transmission electron microscopy. IPC Exo were incubated with primary cultured mouse cortical neurons for 24 h. Confocal microscope was used to observe whether Exo could be uptaked by primary cultured mouse cerebral cortical neurons. The primary cultured cortical neurons were divided into control group, OGD group, OGD+ IPC Exo (5 μg/ml, 10 μg/ml, 20 μg/ml) groups and sham OGD group (treated with Exo secreted by bEnd.3 cultured under normoxia conditions). The cell viability was detected by CCK-8 and cell survival/death detection kit.Results:Transmission electron microscopy showed that the extract of bend.3 culture medium showed typical morphology of Exo, i. e., a double concave disc-shaped vesicle with a diameter of 30-100 nm. Western blot analysis showed that the extract of bEnd.3 medium highly expressed Exo markers Alix and Tsg101. Confocal microscopy showed that Exo could be uptaked by primary cultured mouse cortical neurons, and the uptake of Exo was widely distributed in the cytoplasm and synapses. Compared with the OGD group, the addition of 10 and 20 μg/ml IPC Exo could significantly increased the neuronal viability ( P<0.05), while the addition of sham Exo had no neuroprotective effect. Conclusion:Exo released by cerebral vascular endothelial cells after IPC have protective effect on neurons suffering from OGD.