Abstract.Oleuropein is a polyphenol, that is found in extra-virgin olive oil. Previous studies have shown that oleuropein inhibits cell proliferation and induces apoptosis in breast cancer, colorectal cancer and thyroid cancer. The aim of the present study was to investigate the effects of oleuropein in hepatocellular carcinoma (HCC) cells. The results of Cell Counting Kit 8 and flow cytometric analysis indicated that oleuropein effectively inhibited cell viability and induced apoptosis in HepG2 human hepatoma cells in a dose-dependent manner, through activation of the caspase pathway. Proapoptotic Bcl-2 family members, BAX and Bcl-2, were involved in oleuropein-induced apoptosis. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was also shown to be involved in this process. Oleuropein was demonstrated to suppress the expression of activated AKT. In addition, AKT overexpression promoted cell survival following treatment with oleuropein, while inhibition of AKT promoted cell death. Furthermore, the data demonstrated that oleuropein induces the production of reactive oxygen species (ROS) and that the function of oleuropein is, at least partially, ROS-dependent. These results suggest that oleuropein may be a promising novel chemotherapeutic agent in hepatocellular carcinoma. IntroductionHepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality (1). The predominant risk factors for HCC development are infection with hepatitis B or C virus, obesity and excess alcohol intake. The incidence and mortality of HCC is increasing as a result of the current obesity epidemic and rise in alcohol consumption (2). However, only 10-20% of patients with HCC are eligible for surgical resection, due to poorly preserved liver function, portal vein invasion or extrahepatic spread. Furthermore, the risk of recurrence following HCC resection is high (3,4). The available chemotherapeutic and radiotherapeutic treatment options for patients with advanced HCC are also extremely limited. Therefore, it is necessary to develop effective and practical chemotherapeutic agents with minimal cytotoxicity for use in this disease.A number of previous studies have shown that regular consumption of coffee, vitamin E and fish oil may be associated with a reduced risk of developing HCC (5-7). Ecological studies have investigated the association between dietary fat and certain types of cancer (8,9). Hursting et al (8) demonstrated that the intake of saturated or polyunsaturated fats was associated with incidence of breast and prostate cancer. A causal relationship was identified between cholesterol intake and colon cancer (9). Olive oil is the oil obtained from the fruit of the olive tree (Olea europaea Sativa) and its consumption is associated with lower overall mortality patterns, which are observed in Mediterranean populations (10). The primary component of olive leaf extract is oleuropein. Andreadou et al reported that oleuropein is involved in cardiomyocyte metabolism through the activati...

Background/aims: Patients with glioblastoma multiforme (GBM) that is the most common brain cancer in adults have a rather poor prognosis. The accumulation of immune suppressive myeloid-derived suppressor cell (MDSC) is negatively associated with clinical outcomes in various cancers. A recent study identified that lectin-type oxidized LDL receptor 1 (LOX-1) may serve as a specific marker of human polymorphonuclear neutrophil (PMN)-MDSC. Thus, herein we focused on exploring the role of LOX-1+ PMN-MDSC in GBM progression. Methods: LOX-1, IFN-γ, dichlorodihydrofluorescein diacetate (DCFDA), CD15, CD4 and CD8 expression levels were examined by flow cytometry. ARG1 and iNOS expression levels in PMN were examined by quantitative real-time PCR. LOX-1 and CD15 expression levels in tumor tissue were determined by immunofluorescent microscopy. T cell proliferation was determined by 3H-thymidine incorporation. Results: We identified a protumorigenic subset of PMN, which constitutively expressed LOX-1 and accumulated in the peripheral blood of GBM patients. Compared to LOX-1− PMN, the LOX-1+ PMN exhibited a PMN MDSC profile, with a significant increase in the expression of DCFDA, ARG1 and iNOS, and the capacity of inhibiting the CD3+ T cell proliferation in a dependent-ARG1/iNOS way. Additionally, we found that LOX-1+ PMN negatively correlated with effector immune cells in GBM patients, accumulated in GBM tissues, and was related to early recurrence and disease progression tightly. Conclusion: Our study revealed that LOX-1+ PMN-MDSC inhibited the T cell proliferation to enhance immune suppression, which may play a key role in driving the GBM progression.

Red blood cell distribution width, NLR and eosinophil are independent prognostic factors for IS.

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BackgroundThe aim of this study was to analyze the changing role of thrombelastography (TEG) by detecting the indexes of TEG in patients with acute cerebral hemorrhage and cerebral infarction, combined with pathogenesis, and to find objective laboratory indexes for the diagnosis and treatment of cerebrovascular diseases.Material/MethodsData from 150 patients were collected, including 69 cases identified as the cerebral infarction group and 81 cases identified as the cerebral hemorrhage group. In addition, 50 healthy adults were selected as a control group. The cerebral hemorrhage group was divided into 3 subgroups according to the amount of bleeding: small hemorrhage group, moderate hemorrhage group, and large hemorrhage group. The diagnosis for each participant was mainly based on computed tomography (CT) and magnetic resonance imaging (MRI). TEG indexes [R value (coagulation reaction time), K value (coagulation time), Angle (reflecting the formation rate of blood clot and the function of fibrinogen), MA (maximum thrombus amplitude), CI (coagulation index)] were measured by TEG YZ5000 instrument.ResultsThe cerebral infarction group had lower R and K values and higher Angle and CI (P<0.05). The cerebral hemorrhage group had higher K value; the Angle and MA were lower in the moderate hemorrhage group and in the large hemorrhage groups (P<0.05). In the cerebral hemorrhage group, Angle and MA were negatively correlated with the amount of cerebral hemorrhage (r=−0.475, −0.394 respectively, P<0.05), and the K value was positively correlated with the amount of cerebral hemorrhage (r=0.337, P<0.05), while the R value had no significant correlation with the amount of cerebral hemorrhage (r=0.251, P>0.05). R and K values in the cerebral infarction group were significantly lower, while Angle, MA, and CI were significantly higher in the cerebral hemorrhage group.ConclusionsK value, Angle, and MA may be of value in the assessment of the amount of cerebral hemorrhage.

This study was designed to investigate the factors affecting the in-hospital delay of intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Two hundred and forty-eight consecutive AIS patients treated with intravenous administration of alteplase in Gansu Provincial Hospital from December 2014 to August 2018 were enrolled retrospectively in this study. According to door-to-needle (DTN) time, the patients were divided into either a delay group (DTN time > 60 minutes; n = 184) or a non-delay group (DTN time ≤60 minutes; n = 64). The baseline data, laboratory tests, onset-to-door (OTD) time, door-to-accepting time (DTA), door-to-imaging time (DTI), and decision-making time in both groups were recorded. Multivariate logistic analysis was performed to analyze the data. There were significant differences in previous history of cerebral ischemic attack, emergency system admission, education degree of decision makers, annual income, admission National Institutes of Health Stroke Scale (NIHSS), OTD time, DTA time, decision-making time between the 2 groups (all P < .05). Other baseline data and clinical features showed no significant difference between 2 groups ( P > .05). Multivariate logistic regression analysis revealed that the risk of in-hospital delay was lower for the higher NIHSS score (OR = 0.775, 95% CI: 0.644-0.933, P = .007), the longer OTD time (OR = 0.963, 95% CI: 0.937-0.991, P = .010), the shorter decision-making time (OR = 1.224, 95% CI: 1.004-1.492, P = .045). This study suggested that NIHSS score, OTD time and decision-making time are the independent factors affecting the in-hospital delay of IVT for AIS.

Glioblastoma is the most aggressive malignant brain tumor in adults. Long noncoding RNA HOTAIRM1 (HOX antisense intergenic RNA myeloid 1) has been reported to participate in the progression of various cancers. However, the role of HOTAIRM1 in glioblastoma and its underlying mechanisms are largely unknown. The relative expression levels of HOTAIRM1, miR-137 and specificity protein 1 were detected by quantitative real-time PCR or western blot. The effects of HOTAIRM1 on cell proliferation and invasion were evaluated by Cell Counting Kit-8 assay and Transwell assay, respectively. The interactions among HOTAIRM1, miR-137 and specificity protein 1 were predicted by online softwares and confirmed by luciferase reporter assay and RNA immunoprecipitation assay. The levels of HOTAIRM1 and specificity protein 1 were significantly increased while miR-137 was significantly decreased in glioblastoma tissues and cells. Knockdown of HOTAIRM1 suppressed proliferation and invasion in glioblastoma cells. Moreover, miR-137 was bound to HOTAIRM1, and specificity protein 1 was identified as a target of miR-137. The protein level of specificity protein 1 was repressed by silencing the expression of HOTAIRM1, whereas the effect was restored by inhibiting the expression of miR-137. Downregulation of HOTAIRM1 expression suppressed the proliferation and invasion of glioblastoma cells by down-regulating specificity protein 1 expression via sponging miR-137, indicating a promising strategy for glioblastoma treatment.