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.

No abstract

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.

No abstract

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.

Circular RNA carboxypeptidase A4 (circCPA4) has been shown to involve in the tumorigenesis of glioma. However, the function and the molecular mechanism of circCPA4 in glioma remain inadequate. Levels of circCPA4 and microRNA (miR)-760 were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). The interaction between miR-760 and circCPA4 or MEF2D was analyzed by the dual-luciferase reporter assay or RNA pull-down assay. In vivo experiments were conducted using murine xenograft models. We found circCPA4 was highly expressed in glioma, and circCPA4 knockdown suppressed tumor cell proliferative, migratory and invasive behaviors, but enhanced cell apoptosis and radiosensitivity in glioma. CircCPA4 directly bound to miR-760 to suppress its expression, and miR-760 inhibition reversed circCPA4 knockdown-mediated inhibition of cell malignant phenotypes in glioma. MEF2D was a target of miR-760, and miR-760 performed anti-tumor effects by targeting MEF2D in glioma cells. Meanwhile, we found circCPA4 could indirectly regulate MEF2D by sponging miR-760. Importantly, xenograft analysis suggested that circCPA4 knockdown impeded tumor growth in vivo via regulating miR-760 and MEF2D. In conclusion, circCPA4 knockdown suppressed cell malignant phenotypes in glioma via miR-760/MEF2D axis to impede the progression of glioma, suggesting potential therapeutic targets for glioma treatment.