Thymoquinone induces apoptosis in temozolomide-resistant glioblastoma cells via the p38 mitogen-activated protein kinase signaling pathway.

Temozolomide (TMZ) can cross the blood-brain barrier (BBB) and deliver methyl groups to the purine (guanine) bases of DNA, leading to mispairing during DNA replication and subsequent cell death. However, increased expression of the repair enzyme methyl guanine methyltransferase (MGMT), which removes methyl groups from purine bases, counteracts methylation by TMZ. We evaluated the anticancer potential of thymoquinone (TQ), a hydrophobic flavonoid that inhibits resistance and induces apoptosis in various cancer cells, both in vitro and in vivo. In vitro experiments showed that compared with the Hs683 and M059J cell lines, U251 cells were more sensitive to TMZ. Compared to U251 cells, U251R cells, a TMZ drug-resistant strain established in this study, are characterized by increased expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and MGMT. TQ treatments induced apoptosis in all cell lines. The p38 mitogen-activated protein kinase signal pathway was mainly activated in U251 and U251R cells; however, p-ERK and MGMT upregulation could not suppress TQ effects. Furthermore, si-p38 pretreatment of U251R cells in TQ treatments inhibited cell apoptosis. We speculate that TQ contributed to the phosphorylation and activation of p38, but not of ERK-induced apoptosis (irrespective of TMZ resistance). In vivo, U251R-derived tumors subcutaneously inoculated in nude mice exhibited significant tumor volume reduction after TQ or TQ + TMZ cotreatments. High-performance liquid chromatography assay confirmed the presence of TQ in murine brain tissues. Our findings demonstrate that TQ can effectively cross the BBB and function alone or in combination with TMZ to treat glioblastoma.

A Nomogram to Predict the Risk of Stent Dysfunction After TIPS in Patients with Hepatitis B Cirrhosis.

RATIONALE AND OBJECTIVES: To develop and validate a nomogram for the prediction of stent dysfunction after transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatitis B cirrhosis. MATERIALS AND METHODS: From 2012 to 2020, 355 patients with hepatitis B cirrhosis who underwent TIPS placements were enrolled in this study. A multivariable logistic regression analysis was applied to determine independent risk factors for the nomogram construction. Discrimination, calibration, and clinical usefulness of the prediction model were assessed by using receiver operating characteristic curves, calibration scatter plots, and a decision curve analysis (DCA). RESULTS: Independent factors for TIPS stent dysfunction included diabetes, previous splenectomy, the shunting branch of the portal vein, and stent position, which were used to construct the nomogram. The AUC values in the training and validation cohorts were 0.817 (95% CI: 0.731-0.903) and 0.804 (95% CI: 0.673-0.935), respectively, which suggested a good predictive ability. The calibration curves in both cohorts revealed good agreement between the predictions and actual observations. The DCA curve indicated that when the threshold probability ranged from 2% to 88%, the nomogram could provide clinical usefulness and a net benefit. CONCLUSION: The nomogram that we developed could be conveniently used to predict TIPS stent dysfunction in patients with hepatitis B cirrhosis.

[Spiral computed tomography imaging of internal carotid artery diameter: a report of 260 cases].

OBJECTIVE: To explore the diameter of internal carotid artery by arterial phase imaging of multi-slice spiral computed tomography (CT). METHODS: A total of 260 routine brain CT scans of the examiner were performed. And the arterial phase images of carotid artery were acquired, observed and measured through a three-dimensional reconstruction workstation. On the diameters of target sections were measured on the multiplanar reconstruction (MPR) images of carotid artery. Two groups were categorized according to gender and 3 groups by age (25 - 40 yr, 41 - 60 yr and 61 - 85 yr) for statistical analysis. RESULTS: The diameter data of internal carotid artery had statistical significances among genders and 3 age groups (P < 0.05). CONCLUSION: The diameter of internal carotid artery may be evaluated by the arterial phase imaging of multi-slice spiral CT so that the reference data can be provided for clinical diagnosis.