Shikonin Inhibits Cholangiocarcinoma Cell Line QBC939 by Regulating Apoptosis, Proliferation, and Invasion.

This study was designed to clarify whether Shikonin causes proliferation, apoptosis, and invasion in cholangiocarcinoma cells and to investigate the mechanism of action. QBC939 cells were cultured with different doses of Shikonin, and then 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium assay was used to detect cell viability. Apoptosis of cells was detected using flow cytometry with Annexin V/propidium iodide (PI) assay after being stained with Hoechst 33242. The role of Shikonin on the invasive and metastasis ability was detected using Transwell invasion assay. Real-time polymerase chain reaction and Western blotting were used to detect the expression of caspase-3, caspase-8, epidermal growth factor receptor (EGFR), and matrix metalloproteinase (MMP)-9. Shikonin inhibited proliferation and invasive ability of QBC939 cells in a dose-dependent manner; at the same time, apoptosis of cells was also observed in a concentration-dependent fashion. Moreover, Annexin V/PI assay and Transwell invasion assay results indicated that Shikonin induced apoptosis and invasion inhibitory probably due to upregulation of caspase-3 and caspase-8 expression and downregulation of MMP-9 and EGFR expression in a concentration-dependent fashion. Shikonin could enhance apoptosis and inhibit proliferation and invasion of QBC939 cells; such biological behaviors mainly occurred via upregulating the expression of caspase-3 and caspase-8 and downregulating the expression of MMP-9 and EGFR.

Iron-doped NiCo-MOF hollow nanospheres for enhanced electrocatalytic oxygen evolution.

The development of metal-organic frameworks (MOFs) as high-efficiency electrocatalysts for water splitting has attracted special attention due to their unique structural features including high porosity, large surface areas, high concentrations of active sites, uniform pore sizes and shapes, etc. Most of the related reports focus on the in situ generation of high-efficiency electrocatalysts by annealed MOFs. However, the pyrolysis process usually destroys the porous structure of MOFs and reduces the number of active sites due to the absence of organic ligands and agglomeration of metal centers. In this work, we prepared unique NiCo-MOF hollow nanospheres (NiCo-MOF HNSs) by a solvothermal method and further fabricated Fe-doped NiCo-MOF HNSs (Fe@NiCo-MOF HNSs) by a simple impregnation-drying method. Significant enhancement of electrocatalytic activity of Fe@NiCo-MOF HNSs was witnessed because of the doped Fe. Compared with the parent NiCo-MOF HNSs, the optimized Fe@NiCo-MOF HNSs exhibited a lower overpotential of 244 mV at 10 mA·cm-2 with a smaller Tafel slope of 48.61 mV·dec-1, which was lowered by ca. 90 mV due to the influence of Fe doping on the electronic structure of the active centers of Ni and Co. The above materials also displayed excellent stability without obvious activity decay for at least 16 hours. These findings present a new entry in the design and fabrication of high-efficiency MOF-based electrocatalysts for energy conversion.

High BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma increases diagnostic efficacy in cytologically indeterminate thyroid nodules.

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.

ERα positively regulated DNMT1 expression by binding to the gene promoter region in human breast cancer MCF-7 cells.

Estrogen receptors (ER) are expressed in approximately 65% of human breast cancer. Clinical trials and retrospective analyses showed that ER-positive (ER+) tumors were more vulnerable to development of chemotherapy resistance than ER-negative (ER-) tumors. The underlying mechanism is still to be elucidated. Aberrant DNA methylation has been recognized to be associated with cancer chemotherapy resistance. Recently, steroid hormone and their receptors have been found to be involved in the regulation of methyltransferases (DNMTs) and thereby contribute to chemotherapy resistance. The purpose of this study is to explore whether ERα could directly regulate the DNMTs expression. We first analyzed the methylation alterations and its correlation with the expression levels of three types of DNMTs in our established paclitaxel-resistant breast cancer lines, MCF-7(ER+)/PTX and MDA-MB-231(ER-)/PTX cell lines, using qMSP, real-time PCR and Western blot. Then we determined the function of ERα in regulation of DNMT1 using luciferase report gene systems. Our data demonstrated for the first time that ERα could upregulate DNMT1 expression by directly binding to the DNMT1 promoter region in MFC-7(ER+)/PTX cells.