Background: Flavonoids, despite having low nutritional value, have numerous biological activities and extremely beneficial health effects. This study investigated the anticancer activity of rutin in human glioma CHME cells.Methods: Cytotoxicity was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Protein expression was determined through Western blotting. Apoptosis was detected using annexin V/propidium iodide (PI) and fluorescence microscopy. Results: Rutin induced maximum cytotoxicity in CHME cells, as revealed through MTT assays. Cell death induced by rutin was due to apoptosis via P53 up-regulation. Rutin induced nuclear condensation, fragmentation, and membrane blebbing, as determined through 4',6-diamidino-2-phenylindole (DAPI) staining. Furthermore, rutin increased reactive oxygen species (ROS) levels and caused a loss of mitochondrial membrane potential, activating the intrinsic apoptotic pathway in CHME cells. The induction of apoptosis by rutin was further confirmed by the release of cytochrome c, up-regulation of BAX, and down-regulation of BCL, activated caspase 9, and caspase 3. The knockdown of P53 reversed rutin-induced apoptosis in a concentration-dependent manner. Conclusions: Rutin plays an important role in the induction of apoptosis in CHME cells. Based on these data, rutin should be further investigated as an anticancer agent in human glioma CHME cells.
This study investigates the biokinetics of LGT proteome, a potential biomarker of severe TBI, in serum of severe TBI patients. The LGT proteome presents in the serum of severe TBI patients. The abundance diversity of LGT proteome is closely associated with pathologic condition of TBI patients. Serum LGT proteome may be used as a promising marker for evaluating severity of severe TBI.
Although probiotics have been isolated from different sources, few were isolated from traditional Chinese medicine. The current study firstly isolate Pulsatilla Radix-utilizing Pediococcus pentosaceus PR-1 from human faeces. Subsequently, the tolerance of PR-1 to low pH, bile salts, simulated gastric juice and succus entericus, antioxidant activity, antimicrobial activity, cholesterol-assimilation and antibiotics susceptibility were investigated. After 2 h incubation at pH 2.0, over 80% of PR-1 survived. The cell viability of PR-1 at 2 h under 0.1% bile salt condition was 99.2%. The survival rate of PR-1 in gastric juice and succus entericus were 64.48% and 81.86, respectively. Cell-free supernatant of PR-1 culture also showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium. Besides, antioxidant activity of PR-1 CFS was significantly greater than cell pellet. PR-1 was shown resistant to kanamycin, streptomycin, vancomycin, and norfloxacin and able to lower cholesterol level to 72.5 ± 1.5%. In addition, PR-1 displayed γ-hemolysis and was non-pathogenic.
Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measured the expression levels and role of MDM2 in non-functioning PitNET patients’ combined clinical features and investigated the effect of etoposide on the cell bioactivity of the GT1-1 cell line in vivo and in vitro. Methods: RT-PCR and immunochemistry measured the expression levels and role of MDM2 in 103 NF-PitNET patients’ combined clinical features. Cell proliferation, migration, colony and apoptosis experiments measured the effect of etoposide on the GT1-1 cell line in vivo and in vitro. Results: There was more invasive behavior (p = 0.013) in patients with high MDM2, who were also younger (p = 0.007), were more frequently female (p = 0.049) and had larger tumor sizes (p = 0.018) compared with patients with low MDM2. Patients with high p53 were younger (p = 0.017) and had larger tumor sizes (p = 0.034) compared with patients with low p53. Univariate (p = 0.018) and multivariate (p = 0.023) Cox regression analysis showed that MDM2 was the independent factor for invasive behavior in NF-PitNET patients. Log-rank analysis showed that the average progression-free survival (PFS) time in the low MDM2 patients was longer than that in the high MDM2 patients (p = 0.044). Functional studies indicated that etoposide inhibited cell proliferation and cell migration and induced apoptosis in p53 independence in GT1-1 cells. Furthermore, etoposide significantly inhibited the growth of GT1-1-xenograft in BALB/c nude mice. The tumor growth inhibition rate of etoposide was 67.4 ± 4.6% after 14 d of treatment, which suggested the anti-tumor activity of etoposide. Conclusions: MDM2 played the role of tumorigenesis of NF-PitNET in a p53 independence manner, and an MDM2 inhibitor could be a potential choice for the treatment of NF-PitNET patients.
Metro vehicles have always been known for their high passenger density, frequent traffic flow and strong alternating loads due to their severe running environment. As the major support component, the bogie frame suffers from fatigue damages and receives a high intensity of interest. In this work, a theoretical model is presented between the measured strain and the structural stress via multiple load identification, wherein recognition matrices and stress evaluations of the bogie frame are defined according to the locations found in finite element analysis (FEA). The model is validated through random loading in FE simulation, and the load deviation is within 1.1 kN. A vehicle experiment was performed on the second bogie of the head car on a six-car metro train. The signed von Mises (SVM) stress was calculated at critical locations with the proposed method and compared with what was measured. The excessive part was no more than 14.97%, comparing the reconstructed with the measured amounts. Stress spectra were developed utilizing rain-flow counting and evaluated in terms of the damage accumulation rule with the optimal spectra groups determined from convergence analysis. The evaluation indicates that, when the running mileage increases to the full life cycle of 3,960,000 km, the maximum equivalent damage reaches 0.35 and 0.46 at the gear box base for measured and reconstructed amounts, respectively. Research outcomes suggest that the proposed method offers an alternative for fatigue assessment and maintenance strategies on metro vehicles, as well as other types of rail-transit vehicles.
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