GingerenoneA overcomes dexamethasone resistance by activating apoptosis and inhibiting cell proliferation in pediatric T-ALL cells.

Plant-based combination strategies have been widely considered in cancer therapy to attenuate chemotherapeutics side effects. The anti-leukemic effect of the whole ginger extract was previously portrayed by our team, and the current study is centered around the cytotoxicity and mechanism of action of a phenolic subsidiary of ginger, GingerenoneA, on pediatric acute lymphoblastic leukemia. GingernoneA imposed, dose-dependently, inhibitory effects on the viability of T and B leukemia cell lines confirmed by MTT assays. Resistance to Dexamethasone, a mostly used chemotherapeutic in acute lymphoblastic leukemia treatments, was overcome by GingernoneA. A synergistic effect of Dexamethasone and GingrenoneA on T leukemia cell lines and patient primary cells was confirmed. Annexin-V/PI and acridine orange/ethidium bromide staining illustrated dose-dependent apoptosis in CCRF-CEM cells developed by GingerenoneA. The intrinsic and extrinsic apoptosis induction and antiproliferative attribution of GingerenoneA were validated by western blot and qPCR. Despite the supposed loss of function in CCRF-CEM cells, TP53 showed increased expression levels and functional activity upon treatment with GingernoneA. Bioinformatic studies revealed the conceivable impact of GingerenoneA on the reactivity of mutant P53 through its binding to Cys124. Our findings may provide novel strategies for therapeutic intervention to ameliorate pALL outcomes.

Conformational changes of ß-thalassemia major hemoglobin and oxidative status of plasma after in vitro exposure to extremely low-frequency electromagnetic fields: An artificial neural network analysis.

Electromagnetic fields (EMF) can generate reactive oxygen species and induce oxidative modifications. We investigated the effects of extremely low-frequency electromagnetic fields (ELF-EMF) on oxidative status of plasma and erythrocytes in ß-thalassemia major patients and design artificial neural networks (ANN) for evaluating the oxyHb concentration. Blood samples were obtained from age and sex-matched healthy donors (n = 12) and major ß-thalassemia patients (n = 12) and subjected to 0.5 and 1 mT and 50 Hz of EMF. Plasma oxidative status was estimated after 1 and 2 h exposure to ELE-EMF. Structural changes of plasma proteins were investigated by Native PAGE and SDS-PAGE. Moreover; multilayer perceptron (MLP) method was applied for designing a feed forward ANN model to predict the impact of these oxidative and antioxidative parameters on oxyHb concentration. Two hour exposure to ELF-EMF induced significant oxidative changes on major ß-thalassemia samplesElectrophoretic profiles showed two high molecular weight (HMW) protein aggregates in plasma samples from healthy donors and major ß-thalassemia patients. According to our ANN design, the main predictors of oxyHb concentration were optical density of Hb at 542, 340, 569, 630, 577, and 420 nm and metHb and hemichrome (HC) concentration. Accuracy of the proposed ANN model was shown by predicted by observed chart (y = 1.3 + 0.96x, R2 = 0.942), sum of squares errors (SSR), and relative errors (RE). Our results showed the detailed effects of ELF-EMF on Hb structure and oxidative balance of plasma in major ß-thalassemia patients and significance of ANN analysis during normal and pathologic conditions.