Pathogenesis of chronic myeloid leukemia(CML)has mostly been studied with regard to the oncogenic role of BCR/ABL fusion,however,recent disclosures have declared that the challenges with the treatment of CML patients ...Pathogenesis of chronic myeloid leukemia(CML)has mostly been studied with regard to the oncogenic role of BCR/ABL fusion,however,recent disclosures have declared that the challenges with the treatment of CML patients would not be resolved until the role of other aberrancies is ignored.Given the involvement of cyclin-dependent kinases(CDKs)in the pathogenesis of CML,the present study aimed to investigate the effects of a multi-CDK inhibitor AT7519 on BCR/ABL-harboring CML-derived K562 cells.Our results showed that AT7519 effectively reduced the survival of K562 and induced its anti-proliferative effect through the induction of G2/M arrest due to elevated p21 and p27.The resulting data also revealed that either direct or indirect suppression of c-Myc using specific c-Myc inhibitor 10058-F4 and selective PI3K inhibitor CAL-101 resulted in a superior cytotoxicity,suggesting that the activation of PI3K pathway could attenuate antileukemic effects of the inhibitor,at least partly,through a c-Mycdependent mechanism.To the best of our knowledge,to date,no study has addressed the effect of autophagy on CML cell response to AT7519,and,herein,we proposed for the first time that the suppression of autophagy boosted AT7519 cytotoxicity against K562.Overall,we suggested that selective CDK inhibitor AT7519 exerted antileukemic effect against CML cells and propose a novel therapeutic application for the inhibitor either as a single agent or in combination with c-Myc and/or PI3K inhibitors.展开更多
The mobility,bioavailability,and environmental fate of heavy metals in soil are controlled by their adsorption onto soil minerals and solid organic matter.The adsorption is strongly affected by the presence of various...The mobility,bioavailability,and environmental fate of heavy metals in soil are controlled by their adsorption onto soil minerals and solid organic matter.The adsorption is strongly affected by the presence of various low-molecular-weight organic acids.In this study,effect of hydroxamate siderophore desferrioxamine B (DFOB) on cadmium (Cd) and zinc (Zn) adsorption onto two micaceous clay minerals,muscovite and phlogopite,was evaluated in batch experiments.Results showed that the presence of DFOB diminished the adsorption of Cd and Zn onto both minerals,particularly under neutral to alkaline pH conditions.For instance,at pH 8.2,the presence of DFOB caused a decrease in the adsorption of Zn onto phlogopite by nearly 50%.The equilibrium adsorption of Cd and Zn was satisfactorily described using Freundlich isotherm.The adsorption isotherms showed that the affinity of Cd and Zn onto the minerals decreased in the presence of DFOB.For example,at pH 8.0,the presence of siderophore caused a decrease in the Freundlich adsorption isotherm coefficient KF for Zn adsorption onto muscovite and phlogopite from 4.60 to 0.07 L g^-1 and from 3.56 to 0.36 L g^-1,respectively.These findings confirm the potential influence of siderophore on the fate of Cd and Zn in arid soils containing substantial contributions of micaceous silicate minerals.展开更多
基金the grant number:15425 from Shahid Beheshti University of Medical Sciences(Tehran,Iran)(http://en.sbmu.ac.ir/)achieved byD.B.Conflicts of Interest:The authors declare that they have no conflicts of interest to report regarding the present study.
文摘Pathogenesis of chronic myeloid leukemia(CML)has mostly been studied with regard to the oncogenic role of BCR/ABL fusion,however,recent disclosures have declared that the challenges with the treatment of CML patients would not be resolved until the role of other aberrancies is ignored.Given the involvement of cyclin-dependent kinases(CDKs)in the pathogenesis of CML,the present study aimed to investigate the effects of a multi-CDK inhibitor AT7519 on BCR/ABL-harboring CML-derived K562 cells.Our results showed that AT7519 effectively reduced the survival of K562 and induced its anti-proliferative effect through the induction of G2/M arrest due to elevated p21 and p27.The resulting data also revealed that either direct or indirect suppression of c-Myc using specific c-Myc inhibitor 10058-F4 and selective PI3K inhibitor CAL-101 resulted in a superior cytotoxicity,suggesting that the activation of PI3K pathway could attenuate antileukemic effects of the inhibitor,at least partly,through a c-Mycdependent mechanism.To the best of our knowledge,to date,no study has addressed the effect of autophagy on CML cell response to AT7519,and,herein,we proposed for the first time that the suppression of autophagy boosted AT7519 cytotoxicity against K562.Overall,we suggested that selective CDK inhibitor AT7519 exerted antileukemic effect against CML cells and propose a novel therapeutic application for the inhibitor either as a single agent or in combination with c-Myc and/or PI3K inhibitors.
基金the Vali-e-Asr University of Rafsanjan, Iran, for ?nancial support (No. 436753)
文摘The mobility,bioavailability,and environmental fate of heavy metals in soil are controlled by their adsorption onto soil minerals and solid organic matter.The adsorption is strongly affected by the presence of various low-molecular-weight organic acids.In this study,effect of hydroxamate siderophore desferrioxamine B (DFOB) on cadmium (Cd) and zinc (Zn) adsorption onto two micaceous clay minerals,muscovite and phlogopite,was evaluated in batch experiments.Results showed that the presence of DFOB diminished the adsorption of Cd and Zn onto both minerals,particularly under neutral to alkaline pH conditions.For instance,at pH 8.2,the presence of DFOB caused a decrease in the adsorption of Zn onto phlogopite by nearly 50%.The equilibrium adsorption of Cd and Zn was satisfactorily described using Freundlich isotherm.The adsorption isotherms showed that the affinity of Cd and Zn onto the minerals decreased in the presence of DFOB.For example,at pH 8.0,the presence of siderophore caused a decrease in the Freundlich adsorption isotherm coefficient KF for Zn adsorption onto muscovite and phlogopite from 4.60 to 0.07 L g^-1 and from 3.56 to 0.36 L g^-1,respectively.These findings confirm the potential influence of siderophore on the fate of Cd and Zn in arid soils containing substantial contributions of micaceous silicate minerals.
