| 1 | Inhibition of ROS elevation and damage to mitochondrial function prevents lead-induced neurotoxic effects on structures and functions of AFD neurons in Caenorhabditis elegans显示文摘Here we investigated the possible roles of oxidative stress in the formation of decreased thermotaxis to cultivation temperature in lead(Pb)-exposed nematodes Caenorhabditis elagans.Exposure to Pb at the examined concentrations decreased thermotaxis behaviors,and induced severe deficits in the structural properties of AFD sensory neurons.Meanwhile,Pb exposure caused the induction of severe oxidative damage,reactive oxygen species(ROS) production,and mitochondrial dysfunction in young adults.Moreover,pre-treatment with the antioxidants dimethyl sulfoxide(DMSO),ascorbate and N-acetyl-L-cysteine(NAC),used to inhibit both the ROS elevation and the mitochondrial dysfunction caused by Pb exposure,at the L2-larval stage prevented the induction of oxidative damage and the formation of severe deficits in thermotaxis and structural properties of AFD sensory neurons in Pb-exposed young adults.Therefore,the formation of oxidative stress caused by Pb exposure may be due to both the induction of ROS elevation and damage to mitochondrial function,and oxidative stress may play a key role in inducing the neurotoxic effects on the structures and function of AFD sensory neurons in Pb-exposed nematodes. | Qiuli Wu Peidang Liu Yinxia Li Min Du Xiaojuan Xing Dayong Wang | 2012 | Journal of Environmental Sciences2012，24，4： | 3 |
| 2 | Brain-targeted polymersome codelivery of siRNA and temozolomide for effective glioblastoma chemo-RNAi synergistic therapy显示文摘Temozolomide (TMZ) is a clinically approved drug for glioblastoma (GBM) therapy. However, as a result of methylguanine-DNA-methyltransferase (MGMT), which is able to repair damaged DNA-damage repairing, TMZ usually yields unsatisfactory therapeutic effects. Small interfering RNA (siRNA) is a potential alteration tool for sensitivity of TMZ by targeting DNA repair enzymes. However, a suitable TMZ and siRNA codelivery system that can effectively and actively co-deliver siRNA/TMZ into the brain tumor is lacking. In this study, we constructed an angiopep-2 decorated polymersomal delivery system to co-deliver TMZ/siRNA for synergistic GBM therapy. This targeted polymersomal nanomedicine not only enhanced the circulation time of siRNA/TMZ in blood but also improved their blood-brain barrier (BBB) crossing and GBM targeting ability. Moreover, when we co-administered siRNAs specific to retinoblastoma binding protein 4 (RBBP4) together with TMZ in GBM cells, these RBBP4- specific siRNA (siRBBP4) modulated the sensitivity of TMZ by regulating MGMT, and thus showed a powerful synergistic anti-tumor effect. We demonstrated that angiopep-2 decorated polymersomal siRBBP4/TMZ co-loaded nanomedicines are capable of inhibiting tumor growth and significantly improved life expectancy of orthotropic GBM bearing mice. Overall, our study suggests that such a polymersomal TMZ/siRNA codelivery system provides a robust and potent nanoplatform for targeted GBM chemo-RNAi therapy. | Meng Zheng Chengnan Yan Qingshan Yang Feiyan Zhu Qiuli Du Xue Xia Marco Morsch Albert Lee Jinglong Yin Yan Zou Bingyang Shi | 2022 | ChemPhysMater2022，1，3： | 0 |
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