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Zhang X.S.,The Affiliated Hospital of Innermongolia Medical University | Ha S.,The Affiliated Hospital of Innermongolia Medical University | Wang X.L.,The Affiliated Hospital of Innermongolia Medical University | Shi Y.L.,The Affiliated Hospital of Innermongolia Medical University | And 2 more authors.
Neuroscience | Year: 2015

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (Tan IIA), a major bioactive diterpene quinone of Salva miltiorrhiza, had been proved effective in the MPTP model through its anti-inflammatory activity. Here in this research, we found that Tan IIA prevented the loss of nigrostriatal dopaminergic neurons by activating the NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. The cytotoxicity of 6-hydroxydopamine (6-OHDA) was attenuated by the treatment of Tan IIA in SH-SY5Y cells, which significantly reduced 6-OHDA-induced lactic dehydrogenase release and reactive oxygen species production. Further study indicated that Tan IIA contributed to the nuclear accumulation of Nrf2, which bound to the ARE sequence, and activated ARE-regulated genes, including heme oxygenase-1, glutamate cysteine ligase catalytic subunit (GCLC) and glutamate cysteine ligase modifier subunit (GCLM). Tan IIA also protected against damage to mitochondrial membrane potential, reduced the translocation of cytochrome c from the mitochondria to the cytoplasm and the activation of Caspase-9 and Caspase-3. Moreover, we demonstrated the above effects were performed in Nrf2-dependent manner. Further studies revealed that Tan IIA reduced the enhancement of miR-153 by 6-OHDA, which targeted the 3'-UTR of Nrf2, and suppressed its expression and activation. Additionally, neurodegeneration caused by in vivo stereotaxic injection of 6-OHDA could also be ameliorated by the administration of Tan IIA. Taken together, our results strongly suggest that Tan IIA may be beneficial for the treatment of PD, and also confirm that targeting the Nrf2/ARE pathway is a promising strategy for therapeutic intervention in PD. © 2015 IBRO. Source


Zhang X.,The Affiliated Hospital of Innermongolia Medical University | Ha S.,The Affiliated Hospital of Innermongolia Medical University | Wang X.,The Affiliated Hospital of Innermongolia Medical University | Shi Y.,The Affiliated Hospital of Innermongolia Medical University | And 2 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

Cardiac resynchronization therapy (CRT) is a proven therapy for selected patients with heart failure, it has been shown to improve symptoms and left ventricular (LV) function and prolong survival. Despite proven benefit of CRT, a significant proportion of patients fail to respond to CRT. Multiple factors contribute to the non-response such as patient selection and device implantation including LV lead placement. Speckle tracking echocardiography (STE) derived strain imaging offers detailed characterization of LV function and provides indices of mechanical dyssynchrony, in addition, STE systolic strain could be used to identify area of scar, therefore applications of STE-derived strain imaging in CRT warrant a closer inspection. This review considers and summarizes different indices of mechanical dyssynchrony generated by STE-derived strain imaging and their relevance in patient selection for CRT and their prognostic values in predicting response to CRT. This review further examines applications of STE-derived strain imaging in optimizing LV lead position by detecting site of latest mechanical activation and presence or absence of transmural scar in a particular segment. © 2015, E-Century Publishing Corporation. All rights reserved. Source

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