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Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial–mesenchymal transition (EMT), and also participate in the induction of multi-drug resistance (MDR). In the present study, we demonstrated the discovery of a novel inhibitor for Notch activating/cleaving enzyme ADAM-17, named ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins. ZLDI-8 treatment enhanced the susceptibility of HCC cells to a small molecular kinase inhibitor Sorafenib, and chemotherapy agents Etoposide and Paclitaxel. ZLDI-8 treatment enhanced the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model. These results suggest that ZLDI-8 can be a promising therapeutic agent to enhance Sorafenib’s anti-tumor effect and to overcome the MDR of HCC patients.

To conduct a meta-analysis of clinical trials that examined the effect of music-supported therapy on stroke-induced motor dysfunction, comprehensive literature searches of PubMed, Embase and the Cochrane Library from their inception to April 2016 were performed. A total of 10 studies (13 analyses, 358 subjects) were included; all had acceptable quality according to PEDro scale score. The baseline differences between the two groups were confirmed to be comparable. Compared with the control group, the standardized mean difference of 9-Hole Peg Test was 0.28 (−0.01, 0.57), 0.64 (0.31, 0.97) in Box and Block Test, 0.47 (0.08, 0.87) in Arm Paresis Score and 0.35 (−0.04, 0.75) in Action Research Arm Test for upper-limb motor function, 0.11 (−0.24, 0.46) in Berg Balance Scale score, 0.09 (−0.36, 0.54) in Fugl-Meyer Assessment score, 0.30 (−0.15, 0.74) in Wolf Motor Function Test, 0.30 (−0.15, 0.74) in Wolf Motor Function time, 0.65 (0.14, 1.16) in Stride length and 0.62 (0.01, 1.24) in Gait Velocity for total motor function, and 1.75 (0.94, 2.56) in Frontal Assessment Battery score for executive function. There was evidence of a positive effect of music-supported therapy, supporting its use for the treatment of stroke-induced motor dysfunction. This study was registered at PRESPERO (CRD42016037106).

A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways.

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Accumulated evidence has shown that excessive reactive oxygen species (ROS) have been implicated in neuronal cell death related with various chronic neurodegenerative disorders. This study was designed to explore neuroprotective effects of ethyl acetate extract of Arctium lappa L. roots (EAL) on hydrogen peroxide (H2O2)-induced cell injury in human SH-SY5Y neuroblastoma cells. The cell viability was significantly decreased after exposure to 200 μM H2O2, whereas pretreatment with different concentrations of EAL attenuated the H2O2-induced cytotoxicity. Hoechst 33342 staining indicated that EAL reversed nuclear condensation in H2O2-treated cells. Meanwhile, TUNEL assay with DAPI staining showed that EAL attenuated apoptosis was induced by H2O2. Pretreatment with EAL also markedly elevated activities of antioxidant enzyme (GSH-Px and SOD), reduced lipid peroxidation (MDA) production, prevented ROS formation, and the decrease of mitochondrial membrane potential. In addition, EAL showed strong radical scavenging ability in 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays. Furthermore, EAL inhibited H2O2-induced apoptosis by increases in the Bcl-2/Bax ratio, decreases in cytochrome c release, and attenuation of caspase-3, caspase-9 activities, and expressions. These findings suggest that EAL may be regarded as a potential antioxidant agent and possess potent neuroprotective activity against H2O2-induced injury.

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