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        Mitochondrial NDUFA4L2 attenuates the apoptosis of nucleus pulposus cells induced by oxidative stress via the inhibition of mitophagy

        Wen-Ning Xu,Huo-Liang Zheng,Run-Ze Yang,Tao Liu,Wei Yu,Xin-Feng Zheng,Bo Li,Sheng-Dan Jiang,Lei-Sheng Jiang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

        The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD.

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        Bioethanol from Fermentation of Cassava Pulp in a Fibrous-bed Bioreactor Using Immobilized Δldh, a Genetically Engineered Thermoanaerobacterium aotearoense

        You-Hua Cai,Ze-Xin Liang,Shuang Li,Ming-Jun Zhu,Zhenqiang Wu,Shang-Tian Yang,Ju-Fang Wang 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.6

        There is an increasing worldwide interest in bioethanol production from agricultural, industrial, and urban residues for both ecological and economic reasons. The acid hydrolysis of cassava pulp to reducing sugars and their fermentation to ethanol were evaluated in a fibrousbed bioreactor with immobilized Δldh, a genetically engineered Thermoanaerobacterium aotearoense. A maximum yield of total reducing sugars of 53.5% was obtained after 8 h of hydrolysis at 85oC in 0.4 mol/L hydrochloric acid with a solid-to-liquid ratio of 1:20, which was optimized by using an orthogonal design based on preliminary experiments. In the FBB, the fed-batch fermentation, using glucose as the sole carbon source, gave a maximum ethanol production of 38.3 g/L with a yield of 0.364 g/g in 100 h; whereas the fed-batch fermentation, using xylose as the sole carbon source, gave 34.1 g/L ethanol with a yield of 0.342 g/g in 135 h. When cassava pulp hydrolysate was used as a carbon source, 39.1 g/L ethanol with a yield of 0.123 g/g cassava pulp in185 h was observed, using the fed-batch fermentation model. In addition, for repeated batch fermentation of cassava pulp hydrolysate carried out in the fibrous-bed bioreactor, long-term operation with high ethanol yield and volumetric productivity were achieved. The above results show that the acid hydrolysate of cassava pulp can be used for ethanol production in a fibrous-bed bioreactor, although some inhibition phenomena were observed during the process of fermentation.

      • Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

        Wang, Jian-Jun,Wang, Ze-You,Chen, Rui,Xiong, Jing,Yao, Yong-Liang,Wu, Jian-Hong,Li, Guang-Xin Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.10

        Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.

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