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      • KCI등재

        Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

        Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

      • KCI등재

        Distinctive Slow β Relaxation and Its Impact on Mechanical Property of LaCe Based Bulk Metallic Glasses

        Xiao Cui,Jing Guo,Qi‑dong Zhang,Xiao‑jun Meng,Bing‑chuan Bian,Ren‑gao Zhao,Yu‑bai Ma,Fang‑qiu Zu 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.10

        The slow β relaxation which occurring at temperatures far below glass transition temperature, typically playing importantroles in the plastic deformation behavior of metallic glasses. Compared with polymer glasses, most of the metallic glasses donot exhibit obvious β relaxation based on dynamic mechanical analysis. In the current work, prominent β relaxation behaviorsof a series (LaxCe100−x) Al10Co25(x = 50, 60, 70, 80) bulk metallic glasses (BMGs) at low temperature are observed usingdynamic mechanical analysis. Compared with other BMGs, the LaCe based BMGs show a pronounced β relaxation peak andrelative low peak temperature, the activation energy of the β relaxation based on Arrhenius equation are calculated around79.3 kJ/mol to 86.4 kJ/mol, which obey an empirical rule that Eβ ≈ (26 ± 4) RTg, with the coefficient of 23. Experimentalresults from room temperature compression tests for the LaCe based BMGs indicate that low temperature activated β relaxationbehaviors facilitate the good plasticity of the LaCe based BMGs.

      • KCI등재후보

        MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head

        Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.1

        BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH. BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

      • KCI등재

        NURBS Interpolator with Adaptive Smooth Feedrate Scheduling and Minimal Feedrate Fluctuation

        Taiyong Wang,Yong-Bin Zhang,Jing-Chuan Dong,Run-Ji Ke,Yan-Yu Ding 한국정밀공학회 2020 International Journal of Precision Engineering and Vol.21 No.2

        For an effective NURBS interpolator, generating the smooth feedrate profile and minimizing the feedrate fluctuation are two main tasks, which have a great influence on the machining quality. In this paper, a NURBS interpolator is proposed to solve the problem with offline-online two stages, which contain curving splitting, feedrate scheduling, and real-time interpolation modules. At first, in offline module, the limited feedrate of the curve is calculated with consideration of geometric characteristics and dynamic constraints, and the curve is split into several segments according to the key regions. Thus the necessary information is stored. Then the feedrate scheduling algorithm is applied with constant feedrate scheduling method at each segment, where tangential acceleration and jerk are taken into consideration to generate an adaptive smooth S-type feedrate profile. Moreover, in real-time interpolation module, an average feedrate calculation method is proposed to determine the sampling step size. And to minimize the feedrate fluctuation, a double interpolation algorithm based on the cosine theorem is presented, which use the second-order Taylor’s expansion method two times in one interpolation period. Finally, simulations and experiments are conducted to verify the performance of the proposed interpolator.

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