Melatonin acts synergistically with pazopanib against renal cell carcinoma cells through p38 mitogen-activated protein kinase-mediated mitochondrial and autophagic apoptosis

Background Mounting evidence indicates that melatonin has possible activity against different tumors. Pazopanib is an anticancer drug used to treat renal cell carcinoma (RCC). This study tested the anticancer activity of melatonin combined with pazopanib on RCC cells and explored the underlying mechanistic pathways of its action. Methods The 786-O and A-498 human RCC cell lines were used as cell models. Cell viability and tumorigenesis were detected with the MTT and colony formation assays, respectively. Apoptosis and autophagy were assessed using TUNEL, annexin V/propidium iodide, and acridine orange staining with flow cytometry. The expression of cellular signaling proteins was investigated with western blotting. The in vivo growth of tumors derived from RCC cells was evaluated using a xenograft mouse model. Results Together, melatonin and pazopanib reduced cell viability and colony formation and promoted the apoptosis of RCC cells. Furthermore, the combination of melatonin and pazopanib triggered more mitochondrial, caspase-mediated, and LC3-II-mediated autophagic apoptosis than melatonin or pazopanib alone. The combination also induced higher activation of the p38 mitogen-activated protein kinase (p38MAPK) in the promotion of autophagy and apoptosis by RCC cells than melatonin or pazopanib alone. Finally, tumor xenograft experiments confirmed that melatonin and pazopanib cooperatively inhibited RCC growth in vivo and predicted a possible interaction between melatonin/pazopanib and LC3-II. Conclusion The combination of melatonin and pazopanib inhibits the growth of RCC cells by inducing p38MAPK-mediated mitochondrial and autophagic apoptosis. Therefore, melatonin might be a potential adjuvant that could act synergistically with pazopanib for RCC treatment

Space electric field concentrated effect for Zr:SiO2 RRAM devices using porous SiO2 buffer layer

To improve the operation current lowing of the Zr:SiO(2) RRAM devices, a space electric field concentrated effect established by the porous SiO(2) buffer layer was investigated and found in this study. The resistive switching properties of the low-resistance state (LRS) and high-resistance state (HRS) in resistive random access memory (RRAM) devices for the single-layer Zr:SiO(2) and bilayer Zr:SiO(2)/porous SiO(2) thin films were analyzed and discussed. In addition, the original space charge limited current (SCLC) conduction mechanism in LRS and HRS of the RRAM devices using bilayer Zr:SiO(2)/porous SiO(2) thin films was found. Finally, a space electric field concentrated effect in the bilayer Zr:SiO(2)/porous SiO(2) RRAM devices was also explained and verified by the COMSOL Multiphysics simulation model

Blockage of Autophagy Increases Timosaponin AIII-Induced Apoptosis of Glioma Cells In Vitro and In Vivo

Timosaponin AIII (TSAIII), a saponin isolated from Anemarrhena asphodeloides and used in traditional Chinese medicine, exerts antitumor, anti-inflammatory, anti-angiogenesis, and pro-apoptotic activity on a variety of tumor cells. This study investigated the antitumor effects of TSAIII and the underlying mechanisms in human glioma cells in vitro and in vivo. TSAIII significantly inhibited glioma cell viability in a dose- and time-dependent manner but did not affect the growth of normal astrocytes. We also observed that in both glioma cell lines, TSAIII induces cell death and mitochondrial dysfunction, consistent with observed increases in the protein expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, cytochrome c, and Mcl-1. TSAIII also activated autophagy, as indicated by increased accumulation of the autophagosome markers p62 and LC3-II and the autolysosome marker LAMP1. LC3 silencing, as well as TSAIII combined with the autophagy inhibitor 3-methyladenine (3MA), increased apoptosis in GBM8401 cells. TSAIII inhibited tumor growth in xenografts and in an orthotopic GBM8401 mice model in vivo. These results demonstrate that TSAIII exhibits antitumor effects and may hold potential as a therapy for glioma

Blockage of Autophagy Increases Timosaponin AIII-Induced Apoptosis of Glioma Cells In Vitro and In Vivo

Timosaponin AIII (TSAIII), a saponin isolated from Anemarrhena asphodeloides and used in traditional Chinese medicine, exerts antitumor, anti-inflammatory, anti-angiogenesis, and pro-apoptotic activity on a variety of tumor cells. This study investigated the antitumor effects of TSAIII and the underlying mechanisms in human glioma cells in vitro and in vivo. TSAIII significantly inhibited glioma cell viability in a dose- and time-dependent manner but did not affect the growth of normal astrocytes. We also observed that in both glioma cell lines, TSAIII induces cell death and mitochondrial dysfunction, consistent with observed increases in the protein expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, cytochrome c, and Mcl-1. TSAIII also activated autophagy, as indicated by increased accumulation of the autophagosome markers p62 and LC3-II and the autolysosome marker LAMP1. LC3 silencing, as well as TSAIII combined with the autophagy inhibitor 3-methyladenine (3MA), increased apoptosis in GBM8401 cells. TSAIII inhibited tumor growth in xenografts and in an orthotopic GBM8401 mice model in vivo. These results demonstrate that TSAIII exhibits antitumor effects and may hold potential as a therapy for glioma.</jats:p

Fabrication of 500 nm distributed Bragg reflector using Nb₂O₅-MgF₂ multi-layer films

At first, we use an [Formula: see text] analyzer to measure the optical properties (including refractive index [Formula: see text] and extinction coefficient [Formula: see text]) of MgF2 and Nb2O5 single-layer films, in a wavelength range of 200–1700 nm for MgF2 film and in a wavelength range of 350–1500 nm for Nb2O5 film. After the refractive indexes of MgF2 and Nb2O5 single-layer films are measured, we use the measured results to calculate the needed thicknesses of the quarter-wave (1/4 wavelength) MgF2 and Nb2O5 films for the designed green-light (500 nm) distributed Bragg reflectors (DBRs). After that, an E-beam is used to deposit the MgF2-Nb2O5 bilayer films (called as one period) with different periods (two, four, and six periods are deposited in this study) on glass substrates to fabricate the DBRs with a central wavelength of 500 nm. Then we use the field emission scanning electron microscopy (FESEM) to observe the surface images of Nb2O5 films on the different periods of MgF2-Nb2O5 bilayer films. The important novelty is that we use a Focused Ion Beam (FIB) to prepare the samples for the observations of the cross-sections of MgF2-Nb2O5 bilayer films, and those results can be sued to confirm the thicknesses of the bilayer films with different periods. We also compare the reflective ratio of the fabricated DBRs at the designed central wavelength with those calculated values by using the equation investigated by Sheppard. We find that the measured reflective ratios of the fabricated DBRs meet the calculated results obtained from Sheppard’s equation. </jats:p

Blockage of Autophagy Increases Timosaponin AIII-Induced Apoptosis of Glioma Cells In Vitro and In Vivo

Timosaponin AIII (TSAIII), a saponin isolated from Anemarrhena asphodeloides and used in traditional Chinese medicine, exerts antitumor, anti-inflammatory, anti-angiogenesis, and pro-apoptotic activity on a variety of tumor cells. This study investigated the antitumor effects of TSAIII and the underlying mechanisms in human glioma cells in vitro and in vivo. TSAIII significantly inhibited glioma cell viability in a dose- and time-dependent manner but did not affect the growth of normal astrocytes. We also observed that in both glioma cell lines, TSAIII induces cell death and mitochondrial dysfunction, consistent with observed increases in the protein expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, cytochrome c, and Mcl-1. TSAIII also activated autophagy, as indicated by increased accumulation of the autophagosome markers p62 and LC3-II and the autolysosome marker LAMP1. LC3 silencing, as well as TSAIII combined with the autophagy inhibitor 3-methyladenine (3MA), increased apoptosis in GBM8401 cells. TSAIII inhibited tumor growth in xenografts and in an orthotopic GBM8401 mice model in vivo. These results demonstrate that TSAIII exhibits antitumor effects and may hold potential as a therapy for glioma

Core–shell FTO@Co₃O₄ nanoparticles as active and stable anode catalysts for acidic oxygen evolution reaction and proton exchange membrane water electrolysis

An anode catalyst, FTO-dispersed Co3+-lean and Ovac-free OER-active Co3O4, was developed for the high performance acidic oxygen evolution reaction and proton exchange membrane water electrolysis.</jats:p