Zinc oxide nanoparticles inhibit osteosarcoma metastasis by downregulatingβ-catenin via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway

Osteosarcoma(OS)therapy faces many challenges,especially the poor survival rate once metastasis occurs.Therefore,it is crucial to explore new OS treatment strategies that can efficiently inhibit OS metastasis.Bioactive nanoparticles such as zinc oxide nanoparticles(ZnO NPs)can efficiently inhibit OS growth,however,the effect and mechanisms of them on tumor metastasis are still not clear.In this study,we firstly prepared well-dispersed ZnO NPs and proved that ZnO NPs can inhibit OS metastasis-related malignant behaviors including migration,invasion,and epithelial-mesenchymal transition(EMT).RNA-Seqs found that differentially expressed genes(DEGs)in ZnO NP-treated OS cells were enriched in wingless/integrated(Wnt)and hypoxia-inducible factor-1(HIF-1)signaling pathway.We further proved that Zn^(2+)released from ZnO NPs induced downregulation ofβ-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway.ZnO NPs combined with ICG-001,aβ-catenin inhibitor,showed a synergistic inhibitory effect on OS lung metastasis and a longer survival time.In addition,tissue microarray(TMA)of OS patients also detected much higherβ-catenin expression which indicated the role ofβ-catenin in OS development.In summary,our current study not only proved that ZnO NPs can inhibit OS metastasis by degradingβ-catenin in HIF-1α/BNIP3/LC3B-mediated mitophagy pathway,but also provided a far-reaching potential of ZnO NPs in clinical OS treatment with metastasis.

Role of Cu element in biomedical metal alloy design

Biomedical metals are widely used as implant materials in the human or animal body to repair organs and restore function, such as heart valves, meninges, peritoneum and artificial organs.Alloying element affects the microstructure, mechanical property, corrosion resistance and wear resistance, but also influences the antibacterial and biological activity.Recently, antibacterial metal alloys have shown great potential as a new kind of biomedical materials, in which Cu has been widely used as antibacterial agent element.In addition, biodegradable metal alloys, including magnesium alloy and zinc alloy, also have attracted much attention worldwide.Cu was also used as alloying element to adjust the degradation rate.Thus, the role of Cu in the alloy design will be very important for the development of new alloy.In this paper, we summarized the recent research results on the Cu-containing metal alloy for biomedical application and hoped that this review would give more suggestions for the further development of biomedical metal alloy.

Biocorrosion properties of Ti–3Cu alloy in F ion-containing solution and acidic solution and biocompatibility

Ti–3Cu alloy has shown low melting point and strong antibacterial properties against S.aureus and E.coli and thus has potential application as dental materials and orthopedic application.In this paper, the corrosion properties of Ti–3Cu alloy in five kinds of simulated solutions were investigated in comparison with cp-Ti(commercially pure titanium) by electrochemical technology and immersion experiment.Electrochemical results have demonstrated that Ti–3Cu alloy exhibited much nobler corrosion potential, lower corrosion current density and high corrosion resistance than cp-Ti in all solutions, especially in saliva-pH6.8+0.2 F and saliva-pH3.5, indicating that Ti–3Cu alloy has much better anticorrosion properties than cpTi.Immersion results have shown that Ti ion and Cu ion were released from Ti–3Cu, especially in saliva-pH6.8+0.2 F and saliva-pH3.5 solutions.Both electrochemical data and immersion results have indicated that high corrosion rate and high metal ion release rate were detected in F ion-containing solution and low-pH solution, displaying that F^- and low pH had much strong aggressive attack to cp-Ti and Ti–3Cu alloy.The corroded surface morphology was observed by scanning electron microscopy(SEM), and the roughness was tested in the end.The good corrosion resistance of antibacterial Ti–3Cu alloy suggests its great potential as a long-term biomedical application.

A novel biomedical titanium alloy with high antibacterial property and low elastic modulus

β-type titanium alloys have attracted much attention as implant materials because of their low elastic modulus and high strength,which is closer to human bones and can avoid the problem of stress fielding and extend the lifetime of prosthetics.However,other issues,such as the infection or inflammation postimplantation,still trouble the titanium alloy's clinical application.In this paper,we developed a novel nearβ-titanium alloy(Ti-13Nb-13Zr-13Ag,TNZA)with low elastic modulus and strong antibacterial ability by the addition of Ag element followed by proper microstructure controlling,which could reduce the stress shielding and bacterial infections simultaneously.The microstructure,mechanical properties,corrosion resistance,antibacterial properties and cell toxicity were studied using SEM,electrochemical testing,mechanical test and cell tests.The results have demonstrated that TNZA alloy exhibited an elastic modulus of 75-87 GPa and a strong antibacterial ability(up to 98%reduction)and good biocompatibility.Moreover,it was also shown that this alloy's corrosion resistance was better than that of Ti-13Nb-13Zr.All the results suggested that Ti-13Nb-13Zr-13Ag might be a competitive biomedical titanium alloy.

Improvement in antibacterial ability and cell cytotoxicity of Ti-Cu alloy by anodic oxidation

Ti-Cu alloy has potential to be used in plastic surgery and dental implants due to its strong antibacterialproperties,high strength and good corrosion resistance.In this paper,Ti-5Cu was anodic-oxidized to enhance the surface compatibility.The influence of the oxidation on the corrosion resistance,antibacterial properties and biological properties was investigated.X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS)results showed that a double-layer oxide coating with dense inner layer and porous outside layer was formed on Ti-Cu sample.The oxide coating consisted mainly of TiO2,CuzO and small amount of CuO,improved the corrosion resistance of Ti-Cu alloy by one order of magnitude due to the formation of the dense oxide inner layer,but high Cu ion release was detected.The plate count results showed that the antibac-terial activity of Ti-Cu sample was improved to≥99%due to the comprehensive function of CuO and Cu_(2)O in the coating and Cu^(2+)release.Cell test results showed that thecoating exhibited good cell compatibility,the porous sur-face structure improved the adhesion of cells,and Cu ion release promoted the cell proliferation.

ALD-induced TiO_(2)/Ag nanofilm for rapid surface photodynamic ion sterilization

The daily life of people in the intelligent age is inseparable from electronic device,and a number of bacteria on touch screens are increasingly threatening the health of users.Herein,a photocatalytic TiO_(2)/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction.Ultraviolet-visible(UV-Vis)spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO_(2).The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO_(2)/Ag film against S.aureus and E.coli was 98.2%and 98.6%,under visible light irradiation for 5 min.The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO_(2)reduced the bandgap of TiO_(2)from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO_(2)and Ag.Thus,TiO_(2)/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens.More importantly,the TiO_(2)/Ag film had great biocompatibility with/without light irradiation.The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.

Time-sequential changes of differentially expressed miRNAs during the process of anterior lumbar interbody fusion using equine bone protein extract, rhBMP-2 and autograft

The precise mechanism of bone regeneration in different bone graft substitutes has been well studied in recent researches. However, miRNAs regulation of the bone formation has been always mysterious. We developed the anterior lumbar interbody fusion （ALIF） model in pigs using equine bone protein extract （BPE）, recombinant human bone morphogenetic protein-2 （rhBMP-2） on an absorbable collagen sponge （ACS）, and autograft as bone graft substitute, respectively. The miRNA and gene expression profiles of different bone graft materials were examined using microarray technology and data analysis, including self-organizing maps, KEGG pathway and Biological process GO analyses. We then jointly analyzed miRNA and mRNA profiles of the bone fusion tissue at different time points respectively. Results showed that miRNAs, including let-7, miR-129, m iR-21, miR-133, miR-140, miR-146, miR-184, and miR-224, were involved in the regulation of the immune and inflammation response, which provided suitable inflammatory microenvironment for bone formation. At late stage, several miRNAs directly regulate SMAD4, Estrogen receptor 1 and 5-hydroxytryptamine （serotonin） receptor 2C for bone formation. It can be concluded that miRNAs play important roles in balancing the inflammation and bone formation.