Among the multiple components of propolis, flavonoids contribute greatly to the antioxidant activities of propolis. Flavonoids mainly exist in the form of sugar-conjugated derivatives. Quercetin glycosides represent the predominant flavonoid fraction in propolis. In this work, density functional theory (DFT) calculations were applied to analyze the antioxidative properties of quercetin and its glucosides in the gas and in the liquid phase (ethanol, water). Three main antioxidant mechanisms, hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) were used to analyze the antioxidative capacity of the investigated compounds. Solvent effects dominantly affect SET-PT and SPLET. Thus, the thermodynamically preferred mechanism can be altered. HAT and SPLET are the thermodynamically dominant mechanisms in gas and solvent phases, respectively. Therefore, in the gas phase, the sequence of the antioxidative capacity is similar with the bond dissociation enthalpy values: quercetin > quercetin-5-O-glucoside > quercetin-7-O-glucoside > quercetin-3-O-glucoside > quercetin-3′-O-glucoside > quercetin-4′-O-glucoside. While, in the solvent phases, the sequence is similar with the proton affinity values: quercetin-4′-O-glucoside > quercetin-5-O-glucoside > quercetin > quercetin-3-O-glucoside > quercetin-7-O-glucoside > quercetin-3′-O-glucoside. OH groups in B-ring and C-ring contribute mainly to the antioxidative activities of quercetin and glucosides compared with A-ring.

Treatment of bone defects remains a challenge in the clinic. Artificial bone grafts are the most promising alternative to autologous bone grafting. However, one of the limiting factors of artificial bone grafts is the limited means of regulating stem cell differentiation during bone regeneration. As a weight-bearing organ, bone is in a continuous mechanical environment. External mechanical force, a type of biophysical stimulation, plays an essential role in bone regeneration. It is generally accepted that osteocytes are mechanosensitive cells in bone. However, recent studies have shown that mesenchymal stem cells (MSCs) can also respond to mechanical signals. This article reviews the mechanotransduction mechanisms of MSCs, the regulation of mechanical stimulation on microenvironments surrounding MSCs by modulating the immune response, angiogenesis and osteogenesis, and the application of mechanical stimulation of MSCs in bone regeneration. The review provides a deep and extensive understanding of mechanical stimulation mechanisms, and prospects feasible designs of biomaterials for bone regeneration and the potential clinical applications of mechanical stimulation.

The increasing insight into the molecular and cellular processes within the angiogenic cascade assists in enhancing the survival and integration of engineered bone constructs. Copper-doped bioactive glass (Cu-BG) is now a potential structural component of the novel scaffolds and implants used in orthopedic and dental repairs. However, it is difficult for BG, especially micro-nano particles, to be printed into scaffolds and still retain its biological activity and ability to biodegrade. Additionally, the mechanisms of the copper-stimulating autocrine and paracrine effects of human umbilical vein endothelial cells (hUVECs) during repair and regeneration of bone are not yet clear. Therefore, in this study, we created monodispersed micro-nano spherical Cu-BG particles with varying copper content through a sol–gel process. Through in vitro tests, we found that Cu-BG enhanced angiogenesis by activating the pro-inflammatory environment and the HIF-1α pathway of hUVECs. Furthermore, 2Cu-BG diluted extracts directly promoted the osteogenic differentiation of mouse bone mesenchymal stem cells (BMSCs) in vitro. Then, a new 3D-printed tyramine-modified gelatin/silk fibroin/copper-doped bioactive glass (Gel/SF/Cu-BG) scaffold for rat bone defects was constructed, and the mechanism of the profound angiogenesis effect regulated by copper was explored in vivo. Finally, we found that hydrogel containing 1 wt% 2Cu-BG effectively regulated the spatiotemporal coupling of vascularization and osteogenesis. Therefore, Cu-BG-containing scaffolds have great potential for a wide range of bone defect repairs.

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 Zn²⁺ released from ZnO NPs induced downregulation of β-catenin expression via HIF-1α/BNIP3/LC3B-mediated mitophagy pathway. ZnO NPs combined with ICG-001, a β-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 higher β-catenin expression which indicated the role of β-catenin in OS development. In summary, our current study not only proved that ZnO NPs can inhibit OS metastasis by degrading β-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.

Antibiotics have been considered as effective weapons against bacterial infections since they were discovered. However, antibiotic resistance caused by overuse and abuse of antibiotics is an emerging public health threat nowadays. Fully defeating bacterial infections has become a tough challenge. In this work, cerium oxide was fabricated on medical titanium by thermolysis of cerium-containing metal-organic framework (Ce-BTC). Regulation of Ce (Ⅲ)/Ce (Ⅳ) ratios was realized by pyrolysis of Ce-BTC in different gas environment, and the antibacterial properties were studied. The results indicated that, in acidic conditions, ceria with a high Ce (Ⅲ)/Ce (Ⅳ) ratio owned high oxidase-like activity which could produce reactive oxygen species. Moreover, ceria with high Ce (Ⅲ) content possessed strong ATP deprivation capacity which could cut off the energy supply of bacteria. Based on this, ceria with a high Ce (Ⅲ)/Ce (Ⅳ) ratio exhibited superior antibacterial activity