In this work, Ti—Mg metal-metal composites (MMCs) were successfully fabricated by spark plasma sintering (SPS). In vitro, the proliferation and differentiation of SaOS-2 cells in response to Ti—Mg metal-metal composites (MMCs) were investigated. In vivo, a rat model with femur condyle defect was employed, and Ti—Mg MMCs implants were embedded into the femur condyles. Results showed that Ti—Mg MMCs exhibited enhanced cytocompatibility to SaOS-2 cells than pure Ti. The micro-computed tomography (Micro-CT) results showed that the volume of bone trabecula was significantly more abundant around Ti—Mg implants than around Ti implants, indicating that more active new-bone formed around Ti—Mg MMCs implants. Hematoxylin-eosin (H&E) staining analysis revealed significantly greater osteointegration around Ti—Mg implants than that around Ti implants.
As a typical metal-organic framework (MOF), Mg-MOF74 can release biocompatible Mg2+ when the framework is degraded, and it has the potential to be used as filler in the field of bone tissue engineering (BTE). However, Mg-MOF74 has poor stability in aqueous environment and limited antibacterial ability, which limit its further development and applications. In this work,MgCu-MOF74 particles with different Cu content were synthesized through a facile one-step hydrothermal method. The physicochemical properties and water stability of the synthesized powders were characterized. The osteogenic potential of the MgCu-MOF74 particles on human osteogenic sarcoma cells (SaOS-2) was evaluated. The hybrid MgCu-MOF74 exhibited favorable water stability. These results indicated that MgCu-MOF74 enhanced cellular viability, alkaline phosphatase (ALP) levels, collagen (COL) synthesis and osteogenesis-related gene expression. Moreover, the samples doped with Cu2+ were more sensitive to the acidic microenvironment produced by bacteria, and exhibited stronger antibacterial ability than Mg-MOF74. In conclusion, MgCu-MOF-74 with good water stability, osteogenic ability and antibacterial ability, which could be attributed to the doping of Cu2+. Hence, MgCu-MOF74 shows great potential as a novel medical bio-functional fillers for the treatment of bone defects.
Background: Fibroblast activation protein (FAP) is a type II cell surface-bound integral serine protease, which is an important biomarker of cancer-associated fibroblasts. FAP-α performs several biological activities, including remolding extracellular matrix and acting as an immunosuppressor in the tumor microenvironment. However, the proliferation role of FAP-α in human lung adenocarcinoma has not been fully elucidated.
Methods:The expression of FAP-α in 94-paired human lung adenocarcinoma tissues was identified by immunohistochemistry test. The effect of FAP on cell proliferation was examined by CCK-8 assay. RNAsequencing and bioinformatics analysis were utilized to investigate the underlying mechanism. Western blot analysis, quantitative polymerase chain reaction (qPCR), and nude mice experiments, were also conducted for further validation.Results: The proliferation rates of human fibroblast strains FAP-HFF and FAP-BJ, and human lung adenocarcinoma cell line FAP-SPC-A-1 were higher than those of controls. The nude mice experiment also showed that FAP could promote the proliferation of SPC-A-1 cell line in vivo. qPCR and Western blot analysis indicated that CCNB1 was upregulated by the overexpression of FAP in the lung adenocarcinoma cell line. The expression of FAP-α was higher in both the cytoplasm and stroma of lung adenocarcinoma than in adjacent normal tissues. Survival analysis indicated that patients with higher expression of FAP-α in tumor stroma had a poor prognosis (P=0.019). The Cancer Genome Atlas Program (TCGA) data also showed that the expression of FAP within tumor tissues was higher (in both cytoplasm and stroma) compared with that in normal tissues (P<0.05).Conclusions: Our study indicates that FAP-α could facilitate the proliferation of lung adenocarcinoma cells and can be a prognostic marker in human lung adenocarcinoma.
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