ABSTRACT
The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.
ABSTRACT
The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.
ABSTRACT
BACKGROUND: With the development of chemical synthesis technology, the application of anti-osteoporosis drugs incorporated into scaffolds to promote bone regeneration in osteoporotic bone defects has become a hot issue nowadays. OBJECTIVE: To introduce bone tissue engineering scaffolds, and to discuss and summarize the application of the scaffolds carrying anti-osteoporosis drugs for osteogenesis in osteoporotic bone defects. METHODS: PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases were retrieved with "osteoporosis, bone defect, scaffold" as key words for relevant articles published from 2005 to 2017. Initially, 201 articles were retrieved, and finally 64 articles were selected for further analysis. RESULTS AND CONCLUSION: With the development of biochemical synthesis technology, various types of tissue-engineered bone scaffolds have been used for the treatment of osteoporotic bone defects. For example, the modified calcium phosphate cement, β-tricalcium phosphate, and hydroxyapatite all can promote bone regeneration. However, the ability of conventional scaffolds to promote bone regeneration is severely damaged under the state of osteoporosis. In this case, an anti-osteoporosis therapy becomes necessary. Considering severe adverse effects of systemic anti-osteoporosis drugs and limited local bone regeneration, the combination of scaffold implantation and local drug delivery can promote osteoporotic bone defect healing. Importantly, to incorporate bone regeneration inducers into scaffolds and steadily release with their biological activity is the key to success. Bisphosphonate, strontium, bone morphogenetic protein 2 and parathyroid hormone, traditional Chinese medicine and mesenchymal stem cells are the drugs commonly combined with tissue-engineered bone scaffolds. With the development of biotechnology, genetically modified stem cell-scaffold composites have gradually appealed to researchers.
ABSTRACT
BACKGROUND:Stem cells combined with a three-dimensional scaffold have great potential for the treatment of osteoporotic bone defects. OBJECTIVE:To introduce the application of stem cells combined with the three-dimensional scaffold in repairing osteoporotic bone defects. METHODS:A computer-based search of PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases was performed for relevant articles published from 2007 to 2017 with "stem cells, scaffold, osteoporosis, bone defects" as key words in English and Chinese, repsectively. Initially, 142 articles were retrieved, and finally 45 articles were included in result analysis. RESULTS AND CONCLUSION:Due to the potential of self-renewal and multilineage differentiation, stem cells can be used to repair or regenerate damaged tissues, which are considered as an ideal cell source for the treatment of diseases in orthopedics. The suitable scaffold can provide a favorable microenvironment for repairing the attachment and growth of the cells related to the bone defect, which can promote the healing without additional side effects. Furthermore, stem cells combined with three-dimensional scaffolds provide a promising clinical application for the treatment of osteoporotic bone defects by regulation of bone metabolism. In addition, gene-modified stem cells with three-dimensional scaffolds bring a huge potential in the treatment of osteoporotic bone defects. In conclusion, the combination of stem cells and three-dimensional scaffolds provides a new approach for the treatment of osteoporotic bone defects, which may be one of the future therapeutic strategies.