Repair of bone defects using dynamic fabricated tissue-engineered bone based on a bio-derived porous bone scaffold

Fabrication and transplantation of tissue-engineered bones in a rotating wall vessel bioreactor (RWVB) was studied in the present study aiming to repair segmental bone defects. Osteoblasts were transfected with green fluorescent protein prior to seeding on bio-derived porous bone scaffolds at a density of 1?×?10⁶?cells/mL and cultured in an RWVB for one week. For comparison, constructs were also cultured in a static condition. Morphology and structure of fabricated bones were examined using an inverted microscope, scanning electron microscope and histology analysis via hematoxylin–eosin and toluidine blue staining. Moreover, an animal model for repairing segmental bone defects of a Zelanian rabbit was used to assess the efficacy and biosafety of fabricated bones. In conclusion, tissue-engineered bones grew favorably in RWVB. In animal study, a preliminary repair of bone defects was noticed only in the experimental group after 4 weeks of implantation. Using RWVB, the fabricated tissue-engineered bone constructs were approved with better bio-capability in repairing the segmental bone defect.     

Tiliroside is a new potential therapeutic drug for osteoporosis in mice

Osteoporosis is a class of metabolic bone disease caused by complexed ramifications. Overactivation of osteoclasts due to a sudden decreased estrogen level plays a pivotal role for postmenopausal women suffering from osteoporosis. Therefore, inhibiting osteoclast formation and function has become a major direction for the treatment of osteoporosis. Tiliroside (Tle) is a salutary dietary glycosidic flavonoid extracted from Oriental Paperbush flower, which has been reported to have an anti-inflammation effect. However, whether Tle affects the osteoclastogenesis and bone resorption remains unknown. Herein, we demonstrate that Tle prevents bone loss in ovariectomy in mice and inhibits osteoclast differentiation and bone resorption stimulated by receptor activator of nuclear factor-κB ligand (RANKL) in vitro. Molecular mechanism studies reveal that Tle reduces RANKL-induced activation of mitogen-activated protein kinase and T-cell nuclear factor 1 pathways, and osteoclastogenesis-related marker gene expression, including cathepsin K (Ctsk), matrix metalloproteinase 9, tartrate-resistant acid phosphatase (Acp5), and Atp6v0d2. Our research indicates that Tle suppresses osteoclastogenesis and bone loss by downregulating the RANKL-mediated signaling protein activation and expression. In addition, Tle inhibits intracellular reactive oxygen species generation which is related to the formation of osteoclasts. Therefore, Tle might serve as a potential drug for osteolytic disease such as osteoporosis.     

Salidroside promotes rat spinal cord injury recovery by inhibiting inflammatory cytokine expression and NF-κB and MAPK signaling pathways

Spinal cord injury (SCI) is a public health problem in the world. The SCI usually triggers an excessive inflammatory response that brings about a secondary tissue wreck leading to further cellular and organ dysfunction. Hence, there is great potential of reducing inflammation for therapeutic strategies of SCI. In this study, we aim to investigate if Salidroside (SAD) exerts an anti-inflammatory effect and promotes recovery of motor function on SCI through suppressing nuclear factor-κB (NF-κB) and the mitogen-activated protein kinase (MAPK) pathways. In vitro, real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine the inhibitory effect of SAD on the expression and release of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) activated by lipopolysaccharide (LPS) in astrocytes. In addition, SAD was found to inhibit NF-κB, p38 and extracellular-regulated protein kinases (ERK) signaling pathways by western blot analysis. Further, in vivo study showed that SAD was able to improve hind limb motor function and reduce tissue damage accompanied by the suppressed expression of inflammatory cytokines IL-1β, IL-6, and TNF-α. Overall, SAD could reduce the inflammatory response and promote motor function recovery in rats after SCI by inhibiting NF-κB, p38, and ERK signaling pathways.     

Blue light-induced phosphorylation of Arabidopsis cryptochrome 1 is essential for its photosensitivity

Plants possess two cryptochrome photoreceptors, cryptochrome 1 (CRY1) and cryptochrome 2 (CRY2), that mediate overlapping and distinct physiological responses. Both CRY1 and CRY2 undergo blue light-induced phosphorylation, but the molecular details of CRY1 phosphorylation remain unclear. Here we identify 19 in vivo phosphorylation sites in CRY1 using mass spectrometry and systematically analyze the physiological and photobiochemical activities of CRY1 variants with phosphosite substitutions. We demonstrate that nonphosphorylatable CRY1 variants have impaired phosphorylation, degradation, and physiological functions, whereas phosphomimetic variants mimic the physiological functions of phosphorylated CRY1 to constitutively inhibit hypocotyl elongation. We further demonstrate that phosphomimetic CRY1 variants exhibit enhanced interaction with the E3 ubiquitin ligase COP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1). This finding is consistent with the hypothesis that phosphorylation of CRY1 is required for COP1-dependent signaling and regulation of CRY1. We also determine that PHOTOREGULATORY PROTEIN KINASEs (PPKs) phosphorylate CRY1 in a blue light-dependent manner and that this phosphorylation is critical for CRY1 signaling and regulation. These results indicate that, similar to CRY2, blue light-dependent phosphorylation of CRY1 determines its photosensitivity.     

Cancer metabolism and tumor microenvironment: fostering each other?

Science China Life Sciences - The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live. Metabolic reprogramming supports tumor cell...     

IGF2BP2 maybe a novel prognostic biomarker in oral squamous cell carcinoma

Aim: The main of the present study was to investigate the role of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in oral squamous cell carcinoma (OSCC) with the overarching of providing new biomarkers or potential therapeutic targets for OSCC.Methods: We combined datasets downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and samples collected from the clinic to evaluate the expression of IGF2BP2 in OSCC. IGF2BP2 survival analysis was respectively performed based on TCGA, GEO, and clinical samples. Correlations between IGF2BP2 expression and clinicopathological parameters were then analyzed, and signaling pathways associated with IGF2BP2 expression were identified using gene set enrichment analysis (GSEA 4.1.0). Moreover, an IGF2BP2 co-expressed gene network was constructed, followed by gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on IGF2BP2 co-expressed genes. Finally, TIMER and CIBERSORT were used to analyze the correlations among IGF2BP2, IGF2BP2-coexpressed genes, and tumor-infiltrating immune cells (TICs).Results: IGF2BP2 was highly expressed in OSCC and significantly correlated with overall survival of OSCC patients (P<0.01). High IGF2BP2 expression correlated with poor overall survival. The GSEA results showed that cell apoptosis-, tumor-, and immune-related pathways were significantly enriched in samples with high IGF2BP2 expression. Furthermore, GO and KEGG enrichment analyses results of IGF2BP2 co-expressed genes indicated that these genes are mainly associated with immunity/inflammation and tumorigenesis. In addition, IGF2BP2 and its co-expressed genes are associated with TICs (P<0.01).Conclusion: IGF2BP2 may be a potential prognostic biomarker in OSCC and correlates with immune infiltrates.     

作物产量的模拟模型

产量模拟模型研究的重点是作物产量与生态因子间的关系。根据农业生态系统中限定产量的主要生态因子不同, 可将作物生产划为不同的生产水平, 并建立相应的生产力模型。各生态因子对预测不同范围的生产力都有其固有的适用性。动态模型是在长期定位观测基础上建立的, 空间变异模型用于农田产量预测, 宏观统计模型则用于区域性产量预测。本文在简要评述各类产量模型及其应用后, 提出了对产量模拟模型研究发展的看法。