[Genetic diversity and genetic structure of Sorex isodon in Northeast China]. / ä¸­å›½ä¸œåŒ—åœ°åŒºè¿œä¸œé¼©é¼±é—ä¼ å¤šæ ·æ€§ä¸Žé—ä¼ ç»“æž„.

A total of 64 haplotypes were obtained from the complete Cytochrome b gene (Cyt b) of 77 Sorex isodon collected from three populations (Daxing'anling, Xiaoxing'anling, and Changbai Mountains) in Northeast China. The haplotype diversity was 0.9920 and the nucleotide diversity was 0.0105, indicating high genetic diversity. The genetic diversity of Changbai Mountains population was significantly higher than that of Daxing'anling and Xiaoxing'anling populations. The F-statistics, the number of migrants per generation and the genetic distance results showed that the genetic distances among the populations and among the sampling sites were generally consistent with geographical distance. Analysis of molecular variance showed that the differentiation among populations, among sampling sites, and within sampling site accounted for 33.4%, 10.2% and 56.4% of total variation, respectively. The analysis of population history showed that S. isodon in Northeast China experienced no population expansion. The reported complete sequence of Cyt b gene of S. isodon (GenBank) of Europe and other parts of Asia was downloaded to examine the genetic structure of S. isodon. The phylogenetic tree was divided into two large branches. One branch consisted mainly of Daxing'anling and Xiaoxing'anling samples. The other branch was departed into two sub-branches. Median-joining network analysis showed that there were three lineages: one lineage mainly consisted of haplotypes from Daxing'anling and Xiaoxing'anling, and also four haplotypes of Changbai Mountains, while the other lineage included a few haplotypes of three populations in Northeast China, and those from Baikal Lake, Russia and Finland. The last lineage was entirely composed of haplotypes from Changbai Mountains. The results of genetic diversity, phylogenetic tree and median-joining network all suggested that the Changbai Mountains was the refuge for S. isodon during last glacial.

miR-125a Promotes the Progression of Giant Cell Tumors of Bone by Stimulating IL-17A and ß-Catenin Expression.

Giant cell tumors of bone (GCTBs) exhibit high recurrence and aggressive bone lytic behavior; but, the mechanism of GCTB progression is largely unknown. In GCTB, we detected abundant levels of miR-125a, which were associated with tumor extension, grade, and recurrence. miR-125a stimulates stromal cell tumorigenicity and growth in vivo by promoting the expression of interleukin-17A (IL-17A) and ß-catenin. In contrast, inhibition of miR-125a suppressed stromal cell tumorigenicity and growth. Then, we found that miR-125a stimulates IL-17A by targeting TET2 and Foxp3, and it stimulates ß-catenin expression by targeting APC and GSK3ß in stromal cells. Furthermore, we identified that IL-17A stimulates miR-125a by activating nuclear factor κB (NF-κB) signaling in stromal cells. Finally, our data show that simultaneous inhibition of IL-17A signaling and miR-125a more significantly inhibits stromal cell growth than miR-125a inhibition alone. miR-125a stimulates the progression of GCTB, and it might represent a useful candidate marker for progression. Simultaneously blocking miR-125a and IL-17A might represent a new therapeutic strategy for GCTB.

A high risk of osteosarcoma in individuals who are homozygous for the p.D104N in endostatin.

The D104N polymorphism (p.D104N) in endostatin has been previously identified in many types of cancer, and this polymorphism is believed to be a phenotypic modulator in some tumors. However, it is unknown whether endostatin p.D104N affects the risk and progression of osteosarcoma (OS). Here, we analyzed the p.D104N endostatin variant in 236 patients with OS and 418 healthy individuals. Similar frequencies of wild type and heterozygous p.104DN endostatin were observed in controls and OS patients. Interestingly, the frequency of the homozygous p.D104N (p.104NN) genotype was higher in OS patients group compared to control group, suggesting that individuals with p.104NN endostatin have a significantly increased risk for OS. In addition, OS patients with p.104NN endostatin had a shorter survival time and a higher rate of metastasis than OS patients with wild type endostatin. Animal experiments revealed that overexpression of p.104NN endostatin did not significantly inhibit OS lung metastasis. Interestingly, administration of endostatin dramatically inhibited OS lung metastasis in the p.104NN endostatin xenograft model. Together, these results suggest that p.104NN of endostatin is associated with the risk of OS and demonstrates predictive significance for clinical outcome in OS patients. In addition, endostatin therapy may be necessary for OS patients harboring p.104NN endostatin.

[Proliferation of tissue-engineered cartilage cells under compressive stress].

OBJECTIVE: To investigate the proliferation of tissue-engineered cartilage cells stimulated by different intensities of compressive stress. METHODS: Human embryonic cartilage cells were seeded into type II collagen sponge scaffold. The cells of the pressure groups were stimulated by different compression rate (0-5%, 0-10%, and 0-20%) at a cyclical frequency of 0.1 Hz. The cells of the control group were cultured without pressure. Gross observation, histological section, MTT assay and flow cytometry were used to observe the morphology, cell number and distribution and detect the cell proliferation and cell cycle. RESULTS: Tissue-engineered cartilage cells in 0-10% group showed the largest size and greatest thickness with normal morphology. Tissue biopsies showed the largest number of cartilage cells with more uniform distribution, close alignment, more matrix secretion. The cartilage cell activity was significantly enhanced and the percentage of S phase cells significantly increased in the pressure group compared with those in the control group, and such changes were especially obvious in 0-10% group in which the S phase cells increased by 59.0% compared with that in the control group. CONCLUSION: The proliferation of tissue-engineered cartilage cells is regulated by the cyclic stress intensity, and a pressure frequency of 0.1 Hz with compression rate of 0-10% can better promote the cell proliferation.