Visfatin Facilitates VEGF-D-Induced Lymphangiogenesis through Activating HIF-1α and Suppressing miR-2277-3p in Human Chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.

Development and validity of an intermediate conceptual measurement (ICM) -based measurement tool for the nursing professional values of undergraduate students.

BACKGROUND: Nursing professional values are the foundation of nursing practice. There has been no research to develop an instrument to measure professional values in nursing based on intermediate conceptual measurement theory. OBJECTIVES: To develop an ICM-based measurement tool for the nursing professional values of undergraduate students. DESIGN: A cross-sectional study. METHODS: The Nursing Professional Values-Intermediate Conceptual Measurement (NPV-ICM) was developed using the steps of Cunningham's process to generate questionnaire items. The tool was devised in three stages: identifying the intermediate concepts, developing stories reflecting the intermediate concepts and setting up options for action and justification in the stories and setting up scoring criteria for the measurement tool. The tool was tested through internal consistency reliability, content validity and calibration correlation validity. RESULTS: This study resulted in five nursing professional values situational stories containing five themes (care, altruism, responsibility, respect and justice) respectively. Each situational story contained a varying number of action options and justification options, totalling 72 Richter 5 level options and 20 ranked items. Reliability and validity were found to be good, with a total Cronbach's α of 0.93 and Cronbach's α of 0.75-0.80 for each situational story and calibrated correlational validity was found to correlate significantly between the total Nursing Professional Values Scale Revised (NPVS-R) scores and the NPV-ICM. CONCLUSIONS: The NPV-ICM created in this study possesses high reliability and validity. It alters the values perception research, moving from abstract conceptual measurements to measurements of particular values actions and justifications for participation in activities. And the study presents preliminary evidence supporting the reliability of the NVP-ICM as a measure of professional values.

The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Extracellular vesicles called exosomes are primarily used as mediators of intercellular signal transmission to control tumor metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with exosome generation in chondrosarcoma motility remains undetermined. Our results found that overexpressing visfatin augments the production of exosomes from chondrosarcoma cells. Visfatin-treated chondrosarcoma exosomes educate macrophage polarization towards the M2 but not M1 phenotype. Interestingly, M2 macrophages polarized by exosomes return to chondrosarcoma cells to facilitate cell motility. According to these findings, chondrosarcoma cells emit more exosomes when treated with visfatin. The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma.

Visfatin-Induced Inhibition of miR-1264 Facilitates PDGF-C Synthesis in Chondrosarcoma Cells and Enhances Endothelial Progenitor Cell Angiogenesis.

New treatments for chondrosarcoma are extremely important. Chondrosarcoma is a primary malignant bone tumor with a very unfavorable prognosis. High-grade chondrosarcoma has a high potential to metastasize to any organ in the body. Platelet-derived growth factor (PDGF) is a potent angiogenic factor that promotes tumor angiogenesis and metastasis. The adipocytokine visfatin promotes metastatic potential of chondrosarcoma; however, the role of visfatin in angiogenesis in human chondrosarcoma is unclear. We report that the levels of PDGF-C expression were positively correlated with tumor stages, significantly higher than the levels of expression in normal cartilage. Visfatin increased PDGF-C expression and endothelial progenitor cell (EPC) angiogenesis through the PI3K/Akt/mTOR signaling pathway, and dose-dependently down-regulated the synthesis of miR-1264, which targets the 3'-UTR of PDGF-C. Additionally, we discovered inhibition of visfatin or PDGF-C in chondrosarcoma tumors significantly reduced tumor angiogenesis and size. Our results indicate that visfatin inhibits miR-1264 production through the PI3K/Akt/mTOR signaling cascade, and thereby promotes PDGF-C expression and chondrosarcoma angiogenesis. Visfatin may be worth targeting in the treatment of chondrosarcoma angiogenesis.