Periodontal ligament stem cells (PDLSCs), a new population of mesenchymal stem cells (MSCs), have been isolated from the periodontal ligament (PDL). The capacity of multipotency and self-renewal makes them an excellent cell source for bone regeneration and repair. However, their bone-regeneration ability could be awakened in inflammatory microenvironments, which may be the result of changes in their differentiation potential. Recently, genetic evidences has shown that the Wnt pathway plays an important role in bone homeostasis. In this study we have determined the specific role of b-catenin in osteogenic differentiation of PDLSCs obtained from inflammatory microenvironments (P-PDLSCs). The inflammatory microenvironment, while inhibiting osteogenic differentiation potential, promotes proliferation of MSCs. A higher the level of b-catenin in P-PDLSCs than in H-PDLSCs (PDLSCs obtained from a healthy microenvironment) resulted in the same disparity in canonical Wnt signaling pathway activation between each cell type. Here we show that activation of bcatenin suppresses the noncanonical Wnt/Ca 2þ pathway, leading to increased proliferation but reduced osteogenic differentiation of PPDLSCs. Downregulation of the levels of b-catenin by treatment with dickkopf-1 (DKK-1) leads to activation of the noncanonical Wnt/ Ca 2þ pathway, which, in turn, results in the promotion of osteogenic differentiation in P-PDLSCs. Interestingly, b-catenin can affect both the canonical Wnt/b-catenin pathway and the noncanonical Wnt/Ca 2þ pathway. Our data indicate that b-catenin plays a central role in regulating osteogenic differentiation of MSCs in inflammatory microenvironments. Given the important role of Wnt signaling in osteogenic differentiation, it is possible that agents that can modify this pathway may be of value in bone regeneration by MSCs in chronic inflammatory microenvironments. ß
Human amniotic mesenchymal cells (hAMCs) and human amniotic epithelial cells (hAECs) have attracted increasing attention in recent years as a possible reserve of stem cells that may be useful for clinical application in regenerative medicine. The object of this study was to establish a new model for reconstruction of bilayered tissue-engineered (TE) skin with hAMCs and hAECs (amniotic cells TE skin, AC-TE skin). We studied these two types of cells and confirmed that they possessed the properties of stem cells. Mesenchymal-epidermal interactions are responsible for organogenesis. On the basis of this mechanism, we modified the constructing methods of traditional TE skin (TE skin with human fibroblasts and keratinocytes) and then established a new bilayered TE skin-AC-TE skin. Histological and immunochemical methods were carried out to assess AC-TE skin. The results showed that AC-TE skin was similar in morphology to human skin which had stratified epidermis and underlying dermis. AC-TE skin expressed proliferative cells marker Ki67 and epithelial stem cells marker K19; moreover, the constructed AC-TE skin could successfully repair full thickness skin defects on athymic mice. Our findings suggest that AC-TE skin is a useful skin equivalent which has good application prospects in regenerative medicine.
Accumulating evidence showed that aberrant miRNAs expression was involved in initiation and progression of melanoma. However, the investigation of different miRNAs in melanoma remain attractive. In this research, we demonstrated that miR-610 expression was decreased in melanoma tissues and cell lines. The clinical data showed that the reduced miR-610 expression was obviously associated with adverse prognostic characteristics. Furthermore, our results suggested that miR-610 had a function of prognostic indicator for 5-year predicted-survival of melanoma patients. The ectopic overexpression of miR-610 suppressed cell proliferation, cell cycle progression and promoted apoptosis while miR-610 knockdown reversed the effect in vitro and in vivo. Additionally, miR-610 could modulate LRP6 by directly interacting to its 3’-UTR. In clinical samples of melanoma, miR-610 inversely correlated with LRP6. The biological function of miR-610 on melanoma cells was abrogated by alternation of LRP6 expression. In summary, our research indexed that miR-610 had a function of tumor suppressor in regulating the proliferation, cell cycle and apoptosis of melanoma via targeting LRP6. Hence, it may represent a novel potential therapeutic target and prognostic marker for melanoma.
A high-performance organic photodetector is playing an important role in image sensing technology due to the regulatable photoelectric characteristics of organic semiconductor materials. In this article, four subphthalocyanine donor materials with narrowband green absorption are synthesized and characterized. Photophysical characterizations combined with quantum chemical calculations reveal the charge transfer ability of the subphthalocyanine materials, suggesting that the axial strong electron-withdrawing group is beneficial to the charge transfer in the excited state. By employing these materials as a photoactive layer, high-sensitivity and fast-response organic green photodetectors prepared by the solution process are demonstrated. The optimal photodetector based on SubPc 3a with the axial substituent −NO2 displays an external quantum efficiency (EQE) of 31.91%, a specific detectivity (D*) of 2.40 × 1012 Jones, and a response time (τ) of about 30 ms at 0 V bias under the illumination of 520 nm green light. Moreover, EQE spectroscopy shows that the subphthalocyanine-based photodetectors have a high selective response to green light. The results of the present work could provide insights into the optimal subphthalocyanine molecular design for high photodetection performance.
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