Focal Spot, Winter 1983/84

https://digitalcommons.wustl.edu/focal_spot_archives/1036/thumbnail.jp

Macrophage colony-stimulating factor and its receptor signaling augment glycated albumin-induced retinal microglial inflammation in vitro

<p>Abstract</p> <p>Background</p> <p>Microglial activation and the proinflammatory response are controlled by a complex regulatory network. Among the various candidates, macrophage colony-stimulating factor (M-CSF) is considered an important cytokine. The up-regulation of M-CSF and its receptor CSF-1R has been reported in brain disease, as well as in diabetic complications; however, the mechanism is unclear. An elevated level of glycated albumin (GA) is a characteristic of diabetes; thus, it may be involved in monocyte/macrophage-associated diabetic complications.</p> <p>Results</p> <p>The basal level of expression of M-CSF/CSF-1R was examined in retinal microglial cells <it>in vitro</it>. Immunofluorescence, real-time PCR, immunoprecipitation, and Western blot analyses revealed the up-regulation of CSF-1R in GA-treated microglial cells. We also detected increased expression and release of M-CSF, suggesting that the cytokine is produced by activated microglia via autocrine signaling. Using an enzyme-linked immunosorbent assay, we found that GA affects microglial activation by stimulating the release of tumor necrosis factor-α and interleukin-1β. Furthermore, the neutralization of M-CSF or CSF-1R with antibodies suppressed the proinflammatory response. Conversely, this proinflammatory response was augmented by the administration of M-CSF.</p> <p>Conclusions</p> <p>We conclude that GA induces microglial activation via the release of proinflammatory cytokines, which may contribute to the inflammatory pathogenesis of diabetic retinopathy. The increased microglial expression of M-CSF/CSF-1R not only is a response to microglial activation in diabetic retinopathy but also augments the microglial inflammation responsible for the diabetic microenvironment.</p

1,4-Diazo­niabicyclo­[2.2.2]octane terephthalate

In the title compound, C6H14N2+·C8H4O4 2−, the protonated 1,4-diazo­niabicyclo­[2.2.2]octane cations and the deprotonated terephthalate anions are alternately linked by N—H⋯O hydrogen bonds into chains

The effect of mesoporous bioglass on osteogenesis and adipogenesis of osteoporotic BMSCs

This study evaluated the effect of mesoporous bioglass (MBG) dissolution on the differentiation of bone marrow mesenchymal stem cells (BMSCs) derived from either sham control or ovariectomized (OVX) rats. MBG was fabricated by evaporation-induced self-assembly method. Cell proliferation was tested by Cell Counting Kit-8 assay, and cytoskeletal morphology was observed by fluorescence microscopy. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining and activity, Alizarin Red staining, while adipogenic differentiation was assessed by Oil Red-O staining. Quantitative real-time PCR and Western blot analysis were taken to evaluate the expression of runt-related transcription factor 2 (Runx2) and proliferator-activated receptor-γ (PPARγ). We found that MBG dissolution (0, 25, 50, 100, 200 µg/mL) was nontoxic to BMSCs growth. Sham and OVX BMSCs exhibited the highest ALP activity in 50 µg/mL of MBG osteogenic dissolution, except that sham BMSCs in 100 µg/mL showed the highest ALP activity on day 14. Runx2 was significantly upregulated after 100 µg/mL of MBG stimulation in sham and OVX BMSCs for 7 and 14 days, except that 25 µg/mL showed highest upregulation effect on OVX BMSCs at day 7. PPARγ was downregulated after MBG stimulation. The protein level of Runx2 from the sham BMSCs group was significantly upregulated after lower doses (25 and 50 µg/mL) of MBG stimulation, whereas PPARγ was downregulated in the sham and OVX BMSCs group. Thus, both the osteogenic and adipogenic abilities of BMSCs were damaged under OVX condition. Moreover, lower concentration of MBG dissolution can promote osteogenesis but inhibit adipogenesis of the sham and OVX BMSCs