Chondrogenic Differentiation Alters the Immunosuppressive Property of Bone Marrow-Derived Mesenchymal Stem Cells, and the Effect is Partially due to the Upregulated Expression of B7 Molecules

To investigate the immunosuppressive properties of mesenchymal stem cells (MSCs), in the present study we examined the immunogenicity of undifferentiated and tri-lineage (chondrocytes, osteoblasts and adipocytes) differentiated rat bone marrow-derived MSCs under xenogeneic conditions. After chondrogenic-differentiation, rat bone marrow-derived MSCs stimulated human peripheral blood monocyte-derived DCs (hDCs), leading to 8- and 4-fold higher lymphocyte proliferation and cytotoxicity than that of undifferentiated MSCs. The Chondrogenic-differentiated MSCs were chemotactic to hDCs in Dunn chamber chemotaxis system and were rosetted by hDCs inrosette assays. Flow cytometry analysis revealed that chondrogenic-differentiated MSCs had promoted hDCs maturation causing higher CD83 expression in hDCs, whereas undifferentiated MSCs, osteogenic-and adipogenic-differentiated MSCs showed inhibitory effect on hDCs maturation. The co-stimulatory molecules B7 were up-regulated only in the chondrogenic-differentiated MSCs. After blocking B7 molecules with specific monoclonal antibodies in the chondrogenic-differentiated MSCs, CD83 expression of co-cultured hDCs was greatly reduced. In conclusion, chondrogenic differentiation may increase the immunogenicity of MSCs, leading to stimulation of DCs. The up-regulated expression of B7 molecules on the chondrogenic differentiated MSCs may be partially responsible for this event.

Iron abundances from optical FeIII absorption lines in B-type stellar spectra

The role of optical FeIII absorption lines in B-type stars as iron abundance diagnostics is considered. To date, ultraviolet Fe lines have been widely used in B-type stars, although line blending can severely hinder their diagnostic power. Using optical spectra, covering a wavelength range ~3560-9200Å, a sample of Galactic B-type main-sequence and supergiant stars of spectral types B0.5 to B7 are investigated. A comparison of the observed FeIII spectra of supergiants, and those predicted from the model atmosphere codes TLUSTY [plane-parallel, non-local thermodynamic equilibrium (LTE)], with spectra generated using SYNSPEC (LTE), and CMFGEN (spherical, non-LTE), reveal that non-LTE effects appear small. In addition, a sample of main-sequence and supergiant objects, observed with the Fiber-fed Extended Range Optical Spectrograph (FEROS), reveal LTE abundance estimates consistent with the Galactic environment and previous optical studies. Based on the present study, we list a number of FeIII transitions which we recommend for estimating the iron abundance from early B-type stellar spectra.

Proportioning variability in the dispensation of hand-mixed dental cements

Objectives: The purpose of this investigation was to determine for dispensed multiples (1 through 4) of powder (P) and liquid (L) in hand-mixed dental cement whether: (1) the mean (P/L) ratio (m/m) and (2) the maximum difference in (P/L) ratio is dependent on the number of multiples dispensed. The Null hypotheses were: (a) mean (P/L) ratio is independent of the number of multiples dispensed and (b) maximum difference in (P/L) ratio is independent of the number of multiples dispensed.
Methods: The materials investigated are listed in the Table. The masses of dispensed aliquots of powder and liquid were measured by a single operator (n=10, for multiples 1 through 4) on a 4-place analytical balance. All measurements were made independently and all possible (P/L) ratios calculated for each sample. The effect of multiple dispensations on (P/L) ratios and maximum (P/L) differences was by one-way ANOVA and linear regression, respectively, with the Tukey post-hoc correction for multiple comparisons.MULTIPLE DISPENSEDDISPENSED MU(x1)(x2)(x3)(x4)Zinc phosphateHeraeus12.271(0.691)a13.051(1.269)b13.215(0.824)b13.118(1.149)bFuji IXGC4.209(0.373)a4.085(0.275)b4.095(0.226)b4.095(0.217)bIRMDentsply7.933(0.767)a7.430(0.451)b7.977(0.729)a8.186(0.929)aKetac-Cem3M Espe9.6206(0.613)a9.714(0.523)a9.298(0.314)b9.321(0.292)bMean (SD) powder/liquid ratio (m/m). Superscript letters represent significances (α = 0.05) within each material
Results: Mean (SD) (P/L) ratios are presented in the Table. Null hypothesis (a) is rejected: either (x1) or (x2) dispensation yields a different (P/L) ratio to (x3) or (x4) (p < 0.05). Null hypothesis (b) is rejected: a negative correlation is observed in max (P/L) ratio difference with dispensed multiple for Ketac Cem (p = 0.029).
Conclusion: For hand-mixed dental cements: (1) more consistent (P/L) ratios may be observed with multiple dispensations of powder & liquid; (2) maximum differences in (P/L) ratio may be negatively correlated with dispensation multiple in some materials.

The prognostic significance of PD-L1 in bladder cancer

Immunotherapy is a promising strategy for the treatment of various types of cancer. An antibody that targets programmed death ligand-1 (PD-L1) pathway has been shown to be active towards various types of cancer, including melanoma and lung cancer. MPDL3280A, an anti‑PD-L1 antibody, has shown clear clinical activity in PD-L1-overexpressing bladder cancer with an objective response rate of 40-50%, resulting in a breakthrough therapy designation granted by FDA. These events pronounce the importance of targeting the PD-L1 pathway in the treatment of bladder cancer. In the present study, we investigated the prognostic significance of the expression of three genes in the PD-L1 pathway, including PD-L1, B7.1 and PD-1, in three independent bladder cancer datasets in the Gene Expression Omnibus database. PD-L1, B7.1 and PD-1 were significantly associated with clinicopathological parameters indicative of a more aggressive phenotype of bladder cancer, such as a more advanced stage and a higher tumor grade. In addition, a high level expression of PD-L1 was associated with reduced patient survival. Of note, the combination of PD-L1 and B7.1 expression, but not other combinations of the three genes, were also able to predict patient survival. Our findings support the development of anti-PD-L1, which blocks PD-L1-PD-1 and B7.1-PD-L1 interactions, in treatment of bladder cancer. The observations were consistent in the three independent bladder cancer datasets consisting of a total of 695 human bladder specimens. The datasets were then assessed and it was found that the expression levels of the chemokine CC-motif ligand (CCL), CCL3, CCL8 and CCL18, were correlated with the PD-L1 expression level, while ADAMTS13 was differentially expressed in patients with a different survival status (alive or deceased). Additional investigations are required to elucidate the role of these genes in the PD-L1-mediated immune system suppression and bladder cancer progression. In conclusion, findings of this study suggested that PD-L1 is an important prognostic marker and a therapeutic target for bladder cancer.