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Background and Purpose: A series of benzothiazole derivatives were screened for immunosuppressive activity; of these compounds BD750 was found to be the most effective immunosuppressant. The purpose of the current study was to determine the immunosuppressive activity of BD750 on T cell proliferation and its potential mode of action.Experimental Approach: T cell proliferation, CD25 and CD69 expression and cell cycle distribution were measured in vitro by flow cytometry. Cell viability was determined by CCK-8 assay. Cytokine levels were measured by elisa. The activation of signal-regulated molecules was assessed by Western blot analysis. The effects of BD750 were evaluated in vivo in a mouse model of delayed-type hypersensitivity.Key Results: BD750 significantly inhibited mouse and human T cell proliferation, stimulated either by anti-CD3/anti-CD28 monoclonal antibodies or by an alloantigen, in a dose-dependent manner in vitro. No obvious cytotoxic effects of BD750 were observed in our experimental conditions. Furthermore, BD750 did not inhibit CD25 and CD69 expression or IL-2 and IL-4 secretion, but induced cell cycle arrest at the G(0) /G(1) phase in activated T cells. In IL-2-stimulated CTLL-2 cells and primary activated T cells, BD750 inhibited cell proliferation and STAT5 phosphorylation, but not Akt or p70S6K phosphorylation. BD750 also reduced the T cell-mediated delayed-type hypersensitivity response in mice in a dose-dependent manner.Conclusion and Implications: These data indicate that BD750 inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation. BD750 has the potential to be used as a lead compound for the design and development of new immunosuppressants for preventing graft rejection and treating autoimmune diseases. [ABSTRACT FROM AUTHOR]

This study is conducted to investigate the biocompatibility and biodegradation behavior of calcium phosphate-coated Mg alloy in vivo. Calcium phosphate (Ca–P) was coated on the Mg alloy (AZ31) by a chemical process. Samples of Ca–P coated rods, the naked alloy rods, and degradable polymer as controls were implanted into the thighbone of rabbits to investigate the bone response at the early stage. The reduction in implant volume was determined by micro-computed tomography and three-dimensional reconstruction of the remaining Mg alloy segmented from the bone matrix. It was observed that the biodegradation rate of naked Mg implant is faster than that of the coated ones. The bone–implant interface was characterized in sections by scanning electron microscopy with energy-dispersive spectroscopy. Biodegradation or reaction layer was formed on the surface of Mg alloy implants and direct contact with the surrounding bone. The layer was mainly composed of Ca, P, O, and Mg. After 8 weeks of post-operation, paraffin sections were generated for histomorphologic analysis; 100% implants were fixed and no inflammation was observed. Histological analysis showed that new bone tissue is formed around the Mg implants, and no fibrous capsule was found. Blood examination showed that the biodegradation of the Mg implant caused little change to blood composition. Ca–P coating on Mg alloy substrate might be an effective method to reduce the biodegradation rate of Mg alloy in vivo and improve the surface bioactivity of Mg alloy implants. [ABSTRACT FROM AUTHOR]