Tenascin-C deficiency protects mice from experimental autoimmune encephalomyelitis

The extracellular matrix glycoprotein tenascin-C (TnC) has been increasingly appreciated as a molecule susceptibly reacting to abnormalities in the mammalian immune system. TnC expression is elevated in inflamed tissues outside the immune system, but also in lymphoid organs. It participates in the promotion of inflammatory responses. Here, the role of TnC in a paradigm of CNS autoimmunity was investigated. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, was induced in mice deficient in TnC (TnC(-/-)mice). Amelioration of EAE was observed in these mice in comparison to their wild-type (TnC(+/+)) littermates. Since T helper (Th)1 and Th17 cells play a dominant role in the pathogenesis of EAE, these cells were investigated in addition to analyzing locomotor functions and pro-inflammatory cytokine levels. Smaller numbers of interferon-gamma-producing Th1 cells and reduced ability of Th17 cells to produce interleukin-17 were observed in spleens of TnC(-/-) mice challenged by immunization with the myelin associated glycoprotein (MOG) when compared to TnC(+/+) mice. There was no difference in Th1 and Th17 responses in non-immunized TnC(-/-) and TnC(+/+) mice, thus excluding generalized immunosuppression in TnC(-/-) mice. These results show that TnC is important for the pathogenesis of CNS autoimmunity and that its deficiency interferes with Thl and Th17 encephalitogenic potentials. (C) 2016 Elsevier B.V. All rights reserved

Novel methylene modified cyclohexyl ethylenediamine-N,N '-diacetate ligands and their platinum(IV) complexes. Influence on biological activity

This paper focuses on the synthesis, characterization and biological activity of new N,N'-methylene modified cyclohexyl ethylenediamine-N,N'-diacetate (edda)-type ligands and their Pt(IV) complexes. Both the ligands and complexes were characterized by infrared, UV-vis, ESI-MS, 1D (H-1, C-13, Pt-195) and 2D (COSY, HSQC, HMBC) NMR spectroscopy and elemental analysis. The possible correlation between the reduction potentials and the cytotoxicity of the complexes was examined. The potential antitumoral activity of all compounds was tested in vitro on human melanoma A375, human glioblastoma U251, human prostate cancer PC3, human colon cancer HCT116, mouse melanoma B16 and mouse colon cancer CT26CL25 cells, as well as primary fibroblasts and keratinocytes. The results obtained revealed strong antitumor potential of the newly synthesized drugs with preserved efficacy against cisplatin resistant lines and less toxicity towards nonmalignant counterparts. The mechanism found to be responsible for the observed tumoricidal action of each synthesized compound was induction of apoptosis generally accompanied with caspase activation. Taken together, the effective response to the treatment of a wide range of different cell lines, including cisplatin resistant subclones, as well as induction of apoptosis, as the mechanism suggested to be the most desirable way of eliminating malignant cells, represents a great advantage of this novel group of drugs in comparison to other members in this metallo-drug family. (C) 2012 Elsevier Inc. All rights reserved