637 research outputs found

    Kirenol attenuates experimental autoimmune encephalomyelitis by inhibiting differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells.

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    Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. Here we investigated effects of kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-γ and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced kirenol induced apoptosis. Our findings implicate kirenol as a useful agent for the treatment of MS

    Optimal Immediately-Decodable Inter-session Network Coding (IDNC) Schemes for Two Unicast Sessions with Hard Deadline Constraints

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    In this paper, we study inter-session network coding for sending two unicast sessions over an unreliable wireless channel. Each unicast session transmits a stored video file, whose packets have hard sequential deadline constraints. We first characterize the capacity region (with inter-session network coding) for the transmission rates of the two unicast sessions under heterogeneous channel conditions and heterogeneous deadline constraints. We then develop immediately-decodable network coding (IDNC) schemes for controlling packet transmissions for the unicast sessions subject to hard deadline constraints. In contrast to our prior work that focuses on a single multicast session with homogeneous channel conditions and deadline constraints, the design and performance analysis of the IDNC scheme is much more complicated for unicast-sessions because of the asymmetry due to heterogeneous channel conditions and heterogeneous deadlines. Nonetheless, we establish the optimality of the proposed IDNC scheme when the file sizes are sufficiently large
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