Fig. 10

Long-term safety profile. a A heat-map showing the changes in the expression of a spectrum of inflammatory cytokines in the liver tissue (n = 3 at each time point). Their levels of expression were first analyzed using a protein antibody array, normalized to that of the normal control, and shown in a fold-of-change fashion. Captions I–VI indicate the case of mice received Mito(T)-pep-Nuc(T) (I, II), Mito(T)-pep-Nuc(N) (III, IV), Mito(N)-pep-Nuc(T) (V, VI) at Day 1 (I, III, V) and Day 15 (II, IV, VI) as defined in Fig. 8a. A color bar on the right indicates the color scales. b Profile of systematic pro-inflammatory immunity in responding to Mito(T)-pep-Nuc(T)-mediated therapy. The peripheral level of CD4⁺ and CD8⁺ T cells were analyzed by flow cytometry, and c the population of all four different classes of circulating T cells including CD4 and CD8 dual-positive (CD4⁺/CD8⁺) and dual-negative (CD4⁻/CD8⁻) and singly positive ones (CD4⁺ and CD8⁺). d Pathological study of normal mice received i.v. injection of Mito(T)-pep-Nuc(T). The H&E-stained tissue slices of four organs were shown as a function of time post injection. Scale bar: 100 μm. e Hematological study showing the functions of liver (upper), spleen, and kidney (lower) as a function of time as indicated by the biomarkers for liver (including ALT, TP, TBIL), spleen (PLT, platelet), and kidneys (including BUN (blood urea nitrogen) and CRE (creatinine)). Data are presented as mean ± s.e.m. (n = 3). In the box plot, the upper and lower quartile as outlined by top and bottom boundary was divided by line showing the median value