Both obesity and aging are associated with dysregulated immune and inflammatory responses. There is limited knowledge, however, on differences in the immune system between young and older adults with obesity. The goal of this study was to compare circulating inflammatory cytokines and T cell-mediated immune response between young and older women with obesity. Twenty-three young (23–43 years) and 21 older (60–83 years) women with obesity were recruited at the Weight and Wellness Center at Tufts Medical Center. Circulating inflammatory cytokines (CRP, IL-6, and IL-1β) and ex vivo indicators of T cell-mediated immune function were compared between the groups. Older women with obesity had significantly fewer circulating CD3+, CD8+, CD19+, and natural killer T (NKT) cells compared to young women with obesity (p = 0.016, p < 0.0001, p = 0.0003, and p < 0.0001, respectively). However, with few exceptions, there was no significant difference in inflammation markers or stimulated lymphocyte proliferation and cytokine production by peripheral blood mononuclear cells between young and older participants. These findings are in contrast to those previously reported in young and old subjects with healthy weight and call for further investigation into the impact of obesity on premature aging of the immune system.
Recent studies suggest that leukemia stem cells (LSCs) play a critical role in initiation, propagation, and relapse of leukemia. Herein we show that (−)-15-methylene-eburnamonine, a derivative of the alkaloid, (−)-eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also reduces primary LSC frequency in vitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells, and using a novel humanized bone marrow murine model of leukemia (huBM/NSG), it reduces progenitor cell engraftment.
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