Maternal paraben exposure triggers childhood overweight development.

Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially in recent years. Here we investigate the effect of prenatal paraben exposure on childhood overweight by combining epidemiological data from a mother-child cohort with experimental approaches. Mothers reporting the use of paraben-containing cosmetic products have elevated urinary paraben concentrations. For butyl paraben (BuP) a positive association is observed to overweight within the first eight years of life with a stronger trend in girls. Consistently, maternal BuP exposure of mice induces a higher food intake and weight gain in female offspring. The effect is accompanied by an epigenetic modification in the neuronal Pro-opiomelanocortin (POMC) enhancer 1 leading to a reduced hypothalamic POMC expression. Here we report that maternal paraben exposure may contribute to childhood overweight development by altered POMC-mediated neuronal appetite regulation.

Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment.

Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental stimuli for their survival, provided for example by monocyte-derived nurse-like cells (NLCs). The immunomodulatory drug lenalidomide shows therapeutic effects in subgroups of CLL patients, and is believed to act via the microenvironment. To investigate the effects of lenalidomide on the survival support of NLCs, cocultures of monocytes and CLL cells were treated for 14 days with lenalidomide, which resulted in significantly decreased viability of CLL cells. Among the changes induced by this drug, we observed reduced expression of HLA-DR in NLCs as well as increased secretion of interleukin-10 (IL-10), indicating an altered inflammatory milieu in the cocultures. The increase in IL-10 levels lead to an induction of STAT1 phosphorylation in CLL cells and to enhanced cell-surface expression of intercellular adhesion molecule 1 and altered expression of cytoskeletal and migration-related genes. Chemotaxis assays with lenalidomide-treated CLL cells revealed an impaired migration capability. Our data show that lenalidomide reduces the survival support of NLCs for CLL cells in vitro, suggesting that this drug affects the myeloid microenvironment in CLL in vivo. Furthermore, lenalidomide acts on the migratory potential of CLL cells, which may affect circulation and homing of CLL cells in vivo.

Identification of the translation start site of the human melanocortin 3 receptor.

BACKGROUND: The melanocortin-3-receptor (MC3R) is a G-protein coupled receptor participating in hypothalamic energy metabolism. So far, it was assumed that the translation of the human MC3R starts at the non-conserved first ATG, however, a second evolutionary conserved ATG is located 37 amino acids downstream. One frequent polymorphism, T6K, is located between these two ATGs. METHODS: For characterization of the two potential start ATGs, COS-7 cells were transfected with plasmids encoding the longer and the shorter form of the human MC3R. For signal transduction properties, cAMP was measured. Cell surface expression was determined by using an ELISA method. The translational start point of the MC3R was investigated by a GFP-based method. RESULTS: Signal transduction was comparable for the long and the short receptor form. Cell surface expression via aminoterminal hemagglutinin tag could only be detected in the shorter form, but not in the longer one. In our study we show that the translation of the human MC3R protein starts at the evolutionary conserved ATG codon which results in a shorter protein than previously assumed. CONCLUSION: The polymorphism T6K is not located in the coding region of the human MC3R and has no influence on translation initiation which makes an impact on body weight unlikely.