! ORL via Alexandros G.Sfakianakis on Inoreader: PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti-cancer agents

! ORL via Alexandros G.Sfakianakis on Inoreader

PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti-cancer agents Aug 11th 2015, 00:08 Abstract The effectiveness of chemotherapeutic agents often limits their use due to their negative effects on normal cells. Apoptosis regulatory protein (CARP)-1 functional mimetics (CFMs) belong to a novel class of compounds that possess anti-cancer properties with potential utility in breast and other cancers. In this study, we investigated the growth inhibitory action of CFM-4 and -5 in bone-forming osteoblasts and role of a skeletal regulator, parathyroid hormone (PTH)-related peptide (PTHrP), which is frequently associated with oncologic pathologies. MC3T3E1-clone4 (MC-4) or primary osteoblasts were treated with CFMs. Western blots were performed to determine specific protein expressions. MTT, TUNEL assay, ethidium bromide/acridine orange staining, and ApoAlert caspase profiling were used to investigate cell viability and apoptosis of osteoblasts. Immunofluorescence staining was performed to observe intracellular localization of CARP-1. Our studies revealed that CFM-4 and -5 suppressed growths of mature differentiated, but not proliferating, MC-4 cells and PTHrP attenuated this effect. Mechanistically, induction of CARP-1 protein by CFM-4 and -5 was partially decreased by PTHrP. While CARP-1 increased by CFM-4 or -5 correlated with activated caspase-3, PTHrP remarkably blocked caspase-3 activation. PTHrP also influenced translocation of CFM-induced CARP-1 from the nucleus to the cytoplasm. Our data identify a new function of PTHrP in maintaining osteoblast homeostasis in chemotherapy and define a role of CARP-1 in this process. The crosstalk of PTHrP and CFM-4 and -5 signaling highlights the importance of CFMs as potential anti-cancer therapeutics in breast and other cancers which adversely affect bone.

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! ORL via Alexandros G.Sfakianakis on Inoreader: Tackling inadequate vitamin D intakes within the population: fortification of dairy products with vitamin D may not be enough

! ORL via Alexandros G.Sfakianakis on Inoreader

Tackling inadequate vitamin D intakes within the population: fortification of dairy products with vitamin D may not be enough Aug 11th 2015, 00:08 Abstract Dietary recommendations for vitamin D are designed by authoritative agencies to prevent vitamin D deficiency in the population, and while individual target intakes around the globe vary, they are generally between 10 and 20 μg/day [400–800 IU/day], depending on age, assuming little or no sunshine exposure. National dietary surveys report usual intakes of vitamin D that are much lower than these targets, at about 3–7 μg/day [120–280 IU/day], depending on usual diet, age, sex, and mandatory or voluntary fortification practices, and there is widespread dietary inadequacy around the globe. While acknowledging the valuable contribution fortified milk makes to vitamin D intakes among consumers, particularly in children, and the continued need for fortification of milk and other dairy products, additional strategic approaches to fortification, including biofortification, of a wider range of foods, have the potential to increase vitamin D intakes in the population and minimize the prevalence of low serum 25(OH)D without increasing the risk of excessive dosing. Careful consideration must be given to the range of products used for fortification and the amount of vitamin D used in each; there is a need for well-designed and sustainable fortification, and biofortification strategies for vitamin D, which use a range of foods to accommodate dietary diversity. Clinical patients may require additional consideration in terms of addressing low vitamin D status.

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