Human breast milk cells are positive for the pioneer transcription factor ISL1.

OBJECTIVE: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events.

In silico design of mimosine containing peptides as new efficient chelators of aluminum.

The design of new and efficient chelators that can remove aluminium(iii), a metal with increasing recognition as a potential toxic agent, from biological systems is an area of high therapeutic relevance. In the present paper, we present an extensive computational study of a new promising type of these chelators based on mimosine containing peptides. The reason to choose mimosine is that the sidechain of this residue is similar to deferiprone, a ligand known to tightly interact with highly-valent metals, and in particular with Al(iii). In this article we analyze systematically, using a combination of methods that include QM/MM MD simulations, how the size and sequence of the polypeptides can alter the fundamental binding patterns to aluminum, in comparison with the binding to deferiprone. Particular attention is given towards the identification of the smallest peptide that interacts efficiently with aluminum, since polypeptide size is a fundamental factor to allow a given polypeptide to efficiently cross the cell membrane. The results indicate that the longest peptides, with 8 or 9 amino acids, show no difficulties interacting with Al(iii) in an optimum arrangement. By contrast, when the peptide contains five or six amino acids Al(iii) is pentacoordinated, reducing the stability of the resultant complex. In summary, our study demonstrates that the mimosine containing peptides can efficiently coordinate highly valent metals such as Al(iii), with a subtle dependence of the binding on the specific chain-lengths of the polypeptide. We believe that the present study sheds light on the adequacy of this new type of chelator towards aluminum binding.

Multi analytical technique study of human bones from an archaeological discovery.

In 1953, during the building restoration of San Michele church (Bono, Sardinia, 16th-19th Century), a high number of disarticulated skeletons were recovered. From a group of 412 hip bones, two of these, affected by several pathological lesions, were analysed. The two coxal bones can be referred to the same individual, an adult man. A multi-analytical study, started with the purpose of investigating the bone pathology, was extended to characterize the mineral components of a large representative set of bones from the same ossuary, all attributed to adult men who lived in the region four-two centuries ago. A quantitative ICP-AES analysis for Ca, Fe, Mg, Mn, Na, Pb and Zn was executed, and a chemometric investigation on the results was performed. This approach gave evidence of the effects of diagenesis, allowed some hypothesis of the incidence of the known dietary habits on bone composition, and completely differentiated the pathological bones from those of a normal population on the basis of the mineral composition. Moreover, porosity, crystallinity and FT-IR analysis were conducted on both non- and pathological sample.

Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one.

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe(3+), studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe(3+). The pFe(3+) value 22.0 of P1-iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al(3+), Cu(2+) and Zn(2+) has been studied to evaluate the possible use of P1 against a second toxic metal ion (Al(3+)), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelator.

Nutritional iron deficiency: the role of oral iron supplementation.

Nutritional iron deficiency represents a relevant health problem mainly in developing countries. Children and pregnant women represent the main target of this disease, and the low amount of bio-available iron mostly depends on plant-based diets. Iron deficiency may have serious consequences, with severe impairment of the immune function leading to infectious diseases. The brain development in embryos and fetuses during gestation can be greatly affected by iron deficiency of the mother with heavy outcomes on the cognition status of children. A better understanding of molecular pathways involved in iron absorption and metabolism are the basis for new strategies for developing a therapy for iron deficiency. Different therapeutic strategies are summarized, and iron fortification appears the best tool.