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Summary: Melatonin is a hormone synthesized from the neurotransmitter serotonin and is found mainly in the pineal gland. Melatonin has been suggested to have several properties, acting both as an antioxidant and a neuroprotective agent. Melatonin synthesis decreases with age in all humans, but this decline is more pronounced in Alzheimer’s patients. In fact, melatonin inhibits the formation of β-amyloid protein. The mechanism responsible for this decline has not been fully elucidated, although it is known that the human pineal gland calcifies with age. Such calcification necessarily implies the existence of a tissue injury that, if not reabsorbed by the immune system, will act as heterogeneous nucleant for hydroxyapatite and will induce calcification. For this reason, it is hypothesized that a lack of inhibitors of calcium salt crystallization, such as pyrophosphate and phytate, will favor calcification. Therefore, the absence of crystallization inhibitors may be a risk factor for development of Alzheimer’s disease, and this hypothesis should be evaluated. [Copyright &y& Elsevier]

In this work, shearing interface coassembly in biliquid phase systems is employed to synthesize biocompatible core-shell magnetic mesoporous silica microspheres with uniform size of about 600 nm, perpendicular mesopores of 6.0 nm and large pore volume of 0.77 cm 3 /g. The toxicology assays based on the zebrafish model was conducted to test under a high-throughput manner for the biosafety of Fe 3 O 4 @RF@mSiO 2 microspheres. The highest no observed toxic effect concentration (NOEC) estimated by the acute toxicity assay for the microspheres was 1.6 mg/mL. The estimated number (measured by ICP-MS) of the penetrated microspheres at this concentration was 2 × 10 6 per embryo. The results of three different performed toxicity assays show no overall acute toxicity, teratogenicity, or neurotoxicity of the microspheres on zebrafish embryos at any of the tested concentrations (from 0.1 to 1.6 mg/mL) via its multifunctional microstructure. Here, gemcitabine (GEM) as a model of anti-cancer drug was loaded into the mesopores of Fe 3 O 4 @RF@mSiO 2 microspheres to study their drug release behavior. The microspheres were found to exhibit pH responsive property, which benefits for the GEM release under cancer therapy. Overall, this study offers promising avenue for effective evaluation of magnetic core-shell microspheres for drug delivery and cancer therapy applications. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The present study examined the inhibitory effects of pyrophosphate, etidronate, and phytate on bovine pericardium calcification in vitro. Methods: Bovine pericardium was glutaraldehyde fixed and then placed in a flow chamber in the presence of a synthetic physiological fluid alone (control) or the fluid plus various concentrations of pyrophosphate, etidronate, or phytate. Following a 96-h incubation, fragments were removed and assayed for calcification by measuring calcium and phosphorus levels. Results: The data indicated that both pyrophosphate and etidronate at 1 mg/l (5.75 and 4.95 μM, respectively) inhibited bovine pericardium calcification, whereas neither agent had an effect at 0.5 mg/l (2.87 and 2.47 μM, respectively). Phytate was the most potent inhibitor of calcification, and the effects of this agent were apparent at levels as low as 0.25 mg/l (0.39 μM). Conclusions: While pyrophosphate, etidronate, and phytate were all able to inhibit bovine pericardium calcification in vitro, phytate was found to be the most effective. [Copyright &y& Elsevier]

InsP6 is abundant in cereals and legumes. InsP6 and lower inositol phosphates, in particular InsP3, participate in important intracellular processes. In addition, InsP6 possess significant health benefits, such as anti-cancer effect, kidney stones prevention, lowering serum cholesterol. Because of the insensitivity of existing methods for determination of non-radiolabeled inositol phosphates, little is known about the natural occurrence, much less on the concentrations of InsP6 and InsP3 in biological samples. Using gas chromatography-mass detection analysis of HPLC chromatographic fractions, we report a measurement of unlabeled total InsP3 and InsP6 (a) as they occur within cells culture, tissues, and plasma, and (b) their changes depending on the presence of exogenous InsP6. When rats were fed on a purified diet in which InsP6 was undetectable (AIN-76A) the levels of InsP6 in brain were 3.35 ± 0.57 (SE) μmol·kg−1 and in plasma 0.023 ± 0.008 (SE) μmol·l−1. The presence of InsP6 in diet dramatically influenced its levels in brain and in plasma. When rats were given an InsP6-sufficient diet (AIN-76A + 1% InsP6), the levels of InsP6 were about 100-fold higher in brain tissues (36.8 ± 1.8 (SE)) than in plasma (0.29 ± 0.02 (SE)); InsP6 concentrations were 8.5-fold higher than total InsP3 concentrations in either plasma (0.033 ± 0.012 (SE)) and brain (4.21 ± 0.55 (SE)). When animals were given an InsP6-poor diet (AIN-76A only), there was a 90% decrease in InsP6 content in both brain tissue and plasma (p < 0.001); however, there was no change in the level of total InsP3. In non-stimulated malignant cells (MDA-MB 231 and K562) the InsP6 contents were 16.2 ± 9.1 (SE) μmol·kg−1 for MDA-MB 231 cells and 15.6 ± 2.7 (SE) for K 562 cells. These values were around 3-fold higher than those of InsP3 (4.8 ± 0.5 μmol·kg−1 and 6.9 ± 0.1 (SE) for MDA-MB 231 and K562 cells respectively). Treatment of malignant cells with InsP6 resulted in a 2-fold increase in the intracellular concentrations of total InsP3 (9.5 ± 1.3 (SE) and 10.8 ± 1.0 (SE) μmol·kg−1 for MDA-MB 231 and K562 cells respectively, p < 0.05), without changes in InsP6 levels. These results indicate that exogenous InsP6 directly affects its physiological levels in plasma and brain of normal rats without changes on the total InsP3 levels. Although a similar fluctuation of InsP6 concentration was not seen in human malignant cell lines following InsP6 treatment, an increased intracellular levels of total InsP3 was clearly observed. [Copyright &y& Elsevier]