The interaction of aluminum with catecholamine-based neurotransmitters: Can the formation of these species be considered a potential risk factor for neurodegenerative diseases?

The potential neurotoxic role of Al(iii) and its proposed link with the insurgence of Alzheimer's Disease (AD) have attracted increasing interest towards the determination of the nature of bioligands that are propitious to interact with aluminum. Among them, catecholamine-based neurotransmitters have been proposed to be sensitive to the presence of this non-essential metal ion in the brain. In the present work, we characterize several aluminum-catecholamine complexes in various stoichiometries, determining their structure and thermodynamics of formation. For this purpose, we apply a recently validated computational protocol with results that show a remarkably good agreement with the available experimental data. In particular, we employ Density Functional Theory (DFT) in conjunction with continuum solvation models to calculate complexation energies of aluminum for a set of four important catecholamines: l-DOPA, dopamine, noradrenaline and adrenaline. In addition, by means of the Quantum Theory of Atoms in Molecules (QTAIM) and Energy Decomposition Analysis (EDA) we assessed the nature of the Al-ligand interactions, finding mainly ionic bonds with an important degree of covalent character. Our results point at the possibility of the formation of aluminum-catecholamine complexes with favorable formation energies, even when proton/aluminum competition is taken into account. Indeed, we found that these catecholamines are better aluminum binders than catechol at physiological pH, because of the electron withdrawing effect of the positively-charged amine that decreases their deprotonation penalty with respect to catechol. However, overall, our results show that, in an open biological environment, the formation of Al-catecholamine complexes is not thermodynamically competitive when compared with the formation of other aluminum species in solution such as Al-hydroxide, or when considering other endogenous/exogenous Al(iii) ligands such as citrate, deferiprone and EDTA. In summary, we rule out the possibility, suggested by some authors, that the formation of Al-catecholamine complexes in solution might be behind some of the toxic roles attributed to aluminum in the brain. An up-to-date view of the catecholamine biosynthesis pathway with sites of aluminum interference (according to the current literature) is presented. Alternative mechanisms that might explain the deleterious effects of this metal on the catecholamine route are thoroughly discussed, and new hypotheses that should be investigated in future are proposed

Unusual PLS application for Pd(ii) sensing in extremely acidic solutions

An economic and extremely selective device for Pd(ii) determination in very acidic solutions, TazoC-Mar@ is presented. The sensor was prepared via an ion exchange technique of an azoic ligand, (2-(tetrazolylazo)-1,8 dihydroxy naphthalene-3,6,-disulphonic acid), named TazoC, on a Macroporous Strong Anion Exchange Resin, namely Marathon® (Dow Chemical-USA). The TazoC-Mar@ rapidly forms complexes with palladium(ii) ions, which give an intense blue colour to the solid phase, even at low pH. The reaction is highly selective and no other metal ions react with the device at this pH. Moreover, the quantification of Pd(ii) is reliable when applying partial least squares regression (PLS) to relate the signal to the metal ion concentration. The regression model gives a good fit and correct predictions of Pd(ii) concentrations in unknown samples. The method presented here is highly sensitive with an LOD and LOQ equal to 0.2 nM and 0.5 nM, respectively

Cell starvation increases uptake of extracellular Thymosin β4 and its complexes with calcium

Cell metastasis is the main cause of cancer mortality. Inhibiting early events during cell metastasis and invasion could significantly improve cancer prognosis, but the initial mechanisms of cell transition and migration are barely known. Calcium regulates cell migration, whilst Thymosin β4 is a G-actin and iron binding peptide associated with tumor metastasis and ferroptosis. Under normal cell growth conditions, intracellular free calcium ions and Thymosin β4 concentrations are strictly regulated, and are not influenced by extracellular supplementation. However, cell starvation decreases intracellular Thymosin β4 and increases extracellular peptide uptake above the normal range. Unexpectedly, cell starvation significantly increases internalization of extracellular Ca2+/Thymosin β4 complexes. Elucidating the role of Ca2+/Thymosin β4 in the early events of metastasis will likely be important in the future to develop therapies targeting metastasis

Salicylamide derivatives for iron and aluminium sequestration. From synthesis to complexation studies

This paper presents an easy, fast and economic synthesis of chelating agents for medical, environmental and analytical applications, and the evaluation of the stability of their complexes with Fe3+ and Al3+. Complex formation equilibria with Cu2+ and Zn2+ metal ions were also studied to evaluate if the chelating agents can perturb the homeostatic equilibria of these essential metal ions. Effective chelating agents for metal ions, in addition to their well-known medical uses, find an increasing number of applications in environmental remediation, agricultural applications (supplying essential elements in an easily available form), and in analytical chemistry as colorimetric reagents. Besides the stability of the complexes, the lack of toxicity and the low cost are the basic requisites of metal chelating agents. With these aims in mind, we utilized ethyl salicylate, a cheap molecule without toxic effects, and adopted a simple synthetic strategy to join two salicylate units through linear diamines of variable length. Actually, the mutual position of the metal binding oxygen groups, as well as the linker length, affected protonation and complex formation equilibria. A thorough study of the ligands is presented. In particular, the complex formation equilibria of the three ligands toward Fe3+, Al3+, Zn2+ and Cu2+ ions were investigated by combined potentiometric and spectrophotometric techniques. The results are encouraging: all the three ligands form stable complexes with all the investigated metal ions, involving the oxygen donor atoms from the 2-hydroxybenzamido unit, and nitrogen atoms in copper and zinc coordination

A pilot study of occupational exposure to ultrafine particles during 3D printing in research laboratories

Introduction3D printing is increasingly present in research environments, and could pose health risks to users due to air pollution and particulate emissions. We evaluated the nanoparticulate emissions of two different 3D printers, utilizing either fused filament fabrication with polylactic acid, or stereolithography (SLA) with light curing resin. MethodsNanoparticulate emissions were evaluated in two different research environments, both by environmental measurements in the laboratory and by personal sampling. ResultsThe SLA printer had higher nanoparticulate emissions, with an average concentration of 4,091 parts/cm(3), versus 2,203 particles/cm(3) for the fused filament fabrication printer. The collected particulate matter had variable morphology and elemental composition with a preponderance of carbon, sulfur and oxygen, the main byproducts. DiscussionOur study implies that when considering the health risks of particulate emissions from 3D printing in research laboratories, attention should be given to the materials used and the type of 3D printer

Cooking Particulate Matter: A Systematic Review on Nanoparticle Exposure in the Indoor Cooking Environment

Background: Cooking and fuel combustion in the indoor environment are major sources of respirable suspended particulate matter (RSPM), which is an excellent carrier of potentially harmful absorbed inorganic and organic compounds. Chronic exposure to RSPM can lead to acute pulmonary illness, asthma, cardiovascular disease, and lung cancer in people involved in cooking. Despite this, questions remain about the harmfulness of different particulate matter (PM) sources generated during cooking, and the factors influencing PM physico-chemical properties. The most reliable methods for sampling and analyzing cooking emissions remain only partially understood. Objectives: This review aims to comprehensively assess the risks of PM generated during cooking, considering the main sources of PM, PM chemical composition, and strategies for PM physico-chemical analysis. We present the first systematic analysis of PM sources and chemical composition related to cooking. We highlight significant differences between studies using different experimental conditions, with a lack of a standard methodology. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement rules and the Patient, Intervention, Comparison, and Outcome (PICO) strategy for scientific research, three different scientific databases (PubMed, Scopus, and Web of Science) were screened to find scientific articles that measure, collect, and analyze the chemical composition of nanometer-and micrometer-sized PM generated during cooking activities under different conditions. Data are summarized to assess risk, evaluating the main sources and factors influencing PM generation, their chemical composition, and how they have been collected and analyzed in changing experimental conditions. Results: From 2474 search results, there were 55 studies that met our criteria. Overall, the main variable sources of PM in cooking activities relate to the stove and fuel type. The concentration and chemical–physical properties of PM are also strongly influenced by the food and food additive type, food processing type, cooking duration, temperature, and utensils. The most important factor influencing indoor PM concentration is ventilation. The PM generated during cooking activities is composed mainly of elemental carbon (EC) and its derivatives, and the porous structure of PM with high surface-to-volume ratio is a perfect carrier of inorganic and organic matter. Conclusions: This review reveals a growing interest in PM exposure during cooking activities and highlights significant variability in the chemical–physical properties of particles, and thus variable exposure risks. Precise risk characterization improves possible preventive strategies to reduce the risk of indoor pollutant exposure. However, comprehensive PM analysis needs proper sampling and analysis methods which consider all factors influencing the physico-chemical properties of PM in an additive and synergistic way. Our analysis highlights the need for method standardization in PM environmental analyses, to ensure accuracy and allow deeper comparisons between future studies

Exploring cell surface markers and cell-cell interactions of human breast milk stem cells

Background: Breakthrough studies have shown that pluripotent stem cells are present in human breast milk. The expression of pluripotency markers by breast milk cells is heterogeneous, relating to cellular hierarchy, from early-stage multi-lineage stem cells to fully differentiated mammary epithelial cells, as well as weeks of gestation and days of lactation. Design and methods: Here, we qualitatively analyze cell marker expression in freshly isolated human breast milk cells, without any manipulation that could influence protein expression. Moreover, we use electron microscopy to investigate cell-cell networks in breast milk for the first time, providing evidence of active intercellular communication between cells expressing different cellular markers. Results: The immunocytochemistry results of human breast milk cells showed positive staining in all samples for CD44, CD45, CD133, and Ki67 markers. Variable positivity was present with P63, Tβ4 and CK14 markers. No immunostaining was detected for Wt1, nestin, Nanog, OCT4, SOX2, CK5, and CD34 markers. Cells isolated from human breast milk form intercellular connections, which together create a cell-to-cell communication network. Conclusions: Cells freshly isolated form human breast milk, without particular manipulations, show heterogeneous expression of stemness markers. The studied milk staminal cells show "pluripotency" at different stages of differentiation, and are present as single cells or grouped cells. The adjacent cell interactions are evidenced by electron microscopy, which showed the formation of intercellular connections, numerous contact regions, and thin pseudopods

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

Therapeutic Properties of Vanadium Complexes

Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology

Toward the renal vesicle: Ultrastructural investigation of the cap mesenchyme splitting process in the developing kidney

Background: A complex sequence of morphogenetic events leads to the development of the adult mouse kidney. In the present study, we investigated the morphological events that characterize the early stages of the mesenchymal-to-epithelial transition of cap mesenchymal cells, analyzing in depth the relationship between cap mesenchymal induction and ureteric bud (UB) branching. Design and methods: Normal kidneys of newborn non-obese diabetic (NOD) mice were excised and prepared for light and electron microscopic examination. Results: Nephrogenesis was evident in the outer portion of the renal cortex of all examined samples. This process was mainly due to the interaction of two primordial derivatives, the ureteric bud and the metanephric mesenchyme. Early renal developmental stages were initially characterized by the formation of a continuous layer of condensed mesenchymal cells around the tips of the ureteric buds. These caps of mesenchymal cells affected the epithelial cells of the underlying ureteric bud, possibly inducing their growth and branching. Conclusions: The present study provides morphological evidence of the reciprocal induction between the ureteric bud and the metanephric mesenchyme showing that the ureteric buds convert mesenchyme to epithelium that in turn stimulates the growth and the branching of the ureteric bud