Emerging Roles of the Iron Chelators in Inflammation

Iron is a crucial element for mammalian cells, considering its intervention in several physiologic processes. Its homeostasis is finely regulated, and its alteration could be responsible for the onset of several disorders. Iron is closely related to inflammation; indeed, during inflammation high levels of interleukin-6 cause an increased production of hepcidin which induces a degradation of ferroportin. Ferroportin degradation leads to decreased iron efflux that culminates in elevated intracellular iron concentration and consequently iron toxicity in cells and tissues. Therefore, iron chelation could be considered a novel and useful therapeutic strategy in order to counteract the inflammation in several autoimmune and inflammatory diseases. Several iron chelators are already known to have anti-inflammatory effects, among them deferiprone, deferoxamine, deferasirox, and Dp44mT are noteworthy. Recently, eltrombopag has been reported to have an important role in reducing inflammation, acting both directly by chelating iron, and indirectly by modulating iron efflux. This review offers an overview of the possible novel biological effects of the iron chelators in inflammation, suggesting them as novel anti-inflammatory molecules.     

Temperature modulates the production and activity of a metalloprotease from Pseudomonas fluorescens 07A in milk

This work evaluated the expression and activity of a metalloprotease released by Pseudomonas fluorescens 07A in milk. Low relative expression of the protease by the strain was observed after incubation for 12 h at 25°C while the strain was in the logarithmic growth phase. After 24 h, protease production significantly increased and remained constant for up to 48 h, a time range during which the strain remained in the stationary phase. Conversely, at refrigeration temperatures, at 12 h the strain was still in the lag phase and expressed the protease at higher levels than when the logarithmic phase was reached. Casein fractions were highly degraded by P. fluorescens 07A, the purified protease, and the bacterial pellet on d 7 of incubation at 25°C and to a lesser extent at 10°C for the sample incubated with the bacterium. Heat treatment at 90°C for 5 min completely inactivated the proteolytic activity of the purified protease and the bacterial pellet. This work contributes to the knowledge about the conditions of milk storage that influence the production and activity of this extracellular metalloprotease. The results demonstrate the need to find alternative strategies to control the synthesis and activity of proteolytic enzymes in the dairy industry to ensure the quality of processed products.     

Survival in vitro and virulence of Trypanosoma cruzi in açaí pulp in experimental acute Chagas disease

Chagas disease is a parasitic infection with high socioeconomic impact throughout Latin America. Although this severe, incurable disease can be transmitted by several routes, oral transmission is currently the most important route in the Amazon Basin. A?aí pulp has nutritional properties and is popular throughout Brazil and abroad. However, this pulp has been associated with microepidemics of acute Chagas disease (ACD) in northern Brazil, where a?aí fruit is the main food supplement. In this study, we examined the in vitro survival and in vivo virulence of Trypanosoma cruzi Y strain in a?aí pulp. Aliquots of in natura a?aí pulp produced in Belém city in the northern Brazilian state of Pará were mixed with 10? trypomastigotes. The samples were incubated at room temperature or at 4 or -20°C for various periods, and the parasites were isolated by forced sieving. The resulting eluates were examined by microscopy, and the trypomastigotes were administered intraperitoneally, orally, or by gavage to immunodeficient mice (C.B-17-Prkdc(scid)/PasUnib) that had been pretreated with antibiotics. Parasitemia was quantified by the Brener method, and mortality was recorded daily. All routes of administration resulted in ACD. A 5-day delay in the onset of parasitemia occurred with oral administration. The survival and virulence of the parasites were unaffected by prior incubation at room temperature for 24 h, at 4°C for 144 h, and at -20°C for 26 h. These results indicate that T. cruzi can survive and retain its virulence in a?aí pulp under various conditions and that cooling and freezing are not suitable methods for preventing foodborne ACD.     

Brain Regional Identity and Cell Type Specificity Landscape of Human Cortical Organoid Models

In vitro models of corticogenesis from pluripotent stem cells (PSCs) have greatly improved our understanding of human brain development and disease. Among these, 3D cortical organoid systems are able to recapitulate some aspects of in vivo cytoarchitecture of the developing cortex. Here, we tested three cortical organoid protocols for brain regional identity, cell type specificity and neuronal maturation. Overall, all protocols gave rise to organoids that displayed a time-dependent expression of neuronal maturation genes such as those involved in the establishment of synapses and neuronal function. Comparatively, guided differentiation methods without WNT activation generated the highest degree of cortical regional identity, whereas default conditions produced the broadest range of cell types such as neurons, astrocytes and hematopoietic-lineage-derived microglia cells. These results suggest that cortical organoid models produce diverse outcomes of brain regional identity and cell type specificity and emphasize the importance of selecting the correct model for the right application.     

The Effects of Silencing PTX3 on the Proteome of Human Endothelial Cells

The human long pentraxin PTX3 has complex regulatory roles at the crossroad of innate immunity, inflammation, and tissue repair. PTX3 can be produced by various cell types, including vascular endothelial cells (ECs), in response to pro-inflammatory cytokines or bacterial molecules. PTX3 has also been involved in the regulation of cardiovascular biology, even if ambiguous results have been so far provided in both preclinical and clinical research. In this study, we compared the proteomic profiles of human ECs (human umbilical vein ECs, HUVECs), focusing on differentially expressed proteins between the control and PTX3-silenced ECs. We identified 19 proteins that were more abundant in the proteome of control ECs and 23 proteins that were more expressed in PTX3-silenced cells. Among the latter, proteins with multifunctional roles in angiogenesis, oxidative stress, and inflammation were found, and were further validated by assessing their mRNAs with RT-qPCR. Nevertheless, the knock down of PTX3 did not affect in vitro angiogenesis. On the contrary, the lack of the protein induced an increase in pro-inflammatory markers and a shift to the more oxidative profile of PTX3-deficient ECs. Altogether, our results support the idea of a protective function for PTX3 in the control of endothelial homeostasis, and more generally, in cardiovascular biology.     

Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis

Prenylcysteine Oxidase 1 (PCYOX1) is an enzyme involved in the degradation of prenylated proteins. It is expressed in different tissues including vascular and blood cells. We recently showed that the secretome from Pcyox1-silenced cells reduced platelet adhesion both to fibrinogen and endothelial cells, suggesting a potential contribution of PCYOX1 into thrombus formation. Here, we show that in vivo thrombus formation after FeCl₃ injury of the carotid artery was delayed in Pcyox1^−/− mice, which were also protected from collagen/epinephrine induced thromboembolism. The Pcyox1^−/− mice displayed normal blood cells count, vascular procoagulant activity and plasma fibrinogen levels. Deletion of Pcyox1 reduced the platelet/leukocyte aggregates in whole blood, as well as the platelet aggregation, the alpha granules release, and the α_IIbβ₃ integrin activation in platelet-rich plasma, in response to adenosine diphosphate (ADP) or thrombin receptor agonist peptide (TRAP). Washed platelets from the Pcyox1^−/− and WT animals showed similar phosphorylation pathway activation, adhesion ability and aggregation. The presence of Pcyox1^−/− plasma impaired agonist-induced WT platelet aggregation. Our findings show that the absence of PCYOX1 results in platelet hypo-reactivity and impaired arterial thrombosis, and indicates that PCYOX1 could be a novel target for antithrombotic drugs.     

Synergism and Performance for Systems Containing Binary Mixtures of Anionic/Cationic Surfactants for Enhanced Oil Recovery

The surfactant structure–performance relationship and application properties in enhanced oil recovery (EOR) for binary mixtures of anionic and cationic surfactants are presented and discussed. A polyoxyethylene ether carboxylate anionic surfactant was blended with a quaternary ammonium chloride cationic surfactant and tested for a high-temperature, low-salinity, and high-hardness condition as found in an oil reservoir. These mixtures were tailored by phase behavior tests to form optimal microemulsions with normal octane (n-C8) and crude oil having an API gravity of 48.05°. The ethoxy number of the polyoxyethylene carboxylate anionic surfactant and the chain length of the cationic surfactant were tuned to find an optimal surfactant blend. Interfacial tensions with n-C8 and with crude oil were measured. Synergism between anionic and cationic surfactants was indicated by surface tension measurement, CMC determination, calculation of surface excess concentrations and area per molecule of individual surfactants and their mixtures. Molecular interactions of anionic and cationic surfactants in mixed monolayers and aggregates were calculated by using regular solution theory to find molecular interaction parameters β ^σ and β ^M . Morphologies of surfactant solutions were studied by cryogenic TEM. The use of binary mixtures of anionic/cationic surfactants significantly broadens the scope of application for conventional chemical EOR methods.