Lactoferrin's anti-cancer properties. Safety, selectivity, and wide range of action

Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radio- and chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies

ICE DETECTION ON AIRPLANE WINGS USING A PHOTOGRAMMETRIC POINT CLOUD: A SIMULATION

Abstract. This study describes some tests carried out, within the European project (reference call: MANUNET III 2018, project code: MNET18/ICT-3438) called SEI (Spectral Evidence of ice), for the geometrical ice detection on airplane wings. The purpose of these analysis is to estimate thickness and shape of the ice that an RGB sensor is able to detect on large aircrafts as Boeing 737-800. However, field testing are not available yet, therefore, in order to simulate the final configuration, a steel panel has been used to reproduce the aircraft surface. The adopted methodology consists in defining a reference surface and modelling its 3D shape with and without ice through photogrammetric acquisitions collected by a DJI Mavic Air drone hosting a RGB camera and processed by Agisoft Metashape software. The comparison among models with and without the ice has been presented and results show that it is possible to identify the ice, even though some noise still remains due to the geometric reconstruction itself. Finally, using 3dReshaper and Matlab software, the authors develop various analysis defining the operative limits, the processing time, the correct setting up of Metashape for a more accurate ice detection, the optimization of the methodology in terms of processing time, precision and completeness. The procedure can certainly be more reliable considering the usage of the hyperspectral sensor technique as future implementation

The reaction of Pseudomonas nitrite reductase and nitrite. A stopped-flow and EPR study.

The reaction between reduced Pseudomonas nitrite reductase and nitrite has been studied by stopped-flow and rapid-freezing EPR spectroscopy. The interpretation of the kinetics at pH 8.0 is consistent with the following reaction mechanism (where k1 and k3 much greater than k2). [formula: see text] The bimolecular step (Step 1) is very fast, being lost in the dead time of a rapid mixing apparatus; the stoichiometry of the complex has been estimated to correspond to one NO2- molecule/heme d1. The final species is the fully reduced enzyme with NO bound to heme d1; and at all concentrations of nitrite, there is no evidence for dissociation of NO or for further reduction of NO to N2O. Step 2 is assigned to an internal electron transfer from heme c to reduced NO-bound heme d1 occurring with a rate constant of 1 s-1; this rate is comparable to the rate of internal electron transfer previously determined when reducing the oxidized enzyme with azurin or cytochrome c551. When heme d1 is NO-bound, the rate at which heme c can accept electrons from ascorbate is remarkably increased as compared to the oxidized enzyme, suggesting an increase in the redox potential of the latter heme

ICE DETECTION on AIRPLANE WINGS USING A PHOTOGRAMMETRIC POINT CLOUD: A SIMULATION

This study describes some tests carried out, within the European project (reference call: MANUNET III 2018, project code: MNET18/ICT-3438) called SEI (Spectral Evidence of ice), for the geometrical ice detection on airplane wings. The purpose of these analysis is to estimate thickness and shape of the ice that an RGB sensor is able to detect on large aircrafts as Boeing 737-800. However, field testing are not available yet, therefore, in order to simulate the final configuration, a steel panel has been used to reproduce the aircraft surface. The adopted methodology consists in defining a reference surface and modelling its 3D shape with and without ice through photogrammetric acquisitions collected by a DJI Mavic Air drone hosting a RGB camera and processed by Agisoft Metashape software. The comparison among models with and without the ice has been presented and results show that it is possible to identify the ice, even though some noise still remains due to the geometric reconstruction itself. Finally, using 3dReshaper and Matlab software, the authors develop various analysis defining the operative limits, the processing time, the correct setting up of Metashape for a more accurate ice detection, the optimization of the methodology in terms of processing time, precision and completeness. The procedure can certainly be more reliable considering the usage of the hyperspectral sensor technique as future implementation

Lactoferrin in the prevention and treatment of intestinal inflammatory pathologies associated with colorectal cancer development

The connection between inflammation and cancer is well-established and supported by genetic, pharmacological and epidemiological data. The inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, have been described as important promoters for colorectal cancer development. Risk factors include environmental and food-borne mutagens, dysbalance of intestinal microbiome composition and chronic intestinal inflammation, with loss of intestinal epithelial barrier and enhanced cell proliferation rate. Therapies aimed at shutting down mucosal inflammatory response represent the foundation for IBDs treatment. However, when applied for long periods, they can alter the immune system and promote microbiome dysbiosis and carcinogenesis. Therefore, it is imperative to find new safe substances acting as both potent anti-inflammatory and anti-pathogen agents. Lactoferrin (Lf), an iron-binding glycoprotein essential in innate immunity, is generally recognized as safe and used as food supplement due to its multifunctionality. Lf possesses a wide range of immunomodulatory and anti-inflammatory properties against different aseptic and septic inflammatory pathologies, including IBDs. Moreover, Lf exerts anti-adhesive, anti-invasive and anti-survival activities against several microbial pathogens that colonize intestinal mucosa of IBDs patients. This review focuses on those activities of Lf potentially useful for the prevention/treatment of intestinal inflammatory pathologies associated with colorectal cancer development

Orbit determination of space objects based on sparse optical data

While building up a catalog of Earth orbiting objects, if the available optical observations are sparse, not deliberate follow ups of specific objects, no orbit determination is possible without previous correlation of observations obtained at different times. This correlation step is the most computationally intensive, and becomes more and more difficult as the number of objects to be discovered increases. In this paper we tested two different algorithms (and the related prototype software) recently developed to solve the correlation problem for objects in geostationary orbit (GEO), including the accurate orbit determination by full least squares solutions with all six orbital elements. Because of the presence in the GEO region of a significant subpopulation of high area to mass objects, strongly affected by non-gravitational perturbations, it was actually necessary to solve also for dynamical parameters describing these effects, that is to fit between 6 and 8 free parameters for each orbit. The validation was based upon a set of real data, acquired from the ESA Space Debris Telescope (ESASDT) at the Teide observatory (Canary Islands). We proved that it is possible to assemble a set of sparse observations into a set of objects with orbits, starting from a sparse time distribution of observations, which would be compatible with a survey capable of covering the region of interest in the sky just once per night. This could result in a significant reduction of the requirements for a future telescope network, with respect to what would have been required with the previously known algorithm for correlation and orbit determination.Comment: 20 pages, 8 figure

Young camel ceruloplasmin : purification and partial characterization

La céruloplasmine d'un chamelon âgé de six mois a été isolée et purifiée en une seule étape, utilisant une chromatographie sur Sépharose activée par de la chloroéthylamine. La masse moléculaire de la protéine a été déterminée par électrophorèse avec SDS et a été estimée à 130 000 Da. La protéine possède une mobilité électrophorétique légèrement supérieure à celle de l'homme, ce qui suggère que la céruloplasmine du chamelon est compacte et plus acide. Le nombre d'atomes de cuivre par molécule de céruloplasmine a été de 5,8 ± 0,3. Le spectre optique de la céruloplasmine du chamelon a montré une absorption maximale à 610 nm attribuée au cuivre de type 1 . Le spectre EPR a été totalement dépourvu d'un signal correspondant au cuivre de type 2. Les paramètres cinétiques de l'activité oxidasique, utilisant la p-phénylendiamine comme substrat, ont été déterminés : Km = 0,42 µM NADH/mn/mg céruloplasmine et Vmax = 0,93. Le pH optimal de l'activité a été de 5,7

Lactoferrin Binding to SARS-CoV-2 Spike Glycoprotein Blocks Pseudoviral Entry and Relieves Iron Protein Dysregulation in Several In Vitro Models

SARS-CoV-2 causes COVID-19, a predominantly pulmonary disease characterized by a burst of pro-inflammatory cytokines and an increase in free iron. The viral glycoprotein Spike mediates fusion to the host cell membrane, but its role as a virulence factor is largely unknown. Recently, the antiviral activity of lactoferrin against SARS-CoV-2 was demonstrated in vitro and shown to occur via binding to cell surface receptors, and its putative interaction with Spike was suggested by in silico analyses. We investigated the anti-SARS-CoV-2 activity of bovine and human lactoferrins in epithelial and macrophagic cells using a Spike-decorated pseudovirus. Lactoferrin inhibited pseudoviral fusion and counteracted the deleterious effects of Spike on iron and inflammatory homeostasis by restoring basal levels of iron-handling proteins and of proinflammatory cytokines IL-1β and IL-6. Using pull-down assays, we experimentally proved for the first time that lactoferrin binds to Spike, immediately suggesting a mechanism for the observed effects. The contribution of transferrin receptor 1 to Spike-mediated cell fusion was also experimentally demonstrated. In silico analyses showed that lactoferrin interacts with transferrin receptor 1, suggesting a multifaceted mechanism of action for lactoferrin. Our results give hope for the use of bovine lactoferrin, already available as a nutraceutical, as an adjuvant to standard therapies in COVID-19