•Bovine lactoferrin hinders migration in GL-15 cells, a human glioblastoma cell line.•Bovine lactoferrin reverts epithelial-to-mesenchymal-like process in GL-15 cells.•Bovine lactoferrin inhibits ...interleukin-6/STAT3 axis in GL-15 cells.
Glioblastoma, the most lethal form of brain cancer, is characterized by fast growth, migration and invasion of the surrounding parenchyma, with epithelial-to-mesenchymal transition (EMT)-like process being mostly responsible for tumour spreading and dissemination. A number of actors, including cadherins, vimentin, transcriptional factors such as SNAIL, play critical roles in the EMT process. The interleukin (IL)-6/STAT3 axis has been related to enhanced glioblastoma’s migration and invasion abilities as well.
Here, we present data on the differential effects of native and iron-saturated bovine lactoferrin (bLf), an iron-chelating glycoprotein of the innate immune response, in inhibiting migration in a human glioblastoma cell line. Through a wound healing assay, we found that bLf was able to partially or completely hinder cell migration, depending on its iron saturation rate. At a molecular level, bLf down-regulated both SNAIL and vimentin expression, while inducing a notable increase in cadherins’ levels and inhibiting IL-6/STAT3 axis. Again, these effects positively correlated to bLf iron-saturation state, with the Holo-form resulting more efficient than the native one. Overall, our data suggest that bLf could represent a novel and efficient adjuvant treatment for glioblastoma’s standard therapeutic approaches.
Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key ...element in the host immune defense system. The
and
experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in "pure" M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading
to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp, cytosolic Ftn, and transferrin receptor 1 in "pure" M1 macrophages, as well as in the more heterogeneous macrophage population. In addition, the decrease of IL-10 induced by the LPS/IFN-γ mix was counteracted by bovine lactoferrin. Several drugs capable of modulating macrophagic phenotypes are emerging as attractive molecules for treating inflammation, and in this sense, bovine lactoferrin is no exception.
Este trabajo versa sobre los bancos públicos napolitanos. Estas instituciones son particularmente interesantes en la historia de la banca y de la contabilidad bancaria porque fueron las primeras en ...emitir papel moneda en forma de unos certificados de depósito o fedi di credito en la segunda mitad del siglo XVI. Estos certificados eran transmisibles por endoso y su emisión vino impuesta de alguna manera por la necesidad práctica de remediar la escasez crónica de numerario metálico que padecia el Reino de Nápoles, incorporado en aquella época a la Corona española. El primer banco público, llamado asi, no porque fuera de capital público, sino porque gozaba del apoyo y del reconocimiento de las autoridades gubernamentales, al tiempo que estaba sometido a su control, fue el Monte di Pietà. En el curso del trabajo se explican con detenimiento las circunstancias y dificultades económicas del Virreinato, con las frecuentes quiebras de banqueros privados, la creciente escasez de moneda metálica, la falsificación de la moneda, el recorte y cercenamiento de la buena, la fuga de la misma al exterior, el ambiente enrarecido de la nobleza y sus intentos de rebelión, el fracasado intento de Felipe II, en 1574, de auspiciar la creación en el reino de Nápoles de un banco único, con funciones de banco de Estado, con el fin de desarrollar el servicio de Tesoreria y, sobre todo, de conceder a la Corte préstamos en condiciones ventajosas -curioso paralelismo con los debates en España sobre este mismo tema en esos mismos años-, etc., motivos todos ellos que impulsaron al Virrey, entre finales de los años sesenta e inicios de los setenta, a reconocer valor oficial de moneda a los certificados de depósito emitidos por el Monte, en el sentido de concederles el privilegio de poder ser usados en los pagos a hacer al Estado por cualquier concepto. Ante el éxito obtenido por el Monte di Pietà, este mismo privilegio fue concedido a otros seis bancos más a finales del siglo y comienzos del siglo XVII. Los siete bancos públicos napolitanos cumplieron satisfactoriamente la misión para la que habian surgido y sus certificados de depósito fueron un dinero que gozó de general aceptación, alcanzando un elevado volumen de circulación y una rápida tasa de rotación. A finales del siglo XIX se fusionaron los siete bancos para dar lugar al actual Banco di Napoli. Su impresionante documentación contable se conserva en el Archivo histórico de esta entidad. Especialmente interesante es el sofisticado sistema contable instrumentado para contabilizar la emisión, seguimiento, control y cancelación de los certificados de depósito, como puede apreciarse por las explicaciones ofrecidas en la última parte del trabajo.
Implant-associated infections are characterized by microbial biofilm formation on implant surface, which renders the microbiological diagnosis challenging and requires, in the majority of cases, a ...complete device removal along with a prolonged antimicrobial therapy. Traditional cultures have shown unsatisfactory sensitivity and a significant advance in the field has been represented by both the application of the sonication technique for the detachment of live bacteria from biofilm and the implementation of metabolic and molecular assays. However, despite the recent progresses in the microbiological diagnosis have considerably reduced the rate of culture-negative infections, still their reported incidence is not negligible. Overall, several culture- and non-culture based methods have been developed for diagnosis optimization, which mostly relies on pre-operative and intra-operative (i.e., removed implants and surrounding tissues) samples. This review outlines the principal culture- and non-culture based methods for the diagnosis of the causative agents of implant-associated infections and gives an overview on their application in the clinical practice. Furthermore, advantages and disadvantages of each method are described.
SARS-CoV-2, an enveloped, single-stranded RNA virus causing COVID-19, exerts morbidity and mortality especially in elderly, obese individuals and those suffering from chronic conditions. In addition ...to the availability of vaccines and the limited efficacy of the first dose of vaccine against SARS-CoV-2 variants, there is an urgent requirement for the discovery and development of supplementary antiviral agents. Lactoferrin (Lf), a pleiotropic cationic glycoprotein of innate immunity, has been proposed as a safe treatment combined with other therapies in COVID-19 patients. Here, we present a small retrospective study on asymptomatic, paucisymptomatic, and moderate symptomatic COVID-19 Lf-treated versus Lf-untreated patients. The time required to achieve SARS-CoV-2 RNA negativization in Lf-treated patients (n = 82) was significantly lower (p < 0.001) compared to that observed in Lf-untreated ones (n = 39) (15 versus 24 days). A link among reduction in symptoms, age, and Lf treatment was found. The Lf antiviral activity could be explained through the interaction with SARS-CoV-2 spike, the binding with heparan sulfate proteoglycans of cells, and the anti-inflammatory activity associated with the restoration of iron homeostasis disorders, which favor viral infection/replication. Lf could be an important supplementary treatment in counteracting SARS-CoV-2 infection, as it is also safe and well-tolerated by all treated patients.
The Trans-Activator of Transcription (Tat) of Human Immunodeficiency Virus (HIV-1) is involved in virus replication and infection and can promote oxidative stress in human astroglial cells. In ...response, host cells activate transcription of antioxidant genes, including a subunit of System X
cystine/glutamate antiporter which, in turn, can trigger glutamate-mediated excitotoxicity. Here, we present data on the efficacy of bovine Lactoferrin (bLf), both in its native (Nat-bLf) and iron-saturated (Holo-bLf) forms, in counteracting oxidative stress in U373 human astroglial cells constitutively expressing the viral protein (U373-Tat). Our results show that, dependent on iron saturation, both Nat-bLf and Holo-bLf can boost host antioxidant response by up-regulating System X
and the cell iron exporter Ferroportin via the Nuclear factor erythroid 2-related factor (Nrf2) pathway, thus reducing Reactive Oxygen Species (ROS)-mediated lipid peroxidation and DNA damage in astrocytes. In U373-Tat cells, both forms of bLf restore the physiological internalization of Transferrin (Tf) Receptor 1, the molecular gate for Tf-bound iron uptake. The involvement of astrocytic antioxidant response in Tat-mediated neurotoxicity was evaluated in co-cultures of U373-Tat with human neuronal SH-SY5Y cells. The results show that the Holo-bLf exacerbates Tat-induced excitotoxicity on SH-SY5Y, which is directly dependent on System-X
upregulation, thus highlighting the mechanistic role of iron in the biological activities of the glycoprotein.
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.
Background:
Corneal collagen cross-linking (CXL) is considered an effective procedure for slowing down or eliminating the progression of keratoconus. New techniques, in combination with CXL, have ...been proposed to stop the evolution of keratoconus and improve the visual function.
Objective:
To evaluate the effectiveness of combined photorefractive keratectomy (PRK) with mitomycin-C (MMC) application and CXL in the management of grade 1–2 keratoconus over a 2-year follow-up.
Methods:
Fifteen eyes underwent topography-guided PRK with 0.02% MMC application immediately followed by standard CXL.
Results:
Best corrected visual acuity improved from 0.15 ± 0.11 logMAR to 0.08 ± 0.09 logMAR at 24 months (p < 0.0001) in treated eyes. Mean steepest meridian keratometry reduced from 48.79 ± 3.22 D at baseline to 46.16 ± 3.11 D at 24 months (p < 0.0001). Mean flattest meridian keratometry reduced from 45.18 ± 2.17 D preoperatively to 44.35 ± 2.19 D at 24 months (p < 0.0001).
Conclusion:
Simultaneous topography-guided PRK with MMC 0.02% application and standard CXL is a safe, promising and effective procedure in the treatment of mild and moderate keratoconus.
The Casimir effect is a remarkable macroscopic feature of QED, while recent lattice studies have also shown its potential nontrivial consequences in QCD. In light of having a better understanding of ...the Casimir effect, it is advantageous to have a self-contained path integral formulation of the phenomenon. I will show how the Casimir effect between two uncharged plates in the presence of a chiral medium, modeled with an axion term
θF͂
μv
F
μv
, can be formulated in terms of the path integral, and how such a formulation leads to a 3D effective action of the restricted electromagnetic field.
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