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

Kink Localization under Asymmetric Double-Well Potential

We study diffuse phase interfaces under asymmetric double-well potential energies with degenerate minima and demonstrate that the limiting sharp profile, for small interface energy cost, on a finite space interval is in general not symmetric and its position depends exclusively on the second derivatives of the potential energy at the two minima (phases). We discuss an application of the general result to porous media in the regime of solid-fluid segregation under an applied pressure and describe the interface between a fluid-rich and a fluid-poor phase. Asymmetric double-well potential energies are also relevant in a very different field of physics as that of Brownian motors. An intriguing analogy between our result and the direction of the dc soliton current in asymmetric substrate driven Brownian motors is pointed out

A Single Thermoresponsive Diblock Copolymer Can Form Spheres, Worms or Vesicles in Aqueous Solution

It is well‐known that the self‐assembly of AB diblock copolymers in solution can produce various morphologies depending on the relative volume fraction of each block. Recently, polymerization‐induced self‐assembly (PISA) has become widely recognized as a powerful platform technology for the rational design and efficient synthesis of a wide range of block copolymer nano‐objects. In this study, PISA is used to prepare a new thermoresponsive poly(N‐(2‐hydroxypropyl) methacrylamide)‐poly(2‐hydroxypropyl methacrylate) [PHPMAC‐PHPMA] diblock copolymer. Remarkably, TEM, rheology and SAXS studies indicate that a single copolymer composition can form well‐defined spheres (4 °C), worms (22 °C) or vesicles (50 °C) in aqueous solution. Given that the two monomer repeat units have almost identical chemical structures, this system is particularly well‐suited to theoretical analysis. Self‐consistent mean field theory suggests this rich self‐assembly behavior is the result of the greater degree of hydration of the PHPMA block at lower temperature, which is in agreement with variable temperature 1H NMR studies

Sensing the turbulent large-scale motions with their wall signature

This study assesses the capability of extended proper orthogonal decomposition (EPOD) and convolutional neural networks (CNNs) to reconstruct large-scale and very-large-scale motions (LSMs and VLSMs respectively) employing wall-shear-stress measurements in wall-bounded turbulent flows. Both techniques are used to reconstruct the instantaneous LSM evolution in the flow field as a combination of proper orthogonal decomposition (POD) modes, employing a limited set of instantaneous wall-shear-stress measurements. Due to the dominance of nonlinear effects, only CNNs provide satisfying results. Being able to account for nonlinearities in the flow, CNNs are shown to perform significantly better than EPOD in terms of both instantaneous flow-field estimation and turbulent-statistics reconstruction. CNNs are able to provide a more effective reconstruction performance employing more POD modes at larger distances from the wall and employing lower wall-measurement resolutions. Furthermore, the capability of tackling nonlinear features of CNNs results in estimation capabilities that are weakly dependent on the distance from the wall.This work has been partially supported by Grant No. DPI2016-79401-R funded by the Spanish State Research Agency (SRA) and the European Regional Development Fund (ERDF). A.G. acknowledges Dr. A. Sánchez for insightful discussions about CNN architecture. The authors acknowledge Dr. R. Vinuesa for insightful comments and discussions

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

Letter: faecal microbiota transplantation for irritable bowel syndrome

his article is linked to Lahtinen et al papers. To view these articles, visit https://doi.org/10.1111/apt.15810 and https://doi.org/10.1111/apt.15875

Epid-based in\ua0vivo dose verification for lung stereotactic treatments delivered with multiple breath-hold segmented volumetric modulated arc therapy

We evaluated an EPID-based in-vivo dosimetry (IVD) method for the dose verification and the treatment reproducibility of lung SBRT-VMAT treatments in clinical routine. Ten patients with lung metastases treated with Elekta VMAT technique were enrolled. All patients were irradiated in five consecutive fractions, with total doses of 50 Gy. Set-up was carried out with the Elekta stereotactic body frame. Eight patients were simulated and treated using the Active Breath Control (ABC) system, a spirometer enabling patients to maintain a breath-hold at a predetermined lung volume. Two patients were simulated and treated in free-breathing using an abdominal compressor. IVD was performed using the SOFTDISO software. IVD tests were evaluated by means of (a) ratio R between daily in-vivo isocenter dose and planned dose and (b) gamma-analysis between EPID integral portal images in terms of percentage of points with gamma-value smaller than one (gamma(%)) and mean gamma-values (gamma(mean)) using a 3%(global)/3 mm criteria. Alert criteria of +/- 5% for R ratio, gamma(%) < 90%, and gamma(mean) > 0.67 were chosen. 50 transit EPID images were acquired. For the patients treated with ABC spirometer, the results reported a high level of accuracy in dose delivery with 100% of tests within +/- 5%. The gamma-analysis showed a mean value of gamma(mean) equal to 0.21 (range: 0.04-0.56) and a mean gamma(%) equal to 96.9 (range: 78-100). Relevant discrepancies were observed only for the two patients treated without ABC, mainly due to a blurring dose effect due to residual respiratory motion. Our method provided a fast and accurate procedure in clinical routine for verifying delivered dose as well as for detecting errors

Phase coexistence in consolidating porous media

The appearence of the fluid-rich phase in saturated porous media under the effect of an external pressure is investigated. For this purpose we introduce a two field second gradient model allowing the complete description of the phenomenon. We study the coexistence profile between poor and rich fluid phases and we show that for a suitable choice of the parameters non-monotonic interfaces show-up at coexistence

In-situ liquid phase imaging of block copolymer vesicle assembly

Amphiphilic block copolymers in aqueous solution can assemble into various ordered molecular architectures, which have a wide range of applications in, for example, drug delivery and catalytic nanoreactors.1 While sustained efforts, both experimentally and theoretically, have been made to better understand the mechanism of self- assembly in order to gain more control over this process,2, 3 there has never been a real-time, real space investigation of the assembly process on the nanoscale. Here we show the first observation of block copolymer vesicle assembly via the solvent switch protocol4 using liquid phase transmission electron microscopy (LP-TEM). We also discuss the different mechanisms of self-assembly with the ex-situ cryo-TEM observation and compare them with self-consistent field (SCF) lattice calculations. Our findings illustrate the ability of LP-TEM to implement quantitative visualization of local formation process of the block copolymer vesicles to reveal the formation mechanism on an individual particle level Please click Additional Files below to see the full abstract