Immune cells and microbiota response to iron starvation

Metal ions are essential for life on Earth, mostly as crucial components of all living organisms; indeed, they are necessary for bioenergetics functions as crucial redox catalysts. Due to the essential role of iron in biological processes, body iron content is finely regulated and is the battlefield of a tug-of-war between the host and the microbiota.Iron availability in the intestinal lumen could prevent or promote intestinal dysbiosis, although current data do not provide a definitive response. Recent data demonstrated that nutritional derived polyphenols explicit their anti-inflammatory functions sequestrating iron from immune cells. Here, we discuss whether nutritional iron chelators could be able to change the gut microbiota composition and prevent the intestinal dysbiosis associated with intestinal chronic inflammatory syndromes.Iron is lost by cellular exfoliation and occasional bleeding; it is absorbed from nutritional components. Heme is the most important source of dietary iron, while non-heme iron can be absorbed only in the duodenum and the beginning of the jejunum in pH permissive (acid) conditions. Western diets often contain large quantities of foods characterized by a high heme-iron content like meat, fish, and poultry, and small quantities of non-heme-iron content like vegetables, fruits, and nuts. Furthermore, nutritional substances can affect iron absorption: ascorbic acid is an efficient enhancer of non-heme-iron absorption, vice versa, phytic acid is known to be among the major iron absorption inhibitors, and iron-chelating substances like quercetin inhibit its absorption, likely due to loss of chelated-iron solubility.Iron deficiency is the most common cause of anemia worldwide and one of the most common complications observed in inflammatory bowel disease (IBD) patients due to gastrointestinal hemorrhages. In IBD patients, the guidelines for the management of iron deficiency are not entirely satisfactory because following oral iron supplementation patients sometimes report worsening of the IBD symptoms (1). Interestingly, iron supplemented diets can also show protective effects in dextran sodium sulfate (DSS)-induced colitis models. Constante et al. demonstrated that iron formulation dramatically changed the outcome of the DSS-induced colitis, as oral supplementation with ferrous bisglycinate but not ferric ethylenediaminetetraacetic acid enhanced the beneficial action of probiotics (2)

Women and unpaid family work in the EU

This study provides an analysis of the size and value of unpaid family care work at the European Union level. It proposes a method which relies on harmonised European surveys. It also compares two EU member States, Italy and Poland, whose time use data contain additional detailed information on child care and elderly care work. The study aims at improving the existing indicators in order to have a reliable quantitative picture to use in discussions on unpaid family care work at EU level

Validation of a lab-on-chip assay for measuring sorafenib effectiveness on hcc cell proliferation

Hepatocellular carcinoma (HCC) is a highly lethal cancer, and although a few drugs are available for treatment, therapeutic effectiveness is still unsatisfactory. New drugs are urgently needed for hepatocellular carcinoma (HCC) patients. In this context, reliable preclinical assays are of paramount importance to screen the effectiveness of new drugs and, in particular, measure their effects on HCC cell proliferation. However, cell proliferation measurement is a time-consuming and operator-dependent procedure. The aim of this study was to validate an engineered miniaturized on-chip platform for real-time, non-destructive cell proliferation assays and drug screening. The effectiveness of Sorafenib, the first-line drug mainly used for patients with advanced HCC, was tested in parallel, comparing the gold standard 96-well-plate assay and our new lab-on-chip platform. Results from the lab-on-chip are consistent in intra-assay replicates and comparable to the output of standard crystal violet proliferation assays for assessing Sorafenib effectiveness on HCC cell proliferation. The miniaturized platform presents several advantages in terms of lesser reagents consumption, operator time, and costs, as well as overcoming a number of technical and operator-dependent pitfalls. Moreover, the number of cells required is lower, a relevant issue when primary cell cultures are used. In conclusion, the availability of inexpensive on-chip assays can speed up drug development, especially by using patient-derived samples to take into account disease heterogeneity and patient-specific characteristics

Dependence of brain DTI maps of fractional anisotropy and mean diffusivity on the number of diffusion weighting directions

The rotational variance dependence of diffusion tensor imaging (DTI) derived parameters on the number of diffusion weighting directions (N) has been investigated by several Monte Carlo simulation studies. However, the dependence of fractional anisotropy (FA) and mean diffusivity (MD) maps on N, in terms of accuracy and contrast between different anatomical structures, has not been assessed in detail. This experimental study further investigated in vivo the effect of the number of diffusion weighting directions on DTI maps of FA and MD. Human brain FA and MD maps of six healthy subjects were acquired at 1.5T with varying N (6, 11, 19, 27, 55). Then, FA and MD mean values in high (FAH, MDH) and low (FAL, MDL) anisotropy segmented brain regions were measured. Moreover, the contrast-to-signal variance ratio (CVRFA, CVRMD) between the main white matter and the surrounding regions was calculated. Analysis of variance showed that FAL, FAH and CVRFA significantly (p 0.05) depend on N. Unlike MD values, FA values significantly vary with N. It is noteworthy that the observed variation is opposite in low and high anisotropic regions. In clinical studies, the effect of N may represent a confounding variable for anisotropy measurements and the employment of DTI acquisition schemes with high N (> 20) allows an increased CVR and a better visualization of white matter structures in FA maps

AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.</p> <p>Methods</p> <p>Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.</p> <p>Results</p> <p>Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.</p> <p>Conclusion</p> <p>We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.</p

A tutorial on optimal control and reinforcement learning methods for quantum technologies

Quantum Optimal Control is an established field of research which is necessary for the development of Quantum Technologies. In recent years, Machine Learning techniques have been proved useful to tackle a variety of quantum problems. In particular, Reinforcement Learning has been employed to address typical problems of control of quantum systems. In this tutorial we introduce the methods of Quantum Optimal Control and Reinforcement Learning by applying them to the problem of three-level population transfer. The jupyter notebooks to reproduce some of our results are open-sourced and available on github1

Effectiveness of a controlled 5-fu delivery based on fzd10 antibody-conjugated liposomes in colorectal cancer in vitro models

The use of controlled delivery therapy in colorectal cancer (CRC) reduces toxicity and side effects. Recently, we have suggested that the Frizzled 10 (FZD10) protein, a cell surface receptor belonging to the FZD protein family that is overexpressed in CRC cells, is a novel candidate for targeting and treatment of CRC. Here, the anticancer effect of novel immuno-liposomes loaded with 5-Fluorouracil (5-FU), decorated with an antibody against FZD10 (anti-FZD10/5-FU/LPs), was evaluated in vitro on two different CRC cell lines, namely metastatic CoLo-205 and nonmetastatic CaCo-2 cells, that were found to overexpress FZD10. The anti-FZD10/5-FU/LPs obtained were extensively characterized and their preclinical therapeutic efficacy was evaluated with the MTS cell proliferation assay based on reduction of tetrazolium compound, scratch test, Field Emission Scanning Electron Microscopes (FE-SEM) investigation and immunofluorescence analysis. The results highlighted that the cytotoxic activity of 5-FU was enhanced when encapsulated in the anti-FZD10 /5-FU/LPs at the lowest tested concentrations, as compared to the free 5-FU counterparts. The immuno-liposomes proposed herein possess a great potential for selective treatment of CRC because, in future clinical applications, they can be encapsulated in gastro-resistant capsules or suppositories for oral or rectal delivery, thereby successfully reaching the intestinal tract in a minimally invasive manner