Assessment of the contribution of surfactants to mixture toxicity in French surface waters.

Surfactants are widely used 'down-the-drain' chemicals with the potential to occur at high concentrations in local water bodies and to be part of unintentional environmental mixtures. Recently, increased regulatory focus has been placed on the impacts of complex mixtures in aquatic environments and the substances that are likely to drive mixture risk. This study assessed the contribution of surfactants to the total mixture pressure in freshwater ecosystems.

B7-H3 in Pediatric Tumors: Far beyond Neuroblastoma.

B7-H3 is a 4Ig transmembrane protein that emerged as a tumor-associated antigen in neuroblastoma. It belongs to the B7 family, shows an immunoregulatory role toward NK and T cells, and, therefore, has been included in the growing family of immune checkpoints. Besides neuroblastoma, B7-H3 is expressed by many pediatric cancers including tumors of the central nervous system, sarcomas, and acute myeloid leukemia.

Murine models to study human NK cells in human solid tumors.

Since the first studies, the mouse models have provided crucial support for the most important discoveries on NK cells, on their development, function, and circulation within normal and tumor tissues. Murine tumor models were initially set to study murine NK cells, then, ever more sophisticated human-in-mice models have been developed to investigate the behavior of human NK cells and minimize the interferences from the murine environment. This review presents an overview of the models that have been used along time to study NK cells, focusing on the most popular NOG and NSG models, which work as recipients for the preparation of human-in-mice tumor models, the study of transferred human NK cells, and the evaluation of various enhancers of human NK cell function, including cytokines and chimeric molecules.

Monocyte and Macrophage in Neuroblastoma: Blocking Their Pro-Tumoral Functions and Strengthening Their Crosstalk with Natural Killer Cells.

Over the past decade, immunotherapy has represented an enormous step forward in the fight against cancer. Immunotherapeutic approaches have increasingly become a fundamental part of the combined therapies currently adopted in the treatment of patients with high-risk (HR) neuroblastoma (NB). An increasing number of studies focus on the understanding of the immune landscape in NB and, since this tumor expresses low or null levels of MHC class I, on the development of new strategies aimed at enhancing innate immunity, especially Natural Killer (NK) cells and macrophages.

A Human Ovarian Tumor & Liver Organ-on-Chip for Simultaneous and More Predictive Toxo-Efficacy Assays.

In oncology, the poor success rate of clinical trials is becoming increasingly evident due to the weak predictability of preclinical assays, which either do not recapitulate the complexity of human tissues (i.e., in vitro tests) or reveal species-specific outcomes (i.

Assessment of exposure to pesticide mixtures in five European countries by a harmonized urinary suspect screening approach.

Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites).

Strategies for Potentiating NK-Mediated Neuroblastoma Surveillance in Autologous or HLA-Haploidentical Hematopoietic Stem Cell Transplants.

High-risk neuroblastomas (HR-NB) still have an unacceptable 5-year overall survival despite the aggressive therapy. This includes standardized immunotherapy combining autologous hemopoietic stem cell transplantation (HSCT) and the anti-GD2 mAb. The treatment did not significantly change for more than one decade, apart from the abandonment of IL-2, which demonstrated unacceptable toxicity.

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

In the last 20 years, Natural Killer (NK) cell-based immunotherapy has become a promising approach to target various types of cancer. Indeed, NK cells play a pivotal role in the first-line defense against tumors through major histocompatibility complex-independent immunosurveillance. Their role in the control of leukemia relapse has been clearly established and, moreover, the presence of NK cells in the tumor microenvironment (TME) generally correlates with good prognosis.

Sleep and sleep-modifying factors in chronic migraine patients during the COVID-19 lockdown.

Aims: The objective of the present study was to evaluate sleep features and sleep-modifying factors in patients with chronic migraine (CM) during the first Italian COVID-19 lockdown.

Material And Methods: The study was based on an e-mail survey addressed to CM patients of our headache center. The survey investigated demographic, life-style, sleep, psychological, and migraine features during the first COVID-19 lockdown period and the month before.

A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model.

The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches.

Harmonized Quality Assurance/Quality Control Provisions for Nontargeted Measurement of Urinary Pesticide Biomarkers in the HBM4EU Multisite SPECIMEn Study.

A set of quality assurance/quality control (QA/QC) criteria for nontargeted measurement of pesticide exposure markers in a large-scale study of human urine has been proposed and applied across five laboratories within the HBM4EU project. Quality control material, including reference standards and fortified pooled urine samples (QC urine) were prepared in a centralized way and distributed across participants to monitor analytical performance and consistency of the liquid chromatography coupled to high-resolution mass spectrometry data generated with a harmonized workflow. Signal intensities, mass accuracy, and retention times of selected QA/QC markers covering a broad range of physicochemical properties were monitored across QC solvent standards, QC urine samples, study urine samples, and procedural blanks, setting acceptance thresholds for repeatability and accuracy.

Merging the exposome into an integrated framework for "omics" sciences.

The exposome concept encourages holistic consideration of the non-genetic factors (environmental exposures including lifestyle) that influence an individual's health over their life course. However, disconnect between the concept and practical application has promoted divergent interpretations of the exposome across disciplines and reinforced separation of the environmental (emphasizing exposures) and biological (emphasizing responses) research communities. In particular, while knowledge of biological responses can help to distinguish actual (i.

Biosensors to Monitor Cell Activity in 3D Hydrogel-Based Tissue Models.

Three-dimensional (3D) culture models have gained relevant interest in tissue engineering and drug discovery owing to their suitability to reproduce in vitro some key aspects of human tissues and to provide predictive information for in vivo tests. In this context, the use of hydrogels as artificial extracellular matrices is of paramount relevance, since they allow closer recapitulation of (patho)physiological features of human tissues. However, most of the analyses aimed at characterizing these models are based on time-consuming and endpoint assays, which can provide only static and limited data on cellular behavior.

Tumor Microenvironment and Hydrogel-Based 3D Cancer Models for In Vitro Testing Immunotherapies.

In recent years, immunotherapy has emerged as a promising novel therapeutic strategy for cancer treatment. In a relevant percentage of patients, however, clinical benefits are lower than expected, pushing researchers to deeply analyze the immune responses against tumors and find more reliable and efficient tools to predict the individual response to therapy. Novel tissue engineering strategies can be adopted to realize in vitro fully humanized matrix-based models, as a compromise between standard two-dimensional (2D) cell cultures and animal tests, which are costly and hardly usable in personalized medicine.

Chronic migraine in the first COVID-19 lockdown: the impact of sleep, remote working, and other life/psychological changes.

Aims: The objective of this study was to evaluate the impact of the first Italian COVID-19 lockdown on patients with chronic migraine (CM).

Material And Methods: The study was based on an e-mail survey addressed to CM patients of our headache center. The survey evaluated demographic, life style, sleep, psychological, and migraine features during the COVID-19 lockdown period and the month before.

In vitro models replicating the human intestinal epithelium for absorption and metabolism studies: A systematic review.

Absorption, distribution, metabolism and excretion (ADME) studies represent a fundamental step in the early stages of drug discovery. In particular, the absorption of orally administered drugs, which occurs at the intestinal level, has gained attention since poor oral bioavailability often led to failures for new drug approval. In this context, several in vitro preclinical models have been recently developed and optimized to better resemble human physiology in the lab and serve as an animal alternative to accomplish the 3Rs principles.

Towards a comprehensive characterisation of the human internal chemical exposome: Challenges and perspectives.

The holistic characterisation of the human internal chemical exposome using high-resolution mass spectrometry (HRMS) would be a step forward to investigate the environmental ætiology of chronic diseases with an unprecedented precision. HRMS-based methods are currently operational to reproducibly profile thousands of endogenous metabolites as well as externally-derived chemicals and their biotransformation products in a large number of biological samples from human cohorts. These approaches provide a solid ground for the discovery of unrecognised biomarkers of exposure and metabolic effects associated with many chronic diseases.

Open, High-Resolution EI+ Spectral Library of Anthropogenic Compounds.

To address the lack of high-resolution electron ionisation mass spectral libraries (HR-[EI+]-MS) for environmental chemicals, a retention-indexed HR-[EI+]-MS library has been constructed following analysis of authentic compounds via GC-Orbitrap MS. The library is freely provided alongside a compound database of predicted physicochemical properties. Currently, the library contains over 350 compounds from 56 compound classes and includes a range of legacy and emerging contaminants.

EZH1/2 Inhibitors Favor ILC3 Development from Human HSPC-CD34 Cells.

The dysregulation of epigenetic modifications has a well-established role in the development and progression of hematological malignancies and of solid tumors. In this context, EZH1/2 inhibitors have been designed to interfere with EZH1/2 enzymes involved in histone methylation (e.g.

3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization.

Metastasis is a dynamic process involving the dissemination of circulating tumor cells (CTCs) through blood flow to distant tissues within the body. Nevertheless, the development of an in vitro platform that dissects the crucial steps of metastatic cascade still remains a challenge. We here developed an in vitro model of extravasation composed of (i) a single channel-based 3D cell laden hydrogel representative of the metastatic site, (ii) a circulation system recapitulating the bloodstream where CTCs can flow.

3D fluid-dynamic ovarian cancer model resembling systemic drug administration for efficacy assay.

Recently, 3D in vitro cancer models have become important alternatives to animal tests for establishing the efficacy of anticancer treatments. In this work, 3D SKOV-3 cell-laden alginate hydrogels were established as ovarian tumor models and cultured within a fluid-dynamic bioreactor (MIVO®) device able to mimic the capillary flow dynamics feeding the tumor. Cisplatin efficacy tests were performed within the device over time and compared with (i) the in vitro culture under static conditions and (ii) a xenograft mouse model with SKOV-3 cells, by monitoring and measuring cell proliferation or tumor regression, respectively, over time.

Targeted Therapies: Friends or Foes for Patient's NK Cell-Mediated Tumor Immune-Surveillance?

In the last 20 years there has been a huge increase in the number of novel drugs for cancer treatment. Most of them exploit their ability to target specific oncogenic mutations in the tumors (targeted therapies-TT), while others target the immune-checkpoint inhibitor molecules (ICI) or the epigenetic DNA modifications. Among them, TT are the longest established drugs exploited against a wide spectrum of both solid and hematological tumors, often with reasonable costs and good efficacy as compared to other innovative therapies (i.

Plants radically change the mobility of PCBs in soil: Role of different species and soil conditions.

The mobility of Polychlorinated Biphenyls (PCBs) in soil cultivated with different plant species was evaluated by means of a column experiment to investigate the specific plant influence on PCB environmental fate and the potential for leaching. The soil was collected at a National Relevance Site for remediation located in Northern Italy (SIN Brescia-Caffaro) and underwent a rhizoremediation treatment for 18 months with different plant species (Festuca arundinacea, Cucurbita pepo ssp pepo and Medicago sativa). The same but unplanted soil was also considered as control for comparison.