Towards a risk assessment framework for micro- and nanoplastic particles for human health.

Background: Human exposure to micro- and nanoplastic particles (MNPs) is inevitable but human health risk assessment remains challenging for several reasons. MNPs are complex mixtures of particles derived from different polymer types, which may contain plenty of additives and/or contaminants. MNPs cover broad size distributions and often have irregular shapes and morphologies.

The application of natural language processing for the extraction of mechanistic information in toxicology.

To study the ways in which compounds can induce adverse effects, toxicologists have been constructing Adverse Outcome Pathways (AOPs). An AOP can be considered as a pragmatic tool to capture and visualize mechanisms underlying different types of toxicity inflicted by any kind of stressor, and describes the interactions between key entities that lead to the adverse outcome on multiple biological levels of organization. The construction or optimization of an AOP is a labor intensive process, which currently depends on the manual search, collection, reviewing and synthesis of available scientific literature.

New approach methodologies to enhance human health risk assessment of immunotoxic properties of chemicals - a PARC (Partnership for the Assessment of Risk from Chemicals) project.

As a complex system governing and interconnecting numerous functions within the human body, the immune system is unsurprisingly susceptible to the impact of toxic chemicals. Toxicants can influence the immune system through a multitude of mechanisms, resulting in immunosuppression, hypersensitivity, increased risk of autoimmune diseases and cancer development. At present, the regulatory assessment of the immunotoxicity of chemicals relies heavily on rodent models and a limited number of Organisation for Economic Co-operation and Development (OECD) test guidelines, which only capture a fraction of potential toxic properties.

Salivary concentrations of secretory leukocyte protease inhibitor and matrix metallopeptidase-9 following a single bout of exercise are associated with intensity and hydration status.

Aim: To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests varying in workload and hydration status.

Methods: Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5).

Effects of Exercise during Chemo- or Radiotherapy on Immune Markers: A Systematic Review.

Introduction: Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer.

Natural language processing in toxicology: Delineating adverse outcome pathways and guiding the application of new approach methodologies.

Adverse Outcome Pathways (AOPs) are conceptual frameworks that tie an initial perturbation (molecular initiating event) to a phenotypic toxicological manifestation (adverse outcome), through a series of steps (key events). They provide therefore a standardized way to map and organize toxicological mechanistic information. As such, AOPs inform on key events underlying toxicity, thus supporting the development of New Approach Methodologies (NAMs), which aim to reduce the use of animal testing for toxicology purposes.

DARTpaths, an in silico platform to investigate molecular mechanisms of compounds.

Summary: Xpaths is a collection of algorithms that allow for the prediction of compound-induced molecular mechanisms of action by integrating phenotypic endpoints of different species; and proposes follow-up tests for model organisms to validate these pathway predictions. The Xpaths algorithms are applied to predict developmental and reproductive toxicity (DART) and implemented into an in silico platform, called DARTpaths.

Availability And Implementation: All code is available on GitHub https://github.

Environmentally weathered polystyrene particles induce phenotypical and functional maturation of human monocyte-derived dendritic cells.

Micro- and nanoplastics (MNP) are ubiquitously present in the environment due to their high persistence and bioaccumulative properties. Humans get exposed to MNP via various routes and consequently, they will encounter dendritic cells (DC) which are antigen-presenting cells involved in regulating immune responses. The consequences of DC exposure to MNP are an important, yet understudied, cause of concern.

Chicken-derived RSPO1 and WNT3 contribute to maintaining longevity of chicken intestinal organoid cultures.

Intestinal organoids are advanced cellular models, which are widely used in mammalian studies to mimic and study in vivo intestinal function and host-pathogen interactions. Growth factors WNT3 and RSPO1 are crucial for the growth of intestinal organoids. Chicken intestinal organoids are currently cultured with mammalian Wnt3a and Rspo1, however, maintaining their longevity has shown to be challenging.

Towards a reporting guideline for developmental and reproductive toxicology testing in and other nematodes.

Implementation of reliable methodologies allowing Reduction, Refinement, and Replacement (3Rs) of animal testing is a process that takes several decades and is still not complete. Reliable methods are essential for regulatory hazard assessment of chemicals where differences in test protocol can influence the test outcomes and thus affect the confidence in the predictive value of the organisms used as an alternative for mammals. Although test guidelines are common for mammalian studies, they are scarce for non-vertebrate organisms that would allow for the 3Rs of animal testing.

Short-term associations between barbecue fumes and respiratory health in young adults.

Background: Epidemiological studies have associated biomass combustion with (respiratory) morbidity and mortality, primarily in indoor settings. Barbecuing results in high outdoor air pollution exposures, but the health effects are unknown.

Objective: The objective was to investigate short-term changes in respiratory health in healthy adults, associated with exposure to barbecue fumes.

Enterocytes, fibroblasts and myeloid cells synergize in anti-bacterial and anti-viral pathways with IL22 as the central cytokine.

IL22 is an important cytokine involved in the intestinal defense mechanisms against microbiome. By using ileum-derived organoids, we show that the expression of anti-microbial peptides (AMPs) and anti-viral peptides (AVPs) can be induced by IL22. In addition, we identified a bacterial and a viral route, both leading to IL22 production by T cells, but via different pathways.

Nanomaterials and the Serosal Immune System in the Thoracic and Peritoneal Cavities.

The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria.

Kinetics of Physiological Responses as a Measure of Intensity and Hydration Status During Experimental Physical Stress in Human Volunteers.

Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person's training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality.

The hepatotoxic fluoroquinolone trovafloxacin disturbs TNF- and LPS-induced p65 nuclear translocation in vivo and in vitro.

Idiosyncratic drug-induced liver injury (IDILI) is a severe disease that cannot be detected during drug development. It has been shown that hepatotoxicity of some compounds associated with IDILI becomes apparent when these are combined in vivo and in vitro with LPS or TNF. Among these compounds trovafloxacin (TVX) induced apoptosis in the liver and increased pro-inflammatory cytokines in mice exposed to LPS/TNF.

Deamidation and Enzymatic Hydrolysis of Gliadins Alter Their Processing by Dendritic Cells in Vitro.

Gliadins are major wheat allergens. Their treatment by acid or enzymatic hydrolysis has been shown to modify their allergenic potential. As the interaction of food proteins with dendritic cells (DCs) is a key event in allergic sensitization, we wished to investigate whether deamidation and enzymatic hydrolysis influence gliadin processing by DC and to examine the capacity of gliadins to activate DCs.

The Kiwifruit Allergen Act d 1 Activates NF-κB Signaling and Affects mRNA Expression of TJ Proteins and Innate Pro-Allergenic Cytokines.

Impairment of the intestinal barrier is one of the key events in the initiation of the sensitization process in food allergy. The aim of this study was to explore the effects of kiwifruit allergen Act d 1 on intestinal permeability and tight junction protein (TJP) gene expression in vivo and to explore its potential to activate the NF-ĸB signaling pathway and to regulate expression of epithelial pro-allergenic cytokines. Influences of Act d 1 on TJP gene expression and pro-allergenic cytokines in the mouse intestine was analyzed by qPCR upon allergen administration by oral gavage.

Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models.

Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction.

A network-based approach for identifying suitable biomarkers for oral immunotherapy of food allergy.

Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, concerns with regards to safety and long-term efficacy of OIT remain. There is a need to identify biomarkers that predict, monitor and/or evaluate the effects of OIT.

Non-digestible oligosaccharides scFOS/lcFOS facilitate safe subcutaneous immunotherapy for peanut allergy.

Background: Improving the safety of subcutaneous immunotherapy (SCIT) for food allergy is necessary to reduce side effects and achieve long-term tolerance. We determined the effect of dietary supplementation with 1% non-digestible short- and long-chain fructo-oligosaccharides (scFOS/lcFOS) on safety and efficacy of SCIT using a peanut allergy mouse model.

Methods: After sensitization, mice received a scFOS/lcFOS or control diet for the rest of the study.

Mouse strain differences in response to oral immunotherapy for peanut allergy.

Background: Promising therapies for food allergy are emerging, mostly based on animal experimentation. However, different mouse strains are used, which may make it hard to compare experiments. The current study investigated whether the immunological differences between C3H/HeOuJ (C3H) and BALB/c mice lead to differences in efficacy of peanut-specific immunotherapy.

Butyrate Enhances Desensitization Induced by Oral Immunotherapy in Cow's Milk Allergic Mice.

Background: In previous studies, we showed that a fructo-oligosaccharide- (FOS-) supplemented diet enhanced oral immunotherapy (OIT) efficacy in a mouse model for cow's milk allergy. Fermentation of FOS by intestinal bacteria leads to production of short-chain fatty acids (SCFA) including butyrate.

Aim: To investigate the contribution of butyrate in the enhanced efficacy of OIT + FOS.

Chemically modified peanut extract shows increased safety while maintaining immunogenicity.

Background: Peanuts are most responsible for food-induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity, and immunotherapeutic efficacy of a well-characterized chemically modified peanut extract (MPE) adsorbed to Al(OH) .

Plasma citrulline concentration, a marker for intestinal functionality, reflects exercise intensity in healthy young men.

Background & Aims: Plasma citrulline concentration is considered to be a marker for enterocyte metabolic mass and to reflect its reduction as may occur during intestinal dysfunction. Strenuous exercise can act as a stressor to induce small intestinal injury. Our previous studies suggest that this comprises the intestinal ability to produce citrulline from a glutamine-rich protein bolus.