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Particle and Fibre Toxicology Nov 2020Together with poor biodegradability and insufficient recycling, the massive production and use of plastics have led to widespread environmental contamination by nano-... (Review)
Review
BACKGROUND
Together with poor biodegradability and insufficient recycling, the massive production and use of plastics have led to widespread environmental contamination by nano- and microplastics. These particles accumulate across ecosystems - even in the most remote habitats - and are transferred through food chains, leading to inevitable human ingestion, that adds to the highest one due to food processes and packaging.
OBJECTIVE
The present review aimed at providing a comprehensive overview of current knowledge regarding the effects of nano- and microplastics on intestinal homeostasis.
METHODS
We conducted a literature search focused on the in vivo effects of nano- and microplastics on gut epithelium and microbiota, as well as on immune response.
RESULTS
Numerous animal studies have shown that exposure to nano- and microplastics leads to impairments in oxidative and inflammatory intestinal balance, and disruption of the gut's epithelial permeability. Other notable effects of nano- and microplastic exposure include dysbiosis (changes in the gut microbiota) and immune cell toxicity. Moreover, microplastics contain additives, adsorb contaminants, and may promote the growth of bacterial pathogens on their surfaces: they are potential carriers of intestinal toxicants and pathogens that can potentially lead to further adverse effects.
CONCLUSION
Despite the scarcity of reports directly relevant to human, this review brings together a growing body of evidence showing that nano- and microplastic exposure disturbs the gut microbiota and critical intestinal functions. Such effects may promote the development of chronic immune disorders. Further investigation of this threat to human health is warranted.
Topics: Animals; Gastrointestinal Microbiome; Humans; Immune System; Microplastics
PubMed: 33183327
DOI: 10.1186/s12989-020-00387-7 -
Nucleic Acids Research Jul 2018Advancement in the field of computational research has made it possible for the in silico methods to offer significant benefits to both regulatory needs and requirements...
Advancement in the field of computational research has made it possible for the in silico methods to offer significant benefits to both regulatory needs and requirements for risk assessments, and pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox-II that incorporates molecular similarity, pharmacophores, fragment propensities and machine-learning models for the prediction of various toxicity endpoints; such as acute toxicity, hepatotoxicity, cytotoxicity, carcinogenicity, mutagenicity, immunotoxicity, adverse outcomes pathways (Tox21) and toxicity targets. The predictive models are built on data from both in vitro assays (e.g. Tox21 assays, Ames bacterial mutation assays, hepG2 cytotoxicity assays, Immunotoxicity assays) and in vivo cases (e.g. carcinogenicity, hepatotoxicity). The models have been validated on independent external sets and have shown strong performance. ProTox-II provides a freely available webserver for in silico toxicity prediction for toxicologists, regulatory agencies, computational and medicinal chemists, and all users without login at http://tox.charite.de/protox_II. The webserver takes a two-dimensional chemical structure as an input and reports the possible toxicity profile of the chemical for 33 models with confidence scores, and an overall toxicity radar chart along with three most similar compounds with known acute toxicity.
Topics: Computational Biology; Drug-Related Side Effects and Adverse Reactions; Humans; Internet; Machine Learning; Risk Assessment; Software
PubMed: 29718510
DOI: 10.1093/nar/gky318 -
International Journal of Molecular... Jul 2021The immune system defends the body against certain tumor cells and against foreign agents such as fungi, parasites, bacteria, and viruses. One of its main roles is to... (Review)
Review
The immune system defends the body against certain tumor cells and against foreign agents such as fungi, parasites, bacteria, and viruses. One of its main roles is to distinguish endogenous components from non-self-components. An unproperly functioning immune system is prone to primary immune deficiencies caused by either primary immune deficiencies such as genetic defects or secondary immune deficiencies such as physical, chemical, and in some instances, psychological stressors. In the manuscript, we will provide a brief overview of the immune system and immunotoxicology. We will also describe the biochemical mechanisms of immunotoxicants and how to evaluate immunotoxicity.
Topics: Allergens; Animals; Environmental Illness; Food Hypersensitivity; Humans; Intestinal Mucosa; Respiratory Hypersensitivity; Respiratory Mucosa
PubMed: 34361007
DOI: 10.3390/ijms22158242 -
Frontiers in Toxicology 2022Most disposable plastic products are degraded slowly in the natural environment and continually turned to microplastics (MPs) and nanoplastics (NPs), posing additional... (Review)
Review
Most disposable plastic products are degraded slowly in the natural environment and continually turned to microplastics (MPs) and nanoplastics (NPs), posing additional environmental hazards. The toxicological assessment of MPs for marine organisms and mammals has been reported. Thus, there is an urgent need to be aware of the harm of MPs to the human immune system and more studies about immunological assessments. This review focuses on how MPs are produced and how they may interact with the environment and our body, particularly their immune responses and immunotoxicity. MPs can be taken up by cells, thus disrupting the intracellular signaling pathways, altering the immune homeostasis and finally causing damage to tissues and organs. The generation of reactive oxygen species is the mainly toxicological mechanisms after MP exposure, which may further induce the production of danger-associated molecular patterns (DAMPs) and associate with the processes of toll-like receptors (TLRs) disruption, cytokine production, and inflammatory responses in immune cells. MPs effectively interact with cell membranes or intracellular proteins to form a protein-corona, and combine with external pollutants, chemicals, and pathogens to induce greater toxicity and strong adverse effects. A comprehensive research on the immunotoxicity effects and mechanisms of MPs, including various chemical compositions, shapes, sizes, combined exposure and concentrations, is worth to be studied. Therefore, it is urgently needed to further elucidate the immunological hazards and risks of humans that exposed to MPs.
PubMed: 36238600
DOI: 10.3389/ftox.2022.956885 -
Toxicology and Applied Pharmacology Nov 2022Uranium is a naturally occurring element found in the environment as a mixture of isotopes with differing radioactive properties. Enrichment of mined material results in... (Review)
Review
Uranium is a naturally occurring element found in the environment as a mixture of isotopes with differing radioactive properties. Enrichment of mined material results in depleted uranium waste with substantially reduced radioactivity but retains the capacity for chemical toxicity. Uranium mine and milling waste are dispersed by wind and rain leading to environmental exposures through soil, air, and water contamination. Uranium exposure is associated with numerous adverse health outcomes in humans, yet there is limited understanding of the effects of depleted uranium on the immune system. The purpose of this review is to summarize findings on uranium immunotoxicity obtained from cell, rodent and human population studies. We also highlight how each model contributes to an understanding of mechanisms that lead to immunotoxicity and limitations inherent within each system. Information from population, animal, and laboratory studies will be needed to significantly expand our knowledge of the contributions of depleted uranium to immune dysregulation, which may then inform prevention or intervention measures for exposed communities.
Topics: Animals; Environmental Exposure; Humans; Mining; Soil; Uranium; Water
PubMed: 36152676
DOI: 10.1016/j.taap.2022.116252 -
Biotechnology Advances Dec 2022Fundamental clinical areas such as drug delivery and regenerative medicine require biocompatible materials as mechanically stable scaffolds or as nanoscale drug... (Review)
Review
Fundamental clinical areas such as drug delivery and regenerative medicine require biocompatible materials as mechanically stable scaffolds or as nanoscale drug carriers. Among the wide set of emerging biomaterials, polypeptides offer enticing properties over alternative polymers, including full biocompatibility, biodegradability, precise interactivity, structural stability and conformational and functional versatility, all of them tunable by conventional protein engineering. However, proteins from non-human sources elicit immunotoxicities that might bottleneck further development and narrow their clinical applicability. In this context, selecting human proteins or developing humanized protein versions as building blocks is a strict demand to design non-immunogenic protein materials. We review here the expanding catalogue of human or humanized proteins tailored to execute different levels of scaffolding functions and how they can be engineered as self-assembling materials in form of oligomers, polymers or complex networks. In particular, we emphasize those that are under clinical development, revising their fields of applicability and how they have been adapted to offer, apart from mere mechanical support, highly refined functions and precise molecular interactions.
Topics: Humans; Biocompatible Materials; Proteins; Regenerative Medicine; Polymers; Drug Delivery Systems; Tissue Engineering
PubMed: 36089254
DOI: 10.1016/j.biotechadv.2022.108032 -
Nanomedicine (London, England) Aug 2018Silicon-based materials and their oxides are widely used in drug delivery, dietary supplements, implants and dental fillers. Silica nanoparticles (SiNPs) interact with... (Review)
Review
Silicon-based materials and their oxides are widely used in drug delivery, dietary supplements, implants and dental fillers. Silica nanoparticles (SiNPs) interact with immunocompetent cells and induce immunotoxicity. However, the toxic effects of SiNPs on the immune system have been inadequately reviewed. The toxicity of SiNPs to the immune system depends on their physicochemical properties and the cell type. Assessments of immunotoxicity include determining cell dysfunctions, cytotoxicity and genotoxicity. This review focuses on the immunotoxicity of SiNPs and investigates the underlying mechanisms. The main mechanisms were proinflammatory responses, oxidative stress and autophagy. Considering the toxicity of SiNPs, surface and shape modifications may mitigate the toxic effects of SiNPs, providing a new way to produce these nanomaterials with less toxic impaction.
Topics: Animals; Apoptosis; Autophagy; Cell Survival; DNA Damage; Humans; Immune System; Mitogen-Activated Protein Kinase Kinases; Nanoparticles; Oxidative Stress; Silicon Dioxide; Toll-Like Receptors
PubMed: 30152253
DOI: 10.2217/nnm-2018-0076 -
International Journal of Molecular... Oct 2018Days ago, the Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of...
Days ago, the Nobel Prize in Physiology or Medicine 2018 was awarded jointly to James P. Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation". This news has increased the attention on immunotoxicity and immune evasion mechanisms, which are once again hot research topics. Actually, increasing lines of evidence show that trichothecene mycotoxins have a strong immunosuppressive effect. These mycotoxins suppress the host immunity and make them more sensitive to the infection of pathogens, including bacteria and viruses. However, the underlying mechanism(s) in this context is still poorly understood. Interestingly, recent work showed that an immune evasion mechanism might be involved in trichothecene immunotoxicity. In this work, we discuss the potential immune evasion mechanism in trichothecene immunotoxicity. More importantly, under these circumstances, we are pleased to compile a Special Issue entitled "Biochemistry, Molecular Biology, and Toxicology of Natural and Synthetic Toxins" for the (). Researchers are encouraged to share their latest interesting findings with the readers of .
Topics: Animals; Humans; Immune Evasion; Immunosuppressive Agents; Trichothecenes
PubMed: 30355984
DOI: 10.3390/ijms19113307 -
Toxins Oct 2021Cyanobacteria (blue-green algae) have been present on Earth for over 2 billion years, and can produce a variety of bioactive molecules, such as cyanotoxins. Microcystins... (Review)
Review
Cyanobacteria (blue-green algae) have been present on Earth for over 2 billion years, and can produce a variety of bioactive molecules, such as cyanotoxins. Microcystins (MCs), the most frequently detected cyanotoxins, pose a threat to the aquatic environment and to human health. The classic toxic mechanism of MCs is the inhibition of the protein phosphatases 1 and 2A (PP1 and PP2A). Immunity is known as one of the most important physiological functions in the neuroendocrine-immune network to prevent infections and maintain internal homoeostasis in fish. The present review aimed to summarize existing papers, elaborate on the MC-induced immunotoxicity in fish, and put forward some suggestions for future research. The immunomodulatory effects of MCs in fish depend on the exposure concentrations, doses, time, and routes of exposure. Previous field and laboratory studies provided strong evidence of the associations between MC-induced immunotoxicity and fish death. In our review, we summarized that the immunotoxicity of MCs is primarily characterized by the inhibition of PP1 and PP2A, oxidative stress, immune cell damage, and inflammation, as well as apoptosis. The advances in fish immunoreaction upon encountering MCs will benefit the monitoring and prediction of fish health, helping to achieve an ecotoxicological goal and to ensure the sustainability of species. Future studies concerning MC-induced immunotoxicity should focus on adaptive immunity, the hormesis phenomenon and the synergistic effects of aquatic microbial pathogens.
Topics: Animals; Apoptosis; Fish Diseases; Fishes; Immunotoxins; Inflammation; Microcystins; Oxidative Stress; Protein Phosphatase 1; Protein Phosphatase 2
PubMed: 34822549
DOI: 10.3390/toxins13110765 -
Cureus Oct 2022Despite primary advancements in medication, cancer continues to be one of the main reasons for death globally. Techniques for immunotherapy against malignant improvement... (Review)
Review
Despite primary advancements in medication, cancer continues to be one of the main reasons for death globally. Techniques for immunotherapy against malignant improvement are rising as fantastic treatments for this setback. The rapid development of modern immunotherapeutics has inspired a decrease in stubborn malignancies and led to an emotional improvement in patient endurance. However, a giant barrier to these ongoing treatment modalities is an anomaly in clinical response, specifically articulated amongst targeted spot inhibition, chimeric antigen receptor (CAR) T-cell therapy, oncolytic infections, and recombinant cytokines emerging since sickness cells use a variety of structures to avert immunosurveillance. Other challenges encompass the lack of ability to predict the efficacy of the therapy and the response of the patient, the want for additional biomarkers, the improvement of immunity in opposition to malignant boom immunotherapies, the absence of medical assessment plans that are up-to-date to decide sufficiency, and high therapy costs. The therapy for middle-stage malignant growth and the top five difficulties, setbacks, and drawbacks of immunotherapy are examined in this audit.
PubMed: 36465776
DOI: 10.7759/cureus.30856