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Microbiome Nov 2023Many studies have investigated how nanoplastics (NPs) exposure mediates nerve and intestinal toxicity through a dysregulated brain-gut axis interaction, but there are...
BACKGROUND
Many studies have investigated how nanoplastics (NPs) exposure mediates nerve and intestinal toxicity through a dysregulated brain-gut axis interaction, but there are few studies aimed at alleviating those effects. To determine whether and how vitamin D can impact that toxicity, fish were supplemented with a vitamin D-low diet and vitamin D-high diet.
RESULTS
Transmission electron microscopy (TEM) showed that polystyrene nanoplastics (PS-NPs) accumulated in zebrafish brain and intestine, resulting in brain blood-brain barrier basement membrane damage and the vacuolization of intestinal goblet cells and mitochondria. A high concentration of vitamin D reduced the accumulation of PS-NPs in zebrafish brain tissues by 20% and intestinal tissues by 58.8% and 52.2%, respectively, and alleviated the pathological damage induced by PS-NPs. Adequate vitamin D significantly increased the content of serotonin (5-HT) and reduced the anxiety-like behavior of zebrafish caused by PS-NPs exposure. Virus metagenome showed that PS-NPs exposure affected the composition and abundance of zebrafish intestinal viruses. Differentially expressed viruses in the vitamin D-low and vitamin D-high group affected the secretion of brain neurotransmitters in zebrafish. Virus AF191073 was negatively correlated with neurotransmitter 5-HT, whereas KT319643 was positively correlated with malondialdehyde (MDA) content and the expression of cytochrome 1a1 (cyp1a1) and cytochrome 1b1 (cyp1b1) in the intestine. This suggests that AF191073 and KT319643 may be key viruses that mediate the vitamin D reduction in neurotoxicity and immunotoxicity induced by PS-NPs.
CONCLUSION
Vitamin D can alleviate neurotoxicity and immunotoxicity induced by PS-NPs exposure by directionally altering the gut virome. These findings highlight the potential of vitamin D to alleviate the brain-gut-virome disorder caused by PS-NPs exposure and suggest potential therapeutic strategies to reduce the risk of NPs toxicity in aquaculture, that is, adding adequate vitamin D to diet. Video Abstract.
Topics: Animals; Polystyrenes; Zebrafish; Vitamin D; Nanoparticles; Microplastics; Serotonin; Virome; Water Pollutants, Chemical; Brain; Cytochromes
PubMed: 38008755
DOI: 10.1186/s40168-023-01680-1 -
Particle and Fibre Toxicology Nov 2023Microplastics and nanoplastics (MNPs) are emerging environmental contaminants detected in human samples, and have raised concerns regarding their potential risks to...
BACKGROUND
Microplastics and nanoplastics (MNPs) are emerging environmental contaminants detected in human samples, and have raised concerns regarding their potential risks to human health, particularly neurotoxicity. This study aimed to investigate the deleterious effects of polystyrene nanoplastics (PS-NPs, 50 nm) and understand their mechanisms in inducing Parkinson's disease (PD)-like neurodegeneration, along with exploring preventive strategies.
METHODS
Following exposure to PS-NPs (0.5-500 μg/mL), we assessed cytotoxicity, mitochondrial integrity, ATP levels, and mitochondrial respiration in dopaminergic-differentiated SH-SY5Y cells. Molecular docking and dynamic simulations explored PS-NPs' interactions with mitochondrial complexes. We further probed mitophagy's pivotal role in PS-NP-induced mitochondrial damage and examined melatonin's ameliorative potential in vitro. We validated melatonin's intervention (intraperitoneal, 10 mg/kg/d) in C57BL/6 J mice exposed to 250 mg/kg/d of PS-NPs for 28 days.
RESULTS
In our in vitro experiments, we observed PS-NP accumulation in cells, including mitochondria, leading to cell toxicity and reduced viability. Notably, antioxidant treatment failed to fully rescue viability, suggesting reactive oxygen species (ROS)-independent cytotoxicity. PS-NPs caused significant mitochondrial damage, characterized by altered morphology, reduced mitochondrial membrane potential, and decreased ATP production. Subsequent investigations pointed to PS-NP-induced disruption of mitochondrial respiration, potentially through interference with complex I (CI), a concept supported by molecular docking studies highlighting the influence of PS-NPs on CI. Rescue experiments using an AMPK pathway inhibitor (compound C) and an autophagy inhibitor (3-methyladenine) revealed that excessive mitophagy was induced through AMPK/ULK1 pathway activation, worsening mitochondrial damage and subsequent cell death in differentiated SH-SY5Y cells. Notably, we identified melatonin as a potential protective agent, capable of alleviating PS-NP-induced mitochondrial dysfunction. Lastly, our in vivo experiments demonstrated that melatonin could mitigate dopaminergic neuron loss and motor impairments by restoring mitophagy regulation in mice.
CONCLUSIONS
Our study demonstrated that PS-NPs disrupt mitochondrial function by affecting CI, leading to excessive mitophagy through the AMPK/ULK1 pathway, causing dopaminergic neuron death. Melatonin can counteract PS-NP-induced mitochondrial dysfunction and motor impairments by regulating mitochondrial autophagy. These findings offer novel insights into the MNP-induced PD-like neurodegenerative mechanisms, and highlight melatonin's protective potential in mitigating the MNP's environmental risk.
Topics: Humans; Mice; Animals; Mitophagy; AMP-Activated Protein Kinases; Polystyrenes; Microplastics; Dopaminergic Neurons; Melatonin; Molecular Docking Simulation; Plastics; Mice, Inbred C57BL; Neuroblastoma; Reactive Oxygen Species; Adenosine Triphosphate; Autophagy-Related Protein-1 Homolog; Intracellular Signaling Peptides and Proteins
PubMed: 37993864
DOI: 10.1186/s12989-023-00556-4 -
Journal of Biomedical Optics Jun 2024The ability to observe and monitor cell density and morphology has been imperative for assessing the health of a cell culture and for producing high quality, high yield... (Comparative Study)
Comparative Study
SIGNIFICANCE
The ability to observe and monitor cell density and morphology has been imperative for assessing the health of a cell culture and for producing high quality, high yield cell cultures for decades. Microcarrier-based cultures, used for large-scale cellular expansion processes, are not compatible with traditional visualization-based methods, such as widefield microscopy, due to their thickness and material composition.
AIM
Here, we assess the optical imaging compatibilities of commercial polystyrene microcarriers versus custom-fabricated gelatin methacryloyl (gelMA) microcarriers for non-destructive and non-invasive visualization of the entire microcarrier surface, direct cell enumeration, and sub-cellular visualization of mesenchymal stem/stromal cells.
APPROACH
Mie scattering and wavefront error simulations of the polystyrene and gelMA microcarriers were performed to assess the potential for elastic scattering-based imaging of adherent cells. A Zeiss Z.1 light-sheet microscope was adapted to perform light-sheet tomography using label-free elastic scattering contrast from planar side illumination to achieve optical sectioning and permit non-invasive and non-destructive, , three-dimensional, high-resolution visualization of cells cultured on microcarriers.
RESULTS
The polystyrene microcarrier prevents visualization of cells on the distal half of the microcarrier using either fluorescence or elastic scattering contrast, whereas the gelMA microcarrier allows for high fidelity visualization of cell morphology and quantification of cell density using light-sheet fluorescence microscopy and tomography.
CONCLUSIONS
The combination of optical-quality gelMA microcarriers and label-free light-sheet tomography will facilitate enhanced control of bioreactor-microcarrier cell culture processes.
Topics: Polystyrenes; Mesenchymal Stem Cells; Hydrogels; Cell Adhesion; Optical Imaging; Humans; Gelatin; Cell Culture Techniques; Cells, Cultured; Animals
PubMed: 38872791
DOI: 10.1117/1.JBO.29.S2.S22708 -
The Science of the Total Environment May 2024Polystyrene foam is widely used due to its lightweight, impact resistance, and excellent thermal insulation properties. Meanwhile, weak adhesion between beads in...
Polystyrene foam is widely used due to its lightweight, impact resistance, and excellent thermal insulation properties. Meanwhile, weak adhesion between beads in polystyrene foam leads to fragmentation, generating a substantial amount of microplastics (<5 mm). Such polystyrene foam debris littered on beaches diminishes the aesthetic value of coastal areas, negatively impacting tourism. Due to its density lower than other plastics, polystyrene foam macroplastics float on the sea surface and, thus, they are significantly influenced by wind drag during oceanic transport. In contrast, polystyrene foam microplastics drifting beneath the sea surface are carried mostly by ocean currents. These properties of polystyrene foam macroplastics and microplastics hinder the elucidation of their transport, distribution, and fate in nature, despite their potential to adversely impact marine ecosystems. To elucidate the generation, transport, and fragmentation processes of polystyrene foam ocean plastics, we conducted concurrent visual observations and surface net towing from seven training vessels around Japan during 2014-2020. Overall, the abundances of polystyrene foam ocean plastics were higher in the Sea of Japan than in the North Pacific south of Japan. The average abundances of polystyrene foam microplastics and macroplastics were 0.33 pieces/m and 0.45 pieces/km, respectively, over the entire sea area around Japan. In the Sea of Japan, the peak abundances of polystyrene foam macroplastics occurred in upstream of the Tsushima Current, while the peak for microplastics occurred downstream, suggesting that continuous fragmentation occurred during transport between the two peaks. Backward-in-time particle tracking model experiments suggested that the sources of polystyrene foam macroplastics observed in the Sea of Japan included aquaculture buoys and styrene debris beached around the Tsushima Strait. The present study demonstrated that reducing the release of polystyrene foam aquaculture floats will likely diminish the abundance of ocean plastics in the Sea of Japan.
PubMed: 38442765
DOI: 10.1016/j.scitotenv.2024.171421 -
Journal of Pharmacy & Pharmaceutical... 2023Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease (CKD) that increases in prevalence with the decline of glomerular fltration rate... (Review)
Review
Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease (CKD) that increases in prevalence with the decline of glomerular fltration rate (GFR). Another risk of hyperkalemia is the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and/or mineralocorticoid receptor antagonists (MRAs) in managing CKD and proteinuria. The treatment of chronic hyperkalemia is challenging especially for outpatients. Treatment options for hyperkalemia include the potassium exchange resins of which two new potassium binders, Patiromer Sorbitex Calcium, and Sodium Zirconium Cyclosilicate (SZC) have demonstrated their clinical efficacy in reducing serum potassium with a positive safety profile. The old potassium exchange resin sodium polystyrene sulfonate (Kayexalate™) has some negative side effects including colonic necrosis, hypomagnesemia, and hypernatremia. In this review and literature search, we compare the available oral potassium exchange resins, highlight their advantages and disadvantages and comment on efficacy and safety parameters specifically in CKD patients.
Topics: Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 38173862
DOI: 10.3389/jpps.2023.11892 -
Materials (Basel, Switzerland) Oct 2023Based on flexible polyurethane foam (FPUF), which is reversible after compression, and expanded polystyrene foam (EPS), which has a high cushioning energy absorption...
Based on flexible polyurethane foam (FPUF), which is reversible after compression, and expanded polystyrene foam (EPS), which has a high cushioning energy absorption capacity, the parallel and series combinations of FPUF and EPS are provided. According to experimental data of FPUF and EPS uniaxial compression large deformation, the mechanical properties and cushioning effectiveness of the FPUF-EPS combination materials with different structural scale parameters were investigated by theory analysis and finite element simulation. The mechanical response and the cushioning effectiveness influencing factors of FPUF-EPS parallel (FE-P) and FPUF-EPS series (FE-S) combination materials under single compressive load, single-impact load, and multiple compressive loads were obtained. The differences in mechanical properties and cushioning effectiveness of FE-P, FE-S, FPUF, and EPS are analyzed. The influence law of structural scale parameters and load strength on the mechanical properties and cushioning effectiveness of FE-P and FE-S is provided. It indicates that the cushion properties of combination materials should be adjusted to satisfy product protection requirements. It is beneficial for the design optimization of cushioning and packaging protection.
PubMed: 37959483
DOI: 10.3390/ma16216886 -
Environmental Health Perspectives Feb 2024Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established...
BACKGROUND
Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear.
OBJECTIVES
This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms and .
METHODS
We assessed the impact of polystyrene nanospheres (PNSs; , ) on HMS-induced MCF-7 cell proliferation (HMS: , equivalent to ) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS () with or without PNSs (, ) for 21 d. EDEs were evaluated through gonadal histopathology, fertility tests, steroid hormone synthesis, and gene expression changes in the hypothalamus-pituitary-gonad-liver (HPGL) axis.
RESULTS
Coexposure of HMS and PNSs resulted in higher expression of estrogen receptor () and the mRNAs of target genes (, , and ), a greater estrogen-responsive element transactivation activity, and synergistic stimulation on MCF-7 cell proliferation. Knockdown of serum and glucocorticoid-regulated kinase 1 (SGK1) rescued the MCF-7 cell proliferation induced by PNSs alone or in combination with HMS. In zebrafish, coexposure showed higher expression of and promoted ovary development but inhibited spermatogenesis. In addition, coexposure led to lower egg hatchability, higher embryonic mortality, and greater larval malformation. Coexposure also modulated steroid hormone synthesis genes (, , , , and ), and resulted in higher () release in females. Conversely, males showed lower testosterone, , and gene expressions of , , , , and .
DISCUSSION
PNS exposure exacerbated HMS-induced estrogenic effects via SGK1 up-regulation in MCF-7 cells and disrupting the HPGL axis in zebrafish, with gender-specific patterns. This offers new mechanistic insights and health implications of MNP and contaminant coexposure. https://doi.org/10.1289/EHP13696.
Topics: Adult; Female; Humans; Male; Animals; Nanospheres; Zebrafish; MCF-7 Cells; Polystyrenes; Estrogens; Glucocorticoids; Steroids
PubMed: 38381479
DOI: 10.1289/EHP13696 -
Hepatology Communications Nov 2023Cholesterol levels and bile acid metabolism are important drivers of metabolic dysfunction-associated steatohepatitis (MASH) progression. Using a mouse model, we...
BACKGROUND
Cholesterol levels and bile acid metabolism are important drivers of metabolic dysfunction-associated steatohepatitis (MASH) progression. Using a mouse model, we investigated the mechanism by which cholesterol exacerbates MASH and the effect of colestyramine (a bile acid adsorption resin) and elobixibat (an apical sodium-dependent bile acid transporter inhibitor) concomitant administration on bile acid adsorption and MASH status.
METHODS
Mice were fed a high-fat high-fructose diet with varying concentrations of cholesterol to determine changes in fatty liver according to liver status, water intake, defecation status, insulin resistance, bile acid levels, intestinal permeability, atherosclerosis (in apolipoprotein E knockout mice), and carcinogenesis (in diethylnitrosamine mice). Using small interfering ribonucleic acid (siRNA), we evaluated the effect of sterol regulatory element binding protein 1c (SREBP1c) knockdown on triglyceride synthesis and fatty liver status following the administration of elobixibat (group E), colestyramine (group C), or both (group EC).
RESULTS
We found greater reductions in serum alanine aminotransferase levels, serum lipid parameters, serum primary bile acid concentrations, hepatic lipid levels, and fibrosis area in EC group than in the monotherapy groups. Increased intestinal permeability and watery diarrhea caused by elobixibat were completely ameliorated in group EC. Group EC showed reduced plaque formation rates in the entire aorta and aortic valve of the atherosclerosis model, and reduced tumor counts and tumor burden in the carcinogenesis model.
CONCLUSIONS
Excessive free cholesterol in the liver can promote fatty liver disease. Herein, combination therapy with EC effectively reduced free cholesterol levels in MASH model mice. Our study provides strong evidence for combination therapy as an effective treatment for MASH.
Topics: Animals; Mice; Cholestyramine Resin; Bile Acids and Salts; Non-alcoholic Fatty Liver Disease; Disease Models, Animal; Atherosclerosis; Carcinogenesis
PubMed: 37902528
DOI: 10.1097/HC9.0000000000000285 -
Ecotoxicology and Environmental Safety Mar 2024In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined...
In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 μg/mL) and TCS (15 μM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2-KEAP1-HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.
Topics: Female; Humans; Reactive Oxygen Species; Triclosan; Antioxidants; Kelch-Like ECH-Associated Protein 1; Microplastics; Polystyrenes; NF-E2-Related Factor 2; Oxidative Stress; Granulosa Cells
PubMed: 38402792
DOI: 10.1016/j.ecoenv.2024.116121 -
Environment International Apr 2024Microplastics (MPs) are pervasive pollutants in the natural environment and contribute to increased levels of illness in both animals and humans. However, thespecific...
Microplastics (MPs) are pervasive pollutants in the natural environment and contribute to increased levels of illness in both animals and humans. However, thespecific impacts of MPs on skin damage and alopeciaare not yet well understood. In this study, we have examined the effects of two types of polystyrene MPs (pristine and aged) on skin and hair follicle damage in mice. UV irradiation changed the chemical and physical properties of the aged MPs, including functional groups, surface roughness, and contact angles. In both in vivo and in vitro experiments, skin and cell injuries related to oxidative stress, apoptosis, tight junctions (TJs), alopecia, mitochondrial dysfunction, and other damages were observed. Mechanistically, MPs and aged MPs can induce TJs damage via the oxidative stress pathway and inhibition of antioxidant-related proteins, and this can lead to alopecia. The regulation of cell apoptosis was also observed, and this is involved in the ROS-mediated mitochondrial signaling pathway. Importantly, aged MPs showed exacerbated toxicity, which may be due to their elevated surface irregularities and altered chemical compositions. Collectively, this study suggests a potential therapeutic approach for alopecia and hair follicle damage caused by MPs pollution.
Topics: Alopecia; Microplastics; Oxidative Stress; Apoptosis; Animals; Mice; Polystyrenes; Tight Junctions; Skin; Hair Follicle; Reactive Oxygen Species
PubMed: 38593689
DOI: 10.1016/j.envint.2024.108638