Synergistic toxic effects of high-strength ammonia and ZnO nanoparticles on biological nitrogen removal systems and role of exogenous C10-HSL regulation.

The inhibitory effects of zinc oxide nanoparticles (ZnO NPs) and impacts of N-acyl-homoserine lactone (AHL)-based quorum sensing (QS) on biological nitrogen removal (BNR) performance have been well-investigated. However, the effects of ammonia nitrogen (NH4+-N) concentrations on NP toxicity and AHL regulation have seldom been addressed yet. This study consulted on the impacts of ZnO NPs on BNR systems when high NH4+-N concentration was available. The synergistic toxic effects of high-strength NH4+-N (200 mg/L) and ZnO NPs resulted in decreased ammonia oxidation rates and dropped the nitrogen removal efficiencies by 17.5% ± 0.2%. The increased extracellular polymeric substances (EPS) production was observed in response to the high NH4+-N and ZnO NP stress, which indicated the defense mechanism against the toxic effects in the BNR systems was stimulated. Furthermore, the regulatory effects of exogenous N-decanoyl-homoserine lactone (C10-HSL)-mediated QS system on NP-stressed BNR systems were revealed to improve the BNR performance under different NH4+-N concentrations. The C10-HSL regulated the intracellular reactive oxygen species levels, denitrification functional enzyme activities, and antioxidant enzyme activities, respectively. This probably synergistically enhanced the defense mechanism against NP toxicity. However, compared to the low NH4+-N concentration of 60 mg/L, the efficacy of C10-HSL was inhibited at high NH4+-N levels of 200 mg/L. The findings provided the significant application potential of QS system for BNR when facing toxic compound shock threats.

Effect of titanium dioxide nanoparticle (TiO2-NP) exposure in a novel Amur sturgeon Acipenser schrenckii hepatocyte cell line.

In vitro cell culture is crucial for predicting the toxicity of titanium dioxide nanoparticle (TiO2-NP). However, assessing the toxicity of TiO2-NPs in sturgeon remains difficult given the lack of sufficient cell lines. We established and characterized the first hepatocyte cell line from Acipenser schrenckii liver tissue (ASL). This ASL cell line proliferated well in Dulbecco's modified Eagle's medium at 25°C and 10% fetal bovine serum. ASL cells with a chromosome number of 244 were successfully transfected with the pEGFP-N3 plasmid. The ASL cell line's origin was verified as A. schrenckii through mitochondrial cytochrome C oxidase I and mitochondrial 16S ribosomal RNA (rRNA) sequencing. Using the ASL cell line as an in vitro model, we found that TiO2-NP exposure decreased the viability and promoted the damage of ASL cells (96-h LC50 = 331.8 µg mL-1). Increased reactive oxygen species and malondialdehyde levels in ASL cells suggested oxidative stress under TiO2-NP exposure. We also observed dysregulation of aspartate aminotransferase and alanine aminotransferase levels. By detecting calcium ions and mitochondrial membrane potential indicators, we found that the apoptotic pathway induced by endoplasmic reticulum stress played a major role at low concentrations of TiO2-NP-induced stress. Both mitochondria-mediated and endoplasmic reticulum stress promoted apoptosis under increasing TiO2-NP concentrations. In conclusion, the ASL cell line established in this study is a useful in vitro model for toxicological studies of TiO2-NP exposure in fish.

In vitro determination of genotoxicity and cytotoxicity induced by stainless steel brackets with and without surface coating in cultures of oral mucosal cells.

BACKGROUND: Orthodontics is a speciality of dentistry that uses a plethora of devices made from myriad materials to manage various malocclusions. Prolonged contact of orthodontic appliances with oral tissues can lead to cellular damage, highlighting the need for biocompatible materials to mitigate health risks. OBJECTIVES: To analyze the genotoxicity and cytotoxicity produced by metal brackets and coated metallic brackets with polymeric and nanoparticle coatings in oral mucosal cells. MATERIALS & METHODS: The current study compares the toxicity of 3 different types of orthodontic brackets with control groups of oral mucosal cells. Each of the three treatment groups consisted of 10 samples of orthodontic brackets: stainless steel brackets(Group 1), nanoparticle-coated brackets(Group 2), and polymeric-coated brackets(Group 3) exposed to corrosion eluates employing an oral biomimicry model. Two types of oral mucosal cells- Human Gingival Fibroblasts and Buccal Epithelial Cells were used to study the cytotoxic and/or genotoxic effects of the elutes. Intergroup comparisons were conducted using one-way analysis of variance, while scanning electron microscopy evaluated surface characteristic. RESULTS: The interaction between metal ions and oral mucosal cells showed no statistically significant difference for toxicity assays between the three groups(p > 0.005). However, polymeric and nanoparticle-coated groups showed reduced cellular differentiation when compared with conventional stainless-steel brackets. CONCLUSION: This in-vitro study shows that polymeric or nanoparticle coating of conventional metal brackets aids in enhancing corrosion-resistant characteristics of orthodontic appliances and reduces the toxic oral environment created by metal release in the oral cavity.

Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study.

BACKGROUND: Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. OBJECTIVE: The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. METHODS: In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. RESULTS: In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. CONCLUSIONS: As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63176.

Toxicological screening of zinc oxide nanoparticles in mongrel dogs after seven days of repeated subcutaneous injections.

Zinc oxide nanoparticles (ZnO NPs) have recently been applied in various veterinary and medical fields, however, the toxicological evaluations of these NPs in dogs are lacking. Therefore, the current study is designed to assess the impact of exposure to daily subcutaneous (SC) injections of ZnO NPs at different concentrations on various organs of mongrel dogs. Nine dogs were randomly divided into three groups (n = 3 for each) as follows: group (1) served as the control group, whereas groups (2&3) received SC injections of 50 and 100 ppm ZnO NPs (8 and 16 µg/kg bwt), respectively, once/day for 7 days. Our results revealed that ZnO NPs disrupted the oxidant/antioxidant balance in the lungs, liver, and kidneys of dogs in a dose-dependent manner. ZnO NPs induced dose-dependent radiological, ultrasonographical, and histopathological alterations in various organs especially lungs, spleen, liver, and kidneys along with disturbance in both liver and kidney biomarkers levels. Most organs of both ZnO NPs receiving groups displayed strong caspase-3 protein expression. Additionally, it upregulates the transcriptase levels of TNF-α and VEGF, as well as downregulates the antiapoptotic gene IL-10 in lung, kidney, and liver tissue homogenates. It was concluded that the daily SC injections of dogs with ZnO NPs at concentrations of 50 and 100 ppm caused extensive oxidative stress damage in various organs which provoked serious pathological processes such as apoptosis and inflammation.

Machine Learning-Aided 3D Dynamic SERS Strategy for Physiological Mapping: Biotoxicity of Environmentally Dimensional Aged Nanoplastics and Corresponding Protein Corona Complexes.

Nanoplastics (NPs) are emerging pollutants that undergo inevitable aging in the environment, raising concerns about human exposure and health hazards. Research on the cytotoxicity of various polymer types of NPs, aged nanoplastics (aNPs), and their interactions with proteins (aNPs-protein corona) is still nascent. Traditional cytotoxicity detection methods often rely on end point assays with restricted temporal resolution and analysis of single or multiple biomarkers. Here, we propose a novel approach integrating the 3D dynamic SERS strategy (DSS) with machine learning to rapidly analyze the cell fate and death modes induced by NPs, aNPs, and aNPs-protein corona complexes at the molecular level. PS, PVC, PMMA, and PC products from the water environment were used to prepare the corresponding NPs, and the impact of UV irradiation on their physicochemical properties was examined. DSS systematically maps the molecular changes in the cellular secretome caused by these NPs. Machine learning effectively extracts information from complex spectra, differentiating between biological samples. Results show prolonged UV exposure increases cell sensitivity to ferroptosis and cytotoxicity in various aNPs, while the protein corona on aNPs significantly mitigates toxicity associated with surface oxygen-containing functional groups, resulting in a reduced similarity to ferroptosis signatures. 3D DSS with machine learning technique analyzes the overall metabolite profile at the molecular level rather than individual biomarkers. This study is the first attempt to compare the biotoxicity of diverse polymer NPs, aNPs, and aNPs-protein coronas at cellular and molecular levels in human hepatocytes, enhancing our understanding of the complex biological impacts of NPs.

Maternal exposure to nanopolystyrene induces neurotoxicity in offspring through P53-mediated ferritinophagy and ferroptosis in the rat hippocampus.

There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring.

Cell-nanoparticle stickiness and dose delivery in a multi-model in silico platform: DosiGUI.

BACKGROUND: It is well-known that nanoparticles sediment, diffuse and aggregate when dispersed in a fluid. Once they approach a cell monolayer, depending on the affinity or "stickiness" between cells and nanoparticles, they may adsorb instantaneously, settle slowly - in a time- and concentration-dependent manner - or even encounter steric hindrance and rebound. Therefore, the dose perceived by cells in culture may not necessarily be that initially administered. Methods for quantifying delivered dose are difficult to implement, as they require precise characterization of nanoparticles and exposure scenarios, as well as complex mathematical operations to handle the equations governing the system dynamics. Here we present a pipeline and a graphical user interface, DosiGUI, for application to the accurate nano-dosimetry of engineered nanoparticles on cell monolayers, which also includes methods for determining the parameters characterising nanoparticle-cell stickiness. RESULTS: We evaluated the stickiness for 3 industrial nanoparticles (TiO2 - NM-105, CeO2 - NM-212 and BaSO4 - NM-220) administered to 3 cell lines (HepG2, A549 and Caco-2) and subsequently estimated corresponding delivered doses. Our results confirm that stickiness is a function of both nanoparticle and cell type, with the stickiest combination being BaSO4 and Caco-2 cells. The results also underline that accurate estimations of the delivered dose cannot prescind from a rigorous evaluation of the affinity between the cell type and nanoparticle under investigation. CONCLUSION: Accurate nanoparticle dose estimation in vitro is crucial for in vivo extrapolation, allowing for their safe use in medical and other applications. This study provides a computational platform - DosiGUI - for more reliable dose-response characterization. It also highlights the importance of cell-nanoparticle stickiness for better risk assessment of engineered nanomaterials.

[N-acetylcysteine regulates NF-κB signaling pathway alleviates the pulmonary toxicity induced by indium-tin oxide nanoparticles in rats].

Objective: The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling. Methods: In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed. Results: Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-ß) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased (P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased (P<0.05), the levels of proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased (P<0.05), and the levels of NF-κB p65, IKK-ß, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased (P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased (P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-ß in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased (P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-ß in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased (P<0.05) . Conclusion: The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.

Addressing the relevance of polystyrene nano- and microplastic particles used to support exposure, toxicity and risk assessment: implications and recommendations.

BACKGROUND: There has been an exponential increase in the number of studies reporting on the toxicological effects associated with exposure to nano and microplastic particles (NMPs). The majority of these studies, however, have used monodispersed polystyrene microspheres (PSMs) as 'model' particles. Here we review the differences between the manufacture and resulting physicochemical properties of polystyrene used in commerce and the PSMs most commonly used in toxicity studies. MAIN BODY: In general, we demonstrate that significant complexity exists as to the properties of polystyrene particles. Differences in chemical composition, size, shape, surface functionalities and other aspects raise doubt as to whether PSMs are fit-for-purpose for the study of potential adverse effects of naturally occurring NMPs. A realistic assessment of potential health implications of the exposure to environmental NMPs requires better characterisation of the particles, a robust mechanistic understanding of their interactions and effects in biological systems as well as standardised protocols to generate relevant model particles. It is proposed that multidisciplinary engagement is necessary for the development of a timely and effective strategy towards this end. We suggest a holistic framework, which must be supported by a multidisciplinary group of experts to work towards either providing access to a suite of environmentally relevant NMPs and/or developing guidance with respect to best practices that can be adopted by research groups to generate and reliably use NMPs. It is emphasized that there is a need for this group to agree to a consensus regarding what might best represent a model NMP that is consistent with environmental exposure for human health, and which can be used to support a variety of ongoing research needs, including those associated with exposure and hazard assessment, mechanistic toxicity studies, toxicokinetics and guidance regarding the prioritization of plastic and NMPs that likely represent the greatest risk to human health. It is important to acknowledge, however, that establishing a multidisciplinary group, or an expert community of practice, represents a non-trivial recommendation, and will require significant resources in terms of expertise and funding. CONCLUSION: There is currently an opportunity to bring together a multidisciplinary group of experts, including polymer chemists, material scientists, mechanical engineers, exposure and life-cycle assessment scientists, toxicologists, microbiologists and analytical chemists, to provide leadership and guidance regarding a consensus on defining what best represents environmentally relevant NMPs. We suggest that given the various complex issues surrounding the environmental and human health implications that exposure to NMPs represents, that a multidisciplinary group of experts are thus critical towards helping to progress the harmonization and standardization of methods.

Intergenerational neurotoxicity of polystyrene nanoplastics in offspring mice is mediated by dysfunctional microbe-gut-brain axis.

Nanoplastics (NPs) are ubiquitous in daily life, posing potential risks to the environment and human. While their negative effects on parental organisms have been extensively studied, intergenerational effects are still in the early stages of investigation. Here, we aimed to investigate the impact of maternal exposure to an environmentally relevant level of polystyrene NPs (PSNPs, 100 nm) during gestation and lactation (∼32 days, 50 µg/mouse/day) on neurotoxicity mediated by the microbe-gut-brain axis in offspring mice. Maternal PSNPs exposure significantly increased brain TNF-α level and microglia by 1.43 and 1.48 folds respectively, compared to control, accompanied by nuclear pyknosis and cell vacuolization in cortex and hippocampus. Targeted neurotransmitter metabolomics analysis revealed dysregulation in dopamine and serotonin metabolism. Specifically, dopamine levels increased significantly from 0.007 ng/L to 0.015 ng/L, while N-acetylseroton and 3,4-dihydroxyphenylacetic acid decreased significantly from 0.002 and 0.929 ng/L to 0.001 and 0.680 ng/L, respectively. Through a combination of 16S rRNA sequencing and biochemical analysis, we discovered that maternal PSNPs exposure led to a depletion of anti-inflammatory bacteria and an enrichment of pro-inflammatory bacteria resulting in intestinal barrier damage, elevated levels of lipopolysaccharide in blood, and subsequent activation of neuroinflammation. Meanwhile, gut bacteria dysbiosis interfered with communication between gut and brain by dysregulating neurotransmitter synthesis, as evidenced by significant associations between neurotransmitter-related bacteria (Akkermansia, Family_XIII_AD3011_group, Lachnoclostridium) and dopamine/serotonin related metabolites. Furthermore, transcriptional alterations in dopamine and serotonin related pathways were observed in the enteric nervous system, suggesting abnormal signal transduction from gut to brain contributes to neurotoxicity. This study provides new insights into NPs-induced neurotoxicity within the context of microbe-gut-brain axis and highlights the risk of cerebral dysfunction in offspring with maternal NPs exposure.

Single and combined effects of titanium (TiO2) and zinc (ZnO) oxide nanoparticles in the rainbow trout gill cell line RTgill-W1.

Understanding the environmental impact of nanoparticle (NP) mixtures is essential to accurately assess the risk they represent for aquatic ecosystems. However, although the toxicity of individual NPs has been extensively studied, information regarding the toxicity of combined NPs is still comparatively rather scarce. Hence, this research aimed to investigate the individual and combined toxicity mechanisms of two widely consumed nanoparticles, zinc oxide (ZnO NPs) and titanium dioxide (TiO2 NPs), using an in vitro model, the RTgill-W1 rainbow trout gill epithelial cell line. Sublethal concentrations of ZnO NPs (0.1 µg mL-1) and TiO2 (30 µg mL-1) and a lethal concentration of ZnO NPs causing 10% mortality (EC10, 3 µg mL-1) were selected based on cytotoxicity assays. Cells were then exposed to the NPs at the selected concentrations alone and to their combination. Cytotoxicity assays, oxidative stress markers, and targeted gene expression analyses were employed to assess the NP cellular toxicity mechanisms and their effects on the gill cells. The cytotoxicity of the mixture was identical to the one of ZnO NPs alone. Enzymatic and gene expression (nrf2, gpx, sod) analyses suggest that none of the tested conditions induced a strong redox imbalance. Metal detoxification mechanisms (mtb) and zinc transportation (znt1) were affected only in cells exposed to ZnO NPs, while tight junction proteins (zo1 and cldn1), and apoptosis protein p53 were overexpressed only in cells exposed to the mixture. Osmoregulation (Na + /K + ATPase gene expression) was not affected by the tested conditions. The overall results suggest that the toxic effects of ZnO and TiO2 NPs in the mixture were significantly enhanced and could result in the disruption of the gill epithelium integrity. This study provides new insights into the combined effects of commonly used nanoparticles, emphasizing the importance of further investigating how their toxicity may be influenced in mixtures.

Mechanistic Insights into Toxicity of Titanium Dioxide Nanoparticles at the Micro- and Macro-levels.

Titanium oxide nanoparticles (TiO2 NPs) have been regarded as a legacy nanomaterial due to their widespread usage across multiple fields. The TiO2 NPs have been and are still extensively used as a food and cosmetic additive and in wastewater and sewage treatment, paints, and industrial catalysis as ultrafine TiO2. Recent developments in nanotechnology have catapulted it into a potent antibacterial and anticancer agent due to its excellent photocatalytic potential that generates substantial amounts of highly reactive oxygen radicals. The method of production, surface modifications, and especially size impact its toxicity in biological systems. The anatase form of TiO2 (<30 nm) has been found to exert better and more potent cytotoxicity in bacteria as well as cancer cells than other forms. However, owing to the very small size, anatase particles are able to penetrate deep tissue easily; hence, they have also been implicated in inflammatory reactions and even as a potent oncogenic substance. Additionally, TiO2 NPs have been investigated to assess their toxicity to large-scale ecosystems owing to their excellent reactive oxygen species (ROS)-generating potential compounded with widespread usage over decades. This review discusses in detail the mechanisms by which TiO2 NPs induce toxic effects on microorganisms, including bacteria and fungi, as well as in cancer cells. It also attempts to shed light on how and why it is so prevalent in our lives and by what mechanisms it could potentially affect the environment on a larger scale.

Molecular mechanisms of zinc oxide nanoparticles neurotoxicity.

Zinc oxide nanoparticles (ZnONPs) are widely used in industry and biomedicine. A growing body of evidence demonstrates that ZnONPs exposure may possess toxic effects to a variety of tissues, including brain. Therefore, the objective of the present review was to summarize existing evidence on neurotoxic effects of ZnONPs and discuss the underlying molecular mechanisms. The existing laboratory data demonstrate that both in laboratory rodents and other animals ZnONPs exposure results in a significant accumulation of Zn in brain and nervous tissues, especially following long-term exposure. As a result, overexposure to ZnONPs causes oxidative stress and cell death, both in neurons and glial cells, by induction of apoptosis, necrosis and ferroptosis. In addition, ZnONPs may induce neuroinflammation through the activation of nuclear factor kappa B (NF-κB), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and lipoxygenase (LOX) signaling pathways. ZnONPs exposure is associated with altered cholinergic, dopaminergic, serotoninergic, as well as glutamatergic and γ-aminobutyric acid (GABA)-ergic neurotransmission, thus contributing to impaired neuronal signal transduction. Cytoskeletal alterations, as well as impaired autophagy and mitophagy also contribute to ZnONPs-induced brain damage. It has been posited that some of the adverse effects of ZnONPs in brain are mediated by altered microRNA expression and dysregulation of gut-brain axis. Furthermore, in vivo studies have demonstrated that ZnONPs exposure induced anxiety, motor and cognitive deficits, as well as adverse neurodevelopmental outcome. At the same time, the relevance of ZnONPs-induced neurotoxicity and its contribution to pathogenesis of neurological diseases in humans are still unclear. Further studies aimed at estimation of hazards of ZnONPs to human brain health and the underlying molecular mechanisms are warranted.

Hazardous effects of nickel ferrite nanoparticles and nickel chloride in early life stages of the freshwater snail Biomphalaria glabrata (Say, 1818).

Nickel ferrite nanoparticles (NiF NPs) have growing applications in biomedical and nanomedicine fields. However, knowledge concerning their ecotoxicity during the early developmental stages of invertebrates, such as gastropods, remains scarce. Thus, the current study aimed to evaluate whether NiF NPs and nickel chloride (NiCl2) induce toxic effects on embryos and newly hatched snails of freshwater species Biomphalaria glabrata (Say, 1818). NiF NPs were synthesized and characterized by multiple techniques, and their ecotoxicity was assessed by Biomphalaria embryotoxicity test (BET) during 144 h of exposure and an acute toxicity test (96 h) using newly hatched snails. NiF NPs induced mortality, developmental delay, reduced hatching rate, and promoted morphological changes in B. glabrata. Also, NiF NPs induced higher toxicity in embryos than in newly hatched B. glabrata. Overall, results showed that the early developmental stages of gastropods are a target group for nanoparticle toxicity in freshwater ecosystems.

In vitro safety profile and phyto-ecotoxicity assessment of the eco-friendly calcium oxide nanoparticles.

The present study aims to evaluate the toxicity of the green calcium oxide nanoparticles (CaO-NPs) from golden linseed extract (Linum usitatissimum L.) by phytotoxicity in seeds (Daucus carota, Beet shankar, Lactuca sativa and Brassica oleracea), in vitro safety profile and soil toxicity for CaO-NPs solutions from 12.5 to 100 µg mL-1. Ecotoxicity analysis of the soil was conducted using XRD diffractograms, which revealed characteristic peaks of the nanoparticles at 37.35° (12.5, 25, 50, and 100 µg mL-1), as well as a peak at 67.34° (25 and 100 µg mL-1). Additionally, the in vitro safety assessment indicated favorable cell specification and regulation within the first 24 h, demonstrating reductions of 15.9 ± 0.2%, 17.9 ± 0.2%, 17.6 ± 0.2%, and 32.9 ± 0.2% to 12.5, 25, 50, and 100 µg mL-1, respectively. The dsDNA assay revealed initial protection and controlled release within the cells for 48 h. However, after 72 h, there was an increase of 20 ± 0.2%, 16 ± 0.2%, 32 ± 0.2%, and 43 ± 0.2% to 12.5, 25, and 50 µg mL-1. The analysis of ROS generation demonstrated a reduction of 40 ± 0.2%, 33 ± 0.2%, 20 ± 0.2%, and 9 ± 0.2% to 12.5, 25, 50, and 100 µg mL-1, respectively, within 72 h. When compared to the negative control (NC), there was an increase of 50 ± 0.2%, 56 ± 0.2%, 77 ± 0.2%, and 92 ± 0.2% at the same concentrations, suggesting that the nanoparticles generated free radicals, leading to cellular inflammation. This was attributed to the positive surface charge of the nanoparticles, resulting in reduced interaction with the cell membrane and the subsequent release of hydroxyl (•OH), which caused inflammatory processes in the cells. Therefore, CaO-NPs exhibited a low phytotoxicity and high cytocompatibility, while also promoting plant germination and growth.

Flubendiamide provokes oxidative stress, inflammation, miRNAs alteration, and cell cycle deregulation in human prostate epithelial cells: The attenuation impact of synthesized nano-selenium using Trichodermaaureoviride.

Flubendiamide (FBD) is a novel diamide insecticide extensively used with potential human health hazards. This research aimed to examine the effects of FBD on PrEC prostate epithelial cells, including Oxidative stress, pro-inflammatory responses, modifications in the expression of oncogenic and suppressor miRNAs and their target proteins, disruption of the cell cycle, and apoptosis. Additionally, the research investigated the potential alleviative effect of T-SeNPs, which are selenium nanoparticles biosynthesized by Trichoderma aureoviride, against the toxicity induced by FBD. Selenium nanoparticles were herein synthesized by Trichoderma aureoviride. The major capping metabolites in synthesized T-SeNPs were Isochiapin B and Quercetin 7,3',4'-trimethyl ether. T-SeNPs showed a spherical shape and an average size between 57 and 96.6 nm. FBD exposure (12 µM) for 14 days induced oxidative stress and inflammatory responses via overexpression of NF-κB family members. It also distinctly caused upregulation of miR-221, miR-222, and E2F2, escorted by downregulation of miR-17, miR-20a, and P27kip1. FBD encouraged PrEC cells to halt at the G1/S checkpoint. Apoptotic cells were drastically increased in FBD-treated sets. Treatment of T-SeNPs simultaneously with FBD revealed its antioxidant, anti-inflammatory, and antitumor activities in counteracting FBD-induced toxicity. Our findings shed light on the potential FBD toxicity that may account for the neoplastic transformation of epithelial cells in the prostate and the mitigating activity of eco-friendly synthesized T-SeNPs.

Polystyrene nanoplastics mediate skeletal toxicity through oxidative stress and the BMP pathway in zebrafish (Danio rerio).

The widespread presence of micro(nano)plastics (MNPs) has generated public concern. Studies have indicated that MNPs can accumulate in mammalian bones; however, research on the skeletal toxicity and underlying molecular mechanisms of MNPs in aquatic organisms remains limited. We subjected zebrafish embryos to three varying levels (1, 10, 100 µg/mL) of polystyrene nanoplastics (PSNPs) exposure over a period of 7 days in our research. The results revealed that PSNPs significantly reduced the body length and hatching rate of zebrafish, leading to skeletal deformities. mRNA level analysis showed significant upregulation of sp7, sparc, and smad1 genes transcription by PSNPs. Moreover, PSNPs markedly downregulated the mRNA levels associated with runx2a, bmp2a, and bmp4. Further investigations demonstrated that PSNPs dramatically increased ROS levels in zebrafish larvae, with significant downregulation of transcription levels of sod1 and cat genes, resulting in a sharp increase in transcription levels of apoptosis-related regulatory genes bcl-2 and bax. Furthermore, PSNPs led to a marked rise in Caspase 3 activity in zebrafish larvae, suggesting the initiation of apoptosis. PSNPs also notably inhibited alkaline phosphatase (AKP) activity. Compared to a 4-day exposure, a 7-day exposure to PSNPs intensified abnormalities across multiple indicators. In summary, our research indicates that PSNPs cause significant oxidative stress in zebrafish larvae, resulting in apoptosis. Moreover, PSNPs disrupt the transcription of genes related to skeletal development through the bone morphogenetic protein (BMP) pathway, further disrupting skeletal development processes and ultimately resulting in skeletal deformities in zebrafish larvae. This study provides new insights into the skeletal toxicity of MNPs.

Identifying resistance molecules in TiO2 nanoparticle-tolerant strains to facilitate the development of strategies for combating TiO2 nanoparticle pollution.

The severity of environmental pollution caused by TiO2 nanoparticles (nTiO2) is increasing, highlighting the urgent need for the development of strategies to combat nTiO2 pollution. Insights into resistance molecules from nTiO2-tolerant strains may facilitate such development. In this study, we utilized multi-omics, genetic manipulation, physiological and biochemical experiments to identify relevant resistance molecules in two strains (Physarum polycephalum Z259 and T83) tolerated to mixed-phase nTiO2 (MPnTiO2). We discovered that a competing endogenous RNA (ceRNA) network, comprising one long non-coding RNA (lncRNA), four microRNAs, and nine mRNAs, influenced metabolic rearrangement and was associated with significant resistance in these strains. Additionally, we found that the lncRNA in the ceRNAs network and certain small-weight metabolites associated with the ceRNA exhibited notable mitigation effects not only against MPnTiO2 but also against other types of nTiO2 with broad species applicability (they significantly improved the resistance of several non-nTiO2-tolerant cells/organisms in the laboratory and reduced cell damage of non-nTiO2-tolerant cells/organisms in highly suspected nTiO2-polluted areas of the real world). In summary, this study deepens our understanding of nTiO2-tolerant strains, provides valuable insights into resistance molecules in these strains, and facilitates the development of strategies to combat nTiO2 pollution.

Transgenerational response of germline histone acetyltransferases and deacetylases to nanoplastics at predicted environmental doses in Caenorhabditis elegans.

Nanoplastics could cause toxic effects on organism and their offsprings; however, how this transgenerational toxicity is formed remains largely unclear. We here examined potential involvement of germline histone acetylation regulation in modulating transgenerational toxicity of polyetyrene nanoparticle (PS-NP) in Caenorhabditis elegans. At parental generation (P0-G), PS-NP (1-100 µg/L) decreased expressions of germline cbp-1 and taf-1 encoding histone acetyltransferases, as well as germline expressions of sir-2.1 and hda-3 encoding histone deacetylase. Decrease in these 4 germline genes were also observed in the offspring of PS-NP (1-100 µg/L) exposed nematodes. Germline RNAi of cbp-1, taf-1, sir-2.1 and hda-3 resulted in more severe transgenerational PS-NP toxicity on locomotion and brood size. Meanwhile, in PS-NP exposed nematodes, germline RNAi of cbp-1, taf-1, sir-2.1 and hda-3 increased expression of genes encoding insulin, FGF, Wnt, and/or Notch ligands and expressions of their receptor genes in the offspring. Susceptibility to transgenerational PS-NP toxicity in cbp-1(RNAi), taf-1(RNAi), sir-2.1(RNAi), and hda-3 (RNAi) was inhibited by RNAi of these germline ligands genes. Moreover, histone deacetylase inhibition served as molecular initiating event (MIE) leading to transgenerational toxicity in epigenetic adverse outcome pathway (AOP) for nanoplastics. Our data provided evidence that germline histone acetylation regulation functioned as an important mechanism for transgenerational toxicity of nanoplastics at predicted environmental doses (PEDs) by affecting secreted ligands in organisms.