Examining the in vivo pulmonary toxicity of engineered metal oxide nanomaterials using a genetic algorithm-based dose-response-recovery clustering model

2020 ◽  
Vol 13 ◽  
pp. 100113
Author(s):  
Vignesh Ramchandran ◽  
Jeremy M. Gernand
Keyword(s):  
Genetic Algorithm ◽  
Metal Oxide ◽  
Dose Response ◽  
Pulmonary Toxicity ◽  
Clustering Model ◽  
Response Recovery ◽  
Metal Oxide Nanomaterials

scholarly journals Engineered metal oxide nanomaterials inhibit corneal epithelial wound healing in vitro and in vivo

NanoImpact ◽  
2020 ◽  
Vol 17 ◽  
pp. 100198 ◽  
Author(s):  
Soohyun Kim ◽  
Brooke L. Gates ◽  
Brian C. Leonard ◽  
Megan M. Gragg ◽  
Kent E. Pinkerton ◽  
...  
Keyword(s):  
Wound Healing ◽  
Metal Oxide ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing ◽  
Metal Oxide Nanomaterials

scholarly journals Identifying diverse metal oxide nanomaterials with lethal effects on embryonic zebrafish using machine learning

2021 ◽  
Vol 12 ◽  
pp. 1297-1325
Author(s):  
Richard Liam Marchese Robinson ◽  
Haralambos Sarimveis ◽  
Philip Doganis ◽  
Xiaodong Jia ◽  
Marianna Kotzabasaki ◽  
...  
Keyword(s):  
Machine Learning ◽  
Metal Oxide ◽  
Data Augmentation ◽  
Test System ◽  
Biological Interactions ◽  
Future Studies ◽  
In Vivo Test ◽  
Human Safety ◽  
Metal Oxide Nanomaterials

Manufacturers of nanomaterial-enabled products need models of endpoints that are relevant to human safety to support the “safe by design” paradigm and avoid late-stage attrition. Increasingly, embryonic zebrafish (Danio Rerio) are recognised as a key human safety relevant in vivo test system. Hence, machine learning models were developed for identifying metal oxide nanomaterials causing lethality to embryonic zebrafish up to 24 hours post-fertilisation, or excess lethality in the period of 24–120 hours post-fertilisation, at concentrations of 250 ppm or less. Models were developed using data from the Nanomaterial Biological-Interactions Knowledgebase for a dataset of 44 diverse, coated and uncoated metal or, in one case, metalloid oxide nanomaterials. Different modelling approaches were evaluated using nested cross-validation on this dataset. Models were initially developed for both lethality endpoints using multiple descriptors representing the composition of the core, shell and surface functional groups, as well as particle characteristics. However, interestingly, the 24 hours post-fertilisation data were found to be harder to predict, which could reflect different exposure routes. Hence, subsequent analysis focused on the prediction of excess lethality at 120 hours-post fertilisation. The use of two data augmentation approaches, applied for the first time in nano-QSAR research, was explored, yet both failed to boost predictive performance. Interestingly, it was found that comparable results to those originally obtained using multiple descriptors could be obtained using a model based upon a single, simple descriptor: the Pauling electronegativity of the metal atom. Since it is widely recognised that a variety of intrinsic and extrinsic nanomaterial characteristics contribute to their toxicological effects, this is a surprising finding. This may partly reflect the need to investigate more sophisticated descriptors in future studies. Future studies are also required to examine how robust these modelling results are on truly external data, which were not used to select the single descriptor model. This will require further laboratory work to generate comparable data to those studied herein.

scholarly journals Predicting chromosome damage in astronauts participating in international space station missions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alan Feiveson ◽  
Kerry George ◽  
Mark Shavers ◽  
Maria Moreno-Villanueva ◽  
Ye Zhang ◽  
...  
Keyword(s):  
International Space Station ◽  
Dose Response ◽  
Ex Vivo ◽  
Space Station ◽  
Space Radiation ◽  
Blood Samples ◽  
International Space ◽  
Significant Difference ◽  
Subject Specific

AbstractSpace radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.

scholarly journals Advanced development of metal oxide nanomaterials for H2 gas sensing applications

2021 ◽  
Author(s):  
Yushu Shi ◽  
Huiyan Xu ◽  
Tongyao Liu ◽  
Shah Zeb ◽  
Yong Nie ◽  
...  
Keyword(s):  
Metal Oxide ◽  
Gas Sensors ◽  
Gas Sensing ◽  
The Past ◽  
Sensing Applications ◽  
The Future ◽  
Metal Oxide Nanomaterials ◽  
Nanomaterials Synthesis ◽  
Advanced Development

The scheme of the structure of this review includes an introduction from the metal oxide nanomaterials’ synthesis to application in H2 gas sensors—a vision from the past to the future.

scholarly journals The application prospect of metal/metal oxide nanoparticles in the treatment of osteoarthritis

2021 ◽  
Vol 394 (10) ◽  
pp. 1991-2002
Author(s):  
Junchao Luo ◽  
Yin Zhang ◽  
Senbo Zhu ◽  
Yu Tong ◽  
Lichen Ji ◽  
...  
Keyword(s):  
Metal Oxide ◽  
Metal Oxide Nanoparticles ◽  
Biological Response ◽  
Cell Uptake ◽  
Oxide Nanoparticles ◽  
Therapeutic Effects ◽  
Superoxide Anions ◽  
Metal Metal ◽  
Cartilage Wear

AbstractThe current understanding of osteoarthritis is developing from a mechanical disease caused by cartilage wear to a complex biological response involving inflammation, oxidative stress and other aspects. Nanoparticles are widely used in drug delivery due to its good stability in vivo and cell uptake efficiency. In addition to the above advantages, metal/metal oxide NPs, such as cerium oxide and manganese dioxide, can also simulate the activity of antioxidant enzymes and catalyze the degradation of superoxide anions and hydrogen peroxide. Degrading of metal/metal oxide nanoparticles releases metal ions, which may slow down the progression of osteoarthritis by inhibiting inflammation, promoting cartilage repair and inhibiting cartilage ossification. In present review, we focused on recent research works concerning osteoarthritis treating with metal/metal oxide nanoparticles, and introduced some potential nanoparticles that may have therapeutic effects.

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

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