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Nanotechnology for Tissue Engineering and Regenerative Medicine
Published in Šeila Selimovic, Nanopatterning and Nanoscale Devices for Biological Applications, 2017
Şükran Şeker, Y. Emre Arslan, Serap Durkut, A. Eser Elçin, Y. Murat Elçin
Hepatotoxicity is a medical term that is used to describe liver damage, particularly damage caused by the use of drugs. Recently, liver-on-a-chip systems have been evaluated for use in hepatotoxicity studies. Toh et al. have developed a microfluidic 3-D hepatocyte chip (3D HepaTox Chip), each channel engineered to maintain the synthetic and metabolic functions of hepatocytes, to test in vitro drug toxicity [102]. The results indicate that in vitro toxicity data can be correlated to in vivo toxicity data and the 3D HepaTox Chip (liver-on-a-chip) has potential utility in predicting in vivo toxicity [102].
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Sreejesh Sreedharan, Georgios Zouganelis, Samantha J Drake, Gyanendra Tripathi, Ali Kermanizadeh
In a 2022 in vitro investigation, two disease initiation and maintenance protocols were developed, described and used to mimic steatosis and pre-fibrotic non-alcoholic steatohepatitis (NASH) states in scaffold-free 3D liver tissues composed of primary human hepatocytes, hepatic stellate cells, KCs and sinusoidal endothelial cells. The physiological and pathophysiological tissues were used for comprehensive toxicological assessment of a panel of NMs which included approximately 150 nm ZnO NMs, approximately 50 nm, CeO2 NMs and food grade TiO2 (E171). In these trials the diseased microtissues were exposed to the materials at very low repeated doses (highest dose of 10 µg/ml) for a period of two weeks. (Kermanizadeh et al. (2022) demonstrated significant evidence that pre-existing liver disease was extremely important in intensification of xenobiotic-induced hepatotoxicity as manifested in cell death, inflammation and histopathology. Data showed that NMs were able to fully activate hepatic stellate cells. Therefore, evidence suggests that it is crucial that all stages of the wide spectrum of liver disease are incorporated in xenobiotic hazard assessment strategies (Kermanizadeh et al. 2022b)
Construction of polysaccharide scaffold-based perfusion bioreactor supporting liver cell aggregates for drug screening
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Lei Cao, Huicun Zhao, Mengyuan Qian, Chuxiao Shao, Yan Zhang, Jun Yang
Recently, with the development of liver tissue engineering, different types of bioreactors have shown great potential in hepatocyte culture and hepatotoxicity evaluation at an early stage of drug development [13–15]. However, the uneven distribution of cells in the bioreactor [16], the limited mass transfer of nutrients and metabolites [17], the insufficient expression of hepatic function [18], and the difficulty in cell recovery [19] are still urgently needed to be considered during the bioreactor construction. Moreover, the liver is a complex unit consisting mainly of hepatocytes, non-parenchymal cells (including Kupffer cells, hepatic stellate cells, and endothelial cells) [20]. Techniques for the co-culture of hepatocytes with non-parenchymal cells are continuously being developed to construct a bionic 3 D microenvironment and structure. With the help of a flow medium across the cell surface, the perfusion bioreactors are considered to have unique advantages in liver reconstruction through the biomimetic regulation of mechanical, biological, and chemical signals, which would further improve the expressions of hepatic polarity and function in vitro [21–23].
Expression profiles of long non-coding RNA in mouse lung tissue exposed to radon
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Jihua Nie, Jing Wu, Zhihai Chen, Yang Jiao, Jie Zhang, Hailin Tian, Jianxiang Li, Jian Tong
Long noncoding RNAs (lncRNA) are a class of RNA with transcriptional lengths of more than 200 nucleotides that do not encode proteins (Nagano and Fraser 2011). There is well-documented evidence that lncRNA serve as key regulators of gene expression at transcriptional and post-transcriptional levels and thus, influence various biological functions in human health (Mercer, Dinger, and Mattick 2009; Nagano and Fraser 2011). Several investigators reported that abnormal lncRNA expression was associated with development of various diseases including hepatic fibrosis and lung cancer (Huang et al. 2018; Wu et al. 2018). Upregulated expression of lncRNAs, induced by HPV virus and lipopolysaccharide (LPS), was observed by several investigators (Iancu et al. 2017; Singh et al. 2016). Wen et al. (2018) also noted that microcystin-mediated hepatotoxicity was associated with upregulation of lncRNA. Further, exposure to environmental pollutants such as benzene, particulate matter (PM2.5) and lead was found to upregulate lncRNA expression (Nan et al. 2018; Sun et al. 2017; Xu et al. 2017). Zeng et al. (2016) demonstrated that human primary melanocytes exposed to UVB for 24 hr showed an upregulation in lncRNA. In contrast, Li et al. (2016) found downregulation of lncRNA expression in breast cancer cells. However, the influence of radon on the expression profile of lncRNA in mouse lung tissue is not known. The aim of this study was to examine the influence of radon on mouse lung lncRNA expression and consequent potential functions affected in this target organ.