Retraction notice to "Autophagy regulates the Wnt/GSK3ß/ß-catenin/cyclin D1 pathway in mesenchymal stem cells (MSCs) exposed to titanium dioxide nanoparticles (TiO2NPs)" [Toxicol. Rep. 7C (2020) 1216-1222].

[This retracts the article DOI: 10.1016/j.toxrep.2020.08.020.].

Assessing public health and economic loss associated with black carbon exposure using monitoring and MERRA-2 data.

Black carbon (BC) exposure in China continues to be relatively high, prompting researchers to assess BC exposure levels using data from monitoring sites, satellite remote sensing, and models. However, data regarding the application of a combined strategy comprising the analysis of monitoring data and various types of data to simulate BC exposure levels are lacking. Hence, the current study seeks to estimate short- and long-term BC exposure levels by combining national monitoring data with data from the second Modern-Era Retrospective analysis for Research and Applications (MERRA-2). Furthermore, this study attempts to improve the spatio-temporal resolution of BC exposure levels using Bayesian maximum entropy (BME). The BME model performed well in terms of estimating short- (R2 = 0.74 and RMSE = 1.76 µg/m3) and long-term (R2 = 0.76 and RMSE = 1.3 µg/m3) exposure. Premature mortalities and economic losses were also assessed by applying localised concentration-response coefficients simulated in China. A total of 74,500 (95% confidence interval (CI): 23,900-124,500) and 538,400 (95% CI: 495,000-581,300) all-cause premature mortality cases were found to be associated with short- and long-term BC exposure, respectively. Meanwhile, short-term BC exposure was associated with economic losses ranging from 7.5 to 13.2 billion US dollars (USD) (1 USD = 6.36 RMB on January 19, 2022) based on amended human capital (AHC) and willingness to pay (WTP), accounting for 0.06%-0.1% of China's total gross domestic product (GDP) in 2017 (1.2 × 104 billion USD), respectively. The economic losses for long-term exposure varied from 53 to 93.2 billion USD based on AHC and WTP, accounting for 0.4%-0.8% of China's total GDP in 2017, respectively.

Migrasome biogenesis and functions.

The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we discovered the production of a pomegranate-like structure, which we named migrasomes. The production of migrasomes is highly correlated with the migration of cells. Currently, it has been demonstrated the migrasomes exhibit three modes of action: release of signaling molecules through rupturing or leaking, carriers of damaged mitochondria, and lateral transfer of mRNA or proteins. In this review, we would like to discuss, in detail, the functions, mechanisms, and potential applications of this newly discovered cell organelle.

Autophagy regulates the Wnt/GSK3ß/ß-catenin/cyclin D1 pathway in mesenchymal stem cells (MSCs) exposed to titanium dioxide nanoparticles (TiO2NPs).

The application of titanium dioxide nanoparticles (TiO2NPs) is on the increase, and so the number of studies dedicated to describing this material's biological effects. Previous studies have presented results indicating the controversial impact of TiO2NPs on cell fate regarding death and survival. We speculate that this may be due to focusing on each of the subject cells as an isolated individual. In this study, we made a difference by looking at the subject cells as an interrelated population. Specifically, we exposed mesenchymal stem cells (MSCs) to TiO2NPs and observed cell death and stimulation of proliferation among the cell population. Our data shows that the exposure to TiO2NPs initiated autophagy, which led to an increase in extracellular Wnt protein levels and increased Wnt/GSK3ß/ß-catenin/cyclin D1 signalling in the cell population. Autophagy inhibitor repressed the effects of TiO2NPs, which indicates that ß-catenin regulation was dependent on TiO2NPs-induced autophagy. The inhibition of ß-catenin resulted in dysregulation of cyclin D1 protein expression level. In conclusion, following exposure to TiO2NPs, MSCs undergo autophagy, which induces cell proliferation among the cell population by upregulation of cyclin D1 through the Wnt/GSK3ß/ß-catenin pathway.

Simulative structure and binding sites of lyral with olfactory receptor 10J5 using computational prediction methods.

Olfactory receptor (OR) genes are extensively distributed throughout the human organism. Although these receptors are predominantly located in the olfactory epithelium, binding between odorant chemicals and corresponding ORs initiates downstream events in other tissues. In particular, exposure to allergen fragrances results in the induction of contact dermatitis. At present, current methodologies are limited in their ability to predict the consequences of fragrancy chemicals on humans. The aim of this study was designed to simulate the bindingstructure between lyral and OR10J5, a known allergen which produces contact dermatitis, and its corresponding OR OR10J5 in an effort to predict dermal outcomes using computational methods. Results demonstrated that binding between lyral and OR10J5 involved amino acid residues Phe104, Val105, Cyx178, Ile180, and Tyr258, respectively, which were located on binding sites of the receptor transmembrane 3(TM3), TM3, extracellular loop 2(EL2), EL2, TM6. Evidence indicates that computer simulating binding interactions occurred between an odorant chemical and its receptors which initiated downstream alterations accounting possibly for the observed in vivo contact dermatitis.

Computerized screening of G-protein coupled receptors to identify and characterize olfactory receptors.

Olfactory receptors (ORs) are a group of G protein coupled receptors (GPCRs) that initiate chemical odorant signals. Although ORs are predominantly located in nasal epithelia to detect smell, these receptors are also present in peripherally in non-nasal organs/tissues. Since the quality of life and cognitive and sensorial features of sense of smell are worsened in multiple chemical sensitivity due to the interaction of ORs with offending compounds, it is important to not only differentiate these receptors from other GPCRs but also characterize these organelles to understand the underlying mechanisms of smelling disorders. The aim of this study was develop computerized programs to differentiate ORs from GPCRs. The computer program was developed on the basis of widely accepted basic algorithms. It is noteworthy that an accuracy of 95.5% was attained, a level not achieved using other established techniques for screening of ORs from GPCRs. The high accuracy rate indicates that this method of differential identification appears reliable. Our findings indicate that this novel method may be considered as a tool for identification and characterization of receptors which might aid in therapeutic approaches to human chemical-mediated sensitization.

Molecular mechanisms underlying titanium dioxide nanoparticles (TiO2NP) induced autophagy in mesenchymal stem cells (MSC).

The bone marrow is one of the target tissues for titanium dioxide nanoparticles (TiO2NP) following environmental exposure. At present, the consequences of TiO2NP exposure in bone are not well known. The aim of this study was to investigate the effects of TiO2NP on mesenchymal stem cells (MSCs) and potential underlying mechanisms. Mesenchymal bone marrow-derived cells were cultured and treated with various concentrations of TiO2NP. Results showed that TiO2NP incubation produced cytotoxicity as evidenced by reduced cell viability. Using Western blotting TiO2NP was found to increase autophagy as determined by elevation in ratio of LC3-II from LC3-I without evidence of necrotic cell death as estimated by lactic dehydrogenase (LDH) level. TiO2NP produced a rise in intracellular reactive oxygen species (ROS) levels. The observed alterations in autophagy and oxidant stress were associated with upregulation of protein expression of p38, JNK, and ERK. Data indicate that TiO2NP-mediated decrease in MSC survival involves a complex series of events associated stimulation of mitogen-activated protein kinase (MAPK) pathway and consequent autophagy and oxidative damage.

Terrestrosin D from Tribulus terrestris attenuates bleomycin-induced inflammation and suppresses fibrotic changes in the lungs of mice.

Context: Terrestrosin D (TED), from Tribulus terrestris L. (Zygophyllaceae), exhibits anti-tumour and anti-inflammatory activities. However, its effects on bleomycin (BLM)-induced pulmonary inflammation and the subsequent fibrotic changes remain unclear. Objective: To examine the anti-inflammatory and anti-fibrotic effects of TED against BLM in murine pulmonary tissues. Materials and methods: Male SPF mice received saline (control), TED (10 mg/kg), BLM (2.5 mg/kg), or BLM (2.5 mg/kg) + TED (10 mg/kg) group. BLM was administered as a single intranasal inoculation, and TED was intraperitoneally administered once daily. After 2 and 6 weeks of treatment, cell number and differentiation (Giemsa staining) and TNF-α, IL-6, IL-8, TGF-ß1, and PDGF-AB levels (ELISA) were determined in the bronchoalveolar lavage fluid (BALF). Hydroxyproline (Hyp) content in the left pulmonary tissue was also determined (ELISA). The right pulmonary tissue was H&E-stained and assessed for the severity of pulmonary fibrosis using the Ashcroft scoring method. Compared with the BLM group, TED decreased inflammatory cell infiltration; number of macrophages (p < 0.05), neutrophils (p < 0.05), lymphocytes (p < 0.05); percentage of macrophages in the monocyte-macrophage system (p < 0.05), and levels of TNF-α (p < 0.01), IL-6 (p < 0.01), IL-8 (p < 0.05), TGF-ß1 (p < 0.05), and PDGF-AB (p < 0.05) in the BALF. TED also reduced Hyp content (p < 0.05) in the pulmonary tissue and attenuated the BLM-induced deterioration in lung histopathology. Discussion and conclusions: TED can inhibit BLM-induced inflammation and fibrosis in the lungs of mice, which may be related to reduced inflammatory and fibrotic markers. These results could be further tested in humans through clinical studies.

Computational prediction methods to simulate structure and binding sites of coumarin with olfactory receptor 5P3.

Olfactory receptor 5P3 is coded by OR5P3 gene in human OR5P3 and recognized as the receptor for coumarin present in 30% of fragrances and might adversely affect human health. OR5P3 are also associated with coumarin-related breast cancer development and acquired tamoxifen resistance in breast cancer cells. Previously various investigators noted that coumarin acts as a ligand for OR5P3 and binding of this molecule to OR5P3 leads to downstream changes in the olfactory bulb and central nervous system. However, the interaction between OR5P3 and its ligands at molecular level is not well understood. The aim of this study was to develop a computerized approach to simulate the binding process of coumarin to OR5P3 and determine the binding sites at a molecular level. It is conceivable that understanding this binding mechanism to a specific OR may aid in identification of receptors responsible olfaction and non-olfaction disorders such as breast cancer. The approach employed in this study may thus be utilized in future studies to simulate bind of specific chemicals to ORs and potentially have therapeutic applications.