Effects of Nano-MnO2 on Dopaminergic Neurons and the Spatial Learning Capability of Rats

This study aimed to observe the effect of intracerebrally injected nano-MnO2 on neurobehavior and the functions of dopaminergic neurons and astrocytes. Nano-MnO2, 6-OHDA, and saline (control) were injected in the substantia nigra and the ventral tegmental area of Sprague-Dawley rat brains. The neurobehavior of rats was evaluated by Morris water maze test. Tyrosine hydroxylase (TH), inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) expressions in rat brain were detected by immunohistochemistry. Results showed that the escape latencies of nano-MnO2 treated rat increased significantly compared with control. The number of TH-positive cells decreased, GFAP- and iNOS-positive cells increased significantly in the lesion side of the rat brains compared with the contralateral area in nano-MnO2 group. The same tendencies were observed in nano-MnO2-injected rat brains compared with control. However, in the the positive control, 6-OHDA group, escape latencies increased, TH-positive cell number decreased significantly compared with nano-MnO2 group. The alteration of spatial learning abilities of rats induced by nano-MnO2 may be associated with dopaminergic neuronal dysfunction and astrocyte activation

Effects of Microcystin-LR Exposure on Spermiogenesis in Nematode Caenorhabditis elegans

Little is known about the effect on spermiogenesis induced by microcystin-leucine arginine (MC-LR), even though such data are very important to better elucidate reproductive health. In the current work, with the aid of nematode Caenorhabditis elegans (C. elegans) as an animal model, we investigated the defects on spermiogenesis induced by MC-LR. Our results showed that MC-LR exposure induced sperm morphology abnormality and caused severe defects of sperm activation, trans-activation, sperm behavior and competition. Additionally, the expression levels of spe-15 were significantly decreased in C. elegans exposed to MC-LR lower than 16.0 μg/L, while the expression levels of spe-10 and fer-1 could be significantly lowered in C. elegans even exposed to 1.0 μg/L of MC-LR. Therefore, the present study reveals that MC-LR can induce adverse effects on spermiogenesis, and those defects of sperm functions may be induced by the decreases of spe-10, spe-15 and fer-1 gene expressions in C. elegans

Identification of Plasma Metabolomic Profiling for Diagnosis of Esophageal Squamous-Cell Carcinoma Using an UPLC/TOF/MS Platform

Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors

Epigenetic Repression of miR-218 Promotes Esophageal Carcinogenesis by Targeting ROBO1

miR-218, consisting of miR-218-1 at 4p15.31 and miR-218-2 at 5q35.1, was significantly decreased in esophageal squamous cell carcinoma (ESCC) in our previous study. The aim of this study was to determine whether aberrant methylation is associated with miR-218 repression. Bisulfite sequencing analysis (BSP), methylation specific PCR (MSP), and 5-aza-2′-deoxycytidine treatment assay were applied to determine the methyaltion status of miR-218 in cells and clinical samples. In vitro assays were performed to explore the role of miR-218. Results showed that miR-218-1 was significantly CpG hypermethylated in tumor tissues (81%, 34/42) compared with paired non-tumor tissues (33%, 14/42) (p < 0.05). However, no statistical difference was found in miR-218-2. Accordingly, expression of miR-218 was negatively correlated with miR-218-1 methylation status (p < 0.05). After demethylation treatment by 5-aza-2′-deoxycytidine, there was a 2.53- and 2.40-fold increase of miR-218 expression in EC109 and EC9706, respectively. miR-218 suppressed cell proliferation and arrested cells at G1 phase by targeting 3′ untranslated region (3′UTR) of roundabout guidance receptor 1 (ROBO1). A negative correlation was found between miR-218 and ROBO1 mRNA expression in clinical samples. In conclusion, our results support that aberrant CpG hypermethylation at least partly accounts for miR-218 silencing in ESCC, which impairs its tumor-suppressive function

V-ATPase E mediates Cry2Ab binding and toxicity in Helicoverpa armigera

Cry2Ab is one of the important alternative Bt proteins that can be used to manage insect pests resistant to Cry1A toxins and to expand the insecticidal spectrum of pyramided Bt crops. Previous studies have showed that vacuolar H+-ATPase subunits A and B (V-ATPase A and B) may be involved in Bt insecticidal activities. The present study investigated the role of V-ATPases subunit E in the toxicity of Cry2Ab in Helicoverpa amigera. RT-PCR analysis revealed that oral exposure of H. amigera larvae to Cry2Ab led to a significant reduction in the expression of H. armigera V-ATPase E (HaV-ATPase E). Ligand blot, homologous and heterologous competition experiments confirmed that HaV-ATPases E physically and specifically bound to activated Cry2Ab toxin. Heterologous expressing of HaV-ATPase E in Sf9 cells made the cell line more susceptible to Cry2Ab, whereas knockdown of the endogenous V-ATPase E in H. zea midgut cells decreased Cry2Ab's cytotoxicity against this cell line. Further in vivo bioassay showed that H. armigera larvae fed a diet overlaid with both Cry2Ab and E. coli-expressed HaV-ATPase E protein suffered significantly higher mortality than those fed Cry2Ab alone. These results support that V-ATPases E is a putative receptor of Cry2Ab and can be used to improve Cry2Ab toxicity and manage Cry2Ab resistance at least in H. armigera.12 month embargo; first published 13 December 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Polystyrene Nanoplastics Induce Lung Injury via Activating Oxidative Stress: Molecular Insights from Bioinformatics Analysis

(1) Background: Increasing evidence reveals that airborne plastic particles will continue to degrade into nanoplastics which are then inhaled by humans, causing injury to the respiratory system with controversial molecular mechanisms. (2) Methods: We used polystyrene nanoplastics (PS-NPs) as the representative pollutants to explore the inhalation toxicology of nanoplastics and identified the potential mechanism through high-throughput sequencing. (3) Results: PS-NPs inhibited cell viability in a dose-dependent manner and 0 μg/cm2, 7.5 μg/cm2 and 30 μg/cm2 PS-NP-treated groups were selected for RNA-seq. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that lung injuries caused by PS-NPs were mediated via redox imbalance, which was verified by reactive oxygen species (ROS) staining. Additionally, we obtained ten key transcription factors (TFs) governing differentially expressed genes (DEGs), nine of which were involved in the regulation of oxidative stress. An oxidative stress-associated TF-mRNA regulatory network was constructed on account of the findings above. Further joint analysis with animal experiment data from the GEO database identified a crucial oxidative stress-related molecule, TNFRSF12A. qRT-PCR was performed to confirm the results of RNA-seq. (4) Conclusions: Our study indicates the potential role of oxidative stress in the mechanism of nanoplastics-induced lung injuries, with several key genes being promising targets to analyze in future investigations

Multi-dimensional evaluation of cardiotoxicity in mice following respiratory exposure to polystyrene nanoplastics

Abstract Background Nanoplastics (NPs) could be released into environment through the degradation of plastic products, and their content in the air cannot be ignored. To date, no studies have focused on the cardiac injury effects and underlying mechanisms induced by respiratory exposure to NPs. Results Here, we systematically investigated the cardiotoxicity of 40 nm polystyrene nanoplastics (PS-NPs) in mice exposed via inhalation. Four exposure concentrations (0 µg/day, 16 µg/day, 40 µg/day and 100 µg/day) and three exposure durations (1 week, 4 weeks, 12 weeks) were set for more comprehensive information and RNA-seq was performed to reveal the potential mechanisms of cardiotoxicity after acute, subacute and subchronic exposure. PS-NPs induced cardiac injury in a dose-dependent and time-dependent manner. Acute, subacute and subchronic exposure increased the levels of injury biomarkers and inflammation and disturbed the equilibrium between oxidase and antioxidase activity. Subacute and subchronic exposure dampened the cardiac systolic function and contributed to structural and ultrastructural damage in heart. Mechanistically, violent inflammatory and immune responses were evoked after acute exposure. Moreover, disturbed energy metabolism, especially the TCA cycle, in the myocardium caused by mitochondria damage may be the latent mechanism of PS-NPs-induced cardiac injury after subacute and subchronic exposure. Conclusion The present study evaluated the cardiotoxicity induced by respiratory exposure to PS-NPs from multiple dimensions, including the accumulation of PS-NPs, cardiac functional assessment, histology observation, biomarkers detection and transcriptomic study. PS-NPs resulted in cardiac injury structurally and functionally in a dose-dependent and time-dependent manner, and mitochondria damage of myocardium induced by PS-NPs may be the potential mechanism for its cardiotoxicity. Graphical abstrac