Project description:To understand molecular events of gallbladder cells during nanoplastics exposure, we performed scRNA-seq on gallbladder using 10x Genomics Chromium platform
Project description:Gallbladder cancer is a rare but highly malignant cancer. We performed the transcriptional profile sequencing to figure out the potential mechanisms, which might significantly affect gallbladder cancer progression.
Project description:The complexity of transcriptome in human gallbladder has not been clarified quite clearly so far. Here we collect 20 pairs of gallbladder samples.High-throughput RNA sequecing data was generated for each sample.We characterize the linear and circular transcripts.
Project description:Micro and nanoplastics (MNPLs) are contaminants originated mainly from plastic waste degradation that pose potential health risks. Inhalation is a major exposure route, as evidenced by their detection in human lungs, with polyethylene terephthalate (PET) among the most abundant particles in respiratory airways. However, the harmful effects of particle bioaccumulation remain unclear, as chronic effects are understudied. To assess the long-term effects, specifically the carcinogenic effects, BEAS-2B cell line was exposed to PET-NPLs for 30 weeks. Genotoxicity, carcinogenic phenotypic hallmarks, and a panel of genes and pathways associated with cell transformation and lung cancer were examined and compared across three exposure durations. No significant effects were observed after 24 hours or 15 weeks of exposure. However, 30-week exposure led to increased genotoxic damage, anchorage-independent growth, and invasive potential. Transcriptomic analysis showed upregulation of several oncogenes and lung cancer-associated genes at the end of the exposure. Further analysis revealed an increase in differentially expressed genes over time and a temporal gradient of lung cancer-related genes. Altogether, the data suggest PET-NPLs' potential carcinogenicity after extended exposure, highlighting serious long-term health risks of MNPLs. Assessing their carcinogenic risk under chronic, real-life conditions is crucial to address knowledge gaps and eventually develop preventive policies.
Project description:Nanoplastics are produced by breakdown of plastics in environmental contamination or commercial use for cosmetics or daily expenses. Emerging evidence indicate that ingested nanoplastics with a size smaller than 100 nm have the potential to reach the brain and induces neurotoxicity. However, the potential toxicity of nanoplastics on brain are limited because of difficulties in synthesize of nanoplastics. In present study, we synthesized the fluorescent polystyrene nanoplastics (PSNPs) and examined the toxicity of PSNPs in brain in vivo and in vitro analyses by comparison to IR-813 fluorophore. Synthesized PSNPs were characterized by fluorescence imaging system, scanning electron microscopy, and Fourier-transform infrared spectroscopy. PSNPs were detected in adult mice brain by oral ingestion. In addition, a series of behavioral analyses showed that oral ingestion of PSNPs induced memory impairments. Among brain cells, PSNPs were predominantly internalized in microglia, and uptake of PSNPs induced microglial activation. In addition, the conditioned medium derived from microglia exposed to PSNPs repressed hippocampal neuronal activity. Furthermore, transcriptome analysis showed that PSNPs changed gene expressions in microglia, elevation of neuroinflammation in contrast to suppression of neurotrophic factors. These results indicated that predominant uptake of PSNPs in microglia induced elevation of neuroninflammatory responses whereas suppression of neurotrophic factors that may contribute to the cognitive impairment. Our findings indicate the toxic mechanism and potential detrimental effect of nanoplastic in brain and suggest a potential risk of cognitive impairment by exposure to nanoplastics.
Project description:Nanoplastics, as an emerging persistent pollutant of global concern in recent years, have posed a potential threat to human health. However, there is little known about the adverse effects of nanoplastics on the female reproductive system. Here, polystyrene nanoplastics (PS-NPs) with a diameter of 50 nm were selected as representative nanosized plastic particles to investigate the potential effects of subchronic exposure on placenta development in mice.
Project description:We determined the global microRNA expression profiles of primary human gallbladder cells and genetically reprogrammed human gallbladder cells and compared with pancreatic beta cells to ascertain the degree of cellular transdifferentatiation of insulin-producing human gallbladder cells to become beta-like cells. First, we cultured patient-derived gallbladder cells and then we transduced these with beta cell transcription factors to reprogram gallbladder cells to become beta-like cells. We used a pan-islet surface monoclonal antibody to enrich for insulin-producing reprogrammed human gallbladder cells using FACS.
Project description:We determined the global gene expression profiles of primary human gallbladder cells and genetically reprogrammed human gallbladder cells and compared with pancreatic beta cells to ascertain the degree of cellular transdifferentatiation of insulin-producing human gallbladder cells to become beta-like cells. First, we cultured patient-derived gallbladder cells and then we transduced these with beta cell transcription factors to reprogram gallbladder cells to become beta-like cells. We used a pan-islet surface monoclonal antibody to enrich for insulin-producing reprogrammed human gallbladder cells using FACS.
Project description:Gallstone disease is a worldwide common disease. However, the knowledges concerning the gallbladder in the pathogenesis of cholesterol gallstone formation remains limited. In this study, using single-cell RNA sequencing (scRNA-seq), we showed cellular heterogeneity and transcriptomic dynamics in murine gallbladder cells during the process of lithogenesis. Our results indicated gallbladder wall were subjected to remodeling during the process of lithogenesis. The major molecular events happened included proliferation of epithelial cells, infiltration of immune-cells, activation of angionesis and extracellular matrix modulation. Furthermore, we observed partial reversal of gallbladder cell transcriptomes by ursodeoxycholic acid treatment. This work thus provides novel and integral knowledges on the cellular changes during lithogenesis, which is of great significance to the understanding of pathogenesis and treatment of cholesterol gallstone.
Project description:Nanoplastics were generated from common consumer plastics (PET, HDPE, PS, PVC) and exposed to simulated marine weathering for up to 10 weeks. Fourier-Transform Infrared (FT-IR) spectroscopy and ζ-potentials measurements revealed continuous changes in the composition of the nanoplastics consistent with oxidation. Although the chemical composition and oxidation of the nanoplastics influenced their ability to sorb Polycyclic Aromatic Hydrocarbons (PAHs), for all investigated conditions, sorption of PAH to nanoplastics achieved effective PAH concentrations that were orders of magnitude higher than the solubility limit in water. In an intestinal membrane model, PAH-loaded nanoplastics enhanced the overall PAH transport into and across the membrane, with HDPE achieving the highest intracellular PAH concentration. RNA sequencing of cell membranes exposed to nanoplastics revealed significant transcriptional changes, including upregulation of oxidative stress and detoxification pathways (NQO1, CYP1A1, CYP1B), especially in response to PAH-loaded nanoplastics, while genes associated with basic cell functions, such as cellular migration (NCKAP5, MACROD2) and division (KIF20A) were downregulated. These findings suggest that nanoplastics can increase bioaccessibility and bioavailability of hydrophobic carcinogens and enhance cellular stress, raising concerns about the potential environmental and health impacts associated with nanoplastics as carriers of hydrophobic environmental toxins.