Nanoplastics, including polystyrene nanoplastics (PS-NPs), are widely existed in the atmosphere, which can be directly and continuously inhaled into the human body, posing a serious threat to the respiratory system. Therefore, it is urgent to estimate the potential pulmonary toxicity of airborne NPs and understand its underlying mechanism. In this research, we used two types of human lung epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) and (human pulmonary alveolar epithelial cells, HPAEpiC) to investigate the association between lung injury and PS-NPs. We found PS-NPs could significantly reduce cell viability in a dose-dependent manner and selected 7.5, 15 and 30 μg/cm² PS-NPs as the exposure dosage levels. Microarray detection revealed that 770 genes in the 7.5 μg/cm² group and 1951 genes in the 30 μg/cm² group were distinctly altered compared to the control group. Function analysis suggested that redox imbalance might play central roles in PS-NPs induced lung injury. Further experiments verified that PS-NPs could break redox equilibrium, induce inflammatory effects, and triggered apoptotic pathways to cause cell death. Importantly, we found that PS-NPs could decrease transepithelial electrical resistance by depleting tight junctional proteins. Result also demonstrated that PS-NPs-treated cells increased matrix metallopeptidase 9 and Surfactant protein A levels, suggesting the exposure of PS-NPs might reduce the repair ability of the lung and cause tissue damage. In conclusion, nanoplastics could induce oxidative stress and inflammatory responses, followed by cell death and epithelial barrier destruction, which might result in tissue damage and lung disease after prolonged exposure.

It has been reported that disordered Cu metabolism is associated with several neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying mechanism is still unclear. In this study, 4-week-old male mice were exposed to Cu by free-drinking water for three months. Then, the effects of Cu on cognitive functions in mice were tested by Morris water maze tests, and the potential mechanisms were investigated by the ELISA, immunochemistry, TUNEL, and Western blot tests. It was found that Cu exacerbates learning and memory impairment, and leads to Cu-overload in the brain and urine of mice. The results showed that Cu induces neuronal degeneration and oxidative damage, promotes the expression of apoptosis-related protein Bax, cuproptosis-related proteins FDX1 and DLAT and the proteotoxic stress marker HSP70, and decreases Fe-S cluster proteins. In addition, Cu affects the pre-synaptic and post-synaptic regulatory mechanisms through inhibiting the expression of PSD-95 and SYP. Cu also suppresses phosphorylation levels in CREB and decreases the expression of BDNF and TrkB in the mouse hippocampus. In conclusion, Cu might mediate cuproptosis, damage synaptic plasticity and inhibit the CREB/BDNF pathway to cause cognitive dysfunction in mice.

Recent evidence indicates that exosomes can mediate certain microRNAs (miRNAs) involved in a series of biological functions in tumor occurrence and development. Our previous studies showed that microRNA-21 (miR-21) was abundant in both esophageal cancer cells and their corresponding exosomes. The present study explored the function of exosome-shuttling miR-21 involved in esophageal cancer progression. We found that exosomes could be internalized from the extracellular space to the cytoplasm. The exosome-derived Cy3-labeled miR-21 mimics could be transported into recipient cells in a neutral sphingomyelinase 2 (nSMase2)-dependent manner. miR-21 overexpression from donor cells significantly promoted the migration and invasion of recipient cells by targeting programmed cell death 4 (PDCD4) and activating its downstream c-Jun N-terminal kinase (JNK) signaling pathway after co-cultivation. Our population plasma sample analysis indicated that miR-21 was upregulated significantly in plasma from esophageal cancer patients and showed a significant risk association for esophageal cancer. Our data demonstrated that a close correlation existed between exosome-shuttling miR-21 and esophageal cancer recurrence and distant metastasis. Thus, exosome-shuttling miR-21 may become a potential biomarker for prognosis among esophageal cancer patients.