ENVIRONMENTAL POLLUTION
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2026
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IF 7.2
Xu Li,Xi Yu,Shenghan Zhang,Litong Han,Yingjuan Liu
Polystyrene nanoplastics trigger ROS at subcytotoxic doses before cell death. • Multi-omics reveals nanoplastic disruption of macrophage mitochondrial homeostasis. • Mitochondrial complex I dysfunction precedes ATP loss after nanoplastic exposure. • CPEB4/INO80B dysregulation may contribute to nanoplastic toxicity. • Primary mouse peritoneal macrophages mount inflammatory responses to nanoplastics. Polystyrene nanoplastics (NPs) may affect macrophage function, but the relationships between inflammatory responses and mitochondrial alterations remain unclear. We combined exploratory analysis of public zebrafish intestinal single-cell RNA-sequencing data with transcriptomic, metabolomic, and experimental studies in RAW264.7 cells and primary mouse macrophages. In RAW264.7 cells, NPs increased reactive oxygen species (ROS), nitric oxide (NO), and the secretion of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). ROS and cytokine responses occurred at concentrations below those causing significant cytotoxicity in this cell line. A complex I-associated activity assay detected changes at lower NP concentrations than assays of cellular adenosine triphosphate (ATP) and the NAD + /NADH ratio. MitoSOX and JC-1 measurements further indicated changes in mitochondrial oxidant-sensitive fluorescence and membrane-potential-associated signals. Primary mouse macrophages showed concentration- and time-dependent responses, including increased TNF-α secretion. NPs exposure was also associated with reduced CPEB4 and INO80B protein abundance. CPEB4 knockdown increased ROS and reduced ATP at a later time point, whereas cellular thermal shift assay showed altered CPEB4 thermal behavior after NPs exposure. These findings identify inflammatory and mitochondrial responses associated with NPs exposure and implicate CPEB4 as a candidate contributor. However, they do not establish direct binding of intact NPs to CPEB4 or a causal role for CPEB4 or INO80B. Download: Download high-res image (393KB) Download: Download full-size image
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DOI
高影响因子
Pharmaceutics
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2024
·Vol. 16
·期 12
·1543
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IF 4.9
Min Li,Wenying Li,Fang Xu,Yiping Pu,Jianguang Li
Background:L-Shikonin, an active component of Arnebia euchroma (Royle) Johnst., has remarkable pharmacological effects, particularly in its anti-tumour activity. Nonetheless, the specific targets and mechanisms of action remain to be further explored.Methods:A novel Fe3O4@L-Shikoninwas designed and synthesized in this study by linking Fe3O4andL-Shikoninthrough benzophenone. Fe3O4@L-Shikoninwas characterized using several techniques, including scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and drug removal methods, to determine the content ofL-Shikoninon the surface of the magnetic particles. Target hooking technology was utilized to identify the target proteins of the compound in melanoma. The synthesized Fe3O4@L-Shikoninwas co-incubated with A375 cell lysate, followed by the target proteins, which were purified by magnetic enrichment using magnetic microspheres and identified by high-resolution mass spectrometry.Results:AutoDock Vina software was employed for molecular docking analysis, where it was found thatL-Shikonintargets RPN1, CPEB4, and HNRNPUL1 proteins. Subsequently, A375 cells were treated withL-Shikoninat different concentrations (2.5, 5.0, 10.0 μM) for 48 h, and the expressions of the three proteins were observed. The results showed a significant reduction in the relative expression of CPEB4 in the high-dose group compared to the control group (p< 0.01). Moreover, the relative expression of HNRNPUL1 was decreased in the medium- and high-dose groups (p< 0.05).Conclusions:This study initially revealed from the source thatL-Shikoninmay regulate melanoma-specific markers, melanosomes, tyrosine kinases related to abnormal tyrosine metabolism, and melanoma through multiple targets such as CPEB4 and HNRNPUL1. Proliferation and metastasis work together to exert an anti-melanoma mechanism, which provides a new idea for the follow-up study of the molecular pharmacological mechanism of the complex system of total naphthoquinones inArnebia euchroma(Royle) Johns.
研究领域:
药理学
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肿瘤学
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分子生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Fei Yao,Cao Danping,Li Yanna,Wang Zhixiong,Dong Runyu,Zhu Menglin,Gao Peng,Wang Xiaoming,Cai Juan,Zuo Xueliang
Introduction Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies. Methods High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC. Results We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance. Conclusion Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment. Graphical Abstract
研究领域:
肿瘤学
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分子生物学
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药理学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
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