Increased
release of engineered nanoparticles (ENPs) from widely
used commercial products has threatened environmental health and safety,
particularly the repeated exposures to ENPs with relatively low concentration.
Herein, we studied the response of Chlorella pyrenoidesa (C. pyrenoidesa) to single and repeated exposures
to silver nanoparticles (AgNPs). Repeated exposures to AgNPs promoted
chlorophyll a and carotenoid production, and increased silver accumulation,
thus enhancing the risk of AgNPs entering the food chain. Notably,
the extracellular polymeric substances (EPS) content of the 1-AgNPs
and 3-AgNPs groups were dramatically increased by 119.1% and 151.5%,
respectively. We found that C. pyrenoidesa cells
exposed to AgNPs had several significant alterations in metabolic
process and cellular transcription. Most of the genes and metabolites
are altered in a dose-dependent manner. Compared with the control
group, single exposure had more differential genes and metabolites
than repeated exposures. 562, 1341, 4014, 227, 483, and 2409 unigenes
were differentially expressed by 1–0.5-AgNPs, 1–5-AgNPs,
1–10-AgNPs, 3–0.5-AgNPs, 3–5-AgNPs, and 3–10-AgNPs
treatment groups compared with the control. Metabolomic analyses revealed
that AgNPs altered the levels of sugars and amino acids, suggesting
that AgNPs reprogrammed carbon/nitrogen metabolism. The changes of
genes related to carbohydrate and amino acid metabolism, such as citrate
synthase (CS), isocitrate dehydrogenase (IDH1), and malate dehydrogenase
(MDH), further supported these results. These findings elucidated
the mechanism of biological responses to repeated exposures to AgNPs,
providing a new perspective on the risk assessment of nanomaterials.
The development of well-designed nanoprobes for specific imaging of multiple biomarkers in renal cells will afford beneficial information related to the transmutation process of drug-induced kidney injury (DIKI). However, the most reported nanoprobes for DIKI detection were dependent on single-signal output and lack of kidney targeting. In this work, we reported a renal cell targeting and dual-signal nanoprobe by encapsulating Brite 670 and Dabcyl-KFFFDEVDK-FAM into a low molecular weight chitosan nanoparticle. Confocal fluorescence imaging results demonstrated that the nanoprobe could visualize the upregulation of hydroxyl radical in early stage and activation of caspase-3 in late stage of DIKI at both the renal cell and tissue level. In a mouse DIKI model, the positive time of 8 h using nanoprobe imaging was superior to that of 72 h for serum creatinine or blood urea nitrogen, 16 h for cystatin-C, and 24 h for kidney injury molecule-1 with conventional methods. These results demonstrated that the nanoprobe may be a promising tool for effective early prediction and discriminative imaging of DIKI.
Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, but it remains relatively underdiagnosed. Objective: In this study, we aimed to explore the key regulatory pathways and potential biomarkers related to DN using integrated bioinformatics analysis and validation. Methods: First, the microarray data of the GSE30528 and GSE96804 datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. Then, weighted gene coexpression network analysis (WGCNA), gene ontology (GO) annotation, gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify key pathways and genes. qRT-PCR and receiver operating characteristic (ROC) curves were used to validate our results. Furthermore, single-cell RNA sequencing (scRNA-seq) data were reanalyzed to investigate the expression specificity of C7 in DN cells. An online database search and luciferase reporter assay identified the target relationship between miRNAs and C7. Results: The "complement and coagulation cascades" were significantly enriched, and complement C3 and C7 were candidate markers. The receiver operating characteristic (ROC) curve revealed that C7 had significant diagnostic value (AUC=0.865) in DN. Through scRNA-seq reanalysis, we found that C7 was specifically elevated in mesangial (MES) cells of DN. Moreover, we found that the expression of C7 was regulated by miR-494-3p and miR-574-5p. Conclusion: This is the first study to reveal that C7 is specifically expressed in mesangial cells, is a potential diagnostic biomarker for diabetic nephropathy, and is regulated by miR-494-3p and miR-574-5p.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.