Evaluating the adverse effects and mechanisms of nanomaterial exposure on longevity of C. elegans: A literature meta-analysis and bioinformatics analysis of multi-transcriptome data.

Exposure to large-size particulate air pollution (PM2.5 or PM10) has been reported to increase risks of aging-related diseases and human death, indicating the potential pro-aging effects of airborne nanomaterials with ultra-fine particle size (which have been widely applied in various fields). However, this hypothesis remains inconclusive. Here, a meta-analysis of 99 published literatures collected from electronic databases (PubMed, EMBASE and Cochrane Library; from inception to June 2023) was performed to confirm the effects of nanomaterial exposure on aging-related indicators and molecular mechanisms in model animal C. elegans. The pooled analysis by Stata software showed that compared with the control, nanomaterial exposure significantly shortened the mean lifespan [standardized mean difference (SMD) = -2.30], reduced the survival rate (SMD = -4.57) and increased the death risk (hazard ratio = 1.36) accompanied by upregulation of ced-3, ced-4 and cep-1, while downregulation of ctl-2, ape-1, aak-2 and pmk-1. Furthermore, multi-transcriptome data associated with nanomaterial exposure were retrieved from Gene Expression Omnibus (GSE32521, GSE41486, GSE24847, GSE59470, GSE70509, GSE14932, GSE93187, GSE114881, and GSE122728) and bioinformatics analyses showed that pseudogene prg-2, mRNAs of abu, car-1, gipc-1, gsp-3, kat-1, pod-2, acdh-8, hsp-60 and egrh-2 were downregulated, while R04A9.7 was upregulated after exposure to at least two types of nanomaterials. Resveratrol (abu, hsp-60, pod-2, egrh-2, acdh-8, gsp-3, car-1, kat-1, gipc-1), naringenin (kat-1, egrh-2), coumestrol (egrh-2) or swainsonine/niacin/ferulic acid (R04A9.7) exerted therapeutic effects by reversing the expression levels of target genes. In conclusion, our study demonstrates the necessity to use phytomedicines that target hub genes to delay aging for populations with nanomaterial exposure.

Evaluation of the protective roles of alpha-lipoic acid supplementation on nanomaterial-induced toxicity: A meta-analysis of in vitro and in vivo studies.

Extensive exposure to nanomaterials causes oxidative stress and inflammation in various organs and leads to an increased risk of adverse health outcomes; therefore, how to prevent the toxic effects are of great concern to human. Alpha-lipoic acid (ALA) has anti-oxidant and anti-inflammatory activities, suggesting it may be effective to prevent nanomaterial-induced toxicity. However, the results obtained in individual studies remained controversial. We aimed to comprehensively evaluate the effects of ALA supplementation on nanomaterial-induced toxicity by performing a meta-analysis. Databases of PubMed, EMBASE, and Cochrane Library were searched up to May 2022. STATA 15.0 software was used for statistical analysis. Twelve studies were included. Meta-analysis of eight in vivo studies showed ALA supplementation could exert significant effects on nanomaterial-induced oxidative stress (by reducing MDA, ROS and increasing GSH, CAT, GPx, and SOD), inflammation (by downregulating NO, IgG, TNF-α, IL-6, and CRP), apoptosis (by activation of pro-apoptotic caspase-3), DNA damage (by a reduction in the tail length) and organ damage (by a decrease in the liver biomarker ALT and increases in brain neuron biomarker AChE and heart biomarker CPK). Pooled analysis of four in vitro studies indicated ALA intervention increased cell viability, decreased ROS levels, inhibited cell apoptosis and chelated metal ions. Subgroup analyses revealed changing the levels of GSH, IL-6, and metal ions were the main protective mechanisms of ALA supplementation because they were not changed by any subgroup factors. In conclusion, ALA supplementation may represent a potential strategy for the prevention of the toxicity induced by nanomaterials.

Vitamin Supplementation Protects against Nanomaterial-Induced Oxidative Stress and Inflammation Damages: A Meta-Analysis of In Vitro and In Vivo Studies.

The extensive applications of nanomaterials have increased their toxicities to human health. As a commonly recommended health care product, vitamins have been reported to exert protective roles against nanomaterial-induced oxidative stress and inflammatory responses. However, there have been some controversial conclusions in regards to this field of research. This meta-analysis aimed to comprehensively evaluate the roles and mechanisms of vitamins for cells and animals exposed to nanomaterials. Nineteen studies (seven in vitro, eleven in vivo and one in both) were enrolled by searching PubMed, EMBASE, and Cochrane Library databases. STATA 15.0 software analysis showed vitamin E treatment could significantly decrease the levels of oxidants [reactive oxygen species (ROS), total oxidant status (TOS), malondialdehyde (MDA)], increase anti-oxidant glutathione peroxidase (GPx), suppress inflammatory mediators (tumor necrosis factor-α, interleukin-6, C-reactive protein, IgE), improve cytotoxicity (manifested by an increase in cell viability and a decrease in pro-apoptotic caspase-3 activity), and genotoxicity (represented by a reduction in the tail length). These results were less changed after subgroup analyses. Pooled analysis of in vitro studies indicated vitamin C increased cell viability and decreased ROS levels, but its anti-oxidant potential was not observed in the meta-analysis of in vivo studies. Vitamin A could decrease MDA, TOS and increase GPx, but its effects on these indicators were weaker than vitamin E. Also, the combination of vitamin A with vitamin E did not provide greater anti-oxidant effects than vitamin E alone. In summary, we suggest vitamin E alone supplementation may be a cost-effective option to prevent nanomaterial-induced injuries.

Potential Biomarkers and Drugs for Nanoparticle-Induced Cytotoxicity in the Retina: Based on Regulation of Inflammatory and Apoptotic Genes.

The eye is a superficial organ directly exposed to the surrounding environment. Thus, the toxicity of nanoparticle (NP) pollutants to the eye may be potentially severer relative to inner organs and needs to be monitored. However, the cytotoxic mechanisms of NPs on the eyes remain rarely reported. This study was to screen crucial genes associated with NPs-induced retinal injuries. The gene expression profiles in the retina induced by NPs [GSE49371: Au20, Au100, Si20, Si100; GSE49048: presumptive therapeutic concentration (PTC) TiO2, 10PTC TiO2] and commonly used retinal cell injury models (optic nerve injury procedure: GSE55228, GSE120257 and GSE131486; hypoxia exposure: GSE173233, GSE151610, GSE135844; H2O2 exposure: GSE122270) were obtained from the Gene Expression Omnibus database. A total of 381 differentially expressed genes (including 372 mRNAs and 9 lncRNAs) were shared between NP exposure and the optic nerve injury model when they were compared with their corresponding controls. Function enrichment analysis of these overlapped genes showed that Tlr2, Crhbp, Ccl2, Cxcl10, Fas, Irf8, Socs3, Stat3, Gbp6, Casp1 and Syk were involved in inflammatory- and apoptotic-related processes. Protein-protein interaction network analysis revealed eight of them (Tlr2, Ccl2, Cxcl10, Irf8, Socs3, Stat3, Casp1 and Syk) were hub genes. Moreover, Socs3 could interact with upstream Stat3 and downstream Fas/Casp1/Ccl2/Cxcl10; Irf8 could interact with upstream Tlr2, Syk and downstream Cxcl10. Competing endogenous RNAs network analysis identified Socs3, Irf8, Gdf6 and Crhbp could be regulated by lncRNAs and miRNAs (9330175E14Rik-mmu-miR-762-Socs3, 6430562O15Rik-mmu-miR-207-Irf8, Gm9866-mmu-miR-669b-5p-Gdf6, 4933406C10Rik-mmu-miR-9-5p-Crhbp). CMap-CTD database analyses indicated the expression levels of Tlr2, Ccl2, Cxcl10, Fas, Irf8, Socs3, Stat3, Gbp6, Casp1 and Syk could be reversed by folic acid. Crhbp and Gdf6 were also verified to be downregulated, while Tlr2, Ccl2, Irf8, Socs3 and Stat3 were upregulated in hypoxia/H2O2-induced retinal injury models. Hereby, our findings suggest that Crhbp, Irf8, Socs3 and Gdf6 as well as their upstream mRNAs, lncRNAs and miRNAs may be potential monitoring biomarkers and therapeutic targets for NP-induced retinal injuries. Folic acid supplementation may be a preventive and therapeutic approach.