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Intensification of copper pollution in the environment has led to its excessive accumulation in humans, causing oxidative stress and lipid metabolism disorders. It is necessary to look for effective targets and safe methods to alleviate copper toxicity. Pelargonidin-3-glucoside (Pg3G) is a natural anthocyanin with metal ion chelating ability and multiple physiological activities. In this study, lipid accumulation was investigated under copper exposure in Caenorhabditis elegans which can be improved by Pg3G. Transcriptome analysis revealed that differentially expressed genes are enriched in lipid metabolism and protein folding/degradation. Pg3G activated mitochondrial unfold protein response (UPR mt ) to mitigate mitochondrial damage caused by copper and regulated the expression of genes involved in lipid absorption, transport, and synthesis, thereby reducing lipid levels in C. elegans. This improvement disappeared in the ubl-5 knockout strain, indicating that ubl-5 is one target of Pg3G. Meanwhile, in HepG2 cells, Pg3G enhanced the cellular antioxidant capacity by activating UPR mt for maintaining mitochondrial homeostasis, followed by inhibition of excessive lipid accumulation. Overall, these results suggested that UPR mt activation can be a strategy for mitigating lipid disorders induced by copper and Pg3G with excellent ability to resist oxidative stress specially targeted for ubl-5 has a promising application in controlling copper contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Increasingly copper pollution in the environment exacerbates the risk of neurodegenerative diseases. It is necessary to look for effective targets and safe methods for protecting from copper-induced neurotoxicity. Here we firstly explored the impact of copper-exposure on expression profiles in zebrafish. Copper reduced embryo hatching, increased mortality and caused embryonic developmental abnormalities and behavioral dysfunction in juveniles. Transcriptomic analysis revealed that differential genes related to neuron were highly associated with oxidative stress especially enriched to FoxO pathway. Through further validation in Caenorhabditis elegans, copper resulted in nematode neurodegenerative movement disorders and neuronal damage, along with increased levels of reactive oxygen species (ROS) as well as decreased expressions of antioxidant-related enzymes and downstream genes which was also involved in FoxO signaling pathway. Bacillus smithii XY1, a novel strain with an excellent antioxidative activity, showed a great alleviative effect on copper-induced neurotoxicity that was related to FoxO stimulation, being a potential candidate for copper pollution management. Overall, these results suggested that FoxO pathway activation can regard as a strategy for mitigating neurotoxicity caused by copper and B. smithii XY1 with excellent tolerance and outstanding antioxidation specially targeted for FoxO has a promising application in controlling copper contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Copper (Cu) pollution has become a serious environmental problem especially in recent decades. In this study, the mechanisms of Bacillus coagulans (Weizmannia coagulans) XY2 against Cu-induced oxidative stress were explored through a dual model. In mice, Cu disturbed microbial community structure, revealing an increased level of Enterorhabdus abundance and decreased levels of Intestinimonas, Faecalibaculu, Ruminococcaceae and Coriobacteriaceae_UCG-002 abundance. Meanwhile, B. coagulans (W. coagulans) XY2 intervention reversed this trend along with alleviated Cu-induced metabolic disturbances by increasing levels of hypotaurine and L-glutamate and declining levels of phosphatidylcholine and phosphatidylethanolamine. In Caenorhabditis elegans, nuclear translocation of DAF-16 and SKN-1 was inhibited by Cu, which in turn suppressed antioxidant-related enzymes activities. XY2 mitigated biotoxicity associated with oxidative damage caused by Cu exposure via regulating DAF-16/FoxO and SKN-1/Nrf2 pathways and intestinal flora to eliminate excess ROS. Our study provides a theoretical basis formulating future strategy of probiotics against heavy metal contamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Copper (Cu) is a kind of micronutrient element that is essential for human metabolism. However, it is also considered as an environmental pollutant which is toxic to organisms at a high concentration level. Probiotics, regarded as beneficial microorganisms for promoting human health, have functions of antioxidant capacity, immune-enhancing properties, intestinal barrier protection and regulation. Several studies have reported that probiotics show positive effects on alleviating and intervening heavy metals toxicity. However, evidence for relieving copper-induced toxicity by probiotics is still limited. In this study, we firstly conducted a zebrafish larvae model to screen out microorganisms which are helpful for CuSO 4 toxicity resistance and one novel strain named as Bacillus coagulans XY2 was discovered with the best protective activity. B. coagulans XY2 significantly reduced the mortality of zebrafish larvae exposed to 10 µmol/L CuSO 4 for 96 hr, as well as alleviated the neutrophils infiltration in the larvae lateral line under a 2 hr exposure. B. coagulans XY2 exhibited a high in vitro antioxidant activity and against CuSO 4 -induced oxidative stress in zebrafish larvae by up-regulating sod1, gstp1 and cat gene transcriptional levels and relevant enzymatic activities. CuSO 4 stimulated the inflammation process resulting in obvious increases of gene il-1β and il-10 transcription, which were suppressed by B. coagulans XY2 intervention. Overall, our results underline the bio-function of B. coagulans XY2 on protecting zebrafish larvae from copper toxicity, suggesting the potential application values of probiotics in copper toxicity alleviation on human and the environment. [Display omitted] [ABSTRACT FROM AUTHOR]