BIOCHEMICAL PHARMACOLOGY
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2024
·
IF 5.3
Xiaodan Zhang,Lihong Zhou,Yulong Peng,Shiyu He,Zhen Mao,Jin Cai,Aobo Geng,Hong Yang,Peili Huang
Copper serves as an indispensable cofactor for all living organisms, and its excessive accumulation has been associated with a variety of diseases. Wilson’s disease (WD) serves as an illustrative example of copper toxicity in humans, frequently presenting with liver and/or neuropsychiatric symptoms. The current therapeutic drugs, penicillamine (PA) and zinc gluconate (ZnG), have constraints, and research on their combination efficacy remains insufficient. It has been reported that melatonin (MLT) plays a vital role in binding to transition metals and exhibits strong antioxidant capacity. To investigate the therapeutic efficacy of MLT and combined treatment, rats were randomly divided into the following seven groups: the control (Con) group, copper-laden model rat (Mod) group, PA-treated group, ZnG-treated group, MLT- treated group, PA-ZnG-treated group, and PA-MLT-treated group. Then potential mechanisms and targets were investigated using a combination of metabolomics and network pharmacology and verified by molecular docking and qPCR. The findings revealed that MLT and the combination significantly improved behavior, pathology and copper levels in copper-laden rats. The results of the metabolomics study showed that profoundly altered metabolites were identified, and alanine, aspartate and glutamate metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis were explored. In addition, molecular docking showed that MLT had high binding affinity with key targets, and qPCR results revealed that MLT could reverse the mRNA expression of targets GOT2 and PKM2. It was concluded that MLT effectively improves brain injury in copper-laden rats, and this effect was linked with the altered features of the metabolite profiles.
研究领域:
神经科学
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药理学
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代谢组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Agronomy-Basel
·
2024
·Vol. 14
·期 6
·1302
·
IF 3.3
Xianghan Cheng,Feifei Liu,Peng Song,Xiaolei Liu,Qin Liu,Taiji Kou
The changes in biomass (including yield), copper (Cu) concentration, and the accumulation of wheat (Triticum aestivum. L) in response to soil Cu pollution under nighttime warming had still not been explored. Hence, this study was carried out, and these variations were analyzed from a physiological perspective. Pot trials were performed at two levels of ambient temperatures (no-warming (NT) and average nighttime warming of 0.28 °C (WT)) and two levels of soil Cu concentrations (control check without Cu application (CK) and 100 mg/kg Cu application (Cu)). Soil was collected from the carbonate cinnamon soil region of central China. The warming effects of the passive nighttime warming system were prominent, and the average increment was 0.28 °C. Antioxidant enzyme activities were promoted by warming (p< 0.05) and Cu. The highest yield was achieved in NT-Cu, mainly attributed to relatively strong root activity and photosynthesis caused by supplemental Cu, but the Cu concentration in its grains was close to the threshold (10 mg/kg) for Cu concentration in foodstuff and could present a potential food safety risk. Though nighttime warming did not increase the total biomass and yield of wheat, it decreased the Cu accumulation of wheat grown in Cu-contaminated soil, especially in grains. Moreover, WT-CK and WT-Cu increased the Cu concentration in the roots and glumes and reduced the Cu concentration in grains by 13.09% and 55.84%, respectively, probably because of a lower transpiration rate. Among them, the Cu concentration of grains in WT-Cu was the lowest and significantly lower than other applications. Our findings reveal that nighttime warming has the potential to reduce the Cu risk of grains in wheat grown in the Cu-contaminated carbonate cinnamon soil region of central China and could then provide a theoretical reference for risk assessment of food quality for wheat subjected to dual stress from nighttime warming and Cu pollution.
研究领域:
植物生理学
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环境科学
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农业科学
✓ 已验证
产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2016
·
IF 3.976
Taowu Ma,Shuangjiao Gong,Bin Tian
Copper oxide nanoparticles (CuO-NPs) may pose high ecological risks to aquatic ecosystems. While sediments are the final destinations for CuO-NPs, little is known about the potential ecotoxicity of sediment-associated CuO-NPs on freshwater deposit-feeding macroinvertebrates. The gastropod Bellamya aeruginosa was chosen as an ecotoxicological test species. Adult snails were exposed to Cu (180 μg/g dry weight (DW)) added to sediments in the form of CuO-NPs, CuO microparticles (CuO-MPs, size control), and CuSO 4 (solubility control) for 7, 14, and 28 days, Cu burdens in different tissues and biomarkers of oxidative stress were determined to understand Cu accumulation differences among tissues, potential mechanisms of Cu uptake, time-effect relationships, particle size effects, and the relative contribution of toxicity from CuO-NPs and its soluble Cu ions. There was no difference in Cu ion concentrations in porewaters between the CuO-NPs and CuO-MPs treatments. In addition, relatively low Cu ion concentrations in porewater might indicate their remarkably low solubility. The hepatopancreas and gonad of B. aeruginosa are the primary target tissues for Cu accumulation. Cu accumulation in the hepatopancreas and gonad from CuSO 4 treatments was consistently higher than that from the CuO-NPs and CuO-MPs treatments. After long-term exposure, Cu accumulation was higher from CuO-NPs than from CuO-MPs, especially, the Cu accumulation rate from CuO-NPs was greater than that from CuSO 4 . Short-term exposure to the three Cu forms caused oxidative stress to the hepatopancreas. CuO-MPs did not cause oxidative damage. Long-term exposure to CuO-NPs and CuSO 4 resulted in oxidative damage. Overall, prolonged exposure to CuO-NPs will increase the ecotoxicity risk to B. aeruginosa . Although there was no difference in Cu accumulation between the CuO-NPs and CuO-MPs treatments after 14 days of exposure, pronounced oxidative damage was caused by exposure to CuO-NPs but not to CuO-MPs, implying that toxicity of CuO-NPs could be attributed to specific nanoparticulate effects.
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Ziwei Chen,Jia Liu,Manjia Zheng,Minhua Mo,Xiaowen Hu,Chang Liu,Janak Lal Pathak,Lijing Wang,Liangjiao Chen
Yttrium oxide nanoparticles (Y 2 O 3 NPs), extensively utilized rare earth nanoparticles, exhibited a diverse range of applications across various fields, which leading to increased human exposure. Moreover, potential neurotoxic risks have been associated with their use, yet the underlying mechanism remains unclear. The present study aimed to investigate the effects of Y 2 O 3 NPs on cognitive function in rats with a particular focus on elucidating the pivotal role played by astrocytes in this process. The results demonstrated that Y 2 O 3 NPs induced cognitive and memory impairment in rats, copper (Cu) accumulation and cuproptosis of astrocytes as contributing factors. Furthermore, we elucidated that Y 2 O 3 NPs induced astrocytes cuproptosis by inhibiting TRIM24/DTNBP1/ATP7A signaling pathway-mediated cellular Cu efflux. We provide, for the first time, the important involvement of astrocytes in Y 2 O 3 NPs-induced neurotoxicity, elucidating that cuproptosis as the primary mode of cell death. These results offer valuable insights for the future safe application of rare earth nanoparticles in field of neurology.
研究领域:
神经科学
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毒理学
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纳米技术
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Cells
·
2025
·Vol. 14
·期 6
·391
·
IF 5.2
Yuhan Fu,Lirui Hou,Kai Han,Chong Zhao,Hongbo Hu,Shutao Yin
Background: Cuproptosis is a form of copper-dependent non-apoptotic cell death. Cancer cells that prefer to use aerobic glycolysis for energy generation are commonly insensitive to cuproptosis, which hinders its application for cancer treatment. Epigallocatechin gallate (EGCG) possesses diverse pharmacological activities. However, the association between EGCG and cuproptosis has not been studied. Methods: The cell viability, proliferation, and cuproptosis-related protein levels were detected to investigate whether EGCG enhances the sensitivity of HCC cells to cuproptosis. The intracellular copper level, related copper metabolism proteins, and gene expression were detected to explore the mechanisms. In addition, a nude mouse xenograft model was established to determine the effects of EGCG on cuproptosis in tumor tissues. Results: The combination of EGCG and copper ionophores significantly enhanced the mortality of HCC cells and heightened the sensitivity of HCC cells to cuproptosis. There was a notable reduction in the expression of copper export protein copper-transporting P-type ATPase (ATP7B). EGCG effectively suppressed metal regulatory transcription factor (MTF1) expression and subsequently hindered the transcriptional regulation of ATP7B. EGCG also facilitated the intratumoral accumulation of copper and augmented susceptibility to cuproptosis in vivo. Conclusions: EGCG can increase the sensitivity of hepatocellular carcinoma cells to cuproptosis by promoting intracellular copper accumulation through the MTF1/ATP7B axis.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）