更新于：2024-11-01

GSR x TrxR1

更新于：2024-11-01

基本信息

关联

项与 GSR x TrxR1 相关的药物

SIMR-1281

靶点

GSR x TrxR1

作用机制

GSR inhibitors [+1]

在研机构

University of Sharjah

原研机构

University of Sharjah

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GSR x TrxR1 相关的临床结果

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100 项与 GSR x TrxR1 相关的转化医学

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0 项与 GSR x TrxR1 相关的专利（医药）

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项与 GSR x TrxR1 相关的文献（医药）

2024-03-01·Journal of Hazardous Materials

Nanoparticles with intermediate hydrophobicity polarize macrophages to plaque-specific Mox phenotype via Nrf2 and HO-1 activation

Article

作者: Alves, Colby ; Cui, Xiaomiao ; Qu, Guangbo ; Jiang, Guibin ; Liu, Yujia ; Jiang, Mingdi ; Yan, Bing ; Rotello, Vincent M ; Hirschbiegel, Cristina-Maria ; Liu, Yuanchang ; Lee, Yi-Wei ; Zhang, Xianzhi ; Zhai, Shumei

Mox macrophages were identified recently and are closely associated with atherosclerosis. Considering the potential health risks and the impact on macrophage modulation, this study investigated the Mox polarization of macrophages induced by nanoparticles (NPs) with tunable hydrophobicity. One nanoparticle (C4NP) with intermediate hydrophobicity efficiently upregulated the mRNA expression of Mox-related genes including HO-1, Srxn1, Txnrd1, Gsr, Vegf and Cox-2 through increased accumulation of Nrf2 at a nontoxic concentration in both resting and LPS-challenged macrophages. Additionally, C4NP impaired phagocytic capacity by 20% and significantly increased the secretion of cytokines, including TNFα, IL-6 and IL-10. Mechanistic studies indicated that intracellular reactive oxygen species (ROS) were elevated by 1.5-fold and 2.6-fold in resting and LPS-challenged macrophages respectively. Phosphorylated p62 was increased by 2.5-fold in resting macrophages and maintained a high level in LPS-challenged ones, both of which partially accounted for the significant accumulation of Nrf2 and HO-1. Notably, C4NP depolarized mitochondrial membrane potential by more than 50% and switched macrophages from oxidative phosphorylation-based aerobic metabolism to glycolysis for energy supply. Overall, this study reveals a novel molecular mechanism potentially involving ROS-Nrf2-p62 signaling in mediating macrophage Mox polarization, holding promise in ensuring safer and more efficient use of nanomaterials.

2023-12-01·Biological Trace Element Research

The Effects of In Ovo Feeding of Selenized Glucose on Selenium Concentration and Antioxidant Capacity of Breast Muscle in Neonatal Broilers

Article

作者: Gong, Daoqing ; Shi, Qiao ; Yu, Lei ; Zhao, Minmeng ; Geng, Tuoyu ; Shan, Haoshu ; Li, Jiahui ; Liu, Long

This study aims to investigate the impacts of in ovo feeding (IOF) of selenized glucose (SeGlu) on selenium (Se) level and antioxidant capacity of breast muscle in newborn broilers. After candling on 16 day of incubation, a total of 450 eggs were randomly divided into three treatments. On the 17.5th day of incubation, eggs in a control treatment were injected with 0.1 mL of physiological saline (0.75%), while the 2nd group and 3rd group were supplied with 0.1 mL of physiological saline containing 10 μg Se from SeGlu (SeGlu₁₀ group) and 20 μg Se from SeGlu (SeGlu₂₀ group). The results showed that in ovo injection in both SeGlu₁₀ and SeGlu₂₀ increased the Se level and reduced glutathione concentration (GSH) in pectoral muscle of hatchlings (P < 0.05). Compared with the control group, the SeGlu₂₀-treated chicks significantly enhanced the activity of the superoxide dismutase (SOD) and mRNA expression of NAD(P)H quinone dehydrogenase 1 (NQO1) in breast muscle, while there was upregulation in mRNA expressions of glutathione peroxidase 1 (GPX-1) and thioredoxin reductase 1 (TrxR1) and higher total antioxidant capacity (T-AOC) in SeGlu₁₀ treatment (P < 0.05). However, no significant difference on enzyme activities of glutathione peroxidase (GR), glutathione reductase, thioredoxin reductase, concentration of malondialdehyde, and free radical scavenging ability (FRSA) of superoxide radical (O₂^-•) and hydroxyl radical (OH^•) was observed among the three treatments (P > 0.05). Therefore, IOF of SeGlu enhanced Se deposition in breast muscle of neonatal broilers. In addition, in ovo injection of SeGlu could increase the antioxidant capacity of newborn chicks possibly through upregulating the mRNA expression of GPX1, TrxR1, and NQO1, as well as the SOD activity.

2023-01-01·Computers in Biology and Medicine

Omics-based identification of an NRF2-related auranofin resistance signature in cancer: Insights into drug repurposing

Article

作者: Stefanes, Natália Marcéli ; Dos Santos, Barbara ; Almeida, Karoline ; Zanotto-Filho, Alfeu ; das Neves, Raquel Nascimento ; Santos-Silva, Maria Cláudia ; Zancanaro, Helena ; Delgobo, Marina ; Falchetti, Marcelo ; Bishop, Alexander

Auranofin is a thioredoxin reductase-1 inhibitor originally approved for the treatment of rheumatoid arthritis. Recently, auranofin has been repurposed as an anticancer drug, with pharmacological activity reported in multiple cancer types. In this study, we characterized transcriptional and genetic alterations associated with auranofin response in cancer. By integrating data from an auranofin cytotoxicity screen with transcriptome profiling of lung cancer cell lines, we identified an auranofin resistance signature comprising 29 genes, most of which are classical targets of the transcription factor NRF2, such as genes involved in glutathione metabolism (GCLC, GSR, SLC7A11) and thioredoxin system (TXN, TXNRD1). Pan-cancer analysis revealed that mutations in NRF2 pathway genes, namely KEAP1 and NFE2L2, are strongly associated with overexpression of the auranofin resistance gene set. By clustering cancer types based on auranofin resistance signature expression, hepatocellular carcinoma, and a subset of non-small cell lung cancer, head-neck squamous cell carcinoma, and esophageal cancer carrying NFE2L2/KEAP1 mutations were predicted resistant, whereas leukemia, lymphoma, and multiple myeloma were predicted sensitive to auranofin. Cell viability assays in a panel of 20 cancer cell lines confirmed the augmented sensitivity of hematological cancers to auranofin; an effect associated with dependence upon glutathione and decreased expression of NRF2 target genes involved in GSH synthesis and recycling (GCLC, GCLM and GSR) in these cancer types. In summary, the omics-based identification of sensitive/resistant cancers and genetic alterations associated with these phenotypes may guide an appropriate repurposing of auranofin in cancer therapy.