Theranostics
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2015
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IF 8.022
Chunlei Zhang,Zhijun Zhou,Xiao Zhi,Yue Ma,Kan Wang,Yuxia Wang,Yingge Zhang,Hualin Fu,Weilin Jin,Fei Pan,Daxiang Cui
Chiral gold nanoclusters (Au NCs) exhibit attracting properties owing to their unique physical and chemical properties. Herein we report for the first time chiral gold nanoclusters' cytotoxicity and potential molecular mechanism. The L-glutathione (i.e. L-GSH) and D-glutathione (i.e. D-GSH)-capped Au NCs were prepared and characterized by HRTEM, UV-vis, photoluminescence and circular dichroism (CD) spectroscopy. Results showed that the CD spectra of L-glutathione (i.e. L-GSH) and D-glutathione (i.e. D-GSH)-capped Au NCs exhibited multiple bands which were identically mirror-imaged, demonstrating that the chirality of GSH-capped NCs had contributions from both the metal core and the ligand. The effects of AuNCs@L-GSH and AuNCs@D-GSH on cells were similar based on the cell physiology related cytotoxicity, although the effects became more prominent in AuNCs@D-GSH treated cells, including ROS generation, mitochondrial membrane depolarization, cell cycle arrest and apoptosis. Global gene expression and pathway analysis displayed that both AuNCs@L-GSH and AuNCs@D-GSH caused the up-regulation of genes involved in cellular rescue and stress response, while AuNCs@D-GSH individually induced up-regulation of transcripts involved in some metabolic- and biosynthetic-related response. MGC-803 cells were more sensitive to the oxidative stress damage induced by chiral Au NCs than GES-1 cells, which was associated with GSTP1 hypermethylation. In conclusion, chiral gold nanoclusters exhibit this chirality-associated regulation of cytotoxicity, different gene expression profiling and epigenetic changes should be responsible for observed phenomena. Our study highlights the importance of the interplays between chiral materials and biological system at sub-nano level.
研究领域:
纳米技术
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生物医学工程
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分子生物学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2026
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IF 5.1
Gaiqian Song,Ayixia Abudula,Moyisa Simayi,Hongning Liu,Hao Lin
Taxol remains a cornerstone therapy for non-small cell lung cancer, however, the development of acquired resistance continues to pose a significant clinical hurdle. Glutathione S-transferase P1 (GSTP1) and P-glycoprotein (P-gp) have been identified as key mediators of this multi-drug resistance phenotype. Consequently, the dual-target inhibition of these proteins represents a promising therapeutic strategy to circumvent chemoresistance. Here, pentagalloylglucose has been identified as a potential dual GSTP1/P-gp inhibitor through virtual screening. Molecular dynamics simulations validated the stable binding conformations of pentagalloylglucose with both target proteins. Furthermore, microscale thermophoresis and cellular thermal shift assays confirmed the direct binding interaction between pentagalloylglucose and GSTP1, while enzymatic assays demonstrated its potent inhibitory efficacy against the enzyme. Notably, treatment with pentagalloylglucose significantly enhanced the intracellular accumulation of Rhodamine 123, thereby indicating effective inhibition of P-gp mediated efflux. This effect culminated in a marked restoration of taxol sensitivity in A549/Taxol resistant cells. Additionally, pentagalloylglucose treatment inhibited cell metastasis in a concentration-dependent manner, accompanied by the down-regulation of epithelial-mesenchymal transition-related genes. Transcriptomic analysis further revealed that pentagalloylglucose modulates multiple signaling pathways implicated in cell proliferation and metastasis. Collectively, these findings establish pentagalloylglucose as a promising dual-target inhibitor for overcoming taxol resistance. The strategy of simultaneously targeting GSTP1 and P-gp offers a viable approach for the treatment of drug-resistant lung adenocarcinoma, providing a robust scientific foundation for future drug development and structural optimization.
✓ 已验证
产品关联
DOI
高影响因子
Journal of Agriculture and Food Research
·
2026
·
IF 7.2
Guoyong Li,Haoyu Lei,Xingchen Pan,Angen Yu,Haokun Liu,Mette Sørensen,Dong Han,Zhi Luo,Cui Liu,Yulong Gong
Abnormal pigmentation compromises the commercial value of aquatic products. However, the mechanism of pigment deposition in fish remains elusive. This study employs corn gluten meal (CGM) as a natural source to elucidate the deposition mechanism of key pigment(s) in yellow catfish. We demonstrated that inclusion of 20% CGM with 0.6% lysine in feed significantly improved the yellow-blue axis and chroma values in the dorsal and abdominal skin ( P < 0.05). Metabolic analysis showed that CGM significantly increased the zeaxanthin and lutein deposition in yellow catfish skin ( P < 0.05), with zeaxanthin/zeaxanthin palmitate exhibited the highest increase ( P < 0.001). Using pure carotenoids as pigment sources, we illustrated that zeaxanthin deposition was sufficient to improve the yellow-blue axis and chroma values in the dorsal and abdominal skin of yellow catfish ( P < 0.05). Combining RNA-seq data, we discovered that CGM significantly increased skin apolipoprotein E (ApoE) and glutathione S-transferase Pi 1 (GSTP1) protein levels (27% rise, P < 0.05). The affinity assays further revealed zeaxanthin was transported by ApoE to binding GSTP1, as reflected by a 1.11 °C increase in the protein denaturation temperature of GSTP1. We therefore elucidate the mechanism for pigment deposition in the skin of yellow catfish and provide the accurate target for improving the appearance quality of aquatic products.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Mingbo Wu,Wenwu Ling,Jiaojun Wei,Ran Liao,Haiyue Sun,Dongqiu Li,Ye Zhao,Long Zhao
As a novel non-apoptotic cell death pathway, ferroptosis can effectively enhance the antitumor effects of photodynamic therapy (PDT) by disrupting intracellular redox homeostasis. However, the reported nanocomposites that combined the PDT and ferroptosis are cumbersome to prepare, and the unfavorable tumor microenvironment also severely interferes with their tumor suppressive effects. To address this inherent barrier, this study attempted to explore photosensitizers that could activate ferroptosis pathway and found that the photosensitizer aloe-emodin (AE) could induce cellular ferroptosis based on its specific inhibiting activity to Glutathione S-transferase P1(GSTP1), a key protein for ferroptosis. Herein, we prepared [email protected] /Fe nanocrystals (NCs) with synergistic PDT and ferroptosis therapeutic effects by one-step emulsification to obtain AE NCs cores and further modification of red blood cells (RBC) membranes and ferritin. Benefiting from the involvement of ferritin, the prepared [email protected] /Fe NCs provide not only sufficient oxygen for oxygen-dependent PDT, but also Fe 3+ for iron-dependent ferroptosis in tumor cells. Furthermore, the biomimetic surface functionalization facilitated the prolonged circulation and cancer targeting of [email protected] /Fe NCs in vivo . The in vitro and in vivo results demonstrate that [email protected] /Fe NCs exhibit significantly enhanced therapeutic effects for the combined two antitumor mechanisms and provide a promising prospect for achieving PDT/ferroptosis synergistic therapy.
研究领域:
癌症治疗
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纳米技术
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药理学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iMeta
·
2025
·Vol. 4
·期 6
·e70100
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IF 33.2
Sen-Lin Zhu,Yu-Nan Yan,Ming-Hui Jia,Hou-Cheng Li,Bo Han,Tao Shi,Lian-Bin Xu,Xiao-Wen Wang,Qi Zhang,Wei-Jie Zheng,Jing-Hong Xu,Liang Chen,Wenlingli Qi,Sheng-Jun Cai,Xin-Peng Chen,Feng-Fei Gu,Jian-Xin Liu,George E. Liu,Yu Jiang,Dong-Xiao Sun,Ling-Zhao Fang,Hui-Zeng Sun
Oxygen signaling is essential for cellular homeostasis and tightly linked to metabolism, growth, and survival. In dairy cows, oxidative stress, arising from an imbalance between reactive oxygen species and antioxidants, is a major postpartum challenge that contributes to disease susceptibility. Using single-cell transcriptomes from 1,793,854 cells across 59 tissues, we analyzed oxygen signaling states within 1006 cellular clusters. The gastrointestinal tract (GIT) epithelium, particularly the forestomach, exhibits the strongest antioxidant activity, closely coupled to oxidative phosphorylation (OXPHOS) and glycolysis, with OXPHOS levels surpassing those of cardiomyocytes and hepatocytes (Cohen's d > 3.9, p < 0.001). Pseudotime and spatial transcriptomics demonstrated that both OXPHOS and antioxidant capacity increase progressively along the basal-to-luminal differentiation axis. Functional experiments in primary rumen epithelial cells showed that antioxidant supplementation or GPX1 modulation enhances mitochondrial respiration, boosts intracellular glutathione, and accelerates epithelial differentiation. Limited proteolysis-mass spectrometry (LiP-MS) analysis identified GPX1 , GSTP1 , COX7A2 , and COX6B1 as candidate targets mediating antioxidant-driven metabolic remodeling. Together, these results reveal a redox-governed metabolic program in the forestomach epithelium and highlight antioxidant interventions as a potential strategy to support epithelial development and mitigate oxidative stress-related disorders in dairy cattle. Graphical Single-cell and transcriptomics from 1.79 million cells identify the forestomach epithelium as the dominant site of antioxidant activity and oxidative phosphorylation (OXPHOS) in the bovine gastrointestinal tract. Along the basal-to-luminal differentiation axis, antioxidant capacity and OXPHOS rise in a coordinated metabolic–redox gradient. Primary rumen cell assays show that this gradient is strengthened by Cys-Cys-Cys supplementation or modulation of GPX1 expression, demonstrating a direct causal influence on epithelial metabolism. Key redox-metabolic regulators, including GPX1 and GSTP1 , mediate these responses. Overall, antioxidants actively drive metabolic remodeling and promote epithelial differentiation in the cattle forestomach epithelium. Highlights A single-cell transcriptomic atlas of 1.79 million bovine cells revealed the forestomach epithelium as one of the most antioxidant-active tissues. As the forestomach epithelium differentiates from the basal layer towards the luminal surface, both mitochondrial respiration and antioxidant capacity progressively intensify, establishing a coupled metabolic–redox gradient. Functional assays identified GPX1 as a key antioxidant target mediating OXPHOS and cell differentiation.
研究领域:
动物科学
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反刍动物生理学
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转录组学
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氧化还原生物学
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代谢
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单细胞分析
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）