International Journal of Biological Sciences
·
2026
·Vol. 22
·期 12
·6363
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IF 11.7
Ziyang Ding,Sisi Wang,Junhui Chen,Yali Song,Zhou Zhu,Haibo Tong,Ashok Iyaswamy,Peng Chen,Xu Wei,Wei Zhang,Jigang Wang,Chuanbin Yang,Yulin Feng
Oridonin is a bioactive diterpenoid derived from the widely used traditional Chinese medicinal herb Rabdosia rubescens , exhibits broad-spectrum anti-cancer activity, with several derivatives currently in clinical trials. However, the molecular mechanism underlying its anticancer effects, especially its direct target proteins, remain to be fully elucidated. Here, we found that Oridonin promoted intracellular reactive oxygen species (ROS) accumulation, which in turn induced endoplasmic reticulum (ER) stress-mediated apoptosis. Moreover, ER stress was instrumental in inducing autophagy after Oridonin treatment, while blockade of autophagy further exacerbated Oridonin-induced cytotoxicity. Notably, using activity-based protein profiling (ABPP), we identified the anti-oxidant enzyme Peroxiredoxin 1 (PRDX1) as a key direct covalent target of Oridonin. By binding to Cysteine 173 of PRDX1, Oridonin increased intracellular ROS levels. Furthermore, PRDX1 over-expression mitigated, whereas PRDX1 knockdown potentiated, Oridonin-induced ROS accumulation, autophagy, and subsequently apoptosis. Overall, our results indicate that PRDX1 is a direct covalent binding target mediating Oridonin-induced apoptosis. These findings not only provide fresh insights into the core mechanism of Oridonin-induced cytotoxicity, but also highlight PRDX1 as a potential therapeutic target for renal cancer drug development.
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高影响因子
TALANTA
·
2026
·
IF 6.7
Kun Cheng,Heng-Biao Zhang,Hua-Rong Xie,Li Wang,Tong Zhang,Shun Wan,Jian-Wei Yang,Pan-Guan Hong,Xu-Yan Wang,Pan-Pan Jiao,Chang-Hong Xu,Yi-di Deng,Si-Yu Chen,Li-yun Ding,Li Yang
In this study, integrated proteomic and transcriptomic analyses identified peroxiredoxin 1 (PRDX1) as a novel urinary biomarker for bladder cancer (BC). PRDX1 was significantly upregulated in BC tissues and was associated with poorer overall survival. In vitro experiments further demonstrated that PRDX1 promotes malignant phenotypes of BC cells, including proliferation, migration, and invasion. Silencing PRDX1 in BC cells significantly reduced the invasiveness and proliferation ability.To address the clinical need for rapid and non-invasive detection, we developed an innovative optical fiber biosensor based on surface plasmon resonance (SPR) technology for the quantitative detection of urinary PRDX1. The biosensor exhibited excellent analytical performance, including high sensitivity (limit of detection: 0.06 ng/mL), a wide linear range (0–25 ng/mL), rapid response (∼14 s), as well as good stability and selectivity. In clinical validation involving 97 BC patients and 30 healthy controls, the biosensor demonstrated outstanding diagnostic performance, with an area under the receiver operating characteristic curve (AUC) of 0.91 and an overall diagnostic accuracy of 86.6%, outperforming conventional enzyme-linked immunosorbent assay (ELISA). Collectively, this study not only identifies PRDX1 as a promising biomarker for non-invasive diagnosis and prognostic evaluation of BC, but also establishes an efficient SPR-based optical fiber sensing platform, providing new insights into both clinical detection and the functional role of PRDX1 in BC progression.
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高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Wang Hong,Yao Shun,Mo Qingyun,Chen Mingyue,He Danfeng,Yan Lingfeng,Wang Chang,Zou Tao,Luo Gaoxing,Deng Jun
Excessive oxidative stress and dysregulated macrophage polarisation—characterised by M1/M2 imbalance—drive chronic, persistent inflammation and represent key pathological mechanisms underlying impaired tissue repair in diabetic wounds; however, therapeutic strategies targeting both these processes remain limited. L-Arginine (L-Arg) shows therapeutic potential through its antioxidant properties and ability to promote M1 macrophage polarization. Nevertheless, the mechanisms by which L-Arg regulates mitochondrial homeostasis to exert antioxidant effects remain unclear. Moreover, its clinical translation is hindered by poor retention, inadequate tissue penetration, and damage induced by hypertonicity, thereby necessitating the development of innovative delivery systems. To address these limitations, we developed an L-Arg-loaded microneedle (L-Arg-MN) patch for controlled delivery. Our findings demonstrate that L-Arg alleviated hydrogen peroxide (H2O2)-induced cellular damage through activation of the Kelch-like ECH-associated protein 1(KEAP1)- nuclear factor erythroid 2-related factor 2 (Nrf2)-Heme Oxygenase-1(HO-1) pathway, boosting antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and lowering malondialdehyde (MDA) levels. Mechanistically, L-Arg maintained mitochondrial homeostasis by upregulating peroxiredoxin 1 (PRDX1) expression, restoring mitochondrial membrane potential, and enhancing adenosine triphosphate production. Furthermore, L-Arg suppressed M1 macrophage polarisation and promoted M2 polarisation through PRDX1-mediated mitochondrial metabolic pathways. In models of diabetic wounds, the L-Arg-MN patch markedly enhanced the wound healing process, accelerated wound closure, reduced concentration of reactive oxygen species (ROS), enhanced granulation tissue, collagen formation, and increased M2 macrophage infiltration. This study elucidates how L-Arg reduces oxidative stress and enhances M2 macrophage polarisation by regulating mitochondrial metabolism through the PRDX1 pathway. By integrating the metabolic and immunomodulatory properties of L-Arg with advanced drug delivery technology, the L-Arg-MN patch presents an innovative and efficient approach to treating diabetic wounds.
研究领域:
药剂学
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免疫学
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生物化学
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生物医学工程
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伤口愈合
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氧化应激研究
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