ACS Omega
·
2023
·
IF 4.1
Lina Wen,Xiaoyu Du,Tianci Liu,Wen Meng,Tao Li,Mengjie Li,Man Zhang
Clusterin has the potential to become the biomarker of multiple diseases, but its clinical quantitative detection methods are limited, which restricts its research progress as a biomarker. A rapid and visible colorimetric sensor for clusterin detection based on sodium chloride-induced aggregation characteristic of gold nanoparticles (AuNPs) was successfully constructed. Unlike the existing methods based on antigen–antibody recognition reactions, the aptamer of clusterin was used as the sensing recognition element. The aptamer could protect AuNPs from aggregation caused by sodium chloride, but clusterin bound with aptamer detached it from AuNPs, thereby inducing aggregation again. Simultaneously, the color change from red in the dispersed state to purple gray in the aggregated state made it possible to preliminarily judge the concentration of clusterin by observation. This biosensor showed a linear range of 0.02–2 ng/mL and good sensitivity with a detection limit of 5.37 pg/mL. The test results of clusterin in spiked human urine confirmed that the recovery rate was satisfactory. The proposed strategy is helpful for the development of label-free point-of-care testing equipment for clinical testing of clusterin, which is cost-effective and feasible.
研究领域:
生物传感
·
临床诊断
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Cell Stem Cell
·
2025
·
IF 20.4
Lei Fan,Qi Tang,Yutong Wang,Hang Sun,Ge Li,Yi Yang,Huiying Zhu,Zhaoyuan Liu,He Wang,Hongyan Wang,Qing Jing,Christopher L. Antos,Hui Xiao,Renchu Guan,Gang Pei,Florent Ginhoux,Zhigang Zhou,An Zeng
Adult hearts scar after injury, while neonatal hearts regenerate. The mechanisms underlying this dichotomy remain unclear. Through comparative spatiotemporal single-cell analyses and dual recombinase-mediated lineage tracing, we uncovered an injury-induced Clusterin + cardiomyocyte ( Clu + CM) population that coordinates reparative, anti-inflammatory macrophage activity. Following injury, Clu + CMs emerge in the border zone of regenerative hearts but are scarce in non-regenerative contexts. These CMs secrete CLU, which binds to macrophage Toll-like receptor 4 (TLR4), attenuating inflammation and promoting reparative polarization through Cpt1a -dependent fatty acid oxidation. These macrophages secrete bone morphogenetic protein 2 (BMP2), activating bone morphogenetic protein receptor, type 1A (BMPR1A) signaling in CMs to drive proliferation. Reduced CLU levels in myocardial infarction patients correlate with impaired cardiac function, whereas Clu overexpression or transplantation of engineered CLU + human cardiac organoids recapitulates this regenerative modulation, enhancing myocardial repair in adult mice. Our findings reveal a critical cardio-immune mechanism whereby Clu + CMs reprogram macrophages to resolve inflammation and stimulate CM proliferation, providing potential strategies for cardiac regeneration.
研究领域:
心脏病学
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免疫学
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再生医学
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分子生物学
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细胞信号传导
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DOI
PubMed
高影响因子
Toxicology Research
·
2018
·Vol. 7
·期 6
·1205-1213
·
IF 1.89
Qiu Xuan,Zhou Xiaobing,Miao Yufa,Li Bo
The kidney is one of the major target organs for drug-induced toxicity. During drug development, the traditional markers of nephrotoxicity indicate only severe and late damage, which leads to high costs. The new biomarkers are needed for a more sensitive and reliable evaluation of nephrotoxicity, especially for the regulatory accepted and validated in vitro model. We developed an in vitro model based on the HK-2 cell using the biomarkers of nephrotoxicity as endpoints for the evaluation of nephrotoxicity. The predictive performance of the biomarkers including LDH, GGT, KIM-1, clusterin, CysC, NGAL, TIMP-1, GSTπ and osteopontin was evaluated with 22 well characterized compounds. The area under the curve (AUC) values of KIM-1, clusterin, CysC and osteopontin ranged between 0.79 and 0.84. The combination of clusterin, KIM-1 and/or osteopontin improved the AUC value (ranging between 0.88 and 0.95) compared to one biomarker. Taken together, these results suggest that the model based on the HK-2 cell using clusterin, osteopontin, CysC and KIM-1 as endpoints would allow the prediction of nephrotoxicity at early preclinical stages.
研究领域:
毒理学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
·
2024
·Vol. 28
·期 3
·219-227
·
IF 1.6
Peiyu Lin,Xiyue Yang,Linghui Wang,Xin Zou,Lingli Mu,Cangcang Xu,Xiaoping Yang
Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC 50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2026
·Vol. 83
·期 1
·143
·
IF 6.5
Yucheng Ma,Linhu Liu,Zhongyu Jian,Lede Lin,Yu Liu,Yiqiong Yuan,Jun Wen,Liyuan Xiang,Xi Jin,Kun-Jie Wang
Calcium oxalate (CaOx) kidney stone is prevalent while the molecular mechanisms are not yet fully understood. The organic matrix of stones is rich in protein and has been considered to play a important role in stone aggregation and growth. Through multi-omics approaches, we identified that renal tubular epithelial cell (RTECs)-derived clusterin (CLU), as a matrix protein, promotes renal CaOx stone formation. Proteomics revealed significant enrichment of CLU in CaOx stones. Transcriptomic and single-cell transcriptome data from human kidney specimens confirmed marked upregulation of CLU in RTECs of kidney stone patients. In vitro, CLU accelerated renal CaOx crystal growth. Specifically, conditionally knock out of CLU in RTECs significantly alleviated CaOx crystal deposition in mouse kidneys. Furthermore, hyperoxaluria upregulated CLU in RTECs via the TGF-β1-SMAD2/3-Twist1 pathway, thereby facilitating stone formation. Our study highlights the role of the TWIST1-CLU regulatory axis in renal CaOx stone formation, suggesting CLU as a potential therapeutic target for CaOx kidney stones.
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PubMed
高影响因子
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