TALANTA
·
2025
·
IF 6.1
Mengyu Du,Fangfang Sun,Yilin Sun,Zhenzhen Ma,Chenshuo Wang,Mengyu Liu,Ling Zhu,Hanchun Yao
Acute kidney injury (AKI) is a swiftly advancing condition that may result in kidney failure and pose a significant threat to life. Therefore, diagnosis of AKI is crucial for treating AKI and preventing the worsening of the condition. We developed a near-infrared fluorescent probe, CyO@CD-Ser, designed for the diagnosis of AKI. This probe targets kidney injury molecule-1 (KIM-1) and is activated by ONOO − . It consists of L-serine-modified β-cyclodextrin and compound CyO. In this system, ONOO − , a novel biomarker for AKI, triggers the oxidation of CyO to produce compound CyOH, resulting in a pronounced enhancement of near infrared fluorescence, offering a clear, visual signal for the detection of AKI. Through its modification with L-serine, β-cyclodextrin is able to efficiently penetrate cells by targeting KIM-1 receptors, thereby enhancing its specificity and effectiveness. In vitro and in vivo experiments demonstrate the probe's high sensitivity and biocompatibility, with a detection limit of 42.7 nM for ONOO − . Fluorescence is detectable in cisplatin-induced AKI after 12 hours, becoming significant at 24 hours. This suggests that CyO@CD-Ser can identify AKI earlier than traditional methods, offering a valuable tool for studying and diagnosing drug-induced AKI. Consequently, the probes we constructed can detect AKI early by precisely targeting and identifying biomarkers, preventing the deterioration of the condition, and providing an opportunity for early treatment for patients.
研究领域:
医学诊断
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生物成像
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分子探针
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肾脏病学
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荧光传感器
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药物毒理学
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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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产品关联
DOI
PubMed
高影响因子
Nano Research
·
2023
·
IF 9.9
Liu Yang,He Xuwei,Lian Zewei,Guo Qian,Chi Jimei,Lin Xiaoxue,Zhang Liyue,Liu Zheng,Liu Yingyuan,Su Meng,Wang Keyu,Ao Qiangguo,Cheng Qingli
Urinary kidney injury molecule 1 (uKIM-1) serves as a reliable marker for the early diagnosis of acute kidney injury (AKI). The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis, ultimately improving the prognosis of patients. In this study, we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties, which can detect uKIM-1 levels at the point-of-care. We confirmed its efficacy in the early diagnosis of AKI using clinical urine specimens. Direct quantitative detection of uKIM-1 was achieved within 10 min. The lowest limit of detection is 8.75 pg·mL −1 with an accuracy of 94.2%. The diagnostic efficacy was validated using 86 clinical urine samples, highlighting the high sensitivity and stability of the photonic crystal microarray. Consequently, a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1, which is crucial for the early identification and convenient detection of AKI in hospital or community settings. Rapid, convenient, cost-effective, and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens, preventing the transition from AKI to chronic kidney disease (CKD), improving the quality of life of patients with AKI, and reducing healthcare costs. It highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhiwen Wang,Ge Xie,Yue Xie,Mingcun Hu,Qiao Hu,Min Yang,Lianbin Zhang,Jintao Zhu,Chun Zhang
Efferocytosis, the clearance of apoptotic cells, is an essential process for resolving inflammation. Current evidence suggests that in acute kidney injury (AKI), the inflammatory cascade triggered by oxidative stress in damaged tissues can impair efferocytosis. This disrupts the clearance of apoptotic cells, exacerbates inflammatory reactions, and ultimately leads to tissue damage. To address this challenge, we developed a novel renal dual-targeting nanoplatform for AKI treatment based on black phosphorus nanosheets (BPNSs). Surface modification with LTH and 4-Octyl itaconate (4OI) endowed BPNSs with both renal tubulars targeting specificity and sustained antioxidant properties. This nanoplatform could effectively target damaged renal tubular epithelial cells, scavenge excess reactive oxygen species (ROS), alleviate oxidative stress, enhance efferocytosis, inhibit inflammatory responses, and ultimately achieve the specific therapeutic goal of AKI.
研究领域:
纳米技术
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药学
·
肾脏生理学
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炎症生物学
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产品关联
DOI
高影响因子
MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 6
·387
·
IF 5.4
Yu Zengshan,Wu Yanjun,Guo Shan,Li Zelong,Cui Jiahao,Shi Guochao
Chronic kidney disease (CKD) has become a major global public health issue. Due to its insidious onset and atypical early symptoms, patients often fail to detect it in time and receive effective intervention. Therefore, conducting early screening and diagnosis is of great significance for delaying the progression of renal failure and reducing the burden on patients and society. Combining surface-enhanced Raman scattering (SERS) technology, immunochromatography and artificial intelligence algorithm, this study utilized serum kidney injury molecule-1 (KIM-1) molecule as a key biomarker to construct a serum-based CKD diagnostic model, aiming to achieve efficient and accurate CKD screening. A total of six models were included for comparative analysis, among which the extreme gradient boosting (XGBoost) model successfully achieved precise classification of CKD, with a classification accuracy of 98.42% and an area under the curve (AUC) of 99.96%. Furthermore, leave-one-out cross-validation was used to validate this model, with an overall classification accuracy of 96.79%. These results indicated that the model exhibited good stability and strong robustness. In conclusion, the artificial intelligence-driven immunochromatography SERS biosensing technology with serum KIM-1 molecule as the early warning radar is expected to become a new technical strategy for intelligent early screening and auxiliary diagnosis of CKD. Graphical The alternative text for this image may have been generated using AI.
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Wenjie Zhang,Lingxin Zeng,Ying Li,Xinggang Yang,Wei Xiong
Phosphatidylserine liposomes target injured renal tubules. • Spermine-modified chitosan enables responsive drug release. • Targeted dihydroartemisinin delivery restores Klotho and reduces fibrosis. Restoration of endogenous Klotho represents a promising strategy for suppressing renal fibrosis, but efficient delivery of Klotho-restoring therapeutics to injured renal tubules remains challenging. Here, we developed dihydroartemisinin (DHA)-loaded phosphatidylserine liposomes coated with spermine-modified chitosan (DHA-PSLPs@SC) to achieve sequential kidney injury molecule-1 (KIM-1) targeting and spermine oxidase (SMOX)-responsive release, thereby enhancing renal delivery of DHA to restore endogenous Klotho and attenuate renal fibrosis. Dioleoylphosphatidylserine (DOPS) was incorporated to facilitate uptake by KIM-1-expressing injured tubular epithelial cells, whereas the spermine-modified chitosan (SC) coating was designed to promote cargo release in the SMOX-enriched fibrotic cellular environment. The optimized DHA-PSLPs@SC exhibited a diameter of 102.3 nm, a zeta potential of 33.8 mV, and an encapsulation efficiency of 69.4%. In H₂O₂-injured HK-2 cells, DOPS-containing liposomes displayed enhanced uptake and colocalization with KIM-1, while KIM-1 antibody blockade markedly reduced their internalization. In TGF-β1-stimulated NRK-52E cells, the SC coating preserved cellular uptake and increased cumulative DHA release to 74.2% at 12 h, while DHA-PSLPs@SC more effectively restored Klotho and suppressed fibrotic markers than free DHA or non-targeted liposomes. In unilateral ureteral obstruction (UUO) mice, PSLPs@SC preferentially accumulated in obstructed kidneys, with approximately 2.7-fold higher renal accumulation than non-targeted liposomes at 2 h. DHA-PSLPs@SC improved renal function, reduced tubular injury and collagen deposition, restored renal Klotho, and suppressed fibrosis. These findings support sequential KIM-1 targeting and SMOX-responsive release as a strategy to enhance renal delivery and antifibrotic efficacy of DHA, restore endogenous Klotho, and attenuate renal fibrosis.
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Fan Jia,Bo Yu,Jian Li,Fanghao Cai,Guosheng Fu,Qiao Jin,Jian Ji
Acute kidney injury (AKI) is a life-threatening complication with a considerable occurrence among patients. AKI is typically accompanied by an elevation in reactive oxidative species (ROS) in renal tissues, which is the main contributor to kidney damage. Herein, a supramolecular nano-assembly (Ser-HPEC) containing an ethyl caffeate-strengthened phenylboronic ester with ROS-triggered antioxidative ability was proposed for AKI-targeted therapy. Nano-assemblies can rapidly accumulate in the ischemia-reperfusion-injured kidney via kidney the injury molecule-1 (Kim-1)-mediated homing ability of L-serine. By consuming pathological levels of ROS, two different antioxidants, ethyl caffeate (EC) and 4-hydroxybenzyl alcohol (HBA), were spontaneously released from a single module to relieve oxidative stress and diminish acute inflammation in injured renal tissue. The multistep ROS scavenging strategy combined with a precise targeting capability endowed the aforementioned nano-assembly with effectiveness in preserving the integrity and functions of the injured kidney, providing new inspiration for the treatment of inflammatory diseases, including AKI. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
药学
·
肾脏生理学
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氧化应激研究
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Yu Duan,Qing Wang,Xiaolong Chen,Guanyun Deng,Kunyuan Huang,Fa Sun,Jianguo Zhu,Kehua Jiang
A retrospective study reported that empagliflozin reduced the risk of urinary stone events in patients with diabetes mellitus. To further investigate empagliflozin’s potential, we conducted an animal experiment to determine whether empagliflozin can prevent renal stone formation in hyperoxaluria rats. Hyperoxaluria rat models were constructed by administrating 0.75% ethylene glycol and 1% ammonium chloride in water. The empagliflozin-treated rats were gauged with empagliflozin at different concentrations, and their body weight and blood sugar data were recorded. After 30 days of treatment, we obtained 24-hour urine, kidney, and blood samples. The urine samples were subjected to component detection. Blood samples were prepared for component detection and cytokines detection. Renal samples were subjected to von Kossa staining, transmission electron microscopy, immunohistochemistry, and transcriptome sequencing analysis. Results showed that in empagliflozin-treated hyperoxaluria rats, renal crystal deposition and mitochondria injury, urinary concentration, and excretion of oxalate were significantly decreased. Additionally, plasma levels of VEGF, IL-2, IL-1β, and MCP-1 were decreased. Immunohistochemistry showed that renal expression of KIM-1, MCP-1 was significantly decreased in empagliflozin-treated hyperoxaluria rats. Transcriptome sequencing of renal tissue represented that 25 genes were down-regulated while 12 were up-regulated in empagliflozin-treated hyperoxaluria rats. These regulated genes were mainly enriched in fatty acid metabolism, insulin resistance, muscle contraction, bile secretion, and parathyroid metabolism. Our animal experiments found that empagliflozin could reduce urinary concentration and excretion of oxalate and inhibit renal inflammation, then abating renal calcium oxalate deposition in hyperoxaluria rats in a non-diabetic state.
研究领域:
药理学
·
肾病学
·
泌尿学
·
分子生物学
·
转化医学
✓ 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）