TALANTA
·
2016
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IF 4.035
Lijiang Lei,Jin Zhu,Gangqiang Xia,Hui Feng,Hongman Zhang,Yuwang Han
NGAL is a promising novel biomarker for acute kidney injury (AKI) and chronic kidney disease (CKD). More rapid and user-friendly methods are needed for the timely monitoring of NGAL in human urine and serum. UCP technology-based lateral flow assay (UPT-LFA) was developed for rapid, user-friendly and quantitative detection of the NGAL in human serum specimens and urine specimens. Under optimal conditions, the UPT-LFA displayed a rapid response to NGAL with a LOD of 7.68 ng/mL and detection range from 7.68 to 1000 ng/mL. The UPT-LFA method was compared with commercial immunoturbidimetry (103 urine specimens), and by ELISA (26 serum specimens), respectively. The results demonstrated that the UPT-LFA was consistent with immunoturbidimetry assay, reporting a 97.92% of positive and 92.73% of negative coincidence rates, respectively. Meanwhile, the concordance rate between UPT-LFA and ELISA, as shown by correlative regression analysis, was also high (R 2 =0.95). The whole assay can be completed within 30 min compared to 4 h consuming with ELISA. The research implies that, the UPT-LFA provides a potential to be used in point of care testing (POCT) to define early acute kidney injury with advantages of user-friendly and rapid testing, promising this new assay a bright future.
研究领域:
医学诊断
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生物技术
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2016
·Vol. 183
·期 4
·1417-1423
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IF 4.831
Xiao Deli,Liu Shubo,Liang Liyun,Bi Yanping
Epoxy propyl bonded magnetic microspheres were prepared by atomic layer deposition using Fe 3 O 4 @SiO 2 microspheres as a core support material. Then, a restricted-access magnetic sorbent was prepared that contains diol groups on the external surface and m-aminophenylboronic acid groups on the internal surface. This kind of microspheres achieved excellent specific adsorption of the ortho-dihydroxy compounds (dopamine, adrenaline and noradrenaline). Following desorption with sorbitol, the ortho-dihydroxy compounds were quantified by HPLC. The limits of detection for dopamine, adrenaline and noradrenaline were 0.074, 0.053 and 0.095 μg mL −1 , respectively. Recoveries from spiked mice serum samples range from 80.2 to 89.1 %.
A magnetic restricted-access sorbent with diol groups on the external surface and m-aminophenylboronic acid groups on the internal surface was synthesized for highly selective extraction of adrenaline, dopamine and noradrenaline from biological samples.
研究领域:
分析化学
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生物医学工程
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药物分析
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DOI
高影响因子
MOLECULES
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2022
·Vol. 27
·期 12
·3823
·
IF 4.927
Meng Zhou,Yanpeng Dai,Yong Ma,Yi Yan,Min Hua,Qi Gao,Xue Geng,Qian Zhou
Acute kidney injury (AKI) induced by cisplatin (CP), a first-line anticancer drug for chemotherapy, is common. To date, there is an urgent need to find effective treatments to reduce the nephrotoxicity caused by CP. Meanwhile, the restoration of mitochondrial dysfunction shows potential to be used as an adjunct to conventional therapeutic strategies. This study found that liquiritigenin can ameliorate mitochondrial dysfunction and acute kidney injury induced by CP in mice. The intraperitoneal injection of 15 mg/kg body weight liquiritigenin for 2 days markedly protected against CP-induced mitochondrial dysfunction, restored renal tubule and mitochondrial morphology, decreased blood Scr and BUN levels, and decreased cell apoptosis. Furthermore, the elevated expression of SIRT3 induced by liquiritigenin, which can be upregulated by NRF2, was confirmed in vivo and in vitro. The underlying protective mechanisms of liquiritigenin in CP-induced nephrotoxicity were then investigated. Molecular docking results showed that liquiritigenin has potent binding activities to KEAP1, GSK-3β and HRD1. Further results showed that liquiritigenin induced the nuclear translocation of NRF2 and increased the levels of mitochondrial bioenergetics-related protein such as PGC-1α, and TFAM, which are related to NRF2 activity and mitochondrial biogenesis. In addition, liquiritigenin was found to possibly reverse the decrease in BCL2/BAX ratio induced by CP in live cultured renal tubule epithelial cells. Collectively, these results indicated that liquiritigenin could be used as a potential nephroprotective agent to protect against cisplatin-induced acute kidney injury in a NRF2-dependent manner by improving mitochondria function.Keywords:liquiritigenin;NRF2;cisplatin;SIRT3;mitochondrial biogenesis
研究领域:
药理学
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毒理学
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分子生物学
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肾脏生理学
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DOI
PubMed
高影响因子
Open Life Sciences
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2023
·Vol. 18
·期 1
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IF 2.2
Jiajia Zhai,Zeping Li,Huifeng Zhang,Zuowei Lu,Yi Zhang,Mo Li,Jian Kang,Zelong Yang,Louyan Ma,Li Ma,Zhengquan Ma,Xiaorui Ma,Fanghong Zhao,Xiaoqing Ma,Yuan Gao,Yuanyuan Zhang,Xiaomiao Li
Diabetic nephropathy is a microvascular complication of diabetes mellitus, threatening the health of millions of people. Herein, we explored a blood glucose independent function of coptisine on diabetic nephropathy. A diabetic rat model was established by intraperitoneal administration of streptozotocin (65 mg/kg). Coptisine treatment (50 mg/kg/day) retarded body weight loss and reduced blood glucose. On the other hand, coptisine treatment also decreased kidney weight and the levels of urinary albumin, serum creatinine, and blood urea nitrogen, indicating an improvement of renal function. Treatment with coptisine also mitigated renal fibrosis, with alleviative collagen deposition. Likewise, in vitro study showed that coptisine treatment decreased apoptosis and fibrosis markers in HK-2 cells treated with high glucose. Furthermore, after coptisine treatment, the activation of NOD-like receptor pyrin domain containing protein 3 (NRLP3) inflammasome was repressed, with decreased levels of NLRP3, cleaved caspase-1, interleukin (IL)-1β, and IL-18, indicating that the repression of NRLP3 inflammasome contributed to the effect of coptisine on diabetic nephropathy. In conclusion, this study revealed that coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome. It is indicated that coptisine may have the potential to be used in the diabetic nephropathy treatment.
研究领域:
药理学
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肾病学
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糖尿病
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
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2023
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IF 4.5
Huiling Guo,Caiying Zhang,Wenjing Pu,Xuesheng Chu,Gang Huang,Ting Cui,Bingyan Huang,Hang Liu,Xueyan Dai
Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP 3 /IP 3 R axis, primary duck renal tubular epithelial cells were exposed to 480 μM and 960 μM Mo, and joint of 960 μM Mo and 10 μM 2-APB or 0.125 μM U-73122 for 12 h (U-73122 pretreated for 1 h), respectively. The data revealed that the increment of [Ca 2+ ] c induced by Mo mainly originated from intracellular Ca storage. Mo exposure reduced [Ca 2+ ] ER , elevated [Ca 2+ ] mit , [Ca 2+ ] c , and the expression of Ca homeostasis-related factors (Calpain, CaN, CRT, GRP94, GRP78 and CaMKII). 2-APB could effectively reverse subcellular Ca 2+ redistribution by inhibiting IP 3 R, which confirmed that [Ca 2+ ] c overload induced by Mo originated from ER. Additionally, PLC inhibitor U-73122 remarkably mitigated the change, and dramatically reduced the number of apoptotic cells, the expression of Bak-1, Bax, cleaved-Caspase-3/Caspase-3, and notably increased the expression of Bcl-xL, Bcl-2, and Bcl-2/Bax ratio. Overall, the results confirmed that the Ca 2+ liberation of ER via PLC/IP 3 /IP 3 R axis was the main cause of [Ca 2+ ] c overload, and then stimulated apoptosis in duck renal tubular epithelial cells.
研究领域:
毒理学
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细胞生物学
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肾脏生理学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Zhiwei Huang,Changju Chun,Xinze Li
The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery ( [email protected] ) for AKI treatment. [email protected] could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of [email protected] The results showed that injected [email protected] specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.
研究领域:
纳米技术
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药学
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生物医学工程
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肾脏生理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2022
·Vol. 8
·期 1
·1-10
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IF 7.109
Wang Jingyu,Wang Yaqing,Liu Yi,Cai Xintian,Huang Xin,Fu Wenjing,Wang Lei,Qiu Lihua,Li Junying,Sun Li
Ferroptosis is a non-traditional form of regulated cell death, characterized by iron overload and lipid peroxidation. Exploration of ferroptosis in chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6 nephrectomy, treated CKD rats with the ferroptosis inducer, cisplatin (CDDP), and the ferroptosis inhibitor, deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and fibrosis) and ferroptotic biochemical indices. Kidney iron deposition, lipid peroxidation, mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered iron metabolism. In conclusion, our study shows for the first time that 5/6 nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal fibrosis.
研究领域:
肾病学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
You Zhou,You Wu,Rui Zhu
Background Septic acute kidney injury (S-AKI) is a major cause of acute kidney injury (AKI), but no effective therapies exist to prevent or treat it. Although KLF6 is linked to various pathophysiological processes, its exact role in S-AKI is not yet fully understood. Methods The role of KLF was investigated using both the mouse CLP model and in vitro systems. To identify the transcriptional targets regulated by KLF6, ChIP-qPCR and luciferase reporter assays were carried out. Biochemical and cellular techniques were employed to assess cellular injury and lipid peroxidation levels. The extent of ferroptosis was evaluated through transmission electron microscopy (TEM). Results KLF6 levels were significantly increased in a renal IRI model. Knockdown of KLF6 using AAV9 reduced kidney injury in both in vitro and in vivo models, while KLF6 overexpression aggravated injury. Overexpression of KLF6 promoted ferroptosis, whereas its knockdown reduced lipid peroxidation and ferroptosis. KLF6 regulates NCOA4 expression by binding to its promoter, controlling ferroptosis. Knockdown of NCOA4 in vitro alleviated ferroptosis and cellular damage caused by KLF6 overexpression. Pharmacological inhibition of KLF6 reduced kidney injury and ferroptosis in S-AKI mice. Conclusion Our study uncovered a previously unrecognized role for KLF6 in S-AKI. By facilitating NCOA4 transcription, KLF6 intensified ferroptosis, which, in turn, aggravated septic AKI.
研究领域:
肾脏病学
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分子生物学
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病理生理学
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细胞生物学
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转录调控
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DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
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IF 4.8
Hong-Yu Fu,Yue Li,Han Cui,Jiu-Zhi Li,Wan-Xue Xu,Xi Wang,Rui-Feng Fan
Mercuric chloride (HgCl 2 ), a widespread environmental pollutant, induces ferroptosis in chicken embryonic kidney (CEK) cells. Whereas activating transcription factor 4 (ATF4), a critical mediator of oxidative homeostasis, plays a dual role in ferroptosis, but its precise mechanisms in HgCl 2 -induced ferroptosis remain elusive. This study aims to investigate the function and molecular mechanism of ATF4 in HgCl 2 -induced ferroptosis. Our results revealed that ATF4 was downregulated during HgCl 2 -induced ferroptosis in CEK cells. Surprisingly, HgCl 2 exposure has no significant impact on ATF4 mRNA level. Further investigation indicated that HgCl 2 enhanced the expression of the E3 ligase beta-transducin repeat-containing protein (β-TrCP) and increased ATF4 ubiquitination. Subsequent findings identified that miR-15b-5p as an upstream modulator of β-TrCP, with miR-15b-5p downregulation observed in HgCl 2 -exposed CEK cells. Importantly, miR-15b-5p mimics suppressed β-TrCP expression and reversed HgCl 2 -induced cellular ferroptosis. Mechanistically, HgCl 2 inhibited miR-15b-5p, and promoted β-TrCP-mediated ubiquitin degradation of ATF4, thereby inhibited the expression of antioxidant-related target genes and promoted ferroptosis. In conclusion, our study highlighted the crucial role of the miR-15b-5p/β-TrCP/ATF4 axis in HgCl 2 -induced nephrotoxicity, offering a new therapeutic target for understanding the mechanism of HgCl 2 nephrotoxicity.
研究领域:
毒理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2021
·
IF 5.34
Yongmei Li,Zean Zhao,Jian Luo,Yanqing Jiang,Lu Li,Yanyu Chen,Leqi Zhang,Qinghua Huang,Ying Cao,Pingzheng Zhou,Ting Wu,Jianxin Pang
Background Hyperuricemia (HUA) is characterized by abnormal serum uric acid (UA) levels and demonstrated to be involved in renal injury leading to hyperuricemic nephropathy (HN). Apigenin (API), a flavonoid naturally present in tea, berries, fruits, and vegetables, exhibits various biological functions, such as antioxidant and anti-inflammatory activity. Purpose To investigate the effect of API treatment in HN and to reveal its underlying mechanisms. Methods The mice with HN were induced by potassium oxonate intraperitoneally and orally administered for two weeks. The effects of API on renal function, inflammation, fibrosis, and uric acid (UA) metabolism in mice with HN were evaluated. The effects of API on urate transporters were further examined in vitro . Results The mice with HN exhibited abnormal renal urate excretion and renal dysfunction accompanied by increased renal inflammation and fibrosis. In contrast, API reduced the levels of serum UA, serum creatinine (CRE), blood urea nitrogen (BUN) and renal inflammatory factors in mice with HN. Besides, API ameliorated the renal fibrosis via Wnt/β-catenin pathway suppression. Furthermore, API potently promoted urinary UA excretion and inhibited renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mice with HN. In vitro , API competitively inhibited URAT1 and GLUT9 in a dose-dependent manner, with IC 50 values of 0.64 ± 0.14 μM and 2.63 ± 0.69 μM, respectively. Conclusions API could effectively attenuate HN through co-inhibiting UA reabsorption and Wnt/β-catenin pathway, and thus it might be a potential therapy to HN.
研究领域:
药理学
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Jie Gao,Yanfeng Liu,Bo Jiang,Wenmin Cao,Yansheng Kan,Wei Chen,Meng Ding,Guiyang Zhang,Bowen Zhang,Kai Xi,Xudong Jia,Xiaozhi Zhao,Hongqian Guo
As a reactive oxygen species (ROS)-promoted disease, acute kidney injury (AKI) is associated with high mortality and morbidity, but no effective pharmacological treatment is available. Kidney-targeted and ROS-reactive antioxidants are in urgent demand for AKI treatment. A promising nanotechnology-based strategy for targeting renal tubules offers new perspectives for AKI treatment but remains challenging because of the glomerular filtration barrier, which requires ultrasmall-sized therapeutics for penetration and filtration. Here, we fabricated four potential antioxidative carbon nanodots (CNDs) with ultrasmall size. After balancing the antioxidant properties and biocompatibility, m-phenylenediamine-based CNDs (PDA-CNDs) were chosen for further research. PDA-CNDs demonstrated remarkable antioxidant properties for scavenging multiple toxic free radicals, enabling efficient protection of cells under various oxidative stresses in vitro. Moreover, fluorescence imaging revealed that PDA-CNDs preferentially accumulated in the injured kidney of mice with ischemia–reperfusion (IR)-induced AKI. Blood renal function tests and kidney tissue staining revealed the therapeutic efficacy of PDA-CNDs for AKI in both the murine IR-induced AKI model and cisplatin-induced AKI model. Collectively, this is the first study revealing that specific rationally designed CNDs could be a promising pharmacological treatment for AKI induced by ROS.
研究领域:
纳米技术
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药理学
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肾脏生理学
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氧化应激
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Ke Lin,Wu Luo,Na Yang,Lan Su,Hao Zhou,Xiang Hu,Yi Wang,Zia A. Khan,Weijian Huang,Gaojun Wu,Guang Liang
Background Kidney damage is a frequent event in the course of hypertension. Recent researches highlighted a critical role of non-hemodynamic activities of angiotensin II (Ang II) in hypertension-associated kidney fibrosis and inflammation. These activities are mediated through toll-like receptors (TLRs) but the mechanisms by which Ang II links TLRs to downstream inflammatory and fibrogenic responses is not fully known. In this study, we investigated the role of TLR adapter protein called myeloid differentiation primary-response protein-88 (MyD88) as the potential link. Methods C57BL/6 mice were administered Ang II by micro-osmotic pump infusion for 4 weeks to develop nephropathy. Mice were treated with small-molecule MyD88 inhibitor LM8. In vitro , MyD88 was blocked using siRNA or LM8 in Ang II-challenged renal tubular epithelial cells. Results We show that MyD88 is mainly located in tubular epithelial cells and Ang II increases the interaction between TLR4 and MyD88. This interaction activates MAPKs and nuclear factor-κB (NF-κB), leading to increased production of inflammatory and fibrogenic factors. Inhibition of MyD88 by siRNA or selective inhibitor LM8 supresses MyD88-TLR4 interaction, NF-κB activation, and elaboration of inflammatory cytokines and fibrosis-associated factors. These protective actions resulted in decreased renal pathological changes and preserved renal function in LM8-treated hypertensive mice, without affecting hypertension. Conclusion These results demonstrate that Ang II induces inflammation and fibrosis in renal tubular epithelial cells through MyD88 and present MyD88 as a potential point of intervention for hypertension-associated kidney disease.
研究领域:
药理学
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肾病学
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免疫学
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分子生物学
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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）