SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Xiaomin Cao,Miao Qin,Pan Li,Binbin Zhou,Xianghu Tang,Meihong Ge,Liangbao Yang,Jinhuai Liu
Catecholamine (CA) is neurotransmitters of the biological amines class which play an important role in organism. However, it is quite difficult to realize sensitive and selective detection of CA in complex system. Here, we employ surface-enhanced resonance Raman spectroscopy (SERRS) strategy, iron-nitrilotriacetic acid functionalized PVP-Au NPs (Au-Fe(NTA)) as Raman label for rapid and sensitive detection of CA containing dopamine (DA), norepinephrine (NE) or epinephrine (EP) in complex serum. The Au NPs is sufficient to provide Raman enhancement and Fe-NTA label can rapidly trap CA molecules adjoining gold core to form NTA-Fe-CA resonant structure, which can amplify the signals of CA. More important, we successfully distinguish these three CA molecules in serum since surface-enhanced Raman spectroscopy (SERS) technique can provide fingerprint identification. Furthermore, the SERS signals of Au-O band from PVP stabilized Au NPs can be utilized as a stable internal calibration standard for quantitative detection of target. Additionally, we continue to investigate the binding constants between different CA molecules and functionalized substrate to evaluate the corresponding adsorption property. This SERRS strategy is not only capable to offer exciting opportunities to selectively trap the analyte, but also strongly amplify the Raman signals of CA as well as achieve quantitative measurement.
研究领域:
生物化学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 19
·2597-2604
·
IF 2.378
Wei Zhuang,Yining Li,Jiabi Chen,Weihui Liu,Hongyuan Huang
A simple and portable potentiometric immunoassay was designed for the quantitative detection of matrix metalloproteinase-7 (MMP7) in acute kidney injury and renal cancer on a copper ion-selective electrode (Cu-ISE). To construct such an assay system, a sandwich-type immunoreaction was initially carried out on monoclonal anti-MMP7 capture antibody-coated microplates by using an initiator DNA strand-labeled anti-MMP7 secondary antibody. Thereafter, a hybridization chain reaction (HCR) was used for the signal amplification between copper nanocluster-labeled two hairpin DNA probes. Accompanying the formation of the sandwiched immunocomplex, the labeled DNA initiator strand on the secondary antibody triggered the HCR between two alternating DNA hairpins to form a nicked double-helix with copper nanoclusters. The subsequent potentiometric measurement of copper ions released from the concatenated copper nanoclusters under acidic conditions was conducted on a portable handheld potentiometer. The immuno-HCR assay combined an easy-operation potentiometric assay with signal amplification by using an HCR-induced copper nanocluster concatemer. Under optimum conditions, the developed immuno-HCR assay exhibited a dynamic linear range of 0.01–100 ng mL−1 with a detection limit of 5.3 pg mL−1 and good reproducibility. Also, the immuno-HCR assay gave good anti-interfering capacity toward other biomarkers. The analysis for clinical human serum specimens revealed good accordance with the results obtained by an enzyme-linked immunosorbent assay. Importantly, our strategy is promising for enzyme-free and cost-effective analysis of low-abundance cancer biomarkers.
研究领域:
分析化学
·
生物医学工程
·
临床化学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2017
·Vol. 6
·期 1
·179-188
·
IF 4.21
Jing Li,Cuiting Zhang,Weiming He,Hongzhi Qiao,Jiahui Chen,KaiKai Wang,David Oupický,Minjie Sun
Kidney-specific delivery is critically important for the treatment of renal fibrosis with drugs such as salvianolic acid B (Sal B). Here we report a kidney-specific nanocomplex formed by the coordination-driven assembly of catechol-modified low molecular weight chitosan (HCA-Chi), calcium ions and Sal B. The prepared HCA-Chi-Ca-Sal B (HChi-Ca-Sal B) nanocomplex reversed the TGF-β1-induced epithelial–mesenchymal transition (EMT) in HK-2 cells. In vivo imaging demonstrated a kidney-specific biodistribution of the nanocomplex. The anti-fibrosis effect of HChi-Ca-Sal B was tested in a mouse model of unilateral ureteral obstruction (UUO). Significant attenuation of the morphological lesions and the levels of extracellular matrix (ECM) proteins in the tubulointerstitium was observed in mice treated with HChi-Ca-Sal B, suggesting that the nanocomplex was able to prevent fibrosis better than the treatment with free Sal B. It was concluded that the HChi-Ca-Sal B nanocomplex showed a specific renal targeting capacity and could be utilized to enhance Sal B delivery for treating renal fibrosis.
研究领域:
药理学
·
生物医学工程
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 12
·2910-2923
·
IF 4.109
Yuting Wu,Jiwen Liu,Shuhui Liu,Wentao Fan,Chenchen Ding,Zhangshan Gao,Zhihui Tang,Yan Luo,Xizhi Shi,Lei Tan,Suquan Song
Since the outbreak of COVID-19, widespread utilization of disinfectants has led to a tremendous increase in the generation of disinfection byproducts worldwide. Bromoacetic acid (BAA), one of the common disinfection byproducts in the environment, has triggered public concern because of its adverse effects on urinary system in mammals. Nevertheless, the BAA-induced nephrotoxicity and potential mechanism in birds still remains obscure. According to the detected content in the Taihu Lake Basin, the model of BAA exposure in chicken was established at doses of 0, 3, 300, 3000 μg/L for 4 weeks. Our results indicated that BAA exposure caused kidney swelling and structural disarrangement. BAA led to disorder in renal function (CRE, BUN, UA) and increased apoptosis (Bax, Bcl-2, caspase3). BAA suppressed the expression of mitochondrial biogenesis genes (PGC-1α, Nrf1, TFAM) and OXPHOS complex I genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6). Subsequently, BAA destroyed the expression of Nrf2 antioxidant reaction genes (Nrf2, Keap1, HO-1, NQO1, GCLM, GCLC). Furthermore, renal oxidative damage led to disorder in uric acid metabolism genes (Mrp2, Mrp4, Bcrp, OAT1, OAT2, OAT3) and exacerbated destruction in renal function. Overall, our study provided insights into the potential mechanism of BAA-induced nephrotoxicity, which were important for the clinical monitoring and prevention of BAA.
研究领域:
环境科学
·
毒理学
·
动物生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
·
2024
·Vol. 42
·期 3
·e4005
·
IF 2.8
Nannan Ding,Shanyue Sun,Shuting Zhou,Zhimei Lv,Rong Wang
Tubulointerstitial fibrosis is an inevitable consequence of all progressive chronic kidney disease (CKD) and contributes to a substantial health burden worldwide. Icariin, an active flavonoid glycoside obtained from Epimedium species, exerts potential antifibrotic effect. The study aimed to explore the protective effects of icariin against tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO)-induced CKD mice and TGF-β1-treated HK-2 cells, and furthermore, to elucidate the underlying mechanisms. The results demonstrated that icariin significantly improved renal function, alleviated tubular injuries, and reduced fibrotic lesions in UUO mice. Furthermore, icariin suppressed renal inflammation, reduced oxidative stress as evidenced by elevated superoxide dismutase activity and decreased malondialdehyde level. Additionally, TOMM20 immunofluorescence staining and transmission electron microscope revealed that mitochondrial mass and morphology of tubular epithelial cells in UUO mice was restored by icariin. In HK-2 cells treated with TGF-β1, icariin markedly decreased profibrotic proteins expression, inhibited inflammatory factors, and protected mitochondria along with preserving mitochondrial morphology, reducing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) overproduction, and preserving membrane potential. Further investigations demonstrated that icariin could activate nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway both in vivo and in vitro, whereas inhibition of Nrf2 by ML385 counteracted the protective effects of icariin on TGF-β1-induced HK-2 cells. In conclusion, icariin protects against renal inflammation and tubulointerstitial fibrosis at least partly through Nrf2-mediated attenuation of mitochondrial dysfunction, which suggests that icariin could be developed as a promising therapeutic candidate for the treatment of CKD. Significance statement Tubulointerstitial fibrosis is an unavoidable consequence of advancing chronic kidney disease (CKD) and imposes a substantial global health burden. However, few effective therapeutic agents are available at present. The present study investigated the ameliorative effects of icariin on tubulointerstitial fibrosis (TIF) both in vivo and in vitro, and demonstrated that icariin inhibited inflammation and oxidative stress, at least partially, through improving Nrf2 activity and subsequent mitochondrial function, and eventually mitigated TIF and preserved renal function, suggesting that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.
研究领域:
药理学
·
肾脏生理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 3.8
Haiyan Zhu,Yijing Yang,Yenan Duan,Xin Zheng,Zixiong Lin,Jie Zhou
Sodium aescinate (SA), an active compound found in horse chestnut seeds, is widely used in clinical practice. Recently, the incidence of SA-induced adverse events , particularly renal impairment, has increased. Our previous work demonstrated that SA causes severe nephrotoxicity via nephrocyte ferroptosis ; however, the underlying mechanism remains to be fully elucidated. In the current study, we investigated additional molecular pathways involved in SA-induced nephrotoxicity. Our results showed that SA inhibited cell viability , disrupted cellular membrane integrity, and enhanced reactive oxygen species (ROS), ferrous iron (Fe 2+ ), and malondialdehyde (MDA) levels, as well as lipid peroxidation in rat proximal renal tubular epithelial cell line (NRK-52E) cells. SA also depleted coenzyme Q10 (CoQ10, ubiquinone) and nicotinamide adenine dinucleotide (NADH) and reduced ferroptosis suppressor protein 1 (FSP1) and polyprenyltransferase (coenzyme Q2, COQ2) activity, triggering lipid peroxidation and ROS accumulation in mouse kidneys and NRK-52E cells. The overexpression of COQ2, FSP1, or CoQ10 (ubiquinone) supplementation effectively attenuated SA-induced ferroptosis, whereas iFSP1 or 4-formylbenzoic acid (4-CBA) pretreatment exacerbated SA-induced nephrotoxicity. Additionally, SA decreased nuclear factor-erythroid-2-related factor 2 (Nrf2) levels and inhibited Nrf2 binding to the −1170/-1180 bp ARE site in FSP1 promoter, resulting in FSP1 suppression. Overexpression of Nrf2 or its agonist dimethyl fumarate (DMF) promoted FSP1 expression, thereby improving cellular antioxidant capacity and alleviating SA-induced ferroptosis. These results suggest that SA-triggers renal injury through oxidative stress and ferroptosis, driven by the suppression of the Nrf2/FSP1/CoQ10 axis.
研究领域:
药理学
·
毒理学
·
细胞生物学
·
分子生物学
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Yan-Ting Lv,Tian-Bin Liu,Yue Li,Zhen-Yong Wang,Cai-Yu Lian,Lin Wang
Cadmium (Cd), a prevalent environmental contaminant, has attracted widespread attention due to its serious health hazards. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to the development of various kidney diseases. However, the mechanisms underlying the occurrence of ferroptosis in Cd-induced renal tubular epithelial cells (TECs) have not been fully elucidated. Hereby, both in-vitro and in-vivo experiments were established to elucidate this issue. In this study, we found that Cd elicited accumulation of lipid peroxides due to intracellular ferrous ion (Fe 2+ ) overload and glutathione depletion, contributing to ferroptosis. Inhibition of ferroptosis via chelation of Fe 2+ or reduction of lipid peroxidation can significantly mitigate Cd-induced cytotoxicity. Renal transcriptome analysis revealed that the activation of heme oxygenase 1 (HO-1) was closely related to ferroptosis in Cd-induced TECs injury . Cd-induced ferroptosis and resultant TECs injury are significantly alleviated due to HO-1 inhibition, demonstrating the crucial role of HO-1 in Cd-triggered ferroptosis. Further studies showed that accumulation of lipid peroxides due to iron overload and mitochondrial ROS (mtROS) generation was responsible for HO-1-triggered ferroptosis in Cd-induced cytotoxicity. In conclusion, the current study demonstrates that excessively upregulating HO-1 promotes iron overload and mtROS overproduction to trigger ferroptosis in Cd-induced TECs injury, highlighting that targeting HO-1-mediated ferroptosis may provide new ideas for preventing Cd-induced nephrotoxicity .
研究领域:
毒理学
·
细胞生物学
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FEBS Open Bio
·
2021
·Vol. 11
·期 5
·1395-1405
·
IF 2.693
Dan Wang,Zikun Zhang,Zekun Si,Yanlin Yang,Shuangshuang Li,Yaoming Xue
An imbalance between T helper 17 (Th17) and T regulatory (Treg) cell subsets contributes to the pathogenesis of diabetic kidney disease (DKD). However, the underlying regulatory mechanisms that cause this imbalance are unknown. Serum/glucocorticoid-regulated kinase 1 (SGK1) has been suggested to affect Th17 polarization in a salt-dependent manner, and sodium/glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to regulate sodium-mediated transportation in the renal tubules. This study aimed to evaluate the potential benefits of dapagliflozin (Dap) on DKD, as well as its influence on shifting renal T-cell polarization and related cytokine secretion. We treated male db/db mice with Dap or voglibose (Vog) and measured blood and kidney levels of Th17 and Treg cells using flow cytometry. We found that Th17 cells were significantly increased, while Treg cells were significantly decreased in diabetic mice. Moreover, Dap suppressed the polarization of Th17/Treg cells by inhibiting SGK1 in diabetic kidneys, and this was accompanied by attenuation of albuminuria and tubulointerstitial fibrosis independent of glycemic control. Taken together, these results demonstrate that the imbalance of Th17/Treg cells plays an important role in the progression of DKD. Moreover, Dap protects against DKD by inhibiting SGK1 and reversing the T-cell imbalance.
研究领域:
药理学
·
免疫学
·
糖尿病学
·
肾病学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2020
·
IF 2.971
Zhaohui Wang,Zhi Chen,Bingsheng Li,Bo Zhang,Yongchao Du,Yuhang Liu,Yao He,Xiang Chen
Context Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects.Objective To explore the mechanisms underlying the effects of curcumin on RIF.Materials and methods Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-β1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation.Results In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1β and TNF-α by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and α-smooth muscle actin in TGF-β1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1β and TNF-α by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF- κB and p-IκBα in both LPS- and TGF-β1-induced HK-2 cells.Discussion and conclusions Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.
研究领域:
肾病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2019
·
IF 4.825
Lixia Bai,Jicheng Li,Honglian Li,Jianping Song,Yuan Zhou,Ruirui Lu,Bihao Liu,Yu Pang,Peichun Zhang,Junqi Chen,Xusheng Liu,Junbiao Wu,Chunling Liang,Jiuyao Zhou
Immunoglobulin A nephropathy (IgAN) is an autoimmune kidney disease with complex pathogenesis leading to end-stage renal damage . The prime pathological characteristics of IgAN are IgA immune complexes deposition accompany with mesangial cell proliferation and urine protein elevation. Artemisinin (ART) is extracted from traditional Chinese medicine Artemisia annua L. Hydroxychloroquine (HCQ) is a classical antimalarial drug applied in the treatment of autoimmune diseases. Both of them possess anti-inflammatory and immunomodulatory properties. The purpose of this research was to investigate the pharmacological effects of ART combined with HCQ (AH) and discuss thoroughly the potential molecular mechanisms in IgAN. In vivo , our results demonstrated that AH could efficiently ameliorate kidney damage by improving kidney dysfunction and reducing the levels of 24 h urine protein, IgA and IgG immune complexes deposition in glomerulus of IgAN rats. Interestingly, AH obviously promoted the secretion of exosomes in renal tissues, inhibited the expressions of nuclear factor- κ B (NF- κ B) signaling and NLRP3 inflammasome-related proteins, including I κ B- α , p-p65, NLRP3, ASC, IL-1 β and caspase-1 in IgAN rats. In vitro , further mechanistic study illustrated that exosomes derived from human renal tubular epithelial cells (HK-2) were significantly enhanced by AH, which could be utterly taken up in human mesangial cells (HMCs) and inhibited the activation of NF- κ B pathway and NLRP3 inflammasome after AH intervention. However, GW4869 interdicted the promotive effect of AH on exosomes from HK-2 cells and the suppression of exosomes on NF- κ B/NLRP3 activation in HMCs. Taken together, this study demonstrated that there was an inhibitory effect of AH therapy on NF- κ B/NLRP3 signaling via mediating exosomes release in IgAN rats, which provided an alternative approach for IgAN treatment.
研究领域:
药理学
·
免疫学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2021
·Vol. 11
·期 9
·1370
·
IF 4.879
Shuyi Liao,Wenmin Yang,Ting Yu,Lu Dai,Xiaoliang Liu,Jiangping Zhang,Jinghong Zhao,Chi Liu
Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed aTg(cdh17:Dendra2-NTR)transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.Keywords:acute renal failure (ARF);cardiorenal syndrome (CRS);zebrafish model;drug screening;nitroreductase (NTR);metronidazole (MTZ)
研究领域:
药理学
·
肾脏生理学
·
心脏病学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2019
·Vol. 10
·期 11
·7142-7151
·
IF 3.241
Wenwen Zhao,Xi Zeng,Fancheng Meng,Xiaolin Bi,Dahai Xu,Xiuping Chen,Qiu Li,Yantao Han
We report here an acidic polysaccharide, namely RSP-3, which ameliorates acute kidney injury and is obtained from Sanguisorba officinalis. We extracted and purified two polysaccharides from this herb based on the acidity and screened them for their effect in regulating the immunological activity of macrophages. Among them, RSP-3 exhibited significant anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated macrophages by decreasing TNF-α and IL-6 levels. Subsequently, we found that RSP-3 suppressed ER stress, reduced ROS production and blocked NF-κBp65 translocation. After fully characterizing RSP-3 with a series of analytical technologies, we tested its anti-acute kidney injury (AKI) effect in vivo. In a murine AKI model induced by LPS, treatment with RSP-3 effectively ameliorated renal function. Besides, it decreased the levels of TNF-α and IL-6 in serum and reduced macrophage infiltration in injured kidney tissue. In sum, RSP-3, with a significant protective effect against AKI by showing anti-inflammatory activity, may become a meaningful drug candidate for treatment of AKI.
研究领域:
药理学
·
免疫学
·
分子生物学
·
肾病学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）