ANALYTICAL CHEMISTRY
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2024
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IF 6.7
Jing Wu,Ying Zhang,Jiuchuan Wang,Zhuangzhuang Ling,Xuanhua Yan,Xiaoming Lyu,Jinghuai Fang,Mingfei Cheng,Min Zhao,Tao Ban,Yu Liu,Yang Li
In the realm of disease diagnostics, particularly for conditions such as proteinuria and hemoglobinuria, the quest for a method that combines accurate, label-free detection of protein compositions and their conformational changes remains a formidable challenge. In this study, we introduce an innovative Ag/Au plasmonic hybrid coupling nanoarray (Ag/Au PHCN) architecture marked by sub-10 nm interparticle gaps. These nanoarrays, leveraging plasmonic hybrid coupling and synergistic enhancement mechanisms, create a plethora of uniform surface-enhanced Raman spectroscopy (SERS) hotspots. The Ag/Au PHCN substrates demonstrated unparalleled sensitivity in the unmarked detection of hemoglobin (HGB), bovine serum albumin (BSA), and cytochrome C (Cyt.C) in bodily fluids, incorporating the advantages of high sensitivity, high reproducibility, durability, recyclability, and biocompatibility. Notably, the detection limits for BSA and HGB are unprecedented at 0.5 and 5 ng/mL, respectively. This achievement sets a new benchmark for label-free protein detection using two-dimensional nanostructures. Crucially, the Ag/Au PHCNs possess the novel capability to discern protein conformational changes post denaturation, underscoring their potential in probing protein functionalities. Most importantly, these nanoarrays can differentiate between normal and proteinuria-affected urine samples and monitor protein content variations over time, heralding a new era in clinical diagnostics with particular relevance to proteinuria and hemoglobinuria detection.
研究领域:
生物医学
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纳米技术
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诊断学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2015
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IF 2.729
Huiqing Zou,Mingfeng Xiang,Xinming Ye,Yuanzhen xiong,Baogang Xie,Jianghua Shao
Serum uric acid (UA) concentration is positively associated with proteinuria. However, the relationship between proteinuria and urinary metabolites of purine metabolism remains unknown. This study developed a hydrophilic interaction chromatography (HILIC)-based HPLC method with ultraviolet detection (UV) to quantify creatinine (Cr), UA, xanthine, and hypoxanthine in human urine simultaneously. The urinary concentrations of UA and Cr obtained by our method are consistent with those measured by an autoanalyzer. The HPLC-HILIC-UV method was validated as selective and robust with simple sample preparation for measuring UA, xanthine, hypoxanthine and Cr, which is suitable for large clinical studies. The UA/Cr ratios in random urine samples were 5.5 times lower in proteinuria patients (0.077 ± 0.008) than in healthy individuals (0.424 ± 0.037). Moreover, the UA/hypoxanthine ratio in proteinuria patients was approximately 10 times lower than that in healthy individuals. Our findings revealed a reduced urinary UA excretion, which is one of the factors leading to increased serum UA in proteinuria patients.
研究领域:
医学
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生物化学
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DOI
高影响因子
Journal of Inorganic and Organometallic Polymers and Materials
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2024
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IF 3.9
Zhao Qiong,Duan Jianying
Membranous glomerulonephritis (MN) is clinically marked by significant proteinuria or nephrotic syndrome, and pathologically by a uniform thickening of the glomerular capillary basement membrane due to diffuse subepithelial immune complex deposition without notable cell proliferation. In this study, we synthesized a novel therapeutic agent, compound 1, designed for synergistic use with Eculizumab (Ecu) in MN treatment. To optimize the delivery and therapeutic effect of this combination, we developed an advanced composite drug carrier, mPEG-pHPMA@CP1@1@Ecu, incorporating methoxy polyethylene glycol (mPEG) and poly(2-hydroxypropyl methacrylamide) (pHPMA) with a metal-organic framework known as CP1. Structural and compositional integrity of this carrier was rigorously characterized. Our studies demonstrated that mPEG-pHPMA@CP1@1@Ecu could significantly mitigate hypoxia-induced renal tubular epithelial cell damage, highlighting the synergistic potential of compound 1 and Ecu. This new carrier system shows promising therapeutic potential for MN management.
研究领域:
医学
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药学
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生物材料科学
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产品关联
DOI
高影响因子
NanoImpact
·
2025
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IF 5.5
Yingqi Wang,Shen Zhao,Nengyi Ni,Hongyu Chen,Wenjian Zhao,Kuoran Xing,Xiao Sun,Xiuli Jing
Nanomaterials have been widely used in various fields due to their excellent properties. However, the long-term exposure of humans to the environment of nanomaterials may lead to some pathological and physiological changes, such as the disruption of the glomerular filtration barrier (GFB), which can lead to high permeability and filterable albumin. Glomerular albuminuria results from the failure of the GFB, which may be caused by activation of the Notch1 signaling pathway. The reduction of glomerular endocalyx results in the level of VE-cadherin being diminished between endothelial cells, leading to leakiness in the endothelium. As previously discovered, certain nanoparticles, such as negatively charged gold nanoparticles of appropriate size, can directly facilitate the onset of endothelial leakiness through disrupting connections between vascular endothelial cells, in a process known as nanomaterial-induced endothelial leakiness (NanoEL). In this study, the negatively charged Au NPs with a diameter of 20 nm were synthesized first. Through the co-incubation of 20 nm Au NPs with a single layer of continuous HUVECs, we revealed that the synthesized 20 nm Au NPs could break the tight junctions and cause endothelial cell leakage. In addition, by constructing an endothelial leakage model between glomerular vascular endothelial cells, we confirmed that 20 nm Au NPs can generate NanoEL between glomerular endothelial cells, involving downstream processes coinciding with Notch signaling activation, resulting in the increase of urinary protein. The results of this study add to the understanding of the behaviour of nanoparticles in complex biological systems.
研究领域:
医学
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毒理学
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纳米生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 109
·107732-107738
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IF 3.289
Zhifen Deng,Kai Hu,Liangliang Bi,Hang Yuan,Yanlong Chen,Shengnan Zhao,Huifang Du,Xuesheng Yuan,Yanjie Huang,Shusheng Zhang
Selective removal of highly abundant proteins prior to analysis is an important issue in proteomics. In this study, a core–shell structured magnetic nanocomposite of Fe3O4@SiO2@MAsp-HEMA was found to be an effective and selective adsorbent to remove highly abundant IgG from the urine of patients with proteinuria. This novel magnetic adsorbent was prepared by coating a poly(N-methacryloyl-L-aspartic acid-hydroxyethyl methacrylate) shell on Fe3O4@SiO2 nanoparticles via a coupling agent of KH-570 using the mini-emulsion polymerization method. The as-synthesized nanoparticle was characterized by X-ray diffraction, elemental analysis, thermal gravimetric analysis, infrared spectroscopy, magnetic hysteresis loop curves, scanning electronic microscopy and transmission electron microscopy. A kinetic adsorption experiment was performed to investigate the speed of adsorption and the time to reach the adsorption balance. 1D SDS-PAGE analysis and capillary electrophoresis were used to validate its selective adsorption ability. The resulting Fe3O4@SiO2@MAsp-HEMA showed a uniform spherical shape at nanoscale dimensions of about 200–300 nm, removing efficiency above 80%, and maximum adsorption capacity of 18.08 μg mg−1 at 15 ± 0.5 °C. The binding between IgG and the ligand was confirmed by isothermal titration calorimetry. The hydrogen bonding force was demonstrated as one of the major interactions between the functional groups of the as-synthesized magnetic nanoparticles and IgG by a molecular docking experiment.
研究领域:
蛋白质组学
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纳米技术
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材料科学
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产品关联
DOI
高影响因子
Communications Biology
·
2024
·Vol. 7
·期 1
·1-12
·
IF 5.2
Liu Sishi,Gao Man,Zhang Xue,Wei Jun,Cui Hong
Preeclampsia (PE) is a common pregnancy disorder characterized by hypertension and proteinuria. Trophoblast behavior severely affect PE progression. Transcription factor Forkhead box protein P2 (FOXP2) was involved in cell migration and invasion, but its role in PE progression remains unknown. Laminin subunit alpha 4 (LAMA4) was predicted as a downstream gene of FOXP2 and related to PE. Thus, we supposed that FOXP2 might regulate PE by regulating LAMA4. We found the decreased FOXP2 expression in patients with PE compared with healthy pregnant women. The rat model of PE was induced by L-NAME oral gavage. FOXP2 overexpression lowered systolic and diastolic blood pressure and restored pathological changes of rats with PE. Trophoblasts under the hypoxia/reoxygenation (H/R) treatment were used to mimic PE in vitro. The results revealed that FOXP2 overexpression inhibited apoptosis but promoted migration, invasion, and angiogenesis of H/R-treated trophoblasts. Dual luciferase and chromatin immunoprecipitation-polymerase chain reaction assays confirmed that FOXP2 transcriptionally upregulated the LAMA4 expression in trophoblasts. LAMA4 knockdown reversed the migration and invasion-promoting role of FOXP2 overexpression in trophoblasts with H/R treatment. Collectively, our findings suggest that the FOXP2/LAMA4 axis regulates PE by suppressing trophoblast apoptosis and promoting its migration, invasion, and angiogenesis.
研究领域:
妇产科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Rongjia Xu,Jiajia Zhang,Xingge Hu,Penghao Xu,Shiqi Huang,Shiyan Cui,Yuxin Guo,Hongtao Yang,Xiangmei Chen,Chen Jiang
Ethnopharmacological relevance Controversy persists regarding the treatment of immunoglobulin A nephropathy (IgAN), thereby highlighting the demand for safer more effective therapeutic drugs. Although supplementary treatment using Yi-Shen-Hua-Shi (YSHS) granules has distinct advantages with respect to improving renal function in IgAN, a lack of clarity regarding the underlying mechanisms limits their clinical application. Aim of the study In this study, we aimed to elucidate the therapeutic mechanisms underlying the efficacy of YSHS granules in the treatment of IgAN. Materials and methods A rat model of IgAN was established based on lipopolysaccharide, carbon tetrachloride, and bovine serum albumin induction. In order to evaluate the effects of YSHS granules, we performed a range of techniques, including immunofluorescence assays, hematoxylin and eosin staining, and flow cytometry, to assess inflammation, immunity, and other relevant factors. Direct data-independent acquisition–mass spectrometry (DIA-MS) analysis and parallel reaction monitoring (PRM) were used for functional characterization and quantitative validation of differentially expressed proteins (DEPs), and Western blot analysis is used to identify downstream proteins associated with DEPs. Results Compared with the model group, the levels of proteinuria, urine red blood cells, serum creatinine, blood urea nitrogen, low-density lipoprotein-cholesterol, triglycerides, and pathological kidney damage were reduced in the YSHS group. A high dose of YSHS granules was found to raise the levels of CD8 T cells and reduce the CD4/CD8 ratio in the peripheral serum. To examine the mechanisms underlying the therapeutic effects YSHS granules, we performed direct DIA-MS analysis to identify proteins that were differentially expressed among the model, YSHS, and control groups. A total of 29 proteins were identified as being commonly expressed in all three groups. Further KEGG and protein–protein interaction (PPI) network analysis revealed that YSHS granules can contribute to the regulation of N -glycosylation-associated proteins, such as ALG3 and STT3A, in rats with IgAN. Detected changes in the expression of ALG3 and STT3A were consistent with the PRM results. We also established that the administration of YSHS granules can contribute to regulation of the ALG3-associated PPAR-γ/NF-κB signaling pathway. Conclusions Our findings in this study provide evidence to indicate the efficacy of YSHS granules in the treatment of IgAN, the putative underlying mechanisms of which involve the modulation of N-glycosylation, mediated via the PPAR-γ/NF-κB pathway.
研究领域:
药理学
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免疫学
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肾病学
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蛋白质组学
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中医药
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2017
·
IF 2.981
Lei La,Lili Wang,Fei Qin,Jian Jiang,Songqi He,Chunxia Wang,Yuhao Li
Ethnopharmacological relevance Zhen-wu-tang ( ZWT ), composed of Radix Aconiti lateralis , Rhizoma Atractylodis macrocephalae , Poria , Radix Paeoniae alba and ginger, is a classic Chinese herbal formula for the treatment of chronic kidney diseases that may cause chronic renal failure (CRF). Aim of the study To better understand its clinical use, this study investigated the effects and underlying mechanisms of action of ZWT on CRF. Materials and methods CRF was induced by adenine . ZWT was given via an oral gavage method. The serum biochemical parameters were measured enzymatically or by ELISA . The kidneys were examined pathohistologically. The gene expression was analyzed by real time PCR and Western blot . Results Similar to the positive control losartan , ZWT extract inhibited adenine-induced increase in serum concentrations of creatinine, BUN and advanced oxidation protein products in rats. These effects were accompanied by attenuation of proteinuria and renal pathological changes and suppression of renal mRNA and protein overexpression of Collagen IV and fibronectin , two of the key components of fibrosis . Mechanistically, renal mRNA and protein expression of Wnt4, a Wnt signaling ligand, was increased in the adenine-treated group, compared to the vehicle-treated control. Consistently, Wnt4 downstream genes beta-catenin and Axin were also overexpressed. Treatment with ZWT extract and losartan suppressed adenine-stimulated overexpression of these mRNAs and proteins. Conclusions The present results demonstrate that ZWT extract ameliorates adenine-induced CRF in rats by regulation of the canonical Wnt4/beta-catenin signaling in the kidneys. Our findings provide new insight into the underlying renoprotective mechanisms of the ancient formula.
研究领域:
药理学
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肾病学
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民族药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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
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免疫学
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糖尿病学
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肾病学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Yu Cai,Ji-Cheng Niu,Xin-Li Du,Fang Fang,Zhi-Yong Wu
Field-amplified stacking (FAS) is a commonly used method for enhancing the sensitivity of charged species from low conductive media in capillary electrophoresis . FAS also showed significant sensitivity enhancement effect on a uniform paper fluidic channel by proper design of the electrolyte. In this paper, a novel method of introducing electric field gradient is proposed by geometry design of a 2D paper fluidic channel, and field amplification effect was successfully demonstrated with reduced requirement on the sample's conductivity . Sensitive colorimetric detection of microalbuminuria (MAU) from urine samples was demonstrated by mobile phone camera. Experimental results showed that, with active electric field motivation, up to 93.5% of the loaded protein probe could be effectively transferred and stacked into a narrow band on the newly designed paper fluidic channel. A limit of detection (LOD) of 6.5 mg‧L −1 HSA was achieved with a dynamic range of 10–300 mg‧L −1 (linear in the range of 10–100 mg‧L −1 , R 2 = 0.991). Combined with selective staining of albumin with bromophenol blue (BPB), the established method was applied to the detection of MAU from clinical urine samples, and consistent results with that of the clinical method were obtained. With this paper-based analytical device (PAD), MAU from highly conductive urine samples can be directly loaded and detected without any pretreatment . This method provides a way to develop highly sensitive point-of-care test (POCT) for rapid screening of some diseases.
研究领域:
分析化学
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医学诊断
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生物化学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2020
·Vol. 11
·期 5
·1-19
·
IF 6.304
Tian Yuexin,Guo Huifang,Miao Xinyan,Xu Jie,Yang Ran,Zhao Lu,Liu Jinxi,Yang Lin,Gao Fan,Zhang Wei,Liu Qingjuan,Sun Shaoguang,Tian Yu,Li Hongbo,Huang Jie,Gu Cunyang,Liu Shuxia,Feng Xiaojuan
Podocyte injury is the main cause of proteinuria in lupus nephritis (LN). Nestin, an important cytoskeleton protein, is expressed stably in podocytes and is associated with podocyte injury. However, the role of nestin in the pathogenesis of proteinuria in LN remains unclear. The correlations among nestin, nephrin and proteinuria were analyzed in LN patients and MRL/lpr lupus-prone mice. The expression of nestin in mouse podocyte lines (MPCs) and MRL/lpr mice was knocked down to determine the role of nestin in podocyte injury. Inhibitors and RNAi method were used to explore the role of mitophagy and oxidative stress in nestin protection of podocyte from damage. There was a significantly negative correlation between nestin and proteinuria both in LN patients and MRL/lpr mice, whereas the expression of nephrin was positively correlated with nestin. Knockdown of nestin resulted in not only the decrease of nephrin, p-nephrin (Y1217) and mitophagy-associated proteins in cultured podocytes and the podocytes of MRL/lpr mice, but also mitochondrial dysfunction in podocytes stimulated with LN plasma. The expression and phosphorylation of nephrin was significantly decreased by reducing the level of mitophagy or production of reactive oxygen species (ROS) in cultured podocytes. Our findings suggested that nestin regulated the expression of nephrin through mitophagy and oxidative stress to protect the podocytes from injury in LN.
研究领域:
肾病学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Lei Zhao,Siyuan Han,Chengzhi Chai
Ethnopharmacological relevance Huangkui capsule (HKC), a Chinese patent medicine, has been widely used in China as adjuvant therapy for chronic kidney disease (CKD). It displays superior anti-proteinuria efficacy than losartan in patients with CKD at stages 1–2, however, the mechanism of HKC alleviating proteinuria has not been well elucidated. Aim of the study This study aims to confirm the therapeutic effect and investigate associated underlying mechanism of HKC against proteinuria by in vivo and in vitro experiments. Materials and methods We established a doxorubicin (DOX) induced proteinuria mouse model to evaluate kidney function by biochemical markers measurement and to observe histopathological alterations by hematoxylin and eosin (H&E), Masson's trichrome and Periodic Acid-Schiff (PAS)-stained sections of renal, respectively. Moreover, the expressions of Nephrin and Podocin were measured by immunohistochemistry (IHC) and western blotting analysis to investigate podocyte damage. Furthermore, we established Mouse Podocyte Clone-5 (MPC-5) injury model to identify the active components of HKC against podocyte damage by detecting the expressions of Nephrin, Podocin, and ZO-1 proteins. At last, the key protein levels of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were assessed by western blotting analysis to explore the underlying mechanism of HKC against proteinuria. Results Our results showed that HKC administration for three consecutive weeks dose-dependently ameliorated both renal function and histopathological damages, elevated the expressions of Nephrin and Podocin, the pivotal molecules maintaining filtration function of the podocyte, indicating the promising protective effect against podocyte injury under DOX exposure. Consistently, in vitro experiments showed HKC administration effectively reversed the abnormal expressions of Nephrin and Podocin in MPC-5 cells treated with DOX, suggesting its protective effect against podocyte injury to maintain filtration barrier integrity. In addition, Hibifolin was identified as the most active ingredients in HKC, which suppressed upstream JAK2/STAT3 and PI3K/Akt pathway phosphorylation to maintain the structural and functional integrity of podocyte filtration barrier. Of note, AG490 , a selective JAK2 inhibitor , was used to further affirm the role of Hibifolin involving in regulation JAK2/STAT3. Conclusions Our study suggested that HKC may protect podocytes via JAK2/STAT3 and PI3K/Akt pathway to display its effects of ameliorating proteinuria.
研究领域:
药理学
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肾病学
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民族药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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