ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Wangning Zhang,Zhuoxia Shen,Yan Wu,Wenze Zhang,Tiange Zhang,Bo-Yang Yu,Xianchuang Zheng,Jiangwei Tian
The kidney is a vital organ and susceptible to various diseases. Photoacoustic (PA) imaging provides a powerful technique for studying kidney dysfunction, for which many smart photoacoustic imaging agents have been developed. But the complete clearance of the introduced contrast agents after imaging remains to be challenging, leading to long-term toxicity concerns. In this study, we synthesized black phosphorous quantum dots (BPQDs) with ultra-small size (1.74 ± 0.23 nm after surface modification) and strong PA signal for imaging kidney dysfunction. Importantly, the renal-clearance property and biodegradability of the developed BPQDs help circumvent the long-term toxicity issue for in vivo studies. Based on these BPQDs, both acute kidney injury and chronic kidney disease were successfully detected in the living mice by PA imaging, with higher detection sensitivity than the clinical serum indices examination method. This BPQDs-based PA imaging method should have a promising potential for the early diagnosis of kidney dysfunction in clinic.
研究领域:
生物医学工程
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纳米技术
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医学影像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yudan Mei,Xiaoyu Tong,Yumei Hu,Wenjun Liu,Jiajia Wang,Kaihong Lv,Xu Li,Liang Cao,Zhenzhong Wang,Wei Xiao,Xia Gao
Ethnopharmacological relevance Shen-Wu-Yi-Shen tablets (SWYST), a Chinese patent medicine consisting of 12 herbal medicines, was formulated by a famous TCM nephrologist, Zou Yunxiang. It is clinically used to improve the symptoms of nausea, vomiting, poor appetite, dry mouth and throat, and dry stool in patients with chronic renal failure (CRF) accompanied by qi and yin deficiency, dampness, and turbidity. SWYST can reduce urea nitrogen, blood creatinine, and urinary protein loss, and increase the endogenous creatinine clearance rate. However, little is known about its pharmacokinetics . Aim of study To compare the pharmacokinetics of six bioactive components after oral administration of SWYST in normal and adenine-induced CRF rats. Materials and methods A method based on ultra-performance liquid chromatography coupled with a triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS/MS) was developed and validated to determine the six bioactive compounds (albiflorin, paeoniflorin , plantagoguanidinic acid, rhein , aloe-emodin, and emodin) in rat plasma. Rat plasma samples were prepared using protein precipitation. Chromatography was performed on an Agilent Eclipse Plus C 18 column (3.0 × 50 mm, 1.8 μm) using gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% (v/v) formic acid, while detection was achieved by electrospray ionization MS under the multiple selective reaction monitoring modes. After SWYST administration, rat plasma was collected at different time points, and the pharmacokinetic parameters of six analytes were calculated and analyzed based on the measured plasma concentrations. Results The UPLC-TSQ-MS/MS method was fully validated for its satisfactory linearity ( r ≥ 0.9913), good precisions (RSD <11.5%), and accuracy (RE: -13.4∼13.1%), as well as acceptable limits in the extraction recoveries, matrix effects, and stability (RSD <15%). In normal rats, the six analytes were rapidly absorbed (T max ≤ 2 h), and approximately 80% of their total exposure was eliminated within 10 h. Moreover, in normal rats, the AUC 0-t and C max of albiflorin , plantagoguanidinic acid, and rhein exhibited linear pharmacokinetics within the dose ranges, while that of paeoniflorin is non-linear. However, in CRF rats, the six analytes exhibited reduced elimination and significantly different AUC or C max values. These changes may reflect a decreased renal clearance rate or inhibition of drug-metabolizing enzymes and transporters in the liver and gastrointestinal tract caused by CRF. Conclusions A sensitive UPLC-TSQ-MS/MS method was validated and used to investigate the pharmacokinetics of SWYST in normal and CRF rats. This is the first study to investigate the pharmacokinetics of SWYST, and our findings elucidate the causes of their different pharmacokinetic behaviors in CRF rats. Furthermore, the results provide useful information to guide further research on the pharmacokinetic-pharmacodynamic correlation and clinical application of SWYST.
研究领域:
民族药理学
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药代动力学
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中药学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
·
IF 5.6
Jing Zhang,Xuewei Yang,Xing Zhao,Gang Luo,Hong Jiang
Renal fibrosis is recognized as a critical pathway leading to end-stage renal disease in nearly all cases of chronic kidney disease (CKD). Analysis of the gene expression omnibus (GEO) database revealed that the transcription factor Krüppel-like factor 3 (KLF3) was elevated in kidney tissues of CKD patients, however, its specific role in CKD-associated renal fibrosis is yet to be deciphered. This study aimed to investigate the function of KLF3 on unilateral ureteral obstruction (UUO) mice and transforming growth factor-β1 (TGF-β1)-stimulated HK2 cells. Our data demonstrated that KLF3 was remarkably upregulated in the renal cortex of UUO mice and TGF-β1-treated HK-2 cells. We further confirmed that the upregulation of KLF3 was associated with its N6-methyladenosine (m6A) methylation modification. Knockdown of METTL14 reduced m6A methylation level of KLF3 and inhibited its mRNA stability. In vivo results suggested that KLF3 knockdown alleviated the pathological changes in renal tissues triggered by UUO. Additionally, KLF3 silencing mitigated renal fibrosis both in vivo and in vitro , as accompanied by decreased expression of Collagen I, Vimentin, α-SMA and Fibronectin. Mechanistically, KLF3 transcription activated dimethylarginine dimethylaminohydroxylase 2 (DDAH2) and upregulated its expression. Rescue experiments substantiated that DDAH2 overexpression eliminated the effect of KLF3 knockdown on renal fibrosis. Collectively, our findings suggest that inhibition of KLF3 may serve as a potential strategy to prevent CKD-associated renal fibrosis.
研究领域:
分子生物学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-18
·
IF 10.2
Chen Wei,Wang Bing,Liang Shanshan,Wang Meng,Zheng Lingna,Xu Si,Wang Jiali,Fang Hao,Yang Pu,Feng Weiyue
Background Renal excretion is one of the major routes of nanomaterial elimination from the body. Many previous studies have found that graphene oxide nanosheets are excreted in bulk through the kidneys. However, how the lateral size affects GO disposition in the kidneys including glomerular filtration, active tubular secretion and tubular reabsorption is still unknown.Results The thin, two-dimensional graphene oxide nanosheets (GOs) was observed to excrete in urine through the kidneys, but the lateral dimension of GOs affects their renal clearance pathway and renal injury. The s-GOs could be renal excreted via the glomerular filtration, while the l-GOs were predominately excreted via proximal tubular secretion at a much faster renal clearance rate than the s-GOs. For the tubular secretion of l-GOs, the mRNA level of basolateral organic anion transporters Oat1 and Oat2 in the kidney presented dose dependent increase, while no obvious alterations of the efflux transporters such as Mdr1 and Mrp4 mRNA expression levels were observed, suggesting the accumulation of l-GOs. During the GO renal elimination, mostly the high dose of 15 mg/kg s-GO and l-GO treatment showed obvious kidney injuries but at different renal compartment, i.e., the s-GOs induced obvious glomerular changes in podocytes, while the l-GOs induced more obvious tubular injuries including necrosis of renal tubular epithelial cells, loss of brush border, cast formation and tubular dilatation. The specifically tubular injury biomarkers KIM1 and NGAL were shown slight increase with mRNA levels in l-GO administrated mice.Conclusion sThis study shows that the lateral size of GOs affected their interactions with different renal compartments, renal excretion pathways and potential kidney injuries.
研究领域:
纳米技术
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毒理学
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药代动力学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Zhengqi Zha,Xiaoning Wang,Guoqing Wang,Hongping Yin,Hang Wang
Acetic acid has been shown to be effective in chronic kidney disease (CKD). However, it is a low-molecular-weight compound that allows it to be absorbed in the upper digestive tract so that it cannot function in colon. To overcome these deficiencies, an acetate-releasing xylan derivative, xylan acetate ester (XylA), was synthesized and selected in this study for its potential in the treatment of CKD. IR, NMR and HPGPC were used to characterize the structure of XylA and its antinephritic effects was evaluated in vivo. The results showed that acetate was successfully grafted onto the C-2 and C-3 positions of xylan and with a molecular weight at 69157 Da. XylA treatments could relieve the symptoms of CKD in an adenine-induced chronic renal failure (CRF) model and an adriamycin-induced focal segmental glomerulosclerosis (FSGS) model in SD rats. Further study indicated that XylA could upregulate the short-chain fatty acids (SCFAs) in vitro and vivo . Nevertheless, the relative abundance of Phascolarctobacterium in colon was increased after XylA treatment. XylA could upregulate G-protein-coupled receptor 41 (GPR41) expression, inhibit glomerular cell apoptosis and promoting proliferation. Our study expands the application of xylan and provides a new idea for the treatment of CKD with acetic acid.
研究领域:
药学
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肾脏生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Yanmin Zhang,Jianqiang Hu,Yan Zhang,Xiaolin Yang,Weihua Tong,Xinxin Ci
Background The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a significant cause of kidney failure. Although the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) has been demonstrated to inhibit ferroptosis and alleviate cisplatin-induced AKI, the specific roles of Nrf2 and the alkaloid leonurine in modulating the AKI-CKD transition remain incompletely elucidated. Methods Murine and human proximal tubular epithelial cell models of the AKI-CKD transition were established using repeated low-dose cisplatin (RLDC) to investigate the roles of Nrf2 and leonurine in ferroptosis regulation and disease progression. Key results In mice, RLDC administration induced persistent tubular injury, ferroptosis, and progressive renal fibrosis. In HK-2 cells, RLDC triggered oxidative stress and ferroptosis. Although Nrf2 expression was transiently upregulated during the acute phase (4 weeks post-RLDC), it was downregulated by the chronic phase (8 weeks post-RLDC), correlating with impaired antioxidant capacity and exacerbated ferroptosis. Nrf2 knockout mice exhibited more severe oxidative damage, ferroptosis, and renal dysfunction following RLDC challenge. Pharmacological activation of Nrf2 by leonurine attenuated oxidative injury and ferroptosis and promoted tubular repair. Leonurine also suppressed the epithelial–mesenchymal transition and aberrant extracellular matrix deposition, ultimately mitigating renal fibrosis. The protective effects of leonurine were abolished in Nrf2 knockout mice. Conclusion These findings demonstrate that Nrf2 activation mitigates cisplatin-induced AKI-CKD transition by counteracting oxidative stress and ferroptosis, thereby attenuating renal fibrosis. Leonurine, as a potent Nrf2 activator, represents a promising therapeutic agent for preventing AKI-CKD transition.
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产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2019
·Vol. 393
·期 1
·57-65
·
IF 2.058
Zhai Jiajia,Li Zeping,Zhang Huifeng,Ma Louyan,Ma Zhengquan,Zhang Yi,Zou Jian,Li Mo,Ma Li,Li Xiaomiao
The present study has been designed and carried out to evaluate the potential of coptisine on diabetic nephropathy. Diabetes was induced in SD rats through one single intraperitoneal injection of streptozotocin (65 mg/kg) method, and then diabetic rats were orally administered with 25 mg/kg/day coptisine or 50 mg/kg/day coptisine for 8 weeks. Severe impairment of renal function in rats with diabetes was observed as indicated by increased urine protein excretion, kidney hypertrophy index, serum creatinine level, and blood urea nitrogen level. Oxidative stress damage was observed as indicated by increased levels of reactive oxygen species, malondialdehyde, and decreased levels of glutathione, superoxide dismutase, and catalase. However, these alterations in kidneys of rats with diabetes were alleviated by administration of coptisine. Furthermore, the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its targeted antioxidative genes heme oxygenase 1 and NADPH quinone oxidoreductase 1 in the diabetic kidneys were significantly increased after coptisine treatment. These results suggested that coptisine ameliorated oxidative renal injury in diabetic rats, and the possible mechanisms for the renoprotective effects of coptisine may be related to activation of the Nrf2 signaling pathway.
研究领域:
药理学
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糖尿病
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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
ACTA PHARMACOLOGICA SINICA
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2023
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IF 8.2
Wang Meng-yang,Yu Tian-xiang,Wang Qin-yan,Han Xue,Hu Xiang,Ye Shi-ju,Long Xiao-hong,Wang Yi,Zhu Hong,Luo Wu,Liang Guang
Hypertensive renal disease (HRD) contributes to the progression of kidney dysfunction and ultimately leads to end-stage renal disease. Understanding the mechanisms underlying HRD is critical for the development of therapeutic strategies. Deubiquitinating enzymes (DUBs) have been recently highlighted in renal pathophysiology. In this study, we investigated the role of a DUB, OTU Domain-Containing Protein 1 (OTUD1), in HRD models. HRD was induced in wild-type or Otud1 knockout mice by chronic infusion of angiotensin II (Ang II, 1 μg/kg per min) through a micro-osmotic pump for 4 weeks. We found that OTUD1 expression levels were significantly elevated in the kidney tissues of Ang II-treated mice. Otud1 knockout significantly ameliorated Ang II-induced HRD, whereas OTUD1 overexpression exacerbated Ang II-induced kidney damage and fibrosis. Similar results were observed in TCMK-1 cells but not in SV40 MES-13 cells following Ang II (1 μM) treatment. In Ang II-challenged TCMK-1 cells, we demonstrated that OTUD1 bound to CDK9 and induced CDK9 deubiquitination: OTUD1 catalyzed K63 deubiquitination on CDK9 with its Cys320 playing a critical role, promoting CDK9 phosphorylation and activation to induce inflammatory responses and fibrosis in kidney epithelial cells. Administration of a CDK9 inhibitor NVP-2 significantly ameliorated Ang II-induced HRD in mice. This study demonstrates that OTUD1 mediates HRD by targeting CDK9 in kidney epithelial cells, suggesting OTUD1 is a potential target in treating this disease.
研究领域:
肾病学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Xuan Yang,Yijia Li,Lirong Zheng,Xiaoyun He,Yunbo Luo,Kunlun Huang,Wentao Xu
The incidence of kidney disease has increased rapidly in recent years. One major possible reason for this increase in nephrosis is from foodborne toxins. Since the mechanism of how foodborne toxins are involved in the process of nephrosis is largely unknown, the current study aims to establish a profile for how one of the major toxin threats, ochratoxin A (OTA), induce differential protein expression. In this proteomic study of rat kidneys, 75 kd glucose-regulated protein (Grp75) expression was found to be sensitized by a low concentration of OTA, but inhibited by high doses. In response to OTA, a decrease in Grp75 expression preceded the inhibition of mitochondrial Lon peptidase 1 (Lonp1). Using Grp75 knockdown cell line, it was shown that the inhibition of Grp75 promoted the secretion of kidney injury molecule 1 (Kim1), and suppressed Lonp1 expression in renal injury . Moreover, the acceleration of renal disease was associated with the consumption of Grp75. Our study suggests that the Grp75 protein may be valuable as both a treatment and biomarker for the foodborne diseases that induce renal tubular necrosis . The findings of this research are beneficial for the establishment of nutritional interventions, and the screening of therapeutic targets, in cases of nephrosis.
研究领域:
毒理学
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肾病学
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蛋白质组学
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食品安全
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CARBON
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2022
·
IF 11.307
Pengli Gao,Hui Hui,Chanjuan Guo,Yu Liu,Ya Su,Xiazi Huang,Kunxiong Guo,Wenting Shang,Jingying Jiang,Jie Tian
Real-time renal imaging is indispensable for monitoring kidney-related disease processes and evaluating the nephrotoxicity of nanoprobes . Owing to their small size, tunable photoluminescence properties, and low biotoxicity, carbon dots (CDs) are widely employed as nanoprobes for imaging-guided disease diagnosis. However, the preparation of near-infrared CDs is a stupendous challenging. Here, CDs with near-infrared fluorescence (NIR-CDs) were prepared by one-pot pyrolysis and were comprehensively evaluated for real-time renal imaging. The NIR-CDs possessed super-small size (1.8 ± 0.2 nm) and high quantum yield (14.3% in aqueous solution) at 696 nm. NIR-CDs exhibited high-efficiency renal clearance at 24 h post-treatment (97.47–99.27% ID) via glomerular filtration . The irreversible clearance of NIR-CDs enables effective real-time monitoring of kidney function in the normal and acute kidney injury (AKI) mouse models. Consequently, NIR-CDs can be utilized for imaging analyses of impaired kidney function , pioneering a serviceable guideline for neoapplications of NIR-CDs.
研究领域:
纳米医学
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分子影像学
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肾脏病学
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生物材料
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药物代谢
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诊断学
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转化医学
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DOI
高影响因子
Advanced Science
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2025
·
IF 14.1
Lei Du,Sijie Liu,Yinfei Lu,Dongxue Ren,Xiujuan Yu,Yue Hu,Tingting Yang,Qun Yang,Jingxian Ming,Jiawei Zhang,Xiaoxing Yin,Qian Lu
Abnormal proliferation of mesangial cells is a hallmark of diabetic nephropathy (DN). However, the cellular signaling mechanisms that regulate this proliferation remain poorly understood. In this study, it is demonstrated that GA-binding protein (GABP), a member of the ETS family of transcription factors composed of GABPα and GABPβ, plays a significant role in the development of renal fibrosis by modulating mesangial cell proliferation. Notably, the deficiency of GABP in mesangial cells inhibits hyperglycemia-induced proliferation and mitigates renal fibrosis in a murine model of type 2 diabetes mellitus (T2DM). RNA sequencing analysis identifies GLI Family Zinc Finger 1 (GLI1) as the principal downstream effector of GABP in diabetic mice, serving as a crucial regulator of the G1/S transition within the cell cycle. Subsequent investigations have demonstrated that GABP interacts with the GLI1 promoter, facilitating mesangial cell proliferation via GLI1-dependent pathways. This is evidenced by the fact that GLI1 knockdown abrogates the proliferation of mesangial cells with GABP overexpression. Consequently, GABP emerges as a pivotal regulator of renal fibrosis and represents a promising therapeutic target for the treatment of diabetic nephropathy.
研究领域:
分子生物学
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医学
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肾脏病学
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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）