ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Mengdi Zhang,Jindong Gao,Md. F. Kulyar,Wanhe Luo,Guodong Zhang,Xiaoqi Yang,Tianguang Zhang,Haihang Gao,Yuxuan Peng,Jiabin Zhang,Muhammad Altaf,Samah Attia Algharib,Donghai Zhou,Jianzhong He
Acute renal failure is a common clinical disease in canines, affecting antioxidant levels and decreasing the body's resistance. This study aims to explore the therapeutic mechanism of Nano-selenium in acute renal failure. The histopathological and imaging changes of kidney tissue were observed with the gene and protein expression levels of Keap1, Nrf2, HO-1, and NQO1 in the kidney. According to our findings, adding nano-selenium can effectively reduce the concentration of CRE and BUN in blood and kidney tissues. It increased the activity of GSH-PX and SOD by an effective reduction of MDA. Through pathological and imaging observations, it was found that adding nano-selenium could improve the kidney tissue structure of acute renal failure. The results of the RT-qPCR experiment showed that after the addition of nano-selenium, the mRNA expression of the Keap1 gene decreased significantly. In contrast, the mRNA expression of the Nrf2, HO-1, and NQO1 genes increased significantly. The experimental results were further verified by western blot and immunohistochemical analysis. Hence, the nano-selenium intervention improved kidney function and increased antioxidant levels in canines suffering from acute renal failure with the involvement of the Keap1-Nrf2/ARE signaling pathway.
研究领域:
兽医学
·
分子生物学
✓ 已验证
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
JOURNAL OF MICROENCAPSULATION
·
2020
·
IF 2.287
Mingjia Gu,Lidan Lu,Qingxue Wei,Zhiwei Miao,Hang Zhang,Leiping Gao,Lejun Li
Aims This study was designed to prepare chrysophanol-loaded micelles (CLM) to improve the oral bioavailability, targetability and anti-chronic renal failure (CRF) activity of chrysophanol (CH).Methods The preparation of CLM was achieved via thin-film dispersion technique. The in vitro release of CLM compared with free CH was measured in phosphate buffer solution (PBS) containing 0.5%w/v sodium dodecyl sulphate (pH 6.8) while the pharmacokinetic and anti-CRF activity study was also conducted in rats. Moreover, the tissue distribution of CLM was investigated in the mice.Results The CLM had particle size (PS) of 29.64 ± 0.71 nm, and encapsulation efficiency (EE) of 90.48 ± 1.22%w/w. The cumulative release rate of CH from the micellar system was significantly higher than that of the free CH (86%m/m vs. 15%m/m, p < 0.01). In vivo pharmacokinetic studies showed that the bioavailability of CLM after oral administration was substantially improved (about 3.4 times) compared with free drugs (p < 0.01). Also, it was observed that CLM accumulated well in the liver and brain. Moreover, in vitro renal podocytes study showed that CLM had better protection against renal podocyte damage than the free CH. In addition, CLM significantly (p < 0.01) reduced levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), and serum creatinine (SCr), which obviously improved kidney damage in rats with CRF.Conclusions Collectively, these findings suggest that mixed micelles may be used as a promising drug delivery system for oral bioavailability improvement and concomitantly enhance the anti-CRF activity of CH, as well as provide a basis for the clinical application of CH.
研究领域:
药剂学
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肾病学
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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
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Yanru Liu,Ya Hu,Xiaoxia Xie,Gongjun Yang,Fang Feng
Wen-Pi-Tang (WPT), a Traditional Chinese Medicine (TCM) prescription, is commonly used to treat chronic renal failure. However, the material basis and potential mechanisms of WPT against chronic renal failure have not been clarified. UHPLC-Q-Exactive Orbitrap-MS was utilized in this work to investigate the chemical components of WPT and their prototypes or metabolites in vivo. 227 chemical compounds were identified in the WPT. Meanwhile, 56 exogenous components (24 prototype components and 32 metabolic components) were examined in rat plasma. Meanwhile, network pharmacology revealed that liquiritigenin-O-sulfate, 3-keto-18β-glycyrrhetinic acid, 22-hydroxy-18-β-glycyrrhetinic acid, and hydroxyliquiritigenin (B ring)-O-sulfate with related targets AKT1, EGFR, STAT3, ESR1, SRC, MAPK3, MTOR, and PIK3CA were considered as the effective components and core targets. Furthermore, the findings suggested that the therapeutic effects of WPT on chronic renal failure may be substantially influenced by the PI3K-Akt, HIF-1, and FoxO signaling pathways. The outcomes of molecular docking and molecular dynamics simulations indicate that the key targets have strong binding capacities with effective components. Our study offers a comprehensive method for examining the molecular foundation and underlying mechanisms of WPT against chronic renal failure, opening up new therapeutic opportunities.
研究领域:
中药学
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药理学
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代谢组学
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产品关联
DOI
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
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肾脏生理学
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心脏病学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 9
·1960-1970
·
IF 5.344
Ye Yang,Shiqi Yin,Chao He,Xizheng Wu,Jiarui Yin,Jue Zhang,Lang Ma,Weifeng Zhao,Chong Cheng,Changsheng Zhao
Recently emerged hemoperfusion absorbents, e.g. ion-exchange resin, activated carbon, and other porous materials, provide numerous novel possibilities to cure chronic liver failure (CLF) and renal failure (CRF). However, the limited adsorption performance and unsatisfactory blood compatibility significantly impede the development of the absorbents. Hence, designing safe and self-anticoagulant hemoperfusion absorbents with robust toxin clearance remains a considerable challenge. Here, brand new Kevlar-based composite gel beads for hemoperfusion are prepared by interface assembly based on π–π interaction. First, Kevlar nanofiber–graphene oxide (K–GO) beads are produced by liquid–liquid phase separation. Then, sodium p-styrenesulfonate (SS) is adsorbed onto the K–GO interface by π–π interaction and initiated to achieve the composite gel (K–GO/PSS) beads with an interfacial crosslinked structure. Such composite gel beads possess superior mechanical strength and self-anticoagulation capability, owing to the dual-network structure and heparin-mimicking gel structure, respectively. Furthermore, the K–GO/PSS beads show robust adsorption capacities for different kinds of toxins due to their strong charge and π–π interactions. A simulated hemoperfusion experiment in vitro demonstrates that the concentrations of the toxins in the blood can be restored to normal values within 30 minutes. In general, we envision that such composite gel beads will provide new strategies for future clinical CLF and CRF treatments.
研究领域:
材料科学
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生物医学工程
·
血液透析技术
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DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2022
·Vol. 40
·期 17
·2054-2060
·
IF 5.56
Mengping Chen,Lang Lang,Lei Chen,Xiaomei Wang,Cen Shi,Qiwen Sun,Yigong Xu,Juan Diwu,Shuao Wang
Comprehensive Summary The environmental contamination of uranium will occur in scenarios such as nuclear accidents and leakage from nuclear waste storage sites, which eventually leads to the internal uranium exposure of people, causing consequential injuries of renal failure, osteosarcoma, etc . The development of uranyl specific chelating agents that could sequester uranium in vivo is in urgent need and is important for the safe and efficient development of nuclear industry. Metal organic frameworks (MOFs) already serve as efficient uranium depletion materials in solutions of a wide range of pH and ionic strength for nuclear fuel recycling, uranium extraction from seawater, as well as environmental decontamination. Herein, a chromium-based nano-metal organic framework (nano-MOF) functionalized interiorly with 3,2-HOPO ligands, MIL-101-HOPO, is rationally synthesized. In vitro adsorption experiments show that MIL-101-HOPO exhibits high adsorption selectivity and fast adsorption kinetics for uranyl. The results of in vivo uranyl decorporation assays reveal that MIL-101-HOPO with the decoration of HOPO ligands on the interior wall exhibits significantly increased uranyl removal ratio in kidneys comparing to the pristine nMOFs, and is more effective than the clinically used ZnNa 3 -DTPA. All those results corroborate the interior functionalization of MOFs as an efficient strategy to develop promising uranyl decorporation agents.
研究领域:
环境科学
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材料科学
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核工程
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毒理学
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2015
·
IF 5.636
Henan Li,Yawen Mu,Junrong Yan,Dongmei Cui,Weijun Ou,Yakun Wan,Songqin Liu
Acute renal failure (ARF) represents a very important and potentially devastating disorder in clinical nephrology. Neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for ARF in a wide range of different disease processes, which is frequently detected in clinical diagnosis. Herein, we present a label-free and sensitive photoelectrochemical (PEC) immunosensor for NGAL by utilizing a biotinylated anti-NGAL Nanobody (Nb) orientedly immobilized to streptavidin-coated cobalt 2,9,16,23-tetraaminophthalocyanine (CoPc)-sensitized TiO2 electrode. The Nb was biotinylated at the C-terminus, which is situated at the opposite site of the antigen binding region. Using highly oriented Nb as receptor molecules, a label-free PEC immunosensor for NGAL was developed by monitoring the changes in the photocurrent signals of the electrode resulting from immunoreaction. Immobilization of Nb to streptavidin-coated CoPc-sensitized TiO2 electrode surface provides high binding capacity to NGAL; thus, it can lead to a high sensitivity. The limit of detection (LOD) of the proposed immunosensor has been significantly lowered to 0.6 pg mL–1. This proposed immunosensor reveals high specificity to detect NGAL, with acceptable intra-assay precision and excellent stability. In addition, the present work provides a new approach to design Nb-based PEC immunosensor and increases versatility of Nbs.
研究领域:
临床医学
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生物传感器
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2020
·Vol. 4
·期 9
·853-862
·
IF 18.952
Zheng Di-Wei,Pan Pei,Chen Ke-Wei,Fan Jin-Xuan,Li Chu-Xin,Cheng Han,Zhang Xian-Zheng
Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.
研究领域:
医学
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生物技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2017
·Vol. 40
·期 24
·4872-4879
·
IF 2.557
Tanye Xu,Lihua Zuo,Zhi Sun,Peile Wang,Lin Zhou,Xiaojing Lv,Qingquan Jia,Xin Liu,Xiaofang Jiang,Zhenfeng Zhu,Jian Kang,Xiaojian Zhang
ShenKang injection is traditional Chinese medicine used to treat chronic renal failure in China. It is a compound preparation that consists of four herbs: Rhubarb, Salvia miltiorrhiza, Safflower and Radix Astragali . We developed an ultra high pressure liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high resolution accurate mass spectrometry tandem mass spectrometry method to analyze its chemical compositions, and a total of 90 compounds were identified from ShenKang injection. Among them, 19 major compounds were unambiguously detected by comparing with reference standards. Meanwhile, 13 representative compounds selected as quality control markers were simultaneously quantified in ShenKang injection samples. Chromatographic separation was accomplished on a Waters ACQUITY HPLC® HSS C 18 column using gradient elution. The method was validated with respect to linearity, sensitivity, accuracy and precision, reproducibility and stability. And the validated method was successfully applied for simultaneous determination of 13 bioactive compounds in ShenKang injection from ten batches of samples by liquid chromatography with mass spectrometry. The results were analyzed by principal components analysis method, and three compounds had a significant relationship with the quality control of ShenKang injection. This research established a rapid and reliable method for the integrating quality control, including qualitation and quantification of ShenKang injection.
研究领域:
药理学
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分析化学
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传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Tao Sun,Qinjun Chen,Zheng Zhou,Chao Li,Teng Yu,Chen Jiang
Precisely reporting the inflammatory microenvironment, which can provide important basis for disease diagnosis and progression determination, is always challenging. In this work, we develop a targeting peptide-conjugated chemiluminescent reporter (OFF), which can be recognized by in-situ circulated neutrophils once injected, and then transported to the inflamed tissues characterized with overexpressed superoxide anion (O 2 − ), assisted by the chemotaxis natural of neutrophils. Subsequently, the chemiluminescent probe can particularly respond to O 2 − to release the caged photons (ON) for visualizing inflammatory diseases such as subcutaneous tumor, colorectal cancer peritoneal metastasis (CCPM), ear swelling and kidney failure. The chemiluminescent probe provides a reliable tool to early detect inflammation and precisely excise micrometastatic lesions under optical guidance. This study provides a potential approach for improving the performance of luminophore in advanced bioimaging applications.
研究领域:
生物医学工程
·
成像科学
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炎症生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 22
·4555-4566
·
IF 6.331
Wenhui Chen,Qiu Han,Yang Liu,Yiwen Wang,Fu Liu
Hyperphosphatemia, a common complication of chronic renal failure patients, is described as an excess amount of serum phosphate >4.5 mg dL−1. Current therapy for hyperphosphatemia is limited by low removal efficiency, secondary hyperparathyroidism, uremic bone disease, and the promotion of vascular and visceral calcifications. Metal organic frameworks (MOFs) have aroused great interest in the field of blood purification because of their strong specific adsorption. Herein, we prepared mixed matrix microspheres (MMMs) encapsulated NH2-MIL-101(Fe) with specific adsorption to blood phosphate. Simultaneously, a heparinoid copolymer poly (acrylic acid-sodium 4-vinylbenzenssulfonate) (P(AA-SSNa)) was incorporated to improve the hemocompatibility. The proposed MMMs exhibited excellent phosphate adsorption capacity both in aqueous and human plasma environments. They also showed comprehensive hemocompatibility e.g. low tendency of protein adsorption, low hemolysis rate and extended blood coagulation time. In general, we envision that the MMMs are potentially suitable as highly efficient hemoperfusion adsorbents for hyperphosphatemia treatment.
研究领域:
药学
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肾病学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）