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BIOMEDICINE & PHARMACOTHERAPY · 2019 · IF 3.743

Nano-lanthanum hydroxide, a novel phosphate binder, for treating hyperphosphatemia: A preclinical study

Zixing Ma,Tengfei Yu,Yan Wu,Dandan Liu,Xiaofei Zhang,Xin Miao,Haiyan Xing,Gang Li

This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30–50 nm, width of 10–20 nm, and diameter of 5–10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.

研究领域: 药理学 · 肾病学 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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AQUACULTURE RESEARCH · 2020 ·Vol. 51 ·期 4 ·1592-1601 · IF 1.748

In vivo antiviral efficacy of moroxydine hydrochloride against grass carp reovirus and the drug safety assessment

Xiao-Bo Yu,Kai Hao,Fei Ling,Bin Zhu,Gao-Xue Wang

Our previous studies have verified that moroxydine hydrochloride (Mor) could inhibit replication of grass carp reovirus (GCRV) and suppress apoptosis of Ctenopharyngodon idella kidney cells, but be lack of information whether exists on antiviral activity in vivo. The paper was undertaken to explore the antiviral response of Mor against GCRV in grass carp and investigate the safety of drug for aquatic organisms. The results showed that injection treatment of Mor could more effectively inhibit GCRV replication than immersion administration. All the RNA systheses of vp3 and vp6 on day 7 in head kidney, gill, hepatopancreas and dorsal muscle in the Mor injection group were lesser than 0.07-fold than that of in control group. And the GCRV-inducing grass carp mortality was effectively controlled within 7 days post Mor injection therapy. Additionally, the reduction of superoxide dismutase activity, total antioxidant capacity and catalase activity in serum was effectively controlled by Mor. Moreover, drug safety assessment results showed that 500 mg/L of Mor was safe to C. idella , Bacillus subtilis , Chlorella vulgaris and Tetrahymena thermophila , which was far higher than the therapeutic concentration. The present study proved Mor as harmless formulations or products had potential value in the control of GCRV in aquaculture, with the advantage of super in vivo antiviral activity and environmental safety.

研究领域: 兽医学 · 水产养殖 · 药理学 · 病毒学
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JOURNAL OF CHROMATOGRAPHY A · 2022 · IF 4.601

Preparation of dummy molecularly imprinted polymers for selective extraction of aromatic amine genotoxic impurities

Xiaoya Fu,Xia Wang,Zhining Xia,Yike Huang

To ensure drug safety, the quality monitoring of genotoxic impurities (GTIs) which have very trace content in medicine is important. Therefore, it should be established an efficient sample pretreatment method to extract GTIs to achieve specific enrichment. In this work, dummy template molecular imprinting technology (DMIT) was used as dummy template molecule (DTM) to substitute for the target molecule (TM) for established the pretreatment of the sample containing aromatic amine GTIs. A novel strategy for screening out DTM by calculation of computer simulation is established, where the binding energy between the template and functional monomer has the relatively lowest value (-9.60 kcal/mol). Then dummy template molecular imprinted polymer (DMIP) was prepared by bulk polymerization according to the molar ratio of template molecule-functional monomer-crosslinker = 1:4:8, the prepared DMIP exhibited the highest adsorption ( Q  = 8.6 mg/g) and good blotting effect (IF = 1.3) and can simultaneously adsorb three aromatic amine GTIs. The optimal adsorption conditions were obtained by conditional optimization of solid phase extraction (SPE). The solution of pH 7 was chosen as the loading condition, and methanol/acetic acid (90:10, v/v) was chosen as the elution condition. Finally, we determined 2, 6-dichloroaniline in diclofenac sodium at a 5 ppm level and p-toluidine as the TMs in torasemide sample at 10 ppm by using DMIT-based solid phase extraction and analysis by HPLC, it satisfied the quality control of GTIs in pharmaceutics. DMIT by this strategy has great potential in the sample preparation of GTIs.

研究领域: 药学 · 分析化学 · 药物安全性评价
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

Visualized molecularly-imprinted hydrogel chips for point-of-care SERS assay of N-nitrosodiethylamine contamination in antihypertensive drugs

Fang Wang,Yi-Mei Li,Jing Zhao,Jing Ye,Yuan-Ting Li

This study presents a dual-mode colorimetric and surface enhanced Raman scattering (SERS) platform for the highly sensitive and selective assay of N-nitrosodiethylamine (NDEA) in antihypertensive drugs. A polydopamine embedded molecularly-imprinted agarose hydrogel (MIAG) chip was developed, serving as a multifunctional sensing substrate. Upon exposure to NDEA, the chip facilitates specific target adsorption and enrichment, simultaneously triggering a Griess reaction that yields a deep-red azo compound. This reaction provides the basis for both colorimetric readout and generates a strong Raman signal through azo-enhanced scattering for quantification. This design allows the MIAG chip to function not only as a naked-eye indicator but also as a platform for smartphone-based colorimetric analysis by directly translating color responses into digital barcodes. Furthermore, the in-situ synthesized gold nanoparticles (AuNPs) within the hydrogel matrix generate enhanced SERS activity, leveraging the porous network to create abundant hotspots for ultra-sensitive detection, achieving a limit of detection as low as 2.3 × 10 −14  M. The synergistic combination of dual-mode output offers robust and cross-verification results, significantly improving detection reliability. This integrated smartphone-compatible platform holds great promise for point-of-care testing of drug safety, making accurate screening accessible from regulatory laboratories to the public

研究领域: 分析化学 · 生物传感器 · 纳米技术 · 药物分析 · 材料科学 · 生物医学工程
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TOXICOLOGY AND APPLIED PHARMACOLOGY · 2025 · IF 3.4

Integrative network toxicology and experimental validation reveal novel molecular mediators of omeprazole-induced nephrotoxicity

Qian Huang,Yuqian Li,Zhiliang Gao,Yiming Shao

Omeprazole, a widely used proton pump inhibitor, has been increasingly linked to adverse renal outcomes such as acute kidney injury (AKI) and chronic kidney disease (CKD), yet its nephrotoxic mechanisms remain unclear. In this study, we utilized an integrative network toxicology approach, combined with molecular docking and in vitro validation, to elucidate potential mechanisms underlying omeprazole-induced renal toxicity. By intersecting omeprazole-related genes with those implicated in AKI and CKD, we identified 73 overlapping targets enriched in the PI3K-Akt signaling pathway, EGFR inhibitor resistance, and xenobiotic response. A protein–protein interaction network and topological analysis revealed six hub targets (CASP3, CCND1, EGFR, MMP9, PARP1, PPARG), all showing strong binding affinities to omeprazole in molecular docking simulations. Functional validation in HK-2 cells demonstrated that omeprazole reduced cell viability, induced morphological damage, and increased apoptosis in both acute (300 μM, 24 h) and chronic (20 μM, 7 days) exposure models. qPCR analysis confirmed significant upregulation of CASP3 , EGFR , MMP9 , PARP1 , and PPARG , with CCND1 exhibiting model-dependent expression changes. These findings provide new insights into the molecular basis of omeprazole-associated nephrotoxicity and suggest potential biomarkers and therapeutic targets for mitigating renal injury.

CAS / MDL: 73590-58-6
研究领域: 毒理学 · 药理学 · 分子生物学 · 生物信息学 · 肾脏病学 · 药物安全
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Current Analytical Chemistry · 2017 ·Vol. 13 ·期 3 ·250-255 · IF 1.306

Determination of Cd2+, Cr3+, Cu2+ and Zn2+ in Traditional Chinese Medicine Shuanghuanglian Oral Liquid by High Performance Capillary Electrophoresis

Luan Feng,Lu Yuxi,Tang Lili,Liu Huitao

Background: The safety and level of heavy metal ions in the traditional Chinese medicine has become an important topic. Most of the metal ions are carcinogens and lead to serious health concerns by producing free radicals. It is of great significance to develop simple and effective methods to determine heavy metal ions. The aim of this paper is to develop a CE-indirect UV method for the analysis of the four heavy metal ions for Chinese medicine Shuanghuanglian oral liquid. Methods: The alternative CE method for separation and test of metal ions was developed in this paper, which can help control the safety and level of heavy metal ions in traditional Chinese medicine Shuanghuanglian oral liquid. And the developed HPCE method showed superior analytical performance, including high sensitivity and good selectivity. Results: The experimental conditions of the CE separation method were: 5s hydrodynamic injection at 0.5 psi, 20 kV applied voltage, and UV detection at 218 nm. The results show that the migration time of all the four heavy metal ions was less than 6 min. The calibration curves for four heavy metal ions were linear in the range of 0.5-35 μg mL-1 with linear correlation coefficients of 0.9984-0.9999. The limits of detection were in the range of 0.08-0.61 μg mL-1 along with the recoveries of 93.0% to 109.5%. Conclusion: A simple, rapid and sensitive HPCE method has been developed to separate four heavy metal ions including Cd2+, Cr3+, Cu2+ and Zn2+ in traditional Chinese medicine Shuanghuanglian oral liquid. The comprehensive analysis performance is satisfactory. The proposed HPCE method provides shorter analysis time and lower detection limit. The results demonstrated that the developed CE method can be potentially applied as an good alternative for quality control of TCM.

研究领域: 中药分析 · 药物安全
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JOURNAL OF CHROMATOGRAPHY A · 2025 · IF 4

Rapid Screening of Nitrosamine Impurities in Metformin Hydrochloride Tablets using Headspace Gas Chromatography Ion Mobility Spectrometry

Mengting Huang,Jianna Yu,Xiuqing Zheng,Jiaxu Liu,Peixuan Huang,Guoxing Jing,Wen Liu,Wenshan Li,Wenjie Liu

The detection of potent carcinogenic nitrosamine impurities in pharmaceutical products has attracted significant regulatory attention in recent years, and advanced analytical methods are needed to accurately quantify nitrosamines in pharmaceutical products. In this study, a headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) method was proposed and validated, which addresses two key challenges: achieving the sub-ppb sensitivity required for low-concentration nitrosamine analysis, and reducing matrix interferences in extended-release formulations. Seven investigated nitrosamines showed good linearity (R 2 >0.99) in the range of 0.5-100 ng/mL, with limits of detection (LOD) of 0.05-0.51 ng/mL and limits of quantification (LOQ) of 0.16-1.70 ng/mL. Precision studies (intra-day relative standard deviation RSD<5%, inter-day RSD<13%) and satisfactory spiked recoveries (84.31%-106.60%) in active pharmaceutical ingredient matrices confirmed the robustness of this method. The developed method eliminates the need for complex extraction and pre-concentration procedures, requires minimal sample preparation and enables rapid gas chromatography separation.

研究领域: 药物分析 · 药物质量控制 · 毒理学 · 分析化学 · 药剂学 · 药物安全
✓ 已验证 DOI PubMed 高影响因子
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