JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
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2019
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IF 2.895
Yiming Li,Guanhui Chen,Yi He,Xiliu Zhang,Binghui Zeng,Chao Wang,Chen Yi,Dongsheng Yu
Background Patients with metabolic bone diseases often have high risk of titanium implant failure due to compromised bone regeneration ability. Clinical evidence indicates that the poor osteogenic ability is partly because of excessive oxidative stress. To date, specific treatments for these patients are urgently needed. Ebselen, a non-toxic organoselenium compound, is reported to be a potent antioxidant agent. In this study, we hypothesized that ebselen exerted protective effects on osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) under oxidative stress. Methods BMSCs were isolated from SD rats, and their morphology and multiple differentiation abilities were characterized. Proliferation rates of BMSCs treated with different concentrations of ebselen were analyzed. Then BMSCs were pretreated by hydrogen peroxide (H 2 O 2 ), after which ebselen at different concentrations (0, 1, 5, 10 μM) was added, alkaline phosphatase (ALP) activity, mineralization and osteogenic-related protein levels were evaluated and an optimum concentration of ebselen was selected. Subsequently, intracellular reactive oxygen species (ROS) generation and the role of the PI3K/AKT pathway were also investigated. Results Ebselen within a proper range could promote the proliferation of BMSCs. H 2 O 2 -induced oxidative stress suppressed osteogenic differentiation of BMSCs, which was verified by the decrease in ALP activity, calcium deposition, Runx2 and β-catenin expression. However, ebselen could alleviate osteogenic dysfunction of BMSCs. We also observed that ebselen reduced ROS accumulation in H 2 O 2 -pretreated BMSCs. Moreover, the pro-osteogenic effects afforded by ebselen were almost abolished by the Akt inhibitor. Conclusion We concluded that ebselen could attenuate osteogenic dysfunction of BMSCs induced by H 2 O 2 through an antioxidant effect and the activation of the PI3K/Akt pathway, suggesting that ebselen has a potential therapeutic effect for patients with metabolic bone diseases.
研究领域:
干细胞生物学
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骨科
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small
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2022
·Vol. 18
·期 36
·2106591
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IF 15.153
Kaili Chen,Fei Wang,Rui Ding,Zhengwei Cai,Tianyuan Zou,Andi Zhang,Dongye Guo,Bin Ye,Wenguo Cui,Mingliang Xiang
The least damaging and most economical method to deliver drugs or carriers into the inner ear for treatment of disease is through the middle ear. However, the retention of drug in the middle ear is an obstacle. Here, inspired by the adhesion of mussels, a methacrylate gelatin microspheres (GM) coupling polydopamine (PDA) layer (GM@PDA) with excellent adhesive ability is constructed, and Ebselen liposomes are further loaded into the GM@PDA (GM@PDA@Lipo-Ebselen). The loading capacity of GM@PDA for Ebselen liposomes is 25 ± 1 µg mg −1 microspheres. GM@PDA@Lipo-Ebselen could be injected on round windows membrane (RWM) and tightly adheres to the surface of RWM by PDA, and the microspheres are even still attached to the RWM after 360° rotation and inverted shaking. The in vivo imaging system shows that the adhesive microspheres can prolong the retention of the middle ear cavity for more than 7 days. The hearing of mice in the GM@PDA@Lipo-Ebselen group is significantly recovered, especially on day 14 after noise exposure, and the hearing of each frequency is restored to baseline level. At 32 kHz frequency, the survival of outer hair cells recovers from 48 0± 6% to 93 ± 2%. Therefore, the adhesive and injectable hydrogel microspheres provide a promising strategy for the treatment of hearing loss.
研究领域:
生物材料学
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药剂学
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耳科学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2017
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IF 6.32
Min Zhu,Jinzhang Fang,Jingjing Zhang,Zheng Zhang,Jianhui Xie,Yan Yu,Jennifer Jin Ruan,Zhao Chen,Wei Hou,Gensheng Yang,Weike Su,Benfang Helen Ruan
Glutaminase (KGA/isoenzyme GAC) is an emerging and important drug target for cancer. Traditional methods for assaying glutaminase activity are coupled with several other enzymes. Such coupled assays do not permit the direct and stringent characterization of specific glutaminase inhibitors. Ebselen was identified as a potent 9 nM KGA inhibitor in the KGA/glutamate oxidase (GO)/horse radish peroxidase (HRP) coupled assay but showed very weak activity in inhibiting the growth of glutamine-dependent cancer cells. For rigorous characterization, we developed a direct kinetic binding assay for KGA using bio-layer interferometry (BLI) as the detection method; Ebselen was identified as a GDH inhibitor but not a KGA inhibitor. Furthermore, we designed and synthesized several benzo[d][1,2]selenazol-3(2H)-one dimers which were subjected to SAR analysis by several glutaminolysis specific biochemical and cell based assays. Novel glutamate dehydrogenase (GDH) or dual KGA/GDH inhibitors were discovered from the synthetic compounds; the dual inhibitors completely disrupt mitochondrial function and demonstrate potent anticancer activity with a minimum level of toxicity.
研究领域:
癌症研究
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生物化学
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分子生物学
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药物发现
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Liqing Wang,Menghan Chen,Hanxue Wang,Qihui Sun,Sujuan Zheng,Xiaoyun Liu,Yong Yang,Rong Rong
Clinical studies have demonstrated that many traditional Chinese medicines (TCM) exhibit not only antiviral effects but also efficacy in alleviating clinical symptoms of Coronavirus Disease 2019 (COVID-19). However, the pharmacologically active constituents responsible for their anti-COVID-19 efficacy remain unclear. This study aimed to establish a novel strategy for identifying active ingredients from herbs clinically used for COVID-19. An integrated approach combining data mining with Affinity Ultrafiltration (AUF) was developed. Initially, using a data mining strategy, high-frequency herbs were selected from the herbs clinically used in COVID-19. Furthermore, AUF technology was used to screen for potential bioactive components from the high-frequency herbs. The anti-COVID-19 potential of active compounds was assessed through enzyme activity assays and molecular docking, followed by validation in cellular and animal models. Data mining revealed that Glycyrrhiza uralensis Fisch., Lonicera japonica Thunb. and Forsythia suspensa (Thunb.) Vahl were the high-frequency herbs used in COVID-19. Five potential 3-Chymotrypsin-like protease (3CL pro ) inhibitors were screened from three herbs via AUF and identified using high-resolution mass spectrometry. Further enzymatic and cellular assays demonstrated that Licochalcone C (LCC) and Forsythiaside A (FTA) inhibited Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication at micromolar concentrations. Notably, FTA treatment significantly suppressed the elevation of pulmonary parameters and inflammatory mediators induced by SARS-CoV-2 nucleocapsid protein in mice. In summary, this study proposes a novel strategy integrating data mining with AUF to discover active compounds from TCM. Two components, LCC and FTA, were identified as dose-dependent inhibitors of SARS-CoV-2 Omicron strain replication in vitro.
研究领域:
药理学
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病毒学
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药物化学
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生物信息学
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植物学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
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2024
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IF 6
Yongqin Fan,Junxia Feng,Xudong Yang,Ruike Chen,Dongjie Cui,Chunli Liu,Hangbo Xu,Qisen Xiang,Zhen Jiao,Ruonan Ma
Cold atmospheric plasma (CAP) has shown great promise in mycotoxin degradation. This study compared the degradation efficiency of CAP against DON in the solid phase, aqueous solution, and wheat grains, as well as their degradation pathway and cytotoxicity of degradation products. The degradation efficiency of liquid DON by 12-W and 3.5-min CAP was 95%, while the maximum degradation rate of solid DON was only 56% after 40-W CAP treatment for 20 min. The major individual degradation products of solid and liquid-phase DON were C 15 H 19 NO 9 and C 15 H 18 O 7 . There were also four same degradation products, namely C 14 H 16 O 4 , C 15 H 18 O 6 , C 15 H 18 O 8 , and C 15 H 20 O 5 . The cytotoxicity of solid and liquid-phase DON on human kidney cells was significantly decreased after CAP treatment. Additionally, the degradation rate of 30-min CAP at 10 W against DON in wheat grains was 61%. The pasting and gluten quality of whole wheat flour was altered after CAP treatment.
研究领域:
食品安全
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生物化学
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毒理学
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产品关联
DOI
高影响因子
Biomaterials Science
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2024
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IF 5.8
Chang Liu,Linhua Li,Li Li,Qingyin Li,Jing Liu,Chunle Zhang,Zhengjiang Cao,Liang Ma,Xiaoxi Zeng,Ping Fu
Renal ischemia/reperfusion injury (RIRI) is an inevitable complication following kidney transplantation surgery, accompanied by the generation of massive of free radicals. The cascade of events including oxidative stress, extreme inflammation, cellular apoptosis, thrombosis disrupts the microenvironment of renal cells and the hematological system, ultimately leading to the development of acute kidney injury/ failure. Current research primarily focuses on reducing inflammation and mitigating damage to renal cells through antioxidative approaches. However, studies on simultaneously modulating the renal hematologic system remain unreported. Herein, a potent and novel drug-loaded nanomicelles can be efficiently self-assembled with magnolol (MG) and ebselen (EBS) by the π-π conjugation, hydrophobic action and the surfactant properties of Tween-80. The ultrasmall MG/EBS nanomicelles (Average particle size: 10–25 nm) not only fully preserve the activity of both drugs but also greatly enhance drug utilization (encapsulation rates: MG-90.1%, EBS-49.3%) and reduce drug toxicity. Furthermore, EBS, as a glutathione peroxidase mimic and NO catalyst, synergistically collaborates with the multifunctional MG to scavenge free radicals, significantly inhibiting inflammation and thrombosis while effectively preventing apoptosis of vascular endothelial cells and renal tubular epithelial cells. This study provides a new strategy and theoretical foundation for the simultaneous regulation of kidney cells and blood microenvironment stability.
研究领域:
药理学
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肾脏病学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Xionghua Sun,Xuelei Wan,Li Chen,Yadong Cui,Xihua Chen,Jian Zhang,Xiaogang Jiang
The senescence of alveolar epithelial cells is one of the characteristics of mitomycin pulmonary toxicity, but the direct target of mitomycin-induced alveolar epithelial cell senescence remains unclear. In this study, a method of small-molecule ligand–protein interaction by pulldown/mass spectrometry identified peroxiredoxin I (Prdx I) as the target of mitomycin-induced alveolar epithelial cell senescence, and mitomycin was shown to significantly inhibit the peroxidase activity of Prdx I. Consequently, the levels of cellular reactive oxygen species (ROS) increased, leading to the activation of mitogen-activated protein kinase kinase 1/2 (MEK1/2)-extracellular signal-regulated protein kinases 1/2 (ERK 1/2) and, accordingly, to the increased expression of p53. Both a Prdx I activator and Prdx I overexpression alleviated mitomycin-induced alveolar cell senescence. A ROS scavenger inhibited MEK1/2-ERK1/2-p53 activation and then attenuated the senescence of alveolar epithelial cells triggered by mitomycin. Thus, Prdx I can serve as the first target of mitomycin-induced alveolar epithelial cell senescence, which might represent a promising approach to reduce mitomycin-induced lung toxicity.
研究领域:
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
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2021
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IF 4.098
Minglu Li,Hui Han,Shengmei Song,Shaomin Shuang,Chuan Dong
Fluorescent probes have contributed greatly to our understanding of the biological role of peroxynitrite (ONOO – ). The ONOO – fluorescence probe characterized by the arlyboronate received a moderate opening fluorescence response, and the borate-masked probe significantly increased the sensitivity of ONOO – . Thus, two simple fluorescent probes ( ADB and ANB ) with the recognition receptor of phenyl boronate moiety were constructed for the detection of ONOO – . The change of emission spectrum was affected differently by the electron donating (or withdrawing) of the substituents. ANB was shown to have a low sensitivity and quantum yield towards ONOO – in aqueous solution, whereas ADB with aggregation-induced emission (AIE) process exhibited not only good sensitivity for ONOO – with a detection limit of 75 nM, but also ADB could be used to quantitative detecting ONOO – in response to concentrations of ONOO – within 20 s. Importantly, ADB had good performance for the detection of exogenous ONOO – in the RAW 264.7 cells.
研究领域:
生物化学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
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