Future Medicinal Chemistry
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2021
·Vol. 13
·期 15
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IF 3.808
Yunong Li,Jingbo Yang,Yan Zhang,Qingkang Meng,Andreas Bender,Xiujie Chen
Background: A comprehensive approach to drug repositioning will be required to overcome translational hurdles and identify more neuroprotective drugs. Results & methods: Gene Set Enrichment Analysis was applied to identify related pathways and enriched genes. Candidate genes were optimized using ToppGene, ToppGenet and pBRIT. From the perspective of the local structures, gene–domain–substructure–drug relationships were constructed. Using the MCODE algorithm and K-means clustering, 31 functional subnetworks were obtained, and 252 drugs with proposed neuroprotective function were identified. Using computational analysis, 72 substructures with different scores were found to correspond to neuroprotective functions. The protective effects of benidipine and barnidipine were confirmed in vitro. Conclusion: The authors' research has great potential to discover more neuroprotective drugs and obtain more information regarding mechanisms of action and functional substructures.
研究领域:
生物信息学
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药物研发
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神经科学
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
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2018
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IF 4.211
Yunong Li,Haixia Zhu,Jingbo Yang,Kehui Ke,Yanmei Zhu,Li Chen,Youyang Qu,Rui Suo,Xiujie Chen,Yulan Zhu
As an important protective mechanism against cerebral ischemia, angiogenesis has become a topic of interest in the treatment of ischemic stroke with the challenge that few drugs promote angiogenesis. Previous studies of the identification of drug–target interactions mainly focused on the overall structures of drugs and proteins, which limited the discovery of novel structure drugs. In this article, we proposed a new strategy for discovering proangiogenic drugs based on the assumption that drug–protein interaction is mediated by substructure and domain. First, we identified substructure–domain relationships according to the known drug–protein interactions and established the drug–substructure–domain–protein relationships of genes that are proangiogenic in brain tissue and expressed significantly during ischemic stroke. Then we quantified the intensity of interaction between each drug and each protein. Finally, we obtained 540 interactive relationships between 238 drugs and 54 genes, establishing a drug–gene network with two patterns of independent and complex drug–gene interactions. Both of the patterns facilitated finding not only drugs with the same overall structure but also drugs with a different overall structure based on the same or a similar protein spectrum. In addition, we analyzed the mechanism of action of each predicted drug and extracted drugs with similar mechanisms. In vitro, our results showed that azelnidipine, azilsartan, lercanidipine, nafcillin, and vortioxetine enhanced bEnd.3 cell proliferation, migration, tube formation, and the expression of angiogenic marker PCNA. Azelnidipine, azilsartan, lercanidipine, and nafcillin increased the level of expression of proangiogenic factor VEGF. Unlike previous studies focusing on the overall structures of drugs, our research highlighted local structural similarity, which has great potential in the search for more proangiogenic drugs with novel structures.
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
Journal of Environmental Chemical Engineering
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2022
·
IF 7.968
Lu Yu,Han Zhang,Luna Jia,Weiran Zhao,Pan Li,Yibo Liu,Hao Wang,Pengfei Zhu,Bo Li
The development of oil sorbents with special substructure, high adsorption capacity, reusability and good mechanical properties is of great significance for dealing with frequent maritime oil spill incidents and industrial oil-containing wastewater emission. In this work, the polystyrene (PS)/ polyvinylidene fluoride (PVDF) composite fibrous sponges with high oil adsorption capacity were fabricated by constructing a two-phase dispersion system from the microscopic perspective in fiber forming process used co-blow-spinning method. The special Bead-Curtain fiber substructure was obtained due to the difference in the stretching process of the PS and PVDF solution with different viscosity. The precursor solution of the PS/PVDF composite fibrous sponge with PVDF concentration of 20 % (SF2) increased to 79 mPa·s attributed to the addition of PVDF. The SF2 exhibited a high specific surface area (43.418 m 2 /g), total pore volume (0.4348 cm 3 /g) and adsorption capacity for various organic solvents (especially up to 279 g/g for motor oil), as well as retaining 159 g/g for motor oil after 10 cycles. Moreover, the addition of PVDF enhanced the mechanical properties of the sponges, whereas the tensile strength of the SF6 sponge was 2.36 times that of the pure PS sponge. The co-blow-spinning of two-phase liquid is a novel strategy for controlling the substructure of fibers from the microscopic perspective, which provides a novel point of view in recycling marine spilled oil.
研究领域:
材料科学
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环境工程
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化学工程
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产品关联
DOI
高影响因子
TALANTA
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2023
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IF 6.1
Jinxiu Wei,Siyao Zhang,Jiangnan Yuan,Zhuyuan Wang,Shenfei Zong,Yiping Cui
Tumor cell exosomes play a very important role in the process of tumor cell proliferation and metastasis. However, due to the nanoscale size and high heterogeneity of exosomes, in-depth understanding of their appearance and biological characteristics is still lacking. Expansion microscopy (ExM) is a method that embeds biological samples in a swellable gel to physically magnify the samples to improve the imaging resolution. Before the emergence of ExM, scientists had invented several super-resolution imaging techniques that could break the diffraction limit. Among them, single molecule localization microscopy (SMLM) usually has the best spatial resolution (20–50 nm). However, considering the small size of exosomes (30–150 nm), the resolution of SMLM is still not high enough for detailed imaging of exosomes. Hence, we propose a tumor cell exosomes imaging method that combines ExM and SMLM (i.e. Expansion SMLM, denoted as ExSMLM), which can realize the expansion and super-resolution imaging of tumor cell exosomes. In this technique, immunofluorescence was first performed to fluorescently label the protein markers on the exosomes, then the exosomes were polymerized into a swellable polyelectrolyte gel. The electrolytic nature of the gel made the fluorescently labeled exosomes undergo isotropic linear physical expansion. The expansion factor obtained in the experiment was about 4.6. Finally, SMLM imaging of the expanded exosomes was performed. Owing to the improved resolution of ExSMLM, nanoscale substructures of closely packed proteins were observed on single exosomes, which has never been achieved before. With such a high resolution, ExSMLM would have a great potential in detailed investigation of exosomes and exosome-related biological processes.
研究领域:
生物医学工程
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癌症生物学
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显微技术
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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 POLYMER JOURNAL
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2021
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IF 4.598
Zhisong Wang,Shaopeng Li,Zhujun Zhang,Xianglong Zhang,Ting Xia,Yu Zheng,Menglei Xia,Min Wang
To decipher the formation mechanism of nitrogen-free substructures in melanoidins, methylglyoxal or 3-deoxyglucosone was used as a substrate to react by aldol reaction under different pH conditionst. The obtained products were characterised by chromatography, mass spectrometry, and spectroscopic methods. Overall, the molecular weights of the polymers structural units varied mainly within 54–56 and 72–74 Da, respectively, due to the different dehydration extent of β-hydroxy aldehyde or ketones, and uneven reduction by NaBH 4 . Moreover, the nitrogen-free substructures formed by this reaction can cross-link with gluten and dextran to form melanoidins. Therefore, the nitrogen-free substructures by this reaction to formed with units of 54–56 and 72–74 Da, which are similar as the typical polymers in food melanoidins. It is inferred that the typical polymers in food may also be formed by this pathway and which can be used as a detectable biomarker in melanoidins.
研究领域:
食品化学
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分析化学
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有机化学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）