BMC Complementary Medicine and Therapies
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2025
·Vol. 25
·期 1
·1-13
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IF 3.4
Yang Tian,Yan YiFan,Xu YiYing,Chen YiLong,Zhi DaLong,Zhang Yan,Xiao ChaoNi
Background Loquat (Eriobotrya japonica Lindl.) fruit has been used as a heath food and folk medicine for preventing and treating the respiratory tract inflammation diseases, however, the active compounds responsible for anti-inflammation effects remain unclear.Methods Cysteinyl leukotriene receptor-1 (CysLTR1) has become an important target protein for developing therapeutics to manage the inflammation-associated diseases. Herein, a rapid approach was established by immobilizing CysLTR1 onto microspheres for the column packing, and it was applied in screening the active compounds from Loquat fruit.Results The screened compounds targeting CysLTR1 were identified as corosolic acid, ursolic acid and oleanolic acid in combination with Mass Spectrum. The high-dose combination of the three ones exhibited the stronger anti-inflammatory activity than triterpene acid alone and the Loquat extract, which can significantly decrease the counts of inflammatory cells and inhibit the production of pro-inflammatory mediators as well as increase the secretion of anti-inflammatory mediator in the LPS-inflamed mice. It was proved that three triterpene acids exhibited anti-inflammatory activities by the attenuation of CysLTR1 expression.Conclusion sOur results indicated that CysLTR1-immobilized column was a rapid and effective tool to seek out the target-specific components from herbal extract, and the screened triterpene acids could serve as alternative anti-inflammatory agents to Loquat fruit.
研究领域:
药理学
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植物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
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2025
·
IF 8.4
Guo Qing,Gan Jun,Wang En-ze,Wei Yu-ming,Xu Jie,Xu Yun,Zhang Fei-fei,Cui Meng,Jia Meng-xing,Kong Ming-jian,Tang Qiong-yao,Zhang Zhe
Patients suffering epilepsy caused by the gain-of-function mutants of the hKCNT1 potassium channels are drug refractory. In this study, we cloned a novel human KCNT1B channel isoform using the brain cDNA library and conducted patch-clamp and molecular docking analyses to characterize the pharmacological properties of the hKCNT1B channel using thirteen drugs. Among cinchona alkaloids, we found that hydroquinine exerted the strongest blocking effect on the hKCNT1B channel, especially the F313L mutant. In addition, we confirmed the antitussive drug tipepidine was also a potent inhibitor of the hKCNT1B channel. Subsequently, we proved that these two drugs produced an excellent therapeutic effect on the epileptic model of KCNT1 Y777H mutant male mice; thus, both could be ready-to-use anti-epileptic drugs. On the other hand, we demonstrated that the activation of the KCNT1 channel by loxapine and clozapine was through interacting with pore domain residues to reverse the run-down of the KCNT1 channel. Taken together, our results provide new insights into the mechanism of the modulators in regulating the KCNT1 channel activity as well as important candidates for clinical tests in the treatment of KCNT1 mutant-associated epilepsy.
研究领域:
神经生物学
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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
BIOORGANIC & MEDICINAL CHEMISTRY
·
2021
·
IF 3.641
Yaping Cheng,Jingyuan Wu,Ying Han,Jingyao Xu,Yifan Da,Qian Zhao,Guoying Guo,Yani Zhou,Yimin Chen,Jinghong Liu,Huayao Chen,Xianxing Jiang,Xiaoqing Cai
Covalent target modulation with small molecules has been emerging as a promising strategy for drug discovery. However, covalent inhibitory antibody remains unexplored due to the lack of efficient strategies to engineer antibody with desired bioactivity. Herein, we developed an intracellular selection method to generate covalent inhibitory antibody against human rhinovirus 14 (HRV14) 3C protease through unnatural amino acid mutagenesis along the heavy chain complementarity-determining region 3 (CDR-H3). A library of antibody mutants was thus constructed and screened in vivo through co-expression with the target protease. Using this screening strategy, six covalent antibodies with proximity-enabled bioactivity were identified, which were shown to covalently target HRV14-3C protease with high inhibitory potency and exquisite selectivity . Compared to structure-based rational design, this library-based screening method provides a simple and efficient way for the discovery and engineering of covalent antibody for enzyme inhibition.
研究领域:
药物发现
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蛋白质工程
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病毒学
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分子生物学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Jinwei Zhang,Meilin Sun,Fen Zhang,Tingting Xuanyuan,Xufang Liu,Danyang Yu,Wenming Liu
Microengineered cancer model is exceedingly practical in preclinical screening, while establishing a highly tumor-biomimetic pathophysiological microsystem with multi-function integration remains challenging. Here, an integrated microfluidic biomimetic tumor-on-a-chip (IMBTC) platform is established to reinforce at once the spatiotemporal control of fluid/cell samples and wide-range gradient (WRG), as well as the in vitro multi-feature reconstruction of native tumors for supporting diverse preclinical therapy evaluations. The active pneumatic manipulators enable precise cell capture and array-like organization with high positioning efficiency. The WRG generator can unprecedentedly create a wide range of chemical gradients with up to 8 orders of magnitude, affording efficient therapy screening evaluation in a single chip capable of producing hundreds of tumors with size-uniformity via coculturing under a physiological flow condition. Multiple high-biomimetic characteristics in the engineered tumors, including complex multilayer organization, various phenotypic/biochemical gradients involving proliferation, viability, metabolism, hypoxia, and molecular penetration, and heterogeneous cell and stroma compositions, are validated. The IMBTC system is applied to successively evaluate individual drug chemotherapy, combinatorial chemotherapy, and photosensitive drug-dominant photodynamic therapy, thereby identifying the effective lethal doses from wide-range antitumor concentration screenings. The verified IMBTC system offers considerable benefits for advancing the development of next-generation tumor-on-a-chip and an innovative preclinical screening paradigm.
研究领域:
生物工程
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微流控技术
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癌症研究
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药理学
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2025
·
IF 8.9
Yuexiang CHANG,Hao TIAN,Jia-Huan QU,Jiaming YUAN,Rongkai GU,TingTing ZHANG,Jincai WANG,Zhengjin JIANG
The N -terminal domain of influenza viral polymerase (PA N ), a highly conserved region with critical catalytic function related to viral RNA replication and transcription, is considered as a very promising anti-influenza drug target. There is an urgent need for highly efficient and rapid screening methods to identify potential PA N inhibitors (PA N Is) from complex matrices. In this work, a novel high-throughput screening (HTS) platform was established by coupling high performance liquid chromatography and high-resolution mass spectrometry (HPLC-HRMS) with a fluorescence resonance energy transfer (FRET)-based endonuclease activity assay through an at-line nanofractionation system (ANF). The proposed screening platform could rapidly identify potential PA N Is from plant extracts with good sensitivity (baloxavir at the half maximal inhibitory concentration (IC 50 ) could be detected) and reliability ( Z ’ factor of 0.77). This platform was then successfully applied to the screening of potential inhibitors against PA N /PA N I38T from an aqueous extract of Artemisiae Argyi and 17 potential PA N Is were identified. Among them, three compounds (cynarine, isochlorogenic acid B and isochlorogenic acid C) showed comparable inhibitory activity against PA N and even better activity against PA N I38T compared to baloxavir. This study not only established a novel high-throughput ANF-based PA N Is screening platform, but also proved the feasibility to discover PA N Is from complex TCMs, which has a great potential in future anti-influenza drug discovery.
研究领域:
病毒学
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药物筛选
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植物药理学
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生物分析技术
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产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2023
·Vol. 10
·期 16
·4711-4718
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IF 7
Jingjing Zhang,Ruqing Wei,Daqing Yang,Ying Wang,Bingbing Zhang
Nonlinear optical (NLO) materials have been applied in many high technology fields. In this work, the first-principles high-throughput screening pipeline (FHSP) has been used for searching NLO materials from the silicate system. 253 silicates collected in the Inorganic Crystal Structural Database (ICSD) have been successfully calculated. Among them, 8 crystals were screened out after two-step evaluation. Finally, 3 compounds were selected for synthesis after comprehensive investigation. The SHG intensities tested using the Kurtz–Perry method of KNbSi2O7, PbZnSiO4, and Na2TiSiO5 are 6.7, 2.9, and 2.8 times that of KDP, respectively. Their UV absorption edges are 243 nm, 276 nm, and 280 nm, respectively. This work provides a full view of silicates as NLO materials and obtains excellent candidates for the next step of development.
研究领域:
材料科学
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计算化学
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晶体学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2025
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IF 4.7
Jia Xu,Hongjian Ji,Guozhe Zhang,Jin Cheng,Qin Shi,Jie Zhang
Luteolin, a bioactive flavonoid known for its anti-inflammatory, antioxidant, and anticancer properties, is limited in its clinical application due to poor water solubility and low bioavailability. In this study, we applied an integrated approach combining virtual screening and experimental validation to identify potential coformers that can form cocrystals with luteolin, improving its physicochemical properties. A total of 28 coformers were analyzed using virtual screening, with predictions based on hydrogen bond strength. From this, 12 promising coformers were selected for experimental trials. Our experimental results led to the successful synthesis of five novel luteolin cocrystals with 4,4′-bipyridine, l -ascorbic acid, nicotinic acid, and isonicotinic acid. Notably, the coformers that formed cocrystals in the experiments ranked highly in the virtual screening results, demonstrating the feasibility of the virtual cocrystal screening method. Notably, all synthesized cocrystals exhibited substantially enhanced solubility profiles, achieving a maximum 4.51-fold increase in solubility relative to pure luteolin. These findings not only validate the virtual screening approach but also highlight its potential applications in pharmaceutical cocrystal design to overcome solubility and bioavailability challenges in drug development.
研究领域:
药学
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化学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Jia-Jia Zheng,Xiaoyu Wang,Zeqi Li,Xiaomei Shen,Gen Wei,Pufeihong Xia,Yi-Ge Zhou,Hui Wei,Xingfa Gao
Nanomedicine is promising for disease prevention and treatment, but there are still many challenges that hinder its rapid development. A major challenge is to efficiently seek candidates with the desired therapeutic functions from tremendously available materials. Here, we report an integrated computational and experimental framework to seek alloy nanoparticles from the Materials Project library for antibacterial applications, aiming to learn the inverse screening concept from traditional medicine for nanomedicine. Because strong peroxidase-like catalytic activity and weak toxicity to normal cells are the desired material properties for antibacterial usage, computational screening implementing theoretical prediction models of catalytic activity and cytotoxicity is first conducted to select the candidates. Then, experimental screening based on scanning probe block copolymer lithography is used to verify and refine the computational screening results. Finally, the best candidate AuCu3 is synthesized in solution and its antibacterial performance over other nanoparticles against S. aureus and E. coli. is experimentally confirmed. The results show the power of inverse screening in accelerating the research and development of antibacterial nanomedicine, which may inspire similar strategies for other nanomedicines in the future.
研究领域:
材料科学
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生物医学工程
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Xiuli Wang,Qilin Guo,Jia Guo,Changchun Wang
Rapid extraction and screening of high purity DNA fragments is an indispensable technology in advanced molecular biology. In this article, mesoporous magnetic composite microspheres (MSP@mTiO2) with tunable pore sizes are successfully fabricated for high purity DNA extraction and fragment screening. Due to the strong complexation ability of Ti4+ with DNA phosphate groups and the high specific surface area of mesoporous microspheres, the MSP@mTiO2 microspheres possess excellent adsorption performance, the saturated loading capacity of MSP@mTiO2 with specific surface area of 122 m2/g is as high as 575 g/mg for salmon sperm specimen. ITC experiment demonstrates that the DNA adsorption on MSP@mTiO2 microspheres is mainly driven by entropy, which gives us more potential ways to regulate the balance of adsorption and desorption. Meanwhile, the mesoporous MSP@mTiO2 microspheres exhibit much higher extraction efficiency compared with non-porous MSP@TiO2 for whole genome DNA from Arabidopsis thaliana plants. Interestingly, the DNA frangements with different lengths can be screened by simply regulating the pore size of MSP@mTiO2 or concentration of Na3PO4 in eluent. Small pore size and low phosphate concentration are advantageous for the extraction of short-stranded DNA fragments, the DNA fragments (≤1000 bp) can be efficiently extracted when the mesopore size of MSP@mTiO2 is lower than 7.6 nm. The extraction results from the mesoporous composite microspheres provide new promising insights on the DNA purification and screening from complex biological samples.
研究领域:
分子生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
FeiFei Wang,Taizhi Shen,Changrong Cao,Shuo Shan,Juan Sun,Ruiyu Zhu
Penicillium expansum is a major pathogen critical for the blue mold decay and patulin production in various fruits and vegetables, particularly apples, creating an urgent need to identify safer and more effective compounds for its management. In this study, two pathogenic factors of P. expansum , PeBgl1 and PeSCP, were first time targeted for virtual screening with a database (a combination of TCM Database @ Taiwan and food ingredients database) containing 20,219 molecules, and octyl gallate (OG) was identified as a common candidate inhibitor with high binding energy. Therefore, we investigated the inhibitory impacts of OG against P. expansum and patulin production in vitro and in apples. It’s revealed that OG significantly inhibited the spore germination and mycelia growth by inducing oxidative stress and compromising cell membrane integrity, as well as restrained patulin biosynthesis via suppressing the expression level of patulin synthesis genes including patE, patL , and patK. Molecular docking and dynamics simulation indicated that OG could affect the stability and function of PeBgl1 and PeSCP mainly via Van der Waals forces and hydrogen bonds. qRT-PCR analysis further demonstrated that OG directly inhibited the expression of genes encoding for PeBgl1 and PeSCP. Finally, in vivo application of OG on apples demonstrated that OG can effectively trigger the defensive enzyme system of apples and control the blue mold decay caused by P. expansum . Overall, this study emphasizes the potential of OG as a promising natural compound for the management of blue mold decay and patulin production in the post-harvest fruits and vegetables.
研究领域:
植物病理学
·
食品安全
✓ 已验证
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2018
·
IF 3.716
Yu-Mei Zhao,Lv-Huan Wang,Si-Fan Luo,Qi-Qin Wang,Ruin Moaddel,Ting-Ting Zhang,Zheng-Jin Jiang
Neuraminidase (NA) is a glycoside hydrolase that has been proposed as a potential therapeutic target for influenza. Thus, the identification of compounds that modulate NA activity could be of great therapeutic importance. The aim of this study is to develop a drug discovery tool for the identification of novel modulators of NA from both compound libraries and natural plant extracts. NA was immobilized onto the surface of magnetic beads and the inherent catalytic activity of NA-functionalized magnetic beads was characterized. Based on the enzymatic activity (hydrolysis ratio), the inhibitory activities of 12 compounds from plant secondary metabolites were screened, and the desired anti-NA activities of flavonoids were certified. Ligand fishing with the immobilized enzyme was optimized using an artificial test mixture consisting of oseltamivir, lycorine and matrine prior to carrying out the proof-of-concept experiment with the crude extract of Flos Lonicerae . The combination of ligand fishing and HPLC-MS/MS identified luteolin-7- O -β-D-glucoside, luteolin, 3,5-di- O -caffeoylquinic acid and 3,4-di- O -caffeoylquinic acid as neuraminidase inhibitory ligands in Flos Lonicerae . This is the first report on the use of neuraminidase functionalized magnetic beads for the identification of active ligands from a botanical matrix, and it sets the basis for the de novo identification of NA modulators from complex biological mixtures.
研究领域:
药物发现
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生物化学
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植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2011
·
IF 2.816
Jian Yao,Xin Jiong Fan,Yi Lu,Yu Huan Liu
A novel gene (designated as tan410) encoding tannase was isolated from a cotton field metagenomic library by functional screening. Sequence analysis revealed that tan410 encoded a protein of 521 amino acids. SDS−PAGE and gel filtration chromatography analysis of purified tannase suggested that Tan410 was a monomeric enzyme with a molecular mass of 55 kDa. The optimum temperature and pH of Tan410 were 30 °C and 6.4. The activity was enhanced by addition of Ca2+, Mg2+ and Cd2+. In addition, Tan410 was stable in the presence of 4 M NaCl. Chlorogenic acid, rosmarinic acid, ethyl ferulate, tannic acid, epicatechin gallate and epigallocathchin gallate were efficiently hydrolyzed by recombinant tannase. All of these excellent properties make Tan410 an interesting enzyme for biotechnological application.
研究领域:
微生物学
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生物化学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）