ACS Applied Bio Materials
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2020
·
IF 0
Qin Wang,Liming He,Donghao Fan,Wenlang Liang,Xiaochen Wang,Jiyu Fang
Environment-responsive drug delivery is a promising approach for tailoring the drug release in drug therapy. In this study, we develop lipid tubules by the self-assembly of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC). These lipid tubules are capable of encapsulating hydrophobic dexamethasone (Dex) and hydrophilic dexamethasone sodium phosphate (DSP) simultaneously. In vitro studies show that the lipid tubules can be internalized by cells with no significant toxicity. We find that phospholipase (PLA2) is able to slowly digest the lipid tubules and trigger the sustained release of Dex and DSP. After being subcutaneously administrated to the inflammatory sites of arthritic rats, we show that a single dose of drug-loaded lipid tubules can remarkably inhibit the degree of joint swelling at the inflammatory sites and suppress the content of proinflammatory cytokines in inflamed tissues for a long time by this sustained release of both Dex and DSP triggered by the highly expressed PLA2 at the inflamed sites. Our results highlight the potential of using PLA2-responsive lipid tubules as on-demand carriers for treating inflammatory diseases.
研究领域:
药理学
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药物递送系统
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炎症性疾病
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纳米技术
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产品关联
DOI
PubMed
ACS Sensors
·
2023
·
IF 8.9
Lixin Wang,Yuhong Liu,Jilin Yan,Huiling Li,Yifeng Tu
Coronary heart disease (CHD) poses an important threat to human health, and its pathogenesis is the formation of atheromatous plaques in coronary ventricles. Compared to other biomarkers, lipoprotein-associated phospholipase A2 (Lp-PLA2), which is involved in multiple processes of atherosclerosis, is a noticeable inflammatory biomarker related to CHD. Herein, using a multifunctional nanocomposite containing a CoFe Prussian blue analogue (PBA) and Au nanoparticles (AuNPs) (AuNPs@CoFe PBA) as a sensing substrate, an electrochemiluminescent (ECL) immunosensor was developed for the highly sensitive detection of Lp-PLA2. Benefiting from the synergistic effect of the PBA and AuNPs, the nanocomposite exhibits excellent peroxidase-like activity and can catalyze the luminol–ECL reaction, amplifying the ECL signal by ∼29-fold. Meanwhile, the enlarged specific surface area of the nanocomposite and the presence of abundant AuNPs allow the immobilization of more antibody proteins, thereby improving the sensing response of the immunosensor. When the target Lp-PLA2 is captured by the antibody on the sensor surface, the sensor emits a reduced ECL signal because of the increased mass and electron transfer resistance due to the formation of the immune complex. Under optimized conditions, the constructed ECL immunosensor exhibits a broad linear range from 1 to 2200 ng/mL and a low detection limit of 0.21 ng/mL. Additionally, the ECL immunosensor exhibits high specificity, stability, and reproducibility. This work provides a new approach to diagnose CHD and broadened the application of the PBA in the field of ECL sensors.
研究领域:
医学诊断
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生物传感
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纳米技术
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产品关联
DOI
PubMed
高影响因子
TOXICON
·
2013
·
IF 2.924
Ying Zhang,Li Zhong,Bin Zhou,Jin-yu Chen,Chun-mei Li
To more fully understand the mechanism by which persimmon tannin (PT) inhibited phospholipase A 2 (PLA 2 ) and the structural requirements of PT for the inhibition, the interactions between PLA 2 and seven characteristic structural elements of PT including epigallocatechin-3-gallate (EGCG), myricetin, epicatechin-3-gallate (ECG), epicatechin-3-gallate-(4β → 8, 2β → O → 7)-epicatechin-3-gallate (A-type ECG dimer), epigallocatechin-3-gallate-(4β → 8, 2β → O → 7)-epigallocatechin-3-gallate (A-type EGCG dimer), epicatechin-(4β → 8, 2β → O → 7)-epicatechin (A-type EC dimer) and epicatechin-(4β → 8)-epicatechin (B-type EC dimer) were studied by enzymatic and spectroscopic methods. Molecular docking was also used to explore the possible residues involved in the interactions. The results revealed that A-type EGCG dimer and A-type ECG dimer showed higher inhibitory effects on the catalytic activity of PLA 2 than monomers and B-type dimer. They induced greater conformational changes in PLA 2 than other structural elements. In addition, molecular docking studies revealed that expect for lysine residues, other residues such as Trp18, Try27, Gly29, His47 and Tyr63 were involved in the interactions. We propose that A-type EGCG and ECG dimer units may be structural requirements for the interaction between PT and PLA 2 . Our data provide an additional structural basis for anti-PLA 2 activity of persimmon tannin.
研究领域:
生物化学
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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
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Yun Ying Cheng,Yi Fen Xie,Chun Mei Li,Yuan Fang Li,Cheng Zhi Huang
Förster resonance energy transfer (FRET) by using fluorescent carbon dots (CDs) as energy donors shows potential for biosensing and bioimaging. However, it remains underused and underestimated for CDs as a building block for FRET owing to the low efficiency and complex operation originating from the surface modification of CDs. To overcome these limitations, herein we develop a novel FRET soft nanoball (fretSNB) in which thousands of green CDs and black hole quencher 2 (BHQ-2) dyes are loaded, and FRET occurs from CDs to BHQ-2 dyes with the consequence of effective fluorescence quenching. These fretSNBs can be ruptured in the presence of phospholipase A2 (PLA2) released in a process of duplex-specific nuclease (DSN)-assisted target recycling amplification (TRA), making the fluorescence of CDs recovered. Thus, a dual amplification strategy is successfully developed for amplified detection of microribonucleic acids (miRNAs) in the concentration range 0.025–10 nM with a limit of detection (3σ) reaching 16.5 pM which is about 515 times lower than without fretSNBs. In addition, the developed strategy exhibits high selectivity for discrimination of a single nucleotide difference and capability to detect miRNAs extracted from cells, suggesting excellent potential in biomedical analysis and clinical diagnosis.
研究领域:
生物化学
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分子生物学
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分析化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Junling Ren,Xia Wang,Yuran Sun,Le Yang,Hui Sun,Ye Sun,Ling Kong,Guangli Yan,Ying Han,Xijun Wang
Background Danggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood. Purpose The present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics. Methods DGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism. Results DGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F 2α (PGF 2α )/PGE 2 , uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA 2 , LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. Conclusion Our findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.
研究领域:
药理学
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代谢组学
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脂质组学
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中医
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动物模型
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2025
·
IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
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环境科学
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药理学
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分子生物学
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发育生物学
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生态毒理学
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微生物学
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生物信息学
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药物发现
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2020
·Vol. 413
·期 1
·235-244
·
IF 3.637
Guo Haixin,Su Xiaoping,Su Qingfu,Zhuang Wei,You Zhijiao
A portable photothermal immunoassay based on Au-coated magnetic Fe 3 O 4 core-shell nanohybrids (Au-Fe 3 O 4 ) was developed for point-of-care (POC) testing of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) on a digital near-infrared (NIR) thermometer. Au-Fe 3 O 4 photothermal materials were first synthesized through reverse micelle method, and then functionalized with polyclonal rabbit anti-human Lp-PLA 2 antibody. A sandwiched immunoreaction was carried out in polyclonal mouse anti-human Lp-PLA 2 antibody-coated microplate using Au-Fe 3 O 4 -labeled antibody as the detection antibody. With formation of sandwich-type immunocomplex, the captured Au-Fe 3 O 4 on the plate converted the light into heat under an 808-nm laser irradiation (1.5 W cm −2 ), thereby resulting in the increasing temperature of the detection solution. The temperature variations relative to surrounding temperature was determined on a portable NIR thermometer. Several labeling protocols with gold nanoparticle, Fe 3 O 4 nanoparticle, or Au-Fe 3 O 4 nanohybrids were investigated for determination of Lp-PLA 2 and improved analytical features were achieved with the core-shell Au-Fe 3 O 4 nanohybrids. Under optimum conditions, Au-Fe 3 O 4 -based immunoassay exhibited good photothermal responses for the detection of Lp-PLA 2 with a dynamic linear range of 0.01–100 ng mL −1 at a low detection limit of 8.6 pg mL −1 . Good reproducibility and intermediate precision were less than 9.7%. Other biomarkers or proteins did not interfere with responses of this system. An acceptable accuracy was acquired for analysis of human serum sample between Au-Fe 3 O 4 -based photothermal immunoassay and commercialized human Lp-PLA 2 ELISA kit.
研究领域:
纳米技术
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生物医学工程
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分析化学
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即时检测
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免疫学
✓ 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）