BIOSENSORS & BIOELECTRONICS
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2019
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IF 9.518
Chi Zhang,Zhanfang Ma
The method of transferring the immunoreaction from electrode surface to tube can greatly improve the analytical performance of electrochemical immunosensor. In this work, based on PtCu nanoprobe-mediated and iodide-catalyzed cascade reaction , an improved electrochemical immunosensor was elaborately designed for neuron-specific enolase (NSE) detection. PtCu nanoparticles combined with NSE antibody (Ab 2 ) were used as immunoprobes to trigger cascade reaction. With high catalytic activity towards the oxidation of iodide, PtCu nanoprobes catalyzed iodide to iodine in the presence of H 2 O 2 , leading to the decrease of iodide. Subsequently, as a bridge between the tube and iodide-responsive sensing interface, the residual iodide in tube was employed to catalyze the transition from thiol substances (RSH) to disulfide substances (RSSR) on electrode surface. On the basis of this property, thiol-modified DNA (DNA-SH) and 6-mercaptohexanol (MCH) reacted with H 2 O 2 and the residual iodide to form disulfide substances and detach from the electrode surface, causing the decrease of interface resistance in different degrees. Then square wave voltammetry (SWV) was applied for current signal of electrochemical sensing interface to achieve the quantitative detection of NSE. Under optimal conditions, this improved biosensor demonstrated excellent selectivity, stability and reproducibility with wide linear range from 0.0001 to 100 ng mL −1 and ultralow detection limit of 52.14 fg mL −1 for NSE, thus holding great promise for sensitive determination of tumor markers.
研究领域:
生物传感
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分析化学
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医学检测
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DOI
PubMed
高影响因子
Chinese Medicine
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2023
·Vol. 18
·期 1
·1-20
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IF 4.9
Xu Yang-ding,Guo Yu-jie,Mao He-rong,Xiong Zhi-xiang,Luo Meng-yu,Luo Rui-qi,Lu Shan,Huang Lu,Hong Yi
Background Dermatophyte caused by Trichophyton mentagrophytes is a global disease with a growing prevalence that is difficult to cure. Perilla frutescens (L.) Britt. is an edible and medicinal plant. Ancient books of Traditional Chinese Medicine and modern pharmacological studies have shown that it has potential anti-fungi activity. This is the first study to explore the inhibitory effects of compounds from P. frutescens on Trichophyton mentagrophytes and its mechanism of action coupled with the antifungal activity in vitro from network pharmacology, transcriptomics and proteomics.Methods Five most potential inhibitory compounds against fungi in P. frutescens was screened with network pharmacology. The antifungal activity of the candidates was detected by a broth microdilution method. Through in vitro antifungal assays screening the compound with efficacy, transcriptomics and proteomics were performed to investigate the pharmacological mechanisms of the effective compound against Trichophyton mentagrophytes. Furthermore, the real-time polymerase chain reaction (PCR) was applied to verify the expression of genes.Results The top five potential antifungal compounds in P. frutescens screened by network pharmacology are: progesterone, luteolin, apigenin, ursolic acid and rosmarinic acid. In vitro antifungal assays showed that rosmarinic acid had a favorable inhibitory effect on fungi. The transcriptomic findings exhibited that the differentially expressed genes of fungus after rosmarinic acid intervention were mainly enriched in the carbon metabolism pathway, while the proteomic findings suggested that rosmarinic acid could inhibit the average growth of Trichophyton mentagrophytes by interfering with the expression of enolase in the glycolysis pathway. Comparison of real-time PCR and transcriptomics results showed that the trends of gene expression in glycolytic, carbon metabolism and glutathione metabolic pathways were identical. The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis.Conclusion The key findings of the present study manifested that rosmarinic acid, a medicinal compound extracted from P. frutescens, had pharmacological activity in inhibiting the growth of Trichophyton mentagrophytes by affecting its enolase expression to reduce metabolism. Rosmarinic acid is expected to be an efficacious product for prevention and treatment of dermatophytes.
研究领域:
药理学
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真菌学
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网络药理学
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生物信息学
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分子生物学
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DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
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2021
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IF 3.293
Hexiang Jiang,Tong Wu,Jianan Liu,Xibing Yu,Hongtao Liu,Chuntong Bao,Mengmeng Liu,Yalu Ji,Xin Feng,Jingmin Gu,Wenyu Han,Na Li,Liancheng Lei
Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes meningitis. The ubiquitously expressed 40S ribosome protein SA (RPSA) is a multifunctional protein involved in the pathogenesis of multiple pathogens, especially those causing meningitis. However, the role of RPSA in SS2-induced meningitis is not clear. In this study, immunofluorescence staining revealed that SS2 infection promoted the intracellular transfer of RPSA to the surface of human cerebral microvascular endothelial cells (HCMECs). Moreover, SS2 infection promoted the accumulation of caveolin 1 (CAV1) and the formation of membrane bulges where RPSA enveloped CAV1 on the cell surface. SS2 infection also caused dynamic changes in the localization of RPSA and CAV1 on the cell surface which could be eliminated by disruption of caveolae/rafts by addition of methyl-β-cyclodextrin (MβCD). Co-immunoprecipitation analysis demonstrated that α-enolase (ENO), a key virulence factor of SS2, interacted with RPSA, and promoted the interaction between RPSA and CAV1. Immunofluorescence staining, western blotting and flow cytometry analyses showed that damaged caveolae/rafts significantly enhanced ENO adhesion to HCMECs, promoted the “destruction” of RPSA by ENO, and enhanced the toxic effect of ENO on HCMECs. Importantly, these effects could be relieved upon the addition of cholesterol. We conclude that caveolae/rafts weaken the toxic effect of SS2 ENO on RPSA-mediated events in HCMECs. Our study has led to better understanding of the roles of RPSA and caveolae/rafts upon SS2 infection, and a new pathological role for RPSA in infection.
研究领域:
微生物学
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细胞生物学
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传染病学
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神经科学
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DOI
PubMed
高影响因子
BMC BIOLOGY
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2024
·Vol. 22
·期 1
·1-19
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IF 4.4
Jiang Hexiang,Sun Yi,Li Fengyang,Yu Xibing,Lei Siyu,Du Sulan,Wu Tong,Jiang Xuan,Zhu Junhui,Wang Jun,Ji Yalu,Li Na,Feng Xin,Gu Jingmin,Han Wenyu,Zeng Lei,Lei Liancheng
Background Ribosomal protein SA (RPSA) of human brain microvascular endothelial cells (HBMECs) can transfer from the cytosol to the cell surface and act as a receptor for some pathogens, including Streptococcus suis serotype 2 (SS2), a zoonotic pathogen causing meningitis in pigs and humans. We previously reported that SS2 virulence factor enolase (ENO) binds to RPSA on the cell surface of HBMECs and induces apoptosis. However, the mechanism that activates RPSA translocation to the cell surface and induces ENO-mediated HBMEC apoptosis is unclear.Results Here, we show that RPSA localization and condensation on the host cell surface depend on its internally disordered region (IDR). ENO binds to the IDR of RPSA and promotes its interaction with RPSA and vimentin (VIM), which is significantly suppressed after 1,6-Hexanediol (1,6-Hex, a widely used tool to disrupt phase separation) treatment, indicating that ENO incorporation and thus the concentration of RPSA/VIM complexes via co-condensation. Furthermore, increasing intracellular calcium ions (Ca2+) in response to SS2 infection further facilitates the liquid-like condensation of RPSA and aggravates ENO-induced HBMEC cell apoptosis.Conclusion sTogether, our study provides a previously underappreciated molecular mechanism illuminating that ENO-induced RPSA condensation activates the migration of RPSA to the bacterial cell surface and stimulates SS2-infected HBMEC death and, potentially, disease progression. This study offers a fresh avenue for investigation into the mechanism by which other harmful bacteria infect hosts via cell surfaces’ RPSA.
研究领域:
微生物学
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细胞生物学
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病理学
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分子生物学
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DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
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2020
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IF 3.343
Gang Wang,Yang Yu,Yu-Zhu Wang,Pei-Hao Yin,Ke Xu,Heng Zhang
In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）