Biosensors-Basel
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2023
·Vol. 13
·期 2
·255
·
IF 5.4
Yanbing Tao,Yunong Zhao,Le Wang,Jing Huang,Yan Chen,Qing Huang,Boxiang Song,Hua-Yao Li,Jianjun Chen,Huan Liu
Myeloperoxidase (MPO) has been demonstrated to be a biomarker of neutrophilic inflammation in various diseases. Rapid detection and quantitative analysis of MPO are of great significance for human health. Herein, an MPO protein flexible amperometric immunosensor based on a colloidal quantum dot (CQD)-modified electrode was demonstrated. The remarkable surface activity of CQDs allows them to bind directly and stably to the surface of proteins and to convert antigen–antibody specific binding reactions into significant currents. The flexible amperometric immunosensor provides quantitative analysis of MPO protein with an ultra-low limit of detection (LOD) (31.6 fg mL−1), as well as good reproducibility and stability. The detection method is expected to be applied in clinical examination, POCT (bedside test), community physical examination, home self-examination and other practical scenarios.Keywords:myeloperoxidase;colloidal quantum dot;flexible immunosensor;inflammatory disease;amperometric sensor
研究领域:
生物医学工程
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分析化学
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医学诊断
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DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 5
·1022
·
IF 3.267
Yue Zhang,Yifang Xie,Leifang Zhang,Hang Zhao
Smoke inhalation causes acute lung injury (ALI), a severe clinical disease with high mortality. Accumulating evidence indicates that microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS-1), as mediators of inflammatory response, are involved in the pathogenesis of ALI. In this paper, we explored the proinflammatory mechanism of miR-155 in smoke-inhalation-induced ALI. Our data revealed that smoke inhalation induces miR-155 expression, and miR-155 knockout (KO) significantly ameliorates smoke-inhalation-induced lung injury in mice. Neutrophil infiltration and myeloperoxidase (MPO), macrophage inflammatory protein 2 (MIP-2) and keratinocyte chemoattractant (KC) expressions were decreased in miR-155–/–mice after smoke inhalation as well. Real-time RT-PCR and immunoblotting results showed that SOCS-1 level was remarkably increased in miR-155–/–mice after smoke exposure. Furthermore, the experiments performed in isolated miR-155 KO pulmonary neutrophils demonstrated that the lack of SOCS-1 enhanced inflammatory cytokines (MIP-2 and KC) secretion in response to smoke stimulation. In conclusion, smoke induces increased expression of miR-155, and miR-155 is involved in inflammatory response to smoke-inhalation-induced lung injury by inhibiting the expression of SOCS-1.Keywords:acute lung injury;neutrophils;microRNA-155;suppressor of cytokine signaling-1
研究领域:
呼吸病学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF IMMUNOLOGY
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2025
·
IF 3.4
Huang Saiping,Wu Guoyuan,Xu Tianfu,Lin Dong,Zhan Zhijian
This study investigates the diagnostic potential of matrix metalloproteinase-9 (MMP-9), IL-8, and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF) as combined biomarkers for post-infectious bronchiolitis obliterans (PIBO) in children. BALF samples from children with PIBO were analyzed using ELISA to quantify MMP-9, IL-8, and MPO levels. Receiver operating characteristic (ROC) curves were used to assess their diagnostic values, while Pearson correlation analysis examined their associations with lung function and inflammation markers. A PIBO mouse model was established via nebulized nitric acid inhalation, and targeted inhibition of MMP-9, IL-8, and MPO using small interfering RNAs (siRNAs) was performed given via intratracheal administration. The effects on airway inflammation and pathological lung changes were evaluated. Bioinformatics analysis identified upstream microRNAs (miRNAs) regulating MMP-9, IL-8, and MPO, which were validated using dual-luciferase assay and Western blotting. Results revealed significant upregulation of MMP-9, IL-8, and MPO in the BALF of children with PIBO. Combined detection of these biomarkers demonstrated high diagnostic accuracy. MMP-9, IL-8, and MPO levels in BALF were negatively correlated with lung function indicators but positively correlated with inflammatory factors. Targeted inhibition of these molecules reduced airway hyperresponsiveness and inflammation in PIBO mice. miR-766-3p was downregulated in the lung tissues of PIBO mice and in the BALF of affected children, showing a negative correlation with MMP-9, IL-8, and MPO. Functional assays confirmed that miR-766-3p directly targeted MMP-9, IL-8, and MPO. In conclusion, MMP-9, IL-8, and MPO serve as reliable combined biomarkers for PIBO diagnosis and may aid in early clinical identification. miR-766-3p is an upstream miRNA for MMP-9, IL-8, and MPO.
研究领域:
呼吸病学
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分子生物学
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儿科医学
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产品关联
DOI
PubMed
高影响因子
Innate Immunity
·
2024
·
IF 2.8
Yiqin Shu,Rui Yang,Huijie Wen,Qiannan Dong,Zhiqi Chen,Yang Xiang,Hao Wu
Rheumatoid arthritis (RA) is a chronic disease characterized by joint inflammation and severe disability. However, there is a lack of safe and effective drugs for treating RA. In our previous study, we discovered that myricetin (MC) and celecoxib have a synergistic effect in the treatment of RA. We conducted in vitro and in vivo experiments to further investigate the effects and mechanisms of action of MC. Our findings demonstrated that MC treatment effectively reduced the release of neutrophil extracellular traps (NETs) and alleviated the inflammatory response in RA. Mechanistic studies showed that MC prevents the entry of PADI4 and MPO into the cell nucleus, thereby protecting DNA from decondensation. In a rat arthritis model, MC improved histological changes in ankle joints and suppressed NET-related signaling factors. In conclusion, MC protects the ankle joints against arthritis by inhibiting MPO and PADI4, thereby reducing NET release. The pharmacological mechanism of MC in RA involves the inhibition of NET release.
研究领域:
药理学
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Redox Biology
·
2026
·
IF 16.2
Li He,Jia-Mi Li,Meng-Ting Li,Cai-Ju Zhang,Yu-Fan Lv,Jiao-Jiao Ma,Mao-Lin Zou,Bo Wu,Shi-Wen Huang,Gang Liu,Yong-Chang Wei,Dan Xu,Kai Deng
The sequential monitoring of two pathological processes has clinical significance for early detection of drug-induced acute kidney injury (AKI), but remains challenging due to the lack of spatiotemporal probes. Here, we developed a hydrogen peroxide (H 2 O 2 ) and myeloperoxidase (MPO) programmable responsive magnetic resonance imaging (MRI) probe (PAH-Gd) for spatiotemporal monitoring of renal oxidative stress and inflammation. Upon exposure to H 2 O 2 , PAH-Gd transformed into a kidney-targeting moiety, H–Gd, which selectively accumulated in kidneys and moderately enhanced renal T1-weighted imaging (T1 WI) signal. Subsequently, the H–Gd could be oxidized by MPO to form dimers or adducts with nearby proteins, further enhancing renal T1 WI signal. We found that PAH-Gd could perform spatiotemporal monitoring of renal oxidative stress and inflammation at 12 h and 24 h post-Cisplatin (DDP) administration, enabling early detection of DDP-induced AKI at least 60 h earlier than that of standard clinical assays and permitting dynamic monitoring of renal injury progression. The spatiotemporal T1 WI overcame the limitations in detecting diverse pathological processes with a single MRI probe, accurately reporting the drug-induced AKI in the early stage and contributing to AKI prevention and treatment in the clinic.
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2025
·
IF 6.3
Lin Cheng,Zhirui Du,Xueqiao Yan,Manju Che,Guoguo Zhi,Xiuying Ma,Funeng Geng,Baojie Li
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited effective treatment. Sophora flavescens Aiton (Kushen) exhibits anti-inflammatory properties, but its key active components and mechanisms against AD remain unclear. This study aimed to identify its therapeutic compounds and the underlying molecular mechanisms. Network pharmacology and ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry were applied to screen for the potential bioactive compounds from Kushen, which were validated in AD mouse models. Formononetin (FMN) was topically administered to evaluate its curative efficacy through histopathological and immunofluorescent staining of skin lesions. Transcriptomic profiling explored the molecular mechanisms, with subsequent validation of neutrophil extracellular traps (NETs)-associated markers by immunofluorescent staining and western blotting. Co-treatment with PAD4 inhibitor GSK484 and molecular docking were used to study the underlying mechanisms. The study identified FMN as an important active component in Kushen, which showed therapeutic effects comparable to dexamethasone in AD models. FMN normalized cutaneous hyperplasia, reduced infiltration of CD3 + T cells, mast cells, and neutrophils, and suppressed inflammatory cytokine expression. Mechanistically, FMN inhibited NETs formation evidenced by decreased levels of citrullinated histone H3 (citH3), myeloperoxidase (MPO), and peptidylarginine deiminase 4 (PAD4). GSK484 co-treatment showed non-synergistic effects, suggesting that FMN suppresses NETs formation primarily through PAD4/MPO inhibition, which was confirmed by molecular docking. These findings highlight FMN as a primary anti-AD constituent of Kushen, therapeutically suppressing NETs-driven crosstalk of innate and adaptive immunity. FMN's multitarget mechanisms provide mechanistic insights and position it as a candidate for AD treatment.
研究领域:
药理学
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免疫学
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皮肤科学
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生物信息学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2022
·
IF 8.786
Gu Lingui,Sun Mingjiang,Li Ruihao,Zhang Xingyu,Tao Yihao,Yuan Ye,Luo Xu,Xie Zongyi
Neuroinflammation has been proven to exert an important effect on brain injury after intracerebral hemorrhage (ICH). Previous studies reported that Didymin possessed anti-inflammatory properties after acute hepatic injury, hyperglycemia-induced endothelial dysfunction, and death. However, the role of Didymin in microglial pyroptosis and neuroinflammation after ICH is unclear. The current study aimed to investigate the effect of Didymin on neuroinflammation mediated by microglial pyroptosis in mouse models of ICH and shed some light on the underlying mechanisms. In this study, we observed that Didymin treatment remarkably improved neurobehavioral performance and decreased BBB disruption and brain water content. Microglial activation and neutrophil infiltration in the peri-hematoma tissue after ICH were strikingly mitigated by Didymin as well. At the molecular level, administration of Didymin significantly unregulated the expression of Rkip and downregulated the expression of pyroptotic molecules and inflammatory cytokines such as Nlrp3 inflammasome, GSDMD, caspase-1, and mature IL-1β, TNF-α, and MPO after ICH. Besides, Didymin treatment decreased the number of Caspase-1-positive microglia and GSDMD-positive microglia after ICH. Inversely, Locostatin, an Rkip-specific inhibitor, significantly abolished the anti-pyroptosis and anti-neuroinflammation effects of Didymin. Moreover, Rkip binding with Asc could interrupt the activation and assembly of the inflammasome. Mechanistically, inhibition of Caspase-1 by VX-765 attenuated brain injury and suppressed microglial pyroptosis and neuroinflammation by downregulation of GSDMD, mature IL-1β, TNF-α, and MPO based on Locostatin-treated ICH. Taken together, Didymin alleviated microglial pyroptosis and neuroinflammation, at least in part through the Asc/Caspase-1/GSDMD pathway via upregulating Rkip expression after ICH. Therefore, Didymin may be a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.
研究领域:
神经科学
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药理学
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炎症
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神经病学
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产品关联
DOI
PubMed
高影响因子
Burns & Trauma
·
2021
·
IF 5.099
Liu Lu,Shao Yiming,Zhang Yixuan,Yang Yunxi,Huang Jiamin,Li Linbin,Sun Ran,Zhou Yuying,Su Yicheng,Sun Bingwei
BackgroundBurn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury. However, the pathophysiological mechanism of vascular leakage is still unclear. The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.MethodsNeutrophils were isolated from human peripheral blood by magnetic beads sorting. ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma. The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice, and high-quality video were provided. Adhesion-related molecules were investigated by qRT-PCR. The damage to glycocalyx of mice vascular endothelial cells was observed by transmission electron microscope and scanning electron microscope. Proteomic analysis, flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite (HOCl) and CD44 of human vascular endothelial cells.ResultsIn this study, we found that rapidly increasing activated neutrophils secrete heparin binding protein (HBP) and myeloperoxidase (MPO) after severe burn injury. Increased HBP triggers vascular leakage with synergy of MPO, results in systemic edema and burn shock. Furthermore, we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx. Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage. However, MPO inhibitors partially protect the glycocalyx of vascular endothelial cells. The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.ConclusionsTaken together, these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns. Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.
研究领域:
免疫学
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病理生理学
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烧伤与创伤
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血管生物学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2017
·Vol. 185
·期 1
·1-8
·
IF 4.58
Wen Yilin,Yuan Jianyong,Chen Jun,Zhao Yilin,Niu Yazhen,Yu Chao
This research describes a nanowire network-based method for detecting the activity of myeloperoxidase (MPO), a biomarker of acute coronary syndromes (ACS). Trimetallic CuPdPt nanowire networks (CuPdPt NWNWs) were prepared by a one-step chemical reduction method. The metallic precursors quickly form nanowire network structures without the need for additional capping agents or surfactants. This process creates a product with a clean surface. The NWNWs were dropped onto a glassy carbon electrode (GCE) to obtain a sensor with good catalytic activity towards the reduction of hydrogen peroxide (H 2 O 2 ), which was used as an electrochemical probe working at −0.4 V (vs. SCE). It also provided a large surface for further modification. Next, an antibody against MPO was immobilized on the modified GCE via the stable conjunction between Cu, Pt, Pd and amino groups. Upon binding of MPO to the antibody on the GCE, the current response to H 2 O 2 was reduced by 35 μA·cm −2 . The immunosensor had a linear response within the 100 fg·mL −1 to 50 ng·mL −1 MPO concentration range and a 33 fg·mL −1 detection limit (at an S/N ratio of 3). The recovery of spiked serum samples ranged from 99.8 to 103.6%. This result suggests that the method can be applied to the quantitation of MPO in human serum samples.
A trimetallic CuPdPt nanowire networks was placed on a glassy cabon electrode (GCE) to design an immunosensor for myeloperoxidase (MPO), a biomarker for the acute coronary syndrome (ACS). Antibody against MPO was immobilized on the network via conjugation between Cu, Pt, Pd and amino groups. Amperometric i-t measurements were conducted to quantify the amount of MPO that binds to the antibody on the surface of the modified GCE.
研究领域:
生物化学
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分析化学
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纳米技术
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电化学
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生物传感器
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产品关联
DOI
PubMed
高影响因子
Science China-Chemistry
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2024
·
IF 10.4
Yang Shuguang,Hu Lijun,Xiao Hong,Xiao Zecong,Shuai Xintao
Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTP-ICG, for photodynamic therapy (PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase (MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and MPO. Meanwhile, PDT efficiently incites immunogenic cell death (ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells (DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils (TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels, potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.
研究领域:
癌症治疗
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免疫学
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药理学
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分子生物学
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DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
·
IF 6.8
Yinghui Ding,Xinzhong Ruan,Kun Shu,Weiyuan Xu,Yao Liu,Gengshen Mo,Jiao Xu,Yong Jian,Jilai Zhang,Lingfeng Zhang,Keren Wang,Ji-Ting Hou,Jianliang Shen,Zhihan Yan,Fangfu Ye,Jiang Zhu,Lixiong Dai
Hepatobiliary-specific magnetic resonance imaging contrast agents (MRI CAs) play a crucial role in the early diagnosis of hepatocellular carcinoma (HCC). However, only two acyclic CAs, Gd-BOPTA and Gd-EOB-DTPA, exhibit unfavorable kinetic inertness. Our study focused on the development of superior stable innovative macrocyclic CAs. By introducing a lipophilic benzyloxy group (OBn) into the H4DOTA ring (Gd-L1), we achieved significant enhancement in kinetic inertness. In vivo experiments in mice demonstrated that 40% of the dosage was distributed to the liver at 5 min, providing sustained hepatic enhancement for over 35 min. We also developed an MPO-responsive MRI CA (Gd-L3), which can participate in the “peroxidase cycle” as the substrate, generating oligomers with a 3.8-fold increase in relaxivity, and selectively enhance the lesion in an acute gout mouse model. Overall, our work represents a significant advancement in the field of hepatic and inflammatory MRI, offering promising avenues for early diagnosis and improved imaging outcomes.
研究领域:
医学成像
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 4
·1-15
·
IF 3.3
Wang Yaru,Shang Yunxia,Tang Fengyu,Qiu Kun,Wei Xiaohui,Wang Zhengtao
In this work, self-double-emulsifying drug delivery system enteric-coated capsules (PNS-SDE-ECC) were used to enhance the oral bioavailability and anti-inflammatory effects of Panax notoginseng saponins (PNS), which are rapidly biodegradable, poorly membrane permeable, and highly water-soluble compounds. The PNS-SDEDDS formulated by a modified two-step method spontaneously emulsified to W/O/W double emulsions in the outer aqueous solution, which significantly promoted the absorption of PNS in the intestinal tract. The release study revealed that PNS-SDE-ECC exhibited sustained release of PNS within 24 h and the stability study indicated that PNS-SDE-ECC were stable at room temperature for up to 3 months. Furthermore, compared to PNS gastric capsules, the relative bioavailability of NGR1, GRg1, GRe, GRb1, and GRd in PNS-SDE-ECC was increased by 4.83, 10.78, 9.25, 3.58, and 4.63 times, respectively. More importantly, PNS-SDE-ECC significantly reduced OXZ-induced inflammatory damage in the colon by regulating the expression of TNF-α, IL-4, IL-13, and MPO cytokines. Overall, the prepared PNS-SDE-ECC may serve as a viable vehicle for increasing the oral bioavailability of PNS and its anti-inflammatory action on ulcerative colitis. Graphical Abstract
研究领域:
药剂学
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药理学
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药物递送系统
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药学
✓ 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）