SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2026
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IF 4.8
Ting Cao,Mengjin Li,Hong Ma,Zhefeng Fan
Monoamine oxidase (MAOs) is a key enzyme that maintains amine homeostasis and participates in liver pathological processes. Real time in situ monitoring of its activity is crucial for elucidating the mechanism of drug-induced liver injury (DILI). This study successfully constructed a ratio type fluorescent probe Cy-1 with mitochondrial targeting ability and near-infrared emission characteristics. This probe is based on MAOs catalyzed oxidative deamination reaction, and achieves fluorescence response through a clever “ICT (Intramolecular Charge Transfer) + ESIPT (Excited-State Intramolecular Proton Transfer)” dual mechanism, producing significant ratiometric signal changes in the near-infrared region. Experiments have shown that Cy-1 has a wide linear range (10–115 μg/mL), high sensitivity (0.86 μg/mL), and high selectivity in vitro, and can specifically localize to mitochondria. The probe was successfully used for in situ differential monitoring of endogenous MAOs activity in living cells, and visualized semi quantitative monitoring of MAOs activity changes in vivo was achieved in an acetaminophen (APAP) induced drug-induced liver injury (DILI) model. Cy-1 is expected to become a powerful chemical tool for understanding the mechanisms of MAOs in physiological and pathological processes, especially in the occurrence and development of diseases such as liver injury, as well as evaluating the efficacy of related drugs.
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PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
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2026
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IF 4.4
Ting Cao,Mengjin Li,Hong Ma,Zhefeng Fan
A novel AIE-1 probe integrates “ICT + ESIPT+AIE” tri-modal for ratiometric NIR fluorescence imaging of MAO activity. • AIE-1 exhibits wide linear range (0–140 μg/mL), high sensitivity (LOD 0.23 μg/mL), and excellent selectivity. • AIE-1 semi-quantitatively distinguishes MAO activity in normal/cancer cells and evaluates cellular inhibitor efficacy. • Successful real-time visualization of upregulated MAO activity is achieved in a DILI model. Given the crucial role of monoamine oxidase (MAO) in maintaining amine homeostasis and liver pathology, real-time in situ monitoring of its activity is crucial for elucidating the mechanism of drug-induced liver injury (DILI). This study designed and synthesized a ratio type fluorescent probe AIE-1 based on the “ICT + ESIPT” mechanism, which integrates aggregation induced luminescence (AIE), near-infrared (NIR) emission, and mitochondrial targeting. The probe AIE-1 utilizes MAO catalyzed oxidative deamination reaction to trigger intramolecular charge transfer and excited state proton transfer processes, producing significant ratiometric fluorescence signals at 518 nm and 712 nm. The sensing mechanism was thoroughly validated by 1 H NMR titration, DFT calculations of HOMO-LUMO energy gaps, and solvent-polarity-dependent experiments, collectively confirming the occurrence of both ICT and ESIPT processes. Spectral experiments show that its detection of MAO has a wide linear range (0–140 μg/mL), high sensitivity (0.23 μg/mL), strong selectivity, and anti-interference ability. Cell imaging experiments have confirmed that AIE-1 can successfully semi quantitatively distinguish the differences in MAOs activity between normal liver cells and liver cancer cells, and evaluate the effectiveness of inhibitors. In the drug-induced liver injury model, AIE-1 successfully achieved real-time visualization monitoring of upregulation of MAO activity in vivo with sensitivity and specificity. This probe provides a novel and efficient tool for studying the role of MAO in pathological processes such as DILI.
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高影响因子
ANALYTICAL CHEMISTRY
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2018
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IF 6.042
Xiaoyun Jiao,Yongsheng Xiao,Yong Li,Muwen Liang,Xilei Xie,Xu Wang,Bo Tang
Drug-induced liver injury (DILI) has aroused wide concern. Finding new markers or indicators as well as detoxification molecules for DILI is of great significance and good application prospect, which can help develop effective preclinical screening methodology and corresponding treatment protocols. Herein, in this article, DILI caused by antidepressant drugs of duloxetine and fluoxetine and its remission were evaluated by a two-photon fluorescent probe, RPC-1, through discriminating and imaging HClO and H2S simultaneously. By being applied both in vitro and in vivo, RPC-1 revealed slight up-regulation of HClO and negligible liver damage after administration of either of the two drugs. In contrast, an apparent up-regulation of HClO and obvious liver damage was observed after combined administration of the drugs. Meanwhile, the pretreatment of N-acetyl cysteine (NAC) resulted in the increasing of endogenous H2S level, which contributed to the remission of DILI. The histological analysis and serological test both gave good consistency with the imaging results. These findings demonstrate that HClO may be an appropriate indicator of DILI, and H2S plays an important role in the antidotal effect of NAC. We envision that RPC-1 can be used as a powerful tool to predict clinical DILI and study the effect of antidote, as well as explore the molecular mechanisms involved.
研究领域:
药理学
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毒理学
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生物医学工程
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临床医学
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高影响因子
Autophagy
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2024
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IF 14.6
Jiajia Wang,Yueping Qiu,Lijun Yang,Jincheng Wang,Jie He,Chengwu Tang,Zhaoxu Yang,Wenxiang Hong,Bo Yang,Qiaojun He,Qinjie Weng
Disruption of mitochondrial function is observed in multiple drug-induced liver injuries (DILIs), a significant global health threat. However, how the mitochondrial dysfunction occurs and whether maintain mitochondrial homeostasis is beneficial for DILIs remains unclear. Here, we show that defective mitophagy by OPTN (optineurin) ablation causes disrupted mitochondrial homeostasis and aggravates hepatocytes necrosis in DILIs, while OPTN overexpression protects against DILI depending on its mitophagic function. Notably, mass spectrometry analysis identifies a new mitochondrial substrate, GCDH (glutaryl-CoA dehydrogenase), which can be selectively recruited by OPTN for mitophagic degradation, and a new cofactor, VCP (valosin containing protein) that interacts with OPTN to stabilize BECN1 during phagophore assembly, thus boosting OPTN-mediated mitophagy initiation to clear damaged mitochondria and preserve mitochondrial homeostasis in DILIs. Then, the accumulation of OPTN in different DILIs is further validated with a protective effect, and pyridoxine is screened and established to alleviate DILIs by inducing OPTN-mediated mitophagy. Collectively, our findings uncover a dual role of OPTN in mitophagy initiation and implicate the preservation of mitochondrial homeostasis via inducing OPTN-mediated mitophagy as a potential therapeutic approach for DILIs.Abbreviation: AILI: acetaminophen-induced liver injury; ALS: amyotrophic lateral sclerosis; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DILI: drug-induced liver injury; FL: full length; GCDH: glutaryl-CoA dehydrogenase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GO: gene ontology; GSEA: gene set enrichment analysis; GPT/ALT: glutamic – pyruvic transaminase; INH: isoniazid; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MST: microscale thermophoresis; MT-CO2/COX-II: mitochondrially encoded cytochrome c oxidase II; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TSN: toosendanin; VCP: valosin containing protein, WIPI2: WD repeat domain, phosphoinositide interacting 2.
研究领域:
肝病学
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细胞生物学
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药理学
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分子生物学
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高影响因子
RSC Advances
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2018
·Vol. 8
·期 39
·22062-22068
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IF 2.936
Bailing Ma,Mi Lu,Bo-Yang Yu,Jiangwei Tian
Drug-induced liver injury (DILI) is a serious concern in modern medicine due to its unpredictability. Currently, biochemical serum markers are being used in DILI detection. However, these biomarker-based methods lack sensitivity and specificity. A high intracellular level of hydroxyl radicals (˙OH) has been regarded as an early indicator of DILI. Therefore, we proposed an ˙OH-responsive and hepatocyte-targeted nanoprobe via conjugation of carboxyfluorescein-labeled DNA and pegylated galactose on the surface of gold nanoparticles. The nanoprobe could bind to a hepatocyte-specific asialoglycoprotein receptor through galactose, and it could be internalized into liver cells. In the presence of high levels of ˙OH in DILI, the DNA could be cleaved to release carboxyfluorescein, leading to remarkable fluorescence enhancement for ˙OH detection. Confocal fluorescence imaging demonstrated that the nanoprobe could be successfully applied in monitoring high ˙OH levels resulting from acetaminophen or triptolide-induced liver injury, which may provide a simple but powerful protocol for the prediction of DILI.
研究领域:
药理学
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纳米技术
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医学成像
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毒理学
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PubMed
高影响因子
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