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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2021 · IF 4.098

Copper ion and G-quadruplex-mediated fluorescent sensor for highly selective detection of bleomycin in actual samples

Lingfeng Qin,Bo Feng,Qi Luo,Zihang Zeng,Peng Zhang,Xiaosheng Ye,Taiping Qing

Improper dosage of Bleomycin (BLM) can easily lead to a series of side effects such as pulmonary fibrosis and pulmonary toxicity. Therefore, detecting the content of BLM in actual sample is very helpful to make full use of its therapeutic efficacy and reduce its toxicity. Herein, we constructed a copper ion and G-quadruplex mediated label-free sensor to detect BLM. The strategy mainly relies on the chelation of BLM to copper ions, which makes the copper ions lose the quenching ability to the fluorescent dye N-methylmesoporphyrin (NMM) after chelation. With the assistance of the G-quadruplex, the BLM content in the sample can be detected by observing the change in fluorescence. A good linear relationship can be clearly observed within the BLM concentration range of 0.1 nM-75 nM, and the limit of detection was derived as 0.1 nM. This sensor did not involve any labeling or addition of Fe 2+ , even in the presence of 10 different antibiotics and 11 different metal ions, it still has a good monitoring effect, and can be successfully applied to the detection of BLM in serum and wastewater. Thus, we believe that this work hold great potential in antibiotic monitoring and environmental protection.

研究领域: 生物化学 · 医学检测 · 环境科学
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Canadian Respiratory Journal · 2019 · IF 1.803

CXCL16 Induces the Progression of Pulmonary Fibrosis through Promoting the Phosphorylation of STAT3

Sheng Zuo,Zhen Zhu,Yi Liu,Hong Li,Shuang Song,Shaojun Yin

Aim. The transmembrane chemokine (C-X-C motif) ligand 16 (CXCL16) plays a vital role in the pathogenesis of organ fibrosis, including the liver and kidney. However, the detailed biological function of CXCL16 is still not fully understood in the progression of pulmonary fibrosis (PF). The aim of present study is to examine the function of CXCL16 in PF. Materials and Methods. In this study, we constructed the PF model on mouse by using bleomycin and analyzed the effect of the mouse recombinant protein CXCL16 on mouse lung fibroblast L929 (LF) as well. To further examine the connection between CXCL16 and STAT3 in mouse LF cells, the STAT3 inhibitor AG490 was utilized to inhibit the expression of STAT3. Meanwhile, lipopolysaccharide was used to enhance the phosphorylation of STAT3 (p-STAT3) in mouse LF cells. Results. Our results indicated that the level of CXCL16/CXCR6 was significantly upregulated in the mouse PF model. Moreover, the level of p-STAT3 was also promoted. In addition, the mouse recombinant protein CXCL16 not only contributed to the proliferation of mouse LF cells but also induced the expression of p-STAT3 in LF cells. However, the effect of CXCL16 was deeply abolished by the STAT3 inhibitor AG490 in LF cells. Meanwhile, the antibody of CXCL16 deeply reduced the phosphorylation of STAT3 in lipopolysaccharide (LPS) cultured cells. Conclusions. All these results demonstrated that CXCL16 promoted the phosphorylation of STAT3 and further demonstrated that STAT3 was a critical component in CXCL16/CXCR6 signaling pathway. This research not only enhanced the comprehension of CXCL16 but also indicated its potential value as a target in the treatment for human PF.

研究领域: 肺科学 · 分子生物学 · 免疫学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2023 · IF 4.4

Carbon dots with selective fluorescence response to hydroxyl radical for sensitive detection of bleomycin

Xiaoqin Deng,Menghan Zhang,Yao Wang,Congpei Li,Xintian Zhang,Shaohuang Weng,Yiming Li

In this work, antioxidant carbon dots (ACDs) with high quantum yield (63.98%) were developed through a one-step strategy using citric acid, ethylenediamine, and L-arginine as sources. The ACDs demonstrated excellent in vitro antioxidant activity. Additionally, ACDs displayed a unique fluorescence response to hydroxyl radical ( OH). Leveraging this distinctive feature, a selective and sensitive fluorescence-based sensor was developed for detecting bleomycin (BLM) in the presence of ferrous ions (Fe 2+ ). The studies on the oxidizing properties and dynamic quenching mechanism of ACDs by OH suggested that OH reduced the contents of the amino and hydroxyl groups of ACDs, leading to a decreased electron cloud density of ACDs for dynamic quenching of ACDs. Under optimally refined conditions, the detection limit of this strategy for BLM was 0.58 μg/mL, with a linear range spanning from 1 to 24 μg/mL when employing ACDs as the probe. This fluorescence sensing strategy provides a promising method for the detection of BLM in clinical samples.

研究领域: 分析化学 · 生物医学工程 · 药物分析
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NEW JOURNAL OF CHEMISTRY · 2021 ·Vol. 45 ·期 30 ·13620-13625 · IF 3.591

A ratiometric fluorescence assay for bleomycin based on Cu2+-triggered cascade reactions and nanoparticle-mediated autocatalytic reactions

Fujin Guo,Meng Xia,Jing Sun,Shuyun Zhu

A simple strategy has been designed for ratiometric fluorescence sensing of BLM on the basis of Cu2+-triggered fluorogenic reactions coupled with nanoparticle-mediated autocatalytic reactions. On one hand, Cu2+ can oxidize ascorbic acid (AA) to produce dehydroascorbic acid (DHAA), which condensates with o-phenylenediamine (OPD) to form fluorescent 3-(dihydroxyethyl) furo[3,4-b]quinoxaline-1-one (DFQ) with strong emission at 436 nm. On the other hand, Cu2+ and OPD undergo a redox reaction to form fluorescent 2,3-diaminophenazine (DAP) showing strong emission at 565 nm and copper nanoparticles (CuNPs) that further catalyze this redox reaction. A ratiometric fluorescence system comes into being due to these two well-resolved emission peaks. Ascribed to the complexation of BLM with Cu2+, larger CuNPs are obtained which weaken the autocatalytic reaction between Cu2+ and OPD. Thus, the fluorescence intensities at 565 nm belonging to DAP decrease while those at 436 nm corresponding to DFQ change slightly. With the fluorescence intensity ratio (F436/F565) as a readout, BLM can be detected selectively and sensitively with a detection limit of 50 pM.

研究领域: 生物化学 · 分析化学 · 医学诊断
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BIOCHEMICAL PHARMACOLOGY · 2025 · IF 5.6

Mitomycin induced the senescence of alveolar epithelial cells by targeting peroxiredoxin I

Xionghua Sun,Xuelei Wan,Li Chen,Yadong Cui,Xihua Chen,Jian Zhang,Xiaogang Jiang

The senescence of alveolar epithelial cells is one of the characteristics of mitomycin pulmonary toxicity, but the direct target of mitomycin-induced alveolar epithelial cell senescence remains unclear. In this study, a method of small-molecule ligand–protein interaction by pulldown/mass spectrometry identified peroxiredoxin I (Prdx I) as the target of mitomycin-induced alveolar epithelial cell senescence, and mitomycin was shown to significantly inhibit the peroxidase activity of Prdx I. Consequently, the levels of cellular reactive oxygen species (ROS) increased, leading to the activation of mitogen-activated protein kinase kinase 1/2 (MEK1/2)-extracellular signal-regulated protein kinases 1/2 (ERK 1/2) and, accordingly, to the increased expression of p53. Both a Prdx I activator and Prdx I overexpression alleviated mitomycin-induced alveolar cell senescence. A ROS scavenger inhibited MEK1/2-ERK1/2-p53 activation and then attenuated the senescence of alveolar epithelial cells triggered by mitomycin. Thus, Prdx I can serve as the first target of mitomycin-induced alveolar epithelial cell senescence, which might represent a promising approach to reduce mitomycin-induced lung toxicity.

CAS / MDL: 60940-34-3
研究领域: 药理学 · 分子生物学
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RSC Advances · 2022 ·Vol. 12 ·期 29 ·18296-18300 · IF 4.036

Target-induced activation of DNAzyme for highly sensitive colorimetric detection of bleomycin via DNA scission

Xiaofei Liao,Mengyan Li,Li Zou

In this work, a label-free and sensitive colorimetric sensing strategy for the detection of bleomycin (BLM) was developed on the basis of BLM-mediated activation of G-quadruplex DNAzyme via DNA strand scission. A G-quadruplex based hairpin probe (G4HP) containing the scission site (5′-GT-3′) of BLM at the loop region and guanine (G)-rich sequences at its 5′-end was employed in this protocol. In the presence of BLM, it may cleave the 5′-GT-3′ site of the hairpin probe with Fe(II) as a cofactor, releasing the G-tetrads DNA fragment, which may further bind hemin to form a catalytic G-quadruplex-hemin DNAzyme. The resultant G-quadruplex DNAzyme has notable peroxidase-like activity, which effectively catalyzes the oxidation of 2,2′-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) (ABTS) by H2O2 to produce the blue-green-colored free-radical cation (ABTS·+). Therefore, the detection of BLM can be achieved by observing the color transition with the naked eye or measuring the absorbance at a wavelength of 420 nm using a UV-Vis spectrophotometer. Attributing to the specific BLM-induced DNA strand scission and the effective locking of G-tetrads in the stem of the G4HP, the colorimetric sensing strategy exhibits high sensitivity and selectivity for detection of BLM in human serum samples, which might hold great promise for BLM assay in biomedical and clinical research.

研究领域: 生物医学工程 · 分析化学 · 分子生物学
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PHARMACOLOGICAL RESEARCH · 2022 · IF 10.334

PD-L1 upregulation promotes drug-induced pulmonary fibrosis by inhibiting vimentin degradation

Qing Li,Meng-Sheng Deng,Ren-Tao Wang,Hao Luo,Yuan-Yuan Luo,Dong-Dong Zhang,Kui-Jun Chen,Xiao-Fu Cao,Guang-Ming Yang,Tie-Mei Zhao,Bo Xu,Cheng-Xiong Xu,Jian-Min Wang

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality and limited therapeutic options. The immune checkpoint PD1/PD-L1 axis is related to the pathogenesis of pulmonary fibrosis, and upregulated expression levels of PD-L1 have been demonstrated in IPF patients. However, the mechanism of PD-L1 in pulmonary fibrosis is not fully understood. Here, we demonstrated upregulated expression of PD-L1 in fibrotic lung tissues and sera of IPF patients. Bleomycin (BLM) treatment induced PD-L1 upregulation, EMT (Epithelial-Mesenchymal Transition) and fibrosis-like morphology changes in human pulmonary alveolar epithelial cells (HPAEpiCs). Silencing PD-L1 attenuated BLM-induced EMT and fibrosis-like morphology changes in HPAEpiCs. In addition, we identified that PD-L1 directly binds to vimentin and inhibits vimentin ubiquitination, thereby increasing vimentin levels in HPAEpiCs. Silencing of vimentin inhibited BLM- and PD-L1-induced fibrosis in HPAEpiCs. The correlation between PD-L1 and EMT or vimentin expression was further confirmed in clinical samples and animal models. Finally, we used BLM- and paraquat-induced pulmonary fibrosis animal models to confirm the anti-pulmonary fibrosis effects of PD-L1 silencing. Taken together, our findings suggest that upregulated PD-L1 stimulates EMT of alveolar epithelial cells by increasing vimentin levels by inhibiting vimentin ubiquitination, thereby contributing to pulmonary fibrosis.

研究领域: 呼吸病学 · 免疫学 · 细胞生物学
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Applied Nanoscience · 2022 ·Vol. 12 ·期 12 ·3883-3899 · IF 3.869

Surface engineered AuNPs for paclitaxel-loaded bleomycin delivery as a supplementation therapy

Farooq Muhammad Umar,Sahin Yesim Muge,Naz Muhammad Yasin,Ijaz Salman,Shukrullah Shazia,Makhlouf Mohamed M.

A paradigm transition in cancer treatment gradually moved from "one drug-one target" toward "multi-target selective drugs design", because different drugs simultaneously inhibit tumor progression differently. The underlying mechanism has encountered significant challenges, such as encapsulating chemotherapies into a nanosized particulate system, adverse side effects, and managing multidrug-resistant. To address these issues, herein we engineered the gold nanoparticles’ surfaces with cross-linked polyethylene glycol that have well-controlled morphology and further encapsulated with commonly known chemo-drugs paclitaxel and bleomycin for nanovectorization of therapeutics to the intended site and there act through the concurrent action of dual targeting mechanisms without creating undesired side effects. The structures of the nanovectorization particulate system were confirmed by various spectroscopic techniques. The efficacy of nanovectorization particulate system and non-targeted free drugs was evaluated using the human cervical adenocarcinoma cell model. Our findings indicate that this nanovectorization particulate system had synergic stimuli-responsive characteristics and unrivaled control of efficient transportation of therapeutics agents. This system meets the high demand for multiple targeting delivery and has substantial benefits across multiple fields of nanomedicine, especially in chemotherapy.

研究领域: 纳米医学 · 肿瘤学 · 药剂学
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BIOMEDICINE & PHARMACOTHERAPY · 2019 · IF 3.743

Combination of L-Arginine and L-Norvaline protects against pulmonary fibrosis progression induced by bleomycin in mice

Lu Gao,Jia-Hua Zhang,Xiao-Xu Chen,Hui-Li Ren,Xiu-Ling Feng,Jia-Ling Wang,Jun-Hua Xiao

Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.

CAS / MDL: 327-57-1
研究领域: 药理学 · 免疫学 · 肺病学
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BIOSENSORS & BIOELECTRONICS · 2019 · IF 9.518

Dual-mode visible light-induced aptasensing platforms for bleomycin detection based on CdS–In2S3 heterojunction

Mengjun Sun,Yuhan Zhu,Kai Yan,Jingdong Zhang

CdS–In 2 S 3 heterojunction with enhanced photoelectrochemical (PEC) performance was synthesized to construct dual-mode visible light-induced biosensors for highly sensitive and selective detection of bleomycin (BLM). Due to improved absorption in the visible region and suppressed recombination of electron-hole pairs in the heterojunction, CdS–In 2 S 3 composite exhibited enhanced photocurrent response under visible light illumination. Using CdS–In 2 S 3 as photoactive materials and BLM-binding aptamer as recognition element, a PEC aptasensor displaying a declined photocurrent response to BLM was facilely constructed, which was linear to BLM concentration in the range of 5.0–250 nM. On the other hand, the CdS–In 2 S 3 photoanode was employed to construct a photofuel cell (PFC). In such a PFC, the oxidation of water on CdS–In 2 S 3 photoanode under visible light illumination and the reduction of oxygen on Pt cathode led to the generation of electricity. When BLM-binding aptamer was immobilized on CdS–In 2 S 3 photoanode, the output power of the PFC was inversely proportional to the logarithm of BLM concentration from 10 to 250 nM, offering a visible light-induced self-powered sensing platform for BLM detection. Both of the proposed sensors showed high selectivity , good reproducibility and high stability. They were successfully applied to the determination of BLM in human serum samples.

研究领域: 生物传感 · 材料科学 · 分析化学
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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Niche nanoparticle-based FRET assay for bleomycin detection via DNA scission

Haimeng Pei,Yiqun Zheng,Rongmei Kong,Lian Xia,Fengli Qu

We describe a highly sensitive nanoparticle–based fluorescence resonance energy transfer (FRET) probe developed without using molecular fluorophores as donors and acceptors. The success of this work relies on the strategy that DNA scission was designed to occur to the probe when target presented, which enabled the fluorescence signal “turn-on” of graphene quantum dots (GQDs) and thus quantitative analysis . In particular, amino-modified SiO 2 NPs were initially coated by GQDs to form highly emitting SiO 2 /GQDs, followed by conjunction with DNA functionalized gold nanoparticles (Au NPs–DNA) to form SiO 2 /GQDs–DNA–Au NPs composite. Owing to the FRET interactions between the GQDs and Au NPs, the fluorescence of GQDs was effectively quenched by Au NPs. When bleomycin (BLM), a model analyte , was mixed with the probe, the fluorescence signal of GQDs would be restored due to the removal of Au NPs from the SiO 2 /GQDs surface by DNA scission treatment with BLM in the presence of Fe (II). The current FRET probe shows a good linear relationship between the fluorescence intensity and the concentration of BLM in the range from 0.5   nM to 1   μM with a detection limit of 0.2   nM. The probe also shows satisfactory results for the analysis of clinical serum samples. This method provides versatility to the application of GQDs in FRET biosensing and could be potentially extended to other similar systems by replacing the linker between the GQDs and Au NPs.

研究领域: 生物化学 · 纳米医学 · 分析化学
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BIOSENSORS & BIOELECTRONICS · 2023 · IF 12.6

A cost-effective, “mix & act” G-quadruplex/Cu (II) metal-nanozyme-based ratiometric fluorescent platform for highly sensitive and selective cysteine/bleomycin detection and multilevel contrary logic computing

Jun Wang,Jiawen Han,Juan Wang,Xujuan Lv,Daoqing Fan,Shaojun Dong

Versatile nanozymes with fascinating catalytic properties provide inspiring and effective options for biosensing and pharmaceutical analysis. Herein, we report the first nanozyme-based ratiometric fluorescent platform for cysteine (Cys) and bleomycin (BLM) detection by harnessing the cost-effective and “mix & act” G-quadruplex/Cu(II) (G4/Cu) metal-nanozyme with satisfactory peroxidase-like activity, which was fully proven by circular dichroism (CD), electron paramagnetic resonance (EPR) spectra and reactive oxygen species (ROS) scavenging experiments. Based on the catalytic oxidation of G4/Cu metal-nanozyme toward two fluorescent substrates (Amplex Ultrared, AU; Scopoletin , Sc) with opposite responses in the presence of H 2 O 2 , and the specific interaction between Cu 2+ and targets, we achieved the highly sensitive detection of Cys and BLM. Through recording the fluorescence changes of AU (emission at 590 nm, F590) and Sc (emission at 465 nm, F465), we obtained good linear relationships between ratiometric fluorescence values (F590/F465) and variable contents of targets, resulting in the competitive LODs of Cys (6.7 nM) and BLM (10 nM), respectively. Moreover, this platform presented high selectivity (without the need for masking agent) and acceptable performance in human serum samples. Furthermore, a library of DNA contrary logic pairs (CLPs) and multilevel concatenated circuits were fabricated based on the reverse dual-output of the above platform, enriching the building blocks of biocomputing. This work not only enlightened the design of affordable, “mix & act” type nanozyme-based ratiometric biosensors with high reliability, but also facilitated the pluralistic application of nucleic acid-templated nanozymes to innovative biocomputing.

CAS / MDL: 7440-57-5
研究领域: 生物传感 · 药物分析 · 生物计算
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