Analytical Methods
·
2019
·Vol. 11
·期 19
·2597-2604
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IF 2.378
Wei Zhuang,Yining Li,Jiabi Chen,Weihui Liu,Hongyuan Huang
A simple and portable potentiometric immunoassay was designed for the quantitative detection of matrix metalloproteinase-7 (MMP7) in acute kidney injury and renal cancer on a copper ion-selective electrode (Cu-ISE). To construct such an assay system, a sandwich-type immunoreaction was initially carried out on monoclonal anti-MMP7 capture antibody-coated microplates by using an initiator DNA strand-labeled anti-MMP7 secondary antibody. Thereafter, a hybridization chain reaction (HCR) was used for the signal amplification between copper nanocluster-labeled two hairpin DNA probes. Accompanying the formation of the sandwiched immunocomplex, the labeled DNA initiator strand on the secondary antibody triggered the HCR between two alternating DNA hairpins to form a nicked double-helix with copper nanoclusters. The subsequent potentiometric measurement of copper ions released from the concatenated copper nanoclusters under acidic conditions was conducted on a portable handheld potentiometer. The immuno-HCR assay combined an easy-operation potentiometric assay with signal amplification by using an HCR-induced copper nanocluster concatemer. Under optimum conditions, the developed immuno-HCR assay exhibited a dynamic linear range of 0.01–100 ng mL−1 with a detection limit of 5.3 pg mL−1 and good reproducibility. Also, the immuno-HCR assay gave good anti-interfering capacity toward other biomarkers. The analysis for clinical human serum specimens revealed good accordance with the results obtained by an enzyme-linked immunosorbent assay. Importantly, our strategy is promising for enzyme-free and cost-effective analysis of low-abundance cancer biomarkers.
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BRITISH JOURNAL OF PHARMACOLOGY
·
2018
·Vol. 175
·期 22
·4209-4217
·
IF 6.81
Chaonan Ye,Kun Han,Jinxiu Lei,Kui Zeng,Su Zeng,Haixing Ju,Lushan Yu
Background and Purpose The concentrative nucleoside transporter 2 (CNT2) mediates the uptake of both natural nucleosides and nucleoside-derived drugs. Therefore, it is important both physiologically and pharmacologically. However, CNT2 expression is significantly repressed in colorectal cancer (CRC). Here, we have elucidated the mechanism(s) underlying CNT2 repression in CRC. Experimental Approach Repression of CNT2 in tumour samples from patients with CRC was identified using Western blot and RT-qPCR. The histone acetylation state at the CNT2 promoter region was then evaluated with chromatin immunoprecipitation and trichostatin A (TSA) treatment. To find the key enzyme responsible for hypoacetylation at the CNT2 promoter region, siRNA knockdown and RT-qPCR were used. Effects of combining HDAC inhibitors and cladribine were studied in HCT15 and HT29 cells. Key Results Histone deacetylase 7 was significantly up-regulated in CRC, leading to histone hypoacetylation at the CNT2 promoter region, especially at sites H3K9Ac, H3K18Ac and H4Ac. This hypoacetylation condensed the chromatin structure and reduced CNT2 expression. All these effects were reversed by treatment with TSA, a histone deacetylase inhibitor. In HCT15 and HT29 cells, inhibition of histone deacetylase increased cell uptake and decreased IC 50 for cladribine. Conclusions and Implications Histone hypoacetylation due to increased levels of histone deacetylase 7 results in CNT2 repression in CRC tumour tissue and could lead to decreased uptake of and consequent resistance to nucleoside anti-cancer agents. Such resistance could be overcome by combining inhibitors of histone deacetylase with the nucleoside anti-cancer agent.
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ACS Omega
·
2023
·
IF 4.1
Yue Zhao,Chaoyuan Tang,Jingyi Huang,Hongyan Zhang,Jingbin Shi,Shujun Xu,Lisha Ma,Chun Peng,Qi Liu,Yang Xiong
In this study, we established a simple and rapid in vitro method for screening multidrug resistance (MDR) reversal agents in traditional Chinese medicines (TCMs), which could better correspond to the MDR reversing effect in vivo. Here, D-luciferin, a substrate for the enzyme firefly luciferase and also a substrate for ATP-binding cassette transporters (ABC transporters), was used as the probe to detect its efflux kinetics caused by ABC transporters. First, we established a stable doxorubicin (DOX)-resistant cell line (MCF-7/DOXFluc) that overexpressed luciferase. Then, some kinds of TCMs were chosen for the MDR reversal agents to measure its effect on inhibiting the D-luciferin outflow from MCF-7/DOXFluc, and the ideal reversal agent with the least D-luciferin efflux from MCF-7/DOXFluc was selected to further investigate its effect combined with DOX on MCF-7/DOXFluc tumor-bearing mice. The results indicated that quercetin (Qu) could remarkably increase the retention of D-luciferin in MCF-7/DOXFlucin vitro and in vivo. Also, the combination of Qu and DOX could exceedingly inhibit the tumor growth, which proved the feasibility of this in vitro screening method. The study proposed a feasible method for mass screening of MDR agents from TCMs in vitro.
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ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Jie Liu,Kai Sun,Rui Zhu,Xun Wang,Michael Gatheru Waigi,Shunyao Li
Bisphenol A (BPA) is a ubiquitous endocrine disruptor that poses adverse human health risks. Herein, biotransformation kinetics, products, and mechanisms of BPA undergoing a laccase-producing Trametes hirsuta La-7 metabolism were for the first time reported. Strain La-7 could completely biotransform ≤0.5 mmol·L −1 BPA within 6 d in vivo . Notably, its extracellular crude laccase solution (ECLS) and intracellular homogenized mycelium (HM) only required 6 h to convert 85.71% and 84.24% of 0.5 mmol·L −1 BPA in vitro , respectively. The removal of BPA was noticeably hampered by adding a cytochrome P-450 inhibitor (piperonyl butoxide) in HM, disclosing that cytochrome P-450 monooxygenase participated in BPA oxidation and metabolism. BPA intermediates were elaborately identified by high-resolution mass spectrometry (HRMS) combined with 13 C stable isotope ratios (BPA: 13 C 12 -BPA = 0.25: 0.25, molar concentration). Based on the accurate molecular mass, isotope labeling difference, and relative intensity ratio of product peaks, 6 versatile metabolic mechanisms of BPA, including polymerization, hydroxylation, dehydration, bond cleavage, dehydrogenation , and carboxylation in vivo and in vitro , were confirmed. Germination index values revealed that inoculating strain La-7 in a BPA-contaminated medium presented no phytotoxicity to the germinated radish ( Raphanus sativus L.) seeds. In vivo , Mg 2+ , Fe 2+ , Fe 3+ , and Mn 2+ were conducive to BPA removal, but Cd 2+ and Hg 2+ significantly obstructed BPA elimination. Additionally, strain La-7 also exhibited high-efficiency metabolic ability toward estrone (E1), 17 β -estradiol (E2), and 17 α -ethinylestradiol (EE2), with more than 96.13%, 96.65%, and 100% of E1, E2, and EE2 having been converted, respectively. Our findings provide an environmentally powerful laccase-producing fungus to decontaminate endocrine disruptor-contaminated water matrices by radical polymerization and oxidative decomposition.
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Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 11
·2478-2489
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IF 7
Yanhao Zhang,Ji Wang,Chao Liu,Hanlei Xing,Yuhao Jiang,Xinsong Li
7-Ethyl-10-hydroxyl camptothecin (SN38), a semisynthetic derivative of camptothecin, exhibited extreme pharmacological activities in treating a range of cancers. However, its poor aqueous solubility and low stability hinder its clinical applications. Hence, a redox-responsive SN38 prodrug encapsulated human serum albumin (HSA) nanoparticle is developed to realize its potential in the clinic. First, a disulfide bond bridged 7-ethyl-10-hydroxyl camptothecin-undecanoic acid conjugate (SN38-SS-COOH) was synthesized and characterized structurally. After that, SN38-SS-COOH/HSA nanoparticles (SNH NPs) were prepared by the desolvation method. The SNH NPs with a feed molar ratio of 9 : 1 of SN38-SS-COOH : HSA showed a spherical structure with a diameter range of approximately 120–150 nm revealed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Fluorescence quenching confirmed the formation of SNH NP complexes by dual hydrophobic force and electrostatic interaction. The SNH NPs have a high drug loading of 10.44% and an encapsulation efficiency of 89.59% with good stability. Moreover, the redox responsiveness was validated by glutathione (GSH)-triggered accelerated release of parent drug SN38. In an in vivo pharmacokinetic study, the SNH NPs exhibited a significantly prolonged circulation time (t1/2, 3.77-fold) compared with free SN38. Finally, the in vivo antitumor efficacy and systemic toxicity of SNH NPs in a breast xenograft model were thoroughly evaluated. The inhibition rate of tumor growth induced by the SNH NPs reached 70.1%, while only 50.1% was achieved for irinotecan at an equivalent SN38 dosage of 10 mg kg−1. More importantly, the SNH NPs achieved a higher level of tumor growth inhibition (85.3%) by increasing the dosage to 60 mg kg−1 SN38 without obvious adverse effects. Taken together, the use of redox-responsive SN38 prodrug/HSA NPs could be a promising strategy to deliver highly active SN38 for breast cancer chemotherapy.
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INORGANIC CHEMISTRY
·
2022
·
IF 5.436
Chun-Han Lu,Yi-Ting Tsai,Tzong-Liang Tsai,Ting-Shan Chan,Xuejie Zhang,Chun Che Lin
The analysis of human body composition and food composition requires high-efficiency broadband near-infrared (NIR) lighting sources to achieve a portable, appropriately sized equipment. Herein, we develop a whitlockite-type NIR phosphor Sr9Sc(PO4)7:Cr3+ with an emission centered at 860 nm and full width at half-maximum of 147 nm. Due to the structural characteristics of the matrix, the 60 mol % Cr3+ substitution at the Sc3+ sites gives an internal quantum efficiency up to 56.5%. By replacing Sr with Ba and Ca, we observe a nontypical spectral shift phenomenon and discuss the influence of the second-sphere effect on octahedral Cr3+ ions. To evaluate the diagnostic application, we design a NIR ceramic device with a high optical power of 27.38 mW and high heat dissipation, which can decrease surface working temperature by nearly 50 °C for digital intraoral application. This study provides the research of the second-sphere coordination effect for selective octahedral sites such as Ca, Sr, and Ba coordinated by O atoms on a whitlockite-type crystal. Furthermore, the device promotes a nonionizing solution for detecting dental caries, tooth calcification, and diagnostic application.
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FOOD CHEMISTRY
·
2022
·
IF 9.231
Xin Zhang,Li Tian,Zhuo Sun,Qian Wu,Xiangyu Shan,Yingjie Zhao,Ruizhan Chen,Juan Lu
A molecular-imprinted electrochemiluminescence sensor for procymidone (PCM) detection was reported based on Ru(bpy) 3 2+ @ZIF-7. A novel self-accelerated Ru(bpy) 3 2+ @ZIF-7 was prepared by one-step synthesis method, which exhibited high electrochemiluminescence (ECL) emission as a coreactant in the presence of tri- n -propylamine (TPrA). Concretely, ZIF-7 was not only the carrier of Ru(bpy) 3 2+ , but also the co-reaction promoter of Ru(bpy) 3 2+ /TPrA ECL system. The introduction of molecular imprint polymer (MIP) with PCM gave new characteristics of specific recognition of analyte PCM. The change value of ECL intensity (ΔI) was proportional to the logarithm of PCM concentration, with a wide linear range and a low detection limit of 1.0 × 10 −10 to 1.0 × 10 −6 mol L −1 and 2.0 × 10 −11 mol L −1 , respectively. The presented MIP-ECL sensor had high sensitivity, selectivity and stability, and had great potential in the field of food safety detection.
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Analytical Methods
·
2021
·Vol. 13
·期 36
·4090-4098
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IF 2.896
Zhen Li,Tan Wang,Xianbao Xu,Cong Wang,Daoliang Li
A novel “on–off” fluorescent probe was synthesized for highly sensitive and ultra-trace determination of ammonia nitrogen in aquaculture water. Ammonium can react with formaldehyde and sodium hydroxide to form a ring substance (urotropine), which shows no fluorescence signal. Palmatine hydrochloride (PAL) can enter the hydrophobic cavity of cucurbit[7]uril (CB[7]), eventually forming a 1 : 1 host guest complex called PAL@CB[7] under neutral or acidic conditions, which has strong green fluorescence with the maximum excitation (λex) wavelength at 343 nm, and the maximum emission (λem) wavelength at 500 nm, while urotropine has a fluorescence quenching effect on the fluorescence enhancement system of PAL@CB[7]. Therefore, a fluorescent chemosensor based on PAL@CB[7] and the reaction of ammonia nitrogen with formaldehyde was developed. The results indicate that the linearity range and the limit of detection of the proposed method are 1–300 μg L−1 with a good correlation coefficient (r2 = 0.9966) and 1.8 × 10−2 μg L−1, respectively. Under the optimal conditions, the method was employed for the detection of ammonia nitrogen in real aquaculture water samples, revealing high selectivity and sensitivity. In the future, the combination of the “on–off” fluorescence method, a portable hardware system and intelligent algorithms will provide technology support for the design of on-line sensors for measuring ammonia nitrogen in aquaculture water.
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CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Yunning Chen,Xiaoyan Zhang,Lingling Wang,Xueying Cheng,Qingkun Shang
An Fe-HQLC/TiO 2 (HQLC: 8-hydroxyquinoline-7-carboxylic) flower composite was synthesized and characterized. Phenol and four antibiotics: ciprofloxacin, tetracycline, amoxicillin and erythromycin can be efficiently and rapidly degraded by the Fe-HQLC/TiO 2 flower under visible light. The results indicated that more than 95% of the four antibiotics could be removed within 15 min. The photodegradation products of the four antibiotics were studied by high-performance liquid chromatography and high-resolution liquid chromatography-mass spectrometry. It was found that the adsorption characteristics of the antibiotics and their degradation products had a great influence on the photocatalytic activity of the photocatalyst and on the degradation rate of the antibiotics in recycling. Although the Fe-HQLC/TiO 2 flower did not degrade the four antibiotics completely, the parent structure of the antibiotics was destroyed to some extent. Therefore, the environmental toxicity and cytotoxicity of the antibiotics were significantly decreased. Compared with other related research works, there are a few photocatalysts capable of efficient and rapid removal of antibiotics.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2022
·
IF 5.168
Moath Refat,Guoqiang Zhang,Abdulaziz Ahmed A.Saad,Salem Baldi,Fang Zheng,Xin'an Wu
Cholestasis is primarily caused by bile acid homeostasis dysregulation, resulting in retention, aggregation, and accumulation of the toxic cholate in the hepatocytes. Existing therapies for cholestasis are limited, demanding the urgent development of novel drugs. As a result, targeting FXR specifically promises a unique treatment strategy for cholestasis. The current study aims to evaluate the influence of 7, 8-dihydroxy-4-methyl coumarin (DMC) against alpha-naphthyl isothiocyanate (ANIT)-induced liver injury in mice. The “Computer-Aided Drug Design” (CADD) and molecular docking study anticipated that DMC would proficiently bind and activate the FXR. Accordingly, the hepatoprotective activity of DMC against ANIT-induced hepatotoxicity and cholestasis was investigated in ANIT-treated HepaRG cells and the ANIT-induced cholestatic mouse model. Outcomes indicated the protective effects of DMC against ANIT toxicity in HepaRG cells after 24 h of intervention and animals after seven days of treatment. DMC partially blocks ANIT-induced increases in serum markers of hepatocellular injury , liver and gall bladder enlargement , and hepatic necrosis . Western blotting revealed that DMC alleviates ANIT-induced hepatotoxicity and cholestasis via activating the FXR receptor and regulating CYP7A1 , the enzyme responsible for bile acid synthesis. DMC exhibited protective activity against cholestasis through activating FXR, suggesting it might be a promising strategy for preventing and treating cholestatic liver disease.
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Biomaterials Science
·
2024
·Vol. 12
·期 20
·5266-5273
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IF 5.8
Tao Hu,Ji-Na Hao,Yongsheng Li
Rapid and accurate detection of 7-methylguanine (m7Gua), a biomarker reflecting the degree of DNA methylation that occurs before or in the early stage of cancer, is of particular significance but remains a great challenge. Herein, a luminescent lanthanide-based covalent organic framework (Ln-COF) probe, namely DPA/Eu@ETTA-DHTA, is designed for the first time for the identification of m7Gua by assembling pyridine-2,6-dicarboxylic acid (DPA) as both an energy donor and a recognition molecule and Eu3+ ions as signal reporters into a stable COF matrix with high porosity and available binding sites. Significantly, the characteristic luminescence of Eu3+ ions can be turned on by the grafted DPA in the COF probe and effectively quenched by the addition of m7Gua via a competitive absorption process, thus achieving the sensing of m7Gua. Such a Ln-COF-based fluorescent platform presents high selectivity and a rapid response (<1 min) to m7Gua with a low detection limit (μM level) even in the presence of the main coexisting species in urine, allowing it to serve as a potentially practical probe for point-of-care monitoring of the level of m7Gua in human urine specimens. This study provides a convenient, time-saving, and economical approach for visual detection of m7Gua, and opens up new perspectives for the design of a luminescent COF-based probe for DNA methylation evaluation in diagnostics.
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MEDICINAL CHEMISTRY RESEARCH
·
2015
·Vol. 24
·期 8
·3327-3333
·
IF 1.402
Ye Lianbao,Wu Jie,Yang Jiebo,Chen Weiqiang,Luo Yan,Zhang Yanmei
Abstract HGF/c-Met signaling pathway has come into the spotlight as a promising therapeutic target for inhibiting tumor growth and has become one of the leading molecular targets in cancer. Various strategies are currently in development to disrupt the HGF–Met signal transduction pathway, in which small molecular inhibitors have been a particularly active field. On the basis of the structures of two c-Met inhibitors, PF-04217903 and JNJ-38877605, some novel 7-[(quinolin-6-yl)methyl] purines ( 4a – 4e ) were rationally designed on the principle of bioisosterism strategy. These compounds were synthesized and evaluated as novel c-Met inhibitors. Molecular docking experiments analyzed the results and explained the molecular mechanism of eminent activities to c-Met. The results showed that all the title compounds were active against c-Met enzyme to some extent. Though these compounds did not demonstrate inhibition as we expected, this study provided important information for building diversification of chemical library and molecular docking experiment supplied the basis for further research works. Graphical Abstract Some novel
7-[(quinolin-6-yl)methyl] purines as potential c-Met inhibitors have been designed and prepared. Their synthesis and spectral characterization are reported here.
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