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Nature Communications · 2019 ·Vol. 10 ·期 1 ·1-14 · IF 11.878

ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield

Ou Juanjuan,Peng Yuan,Yang Weiwen,Zhang Yue,Hao Jie,Li Fu,Chen Yanrong,Zhao Yang,Xie Xiong,Wu Shuang,Zha Lin,Luo Xi,Xie Ganfeng,Wang Liting,Sun Wei,Zhou Qi,Li Jianjun,Liang Houjie

The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 9 ·1-10 · IF 5.479

An organic polymer monolith modified with an amino acid ionic liquid and graphene oxide for use in capillary electrochromatography: application to the separation of amino acids, β-blockers, and nucleotides

Zhao Shiyuan,Yu Tao,Du Yingxiang,Sun Xiaodong,Feng Zijie,Ma Xiaofei,Ding Wen,Chen Cheng

The preparation of an organic polymer monolithic column modified with an amino acid ionic liquid and graphene oxide (AAIL-GO) and its application to capillary electrochromatography (CEC) was described. The AAIL tetramethylammonium-L-arginine was bonded to a monolithic column that was previously modified with graphene oxide by using an hydrochloride/N-hydroxysuccinimide coupling reaction. The morphology of a poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith was examined by scanning electron microscopy. The incorporation of AAIL and graphene oxide was detected by infrared spectroscopy and elemental analysis. The resulting monolithic column produced a strong and stable electroosmotic flow from the anode to the cathode in the pH range from 3 to 9. Compared with a column modified with AAIL or graphene oxide only, the AAIL-GO-modified column has a better separation ability for amino acids, β-blockers, and nucleotides (the resolution of three amino acids: 2.231 and 2.036, β-blockers: 2.779 and 2.470 and nucleotides: 8.345 and 3.321). Molecular modeling was applied to demonstrate the separation mechanism of small molecules which showed a good support for experimental results. Schematic representation of capillary electrochromatography (CEC) systems with an amino acid ionic liquid-graphene oxide modified organic polymer monolithic column as stationary phases for separation of amino acids, β-blockers, and nucleotides.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2018 ·Vol. 185 ·期 7 ·1-6 · IF 5.705

Selective, fast and semi-automatic enrichment of nucleosides by using a phenylboronic acid modified hybrid material composed of graphene oxide and melamine sponge

Cheng Ting,Jiao Zhijuan,Liu Xiaoyan,Zhang Haixia

A hybrid material was prepared from graphene oxide and melamine sponge, and modified with phenylboronic acid to obtain a sorbent for the enrichment of the nucleosides cytidine, uridine, inosine, guanosine and adenosine. The loading capacity typically is around 27.8 mg g −1 which is comparable to other sorbents, and highly selectivity for cis-diols is observed even if the concentration of potential interferents is 1500-fold higher. The sorbent was placed in an injector, and the process was operated semiautomatically by using a peristaltic pump. The sorbent is stable and can be re-used six times without decrease in efficiency. It was applied to the selective extraction of the cis -diols (cytidine, uridine, inosine, guanosine, adenosine) from HepG2 cells. It presents good linear between 3 to 5000 μg L −1 and the limits of detection (in HPLC analysis with UV detection) are 1–4 μg L −1 . Good recoveries of 85–101% were obtained with spiked HepG2 cells samples, with relative standard deviation of ≤9.9%. Schematic for the preparation of boronic acid modified graphene oxide/melamine sponge composite for in-syringe solid-phase extraction of nucleosides.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2018 · IF 3.115

Ethanolic extract of Cordyceps cicadae exerts antitumor effect on human gastric cancer SGC-7901 cells by inducing apoptosis, cell cycle arrest and endoplasmic reticulum stress

Hongqing Xie,Xiaotong Li,Yajie Chen,Mingzi Lang,Zhangfei Shen,Liangen Shi

Ethnopharmacological relevance Cordyceps cicadae (Miq.) Massee is a traditional Chinese medicine that has been used for approximately 1600 years in China. C. cicadae , a member of the Cordyceps genus, exerts a therapeutic effect on many diseases, such as cancer. Objective This study aimed to evaluate the antineoplasmic activity of C. cicadae and to identify its molecular mechanism of cell death. Materials and methods The toxicity of the ethanolic extract of C. cicadae (EEC) against different cancer cell lines was determined through MTT assay. Human gastric cancer SGC-7901 cells were treated with EEC for 48 h. Cell morphology was examined by using an Olympus phase-contrast microscope. The cell apoptosis was quantified through Annexin V-FITC/PI staining. Cells were stained with PI and then subjected to flow cytometry for the investigation of cell cycle status. Cells were subjected to mitochondrial membrane potential (MMP) assay after incubation with JC-1 probes and to intracellular Ca 2+ measurement through flow cytometry after incubation with Fluo-3 AM fluorescent probes . Western blot analysis was conducted to quantify the expression of proteins related to apoptosis, cell cycle and endoplasmic reticulum stress. High-performance liquid chromatography (HPLC) analysis was performed to analyse the biological activity components of EEC. Results EEC suppressed the proliferation of SGC-7901 cells and induced the development of abnormal morphological features in a dose-dependent manner. Flow cytometry results indicated that EEC treatment caused cell apoptosis and arrested the cell cycle in the S phase. In addition, EEC treatment triggered MMP depolarization and Ca 2+ overloading in the cytosol of SGC-7901 cells. Western blot analysis demonstrated that EEC increased Bax, AIF, caspase-8, caspase-6 and caspase-3 activities and decreased Bcl-2 activity. The release of cytochrome c from mitochondria was associated with mitochondrial dysfunction, which was caused by the activation of the cell surface receptor Fas and the cleavage of PARP . EEC-induced S phase arrest was associated with the up-regulation of E2F1, cyclin A2 , cyclin E and p53 expression levels and the down-regulation of CDK2 expression. In addition, EEC increased the expression of endoplasmic reticulum stress-related proteins, such as calpain-1, caspase-12 and caspase-9. HPLC assay results suggested that EEC contained adenine , uridine , adenosine and N6-(2-Hydroxyethyl)-adenosine. Conclusion EEC inhibited the proliferation of SGC-7901 cells by inducing caspase-dependent apoptosis, arresting the cell cycle in the S phase and increasing endoplasmic reticulum stress. This study revealed that C. cicadae is a potential natural source of anticancer drugs .

CAS / MDL: 73-24-5 58-61-7 58-96-8
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2018 ·Vol. 185 ·期 10 ·1-7 · IF 5.705

Colorimetric adenosine aptasensor based on DNA cycling amplification and salt-induced aggregation of gold nanoparticles

Kong Caiyun,Gao Linna,Chen Zhengbo

An aptamer based assay is described for the colorimetric detection of adenosine. The presence of adenosine triggers the deformation of hairpin DNA oligonucleotide (HP1) containing adenosine aptamer and then hybridizes another unlabeled hairpin DNA oligonucleotide (HP2). This leads to the formation of a double strand with a blunt 3′ terminal. After exonuclease III (Exo III)-assisted degradation, the guanine-rich strand (GRS) is released from HP2. Hence, the adenosine-HP1 complex is released to the solution where it can hybridize another HP2 and initiate many cycles of the digestion reaction with the assistance of Exo III. This leads to the generation of a large number of GRS strands after multiple cycles. The GRS stabilize the red AuNPs against aggregation in the presence of potassium ions. If, however, GRS forms a G-quadruplex, it loses its ability to protect gold nanoparticles (AuNPs) from salt-induced AuNP aggregation. Therefore, the color of the solution changes from red to blue which can be visually observed. This colorimetric assay has a 0.13 nM detection limit and a wide linear range that extends from 5 nM to 1 μM. Schematic presentation of a colorimetric aptamer biosensor for adenosine detection based on DNA cycling amplification and salt-induced aggregation of gold nanoparticles.

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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2018 · IF 2.831

Succinic acid enhanced quantitative determination of blood modified nucleosides in the development of diabetic nephropathy based on hydrophilic interaction liquid chromatography mass spectrometry

Mengzhe Guo,Dantong Liu,Qian Sha,Houfa Geng,Jun Liang,Daoquan Tang

The epigenetic modification of DNA or RNA may have relationship with the development of diabetic nephropathy (DN). We designed to develop a liquid chromatography mass spectrometry (LC–MS) coupled with mobile phase additive sensitization method for the analysis of the dissociative epigenetic modified nucleosides in serum of patients from different periods of DN with the health comparison. Serum samples were collected from 43 healthy volunteers and 156 patients, which divided into four groups. A succinic acid enhanced LC–MS/MS strategy was developed for the quantitative analysis of seven nucleosides in serum samples. The signal intensity of seven nucleosides increased three to seven times, respectively. A series of statistical analysis were carried out to demonstrate the dynamic changes of modified nucleosides in four groups. This method showed good specific, accuracy, and stability. The results were calibrated and presented through the formation of m 6 A/C, I/C, 5-mdC/C, 5-mC/C, pseU/U to eliminate the individual and age differences. The m 6 A/C, I/C, and pseU/U were found having the dynamic changes in four groups ( p   <  0.05). And these five modified nucleosides can also used as one parameter to distinguish these four groups by ROC and LDA analysis. Additionally, they were found to be connected with several clinical biochemical indexes through multiple linear regression analysis. Our LC–MS/MS method assay successfully quantifies the modified nucleosides in serum. And three modified nucleosides can act as the potential biomarkers to describe the development of DN and help to evaluate the diagnosis, treatment, and prognosis of DN in clinical.

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JOURNAL OF CHROMATOGRAPHY A · 2018 · IF 3.716

Monolithic column with polymeric deep eutectic solvent as stationary phase for capillary electrochromatography

Rong Wang,Zhenkun Mao,Zilin Chen

A novel monolithic column based on the copolymerization of ethylene dimethacrylate and a deep eutectic solvent (DES), which composed of chlorocholine chloride and itaconic acid, was developed for capillary electrochromatography (CEC). The structure and morphology of the obtained monolithic column was characterized by Fourier transform infrared spectra and scanning electron microscopy, which showed a porous monolithic structure with good permeability. The influence of pH value and acetonitrile content on electroosmotic flow (EOF) of DES-based monolithic column was investigated. The DES-based monolithic column was used as the separation column of CEC and exhibited excellent performance for the separation of neutral compounds, phenols, toluidines, nucleosides, nucleotide bases and alkaloids. The retention mechanism might be attributed to synergistic effect of hydrophobic interaction, hydrogen bond interaction and electronic interaction. The DES-based monolithic column showed good repeatability with relative standard deviations of migration time less than 0.80%, 2.15%, 4.26% and 3.08% for intra-day, inter-day, column-to-column and batch-to-batch, respectively. Thus, organic polymer monolithic columns with DESs as functional monomers are a promising option in chromatographic separation.

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JOURNAL OF CHROMATOGRAPHY A · 2014 · IF 4.258

Influence of the crosslinker type on the chromatographic properties of hydrophilic sulfoalkylbetaine-type monolithic columns

Chusheng Liu,Weijia Chen,Guangxin Yuan,Yao Xiao,Jacques Crommen,Shihai Xu,Zhengjin Jiang

In order to investigate the effects of the crosslinker on the separation performance of polar zwitterionic sulfoalkylbetaine-type monolithic columns, three crosslinkers, i.e. 1,4-bis(acryloyl)piperazine (PDA), ethylene dimethacrylate (EDMA) and N , N ′-methylenebisacrylamide (MBA), were copolymerized with the hydrophilic monomer N , N -dimethyl- N -acryloyloxyethyl- N -(3-sulfopropyl)ammonium betaine (SPDA). The chromatographic properties of the three hydrophilic sulfoalkylbetaine-type monolithic columns, including column efficiency, permeability, porosity and separation mechanism, were systematically compared using scanning electron microscopy or micro-HPLC. Good selectivity in micro-HPLC separations was achieved on all three monolithic columns. The results indicate that the polarity of sulfoalkylbetaine-type monolithic columns may be related to the polarity of the crosslinker, which further affects column selectivity and efficiency. A particularly high column efficiency (100,000 plates/m) was obtained on the novel poly(SPDA- co -PDA) monolithic column at a linear velocity of 1   mm/s using thiourea as test analyte. A higher resolution was also observed for nucleobases, nucleosides and hydrophilic organic acids on this novel poly(SPDA- co -PDA) monolithic column compared to the other two columns.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2014 · IF 3.511

Click N-benzyl iminodiacetic acid: Novel silica-based tridentate zwitterionic stationary phase for hydrophilic interaction liquid chromatography

Wei Yin,Huihui Chai,Renhua Liu,Changhu Chu,John A. Palasota,Xiaohui Cai

Iminodiacetic acid (IDA) is dicarboxylic acid amine, which may produce stronger interaction with polar or charged compounds than bidentate α,β-amino acid. In this article, a novel type of tridentate zwitterionic HILIC stationary phase was prepared by covalently bonding N-benzyl IDA on silica gel via copper( I ) catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). The structure of this stationary phase and all related intermediates was confirmed by NMR, FT-IR, MS spectrum and elemental analysis . The new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 44000 plates m −1 in the case of guanosine) in the application of separation of polar compounds, including organic acids , organic bases, as well as highly polar and hydrophilic compounds, such as cephalosporins and carbapenems . Most of them displayed good peak shape and selectivity.

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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2015 ·Vol. 407 ·期 12 ·3525-3529 · IF 3.436

Synthesis of boronic-acid-functionalized magnetic attapulgite for selective enrichment of nucleosides

Cheng Ting,Li Huihui,Ma Ying,Liu Xiaoyan,Zhang Haixia

2,4-Difluoro-3-formyl-phenylboronic acid (DFFPBA)-modified magnetic attapulgite (ATP-Fe 3 O 4 -NH 2 -DFFPBA) was synthesized and employed to capture and enrich cis -diol-containing biomolecules. The resulting material exhibited a high saturation magnetization value of 20.71 emu/g, allowing the absorbent to be conveniently magnetically separated. Combining the Fe 3 O 4 nanoparticles with the high specific surface area of attapulgite yielded a material with a high capture capacity (13.78 mg/g) for adenosine. Furthermore, ATP-Fe 3 O 4 -NH 2 -DFFPBA was found to possess remarkable selectivity for adenosine at a low molar ratio of adenosine/2-deoxyadenosine (1:500). The potential applications of this material were explored by using it to extract five nucleosides from urine samples, and the results demonstrate that it can decrease matrix interference and selectively enrich analytes. Boronic-acid-functionalized magnetic attapulgite could selectively enrich the nucleosides in urine samples with the help of an external magnet

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BIOSENSORS & BIOELECTRONICS · 2015 · IF 6.409

Ultrasensitive and universal fluorescent aptasensor for the detection of biomolecules (ATP, adenosine and thrombin) based on DNA/Ag nanoclusters fluorescence light-up system

Ying Zhu,Xiao-chun Hu,Shuo Shi,Ru-ru Gao,Hai-liang Huang,Yan-yan Zhu,Xiao-yan Lv,Tian-ming Yao

We report here an ultrasensitive strategy based on the recognition-induced conformational alteration of aptamer and fluorescence turn-on abilities of guanine-rich (G-rich) DNA sequence in proximity to silver nanoclusters for adenosine triphosphate (ATP), adenosine (A) and thrombin (TB) detection. Herein, we designed two tailored DNA sequences noted as complementary DNA (abbreviated as c-DNA) and signal probe DNA (abbreviated as s-DNA), respectively. c-DNA is designed as a special structure consisting of a sequence complementary to aptamer at the 3′-end and a guanine-rich DNA sequence at the 5′-end; s-DNA contains a cytosine-rich sequence responsible for Ag NCs templated synthesis at the 3′-end and a link sequence (part of aptamer) complementary to partial of the c-DNA at the 5′-end. In the presence of target, the aptamer associated with the target, resulting in the formation of duplex DNA (dsDNA), the DNA–Ag NCs thereafter could close to the guanine-rich sequence, leading to enhanced fluorescence signal readout. The widespread application of the sensing system is achieved success in the detection of three biomolecules . ATP, adenosine and thrombin in the range of 0.5-8.0   μM, 0.5-7.0   μM and 50-900   nM could be linearly detected with the detection limits of 91.6   nM, 103.4   nM and 8.4   nM, respectively. This label-free and turn-on fluorescent sensing system employing the mechanism proposed here turns out to be sensitive, selective, and convenient for the detection of biomolecules without washing and separation steps.

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ANALYTICA CHIMICA ACTA · 2015 · IF 4.513

The preparation of high-capacity boronate affinity adsorbents by surface initiated reversible addition fragmentation chain transfer polymerization for the enrichment of ribonucleosides in serum

Chaozhan Wang,Huanhuan Xu,Yinmao Wei

Boronate affinity adsorption is uniquely selective for cis-diol-containing molecules. The preparation and application of boronate affinity materials has attracted much attention in recent years. In this work, a high-capacity boronate affinity adsorbent was prepared by surface-initiated reversible addition–fragmentation chain transfer polymerization (SI-RAFT). Commercial aminated poly(glycidyl methacrylate) (PGMA) microspheres were modified with the chain transfer agent (CTA) S-1-dodecyl-S-(α,α-dimethyl-α-acetic acid)trithiocarbonate (DDATC). Boronate-affinity adsorbents were then prepared via SI-RAFT polymerization employing 3-acrylamidophenylboronic acid (AAPBA) as the monomer . The Fourier transform infrared spectroscopy (FT-IR), nitrogen adsorption and desorption measurements have proven the successful grafting of AAPBA on PGMA microspheres surface. The boronate affinity adsorbents thus prepared possess much higher adsorption capacity (99.2 µmol/g of adenosine) and both faster adsorption and desorption speed towards ribonucleosides , the adsorption and desorption could be completed in 2 min. The high selectivity of the adsorbents to ribonucleosides was verified in the presence of a large excess of deoxynucleosides. The boronate affinity adsorbents were then employed for sample pretreatment before HPLC analysis of ribonucleosides in serum. The ribonucleosides were effectively enriched by boronate affinity dispersive solid-phase extraction (BA-DSPE), with high mass recoveries and good precision. The simultaneous determination of uridine and guanosine in calf serum was achieved by utilizing the standard addition method, their contents were determined to be 170 ± 11.6 ng/mL and 39.6 ± 4.4 ng/mL respectively. The results proved that the prepared boronate affinity materials could be applied for sample pretreatment of cis-diol containing molecules in biological samples.

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