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Food & Function · 2019 ·Vol. 10 ·期 6 ·3379-3385 · IF 3.241

Effects of Yak skin gelatin on platelet activation

Qi Chen,Hongxia Yang,Yan Li,Xiaoxi Wang,Lixin Wei,Yuzhi Du

Studies have shown that gelatin is not only a good hemostatic material, but also a food additive with potentially broad use. Yak skin gelatin is a new gelatin resource, but its oral coagulant effects have not been studied. Given the central role of platelets in hemostasis, in this study we examined the pharmacodynamical differences between different molecular Yak skin gelatins on platelet activation. The hemostatic effects of Yak skin gelatins with different molecular weight distributions were evaluated for bleeding time (BT), clotting time (CT), and platelet activity by measuring the contents of P-selectin, platelet membrane glycoprotein Ia/IIa (GP Ia/IIa), platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa), and platelet membrane glycoprotein IV (GP IV). Intragastric administration of Yak skin gelatin resulted in a significant reduction in CT and BT, and an increase in the contents of P-selectin, GP Ia/IIa, GP IIb/IIIa, and GP IV in all groups in comparison with the control group. The strongest activation of platelets by Yak skin gelatin was observed with size between 0.1 μm and 0.22 μm, and activation may have been in response to improving GP IIb/IIIa and GP IV levels. When measuring the levels of an established indicator of platelet activation, platelet activation-dependent granule membrane protein (CD62P), its promotion was observed for all molecular weight ranges of Yak skin gelatins. In brief, Yak skin gelatin has hemostatic effects, and Yak skin gelatin fractions between 0.1 μm and 0.22 μm are the primary effectors of hemostasis via promoting platelet membrane glycoprotein activities and strengthening platelet function.

研究领域: 药理学 · 止血 · 血小板功能
✓ 已验证 DOI PubMed 高影响因子
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CLINICA CHIMICA ACTA · 2021 · IF 3.786

Proteomic screening of potential N-glycoprotein biomarkers for colorectal cancer by TMT labeling combined with LC-MS/MS

Qian Gong,Xiuming Zhang,Aifeng Liang,Sinian Huang,Guangang Tian,Mengjiao Yuan,Qing Ke,Yijun Cai,Bin Yan,Jin Wang,Jinjin Wang

Background and aims Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. Methods This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. Results The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues( P  < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. Conclusion The ICAM1 and APMAP may serve as a potential tumor marker for CRC.

研究领域: 肿瘤学 · 蛋白质组学 · 医学
✓ 已验证 DOI PubMed 高影响因子
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CURRENT DRUG METABOLISM · 2024 ·Vol. 25 ·期 5 ·317-329 · IF 2.1

Role of P-glycoprotein in Regulating the Efficacy, Toxicity and Pharmacokinetics of Yunaconitine

Xiaocui Li,Qi Liang,Caiyan Wang,Huawei Qiu,Tingting Lin,Wentao Li,Rong Zhang,Zhongqiu Liu,Lijun Zhu

BackgroundYunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear.ObjectiveThe objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC.MethodsThe efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice.ResultsThe presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco-2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice.ConclusionYAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.

研究领域: 药理学 · 毒理学 · 中药学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CARBOHYDRATE CHEMISTRY · 2018 · IF 0.629

Detection of glycan-binding proteins using glycan-functionalized quantum dots and gold nanoparticles

Zhenxing Zhang,Xiaoxiao Qi,Jinfeng Chai,Peixing Wu,Xun Lv,Shuihong Cheng,Xuebing Li

Many pathogens can use their glycan-binding proteins (GBPs) to interact with glycan receptors on host cell surface. Here, a novel strategy is presented for the detection of GBPs based on fluorescence resonance energy transfer (FRET). Using mannose-functionalized quantum dots and mannose-functionalized gold nanoparticles, a FRET assay system was developed and a mannose-specific GBP concanavalin A could be detected in 5 min with a detection limit of 3 nM. This result indicated the potential for rapid and sensitive biosensing of various kinds of GBPs and pathogens by changing the glycan structure on the surface of QDs and AuNPs.

CAS / MDL: 16961-25-4 68-04-2
研究领域: 生物化学 · 纳米医学
✓ 已验证 产品关联 DOI 高影响因子
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Science China-Chemistry · 2015 ·Vol. 58 ·期 6 ·1056-1064 · IF 1.695

Polydopamine-mediated immobilization of phenylboronic acid on magnetic microspheres for selective enrichment of glycoproteins and glycopeptides

Zheng Jiangnan,Lin Zian,Zhang Lan,Yang Huanghao

In this work, we demonstrate for the first time, a method to synthesize phenylboronic acid-Fe 3 O 4 @polydopamine (Fe 3 O 4 @PDA-PBA) magnetic microspheres via the combination of mussel-inspired polydopamine coating and click chemistry. Uniform-size and core-shell structured Fe 3 O 4 @PDA-PBA magnetic microspheres with a core diameter of ∼240 nm and a shell thickness of ∼13 nm were obtained as identified by the characterization of the morphology, structure and composition of the synthesized microspheres. We evaluated the selectivity and binding capacity of the Fe 3 O 4 @PDA-PBA magnetic microspheres by using standard glycoproteins (ovalbumin, immunoglobulin G and catalase) and nonglycoproteins (human serum albumin, bovine hemoglobin, myoglobin, lysozyme, and ribonuclease A) as model proteins. Adsorption experiments, SDS-PAGE and mass spectrometry analysis demonstrated that the Fe 3 O 4 @PDA-PBA magnetic microspheres had much high binding capacity and selectivity for glycoproteins/glycopeptides compared to nonglycoproteins/nonglycopeptides. In addition, the practicability of the Fe 3 O 4 @PDA-PBA magnetic microspheres was further assessed by selective capture of glycoproteins from healthy human serum. The good results demonstrated its potential in glycoproteome analysis.

CAS / MDL: 25322-68-3 134-03-2
研究领域: 生物化学 · 分析化学 · 材料科学
✓ 已验证 产品关联 DOI 高影响因子
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Aptamer biorecognition and gold nanoshell-mediated fluorescence quenching for glycoprotein analysis and breast cancer diagnosis

Xingjie Wu,Hong Liu,Jialin Chen,Ling Tao,Shi Zhou,Xiangchun Shen

In recent years, glycoproteins have gained increasing attention due to their pivotal roles in cellular chemistry and signal transduction. However, the limited availability of rapid and wash-free analytical tools has impeded their utilization as circulating biomarkers for disease diagnosis in clinical settings. To address this challenge, we developed a gold nanoshell-mediated method for analyzing glycoprotein composition directly in native biofluids. Initially, glycoproteins are captured at the micelle surface through aptamer-protein interactions and were labeled with fluorescent lectin. Subsequently, the fluorescence of the lectin is locally quenched by the in-situ formation of gold nanoshell on micelle surface, while free-floating lectin remains unresponsive throughout this process. After optimizing the HAuCl 4 dosage for gold nanoshell formation, we achieved rapid and strong fluorescence quenching against fluorescent lectin captured at micelle surface. Using this method, we analyzed the glycan compositions of CEA, HER2 and MUC1 with fluorescent ConA, Jacalin, LCA and PHA. The analyzing results demonstrated that our method can discriminate between glycoprotein compositions of plasma samples obtained from breast cancer patients and those from healthy donors.

研究领域: 生物化学 · 医学诊断 · 纳米技术
✓ 已验证 产品关联 DOI 高影响因子
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ANALYTICAL CHEMISTRY · 2024 · IF 6.7

Glycan-Evocated Metallization for Amplification-Free Electrochemical Detection of Glycoproteins at Low Concentration Levels

Junpeng Lv,Di Wu,Yingming Ma,Xiyao Zhang,Wenhui Xu,Mengge Wang,Songmin Chen,Qiong Hu,Dongxue Han,Li Niu

Glycoproteins have become the most often screened tumor markers in the in vitro diagnostics. Although a large number of electrochemical methods have been proposed to sensitively detect glycoproteins, most of them involve the aid of laborious signal amplification. Herein, we report the use of glycan-evocated metallization (GlyMetal) for the amplification-free electrochemical detection of glycoproteins at low concentration levels. Briefly, the glycoproteins of interest are captured by an aptamer recognition layer, and then the glycans of targets are oxidized by NaIO4 to convert the 1,2-diol sites into aldehyde groups for the silver deposition-based metallization, followed by the electrochemical stripping assay of the deposited metallic silver for glycoprotein quantification via the established solid-state Ag/AgCl voltammetric process. As GlyMetal can enable the deposition of a large amount of metallic silver and a high signal-to-background ratio can be obtained for the solid-state Ag/AgCl voltammetric stripping assay, the developed GlyMetal-based electrochemical method is applicable to the amplification-free detection of glycoproteins. As a proof of concept, a detection limit of 1.65 pg/mL has been achieved for carcinoembryonic antigen (CEA) detection. In addition to the high selectivity, desirable results have been obtained with respect to the use of the method for CEA detection in serum samples. In consideration of the desirable simplicity, short assay time, and cost-effectiveness of the amplification-free approach, the GlyMetal-based electrochemical method shows great promise in the point-of-care detection of glycoproteins.

CAS / MDL: 7447-40-7 93572-42-0
研究领域: 生物化学 · 医学诊断 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICA CHIMICA ACTA · 2020 · IF 5.977

N-glycan structures of target cancer biomarker characterized by two-dimensional gel electrophoresis and mass spectrometry

Sha Liu,Xiaoteng Jiang,Zhi Shang,Yin Ji,Huiyu Wang,Zeyuan Wang,Peng Wang,Yan Zhang,Hua Xiao

Glycoproteins are important biomarkers for cancers, while most glycoproteomics biomarkers suffering from low sensitivity and specificity due to their uncharacterized glycan structures. AZGP1 is a potential biomarker for salivary diagnostics of lung cancer, which is used as a model glycoprotein in this study for method development. We initially analyzed salivary N-glycoproteome by using lectin affinity chromatography and more than 300 N-glycoproteins were identified, including AZGP1. 7 gel spots of AZGP1 were resolved by two-dimensional gel electrophoresis and further confirmed by two-dimensional western blot as well as mass spectrometry. The isomeric glycan structures of AZGP1 in these spots were systematically characterized both at composition level and at structure level. Our results revealed 10 glycan compositions for salivary AZGP1, including core fucosylated glycans on Asn128 and sialylated glycans on Asn109 and Asn112. We further compared the glycan structures of salivary AZGP1 from lung cancer group and control group. Accordingly, 14 and 7 potential glycan structures were successfully revealed, respectively. In total, 15 glycan compositions and 22 potential glycan structures were identified and characterized for AZGP1, including some different structures with the same compositions. In particular, 5 potential glycan structures were identified as lung cancer unique signatures. Our developed strategy holds promise for thorough identification of glycan structures on a target glycoprotein biomarker. In-depth characterization of its glycan structures will ultimately enhance its sensitivity and specificity for cancer detection.

研究领域: 生物化学 · 癌症研究 · 蛋白质组学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2013 ·Vol. 10 ·期 7 ·1379-1386 · IF 7.823

Benzoboroxole-Functionalized Magnetic Core/Shell Microspheres for Highly Specific Enrichment of Glycoproteins under Physiological Conditions

Yuting Zhang,Wanfu Ma,Dian Li,Meng Yu,Jia Guo,Changchun Wang

Efficient enrichment of specific glycoproteins from complex biological samples is of great importance towards the discovery of disease biomarkers in biological systems. Recently, phenylboronic acid-based functional materials have been widely used for enrichment of glycoproteins. However, such enrichment was mainly carried out under alkaline conditions, which is different to the status of glycoproteins in neutral physiological conditions and may cause some unpredictable degradation. In this study, on-demand neutral enrichment of glycoproteins from crude biological samples is accomplished by utilizing the reversible interaction between the cis -diols of glycoproteins and benzoboroxole-functionalized magnetic composite microspheres (Fe 3 O 4 /PAA-AOPB). The Fe 3 O 4 /PAA-AOPB composite microspheres are deliberately designed and constructed with a high-magnetic-response magnetic supraparticle (MSP) core and a crosslinked poly(acrylic acid) (PAA) shell anchoring abundant benzoboroxole functional groups on the surface. These nanocomposites possessed many merits, such as large enrichment capacity (93.9 mg/g, protein/beads), low non-specific adsorption, quick enrichment process (10 min) and magnetic separation speed (20 s), and high recovery efficiency. Furthermore, the as-prepared Fe 3 O 4 /PAA-AOPB microspheres display high selectivity to glycoproteins even in the E. coli lysate or fetal bovine serum, showing great potential in the identify of low-abundance glycoproteins as biomarkers in real complex biological systems for clinical diagnoses.

研究领域: 生物化学 · 分析化学 · 医学诊断
✓ 已验证 DOI PubMed 高影响因子
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PLoS One · 2025 ·Vol. 20 ·期 5 ·e0322835 · IF 2.6

The plant matrix of Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Fujie Xu,Xiaohang Shan,Jialin Li,Jing Li,Jiqiao Yuan,Daozeng Zou,Manyuan Wang

Artemisinin-based combination therapies (ACTs) constitute the principal strategy for combating malaria in contemporary times, and research into the multifaceted components of Artemisia annua L. ( A. annua ) has garnered widespread interest among scientists. The aim of this study was to prepare A. annua extracts (nACTs) and to explore whether nACTs have higher bioavailability and efficacy than artemisinin (ART) alone due to its multiple bioactive components. Initially, the in vivo antimalarial activity of nACTs was evaluated by two murine malaria models. The results revealed that the antimalarial effect of nACTs was about 10-fold higher than that of ART alone when administered at the same dosage of ART. Then, we analyzed the pharmacokinetic characteristics of nACTs in rat plasma. Remarkably, nACTs exhibited significantly enhanced oral bioavailability, longer half-life as well as extended mean retention time in rats. In addition, the impact of nACTs on P-glycoprotein (P-gp) was evaluated using the Caco-2 cell line. The results showed that both ART and nACTs reduced the efflux rate of the P-gp substrate rhodamine 123 (R123) and induced the expression of P-gp in Caco-2 cells over a range of concentrations. nACTs had certain components-deoxyartemisinin (DEART), artemisinic acid (AA), and dihydroartemisinic acid (DHAA)-that inhibited the efflux and translocation of P-gp and facilitated the reduction of ART efflux. In conclusion, A. annua extracts significantly improved the antimalarial efficacy and bioavailability compared with ART.

CAS / MDL: 8001-22-7
研究领域: 药理学 · 寄生虫学 · 植物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICA CHIMICA ACTA · 2017 · IF 4.95

Detection of glycoprotein through fluorescent boronic acid-based molecularly imprinted polymer

Jing-ru Wei,Yan-li Ni,Wei Zhang,Zhi-qi Zhang,Jing Zhang

A novel strategy based on the fluorescent molecularly imprinted polymers (FMIP) for specific recognition and sensitive sensing glycoprotein from biological samples was developed. The FMIP prepared by introducing a fluorescent boronic acid quinoline-based on the P GMA/EDMA bead surface and assembled a glycoprotein molecularly imprinted polymer using surface imprinting technology . The resultant material showed specific recognition to model glycoprotein. At the same time, the change of fluorescence caused by the amount of model glycoprotein could achieve quantitative determination . The method provided a good linear relationship of the concentrations of HRP in the range of 0.05–1 μM, and the detection limit was 0.02 μM. It is 10 times lower than the previous fluorescence nanosensor for glycoprotein. The established method combined the desired selectivity of molecularly imprinted polymers and high sensitivity of fluorescence spectroscopy . The influence of background impurities could be effectively eliminated. The outstanding features guarantee that it can be successfully applied to detect glycoprotein from biological samples under physiological conditions.

研究领域: 生物化学 · 分析化学
✓ 已验证 DOI PubMed 高影响因子
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-14 · IF 15.7

Mutant glycosidases for labeling sialoglycans with high specificity and affinity

Liang Shuyu,Tang Qi,Guo Xunzi,Li Zi’an,Guo Yilan,Chang Jinghan,Cheng Bo,Song Qitao,Sun Jiayu,Dai Peng,Chen Xing

Affinity labeling of biomacromolecules is vital for bioimaging and functional studies. However, affinity probes recognizing glycans with high specificity remain scarce. Here we report the development of glycan recombinant affinity binders (GRABs) based on mutant bacterial sialidases, which are enzymatically inactive but preserve stringent specificity for sialoglycan substrates. By mutating a key catalytic residue of Streptococcus pneumoniae neuraminidase A ( Sp NanA) and Ruminococcus gnavus neuraminidase H ( Rg NanH), we develop GRAB-Sia and GRAB-Sia3 recognizing total sialoglycans and α2,3-sialosides, respectively. The GRABs exhibit strict substrate and linkage specificity, and tetramerization with streptavidin substantially increases their avidity. The GRABs and tetrameric GRABs (tetra-GRABs) are effective tools for probing sialoglycans in immunoblotting, flow cytometry, immunoprecipitation, and fluorescence imaging. Furthermore, multiplex analysis with tetra-GRABs uncovers spatially distinct sialoglycans in the various mouse organs. This work provides a versatile toolkit for labeling and analyzing sialoglycans with high specificity, sensitivity, and convenience.

CAS / MDL: 131-48-6
研究领域: 生物化学 · 分子生物学 · 医学研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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