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COLLOIDS AND SURFACES B-BIOINTERFACES · 2020 · IF 4.389

Enhanced cellular osteogenic differentiation on CoFe2O4/P(VDF-TrFE) nanocomposite coatings under static magnetic field

Bolin Tang,Xiaojun Shen,Yaru Yang,Zhi Xu,Jie Yi,Yongbo Yao,Miao Cao,Yalin Zhang,Hongqin Xia

Cellular responses can be regulated and manipulated through combining stimuli-responsive biomaterial with external stimulus. In this present, the magneto-responsive CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were designed to understand cell behaviors of preosteoblasts, as well as get insight into the underlying mechanism of osteogenic differentiation under static magnetic field (SMF). CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings with differential magnetic property (low, medium and high magnetization) were prepared by incorporation of different mass fraction of CoFe 2 O 4 nanoparticles (6%, 13 %, 20 %) into P(VDF-TrFE) matrix. Cell experiments indicated that all nanocomposite coatings with the assistance of SMF could promote the cell attachment, proliferation and osteogenic differentiation of MC3T3-E1 cells. Among different nanocomposite coatings, low magnetization coating (6%) showed a higher ALP activity and gene expression of Runx2, Col-I, OCN. Molecular biology assays demonstrated that the combination of nanocomposite coatings and SMF could significantly up-regulate the expression level of α2β1 integrin and p-ERK. Whereas, the addition of inhibitor U0126 down-regulated sharply the expression level of p-ERK, which indicated that cellular osteogenic differentiation of MC3T3-E1 cells was governed through α2β1 integrin-mediated MEK/ERK signaling pathways during CoFe 2 O 4 /P(VDF-TrFE) nanocomposite coatings were combined with SMF. This work provided a promising strategy to enhance cellular osteogenic differentiation through a remote-control manner, which exhibited great potential in the application of bone tissue repair and regeneration.

研究领域: 生物材料 · 组织工程 · 细胞生物学 · 磁性材料 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Food & Function · 2017 ·Vol. 8 ·期 9 ·3259-3270 · IF 3.247

The anti-obesity properties of the proanthocyanidin extract from the leaves of Chinese bayberry (Myrica rubra Sieb.et Zucc.)

Xiaozhou Zhou,Shiguo Chen,Xingqian Ye

The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.

CAS / MDL: 121-33-5
研究领域: 药理学 · 营养学 · 分子生物学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2024 · IF 3.8

Reversible addition-fragmentation chain transfer enhanced aggregation signal-on fluorescence detection of alkaline phosphatase

Yu Shuaibing,Li Lianzhi,Kong Qiyun,Zhang Wenqi,Chen Huan,Zhang Xueji,Kong Jinming

The instability of the signal intensity of fluorescent biosensors and the false signals have been significant factors affecting the performance of biosensors. Herein, a novel signaling system is devised through the application of reversible addition-fragmentation chain transfer (RAFT) polymerization with monomers containing the tetraphenylethylene (TPE) groups. TPE exhibits an aggregation-induced emission (AIE) phenomenon in certain solvents, mainly due to the blockage of the rotation of its four benzene rings, which also exist in the aggregated state. With this property, a series of molecules are modified based on click chemistry for RAFT polymerization using Fe 3 O 4 magnetic beads as the carriers, and stable aggregated luminescent TPE polymers are formed on the surface of magnetic beads to realize the transformation of fluorescence signal from “0” to “1”. In addition, the fluorescence signal demonstrates a positive correlation with alkaline phosphatase (ALP) activity, which can be quantified by measuring the fluorescence intensity. The biosensor exhibits high sensitivity and good linearity in the range of 0.1–5 U/L, with a LOD of 0.079 U/L. Furthermore, the designed strategy demonstrated satisfactory performance in the quantitative determination of ALP activity in serum samples, indicating that the signaling system developed by combining RAFT polymerization and AIE molecules has an important application in the field of fluorescent biosensors. Graphical Abstract

研究领域: 分析化学 · 生物技术 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MACROMOLECULAR MATERIALS AND ENGINEERING · 2018 ·Vol. 303 ·期 7 ·1800130 · IF 2.69

Development of Electrospun Composite Fibers in Multiscale Structure and Investigating the Performance on Proliferation and Osteogenic Differentiation of ADSCs

Liuyang Xuan,Ming Shi,Shuangshuang Ma,Feng Ye,Xuetao Shi,Ling Yan,Yan Li

Electrospun composite membranes in multiscale structures are developed for bone tissue engineering. Aligned polycaprolactone (PCL) fibers entrapping CA-HAp microparticles (containing CaCO 3 , hydroxyapatite, and casein in a hierarchical organization) are electrospun to find whether synergistic effects of fiber alignment and CA-HAp microparticles on improving osteogenic differentiation can be obtained. CA-HAp microparticles are in a spherical morphology of 1.42 ± 0.26 µm. Their presence increases fiber diameter and does not significantly affect fiber alignment. On all membranes, adipose derived stem cells (ADSCs) from humans spread very well. On a random group, cells distribute randomly and the presence of CA-HAp microparticles facilitates cell proliferation, especially for the one at CA-HAp/PCL 50 wt%; the one at CA-HAp/PCL 20 wt% shows significantly much higher alkaline phosphatase (ALP) activity (112.0% higher) than the pure PCL membrane. On aligned samples, cells align along fibers and expression of ALP is enhanced. However, at the same composition (CA-HAp/PCL 20 wt%), the random sample has much higher ALP activity than the aligned sample. The expressions of osteogenic marker genes are also evaluated. Combining the results and the applicability of membranes together, the random membrane at CA-HAp/PCL 20 wt% is the best candidate for bone tissue engineering.

CAS / MDL: 25988-63-0
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 干细胞研究
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Nanoscale · 2017 ·Vol. 9 ·期 7 ·2640-2645 · IF 7.367

An enzyme-induced Au@Ag core–shell nanoStructure used for an ultrasensitive surface-enhanced Raman scattering immunoassay of cancer biomarkers

Lin Yang,Ming Xuan Gao,Lei Zhan,Min Gong,Shu Jun Zhen,Cheng Zhi Huang

Early detection of cancer is helpful for the control and prevention of diseases. Due to the low content of cancer biomarkers in the early disease phases, however, an ultrasensitive and selective method is critical. In this contribution, an ultrasensitive surface-enhanced Raman scattering (SERS) immunoassay is newly developed with the principle of introducing a common enzyme-induced deposition (EID) reaction to coat a silver layer on the surface of gold nanoparticles and to form a core–shell nanostructure of Au@Ag. By using alkaline phosphatase (ALP) to dephosphorylate its substrate, 2-phospho-L-ascorbic acid trisodium salt (AAP), to form vitamin C, silver ions could be reduced into silver atoms and coated on the surface of the AuNPs; a greatly enhanced SERS signal was then obtained. As a proof of concept, α-fetoprotein (AFP) was detected as a target, which is a biomarker of liver cancer. Excellent analytical performance of the SERS immunoassay could be achieved in the range from 0.5 to 100 pg mL−1 with a limit of detection of 0.081 pg mL−1 (3σ). Identical results could be obtained by using the newly proposed SERS immunoassay for the clinical detection of AFP in serum samples of patients to those clinically obtained by chemiluminescence immunoassays, demonstrating the potential applications of the developed method in clinical diagnosis.

研究领域: 生物技术 · 纳米技术 · 分析化学 · 癌症研究 · 医学诊断
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Stimuli-responsive colorimetric sensor based on bifunctional pyrophosphate-triggered controlled release and enhancing activity of CoOOH nanozyme

Yanyun Zou,Jinyang Chen,Qingli Chai,Ting Zhu,Shasha Zeng,Yucheng Liu

As a class of intelligent materials, stimuli-responsive hydrogels enable attractive sensors for sensitive and selective detection along with the potential for low production costs. Herein, we proposed a stimuli-responsive colorimetric sensor based on Cu 2+ -crosslinked alginate hydrogel loaded with CoOOH nanozyme. Upon binding of Cu 2+ to pyrophosphate ion (PPi), the hydrogel would be disassembled by PPi, which controlled the release of CoOOH nanoflakes . Interestingly and importantly, it was found that PPi and PPi-Cu 2+ could further enhance the catalytic activity of the released CoOOH nanozyme. Since alkaline phosphatase (ALP) can catalyze the hydrolysis of PPi to phosphate ion (Pi), a sensitive colorimetric sensor for ALP detection was constructed based on PPi-triggered controlled release and enhancing activity of CoOOH nanozyme. The as-constructed sensor exhibited good linear response to ALP over the range from 0.1 to 250 mU/mL with a detection limit of 0.07 mU/mL. Additionally, this sensor was also extended to measure two typical ALP inhibitors (Na 3 VO 4 and EDTA) with reasonable results. Last but not least, it was confirmed that the detection results of ALP in real serum samples with the proposed sensor were in accordance with the data from clinical test, which indicates the robustness and practicability of this stimuli-responsive colorimetric sensor.

研究领域: 材料科学 · 分析化学 · 生物传感器
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ADVANCED FUNCTIONAL MATERIALS · 2021 ·Vol. 31 ·期 42 ·2104418 · IF 18.808

Triple Enzyme-Regulated Molecular Hydrogels for Carrier-Free Delivery of Lonidamine

Can Wu,Chunlu Wang,Yaoyao Zheng,Yaxin Zheng,Ziqi Liu,Keming Xu,Wenying Zhong

Cancerous cells exhibit overexpression of multiple enzymes in various cellular compartments. These enzymes are often undruggable, yet display unique advantages in regulating intracellular self-assembly and dis-assembly of small molecules for cancer targeting. Herein, a self-assembling molecule (LND-1p-ES) for carrier-free delivery of lonidamine specifically to cancerous cells is designed, where LND-1p-ES executes as both a drug and a carrier with combined benefits thereof. Under the precise regulation of phosphatase (ALP) and esterase (CES), LND-1p-ES is capable of self-assembling intracellularly in a spatiotemporal manner, to confer lonidamine-borne nanofibers with enhanced cellular uptake. These nanofibers also facilitate controlled drug release with the aid of cellular proteases. Taking advantages of overexpressing ALP and CES as well as proteases in cancerous cells, the LND-1p-ES formulation demonstrates enhanced potency and selectivity against melanoma cells A375 in vitro and in vivo. In comparison, none/single enzyme responsive compounds fail to show a similar potency or selectivity, further confirming the indispensable roles of these enzymes in the delivery system. Collectively, the research provides a viable strategy to utilize multiple enzymes in cancerous cells for regulation of intracellular self-assembly, which can be expanded to design smart soft materials responsive to multiple biologically relevant biomolecules for enhanced therapeutic efficacy.

研究领域: 癌症研究 · 药物递送系统 · 生物医学工程 · 材料科学 · 药学
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RSC Advances · 2018 ·Vol. 8 ·期 27 ·14995-15000 · IF 2.936

A sensitive fluorescent probe for alkaline phosphatase and an activity assay based on the aggregation-induced emission effect

Wenjuan Zhang,Hanxiao Yang,Nan Li,Na Zhao

In this work, we report a fluorescent probe (TPEQN-P) for detecting alkaline phosphatase (ALP) with high sensitivity and monitoring its activity based on the specific aggregation-induced emission (AIE) effect. TPEQN-P can be constructed by conjugating the phosphate moiety into an AIE molecule (TPE-QI) through a reactive p-hydroxybenzyl group, which exhibits very weak emission in aqueous media due to its good water solubility. In the presence of ALP, TPEQN-P undergoes dephosphorylation and releases the hydrolysis product TPE-QI, which is intensely fluorescent because of its poor water solubility. The detection limit for ALP using TPEQN-P can be as low as 0.0077 U L−1 with a linear range of 0–30 mU mL−1 in solution. TPEQN-P also shows excellent applicability in serum samples, demonstrating potential applications in clinical diagnosis and biomedical research. TPEQN-P also can be applied for the determination of ALP activity and in ALP inhibitor screening.

CAS / MDL: 9048-46-8
研究领域: 分析化学 · 生物化学 · 分子生物学 · 临床化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2024 ·Vol. 191 ·期 11 ·1-9 · IF 5.3

MOF-mediated cascade reaction system for ultrasensitive detection of alkaline phosphatase activity and organophosphorus pesticides

Zhang Shengyuan,Yang Ying,Yang Dezhi,Yang Yaling

A metal–organic-framework (MOF) fluorescent sensor is reported based on NH 2 -MIL-101(Fe) propelled pesticide and alkaline phosphatase (ALP) catalytic reaction. Different from previous reports, a cascade reaction system combined with MOF structural changes to generate fluorescence was employed. The rationale is that ALP can hydrolyze L-ascorbic acid 2-phosphate (AAP) into L-ascorbic acid (AA), which can reduce Fe 3+ to decompose structurally NH 2 -MIL-101(Fe), resulting in 2-aminoterephthalic acid (NH 2 -BDC) with intense fluorescence. The  fluorescence can be decreased to different degrees due to inhibition of organophosphate pesticides (OPPs) on the activity of ALP. By taking chlorpyrifos (CPY) as the model compound of an OPP pesticide and adding ALP and CPY into the NH 2 -MIL-101(Fe) framework, the resulting cascade reaction fluorescence sensors exhibit a good sensitivity for CPY and ALP sensing. The working ranges are  0.02–2 μg/L and 0.2–20 mU/mL with detection limits (LOD) of 5.31 ng/L and 0.05 mU/mL, respectively. The proposed sensor has been actually applied to satisfactory detection of CPY and ALP in food and serum samples. This fluorescence-based assay may extend the application of MOF-based biosensors. Graphical Abstract

研究领域: 分析化学 · 环境科学 · 生物化学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Huazhong University of Science and Technology-Medical Sciences · 2012 ·Vol. 32 ·期 4 ·563-570 · IF 0.385

Synthesis and characterization of UPPE-PLGA-rhBMP2 scaffolds for bone regeneration

Tian Zhichao,Zhu Yuanli,Qiu Jinjun,Guan Hanfeng,Li Liangyu,Zheng Shouchao,Dong Xuehai,Xiao Jun

A novel unsaturated polyphosphoester (UPPE) was devised in our previous research, which is a kind of promising scaffold for improving bone regeneration. However, the polymerization process of UPPE scaffolds was unfavorable, which may adversely affect the bioactivity of osteoinductive molecules added if necessary, such as recombinant human bone morphogenetic protein-2 (rhBMP2). The purpose of this study was to build a kind of optimal scaffold named UPPE-PLGA-rhBMP2 (UPB) and to investigate the bioactivity of rhBMP2 in this scaffold. Furthermore, the cytotoxicity and biocompatibility of UPB scaffold was assessed in vitro . A W1/O/W2 method was used to fabricate PLGA-rhBMP2 microspheres, and then the microspheres were added to UPPE for synthesizing UPB scaffold. The morphological characters of PLGA-rhBMP2 microspheres and UPB scaffolds were observed under the scanning electron microscopy and laser scanning confocal microscopy. The cumulative release of UPB scaffolds was detected by using ELISA. The cytotoxicity and biocompatibility of UPB scaffolds were evaluated through examining the adsorption and apoptosis of bone marrow stromal cells (bMSCs) seeded on the surface of UPB scaffolds. The bioactivity of rhBMP2 in UPB scaffolds was assessed through measuring the alkaline phosphates (ALP) activity in bMSCs seeded. The results showed that UPB scaffolds sequentially exhibited burst and sustained release of rhBMP2. The cytotoxicity was greatly reduced when the scaffolds were immersed in buffer solution for 2 h. bMSCs attached and grew on the surface of soaked UPB scaffolds, exerting well biocompatibility. The ALP activity of bMSCs seeded was significantly enhanced, indicating that the bioactivity of rhBMP2 remained and still took effect after the unfavorable polymerization process of scaffolds. It was concluded that UPB scaffolds have low cytotoxicity, good biocompatibility and preserve bioactivity of rhBMP2. UPB scaffolds are promising in improving bone regeneration.

研究领域: 材料科学 · 生物医学工程 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2022 ·Vol. 414 ·期 9 ·2991-3003 · IF 4.478

A label-free and modification-free ratiometric electrochemical strategy for enhanced natural enzyme detection using a bare electrode and nanozymes system

Rao Honghong,Li Jianying,Luo Mingyue,Zhang Kehui,Gou Hao,Liu Haixia,Xue Zhonghua

Ratiometric electrochemical assays have been demonstrated to be more sensitive and selective in various sensing events, mainly due to their affordable built-in correction and good self-reference capability. But it is known that complicated modification and labeling operations usually are necessary for the construction of ratiometric electrochemical assays, therefore is a hot and important issue needing consideration carefully. We herein report a new yet simple bare electrode-based ratiometric electrochemical bioassay to achieve sensitive and selective analysis of alkaline phosphatase (ALP), using a liquid phase system that contains CoOOH nanozymes and commercially available indicator substrate. This proposed bioassay works based on the ratiometric change of dual electrochemical signals, arising from an exclusive target ALP-triggered hydrolysis of electrochemical substrate p-nitrophenyl phosphate (PNPP). In this design, the two hydrolyzed products of electrochemically active p-nitrophenol (PNP) and electrochemically inactive phosphate anion (PO 4 3− ) are responsible together for the ratiometric electrochemical analysis of ALP. PNP exhibits a straightforward current response toward ALP content; however, PO 4 3− cannot show a direct electrochemical signal thus is rationally designed to offer an alternative response by linking it with the specific CoOOH nanozyme-catalyzed reaction of 3,3′,5,5′-tetramethylbenzidine (TMB) and H 2 O 2 , in which the nanozyme-catalyzed product oxTMB shows a direct reduction current at the GCE, and significantly decreases with increasing PO 4 3− species due to the good inhibition of PO 4 3− toward CoOOH nanozyme activity. As a result, a ratiometric electrochemical strategy for ALP analysis with a low limit of detection of 0.366 U/L (S/N = 3) was successfully achieved by integrating the above direct and indirect dual electrochemical responses. This developed bioassay can allow the quantitative diagnosis of ALP activity especially with a label-free and modification-free merit, therefore paving the way for simple, convenient, and portable electroanalytical tools in biosensing design and application. Graphical abstract

研究领域: 分析化学 · 生物化学 · 电化学 · 纳米技术 · 生物传感器
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science China-Chemistry · 2020 ·Vol. 63 ·期 4 ·554-560 · IF 6.356

In situ formation of fluorescent silicon-containing polymer dots for alkaline phosphatase activity detection and immunoassay

Liu Guoyong,Zhao Jiahui,Yan Mengxia,Zhu Shuyun,Dou Wenchao,Sun Jian,Yang Xiurong

The discovery and application of analyte-triggered fluorophore generation or fluorogenic reaction are significant and beneficial to the development of novel fluorescence (FL) analysis method. In this study, for the first time, we have reported a fluorogenic reaction to prepare fluorescent silicon-containing polymer dots (Si-PDs) by simply mixing N -[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO) and hydroquinone (HQ) in aqueous solution at ambient temperature. Inspired by the alkaline phosphatase (ALP)-catalyzed hydrolysis of the substrate sodium 4-hydroxyphenyl phosphate (4-HPP) into HQ and the resultant HQ-controlled intense green Si-PDs generation, we have established a straightforward ALP activity assay by innovatively employing commercially available 4-HPP as the substrate. More significantly, the specific preparation method, clear formation mechanism and excellent performance enable the Si-PDs as well as its generation process to develop facile and attractive FL immunoassay. With the help of the universal ALP-based enzyme-linked immunosorbent assay (ELISA) platform and corresponding antibody, a convenient and conceptual ALP-based fluorescent ELISA has been constructed and applied in sensing cardiac troponin I (cTnI), a well-known biomarker of acute myocardial infarction. Our research via in situ formation of fluorescent nanomaterials has great potential application in ALP activity assay, inhibitor screening, and disease diagnosis.

CAS / MDL: 1760-24-3
研究领域: 分析化学 · 生物化学 · 纳米材料 · 诊断学 · 免疫分析
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