Drug Metabolism and Pharmacokinetics
·
2019
·
IF 1.874
Yang Zhang,Chen Su,Jinxiu Lei,Lu Chen,Haihong Hu,Su Zeng,Lushan Yu
Mandelic acid (MA) is generally used as a biomarker of the exposure of styrene , which is classified as a class of hazardous environmental pollutants, and also used as an important chiral intermediate in pharmaceutical industry. The previous studies have found the excretion of phenylglyoxylic acid (PGA) in human and rat, a metabolite of MA, was mainly from S- MA rather than R -MA. The metabolic mechanism, however, is not clear. In order to explore the possible metabolic mechanism, the enzyme types involved in the stereoselectivity metabolism of MA were firstly studied, and then human and rat long-chain 2-hydroxy-acid oxidase 2 (HAO2) were recombinantly expressed to study the metabolic profiles of S- MA and its analogues. The results indicated that HAO2 might catalyze the stereoselectivity metabolism of S- MA in rats. Human HAO2 ( h HAO2) and rat HAO2 ( r HAO2) isozymes β 1 and β 2 were successfully cloned and expressed with high purity and good enzyme activities. The enzyme kinetic profiles of these enzymes were different for S- MA and analogues. The order of catalytic efficiency for h HAO2 and r HAO2, however, was reverse. It might be relevance to the difference in active amino acid residues and loop 4 in human and rat L-2-hydroxy acid oxidase isozyme B crystal structures.
研究领域:
环境科学
·
生物化学
·
毒理学
·
药物化学
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DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2025
·Vol. 36
·期 38
·385302
·
IF 2.8
Zhongqiang Min,Qifeng Chen,Xuchao Chen
In this study, L-His-N-carbon quantum dots (CQDs) were synthesized via a microwave-assisted method using homemade hardwood cellulose with a dryness of 20% as the carbon source and L-histidine as the nitrogen source. The results demonstrated that when the mass ratio of cellulose to L-histidine was 1:5 and the reaction time was 40 min, the L-His-N-CQDs exhibited the highest fluorescence quantum yield of 22.43%. A series of characterizations revealed their superior fluorescence performance and uniform size distribution. Subsequently, L-His-N-CQDs were incorporated into a plant oil-based binder to formulate fluorescent anti-counterfeiting ink. Adjusting the mixing ratio of tung oil and soybean oil effectively regulated the ink’s drying properties. When the tung oil–soybean oil ratio was 2:1 or 3:1, the ink achieved optimal drying properties, transparency, and fluidity, ensuring excellent printability and anti-counterfeiting performance in screen printing. Fluorescence spectroscopy tests indicated that the composite fluorescent anti-counterfeiting ink possessed remarkable extended fluorescence stability and anti-quenching properties. The ink’s resin binder, plant oil solvent, and additives did not hinder the luminescence of carbon quantum dots. Thus, the prepared ink is highly applicable in anti-counterfeiting printing technologies and related fields, offering new material options for such printing techniques.
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高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Risheng Zhao,Min Zhang,Gege Yang,Wei Liu,Hui Yu,Shuang Yan,Ting Ren,Linxin Zhang,Mengyang Wang,Haiming Sun
Hypertensive heart failure pathogenesis involves angiotensin II (Ang II)-mediated mechanisms through both hemodynamic overload and direct cellular signaling pathways. This study investigates the therapeutic potential of Portulaca oleracea L. (POL) extract and its active constituent Oleracein E (OE) in attenuating Ang II-induced pathological cardiac remodeling and subsequent heart failure progression. An experimental model of hypertensive heart failure was established in C57BL/6 mice through continuous subcutaneous infusion of Ang II for 4 weeks, with Oleracein E (OE) intervention administered during the final 2 weeks of the protocol. To elucidate the molecular mechanisms underlying OE's cardioprotective effects, we employed an integrated approach combining RNA sequencing analysis, molecular docking simulations, and target validation through drug affinity response target stability (DARTS) and cellular thermal shift assay (CETSA) techniques. The experimental results demonstrated that both POL extract and its active component OE exerted significant cardioprotective effects against Ang II-induced cardiac dysfunction in murine models, primarily through attenuation of pathological cardiac hypertrophy and suppression of inflammatory responses. Transcriptomic profiling via RNA sequencing identified the MAPK signaling pathway as a critical mediator of these protective effects. Subsequent transcription factor analysis revealed STAT2 as a key regulatory component in this pathway. Importantly, OE treatment effectively mitigated inflammatory responses in both in vivo cardiac tissues and in vitro cultured cardiomyocytes by specifically inhibiting the Ang II-activated MAPKs/STAT2 signaling cascade. Genetic ablation experiments further confirmed the essential role of this pathway, as the anti-inflammatory efficacy of OE was completely abolished in cardiomyocytes with MAPKs or STAT2 deficiency. Molecular interaction studies employing in silico docking simulations combined with experimental validation through DARTS and CETSA techniques provided direct evidence of physical binding between OE and the STAT2 protein. Our findings demonstrate that Oleracein E (OE) confers cardioprotection against Ang II-induced myocardial injury through a novel mechanism involving STAT2 targeting and subsequent suppression of MAPK signaling-mediated inflammatory cascades. These results not only elucidate a previously unrecognized pharmacological pathway but also suggest that OE and its derivatives hold significant therapeutic promise for the clinical management of hypertensive heart failure, potentially offering a targeted approach to modulate pathological cardiac remodeling.
研究领域:
药理学
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心血管病学
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分子生物学
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PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 1
·69-78
·
IF 3.929
Yu Haiyang,Tang Zhaohui,Li Mingqiang,Song Wantong,Zhang Dawei,Zhang Ying,Yang Yan,Sun Hai,Deng Mingxiao,Chen Xuesi
A series of novel polypeptide-based graft copolymer poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) was synthesized through a Steglich esterification reaction of PLG with mPEG. The structure of the copolymers was confirmed by nuclear magnetic resonance
spectra (NMR) and gel permeation chromatography (GPC). MTT assay demonstrated that the PLG-g-mPEGs had good cell compatibility. The unreacted carboxyl groups of the PLG-g-mPEGs were used to complex cisplatin to form polymer-metal complex nanoparticles (CDDP/PLG-g-mPEG)
for cancer therapy. The average hydrodynamic radius of the CDDP/PLG-g-mPEG nanoparticles was in the range of 14–25 nm, which was beneficial for solid tumor targeting delivery. A sustained release without initial burst was achieved for the CDDP/PLG-g-mPEG nanoparticles,
indicating that the CDDP-loaded nanoparticles had great potential to suppress the drug release in blood circulation before the nanoparticles had arrived at targeting tumors. The CDDP/PLG-g-mPEG nanoparticles showed a much longer blood retention profile as compared with the free CDDP.
This indicated that the CDDP-loaded nanoparticles had much more opportunity to accumulate in tumor tissue by exerting the EPR effect. In vitro tests demonstrated that the CDDP/PLG-g-mPEG nanoparticles could inhibit the proliferation of HeLa, MCF-7 and A549 cancer cells. At equal
dose (4 mg kg–1), the CDDP/PLG-g-mPEG nanoparticles showed comparable in vivo antitumor efficacy and significantly lower systemic toxicity as compared with free cis-Diaminedichloroplatinum (cisplatin, CDDP) in MCF-7 tumor bearing mice. These suggested that the
CDDP/PLG-g-mPEG nanoparticle drug delivery system had a great potential to be used for cancer therapy.
研究领域:
药学
·
肿瘤学
·
生物材料
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PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2017
·Vol. 17
·期 7
·1600444
·
IF 3.238
Chengfeng Zhang,Ziyuan Liu,Haiye Wang,Xiaofeng Feng,Chunju He
A unique l -cysteine conjugated antifouling amphiphilic conetwork (APCN) is synthesized through end-crosslinking of well-defined triblock copolymers poly(allyl methacrylate)- b -poly(ethylene glycol)- b -poly(allyl methacrylate) via a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and thiol–ene “click” chemistry. The synthesized poly(ethylene glycol) macro-RAFT agent initiates the polymerization of allyl methacrylate in a controlled manner. The vinyl pendant groups of the precursor partially conjugate with l -cysteine and the rest fully crosslink with mercaptopropyl-containing siloxane via thiol–ene click chemistry under UV irradiation into APCNs, which show distinguished properties, that is, excellent biocompatibility, more than 39.6% water content, 101 barrers oxygen permeability, optimized mechanical properties, and more than 93% visible light transmittance. What's more, the resultant APCNs exhibit eminent resistance to protein adsorption, where the bovine serum albumin and lysozyme adsorption are decreased to 12 and 21 µg cm −2 , respectively. The outstanding properties of APCNs depend on the RAFT controlled method, which precisely designs the hydrophilic/hydrophobic segments and eventually greatly improves the crosslinking efficiency and homogeneity. Meantime, the l -cysteine monolayer can effectively reduce the surface hydrophobicity and prevent protein adsorption, which exhibits the viability for antifouling surface over and under ophthalmic devices, suggesting a promising soft contact lens.
研究领域:
材料科学
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聚合物化学
·
生物医学工程
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高影响因子
JOURNAL OF PROSTHETIC DENTISTRY
·
2022
·
IF 4.148
Hao Yang,Xianju Xie,Xiaowei Li,Yuxing Bai
Statement of problem Polymethyl methacrylate (PMMA) is commonly used in dentistry, including as a denture base material. However, the colonization of a PMMA surface by microbial microorganisms could increase the risk of oral diseases such as denture stomatitis and gingivitis. The development of PMMA with antibacterial properties should improve its clinical application, but whether adding ε-poly-L-lysine (ε-PL) and 2-methacryloyloxyethyl phosphorylcholine (MPC) provides antimicrobial effects is unclear. Purpose This in vitro study aimed to develop a novel antibacterial PMMA resin containing the natural nontoxic antibacterial agent ε-PL and the protein repellent agent MPC. The mechanical properties, protein repellency, and antimicrobial activities of the resin were then evaluated. Material and methods Different mass fractions of ε-PL and MPC were mixed into PMMA as the experimental groups, with unaltered PMMA as the control group. The flexural strength (n=10) and surface roughness (n=6) of the resulting mixtures were measured to determine their mechanical properties. The antiprotein properties were measured by using the micro bicinchoninic acid method (n=6). The antimicrobial effect of the resin was assessed using live/dead staining (n=6) and methyltransferase (MTT) assays (n=10). According to the variance homogeneity and normal distribution results, 1-way analysis of variance followed by the Tukey honestly significant difference test or the Welch test and the Games-Howell test were used (α=.05 for all tests). Results No significant differences were found in the flexural strength values and surface roughness of the specimens containing 1.5% MPC and 1.5% ε-PL compared with those of the control ( P >.05). The addition of ε-PL to the PMMA resin alone significantly increased its bactericidal properties ( P <.05). Adding both ε-PL and MPC further increased the antibacterial activity of the PMMA resin without increasing protein adhesion more than in the control group. Conclusions The incorporation of both ε-PL and MPC into PMMA improved its antibacterial capacity without affecting its mechanical properties and did not increase protein adhesion. Therefore, the novel PMMA fabricated in this study shows promise for dental applications.
研究领域:
口腔医学
·
材料科学
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DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2020
·Vol. 104
·期 15
·6635-6646
·
IF 3.53
Huang Kai,Zhang Shurong,Guan Xiao,Liu Jing,Li Sen,Song Hongdong
This study aims to use neutral pH optimum arginase as the catalyst for high-efficiency l -ornithine production. Sulfobacillus acidophilus arginase was firstly cloned and overexpressed in Escherichia coli . The purified enzyme was obtained, and the molecular mass determination showed that this arginase was a hexamer. S. acidophilus arginase possessed similarities with the other arginases such as the conserved sequences, purification behavior, and the necessity for Mn 2+ as a cofactor. The maximum enzyme activity was obtained at pH 7.5 and 70 °C. Thermostability and pH stability analysis showed that the arginase was stable at 30–60 °C and pH 7.0–8.5, respectively. The kinetic parameters suggested that S. acidophilus arginase could efficiently hydrolyze l -arginine. Bioconversion with this neutral pH optimum arginase had the advantages of avoiding producing by-product, high molar yield, and high-level production of l -ornithine. When the bioconversion was performed with a fed-batch strategy and a coupled-enzyme system involving S. acidophilus arginase and Jack bean urease, the final production of 2.87 mol/L was obtained with only 1.72 mmol/L l -arginine residue, and the molar yield was 99.9%. The highest production record suggests that S. acidophilus arginase has a great prospect in industrial l -ornithine production.
研究领域:
生物技术
·
酶学
·
微生物学
·
生物化工
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PubMed
高影响因子
Analytical Methods
·
2025
·
IF 2.6
Minzi Li,Hongying Wang,Shaohong Zhang,Ran Zhang,Zhijuan Wang
A trimetallic (Fe, Co, Zn) nanozyme embedded within a N-doped carbon matrix (FeCoZn-NC-1.5-800) was engineered via coordination-controlled pyrolysis of Fe ions doped core-shell ZIF-8@ZIF-67 (ZIF-8@ZIF-67-Fe-1.5) precursor, which exhibited dual oxidase/peroxidase-mimicking activities. The bifunctional catalyst oxidized 3,3',5,5'-tetramethylbenzidine (TMB) to form a blue product of oxidized TMB (oxTMB) without exogenous H2O2. However, the addition of L-cysteine (L-Cys) acted as a potent inhibitor, quenching oxTMB formation via thiol-mediated electron transfer, leading to a significant decrease in absorbance and the fading of the blue colour to colourless. Consequently, an H2O2-independent colormetric biosensor was developed with a wide linear range (5-50 μM), a low detection limit (0.569 μM, 3σ), good selectivity and anti-interference ability. This work establishes a paradigm for transition metal nanozyme design, offering clinical translation potential in point-of-care thiol monitoring and biocatalytic system development.
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高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Yang Zhou,Yuxin Wei,Runqiu Wang,Yanli Wei,Li Wang
A fluorescent sensing method is presented for the determination of L -Cysteine ( L -Cys) based on sulfur quantum dots (SQDs)/MnO 2 nanosheets (MnO 2 NS) nano system. SQDs was prepared from hydrothermal reaction from sublimed sulfur with β-Cyclodextrin as the surface ligand. SQDs have intense fluorescence which will be quenched in the presence of MnO 2 NS. After the addition of L -Cys, the redox reaction of MnO 2 NS and L -Cys results in the recovery of SQDs fluorescence. Under optimal conditions, the sensing system could achieve a sensitive detection of L -Cys with a wide linearity in the range of 8.0 μM-1.0 mM and a detection of limit as 2.44 μM (3σ/k). This sensing method also shows an excellent specificity and anti-inference, which has a great potential application for the real sample detection. The SQDs-MnO 2 NS served as a promising sensing system for the identification of L -Cys.
研究领域:
分析化学
·
纳米技术
·
生物传感
·
材料科学
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产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Ligang Xing,Yanmei Zhao,Mingzhu Gong,Xia Liu,Yuhui Zhang,Dan Li,Zefeng He,Ping Yan,Jidong Yang
In this study, Graphene Oxide (GO) was used to screen the binding with the aptamers of L-carnitine chiral enantiomers . The ssDNA library was prepared by the method of Lambda exonuclease . In addition, a simple casing device was designed to improve the purification and recovery efficiency of the small ssDNA fragments in the process of screening. Finally, more than 160,000 aptamer sequences were obtained by high-throughput sequencing. We determined the strongest affinity aptamer sequence, CA04, by the Resonance Rayleigh scattering (RRS) technology. We also analyzed the key binding sites (in the 16th position case) of the truncated aptamer sequence CAD10. Interestingly, we found that aptamer CA10 and CA06 were both C-rich bases through sequence alignment and analysis, and the aptamer CA10 was confirmed that the CA10 and CA06 were formed under acidic conditions (pH 4.5) by CD spectrum and ESI-MS analysis. The interaction between gold nanoparticles (AuNPs) and functionalized aptamer CA10 was analyzed. We used Site-directed mutagenesis design and QGRS Mapper to optimize aptamer CA10, where an optimal aptamer CA10-03 were obtained after affinity analysis. It is also proved to be an effective method to obtain stronger affinity aptamer. Meanwhile, Native-PAGE and UV spectrum analysis were performed on the mutation sequences, and the interaction with ThT was analyzed. Finally, it is hoped that my study can provide help for later identification and detection of L-carnitine .
研究领域:
生物化学
·
分子生物学
·
分析化学
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PubMed
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 5
·
IF 6.353
Liu Boxun,Jin Zhizhong,Chen Haiyan,Liang Lun,Li Yao,Wang Guo,Zhang Jing,Xu Tao
Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared with blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically approved poly (L-lactic acid)/gelatine membrane for local and long-term delivery of DOX for the treatment of glioblastoma.
研究领域:
药理学
·
肿瘤学
·
生物材料科学
·
药物递送系统
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DOI
PubMed
高影响因子
ULTRASONICS SONOCHEMISTRY
·
2014
·
IF 3.816
Wang Liju,Keyume Ablajan,Feng Jun
A rapid and efficient ultrasound-promoted one-pot synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives is described here. The reaction of substituted phenylhydrazine and dialkyl acetylenedicarboxylate with substituted isatin and malononitrile is catalyzed by l -proline to give good-to-excellent yields in water/ethanol (v/v, 1:1) at room temperature.
研究领域:
有机化学
·
催化反应
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）