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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2019 ·Vol. 54 ·期 6 ·2266-2276 · IF 2.281

Enhanced bioaccessibility in vitro and bioavailability of Ginkgo biloba extract nanoparticles prepared by liquid anti-solvent precipitation

Lingling Wang,Xiuhua Zhao,Fengjian Yang,Weiwei Wu,Yanjie Liu,Li Wang,Lu Wang,Zijian Wang

Summary The ginkgo biloba extract (GBE) nanoparticles were successfully prepared by adopting the liquid anti-solvent precipitation (LASP) method to enhance the antioxidant activity and oral bioavailability of GBE. Under the optimum preparation conditions, the particle size of GBE nanoparticles had reached 76.90 nm. Moreover, the antioxidant activity and intestinal transmittance of GBE nanoparticles were tested before and after the simulated in vitro digestion, which were both significantly higher than that of raw GBE. Significantly, the AUC ( 0→t) value of flavonoids and terpene lactones in GBE nanoparticles were 2.20 and 2.24 times of that in raw GBE, respectively. What cannot be ignored was that the residual amount of ethanol and n-hexane meets the safety standards for food.

研究领域: 药学 · 纳米技术 · 药理学
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2018 · IF 3.466

Pharmacodynamic and pharmacokinetic characteristics of YMR-65, a tubulin inhibitor, in tumor-bearing mice

Ali Fan,Jiali Wei,Mengru Yang,Qing Zhang,Yaliang Zhang,Qingwang Liu,Ning Li,Di Zhao,Yang Lu,Junxiu Li,Jie Zhao,Shuhua Deng,Bingjie Zhang,Hailiang Zhu,Xijing Chen

YMR-65​, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a potential tubulin inhibitor exhibiting good anticancer activity. In our study, we illustrated the biological activities in HepG2 cells and the pharmacodynamic and pharmacokinetic profiles were evaluated in murine H22 hepatoma-bearing mice. Molecular docking assay and colchicine competition assay indicated that YMR-65 could bind tightly to the colchicine binding site of tubulin. Further investigation demonstrated that YMR-65 arrested cells in the G2/M phase of cell cycle and induced apoptosis in HepG2 cells. Compared with control group, the tumor growth inhibition determined by final relative volume of tumor/the initial tumor volume were 32.57%, 24.00% and 34.95%, respectively, for YMR-65 (10 mg/kg), YMR-65 (20 mg/kg) and CA4P (10 m/kg) groups. Besides there were no obvious body change or tissue damage (enhanced by histopathology study). YMR-65 administration at 10 and 20 mg/kg in H22 tumor-bearing mice resulted in 1.87- and 1.80-fold longer half time (t 1/2 ) and 0.36- and 0.78-fold lower area under concentration-time curve (AUC 0–∞ ) in plasma in contrast with normal mice at 10 mg/kg. Furthermore, YMR-65 showed a wide distribution to various tissues or tumor and the highest distribution index (the ratio of AUC tissue or tumor /AUC plasma ) was found in tumor, which implied that it might accumulate in tumor after administration. In brief, our results indicated that YMR-65 was a promising candidate with high antitumor efficacy and low tissue damage.

CAS / MDL: 64-86-8 168555-66-6
研究领域: 肿瘤学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2023 · IF 12.6

Machine learning-assisted global DNA methylation fingerprint analysis for differentiating early-stage lung cancer from benign lung diseases

Dechan Lu,Yanping Chen,Longfeng Ke,Weilin Wu,Liwen Yuan,Shangyuan Feng,Zufang Huang,Yudong Lu,Jing Wang

DNA methylation plays a critical role in the development of human tumors. However, routine characterization of DNA methylation can be time-consuming and labor-intensive. We herein describe a sensitive, simple surface-enhanced Raman spectroscopy (SERS) approach for identifying the DNA methylation pattern in early-stage lung cancer (LC) patients. By comparing SERS spectra of methylated DNA bases or sequences with their counterparts, we identified a reliable spectral marker of cytosine methylation. To move toward clinical applications, we applied our SERS strategy to detect the methylation patterns of genomic DNA (gDNA) extracted from cell line models as well as formalin-fixed paraffin-embedded tissues of early-stage LC and benign lung diseases (BLD) patients. In a clinical cohort of 106 individuals, our results showed distinct methylation patterns in gDNA between early-stage LC (n = 65) and BLD patients (n = 41), suggesting cancer-induced DNA methylation alterations. Combined with partial least square discriminant analysis, early-stage LC and BLD patients were differentiated with an area under the curve (AUC) value of 0.85. We believe that the SERS profiling of DNA methylation alterations, together with machine learning could potentially offer a promising new route toward the early detection of LC.

CAS / MDL: 71-30-7 554-01-8
研究领域: 癌症生物学 · 分子生物学 · 生物医学工程 · 生物信息学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2020 · IF 4.845

Enhanced oral bioavailability of Bisdemethoxycurcumin-loaded self-microemulsifying drug delivery system: Formulation design, in vitro and in vivo evaluation

Jian Liu,Qilong Wang,Emmanuel Omari-Siaw,Michael Adu-Frimpong,Jing Liu,Ximing Xu,Jiangnan Yu

In this study, we sought to overcome the poor solubility and bioavailability of bismethoxycurcumin (BDMC) by fabricating a BDMC-loaded self micro-emulsifying system (BDMC-SMEDDS). Solubility and compatibility tests, pseudo-ternary phase diagrams (PTPDs) as well as d-optimal concept was applied to design the formulation. The assessment of the prepared BDMC-SMEDDS in-vitro mainly included droplet size (DS) and entrapment efficiency (EE) determination, morphology, drug release and stability testing. Besides, the in vivo behavior was also evaluated after oral administration of BDMC-SMEDDS to rats. The optimal formulation was found to compose of Kolliphor EL (K-EL, emulsifier , 645.3 mg), PEG 400 (co-emulsifier, 147.2 mg), ethyl oleate (EO, oil, 207.5 mg) and BDMC (50 mg). The BDMC-SMEDDS with satisfactory stability had a mean size of 21.25 ± 3.23 nm and EE of 98.31 ± 0.32%. Roughly 70% of BDMC was released from BDMC-SMEDDS within 84 h compared with <20% from the free BDMC. More importantly, the in-vivo behavior of BDMC-SMEDDS showed that the AUC (0-12h) and plasma concentration of BDMC increased substantially as compared to the free BDMC. Altogether, BDMC-SMEDDS has the potential to enhance the solubility and bioavailability of BDMC and could be applied in the clinics.

研究领域: 药剂学 · 药物递送系统 · 药代动力学
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-15 · IF 10.6

Accurate HER2 determination in breast cancer: a prominent COF-immobilized enzyme-enhanced electrochemical aptasensor employing 4-acetamidophenol as an efficient mediator

Zhang Yue,Chen Shuyi,Ma Jie,Zhou Xiaobin,Sun Xinchen,Zhou Chenglin

An effective strategy for enzyme-enhanced electrochemical detection of human epidermal growth factor receptor 2 (HER2) is proposed for breast cancer diagnosis. This strategy utilizes a three-dimensional mesoporous covalent organic framework (COF), immobilized horseradish peroxidase (HRP), and a novel redox mediator, 4-acetamidophenol (APAP). The mesoporous structure, with encapsulation effect, and good biocompatibility of COF, makes the functionalized COF an efficient carrier for HRP immobilization (HRP-Ab-AuNPs@COF). It demonstrates superior catalytic activity, stability, and electrochemical performance compared to free HRP, thus making it an ideal probe for simultaneous target recognition and signal amplification. APAP is screened from four candidate phenolic compounds based on its high formal potential (0.32 V vs. Ag/AgCl), rapid electron transfer activity (k app = 2.80 × 10 5 M − 1 s − 1 ), excellent solubility and stability. These properties prove significantly better than the conventional mediator hydroquinone (HQ), achieving a higher signal-to-background ratio. By integrating decorated multi-walled carbon nanotubes as substrate materials, the electrochemical aptasensor achieves a low HER2 detection limit (0.418 pg mL − 1 ) with high specificity. This method’s selectivity surpasses that of the HQ-mediated method by 59–73%. Moreover, the aptasensor can effectively distinguish breast cancer patients and healthy individuals, as well as patients at different stages of the disease with high accuracy (AUC = 0.928). This performance exceeds traditional biomarkers CEA and CA15-3. This work paves novel avenues for innovative applications of COF-immobilized enzymes and the novel mediator APAP in electrochemical biosensing, thus holding significant promise for individualized breast cancer diagnosis and treatment.

CAS / MDL: 9001-05-2 16940-66-2
研究领域: 生物医学工程 · 癌症诊断 · 电化学 · 纳米技术 · 生物传感器
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Biomaterials Advances · 2024 · IF 5.5

Naturally sourced amphiphilic peptides as paclitaxel vehicles for breast cancer treatment

Rongli Chen,Ergang Liu,Yuefei Fang,Nan Gao,Meng Zhang,Xiaoru Zhang,Wanying Chen,Chuxin Liang,Yu Zhang,Yongzhuo Huang

The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D-α-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGS-AmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL·(min·kg) −1 ) and an enhanced AUC (41.4 μg.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect o v er Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.

CAS / MDL: 129-00-0 62669-70-9
研究领域: 药学 · 肿瘤学 · 药物递送系统 · 生物技术
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AAPS PHARMSCITECH · 2023 ·Vol. 24 ·期 2 ·1-16 · IF 3.3

Transcellular Transport Behavior of the Intact Polymeric Mixed Micelles with Different Polymeric Ratios

Wu Wenting,Ding Quan,Zhou Zhiwei,Kuang Wenliang,Jiang Lipeng,Liu Peng,Ai Weiping,Zhu Weifeng

In order to better promote the application of the polymeric mixed micelles (PMMs) in oral delivery, in addition to focusing on the improvement of micellar structural stability, it is necessary to obtain the absorption characteristics of the intact micellar particles. In this work, the transport behavior across Caco-2 cells of FS/PMMs composed of Pluronic F127 and Solutol HS15 was tracked by encapsulating an environment-responsive probe into the particles. The specific property of the probe is the water-initiated aggregation-caused quenching (ACQ) ability, by which integral particles can be identified accurately. The influence of polymeric ratios (FS) on the transcellular behavior of FS/PMMs was explored and the single pass intestinal perfusion experiment was used to further illustrate it. Moreover, pharmacokinetics parameters were detected to analyze the relationship among FS ratios, transport behavior, and pharmacokinetic parameters. FS ratios were found to hardly affect the endocytosis pathways and intracellular itinerary of FS/PMMs, but do affect the proportion of each path. FS/PMMs with high HS15 content, namely System-I, were found to primarily undergo receptor-mediated endocytosis pathway and be less susceptible to lysosomal degradation, which would lead to more absorption and higher Cmax and AUC than drug suspension. In contrast, despite System-II with high F127 content cannot contribute to drug plasma concentration, it can prolong the in vivo retention time. These findings provided evidence for the role of polymeric ratios in modulating the transcellular absorption and pharmacokinetic parameters of the drug-loaded PMMs, and would be a step forward in helping PMMs’ design to enhance oral drug delivery. Graphical Abstract

研究领域: 药学 · 药物递送系统 · 药理学 · 生物药剂学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Bisulfite-free detection of DNA methylation in early-stage lung cancer with a multiplex SERS immunoassay

Dechan Lu,Yanping Chen,Longfeng Ke,Zufang Huang,Yudong Lu,Jing Wang

DNA methylation is a promising biomarker for early cancer detection; however, traditional detection methods require bisulfite treatment and nucleic acid amplification, which are costly and impractical for point-of-care use. We propose a facile method that leverages immunoassays and surface-enhanced Raman scattering (SERS) readouts for the multiplex, sensitive, and portable detection of lung cancer-related DNA methylation biomarkers. This approach employs 5-methylcytosine antibody-modified magnetic probes to enrich methylated DNA sequences and uses core–shell nanoparticles with Probe DNA as SERS nanotags for multiplex detection, eliminating the need for bisulfite treatment and nucleic acid amplification. The multiplex SERS immunoassay detects synthetic methylated SHOX2 and RASSF1A with detection limits of 0.52 pM and 0.66 pM, respectively. It shows a strong correlation with quantitative PCR results in analyzing methylated SHOX2 and RASSF1A from cell lines and formalin-fixed paraffin-embedded tissue samples (n = 35). Additionally, the random forest analysis based on methylated SHOX2 and RASSF1A expression distinguishes lung cancer from benign lung diseases with a clinical sensitivity of 96 %, specificity of 90 %, and an AUC value of 0.972. This method offers a significant advancement for DNA methylation research and clinical applications.

研究领域: 癌症生物学 · 分子诊断学 · 纳米技术 · 生物化学
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EMBO Molecular Medicine · 2024 · IF 9

Identification and validation of serum metabolite biomarkers for endometrial cancer diagnosis

LiuWanshan,MaJinglan,ZhangJuxiang,CaoJing,HuXiaoxiao,HuangYida,WangRuimin,WuJiao,DiWen,QianKun,YinXia

Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass in the uterine cavity) is essential and remains challenging in clinical practice. Herein, we identified a metabolic biomarker panel for differentiation diagnosis of EC using machine learning of high-performance serum metabolic fingerprints (SMFs) and validated the biological function. We first recorded the high-performance SMFs of 191 EC and 204 Non-EC subjects via particle-enhanced laser desorption/ionization mass spectrometry (PELDI-MS). Then, we achieved an area-under-the-curve (AUC) of 0.957–0.968 for EC diagnosis through machine learning of high-performance SMFs, outperforming the clinical biomarker of cancer antigen 125 (CA-125, AUC of 0.610–0.684, p < 0.05). Finally, we identified a metabolic biomarker panel of glutamine, glucose, and cholesterol linoleate with an AUC of 0.901–0.902 and validated the biological function in vitro. Therefore, our work would facilitate the development of novel diagnostic biomarkers for EC in clinics.

CAS / MDL: 127-09-3
研究领域: 妇科学 · 肿瘤学 · 代谢组学 · 机器学习 · 生物标志物发现
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Analytical Methods · 2025 · IF 2.6

Deciphering the differences in aroma components of tobacco from different origins based on HS-GC-IMS and multivariate statistical analysis

Suxuan Li,Ningyang Mao,Cong Chen,Hui Zhao,Xiaoyu Chen,Liusheng Wang,Fuyun Cui,Wenning Feng,Zhiyong Wu

This study employed headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) technology combined with multivariate statistical analysis methods to analyze the flavor compounds in flue-cured tobacco from five different regions in China: Henan, Hunan, Yunnan, Chongqing, and Fujian. A total of 98 volatile aroma compounds were identified through HS-GC-IMS analysis, including esters, ketones, aldehydes, acids, alcohols, heterocyclic compounds, sulfur-containing compounds, other types of compounds, and 8 uncharacterized compounds. Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) were utilized to conduct dimensionality reduction and distinguish the samples, effectively recognizing differences in volatile compounds among tobacco leaves from various origins. A Random Forest (RF) classification model was constructed, and its reliability was validated through ROC (Receiver Operating Characteristic) analysis, achieving an AUC (Area Under the Curve) value of 0.980, which demonstrates exceptional predictive performance. PCA revealed distinct separations of tobacco leaf samples from different regions on the PCA score plot, and OPLS-DA analysis further validated these differences and confirmed the model's validity through permutation testing. Twenty key aroma compounds with VIP > 1.0 were screened by integrating OPLS-DA with the Random Forest classification model. These compounds showed significant differences in content among different samples, suggesting their potential as chemical markers for distinguishing the origin of flue-cured tobacco. This study not only provides a new method for identifying volatile compounds in tobacco but also offers novel insights into the geographical identification of flue-cured tobacco.

研究领域: 分析化学 · 食品科学 · 植物学 · 化学计量学 · 农业科学
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TALANTA · 2023 · IF 6.1

Serum lipidomic profiling for liver cancer screening using surface-assisted laser desorption ionization MS and machine learning

Qiong Wu,Jing Yu,Mingjin Zhang,Yinran Xiong,Lijia Zhu,Bo Wei,Ting Wu,Yiping Du

The liver is a major organ in metabolism, and alterations in serum lipids are associated with liver disorders. Here, a rapid, easy, and reliable screening technique based on lipidomic profiling was developed using machine learning and surface-assisted laser desorption ionization mass spectrometry (SALDI MS) for liver cancer diagnosis. A graphitized carbon matrix (GCM) was created for serum lipid profiling in SALDI MS and demonstrated a better performance for neutral lipids analysis than conventional organic matrices. The fingerprint of serum lipids, including triacylglycerols (TGs), diacylglycerols (DGs), cholesteryl esters (CEs), glycerophospholipids (GPs), and other components, could be directly obtained by GCM-assisted LDI MS without extraction. Five machine learning methods were applied to distinguish liver cancer (LC) patients from healthy controls (HC) and chronic hepatitis B (CHB) patients. The best diagnostic performance was attained by linear discriminant analysis (LDA), which has a confusion matrix accuracy of 98.3 %. The receiver operating characteristic (ROC) curve for liver cancer exhibited an area under the curve (AUC) of 0.99, indicating a high degree of prediction accuracy. One-way ANOVA analysis revealed that numerous TGs were down-regulated in LC group. The results demonstrated the viability of GCM-assisted LDI MS as a valuable diagnostic tool for liver cancer.

研究领域: 医学诊断 · 质谱技术 · 机器学习 · 癌症研究 · 脂质组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMEDICINE & PHARMACOTHERAPY · 2023 · IF 7.5

Polygoni multiflori radix exacerbates idiosyncratic inflammatory liver injury through the FXR-SHP pathway and altered pharmacokinetic behavior

Guoqin Zhang,Jianhua Sun,Meiqi Liu,Zhixiang Tian,Zicheng Ma,Bingyu Hao,Jintang Ning,Xiaoliang Ren,Meng Wang,Ping Wang,Jiunian Li,Hailin Li,Jian Ni,Yi Liu

Polygoni multiflori radix (PM) is a well-known tonic herb. It has been reported that PM could cause idiosyncratic inflammatory liver injury in some individuals. In this study, we investigated the mechanism of PM-induced idiosyncratic inflammatory liver injury in zebrafish and rat models based on pharmacodynamics and pharmacokinetics. The zebrafish were administered with polygoni multiflori radix extract (PME), emodin (EMO), and 2,3,5,4′-tetrahydroxystilbene-2-Ο-β- D -glucoside (TSG) after lipopolysaccharide (LPS) treatment, to establish an idiosyncratic inflammation model. In zebrafish with idiosyncratic inflammation, PME, EMO, and TSG decreased liver area and brightness and increased the number of immune cells around the colliculi. PME+LPS produced hepatocyte damage, aggravated mitochondrial and endoplasmic reticulum damage, and increased AST and ALT activity. RT-PCR showed that PME and EMO up-regulated the expression of IL-6, IL-1β, and INF-γ, and PME down-regulated expression of FXR and SHP. In rats with idiosyncratic inflammation, AST and ALT activities increased significantly, and liver tissues showed pathological damage. An efficient and sensitive LC-MS/MS method was established for the pharmacokinetic study of EMO and TSG in rats with idiosyncratic inflammation. The AUC 0−t was higher for EMO and TSG in the model group compared with the normal group. The MRT 0−t was significantly prolonged in EMO, while CL z/F was significantly reduced. The present results suggested that the absorption of potentially toxic components of PM increased and metabolism slowed down under inflammatory stress, and PM induced idiosyncratic liver injury via the FXR-SHP axis.

CAS / MDL: 95-47-6
研究领域: 药理学 · 毒理学 · 肝病学 · 药代动力学 · 斑马鱼模型 · 大鼠模型
✓ 已验证 产品关联 DOI PubMed 高影响因子
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