RSC Advances
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2017
·Vol. 7
·期 35
·21837-21847
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IF 3.108
Huixiang Zhong,Liuyang Xuan,Dandan Wang,Jianhua Zhou,Yan Li,Qing Jiang
Lung cancer bone metastases usually involve multiple interactions between cancer cells and host organs. To mimic such a structure, a cell co-culture micropattern of A549 lung cancer cells and osteoblast cells (A549/OB) was developed using a μ-eraser strategy for anti-cancer drug evaluation and also understanding cell–cell communication. When applying the μ-eraser strategy, a PDMS stamp was pressed to induce cell lysis. Hence, the minimum pressure required to induce cell lysis was first quantified. Then the pressure and pressing time for the micropatterning process were optimized to obtain cell micropatterns of high fidelity and repeatability. For different types of cells (A549 and human mesenchymal stem cells) and different substrates (TCP and PLGA nanofiber sheets), the optimized pressure was also different (i.e., for A549 on TCP, a pressure of 24.5 kPa was pressed for 10 s). According to a live/dead assay and Alamar Blue assay, cell viability and proliferation potential were not affected by the micropatterning process. There were several advantages for the μ-eraser strategy: substrates were not pre-treated; cell micropatterns mainly relied on the pattern of the PDMS stamp along with the micropatterning process; cells in the micropattern were not restricted in specified regions. Thus the A549/OB co-culture micropattern on TCP was used to evaluate the efficacy of a therapeutic agent (doxorubicin). In the co-culture micropattern, the efficacy of doxorubicin decreased when the expression of ALP in OB was elevated. The co-culture micropattern model showed the potential to be used for new anti-cancer drug development.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Haolan You,Yihe Song,Yi Yang,Xicheng Wang,Shiqi Pan,Junyang Huang,Qiqi Shao,Donglei Shi,Baoli Li,Jian Li,Xiaokang Li
Beta-amyloid (Aβ), the most pivotal pathological hallmark for Alzheimer's disease (AD) diagnosis and drug evaluation, was recognized by TZ095 , a high-affinity fluorescent probe developed by rational molecular design. With a TICT mechanism, TZ095 exhibited remarkable affinity with Aβ aggregates (K d = 81.54 nM for oligomers; K d = 66.70 nM for fibril) and substantial fluorescence enhancement (F/F 0 = 44), enabling real-time monitoring of Aβ in live cells and nematodes. Significantly, this work used TZ095 to construct a new protocol that can quickly and conveniently monitor Aβ changes at the cellular and nematode levels to evaluate the anti-AD efficacy of candidate compounds, and four reported Aβ-lowering drug candidates were administrated for validation. Imaging data demonstrated that TZ095 can visually and quantitatively track the effect of Aβ elimination after drug treatment. Furthermore, TZ095 excelled in ex vivo histological staining of 12-month-old APP/PS1 mouse brains, accurately visualizing Aβ plaques. Integrating CUBIC technology, TZ095 facilitated whole-brain, 3D imaging of Aβ distribution in APP/PS1 mice, enabling high-resolution in situ analysis of Aβ plaques. Collectively, these innovative applications of TZ095 offer a promising strategy for rapid, convenient, and real-time monitoring of Aβ levels in preclinical therapeutic assessments.
研究领域:
神经科学
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药物化学
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分子生物学
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DOI
高影响因子
LANGMUIR
·
2025
·
IF 3.9
Yue Cheng,Bing Li,Jianping Wang,Yubin Wang,Linshan Wang,Muling Wei,Yuying Wang,Zhongrong Chen,Gang Zhao
Hydrogel microspheres are considered ideal carriers with broad applications in 3D cell culture, drug delivery, and microtissue construction. Although multiple methods have been developed for generating hydrogel microspheres, there is still a lack of a universal approach that combines operability, stability, cost-effectiveness, and biocompatibility. In this work, a novel rotating microfluidic system (RMS) is proposed, which can rapidly fabricate diverse poly(ethylene glycol) diacrylate/sodium alginate (PEGDA/SA) hydrogel microspheres by motor-driven rotation of the oil phase to form a special T-shaped structure with the needle. The main part of the system consists of commercially available motors, a beaker, and needles that do not require precision machining and are user-friendly with low cost. Moreover, by adjusting system parameters such as the needle structure, flow rate, and rotational speed, the platform enables rapid fabrication of hydrogel microspheres with different sizes and diverse cores, including crescent, thick wavy, oval, and spherical. Furthermore, tumor cell-laden hyaluronic acid methacrylate/sodium alginate (HAMA/SA) hydrogel microspheres were fabricated by using this system, which demonstrated good cell viability and proliferation in the subsequent 3D culture. In vitro drug evaluation of tumor models using cisplatin revealed the potential of this system for drug evaluation. These results indicated that RMS has good potential in other 3D cell culture-based biomedical applications.
研究领域:
生物医学工程
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组织工程
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药物开发
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DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
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2019
·Vol. 17
·期 13
·3409-3415
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IF 3.49
Xinyi Wang,Yifu Chen,Junbo Gong,Jinze Hou
Rare multiple fluorescence properties including aggregation-induced emission and polymorphism/shape/size-dependent emission were found coexisting in a class of typical non-steroidal anti-inflammatory analgesic drugs, fenamates, which could provide a new approach toward future drug evaluation. Different from the complexity and biological incompatibility of the traditional AIE molecular design, this work opens new avenues to the development of new AIE systems.
研究领域:
药理学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Translational Lung Cancer Research
·
2024
·Vol. 13
·期 10
·2698
·
IF 4
Ziying Zhao,Xiaoqing Feng,Huijuan Wu,Shuisheng Chen,Changsong Ma,Ziyun Guan,Luwen Lei,Kejing Tang,Xiao Chen,Yong Dong,Yubo Tang
Background Lung cancer is one of the most common malignant tumors worldwide. Despite advances in lung cancer treatment, patients still face challenges related to drug resistance and recurrence. Current methods for evaluating anti-cancer drug activity are insufficient, as they rely on two-dimensional (2D) cell culture and animal models. Therefore, the development of an in vitro drug evaluation model capable of predicting individual sensitivity to anti-cancer drugs would greatly enhance the success rate of drug treatments for lung cancer patients. The purpose of this research is to utilise conditional reprogramming technology to cultivate patient-derived lung cancer cells and to construct an in vitro 3D culture model using sodium alginate (SA) and gelatin. The aim is to study the biological characteristics of cells in the 3D culture model and to further investigate the sensitivity of anti-cancer drugs based on the alginate-gelatin 3D culture model. This approach provides new means and insights for personalized precision anti-cancer therapy and the development of new anti-cancer drugs. Methods Conditional reprogramming technology was used to generate conditionally reprogrammed lung adenocarcinoma cells (CRLCs). Alginate-gelatin hydrogel micro-beads were created to explore their potential use in the assessment of anti-cancer drugs. Cell proliferation was also examined using the MTS assay method. Live/dead staining was performed to estimate cell distribution and viability using calcein acetoxymethyl ester/propidium iodide (calcein-AM/PI) double staining. Protein expression was assessed by Western blot. Results The cells grown in the three-dimensional (3D) culture were in a state of continuous proliferation, and there was an obvious phenomenon of cell mass growth. The drug sensitivity assay results demonstrated that compared with the 2D-grown cells, the CRLCs grown in the alginate-gelatin hydrogel micro-beads exhibited more resistance to anti-cancer drugs. The results also showed that the 3D-cultured CRLCs showed greater protein expression levels of stem cell hallmarks, such as Nanog Homeobox (NANOG), SRY-Box Transcription Factor 2 (SOX-2), and aldehyde dehydrogenase 1 family member A1 (ALDH1A1), than the 2D-grown cells. Conclusions These findings suggest that the 3D hydrogel cell culture models more closely mimicked the in vivo biological and clinical behavior of cells, and demonstrated higher innate resistance to anti-cancer drugs than the 2D cell culture models, and thus could serve as valuable tools for diagnosis, drug screening, and personalized medicine.
研究领域:
肿瘤学
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药理学
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生物技术
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yaqi Wang,Feng Tian,Yujie Duan,Zhuogang Li,Qiaotong Chen,Jiaying Chen,Xiaomin Miao,Yanhong Xu,Chulan Xu,Yadong Tang
The development of three-dimensional (3D) in vitro model to recapitulate the in vivo tumor tissue is essential for studying tumor biology, discovering anti-cancer drugs, and evaluating anti-cancer drug efficacy . However, most of the previous models lack the involvement of vascular barrier. Here, we proposed an in vitro 3D cocultured tumor-vascular barrier model by the combination of alginate hydrogels beads and Transwell system. PC-3 cells and NIH/3T3 cells were encapsulated in alginate hydrogel beads, which were cultured in the bottom chamber of Transwell, while human umbilical vein endothelial cells (HUVECs) were cultured on the porous membrane in the upper chamber to form vascular barrier. The effect of the concentration of alginate sodium on the morphology, diameter and swelling ratio of the beads was studied. The alginate sodium content and cell seeding density were further optimized according to cell proliferation ability. The formation of endothelial barrier was verified by immunostaining with tight junction protein VE-cadherin and transendothelial electrical resistance (TEER) monitoring. Finally, the drug response of 3D cocultured tumor-vascular barrier model to curcumin was evaluated. Compared with two-dimensional (2D) coculture model and 3D coculture spheroid model, 3D tumor-vascular barrier model showed the highest activity of cancer cells and the strongest drug resistance. The developed 3D cocultured tumor-vascular barrier model possesses great potential to be applied for in vitro evaluation of anti-tumor drugs.
研究领域:
癌症生物学
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药理学
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生物医学工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biofabrication
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2023
·
IF 9
Jianpei Dong,Jianhua Zhou,Hao Tang,Baiqi Chen,Lu Huang
Cell-laden hydrogel microstructures have been used in broad applications in tissue engineering, translational medicine, and cell-based assays for pharmaceutical research. However, the construction of cell-laden hydrogel microstructures in vitro remains challenging. The technologies permitting generation of multicellular structures with different cellular compositions and spatial distributions are needed. Herein, we propose a laser-guided programmable hydrogel-microstructures-construction platform, allowing controllable and heterogeneous assembly of multiple cellular spheroids into spatially organized multicellular structures with good bioactivity. And the cell-laden hydrogel microstructures could be further leveraged for in vitro drug evaluation. We demonstrate that cells within hydrogels exhibit significantly higher half-maximal inhibitory concentration values against doxorubicin (DOX) compared with traditional 2D plate culture. Moreover, we reveal the differences in drug responses between heterogeneous and homogeneous cell-laden hydrogel microstructures, providing valuable insight into in vitro drug evaluation.
研究领域:
组织工程
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转化医学
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药物研究
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生物技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Jiarun Sun,Youping Gong,Yuchen He,Jianwei Cui,Haifeng Chen,Nanyan Kang,Yixie Wu,Jiahao Hui,Huipeng Chen,Rougang Zhou,Huifeng Shao,Ying Yu
Vascularized tissue models represent a pivotal approach for enhancing the accuracy of clinical drug prediction by recapitulating the in vivo microenvironment. However, replicating the structural complexity, functional integration, and long-term stability inherent in native vascular tissues remains a significant challenge within the tissue engineering field. Herein, a novel strategy employing aqueous-embedded coaxial bioprinting is proposed. By optimizing the rheological compatibility between alginate-collagen (Alg-Col) bioink and xanthan gum-collagen (XG-Col) support bath, the high-fidelity and efficient fabrication of vascularized tissue models is achieved. Utilizing a triaxial nozzle, synchronous deposition of a bilayered vascular construct containing human umbilical vein endothelial cells (HUVECs) and human lung fibroblasts (HLFs) is performed directly within a tumor cell (human lung adenocarcinoma PC-9 cell line)-laden support bath, resulting in the construction of a perfusable vascularized lung cancer tissue model. Drug assessment revealed significantly lower sensitivity of PC-9 cells to erlotinib within the 3D vascularized model compared to controls. In addition to the physical barrier effect, the vascularized microenvironment activated cancer cell survival pathways primarily through paracrine signaling from endothelial cells and fibroblasts. Gene expression analysis further demonstrated the induction of epithelial-mesenchymal transition (EMT) in the vascularized model. This integrated platform more accurately recapitulates in vivo drug diffusion kinetics and resistance mechanisms, thereby providing an innovative preclinical platform for enhanced anticancer drug screening.
研究领域:
组织工程
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生物打印
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癌症研究
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药物开发
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再生医学
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微环境建模
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药理学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOCHEMICAL ANALYSIS
·
2025
·
IF 2.6
Yan Jiang,Hui Ni,Wen-Jing Zhao,Long Wang,Cai Zhang,Ping Li,Hui-Jun Li
Introduction Multiorigin phenomenon is quite common in Chinese herbal medicine, whereas quality consistency evaluation among the involved plant species is seldom considered. Objectives The present study, taking Taraxaci herba as a typical case, aimed to develop a strategy based on a combination of chemical similarity and in vitro bioequivalence to evaluate the quality consistency of three Taraxacum species. Materials and Methods The chromatographic fingerprints were established through two approaches, namely, high-performance liquid chromatography coupled with photodiode array detector and quadrupole time-of-flight mass spectrometry (HPLC-PDA/QTOF-MS) and gas chromatography coupled with quadrupole time-of-flight mass spectrometry (GC-QTOF-MS). The common characteristic peaks from chromatographic fingerprints were quantified. The bioactivities were tested by antioxidant and anti-inflammatory activity assays. Quality consistency of the three Taraxacum species was globally evaluated by using a combination of chemical similarity and in vitro bioequivalence through univariate and multivariate statistical analysis. Results The statistical results showed no classification of the three species based on contents of quantified analytes and in vitro bioactivities, respectively. Conclusion This study not only demonstrated the medicinal interchangeability of three species of Taraxaci herba but also proposed a comprehensive strategy to evaluate quality consistency of multiorigin Chinese herbal medicines by integrating chemical similarity and in vitro bioequivalence.
研究领域:
生药学
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天然产物化学
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中医药学
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分析化学
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药物评价
✓ 已验证
产品关联
DOI
PubMed
高影响因子