NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 7
·1439-1453
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IF 2.772
Jia Jingjing,Zhang Ting,Chi Jieshan,Liu Xiaoma,Sun Jingjing,Xie Qizhi,Peng Sijia,Li Changyan,Yi Li
CeO 2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO 2 @PAA-LXW7, a new compound that couples CeO 2 @PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H 2 O 2 -induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H 2 O 2 -induced injury. We used H 2 O 2 -induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO 2 @PAA-LXW7. In this study, LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 inhibit H 2 O 2 -induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H 2 O 2 -induced NGF-differentiated PC12 cells, whereas LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO 2 @PAA-LXW7 on H 2 O 2 -induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO 2 @PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H 2 O 2 -induced NGF-differentiated PC12 cells. LXW7, CeO 2 @PAA, and CeO 2 @PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H 2 O 2 in NGF-differentiated PC12 cells. CeO 2 @PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO 2 @PAA.
研究领域:
神经科学
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药理学
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细胞生物学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Kaiyuan Wang,Hao Ye,Xuanbo Zhang,Xia Wang,Bin Yang,Cong Luo,Zhiqiang Zhao,Jian Zhao,Qi Lu,Haotian Zhang,Qiming Kan,Yongjun Wang,Zhonggui He,Jin Sun
Metastasis is closely associated with high breast cancer mortality. Although nanotechnology-based anti-metastatic treatments have developed rapidly, the anti-metastasis efficiency is still far from satisfactory, mainly due to the poor recognition of circulating tumor cells (CTCs) in blood. Herein, we developed an exosome-like sequential-bioactivating prodrug nanoplatform (EMPCs) to overcome the obstacle. Specifically, the reactive oxygen species (ROS)-responsive thioether-linked paclitaxel-linoleic acid conjugates (PTX-S-LA) and cucurbitacin B (CuB) are co-encapsulated into polymeric micelles , and the nanoparticles are further decorated with exosome membrane (EM). The resulting EMPCs could specifically capture and neutralize CTCs during blood circulation through the high-affinity interaction between cancer cell membrane and homotypic EM. Following cellular uptake, EMPCs first release CuB, remarkably blocking tumor metastasis via downregulation of the FAK/MMP signaling pathway . Moreover, CuB obviously elevates the intracellular oxidative level to induce a sequential bioactivation of ROS-responsive PTX-S-LA. In vitro and in vivo results demonstrate that EMPCs not only exhibit amplified prodrug bioactivation, prolonged blood circulation, selective targeting of homotypic tumor cells, and enhanced tumor penetration, but also suppress tumor metastasis through CTCs clearance and FAK/MMP signaling pathway regulation. This study proposes an integrated approach for mechanism-based inhibition of tumor metastasis and manifests a promising potential of programmable-bioactivating prodrug nanoplatform for cancer metastasis inhibition .
研究领域:
纳米技术
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癌症生物学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2022
·
IF 5.942
Shan-Mei Chen,Jun-Nan Feng,Chuan-Ke Zhao,Li-Cheng Yao,Li-Xin Wang,Lin Meng,Shao-Qing Cai,Cai-Yun Liu,Li-Ke Qu,Yan-Xing Jia,Cheng-Chao Shou
Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of Arecaceae and the rhizome of Smilax glabra Roxb . Our preliminary studies revealed that it had potential antiangiogenic and antilymphangiogenic activity by directly targeting VEGFR2/3 and COX2 in endothelial cells. However, the influence of aiphanol on cancer cells per se remains largely undefined. In this study, the effects and related mechanisms of aiphanol on cancer growth and metastasis were evaluated in vitro and in vivo . Acute toxicity assay and pharmacokinetic analysis were utilized to investigate the safety profile and metabolism characteristics of aiphanol. We revealed that aiphanol inhibited the proliferation of various types of cancer cells and the growth of xenograft tumors in mice and zebrafish models. The possible mechanism was associated with the inactivation of multiple kinases, including FAK, AKT and ERK, and the upregulation of BAX and cleaved caspase-3 to promote cancer cell apoptosis. Aiphanol significantly inhibited cancer cell migration and invasion, which was related to the inhibition of epithelial-mesenchymal transition (EMT) and F-actin aggregation. Aiphanol effectively attenuated the metastasis of several types of cancer cells in vivo . In addition, aiphanol exerted no significant toxicity and had fast metabolism. Collectively, we demonstrated the anticancer effects of aiphanol and suggested that aiphanol has potential as a safe and effective therapeutic agent to treat cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Bowen Zhang,Junqing Leng,Zhicong Ouyang,Zijian Yang,Qing Zhang,Qingchu Li,Dichen Li,Huiyu Zhao
Polyetheretherketone (PEEK) has been widely used in the preparation of orthopedic implants due to its biological inertness and similar mechanical modulus to natural bone. However, the affinity between biological tissue (bone and soft tissue) and PEEK surface is weak, leading to low osseointegration and an increased risk of inflammation. The situation could be improved by modifying PEEK surface. Surfaces with good hydrophilicity and proper microtopography would promote cellular adhesion and proliferation. This work presented a two-step surface modification method to achieve the effect. Polyacrylic acid (PAA) chains were grafted on PEEK surface by UV irradiation. Then, ethylenediamine (EDA) was added to introduce amino groups and promote the cross-linking of PAA chains. Furthermore, a mathematical model was built to describe and regulate the surface topography growth process semi-quantitatively. The model fits experimental data quite well (adjusted R 2 = 0.779). Results showed that the modified PEEK surface obtained superhydrophilicity. It significantly improved the adhesion and proliferation of BMSCs and MFBs by activating the FAK pathway and Rho family GTPase. The cellular affinity performed better when the surface topography was in network structure with holes in about 25 μm depth and 20–50 μm diameter. Good hydrophilicity seems necessary for the FAK pathway activation, but simply improving surface hydrophilicity might not be enough for cellular affinity improvement. Surface topography at micron scale should be a more important cue. This simple surface modification method could be contributed to further study of cell-microtopography interaction and have potential applications in clinical PEEK orthopedic implants.
研究领域:
生物材料
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组织工程
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骨科
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 107
·期 6
·1264-1272
·
IF 3.221
Tao Huang,Jiangwei Xiao,Shuhao Wang,Zhaohong Liao,Tao Huang,Ruicai Gu,Junhua Li,Gang Wu,Hua Liao
Introducing or grafting molecules onto biomaterial surfaces to regulate muscle cell destination via biophysical cues is one of the important steps for biomaterial design in muscle tissue engineering. Therefore, it is important to understand the interaction between myoblasts and myofibers with substrates modified by biomimetic layer with different thicknesses. In this study, we used a surface-induced atom transfer radical polymerization method to synthetize and graft poly-phenoxyethyl methacrylate (PHEMA) brushes having different lengths on the glass substrates. C2C12 myoblasts were seeded on the PHEMA brushes and differentiated using horse serum, for analyzing the sensibility of muscle cells to feel environment changing, and further investigating whether the depths of grafting layer on the biomaterial surface are important factors in regulating muscle cell behaviors. Our results demonstrated that on the thicker PHEMA brushes surface (200 and 450 nm), C2C12 myoblasts showed a better survival and proliferation and were favorable for cell fusion and myotube formation. Furthermore, myofibers survived on the thicker brushes were more functional and upregulated cytoskeleton proteins (tubulin, vimentin, and vinculin) and FAK levels, and enhanced the expression levels for mechanical stress molecules (HGF, NOS-1, and c-Met). These results suggest that grafting thickness of PHEMA layer on the substrate led to the myoblasts/myofiber behavior change, which would be valuable for the design and preparation of the modified layer on muscle tissue engineering scaffolds. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1264–1272, 2019.
研究领域:
生物材料
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组织工程
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细胞生物学
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肌肉生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2017
·
IF 4.521
Jing Zhang,Li Li,Yueting Peng,Yu Chen,Xiaoying Lv,Shun Li,Xiang Qin,Hong Yang,Chunhui Wu,Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH 3 , NH 2 , OH), it was found that hydrophobic surfaces modified with CH 3 and NH 2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH 3 and NH 2 triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH 3 - and NH 2 -modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH 3 - and NH 2 -modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）