EXPERIMENTAL EYE RESEARCH
·
2014
·
IF 3.017
Yong-Jie Li,Xiao-Hong Li,Liang-Fen Wang,Xi Kuang,Zhi-Xiong Hang,Yong Deng,Jun-Rong Du
αvβ3 integrin has been reported as a promising therapeutic target for angiogenesis . In the present study, we tested the antiangiogenic activity of 3-[3-(6-guanidino-1-oxoisoindolin-2-yl) propanamido]-3-(pyridin-3-yl) propanoic acid dihydrochloride (GOPPP), a novel non-peptide αvβ3 antagonist. Both human umbilical vein endothelial cells (HUVECs) and a mouse model of oxygen-induced retinopathy (OIR) were investigated separately. HUVEC adhesion, proliferation, migration, ERK1/2 and Akt phosphorylation were assessed. C57BL/6 mice were used for the studies in the OIR model. After exposure to 75% oxygen from postnatal day (PD) 7 to PD12, the mice were returned to room air, and GOPPP was intravitreally administered on PD12. Retinal neovascularization was evaluated on PD17. Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels and ERK1/2 phosphorylation were determined by Western blot analysis of retina proteins. GOPPP significantly inhibited the pro-angiogenic effects of vitronectin on HUVECs, including adhesion, proliferation, and migration, and inhibited ERK1/2 and Akt phosphorylation. Retinal neovascularization in the OIR model was significantly suppressed by intravitreal administration of 50 ng GOPPP. The pro-angiogenic factors HIF-1α and VEGF induced by hypoxia were significantly inhibited by GOPPP in OIR mice. GOPPP administration also inhibited ERK1/2 phosphorylation in the OIR model. These results indicate that GOPPP, a novel αvβ3 integrin antagonist, may have potential for the treatment of pathological retinal angiogenesis.
研究领域:
药理学
·
眼科学
·
分子生物学
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2013
·Vol. 13
·期 4
·483-493
·
IF 3.742
Jin-Lei Wang,Ke-Feng Ren,Hao Chang,Fan Jia,Bo-Chao Li,Ying Ji,Jian Ji
Mussel-inspired poly(dopamine) (PDA) coating is proven to be a simple, versatile, and effective strategy to promote cell adhesion onto various substrates. In this study, the initial adhesive behavior of human umbilical vein endothelial cells (HUVECs) is evaluated on a PDA coating under serum-free conditions. It is found that HUVECs can attach directly to and spread with well-organized cytoskeleton and fibrillar adhesions on the PDA surface, whereas cells adhere poorly to and barely spread on the control polycaprolactone surface. Endogenous fibronectin and α 5 β 1 integrin are found to be involved in the cell adhesion process. These findings will lead to a better understanding of interactions between cells and PDA coating, paving the way for the further development of PDA.
研究领域:
生物材料
·
细胞生物学
·
组织工程
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DOI
PubMed
高影响因子
JOURNAL OF PATHOLOGY
·
2025
·
IF 5.2
Fang Liu,Qingchun Liang,Li Li,Yuan Gong,Mingxi Li,Liyun Feng,An Chen,Yuanzhi Ye,Zirong Lan,Yining Li,Jing-Song Ou,Lihe Lu,Jianyun Yan
Vascular calcification is an important risk factor related to all-cause mortality of cardiovascular events in patients with chronic kidney disease (CKD). Vascular extracellular matrix (ECM) proteins have been demonstrated to regulate vascular calcification. ECM protein thrombospondin 1 (THBS1/TSP-1) plays a critical role in the regulation of vascular diseases. However, whether THBS1 is involved in vascular calcification in CKD patients remains unclear. In this study, RNA sequencing datasets from the Gene Expression Omnibus (GEO) database GSE146638 showed that THBS1 was upregulated in the aortas of CKD rats. Enzyme-linked immunosorbent assay (elisa) revealed that serum THBS1 levels were increased in CKD patients with thoracic calcification. Western blotting and immunofluorescence analysis showed that THBS1 expression was increased in calcified vascular smooth muscle cells (VSMCs) and arteries. THBS1 knockdown exacerbated rat VSMC calcification induced by high phosphorus and calcium, as shown by Alizarin red staining and calcium content assays. Conversely, THBS1 overexpression attenuated VSMC calcification and abdominal aortic calcification in rats with CKD. Moreover, addition of recombinant THBS1 protein inhibited calcification of VSMC S and human arterial rings. Smooth muscle cell-specific knockout of THBS1 mice treated with vitamin D3 displayed aggravated aortic calcification. Mechanistically, the protein–protein interaction database STRING ( http://string-db.org/ ) analysis and coimmunoprecipitation assays revealed THBS1 bound to integrin β3. Reduction of integrin β3 levels abrogated the protective effect of THBS1 on vascular calcification. RNA-seq analysis revealed that THBS1 overexpression modulated the nuclear factor-kappa B (NF-κB) signaling pathway. Of note, the inhibitory effect of THBS1 overexpression on the NF-κB signal was abolished by knockdown of integrin β3. In conclusion, THBS1 interacts with integrin β3 to inhibit vascular calcification through suppression of NF-κB signal, suggesting a promising therapeutic target for vascular calcification in CKD. © 2025 The Pathological Society of Great Britain and Ireland.
研究领域:
医学
·
分子生物学
·
心血管研究
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Haozhi Lei,Haoze Wang,Xiqiu Wang,Zeyu Xiao,Tian Tian,Kai Cui
Detection of progression is of great importance to breast cancer treatment and can benefit patients. Limited by current detection technologies and biomarkers, early breast cancer progression diagnosis remains challenging. Researchers have found blood extracellular vesicles (EVs)-derived integrin α6β4 directly facilitate progression in breast cancer, enabling cancer detection. However, EVs size and heterogeneity hinder protein detection, masked by abundant background EVs. Hence, novel tools for efficient detection of EVs with high selectivity and low interference are significantly desired. Here, a new silver-coated gold nanorods SERS probe, termed as Au@Ag@IDA-B/4MSTP, based on DNA aptamer was established for the detection of integrin α6β4 derived from EVs. Validation of the Au@Ag@IDA-B/4MSTP probes using cell-culture-derived EVs revealed a LOD of 23 particles/μL for EVs detection. This tool was further confirmed to mimic the real state of cancer with subcutaneous tumor model and lung metastasis model in mice. With 10 μL of blood plasma and simple Raman analysis process, the test achieved 85.7 % sensitivity and 83.3 % specificity. Moreover, our method achieves a simplified approach that expedites the detection process. These results demonstrate the good detection performance of Au@Ag@IDA-B/4MSTP probes for EVs integrin α6β4, and suggest that this non-invasive approach could be a promising tool for early detection of breast cancer progression.
研究领域:
癌症研究
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医学诊断
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纳米技术
·
生物标志物检测
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产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2024
·
IF 6
Xueli Ren,Yu Shi,Yanxi Yang,Zhe Liu
Residual tumor margin is one of the major causes of cancer recurrence after surgical resection. Image-guided surgery is conducive to eradication of tumor lesion contributing to the avoidance of local recurrence, potential metastasis, and poor survival rate, which is of significance to malignant tumor, especially invasive gliomas with high incidence and short survive time. Additionally, sonodynamic therapy (SDT) is a favorable method of tumor treatment with deep tissue penetration, non-invasiveness and reliable efficacy. Herein, the engineered carbon dots of RB-CDs@RGD were fabricated for both SDT and fluorescence navigation surgery against gliomas. This engineered RB-CDs@RGD with αvβ3 integrin-targeting ability could generate sufficient reactive oxide species (ROS) induced gliomas cell (rat glioma C6 cell) apoptosis. In vivo studies confirmed superior anti-tumor performance of RB-CDs@RGD with expected biocompatibility. Furthermore, RB-CDs@RGD severed as the tumor-targeted contrast agent was applied for fluorescence-guided surgery of gliomas given its outstanding fluorescence properties. Therefore, RB-CDs@RGD with distinctive fluorescent property, SDT efficiency, and biosafety exhibited distinguished fluorescent imaging-navigated surgery combined with SDT, and could be harnessed as drug delivery nanoplatform for imaging guided-operative treatment with a promising prospect in clinic usage.
研究领域:
癌症研究
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纳米技术
·
生物医学工程
·
神经肿瘤学
·
治疗诊断学
✓ 已验证
产品关联
DOI
高影响因子
Cancer Nanotechnology
·
2021
·Vol. 12
·期 1
·1-15
·
IF 5.095
Wang Jundong,Li Tianhao,Yue Chaochi,Zhong Sen,Yang Xiangdong,Li Jun,Li Yuanzhi
Background The problems associated with the poor water solubility of anticancer drugs are one of the most important challenges in achieving effective cancer therapy. The present study was designed to evaluate the effect of scutellarein on human colon cancer cells in vitro by using a target α v β3 novel scutellarein (Scu)-loaded niosome nanoparticle (β-CD-CL-Scu-cRGD). Results β-CD-CL-Scu-cRGD has a diameter of 140.2 nm and zeta potential of − 11.3 mV with constant physicochemical stability. The MTT assay showed both Scu and β-CD-CL-Scu-cRGD caused a decrease in cell proliferation and viability of LoVo, but β-CD-CL-Scu-cRGD showed better activity in vitro. Colony formation assay and flow cytometry assay showed that β-CD-CL-Scu-cRGD has a better effect on cell proliferation and apoptosis. In vivo, animal experimental results showed that β-CD-CL-Scu-cRGD can significantly inhibit tumor growth, and the bodyweight of mice decreases during the treatment of scutellarein and its derivatives. β-CD-CL-Scu-cRGD could inhibit the protein levels of Ki67 and αvβ3, thereby inhibiting tumor growth. Conclusions Although further in vitro and in vivo studies are necessary, our results suggested that β-CD-CL-Scu-cRGD could be an outstanding carrier to deliver Scu for potential therapeutic approaches into colon cancer.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
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DOI
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 31
·6912-6924
·
IF 5.344
Lei Liu,Xianling Gao,Xiaoyu Li,Guanglin Zhu,Nanying Li,Xuetao Shi,Yingjun Wang
Bioceramic–biopolymer composites have been used extensively as bone tissue engineering scaffolds due to their bioactive properties. However, composite scaffolds are insufficient in inducing osteogenic differentiation of stem cells. In this study, a strategy for the local delivery of bioactive factors by coating calcium alendronate (ALC) on the surface of composite scaffolds was systematically evaluated for the first time. The coated ALC not only displayed excellent cytocompatibility and cell adhesion properties but also resulted in the significant upregulation of osteogenic related gene expression, osteogenic related protein levels, alkaline phosphatase (ALP) activity and calcium deposition of ADSCs. Furthermore, our results suggested that the molecular mechanism of ADSC osteogenic differentiation induced by the constructed ALC may be related to the integrin binding and the activation of FAK/ERK signalling pathways. These findings suggested that ALC-coated composite scaffolds can serve as bone tissue engineering scaffolds, providing a simple and universal method to improve the osteogenic differentiation of ADSCs by calcium phosphate-containing composite materials.
研究领域:
组织工程
·
生物材料
·
干细胞生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Huishang Yang,Chen Lai,Chengkai Xuan,Muyuan Chai,Xuemin Liu,Yunhua Chen,Xuetao Shi
Diabetics face multiple long-term health complications and diabetic foot ulcers affect approximately 15–20% of the diabetic population. The high disability rate of these patients results in substantial mental burden and economic pressure to the individuals as well as the societies. Here, we report a therapeutic integrin-binding pro-survival peptide-engineered silk fibroin nanosheet that can regulate angiogenesis and promote diabetic ulcer healing. The nanosheet with thickness less than 100 nm is highly transparent and flexible, and it can firmly adhere to the biological tissue surfaces in underwater environment. The presence of integrin-binding pro-survival peptide in the nanosheet significantly upregulates the expression of angiogenesis genes and proteins of human umbilical vein endothelial cells (HUVECs). In the diabetic mouse model, the peptide-engineered nanosheet reveals significant acceleration of wound closure, epithelialization and granulation tissue formation. These findings suggest that this functional nanosheet could be a promising therapeutic candidate for complicated diabetic ulcer healing.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
糖尿病研究
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产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Yijie Wang,Hui Zhang,Shiyang Wu,Wanting Wan,Xueping Kang,Bei Gao,Haoyu Shi,Shuyang Zhao,Lin Niu,Rui Zou
The hallmark of orthodontic tooth movement (OTM) is time-consuming during clinical treatments. The acceleration of OTM through modulating proliferation and apoptosis of periodontal ligament cells (PDLCs) possesses the potential application in clinical treatments. Here, we established an in vitro model with a graded increase in substrate stiffness to investigate the underlying mechanism of proliferation and apoptosis of PDLCs. The role of the integrin-linked kinase (ILK) in response to substrate stiffness was investigated by the depletion model of PDLCs. We found that the proliferation and apoptosis of PDLCs show a stiffness-dependent property with stiffer substrates favoring increased bias at the transcript level. Depleting integrin-linked kinase diluted the correlation between PDLCs behaviors and substrate stiffness. Our results suggest that ILK plays a significant role in modulating PDLC proliferation and apoptosis and can serve as a potential target for accelerating OTM.
研究领域:
牙科
·
细胞生物学
·
生物力学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 112
·92292-92302
·
IF 3.84
Meng Cai,Mengyuan Ye,Xingxing Shang,Honghao Sun,Mingxing Liu,Hongmei Sun,Zhuo Ma,Hongda Zhu
Polymeric micelles as nanocarrier-based drug delivery systems provide an innovative platform for selectively delivering active molecules and offer better antitumour activity. However, circulation stability in vivo, controllable drug intracellular release and high targeting efficiency are several practical challenges for micelles. Therefore, we developed cRGD-modified and shell crosslinked micelles (RSCMs) based on amphiphilic poly(styrene-co-maleic anhydride) (SMA). RSCMs exhibited a spherical shape and were homogeneous with an average diameter of 106.1 nm and a low polydispersity of 0.087. In comparison, after crosslinking the micelles possessed better stability against dilution and stronger redox-response towards dithiothreitol (DTT). The SMA micelles displayed high drug loading capacity for hydrophobic DOX with a drug loading of approximately 14.1–19.2% (w/w) and an encapsulation efficiency of 72.1–82.7% (w/w). The in vitro release studies of shell crosslinked micelles showed that DOX release was minimal (<25%, 24 h) under physiological conditions. However, in the presence of 10 mM DTT, accelerated release of DOX was achieved (60%, 24 h). MTT assays in B16F10 cells indicated that RSCMs displayed low cytotoxicity up to a concentration of 500 μg ml−1. Moreover, the IC50 value showed that cRGD-DOX-ss-M could be more effective than other groups. In vitro, cellular uptake was further studied with confocal laser scanning microscopy and flow cytometry, both the qualitative and quantitative results demonstrated that cRGD-DOX-ss-M possessed much better specificity to cancer cells and superior stimulated release property in cytoplasm. Notably, cRGD-DOX-ss-M could more efficiently be delivered to and release into the nuclei of αvβ3 integrin over expressing tumor cell line (B16F10) than counterparts of integrin-deficient tumor cells (Hela). Thus, these cRGD-modified redox-sensitive micelles have appeared as a technology platform with great potential for targeted anticancer drug delivery and release for integrin over expressing tumor cells.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Peptide Science
·
2022
·Vol. 115
·期 2
·e24302
·
IF 2.592
Anqi Wang,Kai Yue,Yiang Wei,Weishen Zhong,Genpei Zhang
The structural change of receptor protein at high temperatures is one of the factors affecting the targeting ability of ligand-installed nanocarriers for combined therapy of hyperthermia and drug delivery. In this study, the binding behaviors and mechanisms of integrin αvβ3 receptor and the arginine-glycine-aspartic acid (RGD) peptide ligand at high temperatures were investigated both theoretically and experimentally. The structural parameters of integrin αvβ3 at different temperatures and the interaction forces between the RGD peptide and integrin αvβ3 at different binding sites were calculated by molecular dynamics simulation. Fourier transform infrared spectroscopy, energy dispersive spectroscopy, ultraviolet–visible absorption spectroscopy, and atomic force microscopy were used to analyze the structural changes of integrin αvβ3 and to measure the ligand-receptor interaction. Results show that the number of hydrogen bonds decreased and the secondary structure of integrin αvβ3 changed with the increase in temperature, indicating the denaturation of integrin αvβ3. The structural stability of the integrin αv subunit was better than that of the integrin β3 subunit at high temperatures. The interaction between the RGD peptide and integrin αvβ3 weakened as the temperature increased because the structure of the integrin αvβ3 binding site became more flexible and the corresponding calcium ions were shed from the binding site. The strongest interaction force was exhibited at the binding site of the integrin β3 subunit at 310 K while it was found at the binding site of the integrin αv subunit at higher temperatures, owing to the smaller structure deformation of the integrin αv subunit. Graphical
研究领域:
生物物理学
·
分子生物学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Song Baiyang,Fang Li,Mao Xufeng,Ye Xianwang,Yan Zejun,Ma Qi,Shi Zewen,Hu Yiwei,Zhu Yabin,Cheng Yue
Introduction: The repair of a diseased ureter is an urgent clinical issue that needs to be solved. A tissue-engineered scaffold for ureteral replacement is currently insufficient due to its incompetent bioactivity, especially in long-segment abnormalities. The primary reason is the failure of urothelialization on scaffolds.Methods: In this work, we investigated the ability of gelatin-grafted tubular scaffold in ureteral repairment and its related biological mechanism. We designed various porous asymmetric poly (L-lactic acid) (PLLA)/poly (L-lactide-co-e-caprolactone) (PLCL) tubes with a thermally induced phase separation (TIPS) method via a change in the ratio of solvents (named PP). To regulate the phenotype of urothelial cells and ureteral reconstruction, gelatin was grafted onto the tubular scaffold using ammonolysis and glutaraldehyde crosslinking (named PP-gel). The in vitro and in vivo experiments were performed to test the biological function and the mechanism of the scaffolds.Results and Discussion: The hydrophilicity of the scaffold significantly increased after gelatin grafting, which promoted the adhesion and proliferation of urothelial cells. Through subcutaneous implantation in rats, PP-gel scaffolds demonstrated good biocompatibility. The in vivo replacement showed that PP-gel could improve urothelium regeneration and maintain renal function after the ureter was replaced with an ∼4 cm-long PP-gel tube using New Zealand rabbits as the experimental animals. The related biologic mechanism of ureteral reconstruction was detected in detail. The gelatin-grafted scaffold upgraded the integrin α6/β4 on the urothelial cell membrane, which phosphorylates the focal adhesion kinase (FAK) and enhances urothelialization via the MAPK/Erk signaling pathway.Conclusion: All these results confirmed that the PP46-gel scaffold is a promising candidate for the constitution of an engineered ureter and to repair long-segment ureteral defects.
研究领域:
生物医学工程
·
组织工程
·
泌尿外科
·
细胞生物学
·
材料科学
✓ 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）