PHYTOTHERAPY RESEARCH
·
2019
·Vol. 33
·期 5
·1579-1591
·
IF 3.766
Li Wan,Qun Zhang,Sheng Wang,Yong Gao,Xiaofei Chen,Yang Zhao,Xiaoping Qian
Angiogenesis is central to a wide range of physiological and pathological processes including wound healing, macular degeneration, and cancer. Excessive or inappropriate vascular supply of tumors is one of the main targets for cancer therapy. Recently, critical and selective transcriptional factors such as yes-associated protein (YAP) that control the expression of angiogenesis factors have gained increasing attention in antiangiogenic therapy. In this study, we have identified and characterized a novel inhibitor of YAP, gambogic acid (GA), which exerted striking antiangiogenic effects both in vitro and in vivo. We demonstrated that GA remarkably inhibited a variety of vascular endothelial growth factor-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of endothelial cells in vitro. In addition, GA resulted in decreased neo-vessel formation in Matrigel plugs of mice and chick chorioallantoic membrane. More importantly, we showed that GA limited tumor growth via preventing tumor angiogenesis and vascular maturation. Further mechanistic studies illustrated that GA directly targeted YAP/STAT3 signaling axis, which is critical for the transcriptional regulation of a series of angiogenic factors. Taken together, these preclinical findings suggest that GA significantly repressed tumor angiogenesis and may serve as a promising drug candidate against cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2023
·
IF 0
Jingtan Zhu,Xiaomei Liu,Jianyi Xu,Zhang Liu,Yating Deng,Junyao Dai,Tingting Yu,Dan Zhu
Summary The majority of fluorescent vessel labeling techniques currently available are limited by their expense, incomplete labeling, or complexity. Here, we present VALID ( v essel l a beling via ge l atin-based l i pophilic d ye solution)—a protocol for complete labeling of different vascular networks. We describe steps for preparing different dye hydrogels, murine vascular casting and tissue harvesting, immunolabeling, tissue clearing, and imaging, as well as detailed analysis of the vascular networks. This protocol is helpful for evaluating vascular lesions in studying different vessel-associated diseases. For complete details on the use and execution of this protocol, please refer to Zhu et al. 1
研究领域:
生物学
·
医学成像
·
血管生物学
✓ 已验证
DOI
PubMed
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Runfeng Cao,Zhenying Chen,Qing Ye,Weiyan Sun,Weikang Lin,Hai Tang,Xingseng Yang,Junhao Liang,Yi Chen,Lei Wang,Qingfeng Bai,Ziying Pan,Yulong Hu,Dong Xie,Deping Zhao,Yong Hu,Chang Chen
The simultaneous regeneration of avascular cartilage ring and vascular connective tissue in one biomimetic tracheal substitute has remained a remarkable challenge in the clinical breakthrough of tissue-engineered trachea for repairing segmental trachea defect. Herein, an unprecedented strategy based on bidirectional modulation of vascular niches is developed through tailoring the tissue-specific scaffolds with programmable functional nucleic acids. Namely, the antiangiogenic characteristic of cartilage-specific scaffold enables development of an avascular niche, and thereby facilitating the regeneration of biomimetic cartilage. Conversely, the angiogenic capability of connective tissue-specific scaffold fosters the creation of a vascular niche, and thus enhancing the regeneration of biomimetic connective tissue. Importantly, the steadily immobilized nucleic acids in specific scaffolds enable the seamless integration of angiogenic and antiangiogenic functions without mutual interference. As such, biomimetic tracheas are successfully engineered with the vascular connective tissue scattering between avascular cartilage rings using the assembly of tissue-specific scaffolds. The results from in vivo trachea regeneration and the in situ trachea reconstruction demonstrate the satisfactory tissue-specific regeneration of (a)vascular niches along with optimal structural, mechanical, and physiological features. This study represents the first demonstration of trachea regeneration promoted by modulation of tissue-specific vascular niches, which adds an additional dimension for the clinical trachea reconstruction.
研究领域:
组织工程
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再生医学
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生物材料
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生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-18
·
IF 9.429
Chen Youlu,Chen Zuoguan,Duan Jianwei,Gui Liang,Li Huiyang,Liang Xiaoyu,Tian Xinxin,Liu Kaijing,Li Yongjun,Yang Jing
Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs.Graphical Abstract
研究领域:
生物医学工程
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分子生物学
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基因治疗
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血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Bingjie Li,Jinbin Pan,Ruijie Zhang,Bing Han,Yujie Zhao,Guijun Liu,Yujie Tong,Yujing He,Guangchao Xie,Ruxia Liu,Ting Zhou,Quan Zhang,Shao-Kai Sun
High-resolution vascular imaging at tens of micrometers in deep tissues in vivo remains a critical challenge. Ultrahigh field susceptibility-weighted imaging (SWI) holds promise but lacking compatible high-sensitivity imaging probes. Herein, we show a holmium (Ho)-based nanoprobes-enhanced SWI strategy for ultrahigh-resolution imaging of cerebral microvessels at 9.4 T. The polyethylene glycol (PEG)-NaHoF 4 nanoprobes (NPs) fabricated via coprecipitation synthesis combined with PEG modification possess uniform size, appropriate hydrodynamic size (20 nm), good biocompatibility, and long circulation half-life (710 min). Notably, the PEG-NaHoF 4 NPs exhibit high r 2 / r 1 742.7) and T 2 * relaxivity ( r 2 *, 73.16 s -1 mM -1 ) under 9.4 T due to the large magnetic moment (∼10.6 μ B ) and short electronic relaxation time (∼10 -13 s) of Ho 3+ . The high susceptibility of PEG-NaHoF 4 NPs in blood vessels induces a significant blooming effect, resulting in a magnified vascular appearance on SWI. In vivo high-resolution imaging of cerebral microvessels with diameters as small as 10 μm is achieved using PEG-NaHoF 4 NPs-enhanced SWI under 9.4 T. In two representative brain disease models, glioma and stroke, this nanoprobe enables high-resolution visualization of tumor vasculature and post-stroke collateral circulation, respectively. Our study offers a new paradigm for precise diagnosis of vascular-related diseases, providing a robust tool for their diagnosis, treatment, and prognosis assessment.
研究领域:
医学影像学
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神经科学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2023
·
IF 2.9
Zhixing Wang,Peng Liu,Peng Ye,Sheng Dai,LuYing Liu,Ping Yang
Dopamine has been widely used for surface modification of cardiovascular medical devices as it forms films on most substrates that provide functional groups for surface chemical modification. However, under oxidative stress, the phenolic hydroxyl group on dopamine can undergo reversible transformation into phenol-semiquinone-quinone, which can cause cytotoxicity and immunotoxicity. In this study, we measured the effects of semiquinone on the behavior of vascular wall cells and inflammatory cells under oxidative stress via ultraviolet irradiation with a hydrogen peroxide diluent. Na2S2O3 was used as a stabilizer to obtain a semiquinone-rich poly-dopamine film, then phenol-semiquinone-quinone ratio on its surface was evaluated at three irradiation-oxidation time points. We found that the poly-dopamine film with ultraviolet irradiation in hydrogen peroxide solution for 15 min had the highest semiquinone occupancy of 19.18%. In the experimental group irradiated for 15 min, endothelial cells were cultured statically for 3 days and the number of surface adherent endothelial cells in the group with added semiquinone stabilizer was reduced to 73% of that in the group without stabilizer, indicating that semiquinone rich surface inhibits adhesion and proliferation of endothelial cells; Smooth muscle cells were cultured statically for 3 days, and the number of adherent smooth muscle on surfaces without stabilizer was reduced to 75% of that on surfaces with stabilizer added, indicating that semiquinone rich surfaces promote smooth muscle proliferation. These results demonstrate that semiquinone can adversely affect the repair effect after implantation of cardiovascular materials. Therefore, our study provides a reference for the application and optimization of dopamine in cardiovascular implant materials.
研究领域:
生物医学工程
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Hui Su,Yucheng Qiu,Jing Luo,Fei Liu,Jun Yang,Xiaofeng Sui,Yue Zhang,Yumei Zhang,Xianyu Zhou
Vascular anastomosis is the cornerstone in microsurgery. To assist complicated microvascular anastomosis with diameters <0.6 mm, nonsuture cuff technique was developed. However, cuff tube made from polyamide is not degradable, and their long-term retention in the body may cause stiffness in blood vessels at the anastomotic site. Thus, development of a biodegradable cuff tube would greatly enhance surgical operability and biosafety. In this study, biocompatible poly-L-lactic acid (PLLA) was chosen as the raw material to prepare cuff tube for nonsuture cuff technique. A customized ‘C’ shaped nozzle was adopted during the melting extruding process, and then was subjected to a water-cooling bath to maintain the round shape and inner diameter of 582 μm ± 20 μm. Its crystallization behavior was controlled through the cooling procedure to achieve the expected mechanical properties and operability. Its good hemocompatibility and genotoxicity were validated by various in vitro assays. Consequently, a PLLA cuff tube with a radial tensile strength of 12 MPa and an elastic modulus of 1685 MPa was prepared and used to assist establishing a rat orthotopic hindlimb transplantation model, which indicated that our PLLA cuff tube was suitable for microvascular anastomosis in organ or tissue repair.
研究领域:
医学
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生物材料学
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外科手术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gels
·
2023
·Vol. 9
·期 5
·373
·
IF 4.6
Qiulin Wang,Xiaoyu Wang,Yakai Feng
Chitosan hydrogels have a wide range of applications in tissue engineering scaffolds, mainly due to the advantages of their chemical and physical properties. This review focuses on the application of chitosan hydrogels in tissue engineering scaffolds for vascular regeneration. We have mainly introduced these following aspects: advantages and progress of chitosan hydrogels in vascular regeneration hydrogels and the modification of chitosan hydrogels to improve the application in vascular regeneration. Finally, this paper discusses the prospects of chitosan hydrogels for vascular regeneration.Keywords:chitosan;hydrogel;tissue engineering;vascular regeneration;angiogenesis
研究领域:
生物材料
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组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-25
·
IF 7.4
Ren Jun-Song,Bai Wen,Ding Jing-Juan,Ge Hui-Min,Wang Su-Yu,Chen Xi,Jiang Qin
Background Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.Methods Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1.Results Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis.Conclusion In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
眼科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
·
2025
·
IF 4.2
Wen Xin,Peng Yuefeng,Yang Wenqing,Zhu Yuzhong,Yu Fan,Geng Li,Wang Xianfeng,Wang Xiaoyan,Zhang Xiaodong,Tang Yi,Feng Lei,Zhou Tingting,Jia Hongliang,Yang Liu
Transient receptor potential canonical 1 (TRPC1) channel, a Ca 2+ -permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. Key messages
AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice.
TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling.
Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.
研究领域:
心血管病学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2010
·
IF 7.365
De-Hong Yu,Qin Lu,Jing Xie,Chao Fang,Hong-Zhuan Chen
Antiangiogenic cancer therapy can be achieved through the targeted delivery of antiangiogenic agents to the endothelial cells of tumor neovasculature. In the present study, we developed a drug delivery system (DDS), nanoparticles conjugated with K237-(HTMYYHHYQHHL) peptides for tumor neovasculature targeting drug delivery. Paclitaxel, a chemotherapeutic agent with potent antiangiogenic activity , was used as a prototype drug. We synthesized the aldehyde poly(ethylene glycol)–poly(lactide) (aldehyde-PEG–PLA) block copolymer by ring opening polymerization . The nanoparticles loading paclitaxel (PTX-NP) were fabricated using the O/W emulsion and evaporation technique. K237 ligand, a peptide that can bind to the KDR receptors predominantly expressed on the surface of tumor neovasculature endothelial cells with high affinity and specificity and inhibit the VEGF-KDR angiogenic signal pathway, was conjugated to the aldehyde group of PEG chain using the N-terminal PEGylation technique. The K237 conjugated paclitaxel-loaded nanoparticles (K237-PTX-NP) had a hydrodynamic diameter of 150 nm. The K237 density on nanoparticle surface was 474 and the mean distance between two neighboring PEG chains linked to K237 peptide was 12 nm. The K237 conjugated nanoparticles could be significantly internalized by human umbilical vein endothelial cells (HUVEC) through the K237-KDR interaction, and this facilitated uptake led to the expected enhanced antiangiogenic activity shown by HUVEC proliferation , migration and tube formation compared to cells treated with the commercial formulation Taxol ® and PTX-NP. The long-circulating property and the K237 ligand of K237-PTX-NP warranted rapid, long-term, and accurate in vivo tumor neovasculature targeting, and thereafter the significant apoptosis of tumor neovasculature endothelial cells and necrosis of tumor tissues of MDA-MB-231 breast tumors implanted in female BLAB/c nude mice . This nanoparticulate DDS offers a new strategy for paclitaxel chemotherapy application and it could also be used to carry other chemotherapeutic drugs, genes, and proteins with antiangiogenic activity for antiangiogenic cancer therapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
STAR Protocols
·
2024
·
IF 1.3
Zongyou Jiang,Zhongzuo Huang,Yating Li,Xiaoxiao Yu,Yannan Ma,Jinyan Yu,Yifan Xiang,Yue Lv,Shaoqi Gao,Yicheng Luo,Bo Wang
Summary In vitro cell culture serves as an efficient system for studying animal cell behavior in a controlled setting. Here, we present a 3D culture model for forming ruminant adipose organoids using stromal vascular fraction cells. We describe steps for forming cell spheroids and growing them on a Matrigel-coated surface. We then detail procedures for inducing organoids to undergo angiogenesis and adipogenesis followed by capillary sprouting. This protocol can be utilized to study the interaction between blood vessels and adipocytes. For complete details on the use and execution of this protocol, please refer to Yu et al. 1
研究领域:
细胞生物学
·
组织工程
·
兽医学
✓ 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）