IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2021
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IF 2.73
Yang Liu,Hua Fu,Li Zuo
Background Angiogenesis and inflammation exhibit a mutually reinforcing relationship in many human diseases. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic mediators. Conbercept is a novel VEGF inhibitor.Method Type II collagen-induced rat rheumatoid arthritis (CIA) model was established to evaluate the anti-chronic inflammation activities of Conbercept. ELISA was used to measure the concentrations of immune factors in the blood of arthritis rats. The xylene-induced ear edema was conducted to evaluate the effect of Conbercept on acute inflammation.Result and discussion Our results showed that Conbercept significantly reduced the paw edema volume and the arthritis index in CIA rats. Furthermore, we found that Conbercept decreased the serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in CIA rats. Xylene-induced ear edema is a widely used method to study acute inflammation. Conbercept significantly inhibited xylene-induced ear edema.Conclusion All results indicate that Conbercept exhibits significant inhibition of acute and chronic inflammation.
研究领域:
药理学
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免疫学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROVASCULAR RESEARCH
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2021
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IF 3.514
Yi Wang,Yang Yao,Rong Li,Binghui Wu,Huiqin Lu,Jing Cheng,Zhe Liu,Junhui Du
Introduction Choroidal neovascularization (CNV) is the main pathological change of wet age-related macular degeneration. Anti-VEGF drugs are the most commonly used treatment for CNV. The biggest drawback of anti-VEGF drugs is the recurrence of CNV, which requires repeated therapy several times. Autophagy activation may be involved in reducing the therapeutic effect of anti-VEGF drugs. So, this study aims to elucidate the effect and mechanism of anti-VEGF drugs on endothelial autophagy and neovascularization in vitro. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O 2 , 5% CO 2 , 94% N 2 ), anti-VEGF group (group1: Ranibizumab 100 μg/ml; group2: Aflibercept , 400 μg/ml; group3: Conbercept , 100 μg/ml). Autophagy-related proteins were examined by Western blot . RFP-GFP-LC3 was used to detect autophagy and autophagic flow. Subsequently, we used autophagy inhibitors (3-MA or CQ) to inhibit Conbercept induced autophagy and to observe its effect on angiogenesis in vitro. Proliferation, migration, and tube formation of endothelial cells can be used to study neovascularization in vitro. In this research, the CCK-8 assay was used to detect cell proliferation . Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Flow cytometry and Tunel were used to detect cell apoptosis . Finally, the mechanism of Conbercept activated autophagy was studied. Western blot was used to detect the expression of p53 and DRAM (damage-regulated autophagy modulator), upstream activators of autophagy. Results The protein levels of Beclin-1 and LC3-2/1 in Ranibizumab and Conbercept groups were significantly higher than in the hypoxia group( P < 0.05). While the expression of P62 was decreased ( P < 0.05). The autophagic flux was showed the same results. However, Aflibercept showed the opposite effect on autophagy. Compared with the Conbercept group, autophagy inhibitor 3-MA or CQ can further inhibit cell proliferation and promotes cell apoptosis ( P < 0.05). Conbercept significantly inhibited cell migration compared with the hypoxia group (633.08 ± 72.52 vs. 546.33 ± 24.61), while the autophagy inhibitor group (3-MA or CQ) had a more obvious inhibition effect (309.75 ± 86.36 and 263.33 ± 68.67) ( P < 0.05). For tube formation, the number of tube formation was decreased significantly in the Conbercept group (32.00 ± 2.00) compared to the hypoxia group (39.00 ± 1.53) and even further reduced in 3-MA or CQ group (24.00 ± 3.61, 20.00 ± 2.65). The length of master segments in the hypoxia group was 15,668.00 ± 894.11. It was decreased in Conbercept (13,885.34 ± 730.03). In 3-MA or CQ group, the length of master segments dropped further (11,997.00 ± 433.66, 10,617.67 ± 543.21). Compare with the hypoxia group, the expression P53 and DRAM were increased in the Conbercept group ( P < 0.05). Autophagy-related proteins LC-3, Beclin-1, and DRAM were inhibited by P53 inhibitor Pifithrin-α (PFTα) ( P < 0.05). Conclusion Ranibizumab and Conbercept can trigger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of Conbercept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of the p53/DRAM pathway.
研究领域:
眼科学
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细胞生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Chen Sun,Shuyue Zhang,Nan Xu,Kun Liu,Fang Wei,Xiaoqian Zhang,Jigang Zhang,Shen Gao,Yuan Yu,Xueying Ding
Introduction Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance.Methods Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue.Results PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection.Conclusion PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.
研究领域:
眼科学
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药学
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药物递送系统
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生物技术
✓ 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）