Frontiers in Pharmacology
·
2018
·
IF 3.831
Jiao Shihong,Tang Binghua,Wang Yong,Li Chun,Zeng Zifan,Cui Lixia,Zhang Xuefeng,Shao Mingyan,Guo Dongqing,Wang Qiyan
Coronary artery disease (CAD) is one of the leading causes of deaths worldwide. Energy metabolism disorders, including a reduction in fatty acids oxidation and upregulation of glycolysis pathway, are involved in the process of CAD. Therapeutic angiogenesis has become a promising treatment for CAD. Traditional Chinese medicines, such as Danqi Pill (DQP), have been proven to be effective in treating CAD in China for many years. However, the pro-angiogenic effects of DQP based on fatty acids oxidation are still unknown and the mechanism is worthy of investigation. In this study, left anterior descending (LAD) coronary artery was ligated to induce the CAD models in vivo, and cardiac functions were examined using echocardiography. Human umbilical vein endothelial cells (HUVEC) were subjected to H2O2-induced oxidative stress in vitro. The effects of DQP on CAD rat models and in vitro HUVEC were detected. Our results showed that DQP had cardio-protective effects in rat model. The intensity of capillaries in the marginal area of infarction of the rat heart was increased remarkably in DQP group, and the expression of PPARα and VEGF-2 were increased. The key enzymes involved in the transportation and intake of fatty acids, including CPT1A and CD36, both increased. In H2O2-induced endothelial cells injury models, DQP also showed protective roles and promoted capillary-like tube formation. DQP up-regulated key enzymes in fatty acids oxidation in H2O2-treated HUVEC. In addition, inhibition of CPT1A compromised the pro-angiogenic effects of DQP. In conclusion, fatty acids oxidation axis PPARα-CD36-CPT1A was involved in the pro-angiogenic roles of DQP against CAD. Cardiac CPT1A may serve as a target in therapeutic angiogenesis in clinics.
研究领域:
心脏病学
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药理学
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分子生物学
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中医
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Lingyu Sun,Yu Wang,Lu Fan,Yuanjin Zhao
Wound healing has become a health concern and economic burden worldwide for its high incidence and complexity. Attempts to improve wound treatment tend to develop biomedical patches with delicate structure design and functionality. In this paper, we present novel multifunctional microneedle patches with aligned carbon nanotube (CNT) sheet basement for promoting wound healing. Because of the outstanding biocompatibility, biodegradability and non-immunogenicity, hyaluronic acid (HA) is utilized to construct the CNT-integrated microneedle patch with vascular endothelial growth factor (VEGF) encapsulation. It was found that the aligned CNT layer basement could not only impart the composite microneedle patch with orientation morphology, but also endow the patch with controllable release performance, due to its photo-thermal or electro-thermal conversion capacity. Based on these features, we have demonstrated that the highly ordered microstructure of CNT could effectively induce the orientation of fibroblasts; while VEGF release could facilitate tubular formation of endothelial cells. Thus, the aligned CNT and VEGF-loaded multifunctional patch is beneficial to the wound repair process in a typical animal experiment. These results indicate that the proposed microneedle patch is potentially promising for regeneration medicine.
研究领域:
生物医学工程
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材料科学
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再生医学
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组织工程
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产品关联
DOI
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Ying Wang,Yongjun Li,Dongxia Liu
Background This study aimed to investigate role of erythropoietin in atherosclerosis and explore whether underlying mechanism is associated with PI3K/AKT/mTOR pathway. Methods High-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice (C57BL/6 genetic background). Mice were randomly divided into the control group and the EPO group. Hematoxylin-eosin was performed for the determination of atherosclerotic lesions. The expression levels of related proteins were detected by western blot analysis . Results Erythropoietin significantly enhanced the incidence of hemorrhage in atherosclerotic plaques compared with the control group. The proteins’ expression signaling pathways (including PI3K , AKT, and mTOR) and angiogenesis-related proteins (VEGF, COX-2, and HIF-1α) were proved to be up-regulated by erythropoietin. Additionally, erythropoietin significantly enhanced the incidence of hemorrhage in the atherosclerotic plaques compared with the control group. The vitro experiments were conducted in macrophages at 21% O 2 or 1% O 2 . The data showed that expression of p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α related proteins increased in 1% O 2 group than 21% O 2 group. Moreover, compared with control group, protein expression including p -PI3K, p -AKT, p -mTOR, VEGF, COX-2, and HIF-1α was markedly increased in EPO group, decreased in inhibitors group, and similar results were observed in EPO+ inhibitors group. Conclusion The present study demonstrated that erythropoietin might promote angiogenesis in atherosclerotic vulnerable by activating PI3K/AKT/mTOR signaling pathway in atherosclerotic, providing a novel therapeutic target for atherosclerotic targeted therapy.
研究领域:
心血管疾病
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分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2022
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IF 5.112
Lili Lin,Saili Xie,Yingzheng Zhao,Zenghui Liang,Qilong Wu,Mingling Fang,Xiaolu Teng,Binbin Shi,Yunjun Yang,Bin Chen
Purpose Acute pancreatitis (AP) involves sudden inflammation caused by abnormal activation of pancreatic enzymes. The mechanisms underlying AP include oxidative stress, high levels of inflammatory mediators and inflammatory cell infiltration. Heparin, a key therapeutic drug, exerts anti-inflammatory, antioxidative, and anticoagulative effects. However, safe and effective drug delivery remains an obstacle. This study is the first to investigate the therapeutic effects of heparin-loaded microbubbles (HPMB) combined with ultrasound (UHPMB) and the role of heparin in acoustic cavitation. Methods The characteristics of the microbubbles, including particle size, concentration, release, stability, and development, were studied. Heparin concentration in the HPMB was measured, and heparin-induced anticoagulation was evaluated. Drug safety was explored using hemolysis and cell viability assessments. The ability of HPMB to alleviate oxidative stress and inflammation were investigated in vitro . L -arginine induces AP in vivo . UHPMB was used for AP treatment. Serum amylase levels were measured and pancreatic architecture and pathological features were evaluated to determine AP severity. In vivo efficacy was evaluated, and the underlying mechanism of heparin action during acoustic cavitation was explored. Results HPMB was spherical and presented as an emulsion-like solution without aggregation. HPMB was visible and stable and effectively released the drug under ultrasound (US). HPMB and UHPMB led to lower AP severity than in the untreated group. US-targeted microbubble destruction (UTMD) enhanced the therapeutic effect by decreasing oxidative stress and inflammation in AP models without injuring vital organs. UHPMB regulated VEGF/Flt-1 and SOD-1 expression. HPMB can also mitigate oxidative stress and inflammation in H 2 O 2 -pretreated cells. Conclusion UHPMB exhibits a strong ability not only to selectively target pancreatic lesions and release heparin but also to provide efficient protection by inhibiting oxidative stress and inflammation.
研究领域:
药理学
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治疗学
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医学成像
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炎症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
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IF 5.6
Yu Dun,Jinxi Xie,Jian Zhou,Hanbing Hu,Fuli Liu,Yiru Shao,Jie Shen
CD34/CD45-DSCs alleviate phosgene-induced acute lung injury (P-ALI) in rats. • CD34 + CD45 + cells reside in bone marrow, peripheral blood, and BALF with dynamic changes post-injury. • CD34/CD45-DSCs exhibit MSC-like properties with osteogenic, adipogenic, and chondrogenic potential in vitro. • CD34/CD45-DSCs showed prolonged lung retention perivascular engraftment, and PVSC-like phenotype acquisition without exacerbating fibrosis. • CD34/CD45-DSCs restore pulmonary vascular barrier via VEGF-PI3K/AKT/eNOS signaling pathway. Phosgene inhalation causes acute lung injury (ALI) with high mortality and no effective antidote, and stem cell therapy is limited by poor cell survival and low engraftment efficiency. Here, we identified a rare endogenous CD34 + CD45 + cell fraction that reside in bone marrow, peripheral blood, and bronchoalveolar lavage fluid (∼1% baseline), exhibits a “decrease-then-recovery” dynamic after phosgene injury, and displays MSC-like properties with trilineage (osteogenic, adipogenic, and chondrogenic) potential in vitro. Intravenous administration of expanded CD34 + CD45 + -derived stromal cells (CD34/CD45-DSCs) significantly alleviated pulmonary vascular leakage and inflammatory in a rat model of phosgene-induced ALI (P-ALI). In vivo bioluminescence imaging further revealed that CD34/CD45-DSCs exhibited prolonged pulmonary retention compared with BMSCs (11.3 days vs. 48 h), proliferated, engrafted around the pulmonary vasculature, and acquired a perivascular stromal cell (PVSC)-like phenotype expressing late-stage mesenchymal progenitor, pericyte, and fibroblast markers. In a bleomycin-induced pulmonary fibrosis model, CD34/CD45-DSCs did not exacerbate fibrotic changes at day 28. Mechanistically, VEGF knockdown or neutralization abolished the barrier-protective effect, which was rescued by an AKT agonist and blocked by an inhibitor. Moreover, CD34/CD45-DSCs upregulated tight junction proteins ZO-1 and Occludin in injured endothelial cells via VEGF-PI3K/AKT/eNOS signaling. Collectively, our study defines the origin, spatiotemporal dynamics, perivasucular engraftment, PVSC-like fate acquisition, and VEGF-PI3K/AKT/eNOS-dependent mechanism of CD34/CD45-DSCs, supporting their potential as a relatively safe, long-engrafting, and mechanistically transparent cell-based strategy for ALI.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Ke Zhu,Kun Wang,Yu Yao,Yinxia Zhu,Ziyang Zhu,Wenyuan Wang,Ruijie Qian,Zhiping Deng,Jun Zhao,Yunli Shen,Fuqiang Shao
Myocardial infarction (MI) is a severe cardiovascular event arising from vascular thrombosis, causing cardiomyocyte fatality. Neovascularization, facilitated by Vascular Endothelial Growth Factor (VEGF), is a crucial therapy that delivers oxygen and nutrients to the surviving myocardium. After MI, a substantial influx of macrophages of the inflammatory phenotype infiltrates the infarcted myocardium. these macrophages secrete factors that exacerbate myocardial injury and orchestrate neovascular regression. A biomimetic nano-buffer system was developed in this study, consisting of VEGF-encapsulated nanoparticles coated with N-acetyl-L-cysteine (NAC)-modified macrophage membrane. These nanoparticles accumulate at the infarcted myocardium by exploiting the macrophage membrane's biomimetic inflammation chemotaxis. It effectively neutralizes detrimental factors in the infarcted myocardium while simultaneously enabling the controlled release of VEGF nanoparticles to promote angiogenesis within the affected tissue. What sets our research apart is the profound impact of the nano-buffer on macrophages, accomplished by its efficient scavenging of reactive oxygen species. This action triggers a vital response—the secretion of PDGF by macrophages—which significantly enhances the maturation of nascent blood vessels. The cumulative effect of these actions creates an exceptionally favorable milieu, fostering neovascularization. This study highlights the potential of the nano-buffer system in treating MI.
研究领域:
心血管疾病
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
高影响因子
EXPERIMENTAL EYE RESEARCH
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2016
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IF 2.998
Xinyi Ren,Jia Li,Xianxing Xu,Chunming Wang,Yuanguo Cheng
Uncontrolled activation of complement and upregulation of vascular endothelial growth factor (VEGF) play fundamental roles in age-related macular degeneration (AMD). However, most drugs used to treat AMD focus on a single target, and the percentage of effectively treated patients in clinical practice needs to be improved. Therefore, novel AMD treatment approaches are needed. IBI302 is a novel bispecific decoy receptor fusion protein designed with both a VEGF inhibition domain and a complement cascade inhibition domain, which are connected by the Fc region of human immunoglobulin . In this study, we systematically evaluated the binding affinity between IBI302 and VEGF isoforms and complement proteins by using surface plasmon resonance (SPR) technology. Anti-VEGF blockers (aflibercept and bevacizumab) and complement receptor 1 were used as references. The SPR assay results indicated that IBI302 could bind different VEGF isoforms and complement proteins with high affinity. The biological activity of IBI302 was also studied. IBI302 showed an inhibitory effect on human primary umbilical vein endothelial cell proliferation and the activation of complement pathways in vitro. Finally, the pharmacokinetic (PK) properties of IBI302 were evaluated in rhesus monkeys . The PK results showed that after a 0.5 mg/eye intravitreal dosage, IBI302 became rapidly distributed from the vitreous humor into targeted tissues and remained active over 504 h. Overall, the favorable anti-angiogenic and anti-complement effects of IBI302 along with the good PK profiles in rhesus monkeys support the selection and development of IBI302 as a promising candidate for AMD treatment.
研究领域:
眼科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
Zhihong Chen,Mingyu Jia,Yangyang Liu,Huajian Zhou,Xiaopan Wang,Min Wu
Background The use of autologous bone grafting is considered the most successful method for managing bone defects, particularly when utilizing cancellous bone grafts for the best outcomes. Nonetheless, the scarcity of cancellous bone presents a notable obstacle in remedying these defects. Consequently, it is essential to create reliable alternatives to cancellous bone grafts to ensure effective management of bone defects.Methods In this research, we created an injectable composite hydrogel stents using gelatin methacrylate (GelMA) hydrogel to mimic the collagen properties of cancellous bone, along with the inclusion of nanohydroxyapatite (nHA) to signify the inorganic element. Furthermore, we incorporated vascular endothelial growth factor (VEGF) to improve regenerative vascular capabilities. Before being implanted into rat cranium defect models, these composite hydrogel stents were co-cultured with human umbilical vein endothelial cells (HUVEC) and bone marrow mesenchymal stem cells (BMSC).Results The composite hydrogel stents exhibited a network structure with porosity, robust mechanical properties, and beneficial degradation traits. In the degradation phase, it steadily releases Ca²⁺ and VEGF, which encourages the proliferation, migration, and osteogenic differentiation of BMSCs from rats. Moreover, this release improves the ability of HUVECs to form tubes. Collectively, these mechanisms support the regeneration of blood vessels and bone in the cranium defect region of rats.Conclusion The composite hydrogel stents demonstrated excellent cytocompatibility and biological characteristics, as evidenced by its ability to enhance both osteogenesis and angiogenesis in vivo and in vitro. Consequently, it has the potential to act as an effective alternative to natural cancellous bone.
研究领域:
组织工程
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再生医学
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生物材料科学
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骨科
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2019
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IF 6.044
Aili Suo,Weijun Xu,Yaping Wang,Tiantian Sun,Lijie Ji,Junmin Qian
In tumor biology, it is widely recognized that 3D rather than 2D cell culture can recapitulate key features of solid tumors, including cell-extracellular matrix (ECM) interactions. In this study, to mimick the ECM of breast cancer, hyaluronic acid (HA) hydrogels were synthesized from two polyvalent HA derivatives through a hydrazone and photo dual crosslinking process. HA hydrogels could be formed within 120 s. The hydrogels had similar topography and mechanical properties to breast tumor and displayed glutathione and hyaluronidase dual-responsive degradation behavior. Biological studies demonstrated that HA hydrogel could support the proliferation and clustering of breast cancer MCF-7 cells. The expression levels of VEGF, IL-8 and bFGF in hydrogel-cultured cells were significantly greater than those in 2D culture. Moreover, cells from hydrogel culture exhibited greater migration/invasion abilities and tumorigenicity than 2D-cultured cells. Therefore, the HA hydrogels are a promising ECM-mimicking matrix for in vitro construction of breast cancer.
研究领域:
生物材料
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癌症生物学
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组织工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 25
·5441-5450
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IF 5.344
Qianmin Zhang,Xiaojuan Wei,Yongli Ji,Li Yin,Zaizai Dong,Feng Chen,Mingqiang Zhong,Jian Shen,Zhenjie Liu,Lingqian Chang
Bio-sourced hydrogels are attractive materials for diagnosing, repairing and improving the function of human tissues and organs. However, their mechanical strength decreases with an increase in water content. Furthermore, it is challenging to mold these hydrogels with high precision, which significantly limits their applications. Herein, we modified a biocompatible and biodegradable material, hyaluronic acid, with methacrylic anhydride and then cured it with a four-arm star structure cross-linking agent under ultraviolet light. The hyaluronic acid hydrogel was finally cured within 15 s with an adjustable cross-linking degree. The results demonstrated that the developed gel maintained good mechanical strength with a water content of 90%, while achieving micropatterns at a precision of 20 μm. The biological experiments showed that it could effectively promote the release of vascular endothelial growth factor (VEGF), which contributed to promoting cell growth, and has favorable biocompatibility. Overall, this hyaluronic acid hydrogel is a promising biomedical material with high forming accuracy, excellent mechanical properties, and favorable biocompatibility, which indicate its potential value in a variety of tissue engineering and biomedical applications.
研究领域:
组织工程
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生物医学材料
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Yudie Wang,Hang Gao,Xin Wang,Dawei Li,Wen Zhang,Xuan Meng,Lijie Wang,Tao Zhu,Peijie Dong,Yao Chen,Xin Meng
A series of intricate and dynamic physiological healing processes are involved in the healing of skin wounds. Herein, a multifunctional hydrogel is firstly designed and constructed by L -arginine-grafted O -carboxymethyl chitosan (CMCA), catechol-modified oxidized hyaluronic acid (DOHA), and dopamine nanoparticles (pDA-NPs). pDA-NPs were loaded in hydrogel for inherently powerful antimicrobial properties and could be as a cross-linking agent to construct hydrogels. Raffinose (Raf) was further incorporated to obtain CMCA-DOHA-pDA2@Raf hydrogel for its function of modulating epidermal differentiation. The hydrogel has good physicochemical properties and could promote cell proliferation and migration, which shows superior hemostatic capabilities in animal models of hemorrhage. The hydrogel significantly promoted wound healing on rat skin defect models by upregulating VEGF and CD31 and decreasing IL-6 and TNF-α, stimulating neovascularization and collagen deposition in epithelial structures. This multifunctional hydrogel implies the potential to be a dynamic wound dressing.
研究领域:
生物材料
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伤口愈合
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纳米技术
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组织工程
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药学
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
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2024
·
IF 3.9
Jingrong Yu,Zhengkun Gao,Qingyue Han,Zi Wang,Wenjie Zhang,Jie Zhao,Shan Qiao,Xinxin Zou,Fengjie Huang
At present, wound dressings in clinical applications are primarily used for superficial skin wounds.However these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address this issue, t this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis.The CSDG hydrogel exhibites acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Both in vitro and in vivo results showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.
研究领域:
生物医学工程
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材料科学
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伤口愈合
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组织工程
✓ 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）