JOURNAL OF ETHNOPHARMACOLOGY
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2017
·
IF 2.981
Zhu-Ming Fan,Da-Ying Wang,Jian-Mei Yang,Zhi-Xiu Lin,Yun-Xiao Lin,Ai-Lin Yang,Hua Fan,Min Cao,Su-yun Yuan,Zong-jun Liu,Xin Zhou,You-Hua Wang
Ethnopharmacological relevance The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. Aim of the study In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro . Materials and methods The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay. And the pro-angiogenic effects of DOE on HUVECs were examined by MTT , scratch assay, protein chip and western blot . Results In the in vivo studies, we found that DOE was able to dose-dependently promote angiogenesis in zebrafish SIVs area. In addition, DOE could also restore the injury in zebrafish ISVs area and upregulate the reduced mRNA expression of VEGFRs including kdr , kdrl and flt-1 induced by VEGF receptor kinase inhibitor II (VRI). In the in vitro studies, we observed that DOE promoted the proliferation, migration of HUVECs and also restored the injury induced by VRI. Moreover, protein chip and western blot experiments showed the PI3K/MAPK cell proliferation/migration pathway were activated by DOE. Conclusions DOE has a therapeutic effects on angiogenesis, and its mechanism may be related to adjusting the VEGFRs mRNA and activation of PI3K/MAPK signaling pathway. These results suggest a strong potential for Dalbergia odorifera to be developed as an angiogenesis-promoting therapeutic.
研究领域:
药理学
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分子生物学
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民族药理学
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血管生成研究
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Pengfei Li,Liming Ruan,Guohua Jiang,Yanfang Sun,Ruofan Wang,Xiaofei Gao,Khaydar E. Yunusov,Uladzislau E. Aharodnikau,Sergey O. Solomevich
Electrospun nanofibrous scaffolds show great application potentials for wound healing owing to their effective simulation of extracellular matrix (ECM). Three-dimensional (3D) nanofibrous dressings exhibit relatively high specific surface areas, better mimicry of native ECM, adjustable hydrophilicity and breathability, good histocompatibility , enhanced wound healing, and reduced inflammation. In the present work, we designed the 3D polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) nanofibrous scaffolds by an electrospinning and gas foaming process. Then, gelatin and heparin (Gel/Hep) were assembled onto the surface of PCL/PCS nanofibers by electrostatic adsorption, and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into Gel/Hep layer to form a multifunctional 3D nanofibrous scaffold (PCL/ [email protected] /Hep+VEGF) for accelerating wound healing. The as-fabricated 3D PCL/ [email protected] /Hep+VEGF nanofibrous scaffold showed excellent antibacterial ability, hemocompatibility and biocompatibility in vitro and wound healing ability in vivo . Immunological analysis showed that the as-fabricated nanofibrous scaffold inhibited inflammation at the wound sites while promoting angiogenesis during the wound healing process. Statement of significance The electrospun 3D fibrous scaffolds using polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) have been fabricated as backbone for mimicking the extracellular matrix (ECM). Gelatin and heparin (Gel/Hep) were wrapped onto the surface of PCL/PCS fibers by electrostatic adsorption and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into surface Gel/Hep layer to form multifunctional 3D fibrous scaffolds. The as-fabricated multifunctional 3D fibrous scaffolds with good antibacterial ability and biocompatibility have been used as dressings for accelerating wound healing by inhibiting inflammation at the wound sites while promoting angiogenesis during the wound healing process.
研究领域:
生物材料
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组织工程
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伤口愈合
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生物医学工程
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DOI
PubMed
高影响因子
Biomaterials Science
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2017
·Vol. 5
·期 11
·2251-2267
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IF 4.21
Jie Wu,Kunxi Zhang,Xi Yu,Jianxun Ding,Lei Cui,Jingbo Yin
The key barrier to the clinical application of tissue engineering scaffolds is the limitation of rapid and sufficient vascularization. Adipose-derived stem cells (ASCs), especially multicellular aggregates, exhibited a promising angiogenic activity. Herein, we designed a series of poly(L-glutamic acid) (PLGA)-based hydrogels with tunable hydration to control the in situ formation of multicellular spheroids. Oligo(ethylene glycol)s (OEGs) were employed to regulate the hydration of hydrogels. The hydrogel cross-linked with ethylene glycol (OEG1) supported the most excellent adhesion and proliferation of human ASCs in vitro. However, as the hydration of hydrogels strengthened, the adherent ASCs were gradually replaced with multicellular spheroids. Moreover, the in situ formation of spheroids was more effective in upregulating hypoxia-adaptive signals (e.g., hypoxia-inducible factor-1α, HIF-1α) and enhancing the secretion of angiogenic factors (e.g., vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2)) compared to adherent cells in OEG1 hydrogels. The hydrogel cross-linked with oligo(ethylene glycol)400 (OEG9) carrying spheroids induced a high angiogenic response of host tissue in vivo, resulting in an improved system vascularization, compared to adherent cells in the OEG1 hydrogel. These features indicated that the PLGA-based hydrogels were expected to be applied toward bone and fat tissue regeneration.
研究领域:
组织工程
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生物材料
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再生医学
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细胞生物学
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血管生成
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Qi Ke,Xinyi Zhang,Yuan Yang,Qi Chen,Jianyu Su,Youhong Tang,Liming Fang
Magnetoelectric stimulation is a promising therapy for various disorders due to its high efficacy and safety. To explore its potential in chronic skin wound treatment, we developed a magnetoelectric dressing, CFO@CTAB/PVDF (CCP), by electrospinning cetyltrimethylammonium bromide-modified CoFe2O4 (CFO) particles with polyvinylidene fluoride. Cetyltrimethylammonium bromide (CTAB) serves as a dispersion surfactant for CFO, with its quaternary ammonium cations imparting antibacterial and hydrophilic properties to the dressing. Electrospinning polarizes polyvinylidene fluoride (PVDF) molecules and forms a fibrous membrane with flexibility and breathability. With a wearable electromagnetic induction device, a dynamic magnetic field is established to induce magnetostrictive deformation of CFO nanoparticles. Consequently, a piezoelectric potential is generated on the surface of PVDF nanofibers to enhance the endogenous electrical field in the wound, achieving a cascade coupling of electric–magnetic–mechanical–electric effects. Bacteria and cell cultures show that 2% CTAB effectively balances antibacterial property and fibroblast activity. Under dynamic magnetoelectric stimulation, the CCP dressing demonstrates significant upregulation of TGF-β, FGF, and VEGF, promoting L929 cell adhesion and proliferation. Moreover, it facilitates the healing of diabetic rat skin wounds infected with Staphylococcus aureus within 2 weeks. Histological and molecular biology evaluations confirm the anti-inflammatory effect of CTAB and the accelerated formation of collagen and vessel by electrical stimulation. This work provides insights into the application of magnetoelectric stimulation in the healing of chronic wounds.
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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生物材料
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纳米技术
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组织工程
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Lanlan Zong,Runxin Teng,Huiqi Zhang,Wenshang Liu,Yu Feng,Zhengmao Lu,Yuxiao Zhou,Zhen Fan,Meng Li,Xiaohui Pu
Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound-responsive hydrogel incorporated with heparin-binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self-assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis-related growth factors (VEGF-A, CD31, and α-SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound-responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection.
研究领域:
生物医学工程
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药学
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伤口愈合
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纳米技术
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生物材料
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
·
IF 6.6
Tingting Chen,Zimei Wu,Qiaodan Hou,Yixin Mei,Kunkun Yang,Jing Xu,Lin Wang
Purpose Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis.Methods MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/β-Tricalcium phosphate (PCL/β-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated.Results Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2–related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions.Conclusion This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.
研究领域:
生物材料
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组织工程
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再生医学
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糖尿病研究
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骨生物学
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药学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2024
·
IF 9.4
Yongsheng Zheng,Dong Yang,Botao Gao,Shuai Huang,Yubo Tang,Qingde Wa,Yong Dong,Shan Yu,Jun Huang,Sheng Huang
Chronic diabetic wounds are a severe complication of diabetes, often leading to high treatment costs and high amputation rates. Numerous studies have revealed that nitric oxide (NO) therapy is a promising option because it favours wound revascularization. Here, base-paired injectable adhesive hydrogels (CAT) were prepared using adenine- and thymine-modified chitosan (CSA and CST). By further introducing S-nitrosoglutathione (GSNO) and binary L-arginine (bArg), we obtained a NO sustained-release hydrogel (CAT/bArg/GSON) that was more suitable for the treatment of chronic wounds. The results showed that the expression of HIF-1α and VEGF was upregulated in the CAT/bArg/GSON group, and improved blood vessel regeneration was observed, indicating an important role of NO. In addition, the research findings revealed that following treatment with the CAT/bArg/GSON hydrogel, the viability of Staphylococcus aureus and Escherichia coli decreased to 14 ± 2% and 6 ± 1%, respectively. Moreover, the wound microenvironment was improved, as evidenced by a 60 ± 1% clearance of DPPH. In particular, histological examination and immunohistochemical staining results showed that wounds treated with CAT/bArg/GSNO exhibited denser neovascularization, faster epithelial tissue regeneration, and thicker collagen deposition. Overall, this study proposes an effective strategy to prepare injectable hydrogel dressings with dual NO donors. The functionality of CAT/bArg/GSON has been thoroughly demonstrated in research on chronic wound vascular regeneration, indicating that CAT/bArg/GSON could be a potential option for promoting chronic wound healing. Statement of significance This article prepares a chitosan hydrogel utilizing the principle of complementary base pairing, which offers several advantages, including good adhesion, biocompatibility, and flow properties, making it a good material for wound dressings. Loaded GSNO and bArg can steadily release NO and L-arginine through the degradation of the gel. Then, the released L-arginine not only possesses antioxidant properties but can also continue to generate a small amount of NO under the action of NOS. This design achieves a sustained and stable supply of NO at the wound site, maximizing the angiogenesis-promoting and antibacterial effects of NO. More neovascularization and abundant collagen were observed in the regenerated tissues. This study provides an effective repair hydrogel material for diabetic wound.
研究领域:
生物医学工程
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材料科学
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药剂学
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伤口愈合
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组织工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Junping Zheng,Man Chen,Cheng Ye,Xiongjie Sun,Nan Jiang,Xiaojuan Zou,Huabing Yang,Hongtao Liu
Ethnopharmacological relevance Seven traditional medicinal plants (including Astragalus membranaceus , Dioscorea hemsleyi , Salvia miltiorrhiza , Scrophularia ningpoensis , Ophiopogon japonicus , Panax ginseng and Fritillariae cirrhosae ) and one insect leech ( Whitmania pigra Whitman ) were combined into BuZangTongLuo formula (BZTLF) under the guidance of traditional Chinese medicine . BZTLF is potentially effective against diabetic vascular complications. Aim of the study Previous studies failed to clarify the molecular mechanism through which BZTLF suppressed diabetic ischemia . In this study, we aimed to explore whether BZTLF treatment could prevent the occurrence of type 2 diabetic (T2D) hindlimb ischemia in mice. Further, we investigated the regulatory effect of BZTLF on angiogenesis-related VEGF signaling pathway and gut microbiota dysfunction in diabetic ischemia mice. Materials and methods C57BL/6J mice fed with high-fat diet (HFD) received STZ injection and femoral artery ligation to build T2D diabetic hindlimb ischemia model. Mice were gavaged with BZTLF (5 g [raw materials]/kg/d) or with metformin plus atorvastatin for three weeks. Laser doppler imaging system was utilized for the visualization of blood flow. Histochemistry analysis was performed for microvascular vessel staining. Western blot was applied to detect the protein changes of signaling molecules responsible for VEGF pathway. Finally, 16S rDNA gene sequencing was conducted for analysis of gut microbiota structure. Results BZTLF treatment remarkably restored blood flow and capillary density of diabetic hindlimb ischemia. And the protein changes of VEGF signaling molecules were reversed in BZTLF-treated diabetic ischemia mice, including the decreased VEGF and HIF-1α, and the increased NO , eNOS and p-ERK1/2. The gut microbiota analysis suggests that BZTLF treatment increased the abundances of several beneficial bacteria ( Akkermansia , Bifidobacterium and Bacteroides ), while decreased the populations of some harmful bacteria( Blautia , Weissella , Escherichia Shigella and Kurthia ). By using Spearman's correlation analysis, these changed gut flora were positively/negatively correlated with VEGF signaling pathway or glycometabolic parameters. Conclusion BZTLF displayed beneficial effects on diabetic hindlimb ischemia by reshaping the gut microbiota structure and stunning the VEGF/HIF-1α pathway.
研究领域:
民族药理学
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药理学
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分子生物学
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微生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Shuaijie Li,Liyan Zhang,Chunyu Liu,Jua Kim,Kun Su,Tingli Chen,Limin Zhao,Xiaomei Lu,Hao Zhang,Yinglin Cui,Xu Cui,Feng Yuan,Haobo Pan
Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro , the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.
研究领域:
生物材料
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组织工程
·
骨科
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Jixi Huang,Shuai Wang,Xiaoping Wang,Jing Zhu,Zhenqiang Wang,Ximu Zhang,Kaiyong Cai,Jixi Zhang
Nanoadhesives can achieve tight wound closure by connecting biomacromolecules from both sides. However, previously developed adhesive systems suffered from suboptimal wound healing efficiency due to the lack of interparticle cohesion, sufficient reactive oxygen species (ROS)-scavenging sites, and angiogenesis consideration. Herein, we developed a polymer entangled porous nanoadhesive system to address the above challenge by synergy of three functional components. Firstly, hybrid mesoporous silica nanoparticles with highly integrated polydopamine (MS-PDA) were prepared by templated synthesis. The entangling between PVA polymer and MS-PDA contributed to much stronger cohesion between nanoparticles, which led to 75% larger adhesion strength . As confirmed by in vitro and in vivo evaluations, the highly exposed catechol groups boosted the scavenging activity of ROS (1.8–4.1 fold enhancement as compared with nonporous counterpart). Consequently, more macrophages exhibited anti-inflammatory phenotype, leading to 2–2.6 fold lower pro-inflammatory cytokine levels. Moreover, the sustained release of bioactive SiO 4 4− by the disintegration of nanoparticles contributed to ∼3-fold higher expression of VEGF and enhanced new blood vessel formation, as well as better wound repair. This platform can provide a new paradigm for developing multifunctional nanoadhesive systems in treating skin wounds. Statement of significance PVA polymer entangled mesoporous nanoadhesives of polydopamine (PDA)/silica hybrids with the combination of excellent wound closure effect, boosted ROS-scavenging activity, and significant angiogenesis ability were developed for improving the suboptimal skin wound healing efficiency. This strategy not only greatly advances our ability to rationally integrate repairing elements in nanoadhesives for manipulating combined processes of interfacial events during wound healing, but also offers general implications toward application of polymers to reinforce the adhesion strength in nanoadhesive systems. In addition, our findings on the impacts of pore effects mediated ROS species conversion and polymer entanglement may also trigger great interests and facilitate the development/broad application of therapeutic adhesives.
研究领域:
生物医学工程
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材料科学
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纳米技术
·
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
Food Bioscience
·
2023
·
IF 5.2
Zuanyuan Huang,Mengwei Hu,Xiuyi Peng,Rui Wang,Xiaoxiao Song,Junyi Yin
Small black soybean ( Vigna Mungo L.) is a kind of medicinal and edible plant with many potential health benefits for the human body. In this study, we investigated the potential anti-gastric ulcer effect of Vigna Mungo L. polysaccharides (VMP) using an acetic acid-induced gastric ulcer model in SD rats . The impact of VMP on the levels of antioxidant factors and growth factors in gastric tissue homogenate , serum metabolites, short-chain fatty acids (SCFAs) and gut microbiota in SD rats were analyzed. The results revealed that VMP exhibited a beneficial role in facilitating the healing process of gastric ulcers, specifically by reducing the area of gastric ulcers, increasing the levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and improving oxidative stress status. Additionally, VMP modulated 20 potential serum biomarkers associated with gastric ulcers, thereby exerting a significant impact on multiple crucial metabolic pathways. Notably, VMP notably increased the levels of SCFAs, including acetic acid, propionic acid , i-butyric acid, n-butyric acid, i-valeric acid, n-valeric acid, in the colonic contents of rats with gastric ulcers. Furthermore, VMP effectively ameliorated gut microbiota dysbiosis in gastric ulcer rats by reducing the relative abundance of Firmicutes , Lachnospiraceae_NK4A136_group , Quinella and Lactobacillus , while increasing the relative abundance of Bacteroidota , Bacteroides , Oscillospiraceae_UCG-005 , Muribaculaceae , Parasutterella and Ruminococcus . Correlation analysis showed that the relative abundance of Parasutterella and Lachnospiraceae_NK4A136_group were closely related to the changes of SCFAs and serum metabolites. These findings provide potential groundwork for the development of health products aimed at preventing and treating gastric ulcers.
研究领域:
药理学
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胃肠病学
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营养科学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Pharmaceutical Analysis
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2023
·
IF 8.8
Si-Yu Gui,Xin-Chen Wang,Zhi-Hao Huang,Mei-Mei Li,Jia-Hao Wang,Si-Yin Gui,Gan-Hua Zhang,Yao Lu,Li-Ming Tao,Hai-Sheng Qian,Zheng-Xuan Jiang
Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of VCAM-1, HIF-1α, and VEGF, causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H 2 O 2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.
研究领域:
药学
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纳米技术
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眼科学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
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