ACS Nano
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2020
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IF 14.588
Qiyue Wang,Xibo Ma,Hongwei Liao,Zeyu Liang,Fangyuan Li,Jie Tian,Daishun Ling
Stem cell therapies are increasingly recognized as the future direction of regenerative medicine, but the biological fate of the administrated stem cells remains a major concern for clinical translation, which calls for an approach to efficiently monitoring the stem cell behaviors in vivo. Magnetic particle imaging (MPI) is an emerging technology for cell tracking; however, its utility has been largely restricted due to the lack of optimal magnetic nanoparticle tracers. Herein, by controlled engineering of the size and shape of magnetic nanoparticles tailored to MPI physics theory, a specialized MPI tracer, based on cubic iron oxide nanoparticles with an edge length of 22 nm (CIONs-22), is developed. Due to the inherent lower proportion of disordered surface spins, CIONs-22 exhibit significantly larger saturation magnetization than that of spherical ones, while they possess similar saturation magnetization but smaller coercivity compared to larger-sized CIONs. These magnetic properties of CIONs-22 warrant high sensitivity and resolution of MPI. With their efficient cellular uptake, CIONs-22 exhibit superior MPI performance for stem cell labeling and tracking compared to the commercialized tracer Vivotrax. By virtue of these advantages, CIONs-22 enable real-time and prolonged monitoring of the spatiotemporal trajectory of stem cells transplanted to hindlimb ischemia mice, which demonstrates the great potential of CIONs-22 as MPI tracers to advance stem cell therapies.
研究领域:
生物医学工程
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再生医学
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纳米技术
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医学成像
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2024
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IF 7.6
Jinmei Cheng,Yushun Dou,Jiaxin Li,Tingting You,Yihai Wang,Mengchuan Wang,Shengjun Shi,Chun-hui Cui,Xiaopin Duan,Jisheng Xiao
Critical limb ischemia (CLI) remains a significant clinical challenge with high morbidity and mortality. Considering the critical role of hypoxia-inducible factor 1α (HIF-1α) in hypoxic site to induce angiogenesis by regulating the expression of growth factors, we prepared a cooperative composite (P-F-HKUST-1) by mixing thermo-responsive hydrogel (PPCN) with folic acid modified copper-based MOFs (F-HKUST-1) for the hindlimb ischemia therapy. The gelation of P-F-HKUST-1 in hindlimb muscle generated a more serious ischemia environment and subsequently induced the expression of HIF-1α, while the slowly released Cu 2+ from P-F-HKUST-1 increased HIF-1α stability by inactivating the factor-inhibiting hypoxia-inducible factor 1 (FIH-1), which synergistically induced the productions of downstream growth factors and finally restored the blood perfusion rapidly. In addition, P-F-HKUST-1 hydrogel exhibited a long in vivo retention time, which endowed the sustaining action on HIF-1α to reduce the frequency of administration. The rapid blood flow recovery, together with the good biocompatibility suggested that P-F-HKUST-1 could be a potential novel combined therapy (HIF-1α stimulation and stabilization) for critical limb ischemia.
研究领域:
生物医学工程
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药学
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组织工程
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分子生物学
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Youlu Chen,Ruihao Li,Xue Fu,Yaming Guo,Suling Yan,Lei Tian,Qinxia Zhou,Yongpeng Diao,Wei Chen
Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H 2 O 2 -induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.
研究领域:
基因治疗
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纳米技术
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分子生物学
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药学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2018
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IF 3.118
Yuzhu Ye,Yuanlu Shan,Caiying Bao,Yi Hu,Liangrong Wang
Background/aims Ginsenoside Rg1 is regarded as the primary bioactive ingredient in Panax notoginseng that has been well recognized for its protective effects against ischemia/reperfusion (IR) injury. However, the mechanisms still remain elusive. Our study aims to investigate the effects of Rg1 against lung injury induced by hind-limb IR in rats. Methods Twenty-four Sprague Dawley rats were randomly submitted to sham operation (SM group), hind-limb IR (IR group), hind-limb IR + Rg1 (Rg1 group), and hind-limb IR + Pro-DTC group (PD group). All the rats except those in SM group were subjected to 3 h of ischemia followed by 6 h of reperfusion , and extra intravenous Rg1 and pyrrolidine dithiocarbamate (Pro-DTC), a selective inhibitor of nuclear factor kappa B (NF-κB), was administered intravenously before ischemia in the Rg1 and PD group, respectively. The activities of myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT), as well as protein expressions of NF-κB p65 and cyclooxygenases-2 (COX-2) in lung tissue, and thromboxane B2 (TXB2) and 6-keto-ProstaglandinF 1α (6-keto-PGF 1α ) levels in bronchoalveolar lavage (BAL) fluid were detected. Morphological changes, index of quantitative assessment of histologic lung injury (IQA), apoptosis index (AI) and lung Wet/Dry ratio were also evaluated. Results The levels of Wet/Dry ratio, IQA, AI, activities of MPO and 6-keto-PGF 1α /TXB 2 ratio were increased, and NF-κB p65 and COX-2 protein expression were upregulated, while SOD and CAT levels were decreased in lung tissue in IR group as compared with SM group ( p < 0.05), all the alterations could be significantly reversed by Rg1 or Pro-DTC pretreatment ( p < 0.05). And Rg1 and Pro-DTC also significantly attenuated the pulmonary histological abnormalities induced by IR. Conclusion Ginsenoside Rg1 potentially attenuated lung injury induced by hind-limb IR by regulating NF-κB/COX-2 signaling pathway .
研究领域:
药理学
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免疫学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2019
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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
Stem Cell Research & Therapy
·
2022
·Vol. 13
·期 1
·1-16
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IF 8.079
Cui XiaoLing,Wang XiaoTan,Wen Jie,Li Xiao,Li Nan,Hao XuXiao,Zhao BaoXiang,Wu Xunwei,Miao JunYing
Background Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs. Methods In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs. Results Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.
研究领域:
细胞生物学
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分子生物学
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血管生物学
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再生医学
✓ 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）