Science Bulletin
·
2025
·
IF 21.1
Min Nie,Danqing Huang,Dandan Wang,Yuanjin Zhao,Lingyun Sun
Refractory wounds (RWs) are a common and severe complication of many diseases; however, the existing therapeutic methods are unsatisfactory in clinical practice. Here, we observed significant downregulation of the hepatocyte growth factor (HGF) in plasma samples from patients with autoimmune diseases. We used electroporation to deliver a plasmid containing HGF to induce its overexpression on mesenchymal stromal cells (MSC HGF ) and loaded them into an injectable hydrogel to treat RWs in patients with clinical autoimmunity. The MSC HGF exhibited stable HGF expression and secretion. In addition, they displayed a self-reinforcing loop, enhanced migration, and improved anti-apoptosis capacity via the autocrine activation of the c-Met-mediated phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Furthermore, the HGF (as well as other bioactive factors) secreted from the MSC HGF significantly augmented the migration and angiopoiesis of vascular endothelial cells, decreased the cellular inflammation of macrophages, and improved extracellular matrix remodeling in fibroblasts. According to these features, we demonstrated that the MSC HGF -loaded injectable hydrogel boosted cellular functions and afforded a long-acting healing efficacy in the treatment of clinical autoimmune patients with RWs. Therefore, the genetically engineered MSC HGF and their dispersed hydrogel system will have clinical significance for wound therapy.
研究领域:
再生医学
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基因治疗
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伤口愈合
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干细胞治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2022
·
IF 5.589
Qiangwei Liang,Yang Lan,Yifan Li,Yongjin Cao,Juan Li,Yanhua Liu
Chemotherapeutic agents can trigger the immune response via inducing immunogenic cell death (ICD), but the weak ICD effect induced by chemotherapy alone limits its lasting antitumor immunotherapy effect. A Cro polymerized prodrug carriers (POEG- b -PCro) with immunostimulatory by ICD induction was developed and co-delivered DOX to generate synergistic ICD induction for chemo-immunotherapy on breast cancer. DOX/POEG- b -PCro micelles displayed prolonged circulation in blood, efficient accumulation in tumors, internalization and then co-released DOX&Cro in tumor cells. Moreover, the DOX/POEG- b -PCro micelles synergistically triggered ICD induction by releasing the nuclear high mobility group box 1 (HMGB1) and down-regulation of c-Met level for generating chemo-immune anti-tumor actions. Importantly, the DOX/POEG- b -PCro micelles synergistically enhanced the tumor cytotoxic T lymphocytes infiltration , concomitant decreasing the immunosuppressive regulatory T (Treg) cells, accompanied with the increased cytokines secretion of IFN-γ and TNF-α, consequently displaying an improved anti-tumor activity in 4 T1 breast cancer mice. Overall, POEG- b -PCro prodrug micelles co-delivered DOX could be served as a promising nano drug delivery system for synergistic ICD induction on breast cancer chemo-immunotherapy.
研究领域:
药学
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肿瘤学
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免疫治疗
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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
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 17
·2102724
·
IF 11.092
Hui Xiong,Xiaoyan Liu,Zuohan Xie,Linyuan Zhu,Haipeng Lu,Cheng Wang,Jing Yao
The clinical anti-vascular endothelial growth factor (anti-VEGF) drugs and metronomic chemotherapy (MET) induced tumor vascular normalization treatment (TVNT) are easily antagonized by tumor microenvironment metabolic cross-talk between tumor cells and endothelial cells (ECs). To overcome this dilemma, nanodrug with the ability of ECs targeted glycolysis inhibition and nanodrug with the ability of tumor cell glycolysis inhibition, anti-VEGF, and MET are combined to prepare Nano-combination the pathways related to angiogenesis, tumor cell proliferation, and immunosuppression and breaking the negative sugar-lipid-protein metabolism balance in tumor microenvironment. Thus, stronger and more lasting normalized tumor vascular network and remarkable antitumor efficacy are obtained after treatment, constructing a positive feedback loop between TVNT and anti-tumor therapy. Above all, this study provides a new insight for solving the bottleneck of clinical TVNT.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
癌症生物学
·
血管生物学
✓ 已验证
DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
·
2021
·Vol. 53
·期 5
·1814-1822
·
IF 2.082
Bin Xue,Huirong Lv,Yanli Liu,Yang Gao
This study was conducted to investigate the effects of replacing dietary lipid source FO with a terrestrial lipid blend (LB) on the growth performance, body composition and immunity of juvenile Japanese sea bass when the dietary n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) requirements are met ( Lateolabrax japonicus ). Two types of experimental diets were formulated with the total FO (the control) or the LB (linseed oil and lard = 1:1). A 56-day feeding trial was conducted in floating cages with three replicates for each treatment. The results indicated that a significantly higher specific growth rate (SGR) and feed efficiency ratio (FER) occurred in fish that were fed the LB diet compared with the control group ( p < 0.05). There was no significant difference in the survival rate, body composition or body indicates between the groups ( p > 0.05). The respiratory burst, alternative complement pathway activity, lysozyme activity, cytokine genes expression and air exposure test results indicated that the replacement of FO with LB did not significantly affect the nonspecific immunity or stress resistance ( p > 0.05). The serum antioxidant enzyme activities and liver tissue antioxidant-related gene expression were significantly higher in the control group than in the other group ( p < 0.05). Therefore, the terrestrial lipid blends from linseed and lard (1:1) could be used as an alternative for dietary fish oil without compromising the growth performance, nonspecific immunity and resistance to stress in juvenile Japanese sea bass.
研究领域:
水产养殖学
·
营养学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yongli Shen,Lin Wang,Binglong Ji,Xinlei Lu,Delong Zhao,Yujie Dai,Xuan Meng
Metabolic reprogramming and altered redox balance are two common hallmarks of cancer. Redox homeostasis is intricately intertwined with tumor energy metabolism, but the potential for metabolic intervention mechanisms to disrupt redox balance has been consistently underestimated. In this study, we present a stimulus-responsive nanocarrier (NC) designed to leverage metabolic intervention mechanisms to enhance redox-based anticancer therapy. These nanoparticles are composed of zeolitic imidazolate framework-90 (ZIF-90) as the ATP- and pH-responsive porous core, enveloped in an amphiphilic pluronic 407 (poloxamer F127) coating to ensure steric stabilization. Within the core of these hybrid NCs, we co-loaded active cargos 3-bromopyruvate (3-BrPA) and metformin (MET). Serving as a multifaceted inhibitor of both aerobic glycolysis and respiration, 3-BrPA impedes the activities of hexokinase II, leading to reduced glucose consumption and an increase in ROS levels. This synergistic effect, in conjunction with MET, results in a decrease in the levels of reducing substances, sensitizing 3-BrPA-induced apoptosis in cancer cells. At both the cellular and animal levels, these hybrid NCs have demonstrated superior anticancer activity by inhibiting metabolism and disrupting redox homeostasis. This study introduces a novel approach targeting the metabolism-redox interplay for tumor treatment, potentially broadening the scope of available antitumor strategies.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
生物化学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）