ACS Nano
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2024
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IF 15.8
Junjie Shen,Yi Sun,Xuanzhe Liu,Yimin Chai,Chunyang Wang,Jia Xu
Peripheral nerve injury is a major societal concern. Black phosphorus (BP) has inherent advantages over cell-based therapies in regenerative medicine. However, controlling spontaneous degradation and size-dependent cytotoxicity remains challenging and poses difficulties for clinical translation. In this study, we constructed zero-dimensional BP quantum dots (QDs) modified with antioxidant β-carotene and comprehensively investigated them in Schwann cells (SCs) to elucidate their potential for peripheral nerve repair. In vitro experiments demonstrated that BPQD@β-carotene has an inappreciable toxicity and good biocompatibility, favoring neural regrowth, angiogenesis, and inflammatory regulation of SCs. Furthermore, the PI3K/Akt and Ras/ERK1/2 signaling pathways were activated in SCs at the genetic, protein, and metabolite levels. The BPQD@β-carotene-embedded GelMA/PEGDA scaffold enhanced functional recovery by promoting axon remyelination and regeneration and facilitating intraneural angiogenesis in peripheral nerve injury models of rats and beagle dogs. These results contribute to advancing knowledge of BP nanomaterials in tissue regeneration and show significant potential for application in translational medicine.
研究领域:
再生医学
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纳米技术
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神经科学
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生物医学工程
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材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2014
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IF 3.785
Rong-Lin Xie,Yoon-jeong Jang,Lei Xing,Bing-Feng Zhang,Feng-Zhen Wang,Peng-Fei Cui,Myung-Haing Cho,Hu-Lin Jiang
The clinical successful application of gene therapy critically depends upon the development of non-toxic and efficient delivery system. Although polycationic non-viral vectors hold great promise in nanomedicine , the exploring of application in clinics still remains a big challenge. To develop a non-toxic and efficient non-viral gene delivery system, two kinds of endogenous substance, citric acid (CA) and spermine (SPE), were used to prepare a new low charge density hyperbranched polyspermine (HPSPE) by one-pot polymerization. The biocompatibility evaluated by hemolytic activity and red blood cell (RBC) aggregation indicated that HPSPE was highly biocompatible without causing hemolysis and RBC aggregation compared with PEI as well as SPE. The MTS assay also demonstrated that the cell viability of HPSPE was above 90% even at 200 μg/mL at different time (24 and 72 h), which much higher than PEI 25 K. Besides, HPSPE showed high transfection efficiency without any toxic effect after aerosol delivery to the mice. Moreover, aerosol delivery of HPSPE/Akt1 shRNA significantly reduced tumor size and numbers and efficiently suppressed lung tumorigenesis ultimately in K- ras LA1 lung cancer model mice. These results suggest that low charge density as well as endogenous substance skeleton endow HPSPE with great potential for toxicity-free and efficient gene therapy.
研究领域:
生物医学工程
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基因治疗
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纳米医学
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癌症研究
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DOI
PubMed
高影响因子
Applied Materials Today
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2020
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IF 8.352
Fanyi Huang,Lingyu Sun,Cheng Zhao,Zeping Qiu,Yuanjin Zhao,Wei Jin
As a severe cardiovascular disease, acute myocardial infarction (AMI) has been attaching increasing attention and research for its high morbidity and mortality. In this paper, the novel protein microcapsules integrated hierarchical scaffold is designed for treating AMI model by using microfluidic templates. Based on advanced microfluidic electrospray technique, core-shell microspheres with controllable size are fabricated to build a double barrier for improving the stability of encapsulated drug. These microspheres are further combined with an electrospun polymer membrane to construct the desired hierarchical structure. Based on these designs, the microcapsules can realize long-term drug release while the polymer membrane scaffold exhibits anti-adhesive effect in vitro . By decreasing the level of Angiotensin Ⅱ and inhibiting the Renin-Angiotensin System (RAS) pathway, ACE2 can increase the concentration of Ang (1–7) and enhance its protective function. To evaluate the therapeutic effect, ACE2-encapsulted hierarchical scaffold is applied to AMI mice model, which achieves regional sustainable release and improves the severity of ischemic lesion, with an additional utility of preventing post-operative adhesion. Compared with injecting intramyocardially, implanting hierarchical scaffold avoids excess injury and shows more obvious therapeutic efficacy. These properties suggest that our hierarchical cardiac scaffolds provide a potential drug administration approach for local treatment of AMI.
研究领域:
心血管疾病
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生物材料
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药物递送系统
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组织工程
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产品关联
DOI
高影响因子
Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-17
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IF 5.3
Gao Jiaming,Guo Hao,Li Junmei,Zhan Min,You Yue,Xin Gaojie,Liu Zixin,Fan Xiaodi,Gao Qinghe,Liu Jianxun,Zhang Yehao,Fu Jianhua
Background Buyang Huanwu Decoction (BYHWD) is a traditional Chinese medicine to treat the syndrome of qi deficiency and blood stasis. Platelets play an important role in regulating thrombus and inflammation after ischemic injury, studies have shown that BYHWD regulate myocardial fibrosis and exert anti-inflammatory effects through IL-17 and TLR4 pathways, but the mechanism of platelet activation by BYHWD in stable coronary heart disease is still unknown. In the present study, model of left anterior descending coronary artery ligation was applied to investigate the mechanisms of BYHWD on modulating platelets hyperreactivity and heart function after fibrosis of ischemic myocardial infarction (MI). Methods Myocardial infarction model was constructed by ligation of the left anterior descending coronary artery. The rats were randomly divided into five groups: sham, model, MI with aspirin (positive), MI with a low dosage of BYHWD (BYHWD-ld) and MI with a high dosage of BYHWD (BYHWD-hd) for 28 days. Results Coronary artery ligation prominently induced left ventricle dysfunction, increased cardiomyocyte fibrosis, which was accompanied by platelets with hyperreactivity, and high levels of inflammatory factors. BYHWD obviously reversed cardiac dysfunction and fibrosis, increased the thickness of the left ventricular wall, and inhibited aggregation ratio and CD62p expression. BYHWD restored the mitochondrial respiration of platelets after MI, concomitant with an increased telomere expression and decreased inflammation. According to the result of transcriptome sequencing, we found that 106 differentially expressed genes compared model with BYHWD treatment. Enrichment analysis screened out the Ras-related protein Rap-1 (Rap1) signaling pathway and platelet activation biological function. Quantitative real-time PCR and Western blotting were applied to found that BYHWD reduced the expression of Rap1/PI3K-Akt/Src-CDC42 genes and attenuated the overactivity of PI3 kinase/Rap1/integrin α(IIb)β(3) pathway. Conclusion BYHWD reduced inflammation and platelet activation via the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway and improved heart function after MI. Graphical Abstract
研究领域:
中医
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心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2019
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IF 1.984
Yueying Tao,Kunming Tian,Ji Chen,Danfeng Tan,Yan Liu,Yongai Xiong,Zehui Chen,Yingbiao Tian
This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.
研究领域:
药理学
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中药学
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分子生物学
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系统生物学
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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）