COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Long Li,Yuyang Zhang,Yujie Liu,Zetao Wang,Luyao Cheng,Yuhan Du,Yangyi Nie,Jing Long,Cairong Li,Yuanchi Zhang,Wei Zhang,Lin Yang,Yuxiao Lai
Background Bone defects pose a significant clinical challenge due to their high morbidity and long-term disability. Simultaneous enhancement of osteogenesis and angiogenesis holds promise for accelerating bone regeneration. MicroRNAs (miRNAs), particularly miR-126, are critical regulators of angiogenesis; however, their therapeutic application requires efficient delivery systems. Designing miRNA carriers with intrinsic osteogenic activity remains a pivotal yet underexplored strategy. Methods Zeolitic imidazolate framework-8 (ZIF-8) was developed as a nanocarrier to deliver proangiogenic miR-126. The miR-126@ZIF-8 nanocomposites were synthesized via a one-pot method, and their physicochemical properties, miRNA loading efficiency, and cytotoxicity were systematically characterized. Cellular uptake, miR-126 release kinetics, and Zn 2 + dissolution was evaluated in vitro . Angiogenic and osteogenic effects were assessed through gene expression analysis, capillary-like tube formation assays, and mineralization studies. Results and discussion The miR-126@ZIF-8 nanoparticles exhibited a high miRNA loading capacity, efficient cellular internalization, and minimal cytotoxicity. Upon intracellular delivery, the nanoparticles decomposed to release miR-126 and Zn 2+ , synergistically enhancing angiogenic (e.g., VEGF, HIF-1α) and osteogenic (e.g., RUNX2, OCN) gene expression. Functional assays demonstrated significant improvements in endothelial cell tube formation and osteoblast mineralization compared to controls. Conclusion Our work presents miR-126@ZIF-8 as a novel dual-functional platform that simultaneously promotes angiogenesis and osteogenesis. By combining the proangiogenic action of miR-126 with the osteoinductive potential of Zn 2+ , our nanocomposite offers a promising strategy for vascularized bone regeneration for the repair of bone defects.
研究领域:
医学
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生物材料学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
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2021
·Vol. 23
·期 8
·e3349
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IF 4.565
Xuyang Li,Zhan Zhang,Aipeng Li,Yubo Hu
Background Propofol (PPF) plays a protective role in ischemia–reperfusion (I/R) in multiple organs, including renal ischemia–reperfusion injury (RIRI). The present study aimed to investigate the underlying mechanisms by which PPF exerts its protective functions in RIRI. Methods BALB/c mice were employed for the construction of RIRI animal model. PPF pre-treatment was carried out before I/R. An in vitro I/R model was established with HK-2 cells after hypoxia/reoxygenation (H/R) culture, and PPF was utilized to treat the cells before H/R. A quantitative-polymerase chain reaction (qPCR) was conducted to detect long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-126-5p expression levels. Flow cytometry was adopted to detect the apoptosis of HK-2 cells. Bioinformatics analysis, qPCR, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were used to determine the regulatory relationship between MALAT1 and miR-126-5p. The expression level of vascular endothelial growth factor A (VEGFA) was examined by western blotting. Results MALAT1 expression was augmented and miR-126-5p was decreased in RIRI models. PPF pre-treatment remarkably reduced creatinine and urea nitrogen levels in the serum of BALB/c mice with RIRI, and diminished the apoptosis of HK-2 cells treated with H/R. In addition, PPF pre-treatment markedly restrained the expression of MALAT1 in both in vivo and in vitro models and up-regulated miR-126-5p expression. MALAT1 could adsorb miR-126-5p to repress it and up-regulate VEGFA. MALAT1 overexpression reversed the protective effects of PPF on RIRI. Conclusions PPF protects the kidney against RIRI by inhibiting MALAT1 and up-regulating miR-126-5p expression, as well as indirectly inhibiting the expression of VEGFA.
研究领域:
药理学
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分子生物学
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肾脏病学
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DOI
PubMed
高影响因子
Pharmaceutics
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2023
·Vol. 15
·期 5
·1379
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IF 5.4
Yongyu Tang,Ying Chen,Qianqian Guo,Lidan Zhang,Huanhuan Liu,Sibu Wang,Xingjie Wu,Xiangchun Shen,Ling Tao
Due to the accompaniment of vascular endothelial inflammation during the occurrence and development of cardiovascular diseases (CVD), treatment modalities against vascular endothelial inflammation have been intensively investigated for CVD prevention and/or treatment. Vascular cell adhesion molecule-1 (VCAM-1) is a typical transmembrane inflammatory protein specifically expressed by inflammatory vascular endothelial. By inhibiting VCAM-1 expression through the miR-126 mediated pathway, vascular endothelial inflammation can be efficiently relieved. Inspired by this, we developed a miR-126-loaded immunoliposome with VCAM-1 monoclonal antibody (VCAMab) decorated at its surface. This immunoliposome can be directly targeted to VCAM-1 at the inflammatory vascular endothelial membrane surface and achieve highly efficient treatment against inflammation response. The cellular experiment results showed the immunoliposome had a higher uptake rate towards inflammatory human vein endothelial cells (HUVECs) and can significantly downregulate the VCAM-1 expression level of inflammatory HUVECs. In vivo investigation further demonstrated that this immunoliposome displayed a higher accumulation rate at vascular inflammatory dysfunction sites than its non-VCAMab-modified counterpart. These results suggest that this novel nanoplatform can effectively deliver miR-126 to vascular inflammatory endothelium, opening a new avenue for the safe and effective delivery of miRNA for potential clinical application.Keywords:vascular endothelial inflammation treatment;miR-126 delivery;VCAM-1 targeting;cationic liposomes
研究领域:
心血管疾病
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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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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2020
·Vol. 45
·期 5
·1107-1119
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IF 3.038
Xiao Zhang Hong,Wang Li,Gan Ping,He Jing,Yan Bing Chun,Ding Li Dong
miR-126 which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia–reperfusion (I-R). Moreover, vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also involved in physiological processes of vascular endothelial cells (ECs). This study investigated how miR-126 changes with reperfusion time in different brain tissues after global cerebral ischemia and focal cerebral ischemia and examined the underlying mechanism miR-126 involving VEGFA, SPRED1, and Raf-1 after I-R. The results indicated decreases in the levels of miR-126-3p and miR-126-5p expression in mice and gerbils after I-R, consistent with the results after oxygen and glucose deprivation and reperfusion (OGD/R) in PC12 cells. Glial cells were activated as neuronal damage gradually increased after I-R. Inhibition of miR-126-3p exacerbated the OGD/R-induced cell death and reduced cell viability. After miR-126-3p inhibition, the levels of SPRED1 and VEGFA expression were increased, and p -Raf-1 expression was decreased after OGD/R. Moreover, based on the intervention of miR-126-3p inhibition, we found that the expression of p -Raf-1 was significantly increased after the intervention of siSPRED1 , while it was not statistically significant after intervention of siVEGFA . The reduction of miR-126 expression after global and focal cerebral ischemia exacerbated neuronal death, which was closely related to increasing the SPRED1 activation and inhibiting the Raf-1 expression.
研究领域:
神经科学
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分子生物学
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脑血管疾病
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DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
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2024
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IF 4.5
Congying Wang,Haodong Jiang,Jia Zhu,Yunpeng Jin
This study prepared and evaluated polymeric polybutylcyanoacrylate (PBCA) nanoparticles (NPs) that can be used as a new agent for contrast-enhanced intravascular ultrasound (IVUS) imaging with drug delivery capacity. The nanoformulation was successfully developed using suspension polymerisation and characterised in terms of size, size distribution, zeta potential, morphology, stability, toxicity effects, imaging effects and drug release study. The results showed that the nanoparticles were round and hollow, with a particle diameter of 215.8 ± 25.3 nm and a zeta potential of −22.2 ± 4.1 mV. In vitro experiments, the nanoparticles were safe, non-toxic, and stable in nature with the capacity to carry and release drug (ant-miR-126). Moreover, the nanoparticles can match the high-frequency probe of commercially IVUS as a contrast agent to improve the resolution of imaging (the mean echo intensity ratio in the vascular wall increased significantly from 10.89 ± 1.10 at baseline, to 24.51 ± 1.91 during injection and 43.70 ± 0.88 after injection, respectively p < .0001). Overall, a new nano agent with drug-carrying capacity was prepared, which can be used in combination with IVUS for simultaneous diagnosis and targeted therapy of coronary atherosclerosis.
研究领域:
药学
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生物医学工程
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纳米技术
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心脏病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2016
·Vol. 38
·期 6
·1871-1878
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IF 2.348
Xusheng Yuan,Junjun Chen,Min Dai
Paeonol (2'-hydroxy-4'-methoxyacetophenone) is an active component isolated from the root of Paeonia Suffruticosa Andrews. We previously found that paeonol inhibited vascular cell adhesion molecule-1 (VCAM‑1) expression, and thus may be useful for the prevention and treatment of rabbit atherosclerosis (AS); however, the underlying mechanisms are not yet well known. Recently, microRNAs (miRNAs or miRs) have been reported to play an important role in the pathogenesis of AS. In the present study, we examined the effects of paeonol on miRNA-126 (miR‑126) expression, and its ability to inhibit monocyte adhesion to oxidized low-density lipoprotein (ox-LDL)-injured vascular endothelial cells (VECs). VECs were isolated from the rat thoracic aorta and stimulated with ox-LDL (20 mg/l) in the presence of paeonol. We found that miR‑126 had a lower expression in the ox-LDL-injured VECs, and VCAM‑1 was identified as a target gene of miR‑126. Furthermore, paeonol promoted miR‑126 expression and suppressed VCAM‑1 expression at the mRNA and protein level. It also inhibited monocyte adhesion to ox-LDL-injured VECs through the promotion of miR‑126 expression. Furthermore, it was demonstrated that paeonol blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway by promoting miR-126 expression. Taken together, and to the best of our knowledge, the findings of this study provide the first evidence that paeonol promotes miR‑126 expression to inhibit monocyte adhesion to ox-LDL-injured VECs and block the activation of the PI3K/Akt/NF-κB signaling pathway. Our data suggest that miR‑126 plays a crucial role in vascular inflammation and may be an important therapeutic target in the treatment of AS with the use of paeonol.
研究领域:
药理学
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分子生物学
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心血管疾病
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产品关联
DOI
PubMed
高影响因子
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