Stem Cells International
·
2019
·
IF 3.902
Si Wu,Yachuan Zhou,Yi Yu,Xin Zhou,Wei Du,Mian Wan,Yi Fan,Xuedong Zhou,Xin Xu,Liwei Zheng
The pulpotomy with pulp capping is aimed at retaining vital pulp with reparative dentin formation. Vascular endothelial growth factor (VEGF) plays a crucial role in dentin regeneration; however, its constant administrations in the human body is still problematic. Chitosan was widely studied as an effective carrier to deliver bioactive molecules in regenerative medicine. In this study, we conducted a chitosan/β-glycerophosphate (CS/β-GP) hydrogel as a VEGF-sustained release system and explored its effects on dental pulp stem cells (DPSCs). CS/β-GP hydrogel was manufactured using a sol-gel method. SEM assay showed the spongy and porous microstructure of the lyophilized hydrogels. DPSCs cultured in the CS/β-GP hydrogel kept adhesion and vitality. CCK-8 assay tested the promoted proliferation activity of DPSCs on the hydrogel. Besides, the added VEGF protein could continually release from VEGF/CS/β-GP hydrogel. The VEGF/CS/β-GP hydrogel could promote the odontogenic differentiation of DPSCs better than VEGF treatment without hydrogel. Our results suggested that CS/β-GP hydrogel could continually release VEGF and contribute to odontogenic differentiation of DPSCs, thus may become a potential carrier of bioactive molecules in pulp capping therapy.
研究领域:
再生医学
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牙科材料
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干细胞生物学
·
组织工程
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PubMed
高影响因子
APOPTOSIS
·
2025
·
IF 8.1
Huang Xiangyang,Liu Yi,Fu Hangling,Rong Xia,Zhao Yiheng
Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by progressive skin and organ fibrosis. Although interferon signaling is dysregulated in SSc, the role of interferon-induced proteins like IFIT3 in the skin fibrosis of SSC remains unclear. Here, we demonstrate that IFIT3 expression is significantly elevated ( p < 0.01) in SSc fibroblasts and promotes fibrosis via SOCS1-dependent activation of the EGFR/VEGF axis. Silencing IFIT3 upregulated SOCS1 ( p < 0.05), suppressed EGFR/VEGF ( p < 0.01), and inhibited fibroblast proliferation/migration ( p < 0.01). In a bleomycin-induced SSc model, IFIT3 knockdown ameliorated skin/lung collagen deposition and fibrosis ( p < 0.05). Our findings reveal a novel mechanism whereby IFIT3 regulates EGFR and VEGF through down-regulating SOCS1 in SSc fibrosis, identifying IFIT3 as a novel therapeutic target for SSc.
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高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Huimin Zhu,Jinfa Ye,Yiming Wu,Yuhang Cheng,Min Su,Qixuan Dai,Yun Han,Jintao Pan,Zhenyu Wu,Chuan Chen,Chenyue Qiu,Wei Li,Gang Liu,Chengchao Chu
Corneal neovascularization (CNV) is one of the leading causes of blindness in the world. In clinical practice, however, it remains a challenge to achieve a noninvasive and safe treatment. Herein, a biocompatible shell with excellent antioxidant and antivascular is prepared by co-assemly of epigallocatechin gallate (EGCG)/gallic acid (GC) and Copper (Cu II). Afther loading gluocose oxidase (GOx) inside, the shell is modified with dimeric DPA-Zn for codelivering vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA. Meanwhile, the Arg-Gly-Asp peptide (RGD) peptide-engineered cell membranes coating improves angiogenesis-targeting and biocompatible for the multifunctional nanomedicine (CEGs/RGD). After eye drops administration, CEGs/RGD targets enrichment in neovascularization and CEGs NPs enter cells. Then, the inner GOx consumes glucose with a decrease in local pH, which in turn leads to the release of EGCE and VEGF-siRNA. As a result, the nanomedicines significantly reduce angiogenesis and inhibit CNV formation through synergistic effect of antioxidant and antivascular via down-regulation of cluster of differentiation 31(CD31) and VEGF. The nanomedicine represents a safe and efficient CNV treatment through the combined effect of antioxidant/gene, which provides important theoretical and clinical significance. This article is protected by copyright. All rights reserved
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高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2022
·Vol. 19
·期 1
·61-72
·
IF 2.294
Xu Shu-Ying,Zeng Chun-Li,Ni Si-Ming,Peng Yong-Jun
Background: Acupuncture has been recommended as an alternative and complementary therapy for preventing and treating cerebral ischemia by the World Health Organization (WHO) for years. However, the mechanisms remain unclear. Accumulating evidence has shown that acupuncture can promote
angiogenesis to attenuate brain damage after ischemic stroke. In recent years, exosome- carried microRNAs (miRNAs) activated by acupuncture have proven effective in regulating pathological changes. We, therefore, investigated whether electro-acupuncture (EA) enhanced angiogenesis in cerebral
stroke via exosome-carried miR-210. Methods: We extracted and identified the exosomes from the serum of MCAO with EA treatment and injected them into MCAO rats for further observation. Simultaneously, miR-120 siRNA and HIF-1α inhibitor were transfected. Then, we evaluated the volume
of infarction, pathological changes, and expression levels of angiogenic related factors of each group of rats by TTC and HE staining, transmission electron microscope (TEM), western blot, and quantitative PCR (qPCR). Results: Compared with the MCAO group, EA-Exosome (EA-EXO) treatment
significantly decreased the infarct volume and the pathological damage, but miR-210 siRNA or HIF-1α inhibitor reversed the protective outcomes induced by EA-EXO. Moreover, EA-EXO treatment upregulated miR-210 and increased CD34, HIF-1α, VEGF, Notch1 protein, and mRNA expressions
compared to the MCAO group. MiR-210 siRNA or HIF-1α inhibitor treatments both down-regulated those angiogenic related proteins and mRNAs. Conclusion: EA treatment could activate the HIF-1α/VEGF/Notch 1 signal pathway to facilitate angiogenesis after ischemic stroke via exosomal
miR-210.
研究领域:
神经科学
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分子生物学
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中医药学
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中风研究
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PubMed
高影响因子
ACS Applied Bio Materials
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2021
·
IF 0
Jiahua Li,Yafeng Hao,Huizhuo Pan,Yingying Zhang,Guohui Cheng,Baona Liu,Jin Chang,Hanjie Wang
Vascular endothelial growth factor (VEGF) is the key regulator in neovascular lesions. The anti-VEGF injection is a major way to relieve retinal neovascularization and treat these diseases. However, current anti-VEGF therapeutics show significant drawbacks. The reason is the inability to effectively control its therapeutic effect. Therefore, how to controllably inhibit the VEGF target is a key point for preventing angiogenesis. Here, a CRISPR-dCas9 optogenetic nanosystem was designed for the precise regulation of pathologic neovascularization. This system is composed of a light-controlled regulatory component and transcription inhibition component. They work together to controllably and effectively inhibit the target gene’s VEGF. The opto-CRISPR nanosystem achieved precise regulation according to individual differences, whereby the expression and interaction of gene was activated by light. The following representative model laser-induced choroid neovascularization and oxygen-induced retinopathy were taken as examples to verify the effect of this nanosystem. The results showed that the opto-CRISPR nanosystem was more efficacious in the light control group (NV area effectively reduced by 41.54%) than in the dark control group without light treatment. This strategy for the CRISPR-optogenetic gene nanosystem led to the development of approaches for treating severe eye diseases. Besides, any target gene of interest can be designed by merely replacing the guide RNA sequences in this system, which provided a method for light-controlled gene transcriptional repression.
研究领域:
分子生物学
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光遗传学
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纳米技术
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眼科学
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基因治疗
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DOI
PubMed
Oncology Letters
·
2018
·Vol. 16
·期 2
·2289-2298
·
IF 1.664
Chunyu Li,Qi Wang,Shen Shen,Xiaolu Wei,Guoxia Li
Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be the most potent anti‑tumor ingredient. However, the molecular mechanisms responsible for its anti‑metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA‑MB‑231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose‑dependent manner. The expression levels of epithelial‑mesenchymal transition (EMT)‑associated marker and the hypoxia inducible factor 1α (HIF‑1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively in vitro. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E‑cadherin, and decreased expression of N‑cadherin, Vimentin and Snail. In addition, oridonin exerted its anti‑angiogenesis activity through significantly decreasing HIF‑1α, VEGF‑A and VEGF receptor‑2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro‑vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF‑1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti‑metastatic agent in breast cancer treatment.
研究领域:
癌症生物学
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药理学
·
分子生物学
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PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 11
·1975-1986
·
IF 3.929
Zhang Min,Jiang Li
Mesoporous silica nanoparticles (MSNs) are widely used nanoparticles with a pore rich structure that is suitable for drug delivery. Here, we used MSNs to carry and deliver doxorubicin hydrochloride (DOX) in vivo to study the features of DOXloaded MSNs (MSNs@DOX). We used TEM
and zeta potential to illustrate that MSNs@DOX increase apoptosis and decrease metastasis of tumor cells. We used MTT, flow cytometry, Western blotting, wound healing, and transwell assays, as well as an in vivo metastasis model to explore the anti-carcinoma efficacy of MSNs@DOX. Our
results showed that DOX was efficiently loaded into MSNs measuring approximately 88±11 nm, which significantly increased the antitumor efficacy of DOX on lung cancer, both in vitro and in vivo, compared to a regular DOX treatment. MSNs@DOX markedly induced apoptosis through
cytochrome C release and the caspase family. Furthermore, cell migration and invasion were sharply inhibited, both in vitro and in vivo. We also found that the enhanced effect of MSNs@DOX might be due to an increased cellular uptake by tumor cells based on the enhanced permeability
and retention time of the nanoparticles. Matrigel plug assays and Western blotting assays revealed that the molecular mechanism behind the anti-metastasis effect might be attributed to the suppression of VEGF-mediated angiogenesis. Our results offer a new perspective on the application of
nanoparticles against metastasis.
研究领域:
纳米技术
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癌症研究
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药学科学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2026
·Vol. 25
·期 7
·
IF 3.3
Wenyu Yan,Xianyue Meng,Yan Wang,Chuanfei Wei,Fabin Han,Xueli Li
Background: Parkinson’s disease (PD) is a neurodegenerative disorder marked by motor dysfunction. No definitive methods exist to repair damaged neurons. Vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are two neuroprotective agents that work synergistically. However, these large molecular proteins have difficulty crossing the blood–brain barrier (BBB). Extracellular vesicles (EVs) offer superior targeting and low immunogenicity, making them excellent carriers. In this study we examined the protective effects of VEGF and NGF in a cell model and evaluated the therapeutic potential of VEGF–NGF contained within EVs in PD rats. Methods: EVs were isolated using sequential differential centrifugation and characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting (WB). VEGF and NGF were loaded into the EVs using a saponin-assisted method to create VEGF@EVs, NGF@EVs, and VEGF/NGF@EVs. The viability of 6-hydroxydopamine hydrochloride (6-OHDA)-induced SH-SY5Y cells was measured using the cell counting kit-8 assay before and after treatment with VEGF and NGF. Autophagy levels were assessed using WB, and the role of autophagy was further explored using the autophagy inhibitor chloroquine. Unilateral PD rat models were established via stereotactic injection of 6-OHDA into male Sprague–Dawley rats. Behavioral changes were monitored before and after treatment. Neuronal recovery, neurotransmitter levels, and autophagy levels in the rat brains were evaluated using immunohistochemistry, enzyme-linked immunosorbent assay, and WB. Results: VEGF/NGF@EVs significantly enhanced the viability of 6-OHDA-induced SH-SY5Y cells. A complete autophagic process was identified as essential for this protective effect. The intranasal administration of VEGF/NGF@EVs improved motor behavior in PD rats, with performance better than that of single growth factor treatments. The number of tyrosine hydroxylase (TH)–positive neurons, TH protein expression, and dopamine content were significantly increased. In addition, the level of autophagy in the rat substantia nigra was elevated. Conclusions: VEGF/NGF@EVs exert protective effects in both in vitro and in vivo 6-OHDA-induced PD models by promoting autophagy, demonstrating greater efficacy than either growth factor alone. By transplanting VEGF/NGF@EVs into PD rats, we showed that these vesicles can effectively cross the BBB and deliver targeted therapy to the central nervous system. This study highlights the significant potential of EV-mediated protein transplantation strategies for treating neurological disorders.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Dantong Li,Jian Chen,Jiaqi An,Ying Gu,Zhikuo Dong,Xingxing Gao,Xiaoying Zhang,Yixin Zhang
Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely linked to intestinal mucosal microcirculatory dysfunction. Sweroside (SOS), a natural iridoid glycoside derived from plants such as Swertia mussotii , Swertia pseudochinensis , and Lonicera japonica , exhibits anti-inflammatory properties. Yet, its therapeutic potential and mechanisms in UC remain unexplored. This study aimed to investigate the effects of SOS on dextran sulfate sodium (DSS)-induced UC and its underlying mechanisms. Methods A DSS-induced UC mouse model was established to evaluate the efficacy of SOS. Inflammatory cytokine levels, intestinal barrier function (assessed via MUC2 immunofluorescence, FITC-dextran permeability, and tight junction protein analysis), and mucosal microcirculation (measured by Laser Speckle Contrast Imaging) were examined. Angiogenesis and endothelial cell (EC) damage were analyzed using ELISA, immunohistochemistry, and transmission electron microscopy. Transcriptomics and molecular docking were utilized to investigate SOS-mediated pathways, with subsequent validation by qRT-PCR, western blot, and immunofluorescence. Additionally, a cellular injury model was generated by treating human umbilical vein endothelial cells (HUVECs) with DSS. Cellular inflammatory and angiogenesis-related factors were quantified via ELISA, while migration and angiogenesis capabilities of HUVECs were assessed through scratch and tube-forming assays. The expression of the VEGF and Hippo pathway-related proteins was determined by western blot. Results SOS significantly ameliorated UC symptoms, reducing weight loss, diarrhea, and DAI scores while suppressing inflammatory infiltration and cytokine release. SOS enhanced intestinal barrier integrity via tight junction upregulation and improved microcirculation by attenuating EC injury and angiogenesis. Mechanistically, SOS regulated the VEGF and Hippo pathways, a key regulator of angiogenesis, as confirmed by transcriptomics and molecular docking. In vitro , SOS protected HUVECs from DSS-induced inflammation and angiogenesis, confirming the improvement of mucosal microcirculation by modulating VEGF and Hippo pathways. Conclusions SOS ameliorates DSS-induced UC by impacting the VEGF and Hippo pathways, thereby suppressing ECs' angiogenesis, restoring mucosal microcirculation, and mitigating intestinal inflammation. These findings highlight SOS as a promising therapeutic candidate for UC.
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高影响因子
International Journal of Nanomedicine
·
2026
·
IF 6.5
Aiqiu Wei,Ziyi Zhong,Yiming Zhang,Jincheng He,Haihe Pang,Xinhua Xia,Xiaoqing Zhang
Purpose: Cantharidin (CTD) is a natural anticancer compound whose clinical application is limited by poor water solubility, low bioavailability, and significant toxicity. To develop a more effective and safer therapeutic strategy, we proposed a synergistic combination therapy by integrating CTD with staurosporine (STS), a protein kinase inhibitor that shares complementary mechanisms of action targeting the mTOR/HIF-1α/VEGF pathway. We further developed an aptamer-guided liposomal nanosystem for the co-delivery of CTD and STS (Apt/CTD-STS/NL), aiming to enhance tumor targeting, improve bioavailability, and reduce the systemic toxicity of both drugs.Methods: We constructed aptamer-guided co-delivery nanoliposomes encapsulating CTD and STS (Apt/CTD-STS/NL). The targeted delivery efficiency, synergistic antitumor efficacy, and biocompatibility of this nanosystem were comprehensively evaluated through both in vitro and in vivo experiments.Results: Apt/CTD-STS/NL achieved approximately 1.3-fold higher cellular uptake in HCC cells compared to non-targeted liposomes in vitro. In vivo, it demonstrated superior tumor accumulation. In a murine HCC model, Apt/CTD-STS/NL exhibited the strongest tumor growth inhibition (79.50 ± 4.39%), significantly outperforming free CTD, STS, or single-drug loaded liposomes. Mechanistic studies revealed that the core synergy between CTD and STS enabled simultaneous inhibition of the key oncoproteins mTOR, HIF-1α, and VEGF, thereby disrupting tumor proliferation, survival, and angiogenesis.Conclusion: This study demonstrates a novel targeted nanoplatform that combines an active ingredient from traditional Chinese medicine with a modern kinase inhibitor. This strategy achieves a synergistic anti-HCC effect through multi-pathway inhibition and offers a promising approach for cancer therapy with enhanced efficacy and reduced toxicity.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Changduo Wang,Yaming Guo,Xiaoyu Liang,Yujie Zhang,Kaijing Liu,Gen Li,Ni Zhu,Chunxiao Qi,Jiajia Shi,Chao Liu,Jianwu Dai,Jing Yang
A novel biodegradable polyester was designed to replace non-degradable cationic lipids, thereby eliminating long-term toxicity risks associated with mRNA delivery. • The ester-rich backbone facilitates endosomal/lysosomal escape, achieving superior VEGF mRNA transfection efficiency compared to conventional MC3- and DOTAP-based LNPs. • This polyester exhibits dual bioactivities: reactive oxygen species (ROS) scavenging and nitric oxide release, which synergistically mitigate oxidative stress and promote angiogenesis. Gene therapy has demonstrated promising efficacy in the treatment of peripheral arterial disease (PAD). However, conventional cationic lipids used in mRNA lipid nanoparticles (LNPs) lack degradable bonds, which may pose potential toxicity and long-term accumulation risks. Although many ionizable lipids have been designed with degradable ester linkages, the development of fully biodegradable cationic alternatives with favorable safety profiles remains of great interest. To address these limitations, we developed a biodegradable cationic alternative via ring-opening polymerization of ε-caprolactone initiated by triethanolamine, forming a three-armed polyester (3s-PCL) with tertiary ammonium groups. Subsequent conjugation with arginine or lysine yielded terminal-functionalized polyesters (3sPA /3sPL) as sustainable substitutes for conventional cationic lipids. In vitro and in vivo studies demonstrated that 3sPA-containing LNPs exhibit higher transfection efficiency than conventional LNPs (e.g., MC3- or DOTAP-based LNPs). Notably, arginine-modified 3sPA-LNPs displayed dual bioactivity: effective reactive oxygen species (ROS) scavenging and nitric oxide (NO) release. When loaded with VEGF mRNA, 3sPA-LNPs synergistically promoted angiogenesis in critical limb ischemia by elevating VEGF expression, reducing inflammation through ROS scavenging, and improving microcirculation via NO release. Collectively, these findings establish 3sPA-LNPs as a potent and safe mRNA delivery platform for critical limb ischemia, offering a promising treatment strategy for regenerative therapy. Download: Download high-res image (109KB) Download: Download full-size image
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高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Han Sun,Jian Dong,Yangyufan Wang,Siyu Shen,Yong Shi,Lei Zhang,Jie Zhao,Xiaoliang Sun,Qing Jiang
The periosteum plays an important role in vascularization and ossification during bone repair. However, in most studies, an artificial periosteum cannot restore both functions of the periosteum concurrently. In this study, a novel nanofiber that can sustain the release of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) was fabricated to enhance the durability of angiogenesis and osteogenesis during bone regeneration. A cell-free tissue engineered periosteum based on an electrospinning poly-l-lactic acid (PLLA) nanofiber was fabricated, on which VEGF and BMP-2 were immobilized through a polydopamine (PDA) coating conveniently and safely (BVP@PLLA membrane). The results indicated a significantly improved loading rate as well as a slow and sustained release of VEGF and BMP-2 with the help of the PDA coating. BMP-2 immobilized on nanofibers successfully induced the osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) in vitro with high expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN), and alkaline phosphatase (ALP). Similarly, angiogenic differentiation of BMSCs with the expression of fetal liver kinase-1 (Flk-1) and vascular endothelial cadherin (VE-cadherin) was observed under the environment of VEGF sustained release. Moreover, an in vivo study revealed that the BVP@PLLA membrane could enhance vascular formation and new bone formation, which accelerates bone regeneration in rat femoral defects along with a massive periosteum defect. Therefore, our study suggests that the novel artificial periosteum with dual growth factor controlled release is a promising system to improve bone regeneration in bone defects along with a massive periosteum defect.
研究领域:
组织工程
·
生物材料
·
再生医学
·
骨修复
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PubMed
高影响因子
危险品化学品经营许可证（带存储）