Open Chemistry
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2023
·Vol. 21
·期 1
·
IF 2.3
Hongmei Yu,Weiwei Liang,Yuan Sun
In this work, a novel In( iii ) coordination polymer, i.e., {[In(L)(im)(H 2 O)](H 2 O)}
n
( 1 ) was produced from the synthetic reactions in water and dimethylformamide mixed solvents and using methyl-3-hydroxy-5-carboxy-2-thiophenecarboxylic acid (H 2 L) and imidazole (Him) as the co-ligands, and then successfully loaded with dexamethasone. The injectable hydrogels were prepared from natural polysaccharide hyaluronic acid with good biocompatibility and successfully loaded with In( iii ) complex. The suppressive inhibitory effect of hydrogels toward U251 human glioma cell line viability was assessed using the Cell Counting Kit-8 assay kit, and the relatively expressed levels of the vascular endothelial growth factor signaling pathway were determined by real-time RT-PCR.
研究领域:
药学
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肿瘤学
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材料科学
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高影响因子
ANNALS OF BIOMEDICAL ENGINEERING
·
2020
·Vol. 48
·期 5
·1511-1523
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IF 3.324
Ding Yilei,Zhao An-sha,Liu Tianmei,Wang Ya-nan,Gao Yuan,Li Jing-an,Yang Ping
In this contribution, an injectable hydrogel was developed with chitosan, gelatin, β-glycerphosphate and Arg-Gly-Asp (RGD) peptide: this hydrogel is liquid in room temperature and rapidly gels at 37 °C; RGD peptide promises better growth microenvironment for various cells, especially endothelial cells (EC), smooth muscle cells (SMC) and mesenchymal stem cells (MSC). Both stromal cell-derived factor-1 (SDF-1) nanoparticle and vascular endothelial growth factor (VEGF) nanoparticles were loaded in the injectable hydrogel to simulate the natural nanoparticles in the extracellular matrix (ECM) to promote angiogenesis. In vitro EC/SMC and MSC/SMC co-culture experiment indicated that the nanocomposite hydrogel accelerated constructing embryonic form of blood vessels, and chick embryo chorioallantoic membrane model demonstrated its ability of improving cells migration and blood vessel regeneration. We injected this nanocomposite hydrogel into rat myocardial infarction (MI) model and the results indicated that the rats heart function recovered better compared control group. We hope this injectable nanocomposite hydrogel may possess wider application in tissue engineering.
研究领域:
生物材料学
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再生医学
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心血管研究
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组织工程
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Yin Guan,Xiaoqian Zhao,Yun Lu,Yue Zhang,Yan Lu,Yue Wang
Background: Rheumatoid arthritis (RA) is a persistent autoimmune disorder marked by inflammation and joint damage. Although current treatments, such as disease-modifying antirheumatic drugs (DMARDs), help control symptoms, they frequently cause substantial side effects, highlighting the urgent need for safer and more effective alternatives. Recent research indicates that gut microbiota might be pivotal in RA development through the “gut-joint axis,” presenting novel therapeutic possibilities.Purpose: This study seeks to explore the therapeutic potential of the traditional Chinese medicine (TCM) compound new bitongling (NBTL) for RA, with an emphasis on its capacity to regulate gut microbiota and suppress angiogenesis via the vascular endothelial growth factor (VEGF) signaling pathway.Methods: We utilized a collagen-induced arthritis (CIA) rat model to assess the impact of NBTL. The study employed 16S ribosomal DNA (16S rDNA) sequencing to analyze gut microbiota composition, machine learning techniques to identify characteristic microbial taxa, and transcriptomic analysis (GSVA) to assess the impact on the VEGF signaling pathway. The findings were further validated through analysis with deep neural network models and in vivo/in vitro experiments, including western blot, immunofluorescence, and miRNA analysis.Results: NBTL treatment markedly diminished inflammation in RA rats, evidenced by the reduced expression of TNF-α, IL-17, IL-6, and ASC in synovial tissues. Histopathological analysis confirmed alleviation of joint damage. Five characteristic microbial taxa, including f_Mycoplasmataceae, s_Metamycoplasma_sualvi, and g_Prevotellaceae_Ga6A1_group, were identified and associated with NBTL’s modulation of the VEGF pathway. Gene set variation analysis (GSVA) revealed significant downregulation of the VEGF signaling pathway following NBTL treatment. Subsequent experiments confirmed that NBTL inhibited VEGF and its receptors, VEGFR1 and VEGFR2, along with HIF-1α (hypoxia-inducible factor 1-alpha), thereby reducing angiogenesis. Additionally, NBTL upregulated miR-20a-5p and miR-223-3p, contributing to its anti-angiogenic effects.Conclusion: NBTL exhibits significant therapeutic potential in RA by modulating gut microbiota and inhibiting the VEGF signaling pathway. These findings support NBTL’s use as a promising candidate for RA treatment, emphasizing the need for further research on its mechanisms and clinical application.
研究领域:
免疫学
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微生物学
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药理学
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生物信息学
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DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2025
·Vol. 22
·期 15
·3839-3853
·
IF 3.2
Wen Weijia,Li Jiaying,Yuan Li,Liao Yan,Shao Caixia,Xu Dingze,Jiang Hongye,Liao Yuandong,Liu Pan,Zhang Chunyu,Yao Shuzhong,Wang Wei
Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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信号转导
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PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2021
·
IF 4.407
Limei Ao,Han Gao,Lifen Jia,Shimin Liu,Jie Guo,Bingzhen Liu,Qiumei Dong
Matrine (Mat) is an alkaloid of tetracycline quinazine, and previous studies have demonstrated its specific effect on relieving rheumatoid arthritis (RA). However, the effect of Mat on joint synovial angiogenesis in the pathogenesis of RA has not been elucidated. In this study, body weight, joint swelling, arthritis index (AI) score, histopathological changes, immunohistochemical, and western blot- were used in collagen-induced arthritis (CIA) rats to detect pro-inflammatory factors and, - expression levels of key cytokines and proteins along the hypoxia-inducible factor (HIF)-endothelial growth factor (VEGF)-angiopoietin (Ang) axis and VEGF-phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) pathway. In vitro experiments were conducted to observe the effect of Mat on the proliferation, migration and lumen formation of RA-fibroblast-like synovial cells (FLS) and human umbilical vein endothelial cells (HUVECs). Results showed that Mat reduced the degree of paw swelling and AI score in CIA rats, joint synovial tissue proliferation, inflammatory cell infiltration, and neovascularization; moreover, it down-regulated the expression levels of inflammatory factors interleukin-1β, interferon-γ, and pro-angiogenic factors VEGF, placental growth factor, HIF-α, Ang-1, Ang-2, Tie-2, and phosphorylation-Akt in the ankle joint of CIA rats. In addition, the in vitro experiments showed that Mat inhibited the proliferation and migration of RA-FLS and inhibited the proliferation and lumen formation of HUVECs. Therefore, Mat exerts an anti-angiogenesis effect by regulating the HIF-VEGF-Ang axis and inhibiting the PI3K/Akt signaling pathway. This inhibits the pathogenesis and improve the symptoms of RA, and may be offered as a candidate drug for the treatment of RA.
研究领域:
药理学
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免疫学
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病理学
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分子生物学
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PubMed
高影响因子
Pharmaceutics
·
2026
·Vol. 18
·期 8
·1025
·
IF 6.9
Qing Sun,Yang Fu,Tianwei Wang,Zongyuan Xu,Zeping Gui,Kun Liu,Xuzhong Liu
Background/Objectives: Renal ischemia–reperfusion injury (IRI) and infection-associated renal damage are characterized by persistent inflammation, oxidative stress, microvascular dysfunction, and impaired tissue regeneration, creating a hostile microenvironment that limits effective repair. We developed an injectable, photocrosslinkable methacrylated chitosan (CSMA) hydrogel for the localized co-delivery of cerium oxide nanoparticles (CeO2NPs) and vascular endothelial growth factor (VEGF), aiming to integrate redox modulation, antibacterial activity, and regenerative support.Methods:Gelation, microstructure, rheology, degradation, and CeO2NP/VEGF were characterized. Tubular epithelial and fibroblast migration and endothelial network formation, angiogenic gene expression, and antibacterial activity againstStaphylococcus aureusandEscherichia coliwere evaluated in vitro. Theraputic performance was assessed by renal surface application in a rat renal IRI model and catheter-mediated interavsical administration in an ascending urinary tract infection model. Systematic biocompatibility was evaluated separately in a 14-day subcutaneous implantation study. Renal response were further investigated using transcriptomic and targeted molecular analyses.Results:The CSMA/VEGF/CeO2NPs hydrogel exhibited rapid in situ gelation, interconnected porous architecture, stable viscoelasticity, gradual degradation, and sustained release of both CeO2NPs and VEGF. The formulation enhanced tubular epithelial and fibroblast migration, promoted endothelial network formation and angiogenic gene expression and effectively inhibited bothS. aureusandE. coli. In a surgically controlled rat renal IRI model, direct renal-surface application of the hydrogel reduced tubular injury, inflammatory infiltration, and fibrotic remodeling. In a separate ascending urinary tract infection model, catheter-based intravesical administration reduced the ascending renal bacterial burden and infection-associated inflammatory injury. No detectable adverse systemic effects observed under the tested conditions over the 14-day observation period in the subcutaneous implantation. Transcriptomic analyses further revealed that CSMA/VEGF/CeO2NPs treatment was associated with marked remodeling of the renal injury microenvironment, characterized by suppression of antigen presentation and immune activation pathways, alongside restoration of metabolic programs associated with amino acid, lipid, and purine metabolism. These molecular changes were accompanied by downregulation of CIITA/CD74/MHC-II signaling, recovery of metabolic regulators AGXT and ACOX1, modulation of Hippo/YAP- and ECM-associated pathways, and preservation of renal structural markers including nephrin and WT1.Conclusions:The localized CSMA-mediated co-delivery of CSMA/VEGF/CeO2NPs hydrogel promotes renal repair through resolution of maladaptive immune activation, metabolic reprogramming, angiogenic enhancement, and preservation of renal structural integrity, providing a promising biomaterial strategy for the treatment of ischemic and infection-associated renal injuries.
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高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Dian-Chao Cao,Yan Liang,Yang Guo,Dong-Yang Wu,Na-Na Wang,Yan-Mei Li,Hong-Fang Sun,Qin Wang,Xia Zhang,Yong-Liang Chi,Pei-Pei Sun,You-Jie Li,Ran-Ran Wang,Ping-Yu Wang,Shu-Yang Xie,Ning Xie
Purpose This study aims to develop an innovative delivery system, (Q+M/MnOx)@Clip, to enhance the bioavailability and therapeutic efficacy of quercetin both in tumor treatment and pain alleviation.Methods The (Q+M/MnOx)@Clip system was evaluated to enhance the release of quercetin, investigate its ability to target cancer cells, alleviate tumor hypoxia, and improve the efficacy of chemodynamic therapy (CDT). Tumor hypoxia markers and immune response activation were assessed, along with the impact on pain relief biomarkers.Results (Q+M/MnOx)@Clip successfully mitigated tumor hypoxia, facilitated controlled Q release, and enhanced CDT in vitro and in vivo. The system demonstrated a dual therapeutic effect: anti-tumor immunity and significant cancer pain relief by reducing HIF-1α and VEGF-A levels.Conclusion The novel (Q+M/MnOx)@Clip system represents a promising advancement in nanomedicine, improving the bioavailability of quercetin and offering a more effective approach to cancer treatment by downregulation of HIF-1α and VEGF-A. This study demonstrates the potential for combining anti-tumor immunity with pain relief for triple-negative breast cancer therapy.
研究领域:
肿瘤学
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药理学
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纳米医学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Wei Shang,Xin Zhao,Fan Yang,Dongyi Wang,Le Lu,Zihan Xu,Zhiming Zhao,Hui Cai,Junyi Shen
Background: Compared with traditional drugs, nanomaterial drugs have the benefits of improving the solubility, bioavailability, and absorption rate of insoluble drugs. Nanoporous complexes can increase the efficiency with which drugs can penetrate the blood-brain barrier and reach target organs. Ginsenoside Rg1 is an effective drug that promotes angiogenesis. Ginsenoside Rg1 composite nanoparticles were employed to induce the expression of several key epigenetic enzymes and then activate the VEGF and Notch pathways after the onset of ischemic brain lesions. Methods: We constructed nanoparticles to fully encapsulate the therapeutic drug (ginsenoside Rg1), which can be transferred into brain tissue via the receptor-mediated transfer of drug-encapsulated nanoparticles. Evaluation of the therapeutic effect of ginsenoside Rg1 complex nanovesicles (CNV) was performed by in vitro and in vivo experiments. Real-time polymerase chain reaction (RT- PCR), Western blot, immunohistochemistry staining (IHC), and Co-immunoprecipitation (co-IP) were employed to screen for epigenetic enzymes with an up-regulated expression post ginsenoside Rg1-CNV intervention. RNA sequencing, shRNA knockdown, and chromatin Immunoprecipitation (ChIP) sequencing were performed to detect the target genes of ginsenoside Rg1-CNV that regulate angiogenesis. Then, bioinformatic analysis was performed to investigate the mechanism of action of epigenetic modifying enzymes in regulating target genes. Results: The average of the synthesized ginsenoside Rg1-CNV was 203.78±6.83 nm, the polydispersion index was 0.135±0.007, and the Zeta potential was 23.13±1.65 mV. Through in vivo and in vitro experiments, we found that it promotes the proliferation, migration, and tubular formation of brain microvascular endothelial cells (BMECs). Meanwhile, the intervention of ginsenoside Rg1-CNV promoted the demethylation of H3K27me3 within the promoter region of VEGF-A and Jagged1 genes and reduced the H3K27me3 modification within this region. Conclusion: The ginsenoside Rg1 nanoparticles may be an available blood-brain barrier penetrating agent for ischemic stroke.
研究领域:
药理学
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神经科学
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分子生物学
·
表观遗传学
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DOI
PubMed
高影响因子
Biomedical Journal
·
2023
·
IF 5.5
Chen Ke,Changhan Chen,Ming Yang,Hao Chen,Youhui Ke,Liqun Li
Background Infantile hemangioma (IH) is a common vascular tumor in female infants, which can lead to aesthetic issues and facial scarring. This study aimed to investigate the inhibitory effects and underlying mechanisms of 755 nm long-pulsed alexandrite laser on IH. Methods Hemangioma endothelial cells (HemECs) were exposed to 755 nm long-pulsed alexandrite laser to evaluate its impact on cell proliferation and apoptosis. A patient-derived xenograft model was established to assess the inhibitory effects of laser treatment on IH in vivo . Results In vitro , 755 nm long-pulsed alexandrite laser effectively suppressed the proliferation of HemECs and induced cell apoptosis. Laser treatment significantly inhibited the volume and weight of tumors, accompanied by significant downregulation of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) expression levels in both hemangioma cells and tumors. Additionally, laser treatment resulted in the conversion of VEGFA 165a to VEGFA 165b . TUNEL staining demonstrated increased apoptosis in tumor cells after laser treatment, along with upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. Conclusion In addition to the principle of selective photothermal decomposition, modulation of the VEGF/PI3K/Akt axis may serve as a potential mechanism for IH treatment using a long pulse-width 755 nm laser. This sheds valuable light on the molecular mechanisms underlying IH pathogenesis and potential therapeutic targets while providing a theoretical basis for the safe and efficient management of proliferative IH using laser therapy.
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高影响因子
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS
·
2020
·
IF 1.624
Kun Wu,Dan Zhao,Huifei Cui
The wound dressing can temporarily replace the skin and play a protective role in the process of wound healing, preventing wound infection and inflammation, and providing a favorable environment for wound healing. In this study, a mixture of collagen and chitosan was lyophilized to be the host material of the sponge. This sponge was soaked into 1-ethyl-(dimethylaminopropyl) carbodiimide/N-hydroxy sulfosuccinimide cross-linking solution containing heparin and experienced secondary lyophilization to prepare the heparinized sponge (CT-CL/Hp). The surface morphology and structural characterization of the sponge was characterized by scanning electron microscope and Fourier transform infrared spectrometer, respectively. Relatively favorable water absorption capability were observed by measuring the physical properties. Satisfactory antibacterial properties against various bacteria and microbial isolation performance were observed by the antibacterial effect analysis in vitro. The sustained-release property of heparin from the sponges was measured using Alcian Blue assay. Experiments in vitro and in vivo showed that the sponges had satisfactory biocompatibility and lower sensitization. Moreover, the effect of sponge on early stages of wound healing was evaluated by guinea pigs wound healing models. Analysis of wound healing rates and histological examination showed satisfactory results. CT-CL/Hp enhanced expression of growth factors, particularly VEGF and EGF at day 7. These results demonstrated that CT-CL/Hp–treated sponges benefit to wound skin healing and regeneration.
研究领域:
生物材料
·
伤口愈合
·
生物医学工程
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Zhang Yuwei,Sun Zhaoyu,Liu Miao,Pang Jinxin,Huang Shanshan,Liu Hongyang,Zheng Huabin,Guan Siyu,Li Jie,Feng Yifan,Ouyang Jiang,Xu Tao,Du Wen
Type 1 diabetes (T1D) arises from autoimmune destruction of pancreatic β-cells, leading to lifelong dependence on exogenous insulin. Clinical islet transplantation offers a potential cure by restoring endogenous insulin secretion; however, its success is critically limited by poor post-transplant vascularization and oxygen deprivation, which cause over 70% of transplanted islets to undergo early necrosis or apoptosis. To address these challenges, we developed an injectable, biodegradable dual-functional hydrogel composed of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMC). This polysaccharide-based platform co-delivers vascular endothelial growth factor (VEGF) and an oxygen-carrying perfluorotributylamine (PFTBA) nanoemulsion, enabling simultaneous enhancement of angiogenesis and oxygenation within the graft microenvironment. The OHA/CMC hydrogel exhibited excellent biocompatibility, tunable gelation, and sustained release of both oxygen and VEGF. In vitro, hydrogel-encapsulated islets demonstrated markedly improved resilience under hypoxic stress, exhibiting an 8.6-fold increase in viability after 6 hours and a 4.0-fold enhancement in glucose-stimulated insulin secretion (GSIS) after 48 hours under 0% O2. In streptozotocin-induced diabetic mice, transplantation with the OHA/CMC–PFTBA–VEGF hydrogel enabled rapid restoration of endogenous insulin secretion, reversal of severe hyperglycemia, prolonged graft function, and enhanced neovascularization at the implant site. Collectively, this multifunctional hydrogel represents a promising and translatable therapeutic platform for improving islet transplantation outcomes in T1D and potentially advancing broader applications in regenerative medicine and complex tissue engineering.
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DOI
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Yao Duan,Chanyuan Jin,Yuwei Wu,Yan Chen,Minjuan Zhang,Jun Qian,Ting Shuai,Jian Li,Huimin Chen,Dan Li
Periodontitis represents a severe inflammatory illness in tooth supporting tissue. It has been supported that cAMP response element binding protein 1 (CREB1), a common transcription factor, extensively participates in osteogenic differentiation. Here, the current study was to look into the impacts of CREB1 on the process of periodontitis and its possible action mechanism. After human periodontal ligament stem cells (PDLSCs) were challenged with zoledronic acid (ZA), CREB1 expression was examined with RT-qPCR and western blotting . CCK-8 assay appraised cell activity. Following CREB1 elevation or/and vascular endothelial growth factor (VEGF) silencing in ZA-treated PDLSCs, CCK-8 and TUNEL assays separately estimated cell viability and apoptosis. Western blotting tested the expression of apoptosis- and osteogenic differentiation-associated proteins. ALP staining measured PDLSCs osteogenic ability and ARS staining estimated mineralized nodule formation. JASPAR predicted the potential binding of CREB1 with VEGF promoter, which was then testified by ChIP and luciferase reporter assays. RT-qPCR and western blotting tested VEGF expression. CREB1 expression was declined in ZA-exposed PDLSCs and CREB1 elevation exacerbated the viability and osteogenic differentiation while obstructed the apoptosis of PDLSCs. Additionally, CREB1 bond to VEGF promoter and transcriptionally activated VEGF expression. Further, VEGF absence partially stimulated the apoptosis while suppressed the osteogenic differentiation of CREB1-overexpressing PDLSCs treated by ZA. To be concluded, CREB1 might activate VEGF transcription to obstruct the apoptosis while contribute to the osteogenic differentiation of ZA-treated PDLSCs.
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高影响因子
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