JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Jia Liu,Mengyu Li,Guobao Chen,Junhui Yang,Ying Jiang,Fang Li,Haibing Hua
Ethnopharmacological relevance Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. Purpose To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. Methods In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. Results Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin , paeoniflorin , lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability , migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 μg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot , immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. Conclusion JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.
研究领域:
药理学
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中医中药
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分子生物学
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病理学
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高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2019
·Vol. 42
·期 6
·886-891
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IF 1.54
Yangbiao He,Xujun Lang,Dong Cheng,Zhihao Yang
Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague–Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.
研究领域:
药理学
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肾病学
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分子生物学
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PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2021
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IF 5.89
Dong Wenpei,Song Zhicheng,Liu Suihong,Yu Ping,Shen Zhipeng,Yang Jianjun,Yang Dongchao,Hu Qinxi,Zhang Haiguang,Gu Yan
Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.
研究领域:
组织工程
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生物材料
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再生医学
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外科研究
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PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
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2023
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IF 3.3
Zeng Xiangfeng,Liu Shengyao,Yang Hua,Jia Menglei,Liu Wei,Zhu Wenting
ObjectivesThe most common cause of osteosarcoma (OS) death is lung metastasis. Currently, doxorubicin is the primary chemotherapy drug used to treat OS, however, it is not effective in inhibiting metastasis, and it has obvious cardiotoxicity. The anticancer activity of ginsenoside Rg3 has been demonstrated in a variety of malignant tumours. The aim of this study was to determine the potential role of ginsenoside Rg3 and doxorubicin in OS and the possible mechanism.MethodsThe potential synergistic effects of ginsenoside Rg3 and doxorubicin on human osteosarcoma cells 143B and U2OS, human umbilical vein endothelial cells, and mice receiving 143B xenografts and lung metastases were investigated.Key findingsOur study demonstrated that the combination of ginsenoside Rg3 and doxorubicin significantly inhibited cell proliferation, metastasis and angiogenesis in vitro. Mechanically, the anti-tumour activity of ginsenoside Rg3 and doxorubicin by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways. Furthermore, ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models. More importantly, ginsenoside Rg3 can effectively ameliorate doxorubicin-induced weight loss and cardiotoxicity in mice.ConclusionsConsequently, we concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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高影响因子
International Journal of Nanomedicine
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2026
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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
Biomedical Materials
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2026
·Vol. 21
·期 3
·035012
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IF 3.9
Xuefei Xiang,Yufang Yang,Heyou Gao,ZhiYun Chen,JingYi Xie,QingChuan Hu,Yu Wang
Composite scaffolds composed of porous polyurethane (PU) block copolymer and nano-hydroxyapatite (n-HA) have demonstrated significant potential in bone defect repair. However, the co-effect of osteogenesis and angiogenesis during the process of large bone defect repair is still not yet fully understood. Recent research has found that erythropoietin (EPO) is essential for both osteogenesis and angiogenesis, offering a new research direction for bone regeneration strategies. In this study, a polydopamine (pDA)-modified, EPO-functionalized HA/PU scaffold was fabricated, and its physicochemical properties, release kinetics, and effects on bone repair were systematically investigated. In vitro, a co-culture system of human umbilical vein endothelial cells and rat bone marrow mesenchymal stem cells was used to evaluate the scaffold’s effects on cell proliferation, osteogenic, angiogenic, and HIF-1α/ vascular endothelial growth factor (VEGF) pathway. In vivo, the modified composite scaffold was implanted onto the cranial bone defects of Sprague-Dawley rats to assess its efficacy in promoting bone repair and HIF-1α/VEGF pathway. In vitro, the EPO/pDA/HA/PU group showed more three-dimensional cell morphology with prominent pseudopodia, facilitating cell adhesion, and significantly increased mRNA expression of ALP, Runx2, CD31, CD34, HIF-1α and VEGF. In vivo, the EPO/pDA/HA/PU group exhibited the most significant bone regeneration, with micro- computed tomography analysis confirming a significantly higher the ratio of bone tissue volume to total tissue volume (BV/TV) compared to the blank and HA/PU control groups. These results indicated that the modified composite scaffold enabled sustained release of EPO, which upregulated the expression of HIF-1α and VEGF, thereby enhancing osteogenic and angiogenic capabilities both in vitro and in vivo. Our research demonstrated that loading of EPO onto the HA/PU composite scaffold could effectively promote osteogenesis and angiogenesis. HIF-1α/VEGF signaling plays a crucial role in this process. This discovery provides novel insights and methods for using HIF-1α/VEGF as a regulatory target to advance the clinical translation of large bone defects repair.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Sheng Ding,Siyu Liu,Shaoyang Kang,Shuwei Wang,Nan Jiang,Yuwei Li,Chunxiao Zhou,Hantao Lou,Chuangnian Zhang,Pingsheng Huang,Wenshuai Liu,Zujian Feng,Weiwei Wang,Deling Kong,Ningbei Yin
Diabetic wound healing poses a major clinical challenge. One of the promising therapy, the flap transplantation surgery exhibited unsatisfactorily low flap survival due to the intertwined pathological barriers: impaired angiogenesis, excessive oxidative stress, and persistent inflammation, leading to poor tissue repair. While the therapeutic platforms based on extracellular vesicles (EVs) emerges as a promising treatment, its efficacy is often limited by the inadequate yield and rapid in vivo clearance. To address this challenge, this study developed a strategy centered on preconditioning human umbilical vein endothelial cells (HUVECs) with high glucose (HG) stress to produce HG-preconditioned extracellular vesicles (hEVs), which significantly improve production, enrich regenerative cargoes (e.g., HIF-1α, VEGF), and enhance homologous cellular internalization. The hEVs derived from HUVECs were encapsulated by microfluidically fabricated gelatin methacryloyl (GelMA) microgels to create GelMA@hEVs. The biodegradable and biocompatible GelMA microgels enabled a sustained hEVs release profile. Therefore, GelMA@hEVs exhibited significant efficacy improvement in promoting endothelial cell proliferation, migration, and tube formation critical for vascularization, mitigating reactive oxygen species, and modulating macrophage polarization toward a pro-reparative phenotype. Mechanistically, these therapeutic effects relied on activating the HIF-1α/VEGF pathway, a core axis for angiogenesis dysregulated in diabetes. In diabetic ischaemic flap models, GelMA@hEVs significantly improved flap survival, restored vascular perfusion, and facilitated tissue regeneration without systemic toxicity. Altogether, this work provides a generalizable strategy for diabetic ischaemic flap repair by combining engineered EVs as bioactive cargo with a microgel scaffold for sustained delivery, offering a promising in situ tissue engineering solution.
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高影响因子
International Journal of Nanomedicine
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2025
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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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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2019
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IF 4.825
Peng-Chao Zhang,Xiao Liu,Man-Mei Li,Yan-Yan Ma,Hong-Tao Sun,Xu-Yan Tian,Yan Wang,Min Liu,Liang-Shun Fu,Yi-Fei Wang,Hong-Yuan Chen,Zhong Liu
The inhibition of angiogenesis is suggested to be an attractive strategy for cancer therapeutics. Heat shock protein 90 (Hsp90) is closely related to tumorigenesis as it regulates the stabilization and activated states of many client proteins that are essential for cell survival and tumor growth. Here, we investigated the mechanism whereby AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and tumor angiogenesis. Based on our results, AT-533 suppressed the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs), and was more effective than the Hsp90 inhibitor, 17-AAG. Furthermore, AT-533 inhibited angiogenesis in the aortic ring, Matrigel plug, and chorioallantoic membrane (CAM) models. Mechanically, AT-533 inhibited the activation of VEGFR-2 and the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK, in HUVECs, and the viability of breast cancer cells and the HIF-1α/VEGF signaling pathway under hypoxia. In vivo, AT-533 also inhibited tumor growth and angiogenesis by inducing apoptosis and the HIF-1α/VEGF signaling pathway in breast cancer cells. Taken together, our findings indicate that the Hsp90 inhibitor, AT-533, suppresses breast cancer growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 may thus be a potentially useful drug candidate for breast cancer therapy.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
Journal of Agriculture and Food Research
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2026
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IF 7.2
Yizhu Chen,Yi Liu,Yurong Fang,Huixue Huang,Zhihong Long,Bomi Ryu,Haisheng Xie,Zhong-Ji Qian
Age related macular degeneration (AMD) is one of the main causes of blindness in. elderly patients, and its treatment methods include intraocular injection and oral. administration, requiring long-term treatment and suboptimal efficacy. Tilapia skin-derived oligopeptides, characterized by high safety and bioactivity, emerge as a promising source of functional food ingredients. Here, we investigated the protective mechanism of TBP-1 (Ser-Val-Val-Ala-Ile), a pentapeptide isolated from tilapia skin, against hypoxia-induced damage in retinal pigment epithelial (ARPE-19) cells and angiogenesis in human umbilical vein endothelial cells (HUVECs). In the functional evaluation, TBP-1 notably attenuated ROS overproduction in CoCl 2 -induced ARPE-19 cells, simultaneously suppressing the stabilization of hypoxia-inducible factor-1α (HIF-1α), which was associated with reduced vascular endothelial growth factor (VEGF) transcription, diminished inflammatory factor levels, and restoration of normal autophagic flux. To validate the ROS-dependent nature of this regulatory pathway, we performed a rescue experiment using N-acetylcysteine (NAC), a well-characterized ROS scavenger. In HUVECs activated by VEGF, TBP-1 decreased the phosphorylation of VEGFR-2 and dampened the activation of the MAPK signaling pathway, resulting in dose-dependent inhibition of cell migration, invasion, and the formation of capillary-like tubular structures. Molecular docking and quantum chemical analyses suggested that the bioactivity of TBP-1 may rely on the electron-donating property of the Ser residue and hydrophobic interactions mediated by Ile, both of which are critical for its ROS scavenging ability and predicted interaction with HIF-1α. Collectively, these findings suggest that TBP-1 is a multi-target functional food supplement for preventing AMD by targeting the ROS/HIF-1α/VEGF axis, providing a theoretical basis for the high-value utilization of tilapia skin.
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高影响因子
Regenerative Biomaterials
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2024
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IF 5.6
Ji Minrui,Yuan Zaixin,Ma Hongdong,Feng Xian,Ye Cong,Shi Lei,Chen Xiaodong,Han Fei,Zhao Caichou
The management of full-thickness skin injuries continues to pose significant challenges. Currently, there is a dearth of comprehensive dressings capable of integrating all stages of wound healing to spatiotemporally regulate biological processes following full-thickness skin injuries. In this study, we report the synthesis of a dandelion-shaped mesoporous strontium-gallium microparticle (GE@SrTPP) achieved through dopamine-mediated strontium ion biomineralization and self-assembly, followed by functionalization with gallium metal polyphenol networks (MPNs). As CroCfunctional wound dressing, GE@SrTPP can release bioactive ions in a spatiotemporal manner akin to dandelion seeds. During the early stages of wound healing, GE@SrTPP demonstrates rapid and effective hemostatic performance while also exhibiting antibacterial properties. In the inflammatory phase, GE@SrTPP promotes M2 polarization of macrophages, suppresses the expression of pro-inflammatory factors, and decreases oxidative stress in wounds. Subsequently, during the stages of proliferation and tissue remodeling, GE@SrTPP facilitates angiogenesis through the activation of the HIF-1α/VEGF pathway. Analogous to the dispersion and rooting of dandelion seeds, the root-like new blood vessels supply essential nutrients for wound healing. Ultimately, in a rat chronic wound model, GE@SrTPP achieved successful full-thickness wounds repair. In summary, these dandelion-shaped GE@SrTPP microparticles demonstrate comprehensive regulatory effects in managing full-thickness wounds, making them highly promising materials for clinical applications.
研究领域:
材料科学
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生物医学工程
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伤口愈合
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生物材料
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PubMed
高影响因子
Acta Biomaterialia
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2017
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IF 6.319
Yongwei Hao,Cuixia Zheng,Lei Wang,Jinjie Zhang,Xiuxiu Niu,Qingling Song,Qianhua Feng,Hongjuan Zhao,Li Li,Hongling Zhang,Zhenzhong Zhang,Yun Zhang
Amorphous biodegradable metal phosphate nanomaterials are considered to possess great potential in cancer theranostic application due to their promise in providing ultra-sensitive pH-responsive therapeutic benefits and diagnostic functions simultaneously. Here we report the synthesis of photosensitising and acriflavine-carrying amorphous porous manganese phosphate (PMP) nanoparticles with ultra-sensitive pH-responsive degradability and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway . Carboxymethyl dextran (CMD) is chemically anchored on the surface of porous manganese phosphate theranostic system through the pH-responsive boronate esters. Upon the stimulus of the tumor acid microenvironment, manganese phosphate disintegrates and releases Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. Meanwhile, the released photosensitizer chlorin e6 (Ce6) produces ROS under irradiation while acriflavine (ACF) inhibits the HIF-1α/VEGF pathway during the burst release of VEGF in tumour induced by photodynamic therapy (PDT), resulting in increased therapeutic efficacy. Considering the strong pH responsivity, MRI signal amplification and drug release profile, the PMP nanoparticles offer new prospects for tumor acidity-activatable theranostic application by amplifying the PDT through inhibiting the HIF-1α /VEGF pathway timely while enhancing the MRI effect. Statement of Significance In this study, we report the synthesis of the tumor acidity-activatable amorphous porous manganese phosphate nanoparticles and their application for a photoactivable synergistic nanosystem that imparts reactive oxygen species (ROS) induced cytotoxicity in synchrony with hypoxia-inducible factor 1α/vascular endothelial growth factor (HIF-1α/VEGF) inhibitor that suppresses tumor growth and treatment escape signalling pathway. Besides, upon the stimulus of the tumor acid microenvironment, the manganese phosphate nanoparticles finally disintegrate and release Mn 2+ ions rapidly, which are responsible for the magnetic resonance imaging (MRI) effect. This nanoplatform is featured with distinctive advantages such as ultra pH-responsive drug release, MRI function and rational drug combination exploiting the blockage of the treatment escape signalling pathway.
研究领域:
癌症治疗
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纳米技术
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分子成像
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生物医学工程
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PubMed
高影响因子
危险品化学品经营许可证（带存储）