Arabian Journal of Chemistry
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2022
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IF 6.212
Zizhen Zhao,Chen Fu,Yuping Zhang,Yingying Zhang,Xiaoxi Yang,Ailing Fu
The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo . The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
高影响因子
JOURNAL OF NATURAL PRODUCTS
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2022
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IF 4.803
Qi Zeng,Xu Nie,Li Li,Hui-Fang Liu,Yang-Yao Peng,Wang-Ting Zhou,Xiao-Jia Hu,Xin-Yi Xu,Xue-Li Chen
Salidroside (Sal), the major active constituent of Rhodiola rosea L., is considered as a potential pro-drug with various activities; however, its role in tumor therapy is not clear. Here, we demonstrated in vitro and in vivo that Sal enhanced the inhibitory activity of doxorubicin (DOX) in drug-resistant cancer cell lines. Our results showed that combination drug treatment (Sal and DOX) significantly decreased cell proliferation, migration, and motility. Besides biological validation, a luciferase-labeled animal tumor xenograft model and bioluminescence imaging (BLI) were applied for assessing the tumor progression. Sal combined with DOX inhibited the growth of HeLa-ADR-luc cells in vivo and downregulated the DOX-induced high expression of MDR1. Also, Sal downregulated the Bcl-2, MMP-2, MMP-9, PI3K, and AKT and upregulated BAX proteins. Sal demonstrated high safety and cardiac protection activity. We discovered that Sal enhances DOX sensitivity through the regulation of PI3K/Akt/HIF-1α and DOX-induced resistance pathways. Our results suggest that Sal could be a novel chemosensitization agent for the treatment of multi-drug-resistance tumors.
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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.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Xudong Xie,Weixian Hu,Yue An,Yuheng Liao,Shengming Zhang,Yanzhi Zhao,Kangkang Zha,Wenqian Zhang,Zhenhe Zhang,Fan Xia,Bobin Mi,Benjie Zhou,Hankun Hu,Mengfei Liu,Guohui Liu
Diabetic wounds are characterized by an imbalance between impaired angiogenesis and persistent pro-inflammatory immune responses, leading to chronic non-healing. Under hyperglycemic and oxidative stress conditions, the glycolytic function of endothelial cells is significantly compromised. However, solely enhancing angiogenesis does not effectively promote diabetic wound healing due to concomitant dysregulation of the local immune microenvironment, which further suppresses vascularization. Notably, Th1 cells dominate the diabetic wound immune milieu and exacerbate inflammatory responses, thereby aggravating immune imbalance. Thus, an optimal therapeutic strategy should simultaneously target both inflammatory dysregulation and vascular dysfunction. To address the phenomenon of cell-specific metabolic reprogramming within diabetic wounds, where glycolytic activity is impaired in endothelial cells yet enhanced in Th1 cells, this study developed a glucose-responsive NG@B87@HA hydrogel system designed to reprogram the local metabolic network and modulate Th1 cell metabolism while restoring endothelial function. The hydrogel incorporates nanoparticles functionalized with CXCR3 antibody to specifically target Th1 cells and deliver the glycolysis inhibitor Bay87-2243 (B87), thereby suppressing their glycolytic flux and inflammatory activity via inhibition of the HIF-1α–GLUT1 signaling axis. Simultaneously, naringin (NG), which acts as a crosslinker, forms dynamic boronic ester bonds with HA-PBA and PVA, enabling glucose-dependent responsiveness. This mechanism not only mitigates local oxidative stress but also enhances the tube-forming capacity of endothelial cells, ultimately promoting angiogenesis. The results demonstrated that the NG@B87@HA hydrogel effectively restores the dysregulated metabolic network in diabetic wounds. By concurrently rectifying immune microenvironment imbalance and endothelial dysfunction, this system provides a novel therapeutic strategy for accelerating diabetic wound healing.
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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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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Ming-Xuan Liu,Yu-Ting Cai,Ruo-Jia Wang,Peng-Fei Zhu,Yan-Chao Liu,Hao Sun,Yong Ling,Wei-Zhong Zhu,Jing Chen,Xiao-Ling Zhang
Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.
研究领域:
材料科学
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生物医学工程
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治疗学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
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2024
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IF 3.2
Mingkang Zhang,Jinru Yang,Yufan Yuan,Yan Zhou,Yazhi Wang,Ruirui Cui,Yimai Maliu,Fen Xu,Xin’an Wu
Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-β1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.
研究领域:
肝病学
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药理学
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病理学
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
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IF 3.973
Nian Liu,Hongsen Liu,Haoran Chen,Gang Wang,Haolin Teng,Yulei Chang
Photodynamic therapy (PDT) is one of the non-invasive and selective treatment methodologies for cancer. However, many highly efficient photosensitizers (PSs) are usually low physiological solubility, limited bioavailability and tending aggregation, impeding the effectiveness of PDT, as well as cancer resistance of PDT further reduce its therapeutic effect. Though some smart delivery systems have been developed, the problem of photosensitizer leakage/release has not been completely solved. Herein, we developed a smart therapeutic nanoplatform based on polyphotosensitizer nanogel as novel nanophotosensitizers and drug carriers. Moreover, by loading of histone deacetylase inhibitors (SAHA), it allows for enhanced synergistic therapy strategy of prostate cancer via inhibiting HIF-1α and VEGF pathways of cancer cells involved in PDT resistance. Our study presents the well-designed nanoplatform of nanogel-Ce6, which could serve as a photodynamic agent without Ce6 molecules release in the responsive environment, offering the potential to encapsulate diverse functional components for smart drug release and imaging-guided combination therapy in vitro and in vivo .
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
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产品关联
DOI
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
Acta Biomaterialia
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2022
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IF 10.633
Yifan Li,Qiangwei Liang,Liyue Zhou,Yongjing Cao,Jiayu Yang,Juan Li,Jinxia Liu,Jiawei Bi,Yanhua Liu
The signaling cascade between nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) can be activated by proinflammatory M1 macrophages in rheumatoid arthritis (RA), which produces reactive oxygen species (ROS) and enhances M1 macrophage polarization, thus aggravating the development of RA. Therefore, an ROS-responsive artesunate prodrug micellar nanosystem for co-delivery of dexamethasone (DEX/HA-TK-ART micelles , abbreviated as DEX/HTA) was developed for synergistic inhibition of the HIF-1α/NF-κB cascade to regulate ROS scavenging and macrophage repolarization in RA combination therapy. DEX/HTA micelles displayed prolonged circulation in blood and efficiently co-delivered ART&DEX in the inflamed joints of adjuvant-induced arthritis (AIA) rats; moreover, they were specifically recognized and internalized into M1 macrophages through CD44 receptor-mediated endocytosis . ROS-responsive co-released ART&DEX then exerted a synergistic action to efficiently perform ROS scavenging and repolarization of M1 to M2 macrophages by inhibition of the HIF-1α/NF-κB cascade. The intravenous administration of DEX/HTA micelles into AIA rat models significantly alleviated inflammatory cell infiltration and repaired cartilage injury in the joint. Collectively, our study highlights the therapeutic potential of DEX/HTA micelles for treating RA through synergistic inhibition of the HIF-1α/NF-κB signaling cascade to regulate ROS scavenging and macrophage repolarization. Statement of significance An ROS-responsive artesunate (ART) prodrug micellar nanosystem for co-delivering dexamethasone (DEX), abbreviated as DEX/HA-TK-ART micelle, was developed for synergistic cascade regulation of the HIF-1α/NF-κB pathway on ROS scavenging and macrophage repolarization in combination therapy for rheumatoid arthritis. The well-designed nanosystem showed prolonged circulation in blood and superior ART&DEX accumulation in the inflamed joints of AIA rats; moreover, the micelles were specifically internalized into M1 macrophages and co-released ART&DEX, subsequently leading to inhibition of the HIF-1α/NF-κB pathway for ROS scavenging and macrophage repolarization, thus generating synergistic anti-inflammatory effects in RAW 264.7 cells and AIA rats. The HIF-1α/NF-κB cascade regulation on ROS scavenging and macrophage repolarization based on ART&DEX combination with smart nanotechnology could serve as a promising approach for rheumatoid arthritis therapy.
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Tao He,Mingshuang Wang,Jiao Kong,Qiang Wang,Yue Tian,Chaofeng Li,Qian Wang,Chuanxin Liu,Jianmei Huang
Ethnopharmacological relevance Coptis Categorized Formula (CCF) is one of the core prescriptions in Treatise on Febrile Diseases . Its efficacy can be available not only in exogenous diseases but widely in various internal injuries and miscellaneous diseases. CCF (i.e., Huanglian Jiedu Decoction, Huanglian Ejiao Decoction, Dahuang Huanglian Xiexin Decoction, Gegen Qinlian Decoction) is different in composition, but they all play a favorable role in curative effect on type 2 diabetes mellitus (T2DM). Therefore, it is of great significance to reveal the common mechanism of CCF in treating T2DM. Aim of the study Based on network pharmacology and non-targeted metabolomics research strategy, the common mechanism of the CCF treating T2DM was discussed. Materials and methods Firstly, Ultra-high performance liquid chromatography-quadrupole-time of flight/mass spectrometry was used to identify the chemical constituents of the CCF. Then, the targets of these chemical components were used for network pharmacology analysis associated with therapeutic effect. Finally, the diabetic zebrafish model was constructed to further verify the common mechanism of the CCF in treating T2DM. Results A total of 160 chemical compositions were identified and 16 of them were common chemical compositions of the four CCF, including berberine , baicalin , coptisine and so forth. Network pharmacology results showed that Dipeptidyl peptidase (DPP)-4, cysteinyl aspartate specific proteinase (CASP)3, nitric oxide synthase (NOS)2, NOS3, and other 37 targets were common targets of CCF, and advanced glycation end products (AGE)-receptor of advanced glycation end products (RAGE) signaling pathway in diabetic complications , mitogen-activated protein kinase (MAPK) signaling pathway and hypoxia inducible factor (HIF)-1 signaling pathway were critical pathways of four CCF in the treatment of T2DM. CCF can lessen the blood glucose of diabetic zebrafish. The contents of 25 differential metabolites in diabetic zebrafish were altered. These metabolites were mainly related to phenylalanine , tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, sphingolipid metabolism, and tyrosine metabolism. Conclusion Our research shows that the common mechanism of CCF in improving T2DM is as follows: berberine, baicalin, coptisine and other chemical components can directionally regulate DPP-4, CASP3, NOS2, NOS3 and other targets, which are mediated by AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and HIF-1 signaling pathway. The content of endogenous metabolites such as L-valine and L-sorbitose changes, and further regulates the metabolism of amino acid metabolism, lipid metabolism, purine metabolism, sphingosine metabolism and arachidonic acid metabolism, so as to play a significant role in regulating glycolipid metabolism, improving insulin resistance, inhibiting cell apoptosis, anti-oxidation and anti-inflammation, and finally ameliorating T2DM.
研究领域:
民族药理学
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网络药理学
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代谢组学
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生物医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYPERTHERMIA
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2024
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IF 3
Yijin Fan,Xi Wang,Yao Liu,Huajun Tang,Chengzhi Li
Objective In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL).Materials and methods The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment.Results After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05).Conclusions These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.
研究领域:
肿瘤学
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妇科
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医学影像学
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分子生物学
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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）