ACS Applied Materials & Interfaces
·
2020
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IF 8.758
Xingguo Zhou,Hanghang Liu,Yanhui Zheng,Yaobao Han,Tingting Wang,Hao Zhang,Qiao Sun,Zhen Li
Radiotherapy has been extensively used to treat cancer patients because it can effectively damage most solid tumors without penetration limits. A hypoxic microenvironment in solid tumors leads to severe radioresistance and expression of hypoxic inducible factor-1 (HIF-1), which results in poor efficacy of radiotherapy alone. Herein, we report the excellent efficacy of radiotherapy achieved using a new type of yolk–shell Cu2–xSe@PtSe (CSP) nanosensitizer functionalized with the HIF-1α inhibitor acriflavine (ACF). We prepare the CSP nanosensitizer through the interfacial redox reactions between chloroplatinic acid and Cu2–xSe nanoparticles (CS) and then functionalize the nanosensitizer with ACF through their electrostatic interactions. We show that the synthesized CSP nanosensitizer can arrest the cell cycle (i.e., at the gap 2/mitosis (G2/M) phases) of tumor cells to enhance their sensitivity to X-rays and decompose endogenous H2O2 into O2 to reduce hypoxia and increase the production of reactive oxygen species, which leads to severe damage to DNA double strands and apoptosis of tumor cells. We also show that the ACF on the surface of CSP nanoparticles can effectively reduce the expression of HIF-1α. All these effects lead to a low vascular endothelial growth factor, low density of microvessels in tumor, decreased cell proliferation, and increased cell apoptosis, which synergistically and drastically enhance the efficacy of radiotherapy. This work provides insights and guidance for developing novel nanosensitizers to enhance the efficacy of radiotherapy.
研究领域:
肿瘤学
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纳米医学
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放射生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2014
·Vol. 4
·期 1
·1-7
·
IF 5.078
Parhira Supawadee,Zhu Guo-Yuan,Jiang Ren-Wang,Liu Liang,Bai Li-Ping,Jiang Zhi-Hong
Two stereoisomeric cardenolides, uscharin (1) and a new compound, 2′- epi -uscharin (2), were isolated from the latex of Calotropis gigantea (Asclepiadaceae). Their structures were fully elucidated based on their spectroscopic data, X-ray crystallographic data and chemical evidences. Both epimers (1 and 2) exhibited strong inhibitory effects on HIF-1 activity with different magnitudes. Compound 1 showed much more potent activity than 2 and digoxin, a well-known HIF-1 inhibitor. Discrepancy in potencies between 1 and 2 revealed the contribution of a β-configuration of 2′ hydroxyl moiety for HIF-1 inhibitory activity. This is a first report of the activity of HIF-1 inhibition of thiazoline ring-containing cardenolides.
研究领域:
植物化学
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药理学
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肿瘤学
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DOI
PubMed
高影响因子
Current Computer-Aided Drug Design
·
2024
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IF 1.5
Na An,Dongxing Zhang,Jile Xin,Xinyi Zhang,Zhijuan Zhang,Ligang Ma,Le Zhao,Huimin Wu,Weisheng Feng,Xiaoke Zheng
Background: Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear. Objective: This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS. Methods: The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis. Results: The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1. Conclusion: The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.
研究领域:
神经药理学
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传统中药研究
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分子生物学
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药效学
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细胞信号传导
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DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2024
·Vol. 81
·期 1
·1-22
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IF 6.2
Feng Chenxi,Yan Jinhua,Luo Ting,Zhang Hong,Zhang Hu,Yuan Yu,Chen Yi,Chen Haiyang
Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.
研究领域:
胃肠病学
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微生物学
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分子生物学
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营养学
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DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2021
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IF 7.963
Siqi Wu,Zhongli Chen,Li Yang,Yulin Zhang,Xiaohe Luo,Jinsong Guo,Ying Shao
Vehicle exhaust, as one of the most important compositions of air pollution, induced various adverse health effects, especially diabetes, on human beings. Even though monitoring and epidemiological data indicates that particle-bound polycyclic aromatic hydrocarbons (PAHs) is an inducing factor of diabetes, the specific causative mechanisms are still unclear. In the current study, the concentration of particulate matters (PMs, including PM 1.0 , PM 2.5 and PM 10.0 ) and PAHs was investigated at rush hour of weekday in three urban underground parking garages (UPGs). To evaluate the impacts of particle-bound PAHs on human beings, analysis of non-target metabolomics and unmetabolized PAHs were conducted for UPG and non-UPG worker urine samples. The results showed that the highest concentrations of PMs and total PAHs were found at the UPG entrance. The concentrations of unmetabolized 5-6 rings PAHs in the UPG worker urine were significantly higher than that in non-UPG worker urine samples, which induced glucose metabolism disorders through hypoxia-inducible factor 1 (HIF-1) signaling pathway. This could be a reason for particle-bound PAHs induced-diabetes on road workers, drivers and garage staff. These findings can serve as a step towards air pollution management and the pathological mechanism analysis of environmental factor induced-diseases.
研究领域:
环境科学
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医学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Current Computer-Aided Drug Design
·
2023
·Vol. 21
·期 1
·50-66
·
IF 1.7
Hongyi Liang,Guoliang Yin,Guangxi Shi,Xiaofei Liu,Zhiyong Liu,Jingwei Li
AimsBreast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC).ObjectivesTo analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC.Materials and MethodsNetwork pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC.ResultsAccording to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels.ConclusionThe study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.
研究领域:
肿瘤学
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网络药理学
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分子生物学
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DOI
高影响因子
Journal of Ginseng Research
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2022
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IF 5.735
Hong-Yan Guo,Yue Xing,Yu-Qiao Sun,Can Liu,Qian Xu,Fan-Fan Shang,Run-Hui Zhang,Xue-Jun Jin,Fener Chen,Jung Joon Lee,Dongzhou Kang,Qing-Kun Shen,Zhe-Shan Quan
Background Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20( R )-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20( R )-panaxotriol and investigate its antitumor activity in vivo and in vitro . Methods Here, 20( R )-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by 1 H-NMR, 13 C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2 H -pyran-2-yl)hexadecahydro-1 H -cyclopenta[a]phenanthren-3-yl( tert -butoxycarbonyl)glycinate ( A11 ). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC 50 < 0.3 μM) was more than 100 times higher than that of 20( R )- panaxotriol (IC 50 > 30 μM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20( R )-panaxotriol ( p < 0.01) in vivo . Conclusion To our knowledge, this is the first study to report the production of derivative A11 from 20( R )-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.
研究领域:
药理学
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肿瘤学
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有机化学
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生物化学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Yutong Kang,Abudureyimu Alimujiang,Fan Zhou,Liangmian Chen,Hongzhi Wang,Wenjing Wei,Jingcheng Zhao,Ziqi Zhu,Wancheng Sun,Xuejiao Xie,Shixia Huo,Dengqiu Xu,Zhijian Li
Objective Psoriasis is a chronic, immune-mediated dermatological disorder characterized by pathological epidermal hyperplasia, aberrant keratinocyte differentiation, and dermal infiltration of inflammatory cells. Sihe Tufuling (SHTFL), a clinically established traditional Chinese medicine formula, has demonstrated therapeutic efficacy in psoriasis management. This study aimed to investigate the anti-psoriatic activity of SHTFL and its principal herb, Smilax glabra Roxb. (SGR), and to elucidate their underlying mechanisms of action. Methods Ultra-performance liquid chromatography-mass spectrometry was used to identify the major chemical constituents of SHTFL and SGR. An imiquimod (IMQ)-induced psoriasis-like mouse model was employed to assess therapeutic efficacy using the psoriasis area and severity index, spleen index, hematoxylin and eosin staining, immunohistochemistry, immunofluorescence. Transcriptomic sequencing, single-cell RNA sequencing, gene knockdown, immunofluorescence, and quantitative reverse-transcription PCR analyses were performed to investigate the molecular mechanisms involved. Results The results of the chemical component identification indicated that flavonoids constitute essential components in both the SHTFL formula and SGR. Treatment with SHTFL and SGR resulted in a significant reduction of the PASI score, skin thickness, splenic index and serum levels of inflammatory cytokines in IMQ-induced mice psoriasis mice. Moreover, both SHTFL and SGR alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response in IMQ-induced mice. Transcriptomic analysis revealed that SHTFL and SGR mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the HIF-1 signaling pathway. Furthermore, HIF-1α knockdown abolished the protective effects of SHTFL in these models. Conclusion Our results indicate that both SHTFL and SGR hinder the excessive growth of keratinocytes and reduce inflammation in psoriasis by inhibiting the HIF-1 signaling pathway. This evidence backs SHTFL as a promising therapeutic approach for psoriasis.
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产品关联
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Shouchun Xiao,Jingna Cui,Yue Cao,Yaru Zhang,Jiaxing Yang,Li Zheng,Fanrong Zhao,Xueke Liu,Zhiqiang Zhou,Donghui Liu,Peng Wang
Chemical-caused reproductive dysfunction has emerged as a global public health concern. This study investigated the adverse effects of the organophosphorus pesticide malathion on reproductive function in adolescent male mice at environmentally relevant concentrations. The results indicated that eight-week malathion exposure reduced testis weight, caused sex and thyroid hormone disorders, and induced testicular spermatogenic epithelium damage and oxidative stress. Testicular RNA sequencing indicated that malathion significantly affected testicular energy metabolism, hypoxia-inducible factor 1 (HIF-1) signaling, and steroid hormone biosynthesis pathways. Malathion significantly increased the gene and protein expression of HIF-1α by upregulating key genes in the mitogen-activated protein kinase (MAPK) pathway ( Map2k2 , Mapk3 , and Eif4e2 ) and the phosphatidylinositol 3-kinase (PI3K) pathway ( Pik3r2 and Akt1 ). Furthermore, malathion downregulated HIF-1α degradation-regulating genes while upregulating anaerobic metabolism and inflammation-related genes, thereby inhibiting normoxia and promoting hypoxia processes. Testicular hypoxia subsequently induced steroid hormone biosynthesis disorders and spermatogenesis dysfunction. Molecular docking verified that malathion interfered with HIF-1α and steroid hormone synthases (CYP11A1, CYP17A1 and CYP19A1) by forming hydrogen bonds and hydrophobic interactions with these proteins. This study presents the first evidence that malathion triggers spermatogenesis dysfunction in mice through activating the HIF-1/MAPK/PI3K pathway, providing a comprehensive understanding of the reproductive toxicity risks associated with organophosphorus pesticides.
研究领域:
毒理学
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生殖生物学
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分子生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MECHANISMS OF AGEING AND DEVELOPMENT
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2024
·
IF 5.3
Zhen-Zhen Yu,Jia-Jun Tu,Mei-Ling Ou,Jin-Xiong Cen,Kun Xue,Shao-Jun Li,Jing Zhou,Guo-Dong Lu
Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans , demonstrating a intriguing “elixir in youth, poison in elder” phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57 , a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans , and C46G7.1 , unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1 / nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.
研究领域:
药理学
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老年学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Yanru Liu,Ya Hu,Xiaoxia Xie,Gongjun Yang,Fang Feng
Wen-Pi-Tang (WPT), a Traditional Chinese Medicine (TCM) prescription, is commonly used to treat chronic renal failure. However, the material basis and potential mechanisms of WPT against chronic renal failure have not been clarified. UHPLC-Q-Exactive Orbitrap-MS was utilized in this work to investigate the chemical components of WPT and their prototypes or metabolites in vivo. 227 chemical compounds were identified in the WPT. Meanwhile, 56 exogenous components (24 prototype components and 32 metabolic components) were examined in rat plasma. Meanwhile, network pharmacology revealed that liquiritigenin-O-sulfate, 3-keto-18β-glycyrrhetinic acid, 22-hydroxy-18-β-glycyrrhetinic acid, and hydroxyliquiritigenin (B ring)-O-sulfate with related targets AKT1, EGFR, STAT3, ESR1, SRC, MAPK3, MTOR, and PIK3CA were considered as the effective components and core targets. Furthermore, the findings suggested that the therapeutic effects of WPT on chronic renal failure may be substantially influenced by the PI3K-Akt, HIF-1, and FoxO signaling pathways. The outcomes of molecular docking and molecular dynamics simulations indicate that the key targets have strong binding capacities with effective components. Our study offers a comprehensive method for examining the molecular foundation and underlying mechanisms of WPT against chronic renal failure, opening up new therapeutic opportunities.
研究领域:
中药学
·
药理学
·
代谢组学
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产品关联
DOI
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2026
·
IF 1.3
Wen-Di Niu,Hao-Wei Liang,Lue Hong,Jin-Xing He,Jia-Hui Qian,Fei Pan,Zhi-Wei Xu,Hui Wang
This study investigates the therapeutic effects and mechanisms of the Yiqi Huoxue Recipe (YHR) on renal injury in Diabetic nephropathy (DN). Through mass spectrometry analysis, animal experiments, and network pharmacology approaches, it was found that YHR can ameliorate renal function indicators and pathological changes in DN rats, and reduce cell apoptosis. Mechanistic studies indicate that YHR alleviates hyperglycemia-induced renal inflammation and damage by inhibiting the HIF-1 signaling pathway, thereby improving DN.
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DOI
高影响因子
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