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  1. Article ; Online: Integrated transcriptomic and proteomic analysis reveals Guizhi-Fuling Wan inhibiting STAT3-EMT in ovarian cancer progression

    Qihong Ma / Fangfang Chen / Ying Liu / Kang Wu / Zixuan Bu / Chentao Qiu / Nouri Neamati / Tiangong Lu

    Biomedicine & Pharmacotherapy, Vol 170, Iss , Pp 116016- (2024)

    2024  

    Abstract: Background: Ovarian cancer (OC) is the most lethal gynecological malignancy. Frequent peritoneal dissemination is the main cause of low survival rate. Guizhi-Fuling Wan (GZFL) is a classical traditional Chinese herbal formula that has been clinically ... ...

    Abstract Background: Ovarian cancer (OC) is the most lethal gynecological malignancy. Frequent peritoneal dissemination is the main cause of low survival rate. Guizhi-Fuling Wan (GZFL) is a classical traditional Chinese herbal formula that has been clinically used for treating ovarian cancer with good outcome. However, its therapeutic mechanism for treating OC has not been clearly elucidated. Purpose: We aim to elucidate the potential mechanisms of GZFL in treating OC with a focus on STAT3 signaling pathway. Methods: In vivo efficacy of GZFL was assessed using an OC xenograft mouse model. Proteomics analysis in OC cells and RNA-seq analysis in mice tumors were performed to fully capture the translational and transcriptional signature of GZFL. Effects of GZFL on proliferation, spheroid formation and reactive oxygen species (ROS) were assessed using wildtype and STAT3 knockout OC cells in vitro. STAT3 activation and transcription activity, hypoxia and EMT-related protein expression were assessed to validate the biological activity of GZFL. Results: GZFL suppresses tumor growth with a safety profile in mice, while prevents cell growth, spheroid formation and accumulates ROS in a STAT3-dependent manner in vitro. GZFL transcriptionally and translationally affects genes involved in inflammatory signaling, EMT, cell migration, and cellular hypoxic stress response. In depth molecular study confirmed that GZFL-induced cytotoxicity and EMT suppression in OC cells are directly corelated to inhibition of STAT3 activation and transcription activity. Conclusion: Our study provides the first evidence that GZFL inhibits OC progression through suppressing STAT3-EMT signaling. These results will further support its potential clinical use in OC.
    Keywords Ovarian carcinoma ; Guizhi Fuling ; STAT3 ; EMT ; Hypoxic stress ; Traditional Chinese Medicine ; Therapeutics. Pharmacology ; RM1-950
    Subject code 570 ; 572
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Network Pharmacology Prediction and Molecular Docking-Based Strategy to Discover the Potential Pharmacological Mechanism of Wen-Yu-Jin against Pulmonary Fibrosis in a Mouse Model

    Lu Wang / Wenxiang Zhu / Rui Sun / Jing Liu / Qihong Ma / Binbin Zhang / Yuanyuan Shi

    Evidence-Based Complementary and Alternative Medicine, Vol

    2022  Volume 2022

    Abstract: Background. Pulmonary fibrosis (PF) is a devastating lung disease, resulting in gas exchange dysfunction until death. The two drugs approved by the FDA, pirfenidone and nintedanib, have obvious side effects. Wen-yu-jin (WYJ), one of the commonly used ... ...

    Abstract Background. Pulmonary fibrosis (PF) is a devastating lung disease, resulting in gas exchange dysfunction until death. The two drugs approved by the FDA, pirfenidone and nintedanib, have obvious side effects. Wen-yu-jin (WYJ), one of the commonly used herbs in China, can treat respiratory diseases. The potential effects and the underlying mechanism of WYJ against PF are unclear. Purpose. Employing network pharmacology, molecular docking, and in vivo and in vitro experiments to explore the potential effects and underlying mechanisms of WYJ in the treatment of PF. Methods. Ultra-high pressure liquid chromatography combined with linear ion trap-orbital tandem mass spectrometry (UHPLC-LTQ-orbital trap) was used to identify compounds of WYJ. We got PF-related targets and WYJ compounds-related targets from public databases and further completed critical targets exploration, network construction, and pathway analysis by network pharmacology. Molecular docking predicted binding activity of WYJ compounds and critical targets. Based on the above results, in vivo and in vitro experiments validated the potential effects and mechanisms of WYJ against PF. Results. 23 major compositions of WYJ were identified based on UHPLC-LTQ-Orbitrap. According to the results of network pharmacology, STAT3, SRC, IL6, MAPK1, AKT1, EGFR, MAPK8, MAPK14, and IL1B are critical therapeutic targets. Molecular docking results showed that most of the compounds have good binding activities with critical targets. The results of in vivo and in vitro experiments showed that WYJ alleviated the process of fibrosis by targeting MAPK and STAT3 pathways. Conclusion. Network pharmacology, molecular docking, and in vivo and in vitro experiments showed the potential effects and mechanisms of WYJ against PF, which provides a theoretical basis for the treatment of WYJ with PF.
    Keywords Other systems of medicine ; RZ201-999
    Subject code 540
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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