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Database-driven protein–protein interaction analysis is followed by single-cell and multi-omics integration to characterize EHH-targeted genes affecting the NSCLC immune microenvironment and immunotherapeutic responsiveness. In vivo and in vitro assays further confirm mitochondrial ROS accumulation, mitochondrial membrane potential alterations, mitochondrial dysfunction, and consequent tumour-cell apoptosis, with CASP3 involvement.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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therapeutic actions and knowledge gap does the study highlight for Euphorbiae Humifusae Herba (EHH)?","Question",{"text":62,"@type":63},"EHH is described as having diverse pharmacological effects, including anti-tumour activity, but the study notes a major gap in understanding its pharmacological properties and anti-tumour mechanisms in detail.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How does the research investigate EHH’s targets in NSCLC?",{"text":67,"@type":63},"Protein–protein interactions are explored using a string database, followed by single-cell analysis and multi-omics to reveal how EHH-targeted genes influence the NSCLC immune microenvironment and immunotherapeutic responses.",{"name":69,"@type":60,"acceptedAnswer":70},"What mitochondrial changes does EHH induce and how are they linked to tumour-cell death?",{"text":71,"@type":63},"EHH increases mitochondrial ROS and alters mitochondrial membrane potential, leading to mitochondrial dysfunction and ultimately apoptosis of NSCLC tumour cells, with involvement of apoptotic gene CASP3.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},342884,1790184133,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & 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Euphorbiae Humifusae Herba-dependent mitochondrial dysfunction in non-small-cell lung cancer  \nChengcheng Zhang1  | Xiaoxue Zhao1 | Feng Li2 | Jingru Qin1 | Lu Yang1 | Qianqian Yin1 | Yiyi Liu1 | Zhiyao Zhu1 | Fei Zhang3 | Zhongqi Wang1  | Haibin Liang3  \n1Department of Medical Oncology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China 2Department of Rheumatology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China 3 Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China  \nCorrespondence  \nZhongqi Wang, Department of Medical Oncology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 725 Wanpingnan Road, Shanghai 200032, China.  \nEmail: [aledx@sina.com](aledx@sina.com)  \nHaibin Liang, Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.  \nEmail: [13921604243@163.com](13921604243@163.com)  \nFunding information  \nShanghai Medical Innovation Research Project of “Science and Technology Innovation Action Plan”, Grant/Award Number: 20Y21902300; Shanghai Municipal Health Commission, Health Youth Talent Project, Grant/Award Number: 2022YQ028; Shanghai Hospital Development Center, Grant/Award Number: SHDC2020CR4050; LongHua Hospital Medical Scholars Scheme, Grant/ Award Number: YM2021023; Shanghai Municipal Hospital Development Center, Grant/Award Number: SHDC12020123  \nAbstract  \nEuphorbiae Humifusae Herba (EHH) is a pivotal therapeutic agent with diverse pharmacological effects. However, a substantial gap exists in understanding its pharmacological properties and anti-tumour mechanisms. This study aimed to address this gap by exploring EHH's pharmacological properties, identifying NSCLC therapyassociated protein targets, and elucidating how EHH induces mitochondrial disruption in NSCLC cells, offering insights into novel NSCLC treatment strategies. String database was utilized to explore protein–protein interactions. Subsequently, single-cell analysis and multi-omics further unveiled the impact of EHH-targeted genes on the immune microenvironment of NSCLC, as well as their influence on immunotherapeutic responses. Finally, both in vivo and in vitro experiments elucidated the anti-tumour mechanisms of EHH, specifically through the assessment of mitochondrial ROS levels and alterations in mitochondrial membrane potential. EHH exerts its influence through engagement with a cluster of 10 genes, including the apoptotic gene CASP3 . This regulatory impact on the immune milieu within NSCLC holds promise as an indicator for predicting responses to immunotherapy. Besides, EHH demonstrated the capability to induce mitochondrial ROS generation and perturbations in mitochondrial membrane potential in NSCLC cells, ultimately leading to mitochondrial dysfunction and consequent apoptosis of tumour cells. EHH induces mitochondrial disruption in NSCLC cells, leading to cell apoptosis to inhibit the progress of NSCLC.  \nK E Y WO R D S  \nEHH, immune, mitochondrial dysfunction, multi-omics, NSCLC, single-cell  \n\n| Chengcheng Zhang, Xiaoxue Zhao and Feng Li have contributed equally to this work. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.\u003Cbr>© 2024 The Author(s) . Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. |\n\nJ Cell Mol Med. 2024;28:e18317 .  \n[https://doi.org/10.1111/jcmm.18317](https://doi.org/10.1111/jcmm.18317)  \n[wileyonlinelibrary.com/journal/jcmm](wileyonlinelibrary.com/journal/jcmm)","cbCaiguFBHrwNWkJ","https://ap.wps.com/l/cbCaiguFBHrwNWkJ","pdf",42946303,22,"English","# Introduction\n## Background on cancer influences and TCM relevance\n## EHH pharmacological effects and reported anti-tumour actions\n# Methods and analyses\n## Protein–protein interaction and target exploration\n## Single-cell and multi-omics integration for immune microenvironment\n## In vivo and in vitro validation of mitochondrial effects\n# Results and mechanisms\n## Mitochondrial ROS and membrane potential changes\n## Mitochondrial dysfunction and apoptosis\n## Gene cluster involvement and immune response prediction\n# Conclusion\n## Implications for novel NSCLC treatment strategies","[{\"question\":\"What therapeutic actions and knowledge gap does the study highlight for Euphorbiae Humifusae Herba (EHH)?\",\"answer\":\"EHH is described as having diverse pharmacological effects, including anti-tumour activity, but the study notes a major gap in understanding its pharmacological properties and anti-tumour mechanisms in detail.\"},{\"question\":\"How does the research investigate EHH’s targets in NSCLC?\",\"answer\":\"Protein–protein interactions are explored using a string database, followed by single-cell analysis and multi-omics to reveal how EHH-targeted genes influence the NSCLC immune microenvironment and immunotherapeutic responses.\"},{\"question\":\"What mitochondrial changes does EHH induce and how are they linked to tumour-cell death?\",\"answer\":\"EHH increases mitochondrial ROS and alters mitochondrial membrane potential, leading to mitochondrial dysfunction and ultimately apoptosis of NSCLC tumour cells, with involvement of apoptotic gene CASP3.\"}]","Integrating single-cell and multi-omic approaches reveals Euphorbiae Humifusae Herba-dependent mitochondrial dysfunction in non-small-cell lung cancer | PDF",1790048624,55]