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Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma
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作者 Li peng Yanyi Jiang +13 位作者 Hengxing Chen Yongqiang Wang Qiusheng Lan Shuiqin Chen Zhanwang Huang Jingyuan Zhang Duanqing Tian Yuntan Qiu Diankui Cai jiangyun peng Daning Lu Xiaoqing Yuan Xianzhu Yang Dong Yin 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第5期2119-2136,共18页
Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development.However,it is extremely challenging to develop small-molecule inhibitors to target abnormally express... Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development.However,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of TFs.Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor complexes.In this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA cells.Importantly,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA.Furthermore,we identified KRAS signaling as a common pathway downstream of EHF and AJUBA.Applicably,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in vivo.In conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway.Targeting of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy. 展开更多
关键词 EHF AJUBA KRAS pathway Enhancer Core transcriptional regulatory circuitry Gastroesophageal adenocarcinoma Gastric adenocarcinoma Esophageal adenocarcinoma Transcription factor COACTIVATOR Lipid nanoparticles
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Elucidating the therapeutic mechanism of Cang Zhu and Huang Bai in rheumatoid arthritis: a comprehensive analysis integrating network pharmacology and GEO data
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作者 Qian Deng Zining peng +6 位作者 Weitian Yan Nian Liu Fanyu Meng Jianmei Yin Haozhe Zhang Xingqiang Wang jiangyun peng 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2024年第10期943-964,共22页
In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of t... In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach. 展开更多
关键词 Network pharmacology GEO Rheumatoid arthritis Cang Zhu Huang Bai Molecular docking
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Exploring the evolution of animal models for gout and hyperuricemia:A bibliometric analysis
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作者 Zining peng Qian Deng +4 位作者 Fanyu Meng Xingqiang Wang Nian Liu Weitian Yan jiangyun peng 《Journal of Chinese Pharmaceutical Sciences》 CAS 2024年第11期1058-1067,共10页
This study aimed to systematically analyze the research status and trends in animal models for gout and hyperuricemia(HUA)through a bibliometric approach.We retrieved relevant literature on animal models of gout and H... This study aimed to systematically analyze the research status and trends in animal models for gout and hyperuricemia(HUA)through a bibliometric approach.We retrieved relevant literature on animal models of gout and HUA from the Web of Science(WOS)database.Utilizing analysis software such as Citespace and VOSviewer,we conducted a comprehensive examination of annual publication trends,contributing countries,institutions,and authors.Our analysis revealed a steady increase in the number of publications in this field.China emerged as the leading country,with 113 publications.Zhen Liu was identified as the most influential author,while Nanjing University stood out as the most influential institution.Keyword analysis elucidated current focal points,uncovering evolving patterns and emerging hotspots within the research landscape.Current research predominantly centered on understanding the pathogenesis and exploring new treatment modalities for gout and HUA.This study offered valuable insights into research trends and hotspots related to animal models for gout and HUA,enabling researchers to stay informed about the latest developments in this field. 展开更多
关键词 Animal model Gout Hyperuricemia Bibliometric analysis
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Fargeted elimination of mutant mitochondria DNA in MELAS-iPSCs by mitoTALENs 被引量:8
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作者 Yi Yang Han Wu +21 位作者 Xiangjin Kang Yanhui Liang Ting Lan Tianjie Li Tao Tan jiangyun peng Quanjun Zhang Geng An Yali Liu Qian Yu Zhenglai Ma Ying Lian Boon Seng Soh Qingfeng Chen Ping Liu Yaoyong Chen Xiaofang Sun Rong Li Xiumei Zhen Yang Yu Xiaoping Li Yong Fan 《Protein & Cell》 SCIE CAS CSCD 2018年第3期283-297,共15页
Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy,... Mitochondrial diseases are maternally inherited hetero- geneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruc- tion of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A〉G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A〉G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Further- more, we successfully achieved reduction in the human m.3243A〉G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA. 展开更多
关键词 MITOCHONDRIA IPSCS TALEN MELAS
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COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors
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作者 Xi He Chenshu Liu +46 位作者 jiangyun peng Zilun Li Fang Li Jian Wang Ao Hu Meixiu peng Kan Huang Dongxiao Fan Na Li Fuchun Zhang Weiping Cai Xinghua Tan Zhongwei Hu Xilong Deng Yueping Li Xiaoneng Mo Linghua Li Yaling Shi Li Yang Yuanyuan Zhu Yanrong Wu Huichao Liang Baolin Liao Wenxin Hong Ruiying He Jiaojiao Li pengle Guo Youguang Zhuo Lingzhai Zhao Fengyu Hu Wenxue Li Wei Zhu Zefeng Zhang Zeling Guo Wei Zhang Xiqiang Hong Wei kang Cai Lei Gu Ziming Du Yang Zhang Jin Xu Tao Zuo Kai Deng Li Yan Xinwen Chen Sifan Chen Chunliang Lei 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2022年第1期270-281,共12页
Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-relat... Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications. 展开更多
关键词 metabolism mechanism resistance
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