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Emerging nanomedicine-based therapeutics for hematogenous metastatic cascade inhibition:Interfering with the crosstalk between “seed and soil”

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2286-2305页

作者： junyu wu Yang Long Man Li Qin He Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of Pharmacy Sichuan UniversityChengdu 610064China

Despite considerable progresses in cancer treatment,tumor metastasis is still a thorny issue,which leads to majority of cancer-related *** hematogenous metastasis,the concept of"seed and soil"suggests that the crosstalk between cancer cells(seeds)and premetastatic niche(soil)facilitates tumor *** efforts have been dedicated to inhibit the tumor metastatic cascade,which is a highly complicated process involving various pathways and biological ***,satisfactory therapeutic outcomes are rarely observed,since it is a great challenge to thwart this multi-phase *** advances in nanotechnology-based drug delivery systems have shown great potential in the field of anti-metastasis,especially compared with conventional treatment methods,which are limited by serious side effects and poor *** this review,we summarized various factors involved in each phase of the metastatic cascade ranging from the metastasis initiation to *** we reviewed current approaches of targeting these factors to stifle the metastatic cascade,including modulating primary tumor microenvironment,targeting circulating tumor cells,regulating premetastatic niche and eliminating established ***,we highlighted the multiphase targeted drug delivery systems,which hold a better chance to inhibit ***,we demonstrated the limitation and future perspectives of nanomedicine-based anti-metastasis strategies.

关键词： Tumor metastasis Drug delivery systems Nanomedicine Metastatic cascade Seed and soil Tumor microenvironment Circulating tumor cells Premetastatic niche

Enhancing Geological Understanding and Identifying Gold Anomalies in the Ailaoshan Orogen

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 441-453页

作者： ZHAO Shiyu YANG Lin SONG Yiwei DONG Yuntao FENG Lihao LI Huajian wu junyu WANG Qingfei State Key Laboratory of Geological Processes and Mineral Resources China University of GeosciencesBeijing 100083China Xi’an Center of Mineral Resources Survey China Geological SurveyXi’an 710010China Yunnan Gold Mining Industry Group Kunming 650299China Jiangxi Provincial Key Laboratory of Genesis and Prospect for Strategic Minerals East China University of TechnologyNanchang 330013China Frontiers Science Center for Deep-time Digital Earth China University of Geosciences(Beijing)Beijing 100083China

The Ailaoshan Orogen in the southeastern Tibet Plateau,situated between the Yangtze and Simao blocks,underwent a complex structural,magmatic,and metamorphic evolution resulting in different tectonic subzones with varying structural lineaments and elemental *** elements can conceal or reduce anomalies due to the mutual effect between different anomaly *** the whole zone into subzones based on tectonic settings,ore cluster areas,or sample catchment basins(Scb),geochemical and structural anomalies associated with gold(Au)mineralization have been identified utilizing mean plus twice standard deviations(Mean+2STD),factor analysis(FA),concentration-area(CA)modeling of stream sediment geochemical data,and lineament density in both the Ailaoshan Orogen and the individual *** FA in the divided 98 Scbs with 6 Scbs containing Au deposits can roughly ascertain unknown rock types,identify specific element associations of known rocks and discern the porphyry or skarn-type Au *** with methods of Mean+2STD and C-A model of data in the whole orogen,which mistake the anomalies as background or act the background as anomalies,the combined methods of FA and C-A in the separate subzones or Scbs works well in regional metallogenic potential *** of lineament densities with a 10-km circle diameter is not suitable to locate Au deposits because of the delineated large areas of medium-high lineament *** contrast,the use of circle diameters of 1.3 km or 1.7 km in the ore cluster scale delineates areas with a higher concentration of lineament density,consistent with the locations of known Au *** analyzing the map of faults and Au anomalies,two potential prospecting targets,Scbs 1 and 63 with a sandstone as a potential host rock for Au,have been identified in the Ailaoshan *** use of combined methods in the divided subzones proved to be more effective in improving geological understanding and identifying

关键词： minerology geochemistry gold stream sediment sample catchment basin concentration-area model lineament density Ailaoshan Orogen

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1554-1567页

作者： Yau-tuen Chan Hor-yue Tan Yuanjun Lu Cheng Zhang Chien-shan Cheng junyu wu Ning Wang Yibin Feng School of Chinese Medicine the University of Hong KongHong KongChina Centre for Chinese Herbal Medicine Drug Development School of Chinese MedicineHong Kong Baptist UniversityHong KongChina Department of Traditional Chinese Medicine Shanghai Jiaotong UniversitySchool of Medicine Affiliated Ruijin HospitalShanghai 200025China

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma(PAAD)*** regulation could improve *** is an endogenous hormone that delivers multiple *** we showed that pancreatic melatonin level is associated with patients'*** PAAD mice models,melatonin supplementation suppressed tumor growth,while blockade of melatonin pathway exacerbated tumor *** anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils(TANs),and TANs depletion reversed effects of *** induced TANs infiltration and activation,therefore induced cell apoptosis of PAAD *** arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor *** of Cxcl2 in tumor cells abolished neutrophil migration and ***-induced neutrophils presented an N1-like anti-tumor phenotype,with increased neutrophil extracellular traps(NETs)causing tumor cell apoptosis through cell-to-cell *** analysis revealed that this reactive oxygen species(ROS)-mediated inhibition was fueled by fatty acid oxidation(FAO)in neutrophils,while FAO inhibitor abolished the anti-tumor *** of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil ***2,or TANs,combined with NET marker,can better predict patients'***,we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

关键词： Pancreatic adenocarcinoma Melatonin Anti-tumor immunity Tumor-associated neutrophils Tumor microenvironment CXCL2 Neutrophil extracellular traps NETosis

PTEN suppresses tumorigenesis by directly dephosphorylating Akt

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2294-2296页

作者： Lang Bu Huan Wang Ji-an Pan Lang Chen Fan Xing junyu wu Shun Li Deyin Guo Institute of Precision Medicine the First Affiliated HospitalSchool of MedicineSun Yat-sen UniversityGuangzhouGuangdongChina Department of Immunology School of Basic Medical SciencesWuhan UniversityWuhanHubeiChina Modern Virology Research Center College of Life SciencesWuhan UniversityWuhanHubeiChina Present address:Institute of Synthetic Biology Institutes of Advanced TechnologiesShenzhenGuangdongChina

Dear Editor,The serine-threonine kinase Akt plays a central role in regulating cell proliferation,migration,angiogenesis,transformation,energy metabolism,and death.1 The stimulation of growth factors recruits the PI3K to the plasma membrane and phosphatidylinositol-3A5-trisphosphate(PIP3),which in turn recruits Akt to the plasma membrane through PH domain of Akt.

关键词： metabolism stimulation death

Nuclear translocation of OsMADS25 facilitated by OsNAR2.1 in reponse to nitrate signals promotes rice root growth by targeting OsMADS27 and OsARF7

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Plant Communications 2023年第6期4卷 329-341页

作者： junyu wu Shuaiqi Yang Nana Chen Qining Jiang Linli Huang Jiaxuan Qi Guohua Xu Lisha Shen Hao Yu Xiaorong Fan Yinbo Gan Zhejiang Key Laboratory of Crop Germplasm Department of AgronomyCollege of Agriculture and BiotechnologyZhejiang UniversityHangzhou 310000China State Key Laboratory of Crop Genetics and Germplasm Enhancement Nanjing Agricultural UniversityNanjing 210095China Temasek Life Sciences Laboratory and Department of Biological Sciences National University of Singapore1 Research LinkSingapore 117604Singapore

Nitrate is an important nitrogen source and signaling molecule that regulates plant growth and *** several components of the nitrate signaling pathway have been identified,the detailed mechanisms are still *** previous results showed that OsMADS25 can regulate root development in response to nitrate signals,but the mechanism is still ***,we try to answer two key questions:how does OsMADS25 move from the cytoplasm to the nucleus,and what are the direct target genes activated by OsMADS25 to regulate root growth after it moves to the nucleus in response to nitrate?Our results demonstrated that OsMADS25 moves from the cytoplasm to the nucleus in the presence of nitrate in an *** immunoprecipitation sequencing,chromatin immunoprecipitation qPCR,yeast one-hybrid,and luciferase experiments showed that OsMADS25 directly activates the expression of OsMADS27 and OsARF7,which are reported to be associated with root ***,OsMADS25-RNAi lines,the Osnar2.1 mutant,and OsMADS25-RNAi Osnar2.1 lines exhibited significantly reduced root growth compared with the wild type in response to nitrate supply,and expression of OsMADS27 and OsARF7 was significantly suppressed in these ***,these results reveal a new mechanismby which OsMADS25 interacts with *** interaction is required for nuclear accumulation of OsMADS25,which promotes OsMADS27 and OsARF7 expression and root growth in a nitratedependent manner.

关键词： OsMADS25 OsNAR2.1 OsMADS27 OsARF7 nitrate signaling rice root

Non-Structural Protein 5 of Zika Virus Interacts with p53 in Human Neural Progenitor Cells and Induces p53-Mediated Apoptosis

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Virologica Sinica 2021年第6期36卷 1411-1420页

作者： Ping Li Hualian Jiang Hong Peng Weijie Zeng Yongheng Zhong Miao He Luyang Xie Junhai Chen Deyin Guo junyu wu Chun-Mei Li MOE Key Laboratory of Tropical Disease Control Centre for Infection and Immunity Study(CIIS)School of MedicineSun Yat-Sen UniversityShenzhen518197China

Zika virus(ZIKV) infection could disrupt neurogenesis and cause microcephaly in neonates by targeting neural progenitor cells(NPCs). The tumor suppressor p53-mediated cell cycle arrest and apoptotic cell death have been suggested to be activated upon ZIKV infection, yet the detailed mechanism is not well understood. In the present study, we investigated the effects of ZIKV-encoded proteins in the activation of p53 signaling pathway and found that, among the ten viral proteins,the nonstructural protein 5(NS5) of ZIKV most significantly activated the transcription of p53 target genes. Using the immunoprecipitation-coupled mass spectrometry approach, we identified that ZIKV-NS5 interacted with p53 protein. The NS5-p53 interaction was further confirmed by co-immunoprecipitation and GST pull-down assays. In addition, the MTase domain of NS5 and the C-terminal domain of p53 were mapped to be responsible for the interaction between these two proteins. We further showed that ZIKV-NS5 was colocalized with p53 and increased its protein level in the nuclei and able to prolong the half-life of p53. Furthermore, lentivirus-mediated expression of ZIKV-NS5 in hNPCs led to an apparent cell death phenotype. ZIKV-NS5 promoted the cleavage of PARP1 and significantly increased the cell apoptosis of h *** together, these findings revealed that ZIKV-NS5 is a previously undiscovered regulator of p53-mediated apoptosis in hNPCs, which may contribute to the ZIKV-caused abnormal neurodevelopment.

关键词： Zika virus(ZIKV) Nonstructural protein 5(NS5) p53 Apoptosis Human neural progenitor cells(hNPCs)

Modulating the tumor microenvironment via oncolytic virus and PI3K inhibition synergistically restores immune checkpoint therapy response in PTEN-deficient glioblastoma

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2328-2330页

作者： Fan Xing Jingshu Xiao junyu wu Jiaming Liang Xiaoyu Lu Liping Guo Ping Li Panpan Hou Chunmei Li Deyin Guo MOE Key Laboratory of Tropical Disease Control Centre for Infection and Immunity Study(CHS)School of MedicineSun Yat-sen UniversityShenzhenChina

Dear Editor,Glioblastoma(GBM)is a lethal primary brain cancer,with a median survival of less than 2 years.1 Immune checkpoint blockades(ICBs)have revolutionized cancer therapy in the last decade,but they have little clinical benefit in GBM.1 Genomic and transcriptomic analysis revealed a significant enrichment of PTEN mutations in GBM patients resistant to ICBs.2 PTEN deficiency activates the phosphatidylinositol 3-kinase(PI3K)-AKT pathway to shape an immunosuppressive microenvironment.

关键词： cancer microenvironment clinical

Effect of miR-375 on non-small cell lung carcinoma invasion,migration,and proliferation through the CIP2A pathway

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Oncology and Translational Medicine 2020年第3期6卷 103-108页

作者： junyu wu Weijun Yuan Yuhuan Wang Xiaodong Zhao Department of Emergency The Fourth Medical Center of General Hospital of Chinese People's Liberation ArmyBeijing 100037China Department of Special Medicine School of Basic Medical CollegeQingdao UniversityQingdao 266021China

Lung cancer is one of the malignant tumors with the fastest increase in morbidity and mortality and the greatest threat to people’s health and ***,lung cancer is the leading cause of cancer death in men and the second leading cause of cancer deaths in women[1].Lung cancer is divided into two major groups,small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC)[2].SCLC accounts for approximately 20%of lung *** has a high degree of malignancy and early metastasis,and is sensitive to chemotherapy and *** initial remission rate is high,but it is prone to secondary drug resistance and *** is the *** includes three major histological subtypes,lung squamous cell carcinoma(SCC),lung adenocarcinoma(ADC),and large cell lung cancer(LCLC),accounting for approximately 80%of lung *** division is slower,and the diffusion shift is relatively late[3].Nevertheless,while current research on the biological characteristics of different histological subtypes of NSCLC is expanding,its basic molecular mechanism is not yet *** example,smoking is more risky for SCC than ADC[4].Micro-RNA is an endogenous small RNA with a length of approximately 19–25 *** a short non-coding RNA,its main function is to regulate the expression level of *** can be used as proto-oncogenes or tumor suppressors,and participate in various processes including proliferation,apoptosis,metabolism,and differentiation of cells through targeted binding to different transcripts[5].miRNAs are expressed in specific tissue and developmental stages under normal physiological conditions,but abnormal expression of miRNAs can lead to a series of pathological states,such as tumorigenesis and metastasis[6–7].miRNA regulates the function of tumor cells by regulating the expression of functional *** example,miR-206 promotes breast cancer proliferation by inhibiting estrogen receptor alpha(ERα)while miR-34a downregulates E2 fac

关键词： miR-375 invasion migration non-small cell lung cancer(NSCLC) CIP2A

A novel phosphorylation site in SARS-CoV-2 nucleocapsid regulates its RNA-binding capacity and phase separation in host cells

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Journal of Molecular Cell Biology 2022年第2期14卷 72-75页

作者： junyu wu Yongheng Zhong Xue Liu Xiaoyu Lu Weĳie Zeng Chunyan wu Fan Xing Liu Cao Fuxiang Zheng Panpan Hou Hong Peng Chunmei Li Deyin Guo Centre for Infection and Immunity Study(CIIS) School of MedicineShenzhen Campus of Sun Yat-sen UniversityShenzhen 518197China

Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a novel emerging coronavirus that has spread worldwide since breaking out in late 2019 and has led to hundreds of millions of infections an... 详细信息

关键词： acute respiratory