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Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He bo Peng Qi Wang Jie Tian ping Liu Jie Feng Yiwei Liao Longyi Chen ping Jia jian Tang Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality rate.Temozolomide(TMZ)is the first-line treatment for high-grade gliomas.However,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their treatment.In the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were evaluated.The decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with glioma.CORT overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in vivo.CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma expression.Importantly,CORT overexpression reduced the resistance of gliomas to TMZ in vivo.CORT expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT expression.In conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT expression.The CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ.Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide

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Biological Function and Mechanism of Long Noncoding RNAs Nuclear-Enriched Abundant Transcript I in Development of Cervical Cancer

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Chinese Medical Journal 2018年第17期131卷 2063-2070页

作者： Hui-Ling Wang Shun-Yu Hou Hai-bo Li jian-ping Qiu Le bo Cai-ping Mao Reproductive Medicine Center The First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China Department of Gynaecology The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Jiangsu 215000 China

Background： Accumulating documents have demonstrated that long noncoding RNAs （lncRNAs） play critical roles in tumorigenesis. As an lncRNA, nuclear-enriched abundant transcript 1 （NEAT1） has been identified to be involved in the progression of many types of cancers. However, the biological function of NE.4T1 in cervical cancer is not fully investigated. The aim of this study was to disclose the specific biological function of lncRNA NEATI in cervical cancer progression. Methods： Quantitative real-time polymerase chain reaction （qRT-PCR） was utilized to identify the expression of lncRNA NE,4 T1 in the cervical cancer tissues and cell lines. All cervical cancer samples used in this study were collected from the Affiliated Suzhou Hospital of Nanjing Medical University between September 2012 and September 2017. The correlation between NE,4T1 expression and the overall survival rate of cervical cancer patients was analyzed by Kaplan-Meier analysis. The effects of NEAT1 knockdown or overexpression on cell proliferation were tested by performing MTT assays and colony formation assays. Transwell assays were conducted to detect the migratory ability of cervical cancer cells, in which NEAT1 was silenced or overexpressed. Western blotting was utilized to validate whether NEAT1 promotes cervical cancer progression through activating PI3K-Akt signaling pathway. Results： High expression of NE,4T1 predicted poor prognosis of cervical cancer patients （χ^2= 0.735, P = 0.005）. Knockdown of NE,4T1 decreased the number of colonies in CaSki cell from 136.667 ± 13.503 to 71.667 ± 7.506 （t = -18.76, P = 0.003） and decreased the number of colonies in HeLa cell from 128.667 ± 13.317 to 65.667 ± 7.024 （t = -5.54, P = 0.031）. However, overexpression of NEA T1 increased the number of colonies in SiHa cell from 84.667 ± 12.014 to 150.667 ± 18.037 （t = 7.27, P = 0.018）. Knockdown of NEAT1 decreased the migratory number of CaSki cell from 100.333 ± 9.866 to 58.333 ± 5.859 （t = -8.08, P = 0.015） and reduced the migratory number in HeLa cell fro

关键词： Cervical Cancer Long Noncoding RNA Nuclear-Enriched Abundant Transcript 1 Migration PI3K/Akt SignalingPathway Proliferation

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Herbal combinations against COVID-19:A network pharmacology,molecular docking and dynamics study

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Journal of Integrative Medicine 2023年第6期21卷 593-604页

作者： jian-bo Song Li-qin Zhao Hong-ping Wen Yuan-ping Li Department of Pharmacy the Fifth Affiliated Hospital of Shanxi Medical University(Shanxi Provincial People’s Hospital)Taiyuan 030012Shanxi ProvinceChina Department of Infectious Disease the First Affiliated Hospital of Shanxi Medical UniversityTaiyuan 030012Shanxi ProvinceChina

Objective:The aim of this study is to identify molecules from traditional Chinese medicine(TCM)with potential activity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants.Methods:We applied the Apriori algorithm to identify important combinations of herbs in the TCM prescriptions for the treatment of coronavirus disease 2019(COVID-19).Then,we explored the active components and core targets using network pharmacology.In addition,the molecular docking approach was performed to investigate the interaction of these components with the main structural and nonstructural proteins,as well as the mutants.Furthermore,their stability in the binding pockets was further evaluated with the molecular dynamics approach.Results:A combination of Amygdalus Communis Vas.,Ephedra Herba and Scutellaria baicalensis Georgi was selected as the important herbal combination,and 11 main components and 20 core targets against COVID-19 were obtained.These components,including luteolin,naringenin,stigmasterol,baicalein,and so on,were the potentially active compounds against COVID-19.The binding affinity of these compounds with the potential targets was as high as the positive controls.Among them,baicalein could interfere with multiple targets simultaneously,and it also interfered with the interaction between spike protein and angiotensin-converting enzyme 2 receptor.Additionally,almost all the systems reached stability during dynamics simulation.Conclusion:The combination of A.communis,Ephedra Herba and S.baicalensis was the most important herbal combination for the treatment of COVID-19.Baicalein may be a potential candidate against SARS-CoV-2 and its variants.

关键词： Herbal medicine Molecular docking Baicalein Severe acute respiratory syndrome coronavirus 2 Coronavirus disease 2019

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Role and mechanism of angiotensin-converting enzyme 2 in acute lung injury in coronavirus disease 2019

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Chronic Diseases and Translational Medicine 2020年第2期6卷 98-105页

作者： Meng-Yuan Liu bo Zheng Yan Zhang jian-ping Li Department of Cardiology Peking University First HospitalBeijing 100034China NHC Key Laboratory'of Cardiovascular Molecular Biology and Regulatory Peptides Beijing 100034China Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education Health Science CenterPeking UniversityBeijing 100034China

Coronavirus disease 2019 is a major threat to public health globally.Though its pathogenesis has not been fully elucidated,angiotensin-converting enzyme 2(ACE2)has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)into the cell.Here,we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism.As a receptor for coronavirus,ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus(SARS-CoV).The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans.On the other hand,ACE2 negatively regulates the renin-angiotensinaldosterone system(RAAS)primarily by converting angiotensinⅡto angiotensin 1-7.which exerts a beneficial effect on coronavirus-induced acute lung injury.Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection.The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor(ACEI)or angiotensinⅡtype 1 receptor blocker(ARB).To date,no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2,and hence,it is not advisable to discontinue such drugs in patients with cardiovascular disease.

关键词： Severe acute respiratory syndrome coronavirus 2 Angiotensin-converting enzyme 2 Acute lung injury

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Characteristics of pathogens detected in adults with hematological malignancies and nosocomial infections in the tropics

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Chinese Medical Journal 2020年第14期133卷 1735-1737页

作者： Li-ping Dou Cheng Hou Ting Yang Long-Can Cheng jian bo Department of Hematology Hainan Branch of Chinese People’s Liberation Army General HospitalSanyaHainan 572013China Department of Hematology The First Medical CenterChinese People’s Liberation Army General HospitalBeijing 100853China

To the Editor:Human pathogens have evolved over a long time to become mesophiles to adapt to the typical 37°C temperature of the human body.Yeast and yeast-like fungi also grow very well at this temperature,while the optimal temperature for the growth of filamentous fungi is 25 to 28℃.Hainan Island in China has a tropical oceanic monsoon climate with indistinct seasons.The mean temperature at this place for many years has been 24.4℃,and the annual temperature variation is small;the precipitation is approximately 1718.6 mm,and the relative humidity is 82%.These unique weather characteristics provide a favorable growth environment for pathogens.Patients with hematologic malignancies have poor immunity and are susceptible to pathogens.This results in high nosocomial infection rates in patients with hematologic malignancies and frequent antibiotic use.Epidemiological surveys of different regions and hospitals can provide more guidance for clinical drug administration by hematologists in treating infections in patients with hematologic malignancies.

关键词： pathogens infections immunity

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An efficient and modular modeling for launch dynamics of tubed rockets on a moving launcher

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Defence Technology（防务技术） 2021年第6期17卷 2011-2026页

作者： Qin-bo Zhou Xiao-ting Rui Guo-ping Wang jian-shu Zhang Institute of Launch Dynamics Nanjing University of Science and TechnologyNanjingJiangsu Province210094PR China

This paper develops a modular modeling and efficient formulation of launch dynamics with marching fire(LDMF)using a mixed formulation of the transfer matrix method for multibody systems(MSTMM)and Newton-Euler formulation.Taking a ground-borne multiple launch rocket systems(MLRS),the focus is on the launching subsystem comprising the rocket,flexible tube,and tube tail.The launching subsystem is treated as a coupled rigid-flexible multibody system,where the rocket and tube tail are treated as rigid bodies while the flexible tube as a beam with large motion.Firstly,the tube and tube tail can be elegantly handled by the MSTMM,a computationally efficient order-N formulation.Then,the equation of motion of the in-bore rocket with relative kinematics w.***.t.the tube using the Newton-Euler method is derived.Finally,the rocket,tube,and tube tail dynamics are coupled,yielding the equation of motion of the launching subsystem that can be regarded as a building block and further integrated with other subsystems.The deduced dynamics equation of the launching subsystem is not limited to ground-borne MLRS but also fits for tanks,self-propelled artilleries,and other air-borne and naval-borne weapons undergoing large motion.Numerical simulation results of LDMF are given and partially verified by the experiment.

关键词： Launch dynamics Marching fire Transfer matrix method for multibody systems Multiple launch rocket system

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Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression

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Chinese Medical Journal 2011年第1期124卷 26-31页

作者： TIAN Xin-rui TIAN Xin-li BO Jian-ping LI Shao-gang LIU Zhuo-la NIU bo Department of Respiratory Diseases Second Hospital of Shanxi Medical University Taiyuan Shanxi 030001 China Capital Institute of Pediatrics Beijing 100020 China

Background The signal transducer and activator of transcription 6 （STAT6） expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 （Th2） cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation. Methods In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide （ASODN） overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA （pANTI-STAT6）, then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma. Results In vitro, we showed suppression of STAT6 expression and interleukin （IL）-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin （OVA）-sensitized mice, local intranasal administration of fluorescein isothiocyanate （FITC）-Iabeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production. Conclusion These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

关键词： signal transducer and activator of transcription 6 antisense asthma lymphocyte Th2 cytokine

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Design, Analysis and Real-time Implementation of Networked Predictive Control Systems

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自动化学报 2013年第11期39卷 1769-1777页

作者： LIU Guo-ping SUN jian ZHAO Yun-bo School of Engineering University of South Wales Pontypridd CF37 1DL UK Center for Control Theory and Guidance Tech-nology Center Harbin Institute of Technology Harbin 150001 China School of Automation Beijing Institute of Technology Beijing 100083 China Department of Chemical Engineering hnperial College London SW7 2AZ UK

这份报纸用预兆的控制策略涉及设计，分析和联网的控制系统的即时实现。联网的控制系统的特征的分析被详细说明，它证明一个联网的控制系统与常规控制系统不同。完成靠近环的联网的控制系统的需要的性能，联网的预兆的控制计划被介绍。... 详细信息

这份报纸用预兆的控制策略涉及设计，分析和联网的控制系统的即时实现。联网的控制系统的特征的分析被详细说明，它证明一个联网的控制系统与常规控制系统不同。完成靠近环的联网的控制系统的需要的性能，联网的预兆的控制计划被介绍。设计，稳定性分析和联网的预兆的控制系统的即时实现被学习。它被联网的预兆的控制计划能补偿随机的网络通讯延期和数据退学学生的模拟和实际实验说明，完成需要的控制性能并且有好靠近环的稳定性。

关键词：闭环网络控制系统预测控制系统实时实现设计预测控制策略控制方案网络预测控制性能

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Human neuroblastoma cells transfected with two Chinese presenilin 1 mutations are sensitized to trophic factor withdrawal and protected by insulin-like growth factor-1

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Chinese Medical Journal 2008年第10期121卷 910-915页

作者： FANG bo-yan JIA jian-ping Department of Neurology First Affiliated Hospital of Liaoning Medical University Jinzhou Liaoning 121001 China Department of Neurology Xuanwu Hospital Capital Medical University Neurodegenerative Lab of Ministry of Education of the People's Republic of China Beijing 100053 China

Background Two novel presenilin 1 （PS1） mutations, V97L and A136G, were recently found to be involved in the early-onset of Alzheimer＇s disease in two Chinese families. This research aimed to verity their pathological effects. Methods The human neuroblastoma SH-SY5Y cells stably transfected with these two Chinese presenilin 1 mutations were established to explore whether they are sensitive to, or influenced by, serum deprivation and protected by insulin-like growth factor-1 （IGF-1）. Apoptosis rate, glucose uptake of the cells and the expression of glucose transport protein 1 （GLUT1） on cell membranes were examined. Results The V97L or A136G mutants significantly decreased the cells viability and increased the apoptosis rate when compare to PSlwt and mock transfected cells. IGF-1 was found to improve the viability of these two kinds of mutant cells significantly, and to show a protective effect for the mutants when they were treated with trophic deprivation. The glucose uptake of each transfected cell line increased to about 25% after IGF-1 treatment, GLUT1 expression on the cell membrane increased modestly by about 15%-20%. Conclusions Enhanced sensitivity to trophic withdrawal in the cells transfected with the two Chinese PS1 mutations may contribute to the neuron apoptosis, IGF-1 provided a protective effect to cells, possibly through an enhanced glucose transport and mitochondrial activities.

关键词： Alzheimer disease presenilin 1 mutation apoptosis insulin-like growth factor 1

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Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia

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Chinese Journal of Integrative Medicine 2023年第12期29卷 1087-1098页

作者： LIN Po-li CAO Jun-ling REN ping CHEN Jia-li CAO bo-ya HE ping ZHENG Chang-hui LI Qi-wen WANG Wei ZHANG jian School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100029)China Department of Pharmacy Dongfang HospitalBeijing University of Chinese MedicineBeijing(100078)China School of Chinese Medicine Beijing University of Chinese MedicineBeijing(100029)China School of Life Sciences Beijing University of Chinese MedicineBeijing(100029)China School of Basic Medical Sciences Guangzhou University of Chinese MedicineGuangzhou(510006)China Beijing Key Laboratory of TCM Syndrome and Formula Beijing(100029)China Key Laboratory of Beijing University of Chinese Medicine Ministry of EducationBeijing(100029)China

Objective:To explore the potential molecular mechanism of tetrahydropalmatine(THP)on acute myocardial ischemia(AMI).Methods:First,the target genes of THP and AMI were collected from SymMap Database,Traditional Chinese Medicine Database and Analysis Platform,and Swiss Target Prediction,respectively.Then,the overlapping target genes between THP and AMI were evaluated for Grene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and protein-protein interaction network analysis.The binding affinity between the protein and THP was assessed by molecular docking.Finally,the protective effects of THP on AMI model and oxygen and glucose deprivation(OGD)model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qP CR in vivo and in vitro.Results:MMP9,PPARG,PTGS2,SLC6A4,ESR1,JAK2,GSK3B,NOS2 and AR were recognized as hub genes.The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways.THP improved the cardiac function,as well as alleviated myocardial cell damage.Furthermore,THP significantly decreased the RNA expression levels of MMP9,PTGS2,SLC6A4,GSK3B and ESR1(Pbolism and the regulation of hormones.

关键词： tetrahydropalmatine acute myocardial infarction inflammation energy metabolism hormone

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