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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China department of Biochemistry and molecular biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

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Ferroptosis: A therapeutic opportunity of inflammatory bowel disease

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中华医学杂志(英文版) 2024年第7期137卷 874-876页

作者： Ye Yulin Liu Limin Jing Yang Yao Shuangzhe Yang Mo Dai Xin Piao Meiyu Xu Xin Feng Zelin Wang Xiaoli Liu Yifei Miao Junming Gao Xingjie Yu Qingxiang Cao Xiaocang department of Gastroenterology and Hepatology Tianjin Medical University General Hospital Tianjin Medical University Tianjin 300070 China department of Biochemistry and molecular biology School of Basic Medical Science

To the Editor:Even to this day,the etiology and pathogenesis of inflammatory bowel disease (IBD) are still unelucidated.Despite significant progress in IBD treatment in recent years,some patients remain insensitive or non-responsive towards existing treatments.Therefore,further exploring IBD pathogenesis to develop novel therapeutic drugs or drug combinations is quite necessary.Recent studies have demonstrated the therapeutic potential of regulating cell death in IBD.The ferroptosis,a novel form of cell death,is also involved in the pathological process of IBD.

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Transcriptional Regulation of Urokinase Receptor in High-(95D) and Low-metastatic (95C) Human Lung Cancer Cells

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 405-411页

作者： Chun-Yang LI, Li TAN, Guo-Jing ZHANG, Ping LI, Chang TONG, Jing FAN, and Yun-Song ZHU* Key Laboratory, the Education Ministry, department of Biochemistry and molecular biology, Shanghai Medical College,Fudan University, Shanghai 200032, China Key Laboratory the Education Ministry Department of Biochemistry and Molecular Biology Shanghai Medical College Fudan UniversityShanghai 200032 China

To study the transcriptional regulation of urokinase receptor (uPAR) in high- (95D) and low-metastatic (95C) human lung cancer cells, we performed PCR to amplify 2238 bp uPAR promoter from 95C and 95D cells. According to the results of sequencing, five different bases are found in uPAR promoter between 95C and 95D cells. The results of luciferase activity assay showed that these differences have no significant effect on the uPAR promoter activity. Based on a normal uPAR promoter, progressive truncated mutants were constructed. The transient transfection/reporter assay showed that the promoter region from –136 to +9 may interact with relevant nuclear factors, which result in different levels of uPAR expression between 95C and 95D cells.

关键词： uPAR promoter transcriptional regulation

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RNase MRP RNA and human genetic diseases

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Cell Research 2007年第3期17卷 219-226页

作者： Allison N Martin department of Biochemistry and molecular biology and Center for Genetics and molecular Medicine School of Medicine University of Louisville 319 Abraham Flexner Way KY 40202 USA

RNase MRP RNA is the RNA subunit of the RNase mitochondrial RNA processing(MRP)enzyme complex that isinvolved in multiple cellular RNA processing events.Mutations on RNase MRP RNA gene(RMRP)cause a recessivelyinherited developmental disorder,cartilage-hair hypoplasia(CHH).The relationship of the genotype(RMRP mutation),RNA processing deficiency of the RNase MRP complex,and the phenotype of CHH and other skeletal dysplasias is yetto be explored.

关键词： RNase MRP RNA cartilage-hair hypoplasia

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Structure and Function of the NS1 Protein of Influenza A Virus

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Acta Biochimica et Biophysica Sinica 2007年第3期39卷 155-162页

作者： Dongzi LIN~1 Jingfang LAN~2 Zhizhen ZHANG~1* 1 department of Biochemistry and molecular biology,Guangdong Medical College,Zhanjiang 524023,China 2 department of Clinical Laboratory,Hejin People's Hospital,Hejin 043300,China department of Biochemistry and molecular biology Guangdong Medical CollegeZhanjiang 524023 China department of Clinical Laboratory Hejin People's HospitalHejin 043300 China

The avian influenza A virus currently prevailing in Asia causes fatal pneumonia and multipleorgan failure in birds and humans.Despite intensive research,understanding of the characteristics of influenzaA virus that determine its virulence is incomplete.NS1A protein,a non-structural protein of influenza Avirus,was reported to contribute to its pathogenicity and virulence.NS1A protein is a multifunctionalprotein that plays a significant role in resisting the host antiviral response during the influenza infection.Thisreview briefly outlines the current knowledge on the structure and function of the NS1A protein.

关键词： influenza A virus NS1A protein RNA-binding domain effector domain dimer resistance antiviral response

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Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

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Chinese Journal of Chemistry 2024年第5期42卷 459-463页

作者： Meng Wang Zhonggui Wang Ping Lu Research Center for molecular Recognition and Synthesis Department of ChemistryFudan University220 Handan LuShanghai200433 China Present address: department of Cancer biology Dana-Farber Cancer Institute department of Biological Chemistry and molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic synthesis.We report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available dichlorocyclobutanones.The substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic conditions.Further transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

关键词： Diastereoselectivity Modular synthesis Nucleophilic substitution Organohalides Oxyallyl cation Precision functionalization Strained molecules 1,2,3,4-Tetrasubstituted cyclobutanes

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Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition

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Chinese Journal of Natural Medicines 2024年第1期22卷 31-46页

作者： QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu ZHOU Fei ZHAO Piwen LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China State Key Laboratory of Medical molecular biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关键词： Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs Cytoskeleton ECM deposition

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Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

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Journal of Pharmaceutical Analysis 2024年第1期14卷 152-155页

作者： Shuyu Zheng Yanlin Xin Jiamin Lin Zejuan Xie Keyu Cheng Shanshan Wang Wenli Lu Hao Yang Tianming Lu Jun Li Ruogu Qi Yuanyuan Guo department of Biochemistry and molecular biology School of Medicine&Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing210023China department of Neurosurgery The Second Affiliated HospitalZhejiang UniversityHangzhou310009China

The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].

关键词： NSCLC eIF4E treatment

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Hormones and cancer

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Cell Research 2007年第4期17卷 277-279页

作者： Yongfeng Shang~1 ~1department of Biochemistry and molecular biology,Peking University Health Science Center,38 Xueyuan Rd,Beijing 100083,China department of Biochemistry and molecular biology Peking University Health Science Center Beijing China

Estrogen exhibits a broad spectrum of physiologicalfunctions ranging from regulation of the menstrual cycleand reproduction to the modulation of bone density,brainfunction,and cholesterol mobilization.However,estrogenis also associated with pathological complications par-ticularly with the onset of gynaecological malignanciesincluding breast cancer and endometrial cancer;estrogenis now considered to be a classical etiological factor forbreast cancer and endometrial cancer.In the early 1970s,it was reported that there was a 20-35% increase in incidence of endometrial cancer in WesternCaucasian women who had undergone estrogen therapy[1].Subsequently,a variety of clinical and epidemiologi-cal investigations,with support from studies in cell cultureand animal models,have demonstrated the association ofestrogen with the development and/or progression of thedisease.In 2002,the US National Toxicology Programlisted steroidal estrogens as carcinogens for the first time.The report cites data from human epidemiologic studies thatshow an association between estrogen replacement therapyand an increase in the risk of endometrial cancer,as well asa less consistent increase in the risk of breast cancer.

关键词： gene NSABP Hormones and cancer ERE SERMs

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