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Role of 3'-untranslated region translational control in cancer development, diagnostics and treatment

World Journal of Biological Chemistry 2014年第1期5卷 40-57页

作者： Andrii Vislovukh Thaiz Rivera Vargas Anna Polesskaya Irina Groisman State Key Laboratory of Molecular and Cellular Biology Institute of Molecular Biology and Genetics NAS of Ukraine 150 Kyiv 03680 Ukraine Université Paris Sud Laboratoire Epigénétique et Cancer Formation de Recherche Evolution 3377 F-91191 Gif-Sur-Yvette France centre National de la Recherche Scientifique (CNRS) F-91191 Gif-Sur-Yvette France Commissariat à l’Energie Atomique (CEA) Saclay F-91191 Gif-sur-Yvette France

The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their *** outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.

关键词： Translational control 3’ -untranslated region MicroRNAs RNA binding proteins Cancer

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Psychosurgery:A History from Prefrontal Lobotomy to Deep brain Stimulation

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Journal of Geriatric Medicine 2019年第3期1卷 1-8页

作者： Aisha Yousaf Krishna Singh Victoria Tavernor Ashley Baldwin Departments of Psychiatry Rydal WardKnowsley Resource and Recovery CentreNorth West Boroughs Healthcare NHS Foundation TrustKnowsleyMerseysideUnited Kingdom Christ’s College Cambridge UniversityCambridgeshir

Neurosurgical treatment for psychiatric disorders features a long and controversial *** article explores a“spectrum of psychosurgery”,describing how old-fashioned and controversial prefrontal lobotomy gradually evolved into modern day,mainstream scientific deep brain stimulation(DBS).We focus on the rise,fall and possible re-emergence of psychosurgery as a therapeutic intervention *** journey through historic indiscriminate use of prefrontal lobotomy,which evoked stern criticism from both public and professionals,through to the development of modern day DBS-performed for patients suffering from severe,treatment resistant symptoms of obsessive-compulsive disorder(OCD),epilepsy and movement *** hope this article will provide a basis for understanding the availability of existing treatment options and potential future opportunities,whilst simultaneously challenging any public/professional preconceptions of psychosurgery,which may indirectly be obstructing patient ***,we carried out a qualitative survey displayed in WordCloud Format,capturing the intellection of 38 mental health professionals working for North West Boroughs NHS Healthcare Foundation Trust,on“psychosurgery”,“prefrontal lobotomy”and“DBS”,which may well reflect wider public *** summary,the article provides a brief,yet comprehensive overview of the controversial history of psychosurgery,present-day practice,and future trends of neurosurgery for psychiatric disorders.

关键词： Psychosurgery Prefrontal lobotomy Deep brain stimulation Obsessive compulsive disorder Tourette syndrome Epilepsy Parkinson's Disease One flew over the cuckoo's nest

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Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)

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Hepatobiliary Surgery and Nutrition 2022年第2期11卷 227-252,I0011-I0014页

作者： Hui-Chuan Sun Jian Zhou Zheng Wang Xiufeng Liu Qing Xie Weidong Jia Ming Zhao Xinyu Bi Gong Li Xueli Bai Yuan Ji Li Xu Xiao-Dong Zhu Dousheng Bai Yajin Chen Yongjun Chen Chaoliu Dai Rongping Guo Wenzhi Guo Chunyi Hao Tao Huang Zhiyong Huang Deyu Li Gang Li Tao Li Xiangcheng Li Guangming Li Xiao Liang Jingfeng Liu Fubao Liu Shichun Lu Zheng Lu Weifu Lv Yilei Mao Guoliang Shao Yinghong Shi Tianqiang Song Guang Tan Yunqiang Tang Kaishan Tao Chidan Wan Guangyi Wang Lu Wang Shunxiang Wang Tianfu Wen Baocai Xing Bangde Xiang Sheng Yan Dinghua Yang Guowen Yin Tao Yin Zhenyu Yin Zhengping Yu Bixiang Zhang Jialin Zhang Shuijun Zhang Ti Zhang Yamin Zhang Yubao Zhang Aibin Zhang Haitao Zhao Ledu Zhou Wu Zhang Zhenyu Zhu Shukui Qin Feng Shen Xiujun Cai Gaojun Teng Jianqiang Cai Minshan Chen Qiang Li Lianxin Liu Weilin Wang Tingbo Liang Jiahong Dong Xiaoping Chen Xuehao Wang Shusen Zheng Jia Fan 无 Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Medical Oncology of PLA Cancer Center Jinling HospitalNanjingChina Department of Infectious Disease Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Liver Surgery The First Affiliated Hospital of USTCHefeiChina Minimally Invasive interventional Division Sun Yat-sen University Cancer CenterGuangzhouChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiation Oncology Beijing Tsinghua Changgung HospitalBeijingChina Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Pathology Fudan University Shanghai Cancer CentreShanghaiChina Department of Liver Surgery Sun Yat-sen University Cancer CentreGuangzhouChina Department of Hepatobiliary Surgery Clinical Medical CollegeYangzhou UniversityYangzhouChina Department of Hepatobiliopancreatic Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Division of Hepatobiliary Surgery Department of General SurgeryRuijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina Department of Hepatobiliary and Splenic Surgery Shengjing Hospital Affiliated to China Medical UniversityShenyangChina The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Sarcoma CenterPeking University Cancer Hospital and InstituteBeijingChina Department of Hepatobili

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response *** has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’***,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being *** the evidence for conversion therapy in HCC and develop consensus statements to guide clinical *** review:Many research centers in China have accumulated significant experience implementing HCC conversion *** findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related *** order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical *** consensus statements on the implementation of conversion therapy for HCC were *** statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

关键词： Hepatocellular carcinoma(HCC) conversion therapy surgical resection systematic treatment locoregional treatment consensus China

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中枢神经系统的神经炎症:神经胶质细胞的交响篇章

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神经损伤与功能重建 2021年第3期16卷 F0003-F0003页

作者： Qiao-Qiao Yang Jia-Wei Zhou 杜一星(编译) Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghaiChina University of Chinese Academy of Sciences Shanghai200031China 不详

中枢神经系统(CNS)中的神经炎症是神经免疫学研究的重要课题。新近证据表明,神经炎症是各种神经系统疾病(包括神经退行性疾病和中枢神经系统损伤)的关键因素。神经炎症是中枢神经系统中各种神经胶质细胞和周围免疫细胞共同完成的复杂且... 详细信息

中枢神经系统(CNS)中的神经炎症是神经免疫学研究的重要课题。新近证据表明,神经炎症是各种神经系统疾病(包括神经退行性疾病和中枢神经系统损伤)的关键因素。神经炎症是中枢神经系统中各种神经胶质细胞和周围免疫细胞共同完成的复杂且精密策划的过程。中枢神经系统神经炎症中各神经胶质细胞群之间的交流是一个极其复杂并且动态的过程,类似于精心安排的交响乐。然而,关于神经胶质细胞如何相互作用以形成中枢神经系统独特的免疫反应仍然知之甚少。每种类型的神经胶质细胞在神经炎症中的作用取决于炎症线索的性质和疾病的特定病程;我们将在本综述中论神经胶质细胞在神经炎症的三个阶段(包括起始、进展和预后,正如三乐章交响乐)的联合作用。神经炎中神经胶质细胞的这种观点可能为各种中枢神经系统疾病的早期诊断和治疗干预提供有用的线索。

关键词：中枢神经系统平衡胶质细胞相互作用神经免疫学神经炎症

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Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa

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Journal of Genetics and Genomics 2023年第6期50卷 434-446页

作者： Collins K.Boahen S.J.C.F.M.Moorlag Kristoffer Jarlov Jensen Vasiliki Matzaraki Stephanie Fanucchi Ivan Monteiro Charlotte de Bree Ezio T.Fok Musa Mhlanga Leo A.B.Joosten Peter Aaby Christine Stabell Benn Mihai G.Netea Vinod Kumar Department of Internal Medicine and Radboud Institute of Molecular Life Sciences(RIMLS) Radboud University Medical CenterNjmegen6525 HPthe Netherlands Department of Internal Medicine and Radboud Center for Infectious Diseases(RCI) Radboud University Medical CenterNjmegen6525 HPthe Netherlands Odense Patient Data Explorative Network University of Southern Denmark/Odense University HospitalOdenseDK-5000Denmark Center for Clinical Research and Prevention Frederiksberg and Bispebjerg HospitalDK-2000FrederiksbergDenmark Lemba therapeutics Nijmegen6525 GAthe Netherlands Bandim Health Project Indepth NetworkBissaucodex 1004Guinea-Bissau Epigenomics&Single Cell Biophysics Group Department of Cell Biology FNWIRadboud Institute for Molecular Life Sciences(RIMLS)Njmegen6525 HPtheNetherlands Department of Human Genetics Radboud University Medical Center6525 HPthe Netherlands Bandim Health Project Statens Serum InstitutCopenhagen SDK-2300Denmark Danish Institute for Advanced Study University of Southern DenmarkOdenseDK-5000Denmark Department of Internal Medicine and Radboud Center for Infectious Diseases Radboud University Medical CenterNijmegen6525 HPthe Netherlands Department for Immunology and Metabolism Life and Medical Sciences Institute(LIMES)University of BonnGermany University of Groningen University Medical Center GroningenDepartment of GeneticsGroningen970o0 RBthe Netherlands Nitte(Deemed to be University) Nitte University Centre for Science Education and Research(NUCSER)Medical Sciences ComplexDeralakatteMangalore575018India

Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is ***,we aimed to identify single-nucleotide polymorphisms(SNPs)controlling cytokine responses after microbial stimulation in infants of West-African ancestry,comprising of low-birth-weight neonates randomized to bacillus Calmette-Gue rin(BCG)vaccine-at-birth or to the usual delayed ***-wide cytokine cytokine quantitative trait loci(cQTL)mapping revealed 12 independent loci,of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs ***,nine distinct cQTLs were found among infants randomized to *** validation confirmed that several complement genes affect cytokine response after BCG *** observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European *** data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.

关键词： Cytokines Geneticvariation West Africa Immunogenomics QTL BCG

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Generation of oxidants and their role in the metabolism of oxygen in the survivability of filarial parasite Setaria digitata in cattle:a possible intervention strategy

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Infectious Diseases Research 2023年第1期4卷 23-27页

作者： Kochukunju Pillai Jayakumar Kottayath G Nevin Department of Biochemistry PMS College of Dental Science and ResearchThiruvananthapuram 695028India centre for Bioactive Substances from Marine Organisms Kerala University of Fisheries and Ocean StudiesKerala 682506India Department of Marine Biosciences Faculty of Ocean Science and TechnologyKerala University of Fisheries and Ocean StudiesKerala 682506India

Background:The goal of the current study was to identify the potential therapeutic targets by analyzing the production of oxidants and their effects on the antioxidant system of Setaria digitata,a filarial worm that was collected from the peritoneal cavity of recently butchered ***:*** was collected and the mitochondria-like particles(MLP),somatic isolates and the post-nuclear fraction were prepared for *** radical intensity and the antioxidant enzyme activity in these fractions were *** effect of diethylcarbamazine(DEC),Q0,omeprazole,and L-methyl arginine on NOS production in the worm was also ***:Experiments showed that coelomic fluid and whole worm showed significant levels of Nitric oxide compared to other *** cytosol of the worm showed higher NOS activity than *** dismutase and nitric oxide(NO)levels were found to be higher in MLP fraction of the *** was also found that DEC did not have any effect on the prevention of NO,while Q0,omeprazole,and L-methyl arginine treatment showed a decrease in NO production ***:The results showed that by using the existing drugs we could reduce the propagation of *** by inhibiting the production of NO.

关键词： Setaria digitata mitochondria-like particles nitric oxide L-methyl arginine

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RING finger 138 deregulation distorts NF-κB signaling and facilities colitis switch to aggressive malignancy

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2555-2567页

作者： Yalan Lu Rong Huang Jianming Ying Xingchen Li Tao Jiao Lei Guo Haitao Zhou Han Wang Amannisa Tuersuntuoheti Jianmei Liu Qichen Chen Yanhong Wang Luying Su Changyuan Guo Fu Xu Ziyi Wang Yan Lu Kai Li Junbo Liang Zhen Huang Xiao Chen Jinjie Yao Hanjie Hu Xiaowen Cheng Yufeng Wan Xinyan Chen Ning Zhang Shiying Miao Jianqiang Cai Linfang Wang Changzheng Liu Wei Song Hong Zhao Department of Biochemistry and Molecular Biology State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Department of Hepatobiliary Surgery State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Gene Editing Screening and R&D of Digestive System Tumor Drugs Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116China Department of Pathology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Clinical Laboratory the First Affiliated HospitalAnhui Medical UniversityHefei 230022China Wellcome centre for Anti-Infectives Research(WCAIR) Division of Biological Chemistry and Drug DiscoverySchool of Life SciencesUniversity of DundeeDundee DD15EHUK

Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling ***,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage ***138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic ***,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)*** importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB *** the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor ***,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.

关键词： malignancy sustained finger

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