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Paracrine function amplifies pro-tumor electrochemical signal within neuron-glioma synapses

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Science China(Life Sciences) 2024年第6期67卷 1318-1320页

作者： Yan Hu Peishan Hu xiaozhong peng Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengdu 610041China Guangdong Institute of Gastroenterology Department of General SurgeryGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100730China State Key Laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100730China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Neuronal activity plays a pivotal role in various physiological processes,including tissue development,homeostasis,and *** in recent years have improved our understanding of neuronal activity in brain cancers,such as glioblastoma(GBM)and diffuse midline gliomas(DMG),which are among the most prevalent and lethal cancers affecting children and ***,the neurons regulate brain cancers via two routes.

关键词： glioma homeostasis function

Neurological complications and infection mechanism of SARS-CoV-2

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3534-3549页

作者： Dandan Wan Tingfu Du Weiqi Hong Li Chen Haiying Que Shuaiyao Lu xiaozhong peng Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatrictsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin Road610041 ChengduSichuanPR China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina State Key Laboratory of Medical Molecular Biology Department of MolecularBiology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Currently,SARS-CoV-2 has caused a global pandemic and threatened many *** SARS-CoV-2 mainly causes respiratory diseases,growing data indicate that SARS-CoV-2 can also invade the central nervous system(CNS)and peripheral nervous system(PNS)causing multiple neurological diseases,such as encephalitis,encephalopathy,Guillain-Barrésyndrome,meningitis,and skeletal muscular *** the increasing incidences of clinical neurological complications of SARS-CoV-2,the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully *** this review,we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current ***,we summarize the experimental models were used to study SARS-CoV-2 *** data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.

关键词： invasion complications infection

Polypyrimidine Tract-Binding Protein Regulates Enterovirus 71 Translation Through Interaction with the Internal Ribosomal Entry Site

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Virologica Sinica 2019年第1期34卷 66-77页

作者： Juemin Xi Fei Ye Guanzhou Wang Wei Han Zhizhong Wei Bin Yin Jiangang Yuan Boqin Qiang xiaozhong peng Institute of Medical Biology Chinese Academy of Medical Sciencesand Peking Union Medical College The 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 College

Enterovirus 71(EV71), a major causative agent of hand, foot, and mouth disease, has caused periodic infection outbreaks in children in the Asia–Pacific region. In order to describe the largely unknown life cycle of EV71, the molecular basis of its virus-host interactions must first be determined. The 50 untranslated region of EV71 contains a cloverleaf-like structure and internal ribosomal entry site(IRES), which play an important role in transcription and translation of viral protein. We found that polypyrimidine tract-binding protein 1(PTB) bound to the IRES of EV71. RNA recognition motifs 1 and 2 of PTB were responsible for its binding to the EV71 IRES. Moreover, PTB protein was shuttled from nucleus to cytoplasm after EV71 infection. Additionally, IRES activity and viral protein production were inhibited by PTB knockdown. These results suggest that PTB interacts with the EV71 IRES, and positively regulates viral protein translation.

关键词： EV71 IRES PTB Translation

Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human A CE2-transgenic mice

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Signal Transduction and Targeted Therapy 2022年第1期7卷 310-321页

作者： Zhenfei Bi Weiqi Hong Haiying Que Cai He Wenyan Ren Jingyun Yang Tianqi Lu Li Chen Shuaiyao Lu xiaozhong peng Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan 610041PR China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunmingYunnanChina

The development of animal models for COVID-19 is essential for basic research and drug/vaccine *** reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2,which greatly limits its application in routine ***,we gen erate a mouse model of COVID-19 un der a gen eral laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome(ARDS)observed in huma ***,human ACE2-tra nsge nic(MCE2)mice were in tratracheally in stilled with the formaldehyde-inactivated SARS-CoV-2,resulting in a rapid weight loss and detrimental changes in lung structure and *** pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation,hemorrhage,necrotic debris,and hyaline membrane *** production of fatal cytokines(IL-β,TNF-α,and IL-6)and the infiltration of activated neutrophils,inflammatory monocyte-macrophages,and T cells in the lung were also determined,suggesting the activation of an adaptive immune *** strategies,such as dexamethasone or passive antibody therapy,could effectively ameliorate the disease progression in this ***,the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.

关键词： distress lung routine

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1147-1164页

作者： Yan Guo Pan Xiang Xiaojiao Sun Wei Liu Jiafeng Zhou Bin Yin Lin Hou Boqin Qiang Huiliang Li pengcheng Shu xiaozhong peng Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina State Key Laboratory of Common Mechanism Research for Major Diseases Beijing 100005China Wolfson Institute for Biomedical Research University College LondonGower StreetLondon WC1E 6BTUK Chinese Institute for Brain Research Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream ***,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and ***,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal ***,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and ***6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and *** finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

关键词： impaired restrain peripheral

Cloning and prokaryotic expression of HGLP cDNA

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Chinese Science Bulletin 2001年第13期46卷 1089-1092页

作者： ZHOU Haijun HUANG Xiaowei ZHOU Yan LI Guangtao YIN Bin MA Yanling peng xiaozhong YUAN Jiangang QIANG Boqin Institute of Basic Medical Sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeNational Center of Human Genome ResearchBeijing 100005China

A novel cDNA, HGLP, which encodes a G-protein coupled receptor (GPCR) like protein, has been isolated and cloned. The coding region of the human HGLP predicts a 7-transmembrane region protein with motifs of rhodopsin-like GPCR superfamily. Northern blot analysis reveals a 3-kb transcript in various human tissues examined. The N- and C-terminal coding regions of HGLP, which are deduced as non-transmembrane regions, have been amplified by PCR and cloned into pET30a+ vector. Then the re-combinant proteins are highly expressed in E. coli.

关键词： G-protein coupled receptor HGLP cDNA prokaryotic expression.

The tumor-enriched small molecule gambogic amide suppresses glioma by targeting WDR1-dependent cytoskeleton remodeling

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5904-5918页

作者： Jiaorong Qu Bojun Qiu Yuxin Zhang Yan Hu Zhixing Wang Zhiang Guan Yiming Qin Tongtong Sui Fan Wu Boyang Li Wei Han xiaozhong peng Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China State Key Laboratory of Common Mechanism Research for Major Diseases BeijingChina Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina State Key Laboratory of Respiratory Health and Multimorbidity BeijingChina National Human Diseases Animal Model Resource Center Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

Glioma is the most prevalent brain tumor,presenting with limited treatment options,while patients with malignant glioma and glioblastoma(GBM)have poor *** physical obstacle to drug delivery imposed by the blood‒brain barrier(BBB)and glioma stem cells(GSCs),which are widely recognized as crucial elements contributing to the unsatisfactory clinical *** this study,we found a small molecule,gambogic amide(GA-amide),exhibited the ability to effectively penetrate the blood-brain barrier(BBB)and displayed a notable enrichment within the tumor ***,GA-amide exhibited significant efficacy in inhibiting tumor growth across various in vivo glioma models,encompassing transgenic and primary patient-derived xenograft(PDX)*** further performed a genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)knockout screen to determine the druggable target of *** the combination of the cellular thermal shift assay(CETSA),the drug affinity responsive target stability(DARTS)approach,molecular docking simulation and surface plasmon resonance(SPR)analysis,WD repeat domain 1(WDR1)was identified as the direct binding target of *** direct interaction with WDR1,GA-amide promoted the formation of a complex involving WDR1,MYH9 and Cofilin,which accelerate the depolymerization of F-actin to inhibit the invasion of patient-derived glioma cells(PDCs)and induce PDC apoptosis via the mitochondrial apoptotic *** conclusion,our study not only identified GA-amide as an effective and safe agent for treating glioma but also shed light on the underlying mechanisms of GA-amide from the perspective of cytoskeletal homeostasis.

关键词： glioma invasion homeostasis

Reverse genetics in virology:A double edged sword

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Biosafety and Health 2022年第5期4卷 303-313页

作者： Hongyu Chen Hongqi Liu xiaozhong peng Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical SchoolKunming 650118China Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical SchoolBeijing 100051China Institute of Laboratory Animals Science Chinese Academy of Medical Sciences and Peking Union Medical SchoolBeijing 100021China

Reverse genetics via targeted modification of gene sequences to obtain a phenotype and the inference of a gene's function or regulatory mechanism is widely used as a potent tool in viral biology and ***,while reverse genetics has contributed significantly to our understanding of molecular biology and the pathogenesis of viruses,its accessibility(operation)and openness(data)have raised many concerns regarding biosafety and *** this review,we retrospectively examine the development of reverse genetics and its applications in virology,then emphasize global biosafety and biosecurity concerns regarding reverse genetics,and summarize global regulations,governance,and laws on reverse *** review seeks to enhance our understanding and rational application of reverse genetics technology for the benefit of humankind.

关键词： Reverse genetics Virology Dual use research of concern Biosafety Biosecurity Regulation

SARS-CoV-2 impairs the disassembly of stress granules and promotes ALS-associated amyloid aggregation

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Protein & Cell 2022年第8期13卷 602-614页

作者： Yichen Li Shuaiyao Lu Jinge Gu Wencheng Xia Shengnan Zhang Shenqing Zhang Yan Wang Chong Zhang Yunpeng Sun Jian Lei Cong Liu Zhaoming Su Juntao Yang xiaozhong peng Dan Li Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric DisordersMinistry of EducationShanghai Jiao Tong UniversityShanghai 200030China School of Life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200030China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunming 650031China State Key Laboratory of Medical Molecular Biology Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Biotherapy Department of Geriatrics and National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversitChengdu 610041China Bio-X-Renji Hospital Research Center Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Zhangjiang Institute for Advanced Study Shanghai Jiao Tong UniversityShanghai 200240China

The nucleocapsid(N)protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation,which enables its incorporation into stress granules(SGs)of host ***,whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow,neither do we know its ***,we used SARS-CoV-2 to infect mam-malian cells and observed the incorporation of N protein into SGs,which resulted in markedly impaired self-dis-assembly but stimulated cell cellular clearance of *** experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific tran-sient interactions,which not only expedites the phase transition of these proteins to aberrant amyloid aggre-gation in vitro,but also promotes the aggregation of FUS with ALS-associated P525L mutation in *** addition,we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian *** work indicates that SARS-CoV-2 infection can impair the dis-assembly of host SGs and promote the aggregation of SG-related amyloid proteins,which may lead to an increased risk of neurodegeneration.

关键词： SARS-CoV-2 nucleocapsid protein stress granule