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Current insights into the oncogenic roles of lncRNA LINC00355

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Cancer Innovation 2023年第6期2卷 448-462页

作者： Jinze Shen Xinming Su Ming Pan Zehua Wang Yufei Ke Qurui Wang Jingyin Dong Shiwei Duan Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhouZhejiangChina

Long noncoding RNAs(lncRNAs)are a class of nonprotein-coding transcripts that are longer than 200 nucleotides.LINC00355 is a lncRNA located on chromosome 13q21.31 and is consistently upregulated in various cancers.It regulates the expression of downstream genes at both transcriptional and posttranscriptional levels,including eight microRNAs(miR-15a-5p,miR-34b-5p,miR-424-5p,miR-1225,miR-217-5p,miR-6777-3p,miR-195,and miR-466)and three protein-coding genes(ITGA2,RAD18,and UBE3C).LINC00355 plays a role in regulating various biological processes such as cell cycle progression,proliferation,apoptosis,epithelial-mesenchymal transition,invasion,and metastasis of cancer cells.It is involved in the regulation of the Wnt/β-catenin signaling pathway and p53 signaling pathway.Upregulation of LINC00355 has been identified as a high-risk factor in cancer patients and its increased expression is associated with poorer overall survival,recurrence-free survival,and disease-free survival.LINC00355 upregulation has been linked to several unfavorable clinical characteristics,including advanced tumor node metastasis and World Health Organization stages,reduced Karnofsky Performance Scale scores,increased tumor size,greater depth of invasion,and more extensive lymph node metastasis.LINC00355 induces chemotherapy resistance in cancer cells by regulating five downstream genes,namely HMGA2,ABCB1,ITGA2,WNT10B,and CCNE1 genes.In summary,LINC00355 is a potential oncogene with great potential as a diagnostic marker and therapeutic target for cancer.

关键词： ceRNA chemotherapy resistance lncRNA LINC00355 miRNA prognosis

Can glial cells save neurons in epilepsy?

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neural Regeneration Research 2023年第7期18卷 1417-1422页

作者： Weida Shen Jelena BogdanovićPristov Paola Nobili Ljiljana Nikolić Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineZhejiang University City CollegeHangzhouZhejiang ProvinceChina Department of Life Sciences University of BelgradeInstitute for Multidisciplinary ResearchBelgradeSerbia Institute of Functional Genomics(IGF) University of MontpellierCNRSINSERMMontpellierFrance Department of Neurophysiology Institute for Biological Research Siniša StankovićNational Institute of Republic of SerbiaUniversity of BelgradeBelgradeSerbia

Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.

关键词： astrocyte cytokines glutamate ion channel microglia myelin neuron oligodendrocyte purinergic signaling seizures

Rapid Eye Movement Sleep Consolidates Social Memory

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Neuroscience Bulletin 2023年第10期39卷 1598-1600页

作者： Jingkai Fan Fang Zhou Junqiang Zheng Han Xu Department of Neurobiology and Department of Neurology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu laboratory MOE Frontier Science Center for Brain Science and Brain-Machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou 311121China NHC and CAMS key laboratory of Medical Neurobiology Zhejiang UniversityHangzhou 310058China Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015China

Social memory is one of declarative memory which is essential for animals to exhibit appropriate social behaviors.Evidence suggests that the hippocampus,particularly the CA2 region,plays an important role in encoding and consolidating social memory[1].Rapid eye movement(REM)sleep has been suggested to contribute to social memory consolidation by up-regulating synaptic plasticity,local field potentials,and dendritic activity[2].

关键词： memory plasticity consolidation

Serotonin:A Bridge for Infant-mother Bonding

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Neuroscience Bulletin 2023年第11期39卷 1741-1744页

作者： Jingkai Fan Han Xu Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou310058China Liangzhu laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS key laboratory of Medical Neurobiology Zhejiang UniversityHangzhou310058China Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou310015China

Maternal affiliation behavior by infants is one of the most important social behaviors of mammalians.Attachment to its mother is optimal to ensure nutrition and protection,and therefore essential for an infant's survival.More importantly,maternal affiliation benefits animals'mental and physical health in adulthood[1].Despite the importance of maternal affiliation,its underlying molecular and circuit mechanisms are only partially understood.Ultrasonic vocalizations(USVs)emitted by mice and rats have been extensively studied in infant-mother behaviors since USVs reflected pups'emotional states and the eagerness to communicate with their mothers[2].

关键词： mother spite emotional

The cGAS-STING pathway:a therapeutic target in chromosomally unstable cancers

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Signal Transduction and Targeted Therapy 2023年第2期8卷 338-340页

作者： Haiyan Yan Weiguo Lu Fangwei Wang Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City University310015HangzhouChina Women’s Hospital Zhejiang University School of Medicine310006HangzhouChina Cancer Center Zhejiang University310058HangzhouChina The MOE key laboratory of Biosystems Homeostasis&Protection and zhejiang Provincial key laboratory of Cancer Molecular Cell Biology Life Sciences InstituteZhejiang University310058HangzhouChina

In a recent study published in Nature,Hong et al.revealed that the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)innate immune pathway is critically required for the IL-6-dependent survival of chromosomally unstable cancer cells,1 implying that chronic inflammation can be therapeutically targeted to kill cancers displaying chromosomal instability(CIN).

关键词： unstable chromosomal therapeutic

CMT2D neuropathy is influenced by vitamin D-mediated environmental pathway

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Journal of Molecular Cell Biology 2023年第4期15卷 64-67页

作者： Huaqing Liu Mingmin Tang Hualin Yu Tongfei Liu Qinqin Cui Linfan Gu Zhi-Ying Wu Nengyin Sheng Xiang-Lei Yang Linghui Zeng Ge Bai Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015China Department of Neurobiology and Department of Neurology of Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu laboratory MOE Frontier Science Center for Brain Science and Brain–Machine IntegrationState Key Laboratory of Brain–Machine IntelligenceZhejiang UniversityHangzhou 311121China The Institute for Brain Science and Disease Chongqing Medical UniversityChongqing 400016China Department of Molecular Medicine The Scripps Research InstituteLa JollaCA 92037USA key laboratory of Medical Neurobiology of zhejiang province Zhejiang University School of MedicineHangzhou 310009China State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China

Dear Editor,Peripheral neuropathy is a group of devastating diseases affecting periphe-ral nerves and may cause symptoms such as extreme numbness,muscle weakness,and paralysis.Currently,there are no effective therapies for these diseases.Great progress has been made in identifying genetic causes for peripheral neuropathy owing to the advances in genetic testing in the last decade.For example,>100 genes have been identified to be associated with Charcot–Marie–Tooth(CMT)neuropathy,a group of disorders among the most common forms of inherited peripheral neuropathy.

关键词： neuropathy vitamin Marie

A biosensing system using a multiparameter nonlinear dynamic analysis of cardiomyocyte beating for drug-induced arrhythmia recognition

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Microsystems & Nanoengineering 2022年第3期8卷 277-290页

作者： Hao Wang Yue Wu Quchao Zou Wenjian Yang Zhongyuan Xu Hao Dong Zhjing Zhu Depeng Wang Tanxing Wang Ning Hu Diming Zhang State key laboratory of Optoelectronic Materials and Technologies Guangdong Province Key Laboratory of Display Material and TechnologySchool of Electronics and Information TechnologySun Yat-sen UniversityGuangzhou 510006China Research Center for Itelligent Sensing Systems Zhejiang LabHangzhou 311121China ZJU-Hangzhou Global Scientific and Technological Innovation Center Department of ChemistryThe Second Affiliated Hospital Zhejiang University School of MedicineDepartment of Clinical Medical EngineeringZhejiang UniversityHangzhou 310058China key laboratory of novel Target and drug study for neural repair of Zhejang province School of MedicineSchool of Computer&Computing ScienceZhejiang University City CollegeHangzhou 310015China School of Brain Science and Brain Medicine Zhejiang UniversityHangzhou 310058China College of Energy and Power Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210016China E-LinkCare Meditech Co LtdHangzhou 310011China State key laboratory of Transducer Technology Chinese Academy of SciencesShanghai 200050China

Cardiovascular disease is the number one cause of death in humans.Therefore,cardiotoxicity is one of the most important adverse effects assessed by arrhythmia recognition in drug development.Recently,cell-based techniques developed for arhythmia recognition primarily employ linear methods such as time-domain analysis that detect and compare individual waveforms and thus fall short in some applications that require automated and efficient arrhythmia recognition from large datasets.We carried out the frst report to develop a biosensing system that integrated impedance measurement and multiparameter nonlinear dynamic algorithm(MNDA)analysis for druginduced arrhythmia recognition and classification.The biosensing system cultured cardiomyocytes as physiologically relevant models,used interdigitated electrodes to detect the mechanical beating of the cardiomyocytes,and employed MNDA analysis to recognize drug-induced arrhythmia from the cardiomyocyte beating recording.The best performing MNDA parameter,approximate entropy,enabled the system to recognize the appearance of sertindoleand norepinephrine-induced arrhythmia in the recording.The MNDA reconstruction in phase space enabled the system to classify the different arrhythmias and quantify the severity of arrhythmia.This new biosensing system utilizing MNDA provides a promising and alternative method for drug-induced arrhythmia recognition and classification in cardiological and pharmaceutical applications.

关键词： arrhythmia cardio analysis

A biosensing system employing nanowell microelectrode arrays to record the intracellular potential of a single cardiomyocyte

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Microsystems & Nanoengineering 2022年第3期8卷 185-198页

作者： Yuting Xiang Haitao Liu Wenjian Yang Zhongyuan xu Yue Wu Zhajian Tang Zhjing Zhu Zhiyong Zeng Depeng Wang Tianxing Wang Ning Hu Diming Zhang Department of Obstetrics and Gynecology Affiliated Dongguan People's HospitalSouthern Medical UniversityDongguan 523058China Research Center for Inelligent Sensing Systems Zhejiang LaboratoryHangzhou 311100China Research Center for Humanoid Sensing Zhejiang LaboratoryHangzhou 311100China key laboratory of novel Target and drug study for neural repair of zhejiang province School of MedicineSchool of Computer&Computing ScienceZhejiang University City CollegeHangzhou 310015China School of Brain Science and Brain Medicine Zhejiang UniversityHangzhou 310058China School of Automation Nanjing University of Science and TechnologyNanjing 210094China College of Energy and Power Engineering Nanjing University of Aeronautics and AstronauticsNanjing 210016China E-Link Care Meditech Co. LtdHangzhou 310011China ZJU-Hangzhou Global Scientific and Technological Innovation Center Department of ChemitryZhejiang UniversityHangzhou 310058China

Electrophysiological recording is a widely used method to investigate cardiovascular pathology,pharmacology and developmental biology.Microelectrode arrays record the electrical potential of cells in a minimally invasive and highthroughput way.However,commonly used microelectrode arays primarily employ planar microelectrodes and cannot work in applications that require a recording of the intracellular action potential of a single cell.In this study,we proposed a novel measuring method that is able to record the intracellular action potential of a single cardiomyocyte by using a nanowell patterned microelectrode array(NWMEA).The NWMEA consists of five nanoscale wells at the center of each circular planar microelectrode.Biphasic pulse electroporation was applied to the NWMEA to penetrate the cardiomyocyte membrane,and the intracellular action potential was continuously recorded.The intracellular potential recording of cardiomyocytes by the NWMEA measured a potential signal with a higher quality(213.76±25.85%),reduced noise root-mean-square(~33%),and higher signal-to-noise ratio(254.36±12.61%)when compared to those of the extracellular recording.Compared to previously reported nanopillar microelectrodes,the NWMEA could ensure single cell electroporation and acquire high-quality action potential of cardiomyocytes with reduced fabrication processes.This NWMEA-based biosensing system is a promising tool to record the intracellular action potential of a single cell to broaden the usage of microelectrode arrays in electrophysiological investigation.

关键词： arrays potential record

Active Compounds and Molecular targets of Chinese Herbal Medicine for Neurogenesis in Stroke Treatment: Implication for Cross Talk between Traditional Chinese Medicine and Biomedical Sciences

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World Journal of Traditional Chinese Medicine 2019年第2期5卷 104-115页

作者： Xi Chen Han-Sen Chen Cheng Peng Jian-Gang Shen School of Chinese Medicine LKS Faculty of MedicineThe University of Hong KongHong KongHong Kong SAR Department of Core Facility The People's Hospital of Bao-an Department of Core Facility The 8th People's Hospital of ShenzhenThe Affiliated Baoan Hospital of Southern Medical University College of Medical Technology and School of Pharmacy Chengdu University of Traditional Chinese Medicine State Key Laboratory Breeding Base of Systematic ResearchDevelopment and Utilization of Chinese Medicine ResourcesSichuan Province and Ministry of Science and TechnologyChengduChina

neural stem/progenitor cells (NSCs) could be attractive therapeutic targets for promoting adult neurogenesis, brain plasticity, and repair in stroke and neurodegenerative diseases, raising great potentials for regeneration therapy. In adult ischemic brains, NSCs have limited capacities of growth, differentiation, and generating new neurons for repairing the damaged central nervous system. However, the spontaneous brain repair seems to be insufficient to recover neurological deficits in most stroke cases. To overcome those problems, pharmacological manipulations targeting on endogenous NSCs or transplanted stem cells could be a promoting strategy for regeneration therapy. Chinese herbal medicine has great potentials for developing novel therapeutic strategies for adult neurogenesis and brain repair in poststroke treatment. Chinese herbal medicine has a long history for poststroke treatment. Recent studies create great opportunity for drug discovery for promoting neurogenesis and improving the recovery of neurological fimctions in poststroke treatment. Many active compounds or extracts from medicinal herbs have shown promising effects on regulating proliferation, self-renewal and differentiation of NSCs, and promoting neural network formation as well as neurological functional recovery with in vitro and in vivo experimental evidence. Therefore, targeting neural stem/progenitor cells can be an important opportunity for the studies of Traditional Chinese Medicine in regeneration medicine. Due to the complex interactions of herbal ingredients in network regulation, huge challenge remains to be resolved for further study.

关键词： Chinese herbal medicine neurogenesis stroke