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Neural Regeneration Research 2024年第5期19卷 953-954页

作者： Xiaowen Bai department of cell biology Neurobiology&AnatomyMedical College of WisconsinMilwaukeeWIUSA

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

关键词： injuries protective drugs

DNA fragmentation in apoptosis

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cell Research 2000年第3期10卷 205-211页

作者： ZHANG JIAN HUA, MING XU (department of cell biology, neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 452670521, USA) department of cell biology Neurobiology and Anatomy University of Cincinnati College of Medicine Cincinnati USA

Cleavage of chromosomal DNA into oligonucleosomal size fragments is an integral part of apoptosis. Elegant biochemical work identified the DNA fragmentation factor (DFF) as a major apoptotic endonuclease for DNA fragmentation in vitro. Genetic studies in mice support the importance of DFF in DNA fragmentation and possibly in apoptosis in vivo. Recent work also suggests the existence of additional endonucleases for DNA degradation. Understanding the roles of individual endonucleases in apoptosis, and how they might coordinate to degrade DNA in different tissues during normal development and homeostasis, as well as in various diseased states, will be a major research focus in the near future.

关键词： DNA fragmentation DFF endonucleases apop tosts.

Identification and Characterization of a Rat Novel Gene RSEP4 Expressed Specifically in Central Nervous System

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 501-507页

作者： Xi-Dao WANG1,2, Ling-Wei KONG1, Zhi-Qin XIE1, Yu-Qiu ZHANG3, Zhi-Xin LIN2, Zhi-Qi ZHAO3,Lei YU4, and Nai-He JING1* 1 Laboratory of Molecular cell biology, Laboratory of Stem cell biology, Institute of Biochemistry and cell biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China School of Life Science and Biotechnology, 2 Shanghai Jiaotong University, Shanghai 200030, China Institute of neurobiology, Fudan University, Shanghai 200433, China 3 4 department of cell biology, neurobiology and Anatomy, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA Laboratory of Molecular cell biology Laboratory of Stem Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of SciencesShanghai 200031 China School of Life Science and Biotechnology Shanghai Jiaotong UniversityShanghai 200030 China Institute of neurobiology Fudan UniversityShanghai 200433 China department of cell biology Neurobiology and Anatomy College of Medicine University of CincinnatiCincinnati Ohio USA

The low-abundantly expressed genes composed the majorities of the mRNAs expressed in the central nervous system (CNS), and were thought to be important for the normal brain functions. Through differential screening a low-abundance cDNA sublibrary with mRNA from neuropathic pain of chronic constriction injury (CCI) model, we have identified a novel rat gene, rat spinal-cord expression protein 4 gene (RSEP4). The total length of RSEP4 cDNA is 2006 bp, with a 501 nucleotide open reading frame (ORF) that encodes a 167 amino acid polypeptide. Northern blot revealed that RSEP4 was expressed specifically in the CNS. In situ hybridization showed that the mRNA of RSEP4 was strongly expressed in the CA1, CA2, CA3 and DG regions of hippocampus, the Purkinje cells of cerebellum, and the small sensory neurons of dorsal horn and large motor neurons of ventral horn of spinal cord. Over-expression of RSEP4-EGFP fusion protein in the human embryonic kidney 293T cells showed that RSEP4 protein was mainly localized in the cell cytoplasm. These results suggest that RSEP4 may play some roles in the CNS.

关键词： central nervous system (CNS) rat Northern blot in situ hybridization

Oncogenic MORC2 in cancer development and beyond

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Genes & Diseases 2024年第2期11卷 861-873页

作者： Shan Zhang Ayao Guo Huan Wang Jia Liu Chenshuang Dong Junyi Ren Guiling Wang Key Laboratory of cell biology Department of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyangLiaoning 110122China department of Breast Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear proteins.Growing evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor suppressors.The present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target genes.This systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

关键词： Cancer development Hallmarks of cancer MORC2 Therapeutic target Treatment resistance

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental biology Department of Biology University of Patras Laboratory of cellular and Molecular neurobiology-Stem cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson's disease substantia

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance

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Genes & Diseases 2024年第1期11卷 148-175页

作者： Divya Ajmeera Rajanna Ajumeera cell biology department ICMR-National Institute of Nutrition(NIN)HyderabadTelangana 500007India

Chemotherapy is an effortless and frequently used approach in cancer therapy.However,in most cases,it can only prolong life expectancy and does not guarantee a complete cure.Furthermore,chemotherapy is associated with severe adverse effects,one of the major complications of effective cancer therapy.In addition,newly published research outputs show that cancer stem cells are involved in cancer disease progression,drug resistance,metastasis,and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.Novel strategies are therefore required for better management of cancer therapy.The prime approach would be to synthesize and develop novel drugs that need extensive resources,time,and endurance to be brought into therapeutic use.The subsequent approach would be to screen the anti-cancer activity of avail-able non-cancerous drugs.This concept of repurposing non-cancer drugs as an alternative to current cancer therapy has become popular in recent years because using existing anticancer drugs has several adverse effects.Micronutrients have also been investigated for cancer ther-apy due to their significant anti-cancer effects with negligible or no side effects and availabil-ity in food sources.In this paper,we discuss an ideal hypothesis for screening available non-cancerous drugs with anticancer activity,with a focus on cancer stem cells and their clinical application for cancer treatment.Further,drug repurposing and the combination of micronu-trients that can target both cancers and cancer stem cells may result in a better therapeutic approach leading to maximum tumor growth control.

关键词： Cancerstem cells Chemotherapy Combination therapy micronutrients Non-cancer drugs Novel strategies

New insights into the role of the endoplasmic reticulum in microglia

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Neural Regeneration Research 2024年第7期19卷 1397-1398页

作者： Veronika E.Neubrand M.Rosario Sepúlveda department of cell biology Faculty of SciencesUniversity of GranadaGranadaSpain

Microglial cells are the only resident immune cells in the central nervous system and constitute its frontline guardian.They are extremely reactive against infections,trauma,or toxins,but are also responsible for mediating inflammation,taking part in the pathogenic course of many neuropathologies(Sierra et al.,2019).cell-specific staining,ultrastructural analysis by transmission electron microscopy(TEM),or two-photonmicroscopy imaging have been relevant for the characterization of microglia as well as their cell-cell interactions。

关键词： inflammation reticulum

Post-transcriptional mechanisms controlling neurogenesis and direct neuronal reprogramming

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Neural Regeneration Research 2024年第9期19卷 1929-1939页

作者： Elsa Papadimitriou Dimitra Thomaidou department of neurobiology Hellenic Pasteur InstituteAthensGreece

Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on

关键词： direct neuronal reprogramming in vivo glia-to-neuron conversion microRNAs neurogenesis post-transcriptional regulation RNA binding proteins

A toast to a zebrafish germ cell induction cocktail

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Science China(Life Sciences) 2024年第6期67卷 1314-1315页

作者： Mary C.Mullins department of cell and Developmental biology University of Pennsylvania Perelman School of MedicinePhiladelphia 19104USA

The zebrafish field is ringing in the new year with a publication from Yonghua Sun's laboratory(Wang et al.,2023)of a cocktail of germline factors that can induce all cells of the zebrafish embryo into primordial germ cells(PGCs)at phenomenal rates.This major advance is not only of great interest to germ cell biologists,but it has important applications to the entire zebrafish field,as shown in Wang et al.(2023).

关键词： fish zebra field

A perspective on age-related changes in cell environment and risk of neurodegenerative diseases

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Neural Regeneration Research 2024年第4期19卷 719-720页

作者： Alice Y.Liu department of cell biology and Neuroscience Rutgers State University of New JerseyPiscatawayNJUSA

“Age-related neurodegenerative disease”underscores human age as the primary risk factor for disease development:Alzheimer’s,Parkinson’s,and Huntington’s disease(HD)as examples.Reasons for the age-dependent delay in disease manifestation,in particular for autosomal dominant forms of the disease,and the underlying cause(s)of specific neuron dysfunction and death to manifest as memory loss,anxiety,depression,and agitation in disease subjects remain unclear.We are interested in understanding age-related changes in cell environment that can modulate the structure,function,aggregation.

关键词： Huntington Alzheimer death