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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 *** 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 *** 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 *** models could also be used to develop protective and therapeutic approaches.

关键词： injuries protective drugs

Physical exercise and traumatic brain injury: is it question of time?

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Neural Regeneration Research 2024年第3期19卷 475-476页

作者： Valentina Mastrorilli Stefano Farioli Vecchioli institute of Biochemistry and cell biology Institute of Biochemistry and Cell BiologyNational Research Council(IBBC/CNR)MonterotondoRomeItaly Plaisant S.R.L. RomeItaly

Is it better to be safe than sorry?This Hamletic dilemma has always stimulated medical-scientific debates in numerous fields of *** among these,the preventive-therapeutic approach to the treatment of brain trauma is one of the most striking *** brain injury(TBI)is a leading cause of brain damage among young and elderly populations with a very high hospitalization and death *** is characterized by two pathologically distinct but strictly consequential phases:a first characterized by an immediate and highly variable mechanical dysfunction of the brain tissue,which involves widespread cell death and tissue degeneration,followed by a second phase which can last from days to even years depending on the severity of the TBI and the patient’s pre-existing health *** processes,including inflammatory phenomena,oxidative stress associated with metabolic,vascular,and neuro-modulatory deficits,are very often responsible for neuro-motor and psychological deficits leading to long-term disabilities(Kaur and Sharma,2018).

关键词： injury striking modulator

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 ***,in most cases,it can only prolong life expectancy and does not guarantee a complete ***,chemotherapy is associated with severe adverse effects,one of the major complications of effective cancer *** 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 *** strategies are therefore required for better management of cancer *** prime approach would be to synthesize and develop novel drugs that need extensive resources,time,and endurance to be brought into therapeutic *** subsequent approach would be to screen the anti-cancer activity of avail-able non-cancerous *** 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 *** 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 *** 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 ***,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

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

Angiogenesis in diseases:A half-century excursion from the initial therapeutic concept to current clinical benefits

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Chinese Medical Journal 2024年第6期137卷 636-637页

作者： Yihai Cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm 17177Sweden

Except a few tissues such as the cornea and cartilage that are avascular,blood vessels constitute a significant proportion of tissue masses in virtually all *** physiological conditions,the adult vasculature remains quiescent to retain tissue and organ homeostatic *** few or too many blood vessels are associated with the onset and progression of many *** response to injuries,most tissues undergo repair by switching on angiogenesis,a key process of new blood vessel formation.^([1])Similarly,angiogenesis is often active in pathological tissues,including tumors and ischemic tissues to aggravate disease progression.

关键词： injuries organs diseases

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 *** 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 *** 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 *** 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 *** 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 *** 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 ***,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the

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

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration Research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao Yun Sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang State Key Laboratory of Stem cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijingChina institute for Stem cell and Regenerative Medicine Chinese Academy of SciencesBeijingChina National Stem cell Resource Center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing institute for Stem cell and Regenerative Medicine BeijingChina State Key Laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

The evolving views of hematopoiesis:from embryo to adulthood and from in vivo to in vitro

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Journal of Genetics and Genomics 2024年第1期51卷 3-15页

作者： Yifan Zhang Feng Liu Shandong Provincial Key Laboratory of Animal cell and Developmental biology School of Life SciencesShandong UniversityQingdaoShandong 266237China State Key Laboratory of Membrane biology Institute of ZoologyInstitute for Stem Cell and RegenerationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China

The hematopoietic system composed of hematopoietic stem and progenitor cells(HSPCs)and their differentiated lineages serves as an ideal model to uncover generic principles of cell fate *** gastrulation onwards,there successively emerge primitive hematopoiesis(that produces specialized he-matopoietic cells),pro-definitive hematopoiesis(that produces lineage-restricted progenitor cells),and definitive hematopoiesis(that produces multipotent HSPCs).These nascent lineages develop in several transient hematopoietic sites and finally colonize into lifelong hematopoietic *** development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental *** to the progressive methodology(e.g.,high-throughput lineage tracing and single-cell functional and omics analyses),our understanding of the developmental origin of hematopoietic lineages and functional properties of certain hematopoietic organs has been updated;meanwhile,new paradigms to characterize rare cell types,cell heterogeneity and its causes,and comprehensive regulatory landscapes have been ***,we review the evolving views of HSPC biology during developmental and postnatal ***,we discuss recent advances in the in vitro induction and expansion of HSPCs,with a focus on the implications for clinical applications.

关键词： Hematopoietic stem and progenitor cell Developmental hematopoiesis Postnatal hematopoiesis In vitro hematopoiesis

Programmable synthetic receptors:the next-generation of cell and gene therapies

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Signal Transduction and Targeted Therapy 2024年第2期9卷 376-400页

作者： Fei Teng Tongtong Cui Li Zhou Qingqin Gao Qi Zhou Wei Li University of Chinese Academy of Sciences Beijing 101408China State Key Laboratory of Stem cell and Regenerative biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem cell and Regenerative Medicine Beijing 100101China

cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat ***,concerns over the safety and efficacy require to be further addressed in order to realize their full *** receptors,a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules,have been rapidly developed and applied as a powerful *** designed and engineered,they can be applied to finetune the therapeutic activities,i.e.,to regulate production of dosed,bioactive payloads by sensing and processing user-defined signals or *** review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical *** a special focus on four synthetic receptor systems at the forefront,including chimeric antigen receptors(CARs)and synthetic Notch(synNotch)receptors,we address the generalized strategies to design,construct and improve synthetic ***,we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

关键词： synthetic landscape payload

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling Wang Xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo Wang Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of cell biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful *** deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental ***,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is ***,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are *** Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF *** find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO *** analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in *** finally show that intracytoplasmic sperm injection overcomes Ccdc38-related *** study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling