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EZH2-dependent myelination following sciatic nerve injury

Neural Regeneration Research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi Huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical School of nantong University NantongJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Critical Care Medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating Schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination Schwann cells sciatic nerve crush sciatic nerve transection

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miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular Drug Target NantongJiangsu ProvinceChina Department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

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Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

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World Journal of Clinical Cases 2025年第3期13卷 20-23页

作者： Xue-Jian Wang Department of Neurosurgery Affiliated Hospital 2 of Nantong UniversityNantong 226000Jiangsu ProvinceChina

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment *** cerebral infarction occurs,the consequences are difficult to *** is also an important reason for the high misdiagnosis rate and mortality of this *** this paper,the characteristics of the disease were analyzed to provide clinical reference.

关键词： Chronic occlusion Misdiagnose Arterial occlusion Middle cerebral artery occlusion Aneurysm

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Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong Lai Zhengliang Gao Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering Research Center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

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Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen Gu Hua Yan Dingding Shen Xiaosong Gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated hospital of nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological *** regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of *** pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota *** results are lacking for conventional treatments for *** resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with ***-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research *** review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of *** also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current *** studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic ***,many new technologies for the diagnosis and treatment of epilepsy are being ***,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

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Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli Shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang Department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National Center for Neurological Disorders ShanghaiChina Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration ShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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Hyaluronic acid-based dual-responsive nanomicelles mediated mutually synergistic photothermal and molecular targeting therapies

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Nano Research 2022年第7期15卷 6361-6371页

作者： Liangliang Cai Ronghua Ni Xiaofei Ma Rongrong Huang Zhiyuan Tang Jinqiu Xu Yong Han Yuehua Guo Zhifeng Gu Department of Pharmacy Affiliated Hospital of Nantong UniversityNantong 226001China Department of Radiation Oncology Affiliated Hospital of Nantong UniversityNantong 226001China Research Center of Clinical Medicine Affiliated Hospital of Nantong UniversityNantong 226001China Department of Rheumatology Affiliated Hospital of Nantong UniversityNantong 226001China

Precise clinical treatment of triple-negative breast cancer(TNBC)is an obstacle in ***-assisted photothermal therapy(PTT)is a superior treatment modality for TNBC in terms of ***,thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of ***13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study,showing satisfactory antitumour activity through molecularly targeted therapy(MTT).Whereas,it has poor *** hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds,forming an amphipathic copolymer that could self-assembled into nanomicelles,followed by encapsulating Cypate and *** nanomicelles exhibited great features,including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs,increasing the solubility of Cypate and AT13387,showing a pH/redox dual response that contributes to drug release,and having the ability of active ***,the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.

关键词： hyaluronic acid nanomicelles dual responsive photothermal therapy molecular targeting therapy

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LncRNA GAS5 enhances tumor stem cell-like medicated sensitivity of paclitaxel and inhibits epithelial-to-mesenchymal transition by targeting the miR-18a-5p/STK4 pathway in prostate cancer

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Asian Journal of Andrology 2022年第6期24卷 643-652页

作者： Ting-Ting Lu Xia Tao Hua-Lei Li Ling Gai Hua Huang Feng Li Department of Laboratory Medicine Affiliated Hospital of Nantong UniversityNantong 226001China Department of Pathology Nantong University Medical SchoolNantong 226001China Department of Pharmacy Affiliated Hospital of Nantong UniversityNantong 226001China Department of Urology Affiliated Hospital of Nantong UniversityNantong 226001China Department of Chemotherapy Affiliated Hospital of Nantong UniversityNantong 226001China Department of Pathology Affiliated Hospital of Nantong UniversityNantong 226001China

The onset of prostate cancer(PCa)is often hidden,and recurrence and metastasis are more likely to occur due to chemotherapy ***,we identified downregulated long noncoding RNA(lncRNA)growth arrest-specific 5(GAS5)in PCa that was associated with metastasis and paclitaxel ***5 acted as a tumor suppressor in suppressing the proliferation and metastasis of paclitaxel-resistant PCa ***5 overexpression in vivo inhibited the tumor growth of xenografts and elevated PCa sensitivity to *** of GAS5 and paclitaxel treatment showed great potential in PCa ***,mechanistic analysis revealed a novel regulatory network of GAS5/miR-18a-5p/serine/threonine kinase 4(STK4)that inhibits epithelial-to-mesenchymal transition(EMT)and enhances tumor stem cell-like-mediated sensitivity to paclitaxel in *** findings provide a novel direction for the development of a potential adjunct to cancer chemotherapy that aims to improve the sensitivity of chemotherapy drugs in PCa.

关键词： epithelial-to-mesenchymal transition growth arrest-specific 5 long noncoding RNA paclitaxel prostate cancer

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