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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma Ke Ye Xue Zhao fangliang ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of Basic Medical Sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Basic Medical Institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Province for genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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Precise and efficient insertion of A673T mutation in APP gene using MSYM

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genes & Diseases 2024年第6期11卷 65-68页

作者： Qing Xia Zijie Liu Xinyu Yang Jiaying Xiao Xue Zhao Yu Zhao Feifei Zheng fangliang ge Ke Ye Lulu Liu Dayong Wang Xu Gao Department of Biochemistry and Molecular Biology Harbin Medical UniversityHarbinHeilongjiang 150000China Dongzhimen Hospital Beijing University of Chinese MedicineBeijing100700China Basic Medical Institute Heilongjiang Medical Science AcademyHarbinHeilongjiang150000China Translational Medicine Center of Northern China HarbinHeilongjiang 150000China Key Laboratory of Heilongjiang Province for genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang 150000China

Alzheimer's disease(AD)is a progressive neurodegenerative disorder causing memory loss,cognitive decline,language impairment,and disorientation,which impose an enormous burden on caregivers and the public health sector.A673T as a protective mutation has great therapeutic potential in AD.1,2 Therefore,a combination of stem cell therapy and A673T mutation existing in natural people based on gene targeting techniques such as CRISPR-Cas9 have been suggested as promising and exciting new developments.

关键词： protective Alzheimer impairment

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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng Fu Shining ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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Posttraumatic stress symptoms among Chinese university students during the COVID-19 pandemic:Prevalence,correlates,and mental health help-seeking

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World Journal of Psychiatry 2025年第1期15卷 145-152页

作者： Rui-Yao Wu Lin-Feng ge Bao-Liang Zhong Department of Psychiatry The Affiliated Wuhan Mental Health CenterTongji Medical College of Huazhong University of Science&TechnologyWuhan 430012Hubei ProvinceChina Department of Psychiatry Wuhan Mental Health CenterWuhan 430012Hubei ProvinceChina

BACKGROUND Revisiting the epidemiology of posttraumatic stress symptoms(PTSSs)among university students during the coronavirus disease 2019(COVID-19)pandemic as well as understanding the mental health help-seeking behavior of individuals with PTSSs has critical implications for public mental health strategies in future medical *** To investigate the prevalence and correlates of PTSSs among university students during the first wave of the COVID-19 pandemic in China and to examine mental health help-seeking behaviors among these *** A total of 2507 Chinese university students were recruited via snowball *** students completed the Seven-item Screening Scale for Post-traumatic Stress Disorder during the first wave of the COVID-19 pandemic in ***-graphic characteristics,pandemic-related characteristics,and mental health help-seeking behaviors of students with PTSSs were also *** The prevalence of PTSSs among the participants was 28.0%.Seven significant correlates of PTSSs were identified(odds ratio=1.23-3.65,P≤0.024):Female sex,being 19 years old or older,living with others or alone,a low level of family economic status,fair or poor interpersonal relationships,severe or very severe local pandemic,and having family members diagnosed with ***,only 3.28%of the students with PTSSs reported seeking help from mental health *** the 23 students who sought help from mental health specialists,13 opted for online or telephone-based psychological *** Our data suggest that there was a high risk of PTSSs among university students and a high level of unmet mental health needs during the COVID-19 *** delivery of mental health services online or via telephone is a promising approach to address these unmet needs.

关键词： Posttraumatic stress symptoms University students COVID-19 Mental health help-seeking China

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小檗碱对多囊卵巢综合征小鼠卵丘扩展的作用及机制研究

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中国医药导报 2024年第13期21卷 1-6页

作者：夏晴王大勇葛方亮郑菲菲赵雪叶可刘璐璐刘雁峰北京中医药大学东直门医院妇科北京100700 哈尔滨医科大学基础医学院生物化学与分子生物学教研室黑龙江哈尔滨150086

目的探索小檗碱(Ber)对多囊卵巢综合征小鼠卵丘扩展的作用及机制。方法选取育龄21~25 d的SPF级雌性C57BL/6小鼠28只,按照随机数字表法将其分为对照组、PCOS组、Ber低剂量组、Ber高剂量组,各7只。对照组皮下注射等体积玉米油溶剂,PCOS... 详细信息

目的探索小檗碱(Ber)对多囊卵巢综合征小鼠卵丘扩展的作用及机制。方法选取育龄21~25 d的SPF级雌性C57BL/6小鼠28只,按照随机数字表法将其分为对照组、PCOS组、Ber低剂量组、Ber高剂量组,各7只。对照组皮下注射等体积玉米油溶剂,PCOS组、Ber低剂量组、Ber高剂量组均皮下注射脱氢表雄酮(6 mg/100 g,溶于玉米油溶剂),连续21 d。以小鼠出现动情周期紊乱为PCOS模型构建成功标准。随后连续28 d,Ber低剂量组灌胃200 mg/kg Ber,Ber高剂量组灌胃400 mg/kg Ber,PCOS组灌胃等剂量的生理盐水。向各组小鼠腹腔注射孕马血清促性腺激素及人绒毛膜促性腺激素,于输卵管壶腹部获取卵丘卵母细胞复合物(COC),体外培养0、6 h观察小鼠卵丘扩展情况。免疫组织化学检测各组小鼠卵丘颗粒细胞中FTO蛋白表达水平。向人颗粒细胞瘤样细胞系(KGN细胞)中转染PC3.1质粒(PC3.1组)及PC3.1-FTO质粒(PC3.1-FTO组),免疫荧光检测两组细胞中透明质酸合成酶2(HAS2)表达水平。向KGN细胞中转染NC si RNA(NC组)及FTO si RNA(si FTO组),免疫荧光检测两组细胞中HAS2表达水平。结果与对照组比较,PCOS组小鼠动情周期失去周期性变化。提示PCOS小鼠模型构建成功。与PCOS组比较,Ber低剂量组小鼠动情周期逐渐恢复,Ber高剂量组小鼠动情周期仍失去周期性变化。与对照组比较,PCOS组小鼠COC卵丘细胞分布更致密,卵丘扩展受阻。与PCOS组比较,Ber低、高剂量组小鼠COC卵丘细胞分布更松散,卵丘扩展受阻明显改善。与对照组比较,PCOS组卵丘颗粒细胞中FTO表达水平升高(P<0.05)。与PCOS组比较,Ber低、高剂量组卵丘颗粒细胞中FTO表达水平均降低(P<0.05)。与PC3.1组比较,PC3.1-FTO组KGN细胞中HAS2表达水平降低(P<0.05)。与NC组比较,si FTO组KGN细胞中HAS2表达水平升高(P<0.05)。结论 Ber可能通过降低卵丘颗粒细胞中FTO表达水平,诱发HAS2表达水平升高,从而改善PCOS卵丘扩展状态。

关键词：多囊卵巢综合征脂肪质量和肥胖相关基因卵丘扩展透明质酸合成酶2

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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ge-semigroup method for controllability of stochastic descriptor linear systems

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Science China(Information Sciences) 2023年第3期66卷 299-300页

作者： Zhaoqiang ge School of Mathematics and Statistics Xi’an Jiaotong University

Dear editor, Nowadays, there are more and more researches on stochastic descriptor systems(see [1–7]). For example, Refs. [4,5] studied the exact controllability of a class of stochastic descriptor systems by a strongly continuous semigroup in Hilbert spaces. In this study, the exact controllability and approximate controllability of the following stochastic descriptor system are studied by using the ge-semigroup theory, respectively:

关键词：

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慢性低度炎症在多囊卵巢综合征排卵障碍中的作用机制

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中国医药导报 2024年第14期21卷 1-5页

作者：夏晴王大勇葛方亮郑菲菲赵雪强若男王文晶刘雁峰北京中医药大学东直门医院妇科北京100700 哈尔滨医科大学基础医学院黑龙江哈尔滨150086

目的验证多囊卵巢综合征(PCOS)小鼠卵巢颗粒细胞炎症状态,并探索慢性低度炎症状态对PCOS排卵障碍的作用机制。方法选取SPF级健康雌性C57BL/6小鼠10只,21~25 d,14~16 g,按照随机数字表法将其分为CONTROL组和PCOS组,每组5只。PCOS组每... 详细信息

目的验证多囊卵巢综合征(PCOS)小鼠卵巢颗粒细胞炎症状态,并探索慢性低度炎症状态对PCOS排卵障碍的作用机制。方法选取SPF级健康雌性C57BL/6小鼠10只,21~25 d,14~16 g,按照随机数字表法将其分为CONTROL组和PCOS组,每组5只。PCOS组每日皮下注射脱氢表雄酮(6 mg/100 g,溶剂:玉米油与DMSO混合液),CONTROL组小鼠每日皮下注射等体积溶剂,连续给药21 d。苏木精-伊红染色观察两组小鼠卵巢组织形态,免疫组织化学染色法检测两组小鼠卵巢颗粒细胞中肿瘤坏死因子-α(TNF-α)表达水平。向KGN细胞中加入脂多糖(LPS)0.1μg/ml(LPS 0.1组)、0.2μg/ml(LPS 0.2组)、0.5μg/ml(LPS 0.5组)、1.0μg/ml(LPS 1.0组)、5.0μg/ml(LPS 5.0组)构建颗粒细胞炎症模型,以KGN细胞作为对照组。Western blot法检测KGN细胞中TNF-α、SMAD4表达水平;免疫荧光检测对照组及LPS 0.2组KGN细胞中YTHDF2表达水平。转染PC3.1-YTHDF2质粒构建YTHDF2过表达颗粒细胞模型(PC3.1-YTHDF2组),转染PC3.1质粒作为对照(PC3.1组)。Western blot法检测PC3.1组和PC3.1-YTHDF2组KGN细胞中SMAD4表达水平。结果 CONTROL组小鼠卵巢中各时期卵泡均存在。与CONTROL组比较,PCOS组小鼠卵巢中存在大量未成熟卵泡。与CONTROL组比较,PCOS组小鼠卵巢颗粒细胞中TNF-α表达水平升高(P<0.05)。与对照组比较,LPS 0.2组、LPS 0.5组、LPS 1.0组、LPS 5.0组KGN细胞中TNF-α表达水平升高(P<0.05);LPS 0.1组、LPS 0.2组、LPS 0.5组、LPS 1.0组、LPS 5.0组KGN细胞中SMAD4表达水平降低(P<0.05)。与对照组比较,LPS 0.2组KGN细胞中YTHDF2表达水平升高(P<0.05)。与PC3.1组比较,PC3.1-YTHDF2组KGN细胞中SMAD4表达水平降低(P<0.05)。结论 PCOS小鼠颗粒细胞中存在炎症状态,PCOS颗粒细胞的炎症状态可影响其排卵功能,PCOS颗粒细胞炎症状态可能通过调控YTHDF2影响SMAD4的表达从而造成PCOS排卵障碍。

关键词：多囊卵巢综合征慢性低度炎症 YTHDF2 排卵障碍

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Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

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Neural Regeneration Research 2025年第2期20卷 518-532页

作者： Conglin Wang Fangyuan Cheng Zhaoli Han Bo Yan Pan Liao Zhenyu Yin Xintong ge Dai Li Rongrong Zhong Qiang Liu Fanglian Chen Ping Lei Department of geriatrics Tianjin Medical University General HospitalTianjinChina School of Medicine Nankai UniversityTianjinChina Tianjin Neurological Institute TianjinChina

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor ***-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system *** this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying *** results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral ***,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory *** sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier *** with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these *** summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

关键词： AKT astrocyte blood-brain barrier cerebral edema exosomes human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells neuroinflammation PI3K

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