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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina shanghai key laboratory of Embryo Original Diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State key laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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A novel target to turn cold tumors into hot tumors: lysosomal 25-hydroxycholesterol activates AMPKα and immunosuppressive tumor-associated macrophages

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Cellular & Molecular Immunology 2024年第8期21卷 801-803页

作者： Shuangshuang Liu Jiaqi Wu Xiao Tong Li-Hao Huang shanghai key laboratory of metabolic remodeling and Health Institute of Metabolism and Integrative BiologyZhongshan HospitalFudan UniversityShanghai200032China

In a recent issue of Immunity,Xiao et *** that cholesterol 25-hydroxylase(CH25H)is a novel immunometabolic checkpoint and a potential drug target for tumor immunotherapy[1].Their study elucidated how CH25H influences macrophage polarization and reshapes the tumor microenvironment(TME)by regulating the lysosomal 25-hydroxycholesterol(25HC)content and AMPKa activation(Fig.1).Fehleisen and Busch,two physicians from Germany,independently observed significant tumor regression following erysipelas infection in the late 19th century,and they provided the earliest scientific evidence for tumor immunotherapy[2].To date,immunotherapy has emerged as a focal point in cancer treatment,with the concept of the TME pivotal for understanding cancer initiation and progression[3].

关键词： cholesterol al. cancer

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina key laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing key laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Protein-based functional hydrogel improves cutaneous nerve repair and diabetic wound healing

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Nano Research 2025年第1期18卷 586-596页

作者： Hanzhi Lu Mingrui Cui Yi Wang Xinran Du Xinyi Zhou Yuhan Fang Xiaoyan Gao Ying Peng Jianyong Zhu Guang Yang Fulun Li Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine College of Biological Science and Medical EngineeringDonghua UniversityShanghai 201620China Clinical laboratory Medicine Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China

Cutaneous nerve regeneration in diabetic wounds remains a challenge for current clinical ***,a natural protein-based functional hydrogel is developed using keratin as the sole matrix,and protocatechuic aldehyde(PA)and zinc ions as the building blocks through dual-dynamic crosslinking reactions of thiol-aldehyde addition and catecholzinc ions *** unique structural design endows the hydrogel with excellent injectability,skin adhesion,self-healing and antibacterial ability,and *** addition,this hydrogel acts as a drug carrier for the loading and sustained release of phellopterin(PP),a natural compound extracted from traditional Chinese medicine Angelica *** findings demonstrate that the PP-loaded hydrogel promotes cutaneous nerve regeneration,angiogenesis and tissue remodeling in the full-thickness wounds in both db/db and streptozotocin-induced C57BL/6 diabetic mice,notably by the synergistic effect of zinc ions and PP,showing a great potential in diabetic wound therapy.

关键词： functional hydrogel cutaneous nerve regeneration dynamic crosslinking diabetic wounds

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Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population

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Biomedical and Environmental Sciences 2022年第1期35卷 4-12页

作者： WANG Jia Lu CAO Qiu Yu XIN Zhuo Jun LIU Shan Shan XU Min WANG Tian Ge LU Jie Li CHEN Yu Hong WANG Shuang Yuan ZHAO Zhi Yun XU Yu NING Guang WANG Wei Qing BI Yu Fang LI Mian Department of Endocrine and metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China shanghai National Clinical Research Center for metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Objective The association between neutrophil-to-lymphocyte ratio(NLR)with subclinical macrovascular and microvascular diseases has been less *** sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese *** From a community cohort,we included 6,430 adults aged≥40 years without subclinical macrovascular and microvascular diseases at *** measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index(ABI),brachial-ankle pulse wave velocity(baPWV),and *** During a mean follow-up of 4.3 years,110 participants developed incident abnormal ABI,746 participants developed incident elevated baPWV,and 503 participants developed incident *** regression analysis indicated that NLR was significantly associated with an increased risk of newonset abnormal ABI,elevated baPWV,and *** to overweight/obese participants,we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal ***,we found an interaction between the NLR and body mass index(BMI)on the risk of new-onset abnormal ABI(P for interaction:0.01).Conclusion NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese ***,in participants with normal weight,the association between NLR and subclinical vascular abnormalities was much stronger.

关键词： Neutrophil-to-lymphocyte ratio Subclinical macrovascular and microvascular diseases Body mass index Prospective cohort study

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Interplay between diet and genetic susceptibility in obesity and related traits

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Frontiers of Medicine 2018年第6期12卷 601-607页

作者： Tiange Wang Min Xu Yufang Bi Guang Ning State key laboratory of Medical Genomics Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of HealthNational Clinical Research Center for Metabolic DiseasesShanghai Institute of Endocrine and Metabolic DiseasesDepartment of Endocrine and Metabolic DiseasesRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

The incidence of obesity has been rapidly increasing, and this condition has become a major public health threat. A substantial shift in environmental factors and lifestyle, such as unhealthy diet, is among the major driving forces of the global obesity pandemic. Longitudinal studies and randomized intervention trials have shown that genetic susceptibility to obesity may interact with dietary factors in relation to the body mass index and risk of obesity. This review summarized data from recent longitudinal studies and intervention studies on variations and diets and discussed the challenges and future prospects related to this area and public health implications.

关键词： diet genetic susceptibility obesity interaction

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Harnessing Interactional Sensory Genes for Rationally Reprogramming Chaotic Metabolism

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Research 2023年第3期2022卷 295-308页

作者： Chunlin Tan Ping Xu Fei Tao State key laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental Sciencesand School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina

Rationally controlling cellular metabolism is of great importance but challenging owing to its highly complex and chaotic *** existing sensory proteins like histidine kinases(HKs)are understood as“sensitive nodes”of biological networks that can trigger disruptive metabolic reprogramming(MRP)upon perceiving environmental ***,the“sensitive node”genes were adopted to devise a global MRP platform consisting of a CRISPR interference-mediated dual-gene combinational knockdown toolbox and survivorship-based metabolic interaction decoding *** platform allows users to decode the interfering effects of n×n gene pairs while only requiring the synthesis of n pairs of primers.A total of 35 HK genes and 24 glycine metabolic genes were selected as the targets to determine the effectiveness of our platform in a Vibrio *** platform was applied to decode the interfering impact of HKs on antibiotic resistance in strain FA2.A pattern of combined knockdown of HK genes(sasA_8 and 04288)was demonstrated to be capable of reducing antibiotic resistance of Vibrio by *** of combined knockdown of glycine pathway genes(e.g.,gcvT and ltaE)and several HK genes(e.g.,cpxA and btsS)were also revealed to increase glycine *** platform may enable an efficient and rational approach for global MRP based on the elucidation of high-order gene interactions.A web-based 1-stop service(https://***)is also provided to simplify the implementation of this smart strategy in a broad range of cells.

关键词： metabolism Rational programming

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New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse wave velocity and albuminuria: a prospective cohort study

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Frontiers of Medicine 2022年第5期16卷 714-722页

作者： Jialu Wang Shanshan Liu Qiuyu Cao Shujing Wu Jingya Niu Ruizhi Zheng Lizhan Bie Zhuojun Xin Yuanyue Zhu Shuangyuan Wang Hong Lin Tiange Wang Min Xu Jieli Lu Yuhong Chen Yiping Xu Weiqing Wang Guang Ning Yu Xu Mian Li Yufang Bi Zhiyun Zhao Department of Endocrine and metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China shanghai National Clinical Research Center for metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Clinical Trials Center Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

A new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)has recently been *** aim to examine the associations of MAFLD,particularly its discordance from non-alcoholic fatty liver disease(NAFLD),with the progression of elevated brachial-ankle pulse wave velocity(baPWV)and albuminuria in a community-based study sample in shanghai,*** 4.3 years of follow-up,778 participants developed elevated baPWV and 499 developed *** comparison with the non-MAFLD group,the multivariable adjusted odds ratio(OR)of MAFLD group for new-onset elevated baPWV was 1.25(95%confidence interval(CI)1.01–1.55)and 1.35(95%CI 1.07–1.70)for *** without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria(OR 1.77;95%CI 1.07–2.94).Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or *** conclusion,MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index,waist circumference,and hip *** without NAFLD but diagnosed as MAFLD had high risk of albuminuria,supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

关键词： metabolic dysfunction-associated fatty liver disease non-alcoholic fatty liver disease fibrosis score brachial-ankle pulse wave velocity albuminuria

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