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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses

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Traditional Medicine Research 2025年第2期10卷 55-64页

作者： Jin-Fang Wu Yi-Sheng Chen Yu-Chun Xie department of Rehabilitation Medicine Jiangsu Province Geriatric HospitalNanjing 210024China Fujian Key Laboratory of Toxicant and Drug Toxicology Medical CollegeNingde Normal UniversityNingde 352100China Central Laboratory Jiangsu Province Geriatric HospitalNanjing 210024China

Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise ***:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker *** visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and ***,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular ***:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius *** showed a significant presence of Olfm3+ganglion ***1 gene knockout revealed changes in SMAD family gene expression,which regulate *** stress levels were also ***:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological *** may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.

关键词： single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing geriatric Medical Research Center BeijingChina department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical Research Center for geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijingChina department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLRP3 tau transcription factor

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Management strategies of Barrett's esophagus

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World Journal of Gastroenterology 2012年第43期18卷 6216-6225页

作者： Giovanni D De Palma department of General Geriatric Oncologic Surgery and Advanced Technologies Center of Excellence for Technical Innovation in Surgery University of Naples Federico II 80131 Naples Italy

Barrett's esophagus is a condition resulting from chronic gastro-esophageal reflux disease with a documented risk of esophageal adenocarcinoma. Current strategies for improved survival in patients with Barrett's adenocarcinoma focus on detection of dysplasia. This can be obtained by screening programs in high-risk cohorts of patients and/or endoscopic biopsy surveillance of patients with known Barrett's esophagus (BE). Several therapies have been developed in attempts to reverse BE and reduce cancer risk. Aggressive medical management of acid reflux, lifestyle modifications, antireflux surgery, and endoscopic treatments have been recommended for many patients with BE. Whether these interventions are cost-effective or reduce mortality from esophageal cancer remains controversial. Current treatment requires combinations of endoscopic mucosal resection techniques to eliminate visible lesions followed by ablation of residual metaplastic tissue. Esophagectomy is currently indicated in multifocal high-grade neoplasia or mucosal Barrett's carcinoma which cannot be managed by endoscopic approach.

关键词： Barrett’s esophagus Diagnosis Management strategies Esophagectomy Esophageal adenocarcinoma

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Role of gut microbiota in Crohn’s disease pathogenesis:Insights from fecal microbiota transplantation in mouse model

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World Journal of Gastroenterology 2024年第31期30卷 3689-3704页

作者： Qiang Wu Lian-Wen Yuan Li-Chao Yang Ya-Wei Zhang Heng-Chang Yao Liang-Xin Peng Bao-Jia Yao Zhi-Xian Jiang geriatric surgery of department of General surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina

BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and *** To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in *** Intestinal tissue and MAT were collected from 12 patients with *** manifestations and protein expression levels were analyzed to determine lesion *** samples were collected from five recently treated CD patients and five control subjects and transplanted into *** intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control *** Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota *** microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD ***,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and ***,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced *** Gut microbiota play a critical role in the histopathology of *** MAT and creeping fat may therefore have potential in the treatment of patients with CD.

关键词： Mesenteric adipose tissue Crohn’s disease Fecal microbiota transplantation Intestinal fibrosis Intestinal barrier

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Clinical characteristics, target organ damage and associate risk factors ofresistant hypertension determined by ambulatory blood pressure monitoringin patients aged ≥80 years

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Journal of geriatric Cardiology 2017年第5期14卷 308-314页

作者： Zhi-Ru LIANG Ling-Gen GAO Jian CAO Hua CUI Li FAN De-Wei GAO department of Comprehensive surgery Chinese PLA General Hospital Beijing China department of geriatric Cardiology Chinese PLA General Hospital Beijing China

Objectives To investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 yearswith true resistant hypertension （RH）. Methods Patients aged ≥ 80 years with hypertension （n = 1163） were included in this study. Theincluded participants attended a structured clinical examination and an evaluation of RH was carried out. The prevalence, clinical characteristicsand target organ damage of patients with RH were assessed. The associated clinical risk factors were analyzed by using logistic *** The prevalence of RH diagnosis by 24-h ambulatory blood pressure monitoring assessment was 21.15%. End-diastolic left ven-tricular internal dimension, left ventricular mass index as well as prevalence of left ventricular hypertrophy were significantly greater in pa-tients with RH than in control group. The common carotid artery intimal media thickness, carotid walls thickness, common carotid arterydiameter and relative wall thickness were significant greater in RH group than in control. A relatively higher level of creatinine, estimatedglomerular filtration rate, microalbuminuria and retinal changes was found in RIt group than in control. A multivariate analysis showed thatpatients with a history of diabetes, higher body mass index （BMI） and lipid profiles were independent risk factors of RH. Conclusions Theprevalence of RH in patients aged ≥ 80 years was within the range of reported rates of the general population. Subjects with RH diagnosisshowed a higher occurrence of target organ damage than patients with well controlled blood pressure. Patients with diabetes, higher BMI andserum lipid profiles were independent risk factors for RH in patients aged ≥ 80 years.

关键词： Blood pressure Organ damage Resistant hypertension

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Protein quality control systems in hypertrophic cardiomyopathy:pathogenesis and treatment potential

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Journal of geriatric Cardiology 2022年第10期19卷 780-784页

作者： Fan-Yan LUO Yong-Ping BAI Hai-Song BU department of Cardiovascular surgery Xiangya HospitalCentral South UniversityChangshaChina department of geriatric Medicine Xiangya HospitalCentral South UniversityChangshaChina

Hypertrophic cardiomyopathy(HCM)is genetic cardiomyopathy with the risk of sudden death characterized by abnormal sarcomere protein.^([1])Although some pathogenic genes related to HCM have been reported,^([2])the disease phenotype and pathogenesis cannot be fully elucidated,which brings great difficulties to the diagnosis and treatment of HCM,especially the exploration of HCM treatment strategies.

关键词： diagnosis treatment death

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Inhibition of Proliferation of Human Hela Cells by Small Interference RNA against Pokemon Gene

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Chinese Journal of Cancer Research 2008年第1期20卷 5-11页

作者：邓一静倪兵姜曼杨玓李凡吴玉章 department of geriatric Gastroenterology Chinese PLA General Hospital

Objective： The transcriptional repressor Pokemon （encoded by the Zbtb7 gene） is a critical factor in oncogenesis. Pokemon overexpression leads to overt oncogenic transformation both in vitro and in vivo in transgenic mice, The objective of this study was to investigate the effect of retrovirus expressing the siRNA targeting Pokemon in human cervical cancer cells. Methods： We constructed and identified the recombinant retrovirus particle expressing siRNA of Pokemon gene, and then testified the suppression of recombinant plasmid and evaluated the gene-silencing effect. Results： We got the positive evaluation from colony forming experiment we found that the retrovirus expressing siRNA targeting Pokemon had repressing effect. Conclusion： Our work provides basis for the study of suppression effect of retrovirus in vivo and the design of the target-complex.

关键词： Pokemon Retrovirus, siRNA Colony forming assay

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Circulating lncRNA MHRT predicts survival of patients with chronic heart failure

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Journal of geriatric Cardiology 2019年第11期16卷 818-821页

作者： Lie ZHANG Yan-Jun WU Sui-Long ZHANG department of geriatric Cardiovascular Disease the Second Affiliated Hospital of Xi'an Jiaotong UniversityXianChina department of General surgery Xi’an Northern HospitalXianChina

Background It has been reported that lncRNA myosin heavy-chain-associated RNA transcripts(MHRT)can inhibit the apoptosis of *** is one of the major pathological changes leading to chronic heart *** The expression level of lncRNA MHRT was assessed by *** values of lncRNA MHRT for chronic heart failure were analyzed by ROC curve *** apoptosis was detected by cell apoptosis *** The results demonstrated that expression of lncRNA MHRT in plasma was down-regulated in patients with chronic heart failure compared to that in healthy ***-regulation of lncRNA MHRT distinguished chronic heart failure from healthy ***-expression of lncRNA MHRT inhibited the apoptosis of human cardiomyocyte cell line AC16 after H2O2 ***-up study showed that chronic heart failure patients with lower expression levels of lncRNA MHRT had worse survival conditions compared to patients with higher expression levels of lncRNA *** We concluded that circulating lncRNA MHRT might serve as a diagnostic and prognostic marker for chronic heart failure treatment.

关键词： Apoptosis Cardiomyocytes Chronic heart failure lncRNA MHRT

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