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

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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The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui Department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

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Neural Regeneration Research 2025年第5期20卷 1277-1292页

作者： Yuxiao Zheng Zilin Ren Ying Liu Juntang Yan Congai Chen Yanhui He Yuyu Shi Fafeng Cheng Qingguo Wang Changxiang Li Xueqian Wang School of traditional chinese medicine Beijing University of Chinese MedicineBeijingChina Library Beijing University of Chinese MedicineBeijingChina Dongzhimen hospital Beijing University of Chinese MedicineBeijingChina

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue *** the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the *** an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune *** review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic *** found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic ***1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain ***2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain *** interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke *** trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic ***,such studies have been relatively infrequent,and clinical experience is still *** summary,in ischemic stroke,T cell subsets and activated micro

关键词： brain immune inflammation interaction ischemic stroke mechanism microglia neuron secondary injury T cells

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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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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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Neural Regeneration Research 2025年第3期20卷 695-714页

作者： Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng Department of Integrated traditional chinese&Western medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina Yangsheng College of traditional chinese medicine Guizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co. LtdQinhuangdaoHebei ProvinceChina National Clinical Research Center for Mental Disorder The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary *** amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease *** abnormalities are commonly observed in patients with Alzheimer's *** liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's ***,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's *** this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol ***,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

关键词： ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid

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Successful emergency surgical intervention in acute non-STsegment elevation myocardial infarction with rupture:A case report

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World Journal of Clinical Cases 2025年第4期13卷 41-47页

作者： Xing-Po Li Zi-Shan Wang Hong-Xia Yu Shan-Shan Wang Department of Cardiovascular medicine Huantai County Hospital of Traditional Chinese MedicineZibo 256400Shandong ProvinceChina Department of Cardiovascular medicine Zibo Hospital of Integrated Traditional Chinese and Western MedicineZibo 255500Shandong ProvinceChina

BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with *** of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle *** FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be *** septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair *** SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary *** resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient *** This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.

关键词： Acute non-ST segment elevation myocardial infarction Cardiac rupture Acute myocardial infarction Free wall rupture Case report

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Bullous pemphigoid associated with acquired hemophilia A: A case report

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World Journal of Clinical Cases 2025年第4期13卷 28-33页

作者： Su-Ye Hu Meng-Can Li Zi-Jia Hao Xu-Ya Chai Pei-Sai Li Yang Liu Li-Xia Liu Ying Xu Pan-Pan Yang Ling-E Li Department of Dermatology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina Graduate School Hebei University of Traditional Chinese MedicineShijiazhuang 050051Hebei ProvinceChina Department of Pathology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must *** SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (hospitalfor effective treatment;however, he died after 2 *** AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

关键词： Bullous pemphigoid Acquired hemophilia A Acquired hemophilia A FactorⅧ Case report

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Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2982-2997页

作者： Hongli Li Jianhua Huang Di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng Department of Integrated traditional chinese&Western medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina National Clinical Research Center for Metabolic Diseases ChangshaHunan ProvinceChina Hunan Academy of chinese medicine ChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut *** aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease *** do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of ***-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 ***,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 *** findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

关键词： Alzheimer’s disease APP/PS1 mice brain-kidney axis gut microbiota heart-brain axis liver-brain axis lung-brain axis microbiota-gut-brain axis peripheral organ metabolism spleen-brain axis

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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei Niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin University of traditional chinese medicine TianjinChina Characteristic Medical Center of People’s Armed Police Forces TianjinChina Fujian Maternity and Child Health hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

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Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology research 2025年第1期33卷 67-81页

作者： Xiang Li Wenke Jin Lifeng Wu Huan Wang Xin Xie Wei Huang B O Liu State Key Laboratory of Southwestern chinese medicine Resources School of Pharmacy and College of Medical Technology Chengdu University of Traditional Chinese Medicine Chengdu 611137 China. Department of Biotherapy Cancer Center and State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China.

Background:Triple-negative breast cancer (TNBC), characterized by its lack of traditional hormone receptors and HER2, presents a significant challenge in oncology due to its poor response to conventional therapies. Autophagy is an important process for maintaining cellular homeostasis, and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors. In contrast to targeting protein activity, intervention with protein-protein interaction (PPI) can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here, we employed Naive Bayes, Decision Tree, and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC, aiming to uncover novel therapeutic targets. Meanwhile, the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay, and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection. Colony formation, cellular immunofluorescence, cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets, we identified 3733 previously unknown autophagy-related PPIs. Our network analysis revealed the central role of Beclin 2 in autophagy regulation, uncovering its interactions with 39 newly identified proteins. Notably, the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1, which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results. Subsequently, investigations showed that overexpressing Beclin 2 increased Ubiquilin 1, promoted autophagy-dependent cell death, and inhibited proliferation and metastasis in MDA-MB-231 cells.

关键词： Artificial intelligence (AI) Autophagy Beclin 2 Protein-protein interactions (PPI) Triple-negative breast cancer (TNBC) Ubiquilin 1

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