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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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Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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Oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN JIANG YICHUN TANG FENG MA YUCHUN NIU LEI SUN Department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China Department of Pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China Department of Radiation Oncology The First People’s Hospital of FoshanFoshan528000China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China Department of Oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape

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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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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

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Neural Regeneration Research 2025年第10期20卷 2807-2822页

作者： Xizi Song Ruixin Li Xiaolei Chu Qi Li Ruihua Li Qingwen Li Kai-Yu Tong Xiaosong Gu Dong Ming Academy of Medical Engineering and Translational medicine Tianjin UniversityTianjinChina Haihe Laboratory of Brain-Machine Interface and Human-Machine Fusion TianjinChina Department of Rehabilitation Tianjin University Tianjin HospitalTianjinChina Department of Hand Microsurgery Tianjin University Tianjin HospitalTianjinChina School of Exercise and Health Tianjin University of SportTianjinChina Department of Biomedical Engineering the Chinese University of Hong KongHong Kong Special Administrative RegionChina

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and *** on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target *** has led to restrictions on current therapeutic *** this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target *** peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal *** nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury *** damage to target organs can occur,including skeletal muscle atrophy and sensory receptor *** then provide a brief review of the research advances in therapeutic approaches to peripheral nerve *** main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical ***,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ ***,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

关键词： central nervous system central peripheral target organ multilevel pathological analysis nerve regeneration peripheral nerve injury peripheral nervous system target organs therapeutic approach

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Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

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Neural Regeneration Research 2025年第3期20卷 900-912页

作者： Baoqi Hu Rui Wang Hanyue Zhang Xiou Wang Sijia Zhou Bo Ma Yan Luan Xin Wang Xinlin Chen Zhichao Zhang Qianyan Kang Department of Ophthalmology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology The First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina Institute of Neurobiology Xi’an Jiaotong University Health Science CenterXi’anShaanxi ProvinceChina

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell ***,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development ***,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo *** this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in ***,we used SOX2 and PAX6 immunostaining to identify retinal progenitor *** then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,***-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between ***,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,*** timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant *** study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina *** findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

关键词： bipolar cells differentiation in vivo microglia Müller glia organotypic retinal explant culture postnatal retina development proliferation retinal progenitor cells

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Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach

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traditional medicine Research 2025年第2期10卷 65-76页

作者： Huan Pei Ren-Lin Li Xin-Ran Song Qian-Qian Wan Yu-Ming Wang Han-Zhou Li Wei-Quan Xu Jia-Bao Liao Wei-Bo Wen Jing Miao Huan-Tian Cui School of Basic medicine Yunnan University of Chinese MedicineKunming 650599China School Clinical Medical College Yunnan University of Chinese MedicineKunming 650599China first School of Clinical medicine Yunnan University of Chinese MedicineKunming 650599China School of Integrative chinese and Western medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Tianjin Second People's HospitalTianjin 300192China

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver *** studies showed that metabolic dysfunction can promote NAFLD *** Zhugan Decoction(LGZGD)has therapeutic effects on *** mechanism of LGZGD still remains *** study was to examine the impact of LGZGD on the metabolic processes involved in the development of ***:A mice model of NAFLD was treated with *** therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of ***,this study also evaluated the influence of LGZGD on liver inflammation and oxidative ***:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD *** improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the *** metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate *** RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关键词： NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle

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The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning Shi Lv Qian Wang Yuzhen Xu Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

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Systematic Acupuncture Explains Acupuncture at Baihui(GV20) and Fengchi(GB20) Targeting the Inflammatory Response to Regulate Migraine

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Journal of traditional chinese medicine 2025年

作者： MIN Yu ZHENG Meifeng SUN Ju PENG Zetong CAO Zhixian HUANG Xiaohua Medical College of Acu-Moxi and Rehabilitation， Guangzhou university of chinese medicine Department of Rehabilitation medicine， the affiliated Panyu Central hospital of Guangzhou Medical university

Objective: To take Baihui (GV20) and Fengchi (GB20) targeting inflammatory response to regulate migraine as an example to describe a new method for studying the mechanism of stimulating ***: The target information of Baihui (GV20) and Fengchi (GB20) was retrieved， and after intersection with migraine， Kyoto Encyclopedia of Genes and Genomes (KEGG)， Reactome， and UniProt Keywords were used for functional enrichment. After selecting the main pathway， rats were selected and nitroglycerin was used for modeling， and the behavioral scores， inflammatory factors， heme oxygenase 1 (HMOX1)， protein kinase B (AKT1)， signal transducer and activator of transcription 3 (STAT3)， phosphorylated extracellular signal-regulated kinase 1/2 (P-ERK1/ERK2) and other states of the rats in the acupuncture， twisting， and electroacupuncture groups were ***: A total of 135 Baihui (GV20) targets and 27 Fengchi (GB20) targets were collected. A total of 73 target information were obtained after the intersection of these targets in migraine. These 73 targets have three main pathways: hypoxia-inducible factor 1 (HIF-1) signaling pathway， signaling by interleukins and inflammatory response. The main targets in the pathway were verified and found that interleukin-1 beta (IL-1β)， interleukin-6 (IL-6)， tumor necrosis factor-alpha (TNF-α) and HMOX1， AKT1， STAT3， P-ERK1/ERK2 can be regulated by Baihui (GV20) and Fengchi (GB20).Conclusion: Baihui (GV20) and Fengchi (GB20) can regulate migraine by regulating inflammatory factors and HMOX1， AKT1， STAT3， P-ERK1/ERK2 and other changes in HIF-1 signaling pathway， Signaling by Interleukins and Inflammatory response pathways. Based on systems biology and network pharmacology， and with the model of "acupoint-target-disease"， explore the research methods of systematic acupuncture and moxibustion. We believe this is a usable research direction for exploring the mechanism of acupuncture stimulation.

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