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Lin28 as a therapeutic target for central nervous system regeneration and repair

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neural Regeneration Research 2024年第2期19卷 397-398页

作者： Shuo Wang Shuxin Li Shriners Hospitals Pediatric Research Center Department of Neural SciencesLewis Katz School of Medicine at Temple UniversityPhiladelphiaPAUSA

Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).

关键词： paralysis therapeutic system

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li Beijing Key Laboratory for Biomaterials and neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration

Dawn of CAR-T cell therapy in autoimmune diseases

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Chinese Medical Journal 2024年第10期137卷 1140-1150页

作者： Yuxin Liu Minghao Dong Yunhui Chu Luoqi Zhou Yunfan You Xiaowei Pang Sheng Yang Luyang Zhang Lian Chen Lifang Zhu Jun Xiao Wei Wang Chuan Qin Daishi Tian department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Hubei Key Laboratory of neural Injury and Functional Reconstruction Huazhong University of Science and TechnologyWuhanHubei 430030China

Chimeric antigen receptor(CAR)-T cell therapy has achieved remarkable success in the treatment of hematological *** on the immunomodulatory capability of CAR-T cells,efforts have turned toward exploring their potential in treating autoimmune *** analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases,covering a range of subtypes such as systemic lupus erythematosus,multiple sclerosis,among ***-T therapy holds promise in mitigating several shortcomings,including the indiscriminate suppression of the immune system by traditional immunosuppressants,and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic *** persisting and proliferating in vivo,CAR-T cells can offer a tailored and precise *** paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases,incorporating innovations well-studied in the field of hematological tumors,aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

关键词： CAR-T cell therapy Autoimmune disease Immunotherapy Multiple sclerosis Neuromyelitis optica spectrum disorder Systemic lupus erythematosus

D-band center coordination modulated enzyme-like activity in Fe-Cu dual-metal single-atom nanozymes

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Nano Research 2024年第7期17卷 5872-5883页

作者： Ling Liu Shaofang Zhang Guo Li Yadong Zhe Jiamin Liu Xinxu Zhang Jiahao Wei Xin Sun Yonghui Li Xiao-Dong Zhang Tianjin Key Laboratory of Brain Science and neural Engineering Academy of Medical Engineering and Translational MedicineTianjin UniversityTianjin 300072China department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology School of SciencesTianjin UniversityTianjin 300350China

After explorations in a diversity of single-atom nanozymes(SAzymes),developing dual-centered SAzymes becomes a promising approach for superior catalytic *** confusing mechanisms including atomic coordination,spatial configuration,and metal–metal atom interaction hinder the development and design of ***,a dual-centered Fe-Cu-N_(x)SAzyme exhibits excellent peroxidase(POD)-and catalase(CAT)-like activities with d-band center(ε_(d))coordination of Fe and Cu in multiple reaction stages,which plays a critical role in the adsorption of H_(2)O_(2)molecule and H_(2)O and O_(2)***,the dband center coordination,which can be represented byε_(d)(Fe)–ε_(d)(Cu)shifts,leads to the competition between one-side and bilateral adsorption,which determines the favorable reaction path with lower energy *** on experimental statistics,simulated formation energies,and reaction barriers,3 configurations,Fe-Cu-N6-I,Fe-Cu-N_(8)-II,and Fe-Cu-N_(8)-III,are modeled and ***,configuration-dependent catalytic selectivity and the competition between one-side and bilateral adsorption can be unveiled by d-band center coordination paradigm *** simulations suggest that the unsymmetrical charge distribution over the three Fe-Cu configurations could tune the adsorption strength compared with the counterparts FeN_(4)and CuN_(4).The present work provides a potential route for optimizing enzyme-like catalysis by designing the dual-or even triple-metal SAzymes,which demonstrates the large space to modulate the metal atomic configuration and interaction.

关键词： single-atom catalysis Fe-Cu dual-metal d-band center coordination enzyme mimicking competitive adsorption mechanisms

PML nuclear bodies:new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?

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neural Regeneration Research 2024年第9期19卷 1875-1876页

作者： Anand Goswami Serena Carra Institute of Neuropathology RWTH Aachen University HospitalAachenGermany department of Neurology Eleanor and Lou Gehrig ALS CenterColumbia UniversityNew YorkNYUSA department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly

Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).

关键词： clinical familial

Long COVID:From olfactory dysfunctions to viral Parkinsonism

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 137-147页

作者： Sanyukta Pandey Vibha Bapat Jancy Nixon Abraham Nixon M.Abraham department of Biology Laboratory of Neural Circuits and Behaviour(LNCB)Indian Institute of Science Education and Research(IISER)PuneMaharashtraIndia department of Life Sciences Centre of Excellence in EpigeneticsShiv Nadar Institution of EminenceGautam Buddha NagarUttar PradeshIndia

Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional ***,the surge of neurological disorders followed the viral pandemics,for example,the emergence of Encephalitis Lethargica after the outbreak of Spanish *** and after COVID-19 infection,the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's *** reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these *** this manuscript,we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical ***,we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.

关键词： long COVID neurodegeneration neurotropism olfactory dysfunctions viral parkinsonism

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine BeijingChina Key Laboratory of Trauma and neural Regeneration(Peking University) Ministry of EducationBeijingChina department of Orthopedics China-Japan Friendship HospitalBeijingChina department of Central Laboratory and Institute of Clinical Molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

Music as medicine for traumatic brain injury:a perspective on future research directions

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neural Regeneration Research 2024年第10期19卷 2105-2106页

作者： Anthony E.Kline Eleni H.Moschonas Corina O.Bondi department of Physical Medicine&Rehabilitation University of PittsburghPittsburghPAUSA Safar Center for Resuscitation Research University of PittsburghPittsburghPAUSA Center for Neuroscience University of PittsburghPittsburghPAUSA department of Critical Care Medicine University of PittsburghPittsburghPAUSA Center for the neural Basis of Cognition University of PittsburghPittsburghPAUSA department of Psychology University of PittsburghPittsburghPAUSA department of Neurobiology University of PittsburghPittsburghPAUSA

Traumatic brain injury(TBI) impacts 69 million individuals globally each year and is a leading cause of death and disability(Dewan et al.,2019).The majority of moderate-to-severe TBI survivors endure long-lasting disturbances in motor,cognitive,and affect that negatively impacts their *** a plethora of research on pharmacological interventions for TBI has been conducted,none has translated to the clinic,thus advocating for the evaluation of nonpharmacological therapeutic approaches that may increase translational success.

关键词： injury traumatic

Effect of tubastatin A on NLRP3 inflammasome activation in macrophages under hypoxia/ reoxygenation conditions

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World Journal of Emergency Medicine 2024年第4期15卷 289-296页

作者： Hao Li Chang Liu Ying Cui Panpan Chang Wei Chong department of Emergency Medicine the First Hospital of China Medical UniversityShenyang 110001China Trauma Medicine Center Peking University People's HospitalBeijing 100871China Key Laboratory of Trauma and neural Regeneration Peking UniversityBeijing 100871China National Center for Trauma Medicine of China Beijing 100871China

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)***:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)***,2.5μmol/L TubA was used with RAW264.7 cells under H/R ***264.7 cells were divided into three groups,namely the control,H/R,and TubA *** levels of reactive oxygen species(ROS)in the cells were detected using fluorescence *** protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western *** levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA).RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1βand IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01).CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages

关键词： Hemorrhagic shock Hypoxia/reoxygenation Macrophage NLRP3 Tubastatin A