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Stroke & Vascular Neurology 2024年第3期9卷 252-257页

作者： Angel Miraclin T John Davis Prasad George Abraham Ninan Mahasampath Gowri Deepti Bal Atif Iqbal Ahmed Shaikh Rohit N Benjamin Appaswamy Thirumal Prabhakar Ajith Sivadasan Vivek Mathew Sanjith Aaron department of neurological sciences Christian Medical CollegeVelloreTamil NaduIndia department of Biostatistics Christian Medical CollegeVelloreTamil NaduIndia

Background Multiple cerebral venous sinus thrombosis(CVT)registries from various geographical regions indicate that female gender,the use of contraceptive pills,pregnancy and puerperium are important risk *** this study,we report the changes in the epidemiology of patients with CVT managed over the past 26 *** The CMC Vellore CVT registry is a prospectively maintained database at the Christian Medical College,Vellore since January *** software was used to analyse the data and assess the changes in the incidence,age and gender distribution over the previous 26 *** Among 1701 patients treated during the study period,908(53%)were women and 793(47%)were *** mean incidence of CVT was 49 per 100000 admissions before 2010,which increased to 96 per 100000 after *** gender had a higher odds of developing CVT OR–2.07(CI 1.68 to 2.55,p<0.001).This could be attributed to the declining incidence of postpartum CVT after 2010 compared with the decade before 2010(50%vs 20%).The mean age at presentation had increased from 24.5 to 33.2 years in the last *** There was a clear change in the gender pattern from being a condition with female preponderance,to one where equal or more men are being *** incidence of postpartum CVT cases could be the driving *** increase in the overall incidence of CVT cases was noted,probably due to a higher index of clinical suspicion and better diagnostic imaging modalities.

关键词： CVT driving maintained

Model based on single-nucleotide polymorphism to discriminate aspirin resistance patients

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Stroke & Vascular Neurology 2024年第3期9卷 212-220,I0110-I0129页

作者： Qingyuan Liu Shuaiwei Guo Nuochuan Wang Kaiwen Wang Shaohua Mo Xiong Li Yanan Zhang Hongwei He Shuo Wang Jun Wu department of Neurosurgery and China National Clinical Research Center for neurological Diseases Beijing Tiantan HospitalBeijingChina department of Blood Transfusion Beijing Tiantan HospitalBeijingChina department of Neurosurgery Beijing Chao-Yang Hospital Capital Medical UniversityBeijingChina Beijing neurosurgical institution Capital Medical UniversityBeijingChina

Background Aspirin is widely used for preventing ischaemic *** 20%–40%of patients have aspirin resistance(ASR),which prevents them from benefiting from aspirin *** study aimed to develop and validate a model based on single-nucleotide polymorphism(SNP)to distinguish ASR *** We included patients with spontaneous intracerebral haemorrhage and continuing antiplatelet therapy from a multicentre,prospective cohort study as the derivation ***(inhibition of arachidonic acid channel<50%)was used to identify *** was performed to identify the ASR-related *** on the result of the logistic analysis,the aspirin resistance in the Chinese population score(ASR-CN score)was established,and its accuracy was evaluated using the area under the curve(AUC).Patients receiving dual antiplatelet therapy for unruptured intracranial aneurysm embolism were prospectively included in the validation *** embolism,30-day ischaemic events,including ischaemic stroke,new or more frequent transient ischaemic attack,stent thrombosis and cerebrovascular death,were *** The derivation cohort included 212 patients(155 male patients and the median age as 59).87(41.0%)individuals were identified with *** multivariate logistic analysis demonstrated six SNPs of GP1BA,TBXA2R,PTGS2 and NOS3 as risk factors related to *** ASR-CN score integrating these SNPs performed well to discriminate ASR patients from non-ASR patients(AUC as 0.77).Based on the validation cohort of 372 patients receiving antiplatelet therapy after embolism(including 130 ASR patients),the ASR-CN score continued to distinguish ASR patients with good accuracy(AUC as 0.80).Patients with high a ASR-CN score were more likely to suffer from 30-day ischaemic events after embolism(OR,1.28;95%CI,1.10 to 1.50;p=0.002).Conclusion GP1BA,TBXA2R,PTGS2 and NOS3 were SNPs related to *** ASR-CN score is an effective tool to discriminate ASR patients,which

关键词： patients aspirin resistance

Merging non-covalent and covalent crosslinking:En route to single chain nanoparticles

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Chinese Chemical Letters 2024年第6期35卷 307-311页

作者： Yifei Zhang Yuncong Xue Laiwei Gao Rui Liao Feng Wang Fei Wang CAS Key Laboratory of Soft Matter Chemistry Department of Polymer Science and EngineeringUniversity of Science and Technology of ChinaHefei 230026China department of neurosurgical The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineHefei 230026China

Single-chain nanoparticles represent an emerging class of nanomaterials designed to mimic protein's folding *** covalent crosslinking toward the formation of single-chain nanoparticles encounters complex energy landscapes,leading to the potential occurrence of misfolding *** noncovalent crosslinking can circumvent this issue,the resulting single-chain nanoparticles exhibit lower structural stability compared to their covalently crosslinked *** this study,we present a novel approach for the synthesis of single-chain nanoparticles,achieved through the combination of non-covalent and covalent intramolecular *** grafted onto the linear polymer form intrachain non-covalent stacks aided by hydrogen bonds,leading to the formation of non-covalently crosslinked single-chain *** nanoparticles undergo conversion to covalently crosslinked nanostructures through subsequent photo-irradiation using[2+2]photocycloaddition,a process facilitated by the supramolecular confinement ***,the resulting single-chain nanoparticles demonstrate both intrachain folding efficiency and substantial stability,offering significant potential for advancing applications across diverse fields.

关键词： Single chain nanoparticles Intrachain folding Supramolecular confinement Cyanostilbenes [2+2]photocycloaddition

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and Dentistry Western UniversityLondonONCanada Deparment of Clinical neurological sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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Neural Regeneration Research 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica S.Brady Michael T.Craig department of Clinical and Biomedical sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for neurological Disease San FranciscoCAUSA School of Psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday *** is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 *** 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape

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Signal Transduction and Targeted Therapy 2024年第1期9卷 326-337页

作者： You Zhai Yicong Du Guanzhang Li Mingchen Yu Huimin Hu Changqing Pan Di Wang Zhongfang Shi Xu Yan Xuesong Li Tao Jiang Wei Zhang department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingPR China department of Urology Peking University First HospitalInstitute of UrologyPeking UniversityNational Urological Cancer CenterBeijingPR China department of Pathophysiology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China China National Clinical Research Center for neurological Diseases BeijingPR China Center of Brain Tumor Beijing Institute for Brain DisordersBeijingPR China Research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingPR China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingPR China

Chimeric antigen receptor(CAR)T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid *** instances of rapid tumor remissions have been observed in animal models and clinical trials,tumor relapses occur with multiple therapeutic resistance ***,while the mechanisms underlying the long-term therapeutic resistance are well-known,short-term adaptation remains less ***,more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term *** this study,we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells,a reversal of previously documented *** mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction,also leading to short-term antigen loss and antigen *** type of intercellular communication is independent of CAR downstream signaling,CAR-T cell condition,target antigen,and tumor cell ***,it is mainly dependent on antigen density and CAR sensitivity,and is associated with tumor cell cholesterol *** mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR ***,our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

关键词： Together instance depletion

In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

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Neural Regeneration Research 2025年第8期20卷 2309-2310页

作者： Takashi Irie Taito Matsuda department of Stem Cell Biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan department of Neurology Neurological InstituteGraduate School of Medical SciencesKyushu UniversityFukuokaJapan

Stroke causes neuronal loss,which ultimately results in persistent neurological ***,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart *** that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

关键词： neonatal death therapeutic

RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of Clinical Medicine Shandong UniversityJinanChina Core Unit of National Clinical Research Center for Laboratory Medicine HefeiChina neurosurgical department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina department of Clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

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Neural Regeneration Research 2024年第12期19卷 2708-2722页

作者： He Fang Mengjie Li Jingchen Yang Shunping Ma Li Zhang Hongqi Yang Qiongyan Tang Jing Cao Weimin Yang department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of Nutrition The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Neurology Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina department of Human Anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Neuroscience Research Institute Zhengzhou University Academy of Medical SciencesZhengzhouHenan ProvinceChina

Thalamic hemorrhage can lead to the development of central post-stroke *** in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic ***,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea ***,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus *** this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central ***,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain ***,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain *** results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

关键词： central post-stroke pain hemorrhagic stroke histone deacetylase iron overload voltage-gated potassium ion channel 1.2

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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Neural Regeneration Research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for neurological Diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2