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Silvestrol alleviates glioblastoma progression through ERK pathway modulation and MANBA and NRG-1 expression

BIOCELL 2024年第7期48卷 1081-1093页

作者： LAN ZHOU QI ZHANG BO TIAN FENG YANG neurosurgery department The First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina neurosurgery department Changdu People’s Hospital of TibetChangduChina

Background:Glioblastoma,a notably malignant tumor within the central nervous system,is distinguished by its aggressive ***,a robust inhibitor of the RNA helicase eukaryotic initiation factor 4A(eIF4A),has shown significant potential as an anticancer ***,the impact of silvestrol on glioblastoma,especially its molecular mechanisms,has not been fully ***:This investigation employed a variety of in vitro assays,such as cell counting kit-8(CCK-8),clonogenic,5-ethynyl-2′-deoxyuridine(EDU),wound healing,and flow cytometry,to evaluate cell cycle progression,apoptosis,cell viability,and *** blot analysis was also performed to study the apoptosis and extracellular regulated kinase(ERK)*** the ERK pathway was inhibited,differentially expressed genes(DEGs)in U87 cells were identified,followed by an analysis of target genes using the gene expression profiling interactive analysis(GEPIA)***:Silvestrol significantly suppressed the proliferation,migration,and colony formation of glioma *** caused cell cycle arrest and enhanced apoptosis in these ***,silvestrol stimulated the ERK pathway,with these effects being reversible by an ERK phosphorylation *** combined with GEPIA,GSCA,UALCAN,TIMER database screened 4 potential drug targets of silvestrol:chromosome 1 open reading frame 226(C1ORF226),mannosidase beta A(MANBA),IQ motif and Sec7 domain 2(IQSEC2),neuregulin 1(NRG-1).Among them,C1ORF226 was lower risk gene while MANBA,IQSEC2,and NRG-1 were high-risk ***,silvestrol notably reduced MANBA mRNA levels,which could be reversed by inhibiting ERK ***,silvestrol markedly decreased NRG-1 protein levels,with an additional reduction observed when the ERK pathway was ***:Silvestrol’s anti-glioma effects are primarily due to the suppression of MANBA expression via the ERK pathway and possibly by hindering the translation of N

关键词： Glioblastoma Silvestrol ERK pathway MANBA NRG-1

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Ferroptosis:a potential therapeutic target for stroke

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Neural Regeneration Research 2024年第5期19卷 988-997页

作者： Chengli Liu Guijun Wang Wenrui Han Qi Tian Mingchang Li department of neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several *** is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism *** this review,we discuss ferroptosis-related metabolisms,important molecules directly or indirectly targeting iron metabolism and lipid peroxidation,and transcriptional regulation of ferroptosis,revealing the role of ferroptosis in the progression of *** present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on *** review facilitates further understanding of ferroptosis pathogenesis in stroke,proposes new targets for the treatment of stroke,and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.

关键词： cell death ferroptosis oxidative stress stroke treatment

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Metabolic and proteostatic differences in quiescent and active neural stem cells

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Neural Regeneration Research 2024年第1期19卷 43-48页

作者： Jiacheng Yu Gang Chen Hua Zhu Yi Zhong Zhenxing Yang Zhihong Jian Xiaoxing Xiong department of neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Adult neural stem cells are neurogenesis progenitor cells that play an important role in ***,neural regeneration may be a promising target for treatment of many neurological *** regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and *** adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell *** adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural *** review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein ***,we discuss the physiological significance and underlying advantages of these diffe *** to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

关键词： adult neurogenesis cell metabolic pathway cellular proliferation neural stem cell niches neural stem cells neuronal differentiation nutrient sensing pathway proteostasis

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GNAS mutations suppress cell invasion by activating MEG3 in growth hormone–secreting pituitary adenoma

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Oncology Research 2024年第6期32卷 1079-1091页

作者： CHAO TANG CHUNYU ZHONG JUNHAO ZHU FENG YUAN JIN YANG YONG XU CHIYUAN MA department of neurosurgery Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjing210002China department of neurosurgery Children’s Hospital of Nanjing Medical UniversityNanjing210019China Affiliated Eye Hospital Nanjing Medical UniversityNanjing210029China department of neurosurgery Jinling HospitalSouthern Medical UniversityNanjing210002China department of neurosurgery Jinling HospitalNanjing Medical UniversityNanjing210002China

Approximately 30%–40%of growth hormone–secreting pituitary adenomas(GHPAs)harbor somatic activating mutations in GNAS(αsubunit of stimulatory G protein).Mutations in GNAS are associated with clinical features of smaller and less invasive ***,the role of GNAS mutations in the invasiveness of GHPAs is *** mutations were detected in GHPAs using a standard polymerase chain reaction(PCR)sequencing *** expression of mutation-associated maternally expressed gene 3(MEG3)was evaluated with ***3 was manipulated in GH3 cells using a lentiviral expression *** invasion ability was measured using a Transwell assay,and epithelial–mesenchymal transition(EMT)-associated proteins were quantified by immunofluorescence and western ***,a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and *** invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type ***,the invasiveness of mutant GNASexpressing GH3 cells ***3 is uniquely expressed at high levels in GHPAs harboring mutated ***,MEG3 upregulation inhibited tumor cell invasion,and conversely,MEG3 downregulation increased tumor cell ***,GNAS mutations inhibit EMT in ***3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway,which was further validated in *** data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway.

关键词： GHPAs GNAS mutation MEG3 β-catenin EMT

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Mitochondrial recruitment in myelin:an anchor for myelin dynamics and plasticity?

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Neural Regeneration Research 2024年第7期19卷 1401-1402页

作者： Jean-David M.Gothié Timothy E.Kennedy department of Neurology and neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealQCCanada

Optimal propagation of neuronal electrical impulses depends on the insulation of axons by myelin,produced in the central nervous system by *** is an extension of the oligodendrocyte plasma membrane,which wraps around an axon to form a compact multi-layered *** is composed of a substantially higher proportion of lipids compared to other biological membranes and enriched in a small number of specialized proteins.

关键词： plasticity insulation dynamics

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Neural network mapping of gelastic behavior in children with hypothalamus hamartoma

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World Journal of Pediatrics 2024年第7期20卷 735-745页

作者： Zhi‑Hao Guo Jian‑Guo Zhang Xiao‑Qiu Shao Wen‑Han Hu Lin Sang Zhong Zheng Chao Zhang Xiu Wang Chun‑De Li Jia‑Jie Mo Kai Zhang department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityNo.119 South 4th Ring West RoadFengtai DistrictBeijing 100070China department of neurosurgery Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of neurosurgery Beijing Fengtai HospitalBeijingChina

Background Hypothalamus hamartomas(HHs)are rare,congenital,tumor-like,and nonprogressive malformations resulting in drug-resistant epilepsy,mainly affecting *** seizures(GS)are an early hallmark of epilepsy with *** aim of this study was to explore the disease progression and the underlying physiopathological mechanisms of pathological laughter in *** We obtained clinical information and metabolic images of 56 HH patients and utilized ictal semiology evaluation to stratify the specimens into GS-only,GS-plus,and no-GS subgroups and then applied contrasted trajectories inference(cTI)to calculate the pseudotime value and evaluate GS *** logistic regression was performed to identify neuroimaging-clinical predictors of GS,and then voxelwise lesion network-symptom mapping(LNSM)was applied to explore GS-associated brain *** cTI inferred the specific metabolism trajectories of GS progression and revealed increased complexity from GS to other seizure *** was further validated via actual disease duration(Pearson R=0.532,P=0.028).Male sex[odds ratio(OR)=2.611,P=0.013],low age at seizure onset(OR=0.361,P=0.005),high normalized HH metabolism(OR=−1.971,P=0.037)and severe seizure burden(OR=−0.006,P=0.032)were significant neuroimaging clinical *** revealed that the dysfunctional cortico-subcortico-cerebellar network of GS and the somatosensory cortex(S1)represented a negative *** This study sheds light on the clinical characteristics and progression of GS in children with *** identified distinct subtypes of GS and demonstrated the involvement of specific brain regions at the cortical–subcortical–cerebellar *** valuable results contribute to our understanding of the neural correlates of GS.

关键词： Contrasted trajectories inference Gelastic seizure Hypothalamus hamartoma Lesion network-symptom mapping Neural basis

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Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

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Neural Regeneration Research 2024年第8期19卷 1660-1670页

作者： Li Zhang Zhigang Hu Zhenxing Li Yixing Lin department of neurosurgery Jinling HospitalSchool of MedicineNanjing UniversityNanjingJiangsu ProvinceChina

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are *** cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain *** this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro *** also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system *** conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

关键词： central nervous system injuries death pyroptosis ferroptosis inflammation mitophagy necroptosis programmed cell

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Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

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Neural Regeneration Research 2024年第1期19卷 171-179页

作者： Weilin Tan Jun Ma Jiayuanyuan Fu Biying Wu Ziyu Zhu Xuekang Huang Mengran Du Chenrui Wu Ehab Balawi Qiang Zhou Jie Zhang Zhengbu Liao department of neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain ***,the precise mechanism of action remains unclea *** this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive *** sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular *** Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK *** competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and *** the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was ***6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro *** findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

关键词： axon guidance bioinformatics analysis competing endogenous RNA erythropoietin Gene Ontology Kyoto Encyclopedia of Genes and Genomes non-coding RNA RNA sequencing transcriptomics traumatic brain injury

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A model with multiple intracranial aneurysms: possible hemodynamic mechanisms of aneurysmal initiation, rupture and recurrence

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中华神经外科杂志(英文) 2024年第02期10卷 107-114页

作者： Li Wenqiang Wang Chao Wang Yanmin Zhao Yapeng Yang Xinjian Liu Xianzhi Liu Jian department of Interventional Neuroradiology and neurosurgery Beijing Neurosurgical Institute and Beijing Tiantan Hospital Beijing China department of neurosurgery The First Affiliated Hospital of Zhengzhou University Zhengzhou China

Background Hemodynamic factors play an important role in aneurysm initiation, growth, rupture, and recurrence, while the mechanism of the hemodynamic characteristics is still controversial. A unique model of multiple aneurysms (initiation, growth, rupture, and recurrence) is helpful to avoids the confounders and further explore the possible hemodynamic mechanisms of aneurysm in different *** We present a model with multiple aneurysms, and including the states of initiation, growth, rupture, and recurrence, discuss the proposed mechanisms, and describe computational fluid dynamic model that was used to evaluate the likely hemodynamic effect of different states of the *** The hemodynamic analysis suggests that high flow impingement and high WSS distribution at normal parent artery was found before aneurysmal initiation. The WSS distribution and flow velocity were decreased in the new sac after aneurysmal growth. Low WSS was the risk hemodynamic factor for aneurysmal rupture. High flow concentration region on the neck plane after coil embolization still marked in recanalized *** Associations have been identified between high flow impingement and aneurysm recanalization, while low WSS is linked to the rupture of aneurysms. High flow concentration and high WSS distribution at normal artery associated with aneurysm initiation and growth, while after growth, the high-risk hemodynamics of aneurysm rupture was occurred, which is low WSS at aneurysm dome.

关键词： Multiple intracranial aneurysms Hemodynamic Aneurysm initiation and growth Rupture Recurrence

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Multimodality management for chronic subdural hematoma in China: protocol and characteristics of an ambidirectional, nationwide, multicenter registry study

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中华神经外科杂志(英文) 2024年第02期10卷 124-133页

作者： Liu Tao Zhao Zhihao Huang Jinhao Zhu Xide Chen Weiliang Lin Kun Yu Yunhu Li Zhanying Fan Yibing Liu Mingqi Nie Meng Liu Xuanhui Gao Chuang Quan Wei Qian Yu Wu Chenrui Yuan Jiangyuan Wu Di Lv Chuanxiang Dong Shiying Mi Liang Tian Yu Tian Ye Zhang Jianning Jiang Rongcai department of neurosurgery Tianjin Medical University General Hospital Tianjin China Ministry of Education Tianjin Neurological Institute Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System Tianjin Medical University General Hospital Tianjin China department of neurosurgery Linyi People’s Hospital Shandong China department of neurosurgery Haining People’s Hospital Zhejiang China department of neurosurgery Fujian Provincial Hospital Fujian China department of Clinical Research Center for Neurological Disease the People’s Hospital of HongHuaGang District of ZunYi Guizhou China department of neurosurgery Kailuan General Hospital Hebei China department of neurosurgery Tianjin First Central Hospital Tianjin China department of neurosurgery The First Hospital of Jilin University Changchun China

Background Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese ***/design A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years *** Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%.Conclusion This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical *** registration ChiCTR2200057179

关键词： Chronic subdural hematoma Multimodality therapy Outcome Recurrence

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