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Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

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Nano Research 2017年第8期10卷 2743-2760页

作者： dong-wan kang Chi Kyung Kim Han-Gil Jeong Min Soh Taeho Kim In-Young Choi SeuI-Ki Ki Do Yeon Kim Wookjin Yang Taeghwan Hyeon Seung-Hoon Lee Laboratory of Innovative Nanobiotechnology Biomedical Research Institute Seoul National University Hospital Seoul 03080 Republic of Korea Department of Neurology Seoul National University Hospital Seou103080 Republic of Korea Department of Neurology Korea University Guro Hospital and Korea University College of Medicine Seou108308 Republic of Korea Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 151-742 Republic of Korea School of Chemical and Biological Engineering and Institute of Chemical Processes Seoul National University Seoul 151-742 Republic of Korea

Intracerebral hemorrhage （ICH） is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles （CeNPs） are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol （PEG） to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood-brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.

关键词： ceria nanoparticles intracerebral hemorrhage free radical injury anti-inflammation neuroprotective agents biomedical application

Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage

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Nano Research 2018年第7期11卷 3582-3592页

作者： Bong Geun Cha Han-Gil Jeong dong-wan kang Myong-Joo Nam Chi Kyung Kim Do Yeon Kim In-Young Choi Seul Ki Ki Song I Kim Ju hee Han Jaeyun Kim Seung-Hoon Lee School of Chemical Engineering Sungkyunkwan University Suwon 16419 Republic of Korea Department of Laboratory of Innovative Nanobiotechnology Biomedical Research Institute Seoul National University Hospital 101 Daehak-ra Jongno-gu Seou103080 Republic of Korea Department of Neurology Seoul National University Hospital 101 Daehak-ro Jongno-gu Seou103080 Republic of Korea Department of Neurology Korea University Guro Hospital and Korea University College of Medicine Seoul 08308 Republic of Korea Department of Health Sdences and Technology Samsung Advanced Institute for Health Science & Technology (SAIHST) Sungkyunkwan University Suwon 16419 Republic of Korea Biomedical Institute for Convergence at SKKU (BICS) Sungkyunkwan University Suwon 16419 Republic of Korea

Intracerebral hemorrhage （ICH）, caused by the sudden rupture of an artery within the brain, is a devastating subtype of stroke, which currently has no effective treatment. Intense inflammatory reactions that occur in the peri-hematomal area after ICH are more deleterious than the hematoma itself, resulting in subsequent brain edema and neurologic deterioration. Thus, we developed lipid-coated magnetic mesoporous silica nanoparticles doped with ceria nanoparticles （CeNPs）, abbreviated as LMCs, which have both potent anti-inflammatory therapeutic effects via scavenging reactive oxygen species and help in increasing the efficacy of magnetic resonance imaging enhancement in the peri-hematomal area. LMCs consist of mesoporous silica nanopartide-supported lipid bilayers, which are loaded with large amounts of CeNPs for scavenging of reactive oxygen species, and iron oxide nanoparticles for magnetic resonance imaging contrast. LMCs loaded with CeNPs exhibited strong anti-oxidative and anti-inflammatory activities in vitro. In the rodent ICH model, intracerebraUy injected LMCs reached the peri-hematomal area and were engulfed by macrophages, which were clearly visualized by magnetic resonance imaging of the brain. Moreover, LMCs reduced inflammatory macrophage infiltration, and thus significantly reduced brain edema. Finally, LMC treatment markedly improved neurologic outcomes of the animals with ICH. Thus, LMC is the first nanobiomaterial that successfully showed theragnostic effects in ICH.

关键词： magnetic mesoporous silica nanoparticle ceria nanoparticles intracerebral hemorrhage reactive oxygen species therapeutics imaging

Dose verifying system used in Leksell GammaKnife Radiosurgery:Variable Ellipsoid Modeling Technique（VEMT）

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Dose verifying system used in Leksell GammaKnife Radiosurger...

A low redox potential and long life organic anode material for sodium-ion batteries

中国抗癌协会神经肿瘤专业委员会第八届学术会议

作者： Beong Ik Hur dong wan kang Won Ho Cho Seung Heon Cha Chang Hwa Choi Byung Kwan Choi Department of Neurosurgery Pusan National University Hospital

＜正＞Purposes:The secondary,independent verification of Leksell Gamma Knife treatment planning system（LGP） is extremely important in order to minimize the risk of treatment errors.

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Journal of Energy Chemistry 2025年第1期100卷 557-564页

作者： Zhi Li Yang Wei kang Zhou Xin Huang Xing Zhou Jie Xu Taoyi Kong Junwei Lucas Bao Xiaoli dong Yonggang wang Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Institute of New Energy Collaborative Innovation Center of Chemistry for Energy Materials (iChEM) Fudan University Department of Chemistry Boston College School of Materials Science and Engineering Anhui University of Technology

Sodium-ion batteries （SIBs） with organic electrodes are an emerging research direction due to the sustainability of organic materials based on elements like C,H,O,and sodium ***,organic electrode materials for SIBs are mainly used as cathodes because of their relatively high redox potentials（>1 V）.Organic electrodes with low redox potential that can be used as anode are ***,a novel organic anode material （tetrasodium 1,4,5,8-naphthalenetetracarboxylate,Na4TDC） has been developed with low redox potential （<0.7 V） and excellent cyclic *** three-sodium storage mechanism was demonstrated with various in-situ/ex-situ spectroscopy and theoretical calculations,showing a high capacity of 208 mAh/g and an average decay rate of merely 0.022%per ***,the Na4TDC-hard carbon composite can further acquire improved capacity and cycling stability for 1200 cycles even with a high mass loading of up to 20 mg *** pairing with a thick Na3V2（PO4）3cathode (20.6 mg cm-2),the as-fabricated full cell exhibited high operating voltage （2.8 V）,excellent rate performance and cycling stability with a high capacity retention of 88.7% after 200 cycles,well highlighting the Na4TDC anode material for SIBs.

关键词： Organic anode material Low redox potential Composite anode Sodium-ion batteries

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran kang Renwen wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 139-158页

作者： Fengjuan Jiao Lingyan Meng kang Du Xuezhi Li School of Mental Health Jining Medical UniversityJiningShandong ProvinceChina Shandong Collaborative Innovation Center for Diagnosis Treatment and Behavioral Interventions of Mental DisordersInstitute of Mental HealthJining Medical UniversityJiningShandong ProvinceChina

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in *** one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these *** evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s ***,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome ***,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s *** this review,we briefly introduce the machinery of ***,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome ***,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

关键词： autophagy chemical therapy gene therapy Parkinson’s disease α-synuclein

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

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Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第1期68卷 288-296页

作者： Shuai Liu Wen-Qiang Xu Ying-Tong Di Man-Cheng Tang Ding-kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu Ying Zeng Yun-dong Wu Xiao-Jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

关键词： metabolon Diels-Alder reaction semipinacol rearrangement biosynthesis notoamides spiro polycyclic alkaloids