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Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide

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Neural Regeneration research 2024年第7期19卷 1532-1540页

作者： Qin Huang Minping Wei Xianjing Feng Yunfang Luo Yunhai Liu Jian Xia Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology Peking University People’s HospitalBeijingChina clinical research center for cerebrovascular disease of hunan province Central South UniversityChangshaHunan ProvinceChina National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases *** of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation *** aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro *** observational retrospective study was *** May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy *** with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy *** gut microbiota was assessed through 16S ribosomal ribonucleic acid *** also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble *** observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy *** patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae *** lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation ***,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte ***,the role of the gut microbiota in hemorrhagic transformation was evaluated using

关键词： gut microbiota hemorrhagic transformation inflammation lipopolysaccharide stroke

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Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

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Neural Regeneration research 2024年第5期19卷 1064-1071页

作者： Mingxiang Ding Lei Jin Boyang Wei Wenping Cheng Wenchao Liu Xifeng Li Chuanzhi Duan Neurosurgery center Department of Cerebrovascular SurgeryThe National Key Clinical SpecialtyThe Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular DiseaseGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationThe Neurosurgery Institute of Guangdong ProvinceZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of cerebrovascular Intervention Zhongshan City People’s HospitalZhongshanGuangdong ProvinceChina

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective *** is a crucial mechanism underlying early brain injury after subarachnoid *** studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and ***,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid *** this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation *** results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological *** explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral *** TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological ***,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte *** summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

关键词： astrocyte early brain injury inflammasome NLRC4 pyroptosis subarachnoid hemorrhage tumor necrosis factor-stimulated gene-6(TSG-6)

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Glymphatic system:a gateway for neuroinflammation

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Neural Regeneration research 2024年第12期19卷 2661-2672页

作者： Kailu Zou Qingwei Deng Hong Zhang Changsheng Huang Department of Anesthesiology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Xiangya School of Medicine Central South UniversityChangshaHunan ProvinceChina National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the *** evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic *** diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous *** review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system *** addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and *** research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

关键词： aquaporin-4 central nervous system disease cerebrospinal fluid chronic neuroinflammation glymphatic dysfunction neurodegeneration peripheral nerve injury perivascular space systemic disease vicious cycle

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Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

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Genes & diseases 2024年第4期11卷 314-326页

作者： Yinyin Chen Yushun Gong Jia Zou Guoli Li Fan Zhang Yiya Yang Yumei Liang Wenni Dai Liyu He Hengcheng Lu Department of Nephrology Hunan Provincial People's HospitalThe First Affliated Hospital of Hunan Normal UniversityHunan Clinical Research Center for Chronic Kidney DiseaseChangshaHunan 410000China Department of Nephrology The Second Xiangya Hospital of Central South UniversityHunan Key Laboratory of Kidney Disease and Blood PurificationChangshaHunan 410011China Cardiovascular research Institute of Jiangxi province Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi 330006China

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal *** have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene *** define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA *** report for the first time that immune cells,including T cells and B cells,are decreased in ORG *** analysis indicated that SPP1 was significantly up-regulated in T cells and B *** gene is related to inflammation and cell *** of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress ***,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and ***,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

关键词： Fluid shear stress Inflammation Obesity-related glomerulopathy Oxidative phosphorylation Single-cell RNA seq

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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1359-1388页

作者： Qian Zhou Yu Meng Daishi Li Lei Yao Jiayuan Le Yihuang Liu Yuming Sun Furong Zeng Xiang Chen Guangtong Deng Department of Dermatology Xiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina National Engineering research center of Personalized Diagnostic and Therapeutic Technology 87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Furong Laboratory 87 Xiangya RoadChangsha 410008 Hunan ProvinceChina hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina National clinical research center for Geriatric Disorders Xiangya Hospital87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Department of General Surgery Xiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Department of Plastic and Cosmetic Surgery Xiangya HospitalCentral South University87 Xiangya RoadChangsha 410008 Hunan ProvinceChina Department of Oncology Xiangya HospitalCentral South University87Xiangya RoadChangsha 410008Hunan ProvinceChina

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation of iron-dependent membranelocalized lipid *** acts as an innate tumor suppressor mechanism and participates in the biological processes of ***,mesenchymal and dedifferentiated cancer cells,which are usually resistant to apoptosis and traditional therapies,are exquisitely vulnerable to ferroptosis,further underscoring its potential as a treatment approach for cancers,especially for refractory ***,the impact of ferroptosis on cancer extends beyond its direct cytotoxic effect on tumor *** induction not only inhibits cancer but also promotes cancer development due to its potential negative impact on anticancer ***,a comprehensive understanding of the role of ferroptosis in cancer is crucial for the successful translation of ferroptosis therapy from the laboratory to clinical *** this review,we provide an overview of the recent advancements in understanding ferroptosis in cancer,covering molecular mechanisms,biological functions,regulatory pathways,and interactions with the tumor *** also summarize the potential applications of ferroptosis induction in immunotherapy,radiotherapy,and systemic therapy,as well as ferroptosis inhibition for cancer treatment in various *** finally discuss ferroptosis markers,the current challenges and future directions of ferroptosis in the treatment of cancer.

关键词： cancer mechanisms treatment

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CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

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research 2024年第1期2023卷 509-523页

作者： Chao Chen Xiaoqing Yi Panpan Liu Jie Li Bei Yan Detian Zhang Lei Zhu Pian Yu Lei Li Jiaxiong Zhang Yehong Kuang Shuang Zhao Wu Zhu Cong Peng Xiang Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina National Engineering research center of Personalized Diagnostic and Therapeutic Technology ChangshaHunanChina Furong Laboratory ChangshaHunanChina hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangshaHunanChina National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal *** elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain *** investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse *** mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic *** found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in *** CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of *** non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).

关键词： CD147 pathogenesis markedly

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The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

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Neural Regeneration research 2024年第1期19卷 205-211页

作者： Sen Zeng Honglan Yang Binghao Wang Yongzhi Xie Ke Xu Lei Liu Wanqian Cao Xionghao Liu Beisha Tang Mujun Liu Ruxu Zhang Department of Neurology The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Radiology The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Health Management center The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina center for Medical Genetics&hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina National clinical research center for Geriatric Disorders Central South UniversityChangshaHunan ProvinceChina Department of Cell Biology School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical *** aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment *** cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor ***-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem *** proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like ***2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem *** r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor *** findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stag

关键词： antisense oligonucleotides cell cycle arrest Charcot-Marie-Tooth disease 2Z induced pluripotent stem cells MAPK/ERK PI3K/Akt proliferation spinal muscular atrophy-like

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Validation of proposed diagnostic criteria for allergic bronchopulmonary aspergillosis

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Chinese Medical Journal 2024年第9期137卷 1132-1134页

作者： Runjin Cai Yifei Yang Huan Ge Xuemei Chen Xinyue Hu Yuanyuan Jiang Lisha Luo Shuanglinzi Deng Jiale Tang Chendong Wu Huan Tang Xiaoxiao Gong Xiaozhao Li Juntao Feng Department of Respiratory Medicine National Key Clinical SpecialtyBranch of National Clinical Research Center for Respiratory DiseaseXiangya HospitalCentral South UniversityChangshaHunan 410008China National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Nephrology Xiangya HospitalCentral South UniversityChangshaHunan 410008China

To the Editor:Allergic bronchopulmonary aspergillosis(ABPA)is an allergic lung disease caused by hypersensitivity to antigens from Aspergillus,and it most commonly occurs in patients with asthma or cysticbrosis.[1]The main clinical characteristics of the disease are those related to elevated serum immunoglubulin(Ig)E level,positive Aspergillus fumigatus(***)specic IgE/IgG,repeated pulmonary inltration,and ***,due to the lack of unied diagnostic criteria and screening methods,ABPA is always *** 2021,new diagnostic criteria were proposed for allergic bronchopulmonary mycosis(ABPM)in the Japanese population.

关键词： allergic elevated aspergillosis

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Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

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Neural Regeneration research 2024年第10期19卷 2132-2143页

作者： Chengfu Zhang Mengsheng Qiu Hui Fu center for Cognition and Brain Disorders The Affiliated Hospital of Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Institute of Life Sciences Key Laboratory of Organ Development and Regeneration of Zhejiang ProvinceCollege of Life and Environment SciencesHangzhou Normal UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Aging and Cancer Biology of Zhejiang province School of Basic Medical SciencesHangzhou Normal UniversityHangzhouZhejiang ProvinceChina

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

关键词： astrocyte central nervous system disease CXC chemokine cytokine interferonγ interleukin microglia oligodendrocyte oligodendrocyte precursor cell tumor necrosis factorα

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Genetic analysis of transcription factors in dopaminergic neuronal development in Parkinson’s disease

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Chinese Medical Journal 2024年第4期137卷 450-456页

作者： Yuwen Zhao Lixia Qin Hongxu Pan Tingwei Song Yige Wang Xiaoxia Zhou Yaqin Xiang Jinchen Li Zhenhua Liu Qiying Sun Jifeng Guo Xinxiang Yan Beisha Tang Qian Xu Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Neurology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Bioinformatics center National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Geriatrics Xiangya HospitalCentral South UniversityChangshaHunan 410008China Centre for Medical Genetics and hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China Key Laboratory of hunan province in Neurodegenerative Disorders Central South UniversityChangshaHunan 410008China

Background:Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease(PD)risk factors;however,no comprehensive analyses of these genes in patients with PD have been ***,we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with ***:Whole-exome sequencing(WES)was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 ***,whole-genome sequencing(WGS)was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 ***:We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts,***-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset ***,the significance did not pass the Bonferroni ***,72 and 1730 common variants were found in the WES and WGS cohorts,***,single-variant logistic association analyses did not identify significant associations between common variants and ***:Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese ***,we highlight the complexity of PD and the need for extensive research elucidating its etiology.

关键词： Parkinson’s disease Transcription factors Dopaminergic neurons Genetic Variants

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