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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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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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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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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong clinical research center of Neurological disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University Department of Neurology and clinical research center of Neurological disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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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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Non-alcoholic fatty liver degree and long-term risk of incident inflammatory bowel disease: A large-scale prospective cohort study

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中华医学杂志(英文版) 2024年第14期137卷 1705-1714页

作者： Zhang Qian Liu Si Wu Jing Zhu Shengtao Wu Yongdong Wu Shanshan Zhang Shutian Department of Gastroenterology Beijing Friendship Hospital Capital Medical University National Clinical Research Center for Digestive Disease Beijing Digestive Disease Center Beijing Key Laboratory for Precancerous Lesion of Digestive Disease Beijing China

Background: Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective ***: Participants from the United Kingdom Biobank cohort (https://***/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years’ follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HRQ4vs. Q1 =1.36, 95% CI: 1.19-1.55,Ptrend <0.001), UC (HRQ4vs. Q1 =1.25, 95% CI: 1.07-1.46,Ptrend=0.047), and CD (HRQ4vs. Q1 =1.58, 95% CI: 1.26-1.97,Ptrend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR=1.13, 95% CI: 1.04-1.24) and CD (HR =1.36, 95% CI: 1.17-1.58).Conclusions: Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatm

关键词： Non-alcoholic fatty liver disease Inflammatory bowel disease Ulcerative colitis Crohn’s disease Cohort study

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Molecular and therapeutic landscape of ferroptosis in skin diseases

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中华医学杂志(英文版) 2024年第15期137卷 1777-1789页

作者： Le Jiayuan Meng Yu Wang Ying Li Daishi Zeng Furong Xiong Yixiao Chen Xiang Deng Guangtong Department of Dermatology Xiangya Hospital Central South University Changsha Hunan China National Engineering research center of Personalized Diagnostic and Therapeutic Technology Changsha Hunan China Furong Laboratory Changsha Hunan China hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University Changsha Hunan China National clinical research center for Geriatric Disorders Xiangya Hospital Changsha Hunan China Department of Oncology Xiangya Hospital Central South University Changsha Hunan China Department of Dermatology Tongji Hospital Huazhong University of Science and Technology Wuhan Hubei China

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

关键词： Ferroptosis Skin diseases Regulated cell death Homeostasis Melanoma Psoriasis Systemic lupus erythematosus Vitiligo

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m^(6)A modification of lncRNA in middle ear cholesteatoma

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中南大学学报（医学版） 2024年第5期49卷 667-678页

作者： HE Jun XIE Shumin JIN Li FU Jinfeng YUAN Qiulin LIU Wei Department of Otolaryngology-Head and Neck Surgery Second Xiangya HospitalCentral South UniversityChangsha 410011 clinical Medical research center for Otology in hunan Province Changsha 410011 Department of Otolaryngology-Head and Neck Surgery Xiangya HospitalCentral South UniversityChangsha 410008 Otolaryngology Major disease research Key Laboratory of hunan Province Changsha 410008 clinical research center for Pharyngolaryngeal diseases and Voice Disorders in hunan Province Changsha 410008 National clinical research center for Geriatric Disorders Xiangya HospitalChangsha 410008China

Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe *** surgery being the primary treatment,the recurrence rate remains ***,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic *** study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear ***:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear *** RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin ***:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor *** lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA *** analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in ***

关键词： long non-coding RNA m6A modifications middle ear cholesteatoma

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p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

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Neural Regeneration research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National clinical research center for Geriatric diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

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P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

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Neural Regeneration research 2024年第8期19卷 1849-1856页

作者： Meihui He Mingfang Xia Qian Yang Xingyi Chen Haibo Li Xiaobo Xia Eye center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of ***,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal *** the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of ***,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult *** rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell ***,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia *** together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

关键词： Achaetescute complex-like 1a(Ascl1a) metabolomics Müller glia p-aminobenzoic acid(PABA) retina regeneration zebrafish

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