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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3βSignaling Pathway

Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia ZHAO Yan-na YU Xiao-ling YIN Li-ming department of hematology Tongde Hospital of Zhejiang ProvinceHangzhou310012China institute of hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China

Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell *** AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow *** morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,*** protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3β),GSK3βand signal transducer and activator of transcription 1(STAT1)were detected by Western ***-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were *** of subcutaneous tumor tissue were observed after hematoxylin and eosin ***1 and GATA-1 expressions were detected by immunohistochemical *** The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(p<0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(p<0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3βand STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P<0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P<0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor ti

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes hematology Hospital SuzhouChina department of hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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Acquired immune thrombotic thrombocytopenic purpura(TTP)associated with inactivated COVID-19 vaccine CoronaVac

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Frontiers of Medicine 2024年第4期18卷 744-751页

作者： Zhangbiao Long Suyu Jiang Honglei Xin Lu Zhang Ruinan Lu Fengqi Liu Yong Xu Linv Wang Jun Wang Xuezhong Zhang Hui Liao Jinning Shi Xue Yan Xiang Zhu Ruonan Shao Zijian Li Yilin Zhu Han Yan Jiao Wu Chao Fang Xiaodong Xi Xiaofeng Shi department of hematology The First Affiliated Hospital of Anhui Medical UniversityHefei230022China department of hematology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210003China department of hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjing210029China department of hematology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing210008China department of hematology The Affiliated Hospital of Nanjing University of Chinese MedicineThe First Clinical Medical College of Nanjing University of Chinese MedicineNanjing210009China department of hematology Zhongda Hospital of Southeast UniversityNanjing210044China department of hematology Nanjing First HospitalNanjing Medical UniversityNanjing210006China department of hematology The Air Force Hospital of Eastern Theater commandNanjing210016China department of hematology Jiangning Hospital Affiliated of Nanjing Medical UniversityNanjing211199China department of hematology Nanjing Hospital of Chinese MedicineNanjing210006China department of Pharmacology School of Basic MedicineTongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesHuazhong University of Science and TechnologyThe Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei ProvinceWuhan430030China Shanghai institute of hematology State Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China

Corona virus disease 2019(COVID-19)due to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the whole *** thrombotic thrombocytopenic purpura(TTP)has been reported after administration of mRNA-or adenoviral vector-based COVID-19 vaccines,including ***2-S,BNT162b2,mRNA-1273,and ChAdOx1 ***,whether inactivated vaccines,such as CoronaVac,could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are *** this study,two cases were *** cases developed TTP after the second CoronaVac vaccination shot,but not the *** demonstrated symptoms of fever,neurological abnormalities,renal dysfunction,thrombocytopenia,and *** patients achieved complete remission through several sessions of plasma exchanges and immune *** incidence of TTP in Nanjing area was *** number of patients with TTP was 12 in 2019,6 in 2020,16 in 2021,and 19 in *** the authors’knowledge,this report is the first report of TTP associated with inactivated COVID-19 vaccine(CoronaVac).The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based *** plasma exchange is a vital treatment for CoronaVac-related TTP,similar to activated vaccine-related TTP.

关键词： thrombotic thrombocytopenia purpura(TTP) corona virus disease 2019(COVID-19) CoronaVac acute respiratory syndrome coronavirus 2(SARS-CoV-2) vaccine

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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of Medicine 2024年第2期18卷 357-374页

作者： Haoyu Wang Zhengyuan Wang Zheng Wang Xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying Liang Jiale Wu Huaxin Song Qing Qu Jiahui Huang Chunkang Chang Kunwei Shen Xiaosong Chen Min Lu department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai institute of hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China department of hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China department of hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132 TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT03295552),decitabine with carboplatin produced an objective response rate(ORR)of 42%in 12 patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong Zhang Jing Qiao Hongming Zhu Li Chen Hai Fang Tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai institute of hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China department of hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine *** an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly ***,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction *** study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma *** was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/***,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular ***,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

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Post-transcriptional regulation of DEAD-box RNA helicases in hematopoietic malignancies

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Genes & Diseases 2024年第5期11卷 315-323页

作者： Jiankun Fan Zhigang Li Li Pei Yu Hou institute of Life Sciences Chongqing Medical UniversityChongqing 400016China department of hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Hematopoiesis represents a meticulously regulated and dynamic biological *** aberrations affecting blood cells,induced by various factors,frequently give rise to hematological *** instances are often accompanied by a multitude of abnormal post-transcriptional regulatory events,including RNA alternative splicing,RNA localization,RNA degradation,and ***,post-transcriptional regulation plays a pivotal role in preserving hematopoietic *** DEAD-Box RNA helicase genes emerge as crucial post-transcriptional regulatory factors,intricately involved in sustaining normal hematopoiesis through diverse mechanisms such as RNA alternative splicing,RNA modification,and ribosome *** review consolidates the existing knowledge on the role of DEAD-box RNA helicases in regulating normal hematopoiesis and underscores the pathogenicity of mutant DEADBox RNA helicases in malignant *** is placed on elucidating both the positive and negative contributions of DEAD-box RNA helicases within the hematopoietic system.

关键词： DEAD-box RNA helicase Hemopoietic system Post-transcriptional regulation Ribosomes assembly RNA alternative splicing

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Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2193-2201页

作者： Huaqing Wang Jifeng Feng Yanyan Liu Zhengzi Qian Da Gao Xuehong Ran Hui Zhou Lihong Liu Binghua Wang Meiyun Fang Hebing Zhou Zhenqian Huang Shi Tao Zhuowen Chen Liping Su Hang Su Yu Yang Xiaobao Xie Huijing Wu Ping Sun Guoyu Hu Aibin Liang Zhiming Li department of Oncology Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China The institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300121PR China department of Medical Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009PR China department of Medical Oncology Henan Cancer HospitalThe Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003PR China department of Medical Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China department of hematology The Affiliated Hospital of Inner Mongolia Medical College010050 HohhotPR China department of hematology Weifang People’s HospitalThe First Affiliated Hospital of Weifang Medical University261000 WeifangPR China department of Lymphoma&hematology Hunan Cancer HospitalThe Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University410013 ChangshaPR China department of hematology The Fourth Hospital of Hebei Medical University and Hebei Tumor Hospital050011 ShijiazhuangPR China department of Lymphoma Weihai Central Hospital264400 WeihaiPR China department of hematology and Rheumatology The Affiliated Zhongshan Hospital of Dalian University116001 DalianPR China department of hematology Beijing Luhe Hospital101199 BeijingPR China department of hematology The First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouPR China department of hematology The First Affiliated Hospital of Hainan Medical College570102 HaikouPR China department of hematology The First People’s Hospital of Foshan528000 FoshanPR China department of hematology Shanxi Cancer Hospital030013 TaiyuanPR China department of Lymphoma Senior Department of HematologyThe Fifth Medical Center of Chinese PLA General Hospital100039 BeijingPR China department of Lymphoma and Head and Neck Cancer Fujian Cancer Hospital350014 FuzhouPR China department of hematology The First People’s Hospit

This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(*** *** March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease *** endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety *** received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at *** stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete *** control rate was 95.1%due to 7(8.5%)stable *** time to response was 1.8 *** 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)*** overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all *** 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being ***-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

关键词： lymphoma assessed initiated

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LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

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Current Medical Science 2024年第1期44卷 81-92页

作者： Feng ZHANG Mohammed Awal Issah Hai-ying FU Hua-rong ZHOU Ting-bo LIU Jian-zhen SHEN Fujian Provincial Key Laboratory on hematology Fujian Medical Center of HematologyFujian Institute of HematologyClinical Research Center for Hematological Malignancies of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Tamale Technical University Faculty of Allied Health and Pharmaceutical SciencesDepartment of Medical Laboratory TechnologyTamale NS-011-2000Ghana department of hematology The Third Affiliated People's Hospital of Fujian University of Traditional Chinese MedicineThe Third People's Hospital of Fujian ProvinceFuzhou 350122China

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation *** specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently ***,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient *** The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis *** expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 *** Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation ***1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 *** of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 *** and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 ***,YAP1 was distributed in the *** LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

关键词： acute lymphoblastic leukemia large tumor suppressor kinase 1 phosphorylation RNA-Seq Yesl-associated protein

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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER Division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann institute for hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

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Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

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Neural Regeneration Research 2024年第3期19卷 519-528页

作者： Xiaodi Xie Lei Wang Shanshan Dong ShanChun Ge Ting Zhu institute of Neuroregeneration&Neurorehabilitation Department of PathophysiologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina School of Traditional Chinese Pharmacy China Pharmaceutical UniversityNanjingJiangsu ProvinceChina department of Rehabilitation Medicine The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are *** the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic *** microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier *** addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each ***,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain *** found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic *** review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

关键词： enteric glia cells gut microbiota gut-brain axis immune response inflammation ischemic stroke lung-brain axis microglia

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