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Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue Wenshi Li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu State Key Laboratory of Virology and department of Medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province Key Laboratory of allergy&immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years *** these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of ***,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with ***,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated *** data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal *** in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in *** indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce *** research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter ***,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by *** conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

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Harnessing SARS-CoV-2-specific CD8^(+)T cells to kill target tumor cells for cancer immunotherapy

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Cancer Communications 2024年第1期44卷 173-177页

作者： Keunok Jung Deok-Han Ko Jeong-Yun Jang Young Rong Kim Jung Yeon Heo Yong-Sung Kim department of allergy and Clinical immunology Ajou University School of MedicineSuwonRepublic of Korea department of Molecular Science and Technology Ajou UniversitySuwonRepublic of Korea department of Infectious Diseases Ajou University School of MedicineSuwonRepublic of Korea

Dear Editor,During the coronavirus disease 2019(COVID-19)pan-demic era,many individuals were naturally infected with or vaccinated against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),resulting in the p... 详细信息

关键词： acute respiratory immunotherapy

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Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

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Cancer Biology & Medicine 2024年第6期21卷 513-540页

作者： Zhihong Luo Xiaohua Huang Xinyi Xu Kefeng Wei Yi Zheng Ke Gong Wenhua Li Hubei Key Laboratory of Cell Homeostasis College of Life SciencesWuhan UniversityWuhan 430072China Wuhan University Shenzhen Research Institute Shenzhen 518057China Central Laboratory University of Chinese Academy of Sciences-Shenzhen HospitalShenzhen 518107China Hubei Province Key Laboratory of allergy and immunology and department of immunology School of Basic Medical SciencesWuhan UniversityWuhan 430071China

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains ***: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell ***: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some ***: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regula

关键词： Breast cancer lactate dehydrogenase B lactic acid NK cells tumor immunity

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COVID-19 and cardiac complications:Myocarditis and multisystem inflammatory syndrome in children

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World Journal of Cardiology 2024年第5期16卷 260-268页

作者： Muhammed Gunes Oner Ozdemir department of Pediatric Cardiology Research and Training Hospital of SakaryaAdapazarı54100SakaryaTürkiye department of Pediatric allergy and immunology Research and Training Hospital of SakaryaSakarya University Medical FacultyAdapazarı54100SakaryaTürkiye

Coronavirus is an important pathogen causing disease in humans and *** the end of 2019,an investigation into an increase in pneumonia cases in Wuhan,Hubei Province,China,found that the cause was a new *** disease,which spread rapidly across China and caused an outbreak worldwide,resulted in a *** this virus has previously been referred to as 2019-nCoV,which causes coronavirus disease 2019(COVID-19),later it was named severe acute respiratory syndrome coronavirus *** were usually asymptomatic and rarely severely *** April 2020,reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock *** clinical picture was later defined as multisystem inflammatory syndrome in *** then,similarly affected children as well as cases with other cardiac complications have been reported in other parts of the *** this review,we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

关键词： COVID-19 Cardiac complication Myocarditis Multisystem inflammatory syndrome in children SARS-CoV-2

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Relation between dysbiosis and inborn errors of immunity

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World Journal of Methodology 2024年第4期14卷 104-109页

作者： Öner Özdemir department of Pediatric allergy and immunology Sakarya UniversityMedical FacultyAdapazarı54100SakaryaTürkiye

Inborn errors of immunity(IEI)disorders,formerly primary immune deficiency diseases,are a heterogeneous group of disorders with variable hereditary transitions,clinical manifestations,complications and varying disease *** of the clinical symptoms,signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity(dysbiosis).For example,in common variable immunodeficiency patients,the diversity of bacteria,but not fungi,in the gut microbiota has been found to be reduced and significantly ***,this was associated with a more severe disease *** of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients,causing Candida albicans to switch from commensal to *** of the microbiota can be used as a therapeutic approach in patients with ***,probiotics,postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI *** trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.

关键词： Immunodeficiency Microbiome Microbiota Fecal microbiota transplantation Immunoglobulin

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Aryl hydrocarbon receptor:Linking environment to aging process in elderly patients with asthma

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Chinese Medical Journal 2024年第4期137卷 382-393页

作者： Tianrui Yang Rongjun Wan Wei Tu Sai Nithin Avvaru Peisong Gao Division of allergy and Clinical immunology Department of MedicineJohns Hopkins University School of MedicineBaltimoreMD 21224USA department of Geriatric Medicine The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650032China department of Respiratory Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China The State Key Laboratory of Respiratory Disease for allergy Shenzhen Key Laboratory of Allergy and ImmunologyShenzhen University School of MedicineShenzhenGuangdong 518055China

Aging is a significant risk factor for various diseases,including asthma,and it often leads to poorer clinical outcomes,particularly in elderly *** is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage,resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic *** effects of aging affect not only the elderly but also those of younger ages,posing significant challenges to global ***,understanding the molecular mechanisms associated with aging in different diseases is *** intriguing factor is the aryl hydrocarbon receptor(AhR),which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging ***,we review the literature on several major hallmarks of aging,including mitochondrial dysfunction,cellular senescence,autophagy,mitophagy,epigenetic alterations,and microbiome ***,we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures,particularly in relation to the immune ***,we explore how aging hallmarks affect clinical characteristics,inflammatory features,exacerbations,and the treatment of *** is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

关键词： Aging Environment Reactive oxygen species Senescence Aryl hydrocarbon receptor Asthma

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Clinical-based phenotypes in children with pediatric post-COVID-19 condition

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World Journal of Pediatrics 2024年第7期20卷 682-691页

作者： Lieke C.E.Noij Jelle M.Blankestijn Coen R.Lap Marlies A.van Houten Giske Biesbroek Anke-Hilse Maitland-van der Zee Mahmoud I.Abdel-Aziz Johannes B.van Goudoever Mattijs W.Alsem Caroline L.H.Brackel Kim J.Oostrom Simone Hashimoto Suzanne W.J.Terheggen-Lagro department of Pediatric Pulmonology and allergy Amsterdam UMCLocation AMCEmma Children’s HospitalAmsterdam University Medical CenterRoom G2-222Meibergdreef 91105AZAmsterdamThe Netherlands department of Pulmonary Medicine Amsterdam UMCAmsterdamThe Netherlands department of Pediatrics Spaarne GasthuisHoofddorpThe Netherlands department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterAmsterdamThe Netherlands department of Rehabilitation Medicine Amsterdam Movement SciencesMeibergdreef 9AmsterdamThe Netherlands department of paediatric Pulmonology Department of PaediatricsTergooi MCHilversumThe Netherlands department of Child and Adolescent Psychiatry and Psychosocial Care Amsterdam UMCAmsterdam Reproduction and DevelopmentAmsterdamThe Netherlands

Background Pediatric post coronavirus disease 2019(COVID-19)condition(PPCC)is a heterogeneous syndrome,which can significantly affect the daily lives of *** study aimed to identify clinically meaningful phenotypes in children with PPCC,to better characterize and treat this *** Participants were children with physician-diagnosed PPCC,referred to the academic hospital Amsterdam UMC in the Netherlands between November 2021 and March *** factors and information on post-COVID symptoms,comorbidities,and impact on daily life were *** clusters were identified using an unsupervised and unbiased approach for mixed data *** Analysis of 111 patients(aged 3–18 years)revealed three distinct clusters within *** 1(n=62,median age=15 years)predominantly consisted of girls(74.2%).These patients suffered relatively more from exercise intolerance,dyspnea,and smell *** 2(n=33,median age=13 years)contained patients with an even gender distribution(51.5%girls).They suffered from relatively more sleep problems,memory loss,gastrointestinal symptoms,and *** 3(n=16,median age=11 years)had a higher proportion of boys(75.0%),suffered relatively more from fever,had significantly fewer symptoms(median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively),and experienced a lower impact on daily *** This study identified three distinct clinical PPCC phenotypes,with variations in sex,age,symptom patterns,and impact on daily *** findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-COVID symptoms in children.

关键词： Adolescents Clusters Long COVID Pediatric Phenotypes Post-COVID syndrome

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Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation

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Current Medical Science 2024年第3期44卷 475-484页

作者： Min-shan LI Xiang-hong WANG Heng WANG department of Otolaryngology-Head and Neck Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Institute of allergy and Clinical immunology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Clinical Research Center for Nasal Inflammatory Diseases Wuhan430030China

Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various *** receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and ***-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular *** detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune *** this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.

关键词： proton-activated G protein-coupled receptors inflammation immunomodulation disease

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Sex Disparities in the Association of Blood Pressure Parameters and Arterial Sclerosis Risk

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Biomedical and Environmental Sciences 2024年第7期37卷 795-799页

作者： Dongdong Zhang Weiling Chen Minqi Gu Xi Li Yuying Wu Xueru Fu Ping Tang Fulan Hu Jing Li Xizhuo Sun Dongsheng Hu Ming Zhang department of General Practice The Affiliated Luohu Hospital of Shenzhen University Medical SchoolShenzhen 518060GuangdongChina department of allergy and Clinical immunology State Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120GuangdongChina department of Biostatistics and Epidemiology School of Public HealthShenzhen University Medical SchoolShenzhen 518060GuangdongChina

Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of *** pulse wave velocity(PWV)measurements could reflect early progression of *** on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.

关键词： Blood Arterial atherosclerosis

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Tubularized incised plateurethroplasty and grafted tubularized incised plate urethroplasty: systematic review, metaanalysis and trial sequential analysis

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World Journal of Pediatric Surgery 2024年第1期7卷 10-19页

作者： Nitinkumar Borkar Charu Tiwari Abhijit Nair Debajyoti Mohanty C K Sinha Jai Kumar Mahajan paediatric Surgery All India Institute of Medical Sciences-RaipurRaipurChhattisgardhIndia department of Anaesthesiology Ibra HospitalbraOman General Surgery All India Institute of Medical Sciences-RaipurRaipurChhattisgardhIndia paediatric Surgery St George's University Hospitals NHS Foundation TrustLondonUK Pediatric Surgery PGIMERChandigarhIndia

Background Hypospadias is one of the most common genital birth *** are around 300 various techniques available for the repair of *** study aims to compare the reported outcomes of Tubularized incised plate urethroplasty(TIP)and Grafted TIP(GTIP)repair in children undergoing primary *** This meta-analysisadhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,and we framed our research question using the population,intervention,control and outcomes *** conducted comprehensive electronic searches across various databases,employing a Boolean search strategy with predefined search *** randomized controlled trials(RCTs)were included for quantitative *** Totally,10 RCTs met our inclusion criteria for quantitative *** results indicated that urethrocutaneous fistula,glans dehiscence,and stricture rates were comparable between the two *** incidence of meatal stenosis was found to be significantly lower in the GTIP group with a relative risk(RR)of 0.32(95%confidence interval(Cl)0.15 to 0.67).Conclusion The coucomes UCF,glans dehiscence,and stricture rates were comparable between the two ***,the incidence of meatal stenosis was found to be significantly lower in the grafted TIP *** terms of operative time,our quantitative synthesis demonstrated that the TIP group had a shorter operative time than the GTIP group with significant heterogeneity.

关键词： plate grafted analysis

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