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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

Cellular & Molecular immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and immunology Midwestern UniversityDowners GroveILUSA division of rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Interleukin-10 suppresses lipid metabolism-mediated intestinal inflammation

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Life Metabolism 2024年第3期3卷 3-5页

作者： Tristram A.J.Ryan Ivan Zanoni division of immunology and division of Gastroenterology Boston Children’s Hospital and Harvard Medical SchoolBostonMA 02115United States

In a recent paper published in Nature,York et *** that the anti-inflammatory cytokine interleukin(IL)-10 regulates sphingolipid metabolism to limit NF-κB-mediated *** of Il10 in mice,or genetic mutation of IL10 in humans,predisposes to inflammatory bowel disease,which may be overcome by restoring homeostatic sphingolipid metabolism.

关键词： metabolism inflammation al.

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Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

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World Journal of Gastroenterology 2024年第17期30卷 2343-2353页

作者： Oraphan Jitpraphawan Witchakorn Ruamtawee Mala Treewatchareekorn Supatsri Sethasine division of Gastroenterology and Hepatology Department of MedicineNavamindradhiraj UniversityDusit 10300BangkokThailand Clinical Research Center Research Facilitation DivisionNavamindradhiraj UniversityDusit 10300BangkokThailand division of Clinical Chemistry and immunology Navamindradhiraj UniversityDusit 10300BangkokThailand

BACKGROUND The GALAD score has improved early hepatocellular carcinoma(HCC)detection *** role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular *** To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis,tumor features,and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum *** This prospective,diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira *** patients had HCC staging allocation using the Barcelona Clinic Liver Cancer(BCLC)***,HCC etiology,and HCC features were *** and the GALAD score were obtained at *** performance of the GALAD score and biomarkers were prospectively *** Exactly 115 individuals were diagnosed with *** GALAD score increased with disease *** BCLC-0/A and BCLC-B/C/D,the GALAD score predicted HCC staging with an area under the curve(AUC)of 0.868(95%CI:0.80–0.93).For identifying the curative HCC,the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein(AFP)(0.753)and Lens culinaris agglutinin-reactive fraction of AFP-L3(0.706),and as good as that of Protein induced by vitamin K absence-II(PIVKA-II)(0.897).For detecting aggressive features,the GALAD score gave an AUC of 0.839(95%CI:0.75–0.92)and significantly outperformed compared to that of AFP(0.761)and AFP-L3(0.697),with a trend of superiority to that of PIVKA-II(0.772).The performance to predict 1-year mortality of GALAD score(AUC:0.711,95%CI:0.60–0.82)was better than that of AFP(0.541)and as good as that of PIVKA-II(0.736).The optimal cutoff value of GALAD score was≥6.83,with a specificity of 72.63%for exhibiting substantial reduction in the 1-year *** The GALAD model can diagnose HCC at the curative stage,includin

关键词： Alpha-fetoprotein Barcelona clinic liver cancer GALAD score Hepatocellular carcinoma Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein Protein induced by vitamin K absence-II

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Ten- year follow- up investigation of stroke risk in systemic lupus erythematosus

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Stroke & Vascular Neurology 2024年第1期9卷 1-7页

作者： Jin-An Huang Ching-Heng Lin Ming-Ju Wu Yi-Hsing Chen Kuo-Cheng Chang Chung-Wei Hou division of Neurology Neurological InstituteTaichung Veterans General HospitalTaichungTaiwan Department of Health Business Administration Hungkuang UniversityTaichungTaiwan Department of Medical Research Taichung Veterans General HospitalTaichungTaiwan division of Nephrology Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine Chung Shan Medical UniversityTaichungTaiwan College of Medicine National Chung Hsing UniversityTaichungTaiwan division of Allergy Immunology and RheumatologyDepartment of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine National Yang-Ming Chiao Tung UniversityTaichungTaiwan

Background and purpose To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus(SLE).Methods A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research *** with SLE between 2000 and 2008 were registered and matched with two controls by the index date,age,gender and Charlson Comorbidity Index(CCI).These subjects were followed until either stroke event or 31 December *** HRs(aHRs)for strokes were estimated with Cox regression models,and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival *** In total,8310 patients with SLE and 16620 patients without SLE were *** general,patients with SLE had higher rates of ischaemic stroke(5.4%vs 3.3%)and haemorrhagic stroke(1.5%vs 0.6%)than in *** multivariate analysis adjusted to age,gender,CCI,urbanisation level and antithrombotics uses,aHRs of all strokes,ischaemic stroke and haemorrhagic stroke were 1.73(95%CI:1.54 to 1.94),1.65(95%CI:1.45 to 1.87)and 2.24(95%CI:1.71 to 2.95),respectively,in patients with *** with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE,even 10 years after SLE diagnosis(6.12%vs 3.50%,p<0.001).Antiplatelet use increased the risk of haemorrhagic stroke in SLE group(aHR=1.74,95%CI:1.18 to 2.57).Conclusions Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 *** should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

关键词： erythematosus diagnosis likely

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Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun Sun Yinglin Xia division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological *** is emerging as a powerful tool generally for pre-cision ***,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and ***,metabo-lomics data are very ***/pretreating and normalizing procedures on metabolomics data are usually required before statistical *** this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data *** discuss the advantages and limitations of each *** choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis *** then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

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The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & Molecular immunology 2024年第2期21卷 197-200页

作者： Valeria Fumagalli Matteo Iannacone division of immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly Experimental Imaging Centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative *** vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be *** review delves into the potential influence of nirmatrelvir on enduring *** parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory *** importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

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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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The immune system: uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan José Lasarte immunology and Immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei Zhang Yongguo Zhang Yinglin Xia Jun Sun division of Gastroenterology and Hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer Center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown VA Medical Center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 *** CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized *** infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection *** with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental ***,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long *** highlight the potential mechanisms and possible treatment based on Gl health and ***,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

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Monocyte and macrophage function in respiratory viral infections

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Animal Diseases 2024年第1期4卷 40-47页

作者： Mohd Arish Jie Sun Beirne B.Carter Center for immunology Research University of VirginiaCharlottesvilleVA 22908USA division of Infectious Disease and International Health Department of MedicineUniversity of VirginiaCharlottesvilleVA 22908USA

Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased *** tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral *** sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological *** this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.

关键词： Alveolar macrophages Interstitial macrophages Monocytes derived macrophages Viral infection IAV RSV SARS-COV-2

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