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Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim Böttrich Pascal Bauer Vincent Gröβer Magdalena Huber Hartmann Raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer Robert Ringseis Klaus Eder Karsten Krüger Christopher Weyh Department of Exercise physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany Department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany Department of internal medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition physiology Justus-Liebig-University GiessenGiessen 35390Germany

Background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly Regulatory T cells Subclinical atherosclerosis

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and integrative physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Cryo-EM structure of cannabinoid receptor CB1-β-arrestincomplex

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Protein & Cell 2024年第3期15卷 230-234页

作者： Yuxia Wang Lijie Wu Tian Wang Junlin Liu Fei Li Longquan Jiang Zhongbo Fan Yanan Yu Na Chen Qianqian Sun Qiwen Tan Tian Hua Zhi-Jie Liu iHuman Institute ShanghaiTech UniversityShanghai 201210China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Institute of molecular and Clinical medicine Kunming Medical UniversityKunming 650500China

Dear Editor,G protein-coupled receptors(GPCRs)play a vital role in regulating almost every aspect of human physiology,making up more than one-third of marketed drug targets(Santos et al.,2017).GPCRs orchestrate their signalling through interactions with three distinct downstream protein families:G proteins,G protein-coupled receptor kinases(GRKs),and arrestins(Santos et al.,2017).While G protein-mediated signalling is initiated upon GPCR stimulation,activated GPCRs return to their basal levels through a GRK-and arrestin-regulated desensitization process(Santos et al.,2017).In addition to modulating receptor desensitization,β-arrestin also regulates downstream events that are distinct from classical G protein signalling(Ahn et al.,2020).

关键词： stimulation return

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Ferroptosis mechanism and Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1741-1750页

作者： Lina Feng Jingyi Sun Ling Xia Qiang Shi Yajun Hou Lili Zhang Mingquan Li Cundong Fan Baoliang Sun Shandong Key Laboratory of TCM Multi-Target Intervention and Disease Control the Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of internal medicine Taian Traffic HospitalTaianShandong ProvinceChina Department of Neurology the Third Affiliated Clinical Hospital of Changchun University of Chinese MedicineChangchunJilin ProvinceChina

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living *** process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living *** is a classic regulatory mode of cell *** studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s *** review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s *** findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

关键词： Alzheimer’s disease apolipoprotein E Fe^(2+) ferroptosis glial cell glutathione peroxidase 4 imbalance in iron homeostasis lipid peroxidation regulated cell death system Xc^(-)

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Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis

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World Journal of Hepatology 2024年第5期16卷 822-831页

作者： Irina Efremova Roman Maslennikov Elena Poluektova Oleg Medvedev Anna Kudryavtseva George Krasnov Maria Fedorova Filipp Romanikhin Maria Zharkova Oxana Zolnikova Gyunay Bagieva Vladimir Ivashkin Department of internal medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Department of Scientific Scientific Community for the Promotion of the Clinical Study of the Human MicrobiomeMoscow 119435Russia Department of Pharmacology Lomonosov Moscow State UniversityMoscow 119192Russia Department of Post-Genomic Research Laboratory Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscow 119991Russia

BACKGROUND The gut–liver axis and bacterial translocation are important in cirrhosis,but there is no available universal biomarker of cellular bacterial translocation,for which presepsin may be a *** To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious *** This study included 48 patients with Child–Pugh cirrhosis classes B and C and 15 healthy *** fecal microbiome was assessed using 16S rRNA gene *** levels of presepsin were measured.A total of 22 patients received a probiotic(Saccharomyces boulardii)for 3 *** Presepsin levels were higher in patients with cirrhosis than in healthy individuals[342(91-2875)vs 120(102-141)pg/mL;P=0.048].Patients with elevated presepsin levels accounted for 56.3%of all included *** had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child–Pugh *** with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation,namely Bacilli and Proteobacteria(including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas),and a low abundance of bacteria from the family Lachnospiraceae(including the minor genus Fusicatenibacter),which produce short-chain fatty acids that have a positive effect on intestinal barrier *** presepsin level directly correlated with the relative abundance of Bacilli,Proteobacteria,and inversely correlated with the abundance of Lachnospiraceae and *** 3 months of taking the probiotic,the severity of cirrhosis on the Child–Pugh scale decreased significantly only in the group with elevated presepsin levels[from 9(8-11)to 7(6-9);P=0.004],while there were no significant changes in the group with normal presepsin levels[from 8(7-8)to 7(6-8);P=0.123].A high level of presepsin

关键词： Dysbiosis Gut Intestinal permeability Leaky gut Gut-liver axis Liver Microbiota

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Disease clearance in ulcerative colitis:A new therapeutic target for the future

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World Journal of Gastroenterology 2024年第13期30卷 1801-1809页

作者： Syed Adeel Hassan Neeraj Kapur Fahad Sheikh Anam Fahad Somia Jamal Division of Digestive Disease and Nutrition University of KentuckyLexingtonKY 40536United States Department of Pathology and Laboratory medicine Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkNY 10461United States Division of Primary Care Essen HealthcareNew YorkNY 10457United States Department of internal medicine Karachi Medical and Dental CollegeKarachi 74700SindhPakistan

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and *** has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic ***,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal *** the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic *** recommendations lack consideration of histological *** simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully *** has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

关键词： Inflammatory bowel disease Ulcerative colitis Clinical remission Endoscopic remission Histological remission Mucosal healing Disease clearance

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and medicine TIGEMPozzuoliNaples 80131Italy Medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of internal medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications

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World Journal of Gastroenterology 2024年第22期30卷 2866-2880页

作者： Alfonso Rodriguez-Espada Moises Salgado-de la Mora Briana Mariette Rodriguez-Paniagua Nathaly Limonde la Rosa Monica Itzel Martinez-Gutierrez Santiago Pastrana-Brandes Nalu Navarro-Alvarez Department of molecular Biology Universidad Panamericana School of MedicineCampus MéxicoMexico 03920Mexico Department of internal medicine Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico 14080Mexico Department of Surgery University of Colorado Anschutz Medical CampusDenverCO 80045United States PECEM Facultad de MedicinaUniversidad Nacional Autónoma de MéxicoMexico 04360Mexico Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico 14080Mexico

Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and *** extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains *** liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully *** mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/***,evidence often relies on blood tests with liver enzyme *** this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver *** present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte *** ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular *** also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing *** the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

关键词： Liver SARS-CoV-2 COVID-19 Angiotensin-converting enzyme 2 Histopathology Liver biopsies Liver autopsy In vitro

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Research and Exploration of Ideological and Political Education in the Course of Pathophysiology

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Open Journal of Applied Sciences 2024年第5期14卷 1364-1379页

作者： Tongtong Lv Qiong Wang Yanhua Zhang Xiaochun Peng Department of Pathophysiology School of Basic Medicine Health Science Center Yangtze University Jingzhou China Department of Nursing Health Science Center Yangtze University Jingzhou China Department of physiology School of Basic Medicine Health Science Center Yangtze University Jingzhou China Laboratory of Oncology Center for Molecular Medicine School of Basic Medicine Health Science Center Yangtze University Jingzhou China

Course based ideological and political education (CIPE) is an important way to improve the quality of ideological and political work and talent cultivation. This study explores for the first time the implementation of ideological and political education in the teaching of pathophysiology courses, and also analyzes the evaluation of student psychological status and the importance of mental health education in the implementation of IPE courses. A survey was conducted on 211 students at Yangtze University to understand their motivation and behavior towards learning ideological, political, and pathophysiological courses. In addition, a questionnaire survey was used to explore the relationship between pathophysiology and ideological and political courses, as well as the importance of their satisfaction with the implementation of ideological and political courses in pathophysiology and mental health education. The research results indicate that factors such as educational background and gender differences affect the learning of CIPE. Graduate students are more interested in ideological and political courses, while female students find it difficult to study pathophysiology;In addition, the results of one-way ANOVA indicate that the implementation effect of IPE in pathophysiology courses depends on the level of interest in IPE and pathophysiology courses, the level of consideration for the importance of professional courses, the professional gains after studying pathophysiology, and the level of understanding of the relationship between IPE and CIPE. 81.04% of students believe that in the CIPE process, telling stories by teachers themselves is the most popular way of communication and education. This reflects the importance of mental health education from the perspective of CIPE. In addition, this study also indicates that PBL and flipped classroom teaching models are popular teaching models in CIPE. This study is beneficial for promoting the improvement and implementation

关键词： Pathophysiology Curriculum Ideological and Political Education Higher Education Psychology Questionnaire Survey

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Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： Cecilie Skarstad Norevik Aleksi M.Huuha Ragnhild N.RФsbjФrgen Linda Hildegard Bergersen Kamilla Jacobsen Rodrigo Miguel-dos-Santos Liv Ryan Belma Skender Jose Bianco N.Moreira Asgeir Kobro-Flatmoen Menno P.Witter Nathan Scrimgeour Atefe R.Tari Cardiac Exercise Research Group(CERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of Neurology and Clinical Neurophysiology St.Olavs University Hospital7030TrondheimNorway Institute of Oral Biology University of Oslo0372OsloNorway Department of physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil Centre of molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli Institute for Systems Neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen Centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(p<0.001)in amyloid-β-treated *** vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： Cytokines High-intensity interval training Inflammation Neurons Plasma transfusion

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