{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:14:35Z","timestamp":1787724875967,"version":"build-2784847793"},"reference-count":50,"publisher":"Impact Journals, LLC","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging"],"published-print":{"date-parts":[[2024,1,31]]},"DOI":"10.18632\/aging.205432","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T12:03:41Z","timestamp":1706529821000},"page":"1374-1389","source":"Crossref","is-referenced-by-count":19,"title":["Treadmill exercise can regulate the redox balance in the livers of APP\/PS1 mice and reduce LPS accumulation in their brains through the gut-liver-kupffer cell axis"],"prefix":"10.18632","volume":"16","author":[{"given":"Shunling","family":"Yuan","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Sports Vocational College, Changsha 410019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialun","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhe","family":"Tang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Wu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyuan","family":"Meng","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Jian","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Lei","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changfa","family":"Tang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha 410199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7892","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias. Nat Genet. 2022; 54:412-36. https:\/\/doi.org\/10.1038\/s41588-022-01024-z.","DOI":"10.1038\/s41588-022-01024-z"},{"key":"2","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1177\/1039856218762308","article-title":"Alzheimer\u2019s disease: clinical update on epidemiology, pathophysiology and diagnosis.","volume":"2","author":"Looi","year":"2018","journal-title":"Australas Psychiatry"},{"key":"3","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1007\/s11427-016-5083-9","article-title":"Alzheimer\u2019s disease and gut microbiota.","volume":"5","author":"Jin","year":"2016","journal-title":"Sci China Life Sci"},{"key":"4","doi-asserted-by":"publisher","first-page":"e100751","DOI":"10.1136\/gpsych-2022-100751","article-title":"The China Alzheimer Report 2022.","volume":"3","author":"Cui","year":"2022","journal-title":"Gen Psychiatr"},{"key":"5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","article-title":"The global prevalence of dementia: a systematic review and metaanalysis.","volume":"9","author":"Ferri","year":"2013","journal-title":"Alzheimers Dement"},{"key":"6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13195-022-00985-x","article-title":"A deep learning MRI approach outperforms other biomarkers of prodromal Alzheimer\u2019s disease.","volume":"1","author":"Small","year":"2022","journal-title":"Alzheimers Res Ther"},{"key":"7","doi-asserted-by":"publisher","first-page":"12717","DOI":"10.1021\/acs.jafc.1c04687","article-title":"Sesamol Attenuates Amyloid Peptide Accumulation and Cognitive Deficits in APP\/PS1 Mice: The Mediating Role of the Gut-Brain Axis.","volume":"6","author":"Yuan","year":"2021","journal-title":"J Agric Food Chem"},{"key":"8","doi-asserted-by":"publisher","first-page":"e197978","DOI":"10.1001\/jamanetworkopen.2019.7978","article-title":"Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.","volume":"2","author":"Shaw","year":"2019","journal-title":"JAMA Netw Open"},{"key":"9","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/cells9040853","article-title":"Gut Microbiota, Its Role in Induction of Alzheimer\u2019s Disease Pathology, and Possible Therapeutic Interventions: Special Focus on Anthocyanins.","volume":"9","author":"Kim","year":"2020","journal-title":"Cells"},{"key":"10","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1097\/CM9.0000000000002212","article-title":"Gut microbiota: a new insight into neurological diseases.","volume":"13","author":"Xie","year":"2023","journal-title":"Chin Med J (Engl)"},{"key":"11","doi-asserted-by":"publisher","first-page":"634069","DOI":"10.3389\/fcell.2020.634069","article-title":"Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer\u2019s Disease.","volume":"8","author":"Wu","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"12","doi-asserted-by":"publisher","first-page":"318","DOI":"10.3389\/fcimb.2017.00318","article-title":"Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer\u2019s Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus.","volume":"7","author":"Lukiw","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"13","doi-asserted-by":"publisher","first-page":"G377","DOI":"10.1152\/ajpgi.00147.2005","article-title":"On the role and fate of LPS-dephosphorylating activity in the rat liver.","volume":"29","author":"Poelstra","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"14","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fcimb.2020.00022","article-title":"Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins-Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain.","volume":"1","author":"Lukiw","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"15","doi-asserted-by":"publisher","first-page":"1149366","DOI":"10.3389\/fimmu.2023.1149366","article-title":"Regulatory mechanisms of macrophage polarization in adipose tissue.","volume":"1","author":"Hu","year":"2023","journal-title":"Front Immunol"},{"key":"16","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1002\/path.4133","article-title":"Macrophage plasticity and polarization in tissue repair and remodelling.","volume":"22","author":"Locati","year":"2013","journal-title":"J Pathol"},{"key":"17","doi-asserted-by":"publisher","first-page":"4298","DOI":"10.3390\/nu14204298","article-title":"Targeting Alzheimer\u2019s Disease: The Critical Crosstalk between the Liver and Brain.","volume":"1","author":"Zong","year":"2022","journal-title":"Nutrients"},{"key":"18","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.3390\/antiox11051028","article-title":"The Systemic Effects of Exercise on the Systemic Effects of Alzheimer\u2019s Disease.","volume":"1","author":"Radak","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"19","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.3390\/nu15112495","article-title":"Impact of Diet and Exercise Interventions on Cognition and Brain Health in Older Adults: A Narrative Review.","volume":"1","author":"Szabo-Reed","year":"2023","journal-title":"Nutrients"},{"key":"20","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.3390\/nu14194134","article-title":"Treadmill Exercise Modulates Intestinal Microbes and Suppresses LPS Displacement to Alleviate Neuroinflammation in the Brains of APP\/PS1 Mice.","volume":"1","author":"Liu","year":"2022","journal-title":"Nutrients"},{"key":"21","doi-asserted-by":"publisher","first-page":"110375","DOI":"10.1016\/j.intimp.2023.110375","article-title":"Leonurine alleviates acetaminophen-induced acute liver injury by regulating the PI3K\/AKT signaling pathway in mice.","volume":"12","author":"Chen","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jcmgh.2023.03.007","article-title":"AXL Expression on Homeostatic Resident Liver Macrophages Is Reduced in Cirrhosis Following GAS6 Production by Hepatic Stellate Cells.","volume":"1","author":"Tatham","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"23","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s13054-022-04090-1","article-title":"The gut-liver axis in sepsis: interaction mechanisms and therapeutic potential.","volume":"2","author":"Zhang","year":"2022","journal-title":"Crit Care"},{"key":"24","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/ni1246","article-title":"Lipopolysaccharide deacylation by an endogenous lipase controls innate antibody responses to Gram-negative bacteria.","volume":"6","author":"Munford","year":"2005","journal-title":"Nat Immunol"},{"key":"25","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.tips.2022.12.003","article-title":"Advances and challenges in therapeutic targeting of NRF2.","volume":"4","author":"Copple","year":"2023","journal-title":"Trends Pharmacol Sci"},{"key":"26","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1136\/gut.2007.122168","article-title":"Immunology of the gut and liver: a love\/hate relationship.","volume":"5","author":"Curbishley","year":"2008","journal-title":"Gut"},{"key":"27","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40035-020-00195-1","article-title":"Peripheral clearance of brain-derived A\u03b2 in Alzheimer\u2019s disease: pathophysiology and therapeutic perspectives.","volume":"9","author":"Wang","year":"2020","journal-title":"Transl Neurodegener"},{"key":"28","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/nrneurol.2017.147","article-title":"A systemic view of Alzheimer disease - insights from amyloid-\u03b2 metabolism beyond the brain.","volume":"1","author":"Wang","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"29","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s00401-015-1477-1","article-title":"Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer\u2019s disease.","volume":"13","author":"Wang","year":"2015","journal-title":"Acta Neuropathol"},{"key":"30","doi-asserted-by":"publisher","first-page":"7451","DOI":"10.3390\/ijms22147451","article-title":"Liver Bile Acid Changes in Mouse Models of Alzheimer\u2019s Disease.","volume":"2","author":"Combs","year":"2021","journal-title":"Int J Mol Sci"},{"key":"31","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1021\/acs.jproteome.8b00847","article-title":"Tissue-Specific Metabolomics Analysis Identifies the Liver as a Major Organ of Metabolic Disorders in Amyloid Precursor Protein\/Presenilin 1 Mice of Alzheimer\u2019s Disease.","volume":"1","author":"Gao","year":"2019","journal-title":"J Proteome Res"},{"key":"32","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.3233\/JAD-201241","article-title":"Low Liver Enzymes and Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study.","volume":"7","author":"Heiss","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"33","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jalz.2008.10.004","article-title":"Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer\u2019s disease.","volume":"5","author":"Quinn","year":"2009","journal-title":"Alzheimers Dement"},{"key":"34","doi-asserted-by":"publisher","first-page":"117599","DOI":"10.1016\/j.lfs.2020.117599","article-title":"New molecular and biochemical insights of doxorubicin-induced hepatotoxicity.","volume":"25","author":"Valsala Gopalakrishnan","year":"2020","journal-title":"Life Sci"},{"key":"35","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1476-5926-10-2","article-title":"Characterization of Kupffer cells in livers of developing mice.","volume":"1","author":"Robertson","year":"2011","journal-title":"Comp Hepatol"},{"key":"36","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.3389\/fimmu.2019.03112","article-title":"Macrophage Phenotype and Function in Liver Disorder.","volume":"1","author":"Gao","year":"2020","journal-title":"Front Immunol"},{"key":"37","doi-asserted-by":"publisher","first-page":"716","DOI":"10.3390\/antiox9080716","article-title":"Current Landscape of NRF2 Biomarkers in Clinical Trials.","volume":"9","author":"Kensler","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"38","doi-asserted-by":"publisher","first-page":"e0207949","DOI":"10.1371\/journal.pone.0207949","article-title":"NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism.","volume":"1","author":"Kapuy","year":"2018","journal-title":"PLoS One"},{"key":"39","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.freeradbiomed.2007.02.001","article-title":"Moderate exercise is an antioxidant: upregulation of antioxidant genes by training.","volume":"4","author":"Vi\u00f1a","year":"2008","journal-title":"Free Radic Biol Med"},{"key":"40","doi-asserted-by":"publisher","first-page":"1117666","DOI":"10.3389\/fphys.2023.1117666","article-title":"Maternal high-intensity interval training as a suitable approach for offspring\u2019s heart protection in rat: evidence from oxidative stress and mitochondrial genes.","volume":"1","author":"Salehi","year":"2023","journal-title":"Front Physiol"},{"key":"41","doi-asserted-by":"publisher","first-page":"1052608","DOI":"10.3389\/fphys.2022.1052608","article-title":"Exercise alleviates diabetic complications by inhibiting oxidative stress-mediated signaling cascade and mitochondrial metabolic stress in GK diabetic rat tissues.","volume":"1","author":"Raza","year":"2022","journal-title":"Front Physiol"},{"key":"42","doi-asserted-by":"publisher","first-page":"4646","DOI":"10.1021\/acs.jafc.3c00652","article-title":"Bifidobacterium breve HNXY26M4 Attenuates Cognitive Deficits and Neuroinflammation by Regulating the Gut-Brain Axis in APP\/PS1 Mice.","volume":"7","author":"Chen","year":"2023","journal-title":"J Agric Food Chem"},{"key":"43","doi-asserted-by":"publisher","first-page":"960026","DOI":"10.3389\/fnins.2022.960026","article-title":"Benign regulation of the gut microbiota: The possible mechanism through which the beneficial effects of manual acupuncture on cognitive ability and intestinal mucosal barrier function occur in APP\/PS1 mice.","volume":"1","author":"Li","year":"2022","journal-title":"Front Neurosci"},{"key":"44","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1212\/WNL.0000000000003391","article-title":"Gram-negative bacterial molecules associate with Alzheimer disease pathology.","volume":"8","author":"Sharp","year":"2016","journal-title":"Neurology"},{"key":"45","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1097\/00001756-200006050-00032","article-title":"LPS-induced neuroinflammatory effects do not recover with time.","volume":"1","author":"Wenk","year":"2000","journal-title":"Neuroreport"},{"key":"46","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.bbr.2012.01.010","article-title":"Prolonged elevation in hippocampal A\u03b2 and cognitive deficits following repeated endotoxin exposure in the mouse.","volume":"22","author":"Chumley","year":"2012","journal-title":"Behav Brain Res"},{"key":"47","doi-asserted-by":"publisher","first-page":"554","DOI":"10.3389\/fphar.2020.00554","article-title":"Like Cures Like: Pharmacological Activity of Anti-Inflammatory Lipopolysaccharides From Gut Microbiome.","volume":"1","author":"Lu","year":"2020","journal-title":"Front Pharmacol"},{"key":"48","doi-asserted-by":"publisher","first-page":"1146946","DOI":"10.3389\/fnins.2023.1146946","article-title":"Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role.","volume":"1","author":"Meng","year":"2023","journal-title":"Front Neurosci"},{"key":"49","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1007\/s00401-023-02559-z","article-title":"Physiological \u03b2-amyloid clearance by the liver and its therapeutic potential for Alzheimer\u2019s disease.","volume":"14","author":"Shen","year":"2023","journal-title":"Acta Neuropathol"},{"key":"50","doi-asserted-by":"publisher","first-page":"9921","DOI":"10.3390\/ijms23179921","article-title":"Aerobic Exercise Alleviates Abnormal Autophagy in Brain Cells of APP\/PS1 Mice by Upregulating AdipoR1 Levels.","volume":"2","author":"Liu","year":"2022","journal-title":"Int J Mol Sci"}],"container-title":["Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.aging-us.com\/lookup\/doi\/10.18632\/aging.205432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T17:55:07Z","timestamp":1707155707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aging-us.com\/lookup\/doi\/10.18632\/aging.205432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,29]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,1,31]]}},"alternative-id":["205432","38295303"],"URL":"https:\/\/doi.org\/10.18632\/aging.205432","relation":{},"ISSN":["1945-4589"],"issn-type":[{"value":"1945-4589","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,29]]}}}