{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:20:05Z","timestamp":1790814005464,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T00:00:00Z","timestamp":1521936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To detect the expression of high\u2010mobility group box protein 1 (HMGB1) and toll\u2010like receptor 4 (TLR4) and their downstream signaling factors\u2014myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF\u2010\u03baB), and tumor necrosis factor alpha (TNF\u2010\u03b1)\u2014in the sera of patients with Parkinson's disease (PD) in order to evaluate the relationship of the HMGB1\u2013TLR4 axis with PD development and progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The serum HMGB1 and TLR4 protein levels of 120 patients with PD and 100 healthy volunteers were measured using double\u2010antibody sandwich ELISA, and their correlations with PD staging, disease duration, drug treatment effectiveness, and clinical classification were analyzed. In addition, their correlations with the key downstream factors of the HMGB1\u2013TLR4 axis (MyD88, NF\u2010\u03baB, and TNF\u2010\u03b1) were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HMGB1 and TLR4 expressions were higher in the peripheral blood of patients with PD than in healthy volunteers. PD patients with poor drug treatment outcomes had significantly higher HMGB1 and TLR4 expressions than PD patients with stable drug treatment outcomes. Higher HMGB1 and TLR4 expressions were found in patients at higher PD stages, and patients with &gt;4\u2010year disease duration had significantly higher HMGB1 and TLR4 expressions than patients with &lt;4\u2010year disease duration. No significant difference in HMGB1 and TLR4 expressions was found among patients with tremor\u2010dominant, akinetic\u2010rigid, and mixed subtypes of PD. NF\u2010\u03baB and TNF\u2010\u03b1 expressions were positively correlated with high expression of the HMGB1\u2013TLR4 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High expression of the HMGB1\u2013TLR4 axis is closely associated with PD development, progression, drug treatment effectiveness, staging, and disease duration and has great significance for PD diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.948","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T14:37:01Z","timestamp":1521988621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["High expression of the HMGB1\u2013TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6483-7286","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neonatologe The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neonatologe The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neonatologe The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaobin","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Neonatologe The Second Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140918"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E16-02-0126"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.08.001"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31895"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3732-10.2011"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.12.001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1206751"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.10.014"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ensci.2016.11.010"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0884533610373932"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-016-0307-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0822-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00897-16"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2015.05.011"},{"issue":"5","key":"e_1_2_6_16_1","first-page":"4363","article-title":"Advanced glycation end products and lipopolysaccharides stimulate interleukin\u20106 secretion via the RAGE\/TLR4\u2010NF\u2010\u00ce\u00baB\u2010ROS pathways and resveratrol attenuates these inflammatory responses in mouse macrophages","volume":"14","author":"Ohtsu A.","year":"2017","journal-title":"Experimental & Therapeutic Medicine"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04120.x"},{"issue":"3","key":"e_1_2_6_18_1","first-page":"507","article-title":"Lecture: Non\u2010motor symptoms of Parkinson's disease","volume":"16","author":"Pfeiffer R.","year":"2006","journal-title":"Movement Disorders"},{"key":"e_1_2_6_19_1","first-page":"CD008454","article-title":"Non\u2010steroidal anti\u2010inflammatory drugs as disease\u2010modifying agents for Parkinson's disease: Evidence from observational studies","volume":"11","author":"Rees K.","year":"2011","journal-title":"Cochrane Database Systematic Review"},{"key":"e_1_2_6_20_1","first-page":"S626","article-title":"HMGB\u20101 \u2010 an inflammatory mediator in MPTP\u2010induced neuronal damage","volume":"25","author":"Sathe K.","year":"2010","journal-title":"Movement Disorders"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i25.7764"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.863876"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2014.2089"},{"issue":"12","key":"e_1_2_6_24_1","first-page":"1811","article-title":"Nonmotor symptoms of Parkinson's disease","volume":"6","author":"Zesiewicz T. 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