{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:31:10Z","timestamp":1787632270330,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670766"],"award-info":[{"award-number":["81670766"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic foot ulcers (DFUs) are among the most common complications in patients with diabetes and a leading cause of lower extremity amputation. DFUs are exacerbated by prolonged bacterial infection; therefore, there is an urgent need for effective treatments to alleviate the burden associated with this condition. Although autophagy plays a unique role in pathogen phagocytosis and inflammation, its role in diabetic foot infections (DFIs) remains unclear. <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (PA) is the most frequently isolated gram\u2010negative bacterium from DFUs. Here, we evaluated the role of autophagy in ameliorating PA infection in wounds in a diabetic rat model and a bone marrow\u2010derived macrophage (BMDM) hyperglycemia model. Both models were pretreated with or without rapamycin (RAPA) and then infected with or without PA. Pretreatment of rats with RAPA significantly enhanced PA phagocytosis, suppressed wound inflammation, reduced the M1:M2 macrophage ratio, and improved wound healing. In vitro investigation of the underlying mechanisms revealed that enhanced autophagy resulted in decreased macrophage secretion of inflammatory factors such as TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2 but increased that of IL\u201010 in response to PA infection. Additionally, RAPA treatment significantly enhanced autophagy in macrophages by increasing LC3 and beclin\u20101 levels, which led to altered macrophage function. Furthermore, RAPA blocked the PA\u2010induced TLR4\/MyD88 pathway to regulate macrophage polarisation and inflammatory cytokine production, which was validated by RNA interference and use of the autophagy inhibitor 3\u2010methyladenine (3\u2010MA). These findings suggest enhancing autophagy as a novel therapeutic strategy against PA infection to ultimately improve diabetic wound healing.<\/jats:p>","DOI":"10.1111\/wrr.13074","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:11:56Z","timestamp":1678165916000},"page":"305-320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Autophagy ameliorates <i>Pseudomonas aeruginosa<\/i>\u2010infected diabetic wounds by regulating the toll\u2010like receptor 4\/myeloid differentiation factor 88 pathway"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8044-2276","authenticated-orcid":false,"given":"Xiaoyan","family":"Ji","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien\u2010I Memorial Hospital &amp;Tianjin Institute of Endocrinology Tianjin Medical University  Tianjin China"},{"name":"Department of Emergency Ward First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Gastric Surgery Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer  Tianjin China"},{"name":"Key Laboratory of Cancer Prevention and Therapy  Tianjin China"},{"name":"Tianjin's Clinical Research Center for Cancer  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Yu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien\u2010I Memorial Hospital &amp;Tianjin Institute of Endocrinology Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghua","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien\u2010I Memorial Hospital &amp;Tianjin Institute of Endocrinology Tianjin Medical University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32374-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.151"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1962"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jfas.2014.06.011"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.10.029"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2018.02.013"},{"issue":"7","key":"e_1_2_11_8_1","first-page":"827","article-title":"Determination of antimicrobial effect of protamine by transmission electron microscopy and SDS PAGE on Pseudomonas aeruginosa isolates from diabetic foot infection","volume":"22","author":"Aziz M","year":"2019","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjm.2017.09.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534734619884430"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00147"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09782"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00362"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.800813"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73945"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2014.12.005"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S34859"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-416618-9.00002-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2697"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.03.048"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.09.001"},{"issue":"33","key":"e_1_2_11_22_1","first-page":"23","article-title":"Autophagy\u2010related protein expressions in wound granulation tissues from diabetic foot patients infected with Pseudomonas aeruginosa","volume":"2017","author":"Ma YHX","year":"2017","journal-title":"Chin. 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