{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:12:37Z","timestamp":1776265957896,"version":"3.50.1"},"reference-count":26,"publisher":"Centre for Evaluation in Education and Science (CEON\/CEES)","issue":"4","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/BY\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Biochemistry"],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:p>Background: To explore the predictive value of serum forkhead box protein O3 (FOXO3) and Irisin in evaluating posterior cruciate ligament (PCL) and knee functional recovery after surgical treatment of tibial avulsion fractures (TAFs) of the PCL insertion (PCL-TAFs). Methods: In this prospective cohort study, we recruited 125 patients with PCL-TAFs (research group) and 111 healthy controls (control group) between October 2023 and December 2024. Serum FOXO3 and Irisin levels were detected at preoperative baseline and 6-month follow-up. Clinical evaluations included Lysholm scores, knee joint range of motion (ROM), posterior drawer testing, and International Knee Documentation Committee Subjective Knee Form (IKDC) scores. Pearson correlation and ROC analyses examined biomarker associations with functional recovery. Results: PCL-TAF patients exhibited higher preoperative FOXO3 levels than controls, which decreased following treatment (P &amp;lt; 0.05). Conversely, Irisin levels were initially lower than controls but increased post-treatment (P &amp;lt; 0.05). The predictive performance of combined FOXO3 and Irisin yielded 70.59% sensitivity and 94.51% specificity for detecting posterior drawer test positivity (AU C= 0.880). FOXO3 and Irisin together could identify severe dysfunction (IKDC III-IV) with 75.76% sensitivity and 77.17% specificity (AU C= 0.784). Conclusions: Serum FOXO3 and Irisin show clinical utility as potential biomarkers for functional recovery monitoring following PCL-TAF surgery, providing an objective molecular basis, as evidenced by ROC analysis, for the formulation of individualized rehabilitation plans.<\/jats:p>","DOI":"10.5937\/jomb0-60053","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T07:11:36Z","timestamp":1759129896000},"page":"802-810","source":"Crossref","is-referenced-by-count":0,"title":["The role of FOXO3 and Irisin in evaluating posterior cruciate ligament and knee functional recovery after surgical treatment of tibial avulsion fracture of the posterior cruciate ligament insertion"],"prefix":"10.5937","volume":"45","author":[{"given":"Wenbin","family":"Shen","sequence":"first","affiliation":[{"name":"Yiling People's Hospital of Yichang City, Department of Orthopaedics, Yichang, Hubei"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Yiling People's Hospital of Yichang City, Department of Orthopaedics, Yichang, Hubei"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Yiling People's Hospital of Yichang City, Department of Orthopaedics, Yichang, Hubei"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yiling People's Hospital of Yichang City, Department of Orthopaedics, Yichang, Hubei"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3964","reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Li Y, Liu JC, Wu J, Peng X, Sun GJ, Li Z, et al. Bio-mechanical study of posterior cruciate ligament tibial arrest avulsion fracture fixation with triple tibial channel net sutures. Scientific Reports 2023; 13(1): 22980;","DOI":"10.1038\/s41598-023-50479-5"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Xiong HZ, Yang HJ, Du LR, Liu XQ, Sun L, Jin Y, et al. The effect of posterior cruciate ligament tibial avulsion fracture on functional outcomes in knees with concomitant ipsilateral lower limb fractures: a matched-cohort analysis. BMC Musculoskelet Disord 2023; 24(1): 404;","DOI":"10.1186\/s12891-023-06529-0"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Tang J, Zhao J. Arthroscopic Suture-to-Loop Fixation of Posterior Cruciate Ligament Tibial Avulsion Fracture. Arthrosc Tech 2021; 10(6): e1595-e602;","DOI":"10.1016\/j.eats.2021.02.029"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Moran J, Homan MD, LaPrade CM, Kennedy NI, LaPrade RF Treatment of a Failed Posterior Cruciate Ligament Avulsion Fracture Fixation in a Skeletally Immature Patient: A Case Report. JBJS Case Connect 2023; 13(3);","DOI":"10.2106\/JBJS.CC.23.00165"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Kirk B, Feehan J, Lombardi G, Duque G. Muscle, Bone, and Fat Crosstalk: the Biological Role of Myokines, Osteokines, and Adipokines. Curr Osteoporos Rep 2020; 18(4): 388-400;","DOI":"10.1007\/s11914-020-00599-y"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Shan XQ, Zhou N, Pei CX, Lu X, Chen CP, Chen HQ. Tetrandrine induces muscle atrophy involving ROS-mediated inhibition of Akt and FoxO3. Mol Med 2024; 30(1): 218;","DOI":"10.1186\/s10020-024-00981-x"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Wang M, Ren J, Chen X, Liu J, Xu X, Li X, et al. 20(S)-ginsenoside Rg3 promotes myoblast differentiation and protects against myotube atrophy via regulation of the Akt\/mTOR\/FoxO3 pathway. Biochem Pharmacol 2020; 180: 114145;","DOI":"10.1016\/j.bcp.2020.114145"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Momenzadeh S, Jami MS, Jalalvand A, Esfarjani F, Shahabi S, Zamani S. Irisin, A Mediator of Muscle Crosstalk with Other Organs: From Metabolism Regulation to Protective and Regenerative Effects. Curr Protein Pept Sci 2022; 23(2): 89-104;","DOI":"10.2174\/1389203723666220217141918"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"He Z, Li H, Han X, Zhou F, Du J, Yang Y, et al. Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice. Bone 2020; 141: 115573;","DOI":"10.1016\/j.bone.2020.115573"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Gellhaus B, Boker KO, Gsaenger M, Rodenwaldt E, Huser MA, Schilling AF, et al. Foxo3 Knockdown Mediates Decline of Myod1 and Myog Reducing Myoblast Conversion to Myotubes. Cells 2023; 12(17);","DOI":"10.3390\/cells12172167"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Guo A, Li K, Tian HC, Fan Z, Chen QN, Yang YF, et al. FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK\/SIRT-1\/PGC-alpha pathway. J Cell Mol Med 2021; 25(7): 3585-600;","DOI":"10.1111\/jcmm.16448"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Seeber GH, Thalhamer C, Matthijs OC, Doskar W, Sizer PS, Jr., Lazovic D. Clinical Accuracy of the Lateral-Anterior Drawer Test for Diagnosing Posterior Cruciate Ligament Rupture. Sports Med Open 2022; 8(1): 106;","DOI":"10.1186\/s40798-022-00500-4"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Ilahi OA. International Knee Documentation Committee Radiographic Knee Joint Grading More Reliable Than Kellgren-Lawrence Grading and Other Grading Systems. Arthroscopy 2024; 40(5): 1716-9;","DOI":"10.1016\/j.arthro.2023.11.036"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"James EW, Taber CE, Marx RG. Complications Associated with Posterior Cruciate Ligament Reconstruction and Avoiding Them. J Knee Surg 2021; 34(6): 587-91;","DOI":"10.1055\/s-0041-1723016"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"El-Masri BM, Andreasen CM, Laursen KS, Kofod VB, Dahl XG, Nielsen MH, et al. Mapping RANKLand OPG-expressing cells in bone tissue: the bone surface cells as activators of osteoclastogenesis and promoters of the denosumab rebound effect. Bone Res 2024; 12(1): 62;","DOI":"10.1038\/s41413-024-00362-4"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Vumbaca S, Giuliani G, Fiorentini V, Tortolici F, Cerquone Perpetuini A, Riccio F, et al. Characterization of the Skeletal Muscle Secretome Reveals a Role for Extracellular Vesicles and IL1 alpha\/IL1 beta in Restricting Fibro-Adipogenic Progenitor Adipogenesis. Biomolecules 2021; 11(8);","DOI":"10.3390\/biom11081171"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Niu J, Yan T, Guo W, Wang W, Ren T, Huang Y, et al. The COPS3-FOXO3 positive feedback loop regulates autophagy to promote cisplatin resistance in osteosarcoma. Autophagy 2023; 19(6): 1693-710;","DOI":"10.1080\/15548627.2022.2150003"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Jing Y, Zuo Y, Yu Y, Sun L, Yu Z, Ma S, et al. Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging. Protein Cell 2023; 14(7): 497-512;","DOI":"10.1093\/procel\/pwac061"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Cao G, Lin M, Gu W, Su Z, Duan Y, Song W, et al. The rules and regulatory mechanisms of FOXO3 on inflammation, metabolism, cell death and aging in hosts. Life Sci 2023; 328: 121877;","DOI":"10.1016\/j.lfs.2023.121877"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Akbulut T, Cinar V, Aydin S, Yardim M. The role of different exercises in irisin, heat shock protein 70 and some biochemical parameters. J Med Biochem 2022; 41(2): 149-55;","DOI":"10.5937\/jomb0-31551"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Villanueva CJ. Finding a Needle in a Haystack: Identification of a Beige Fat Progenitor. Cell 2020; 182(3): 537-9;","DOI":"10.1016\/j.cell.2020.07.014"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Sun B, Wu H, Lu J, Zhang R, Shen X, Gu Y, et al. Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-beta\/Smad signaling in a growing mouse model of osteogenesis imperfecta. J Orthop Translat 2023; 38: 175-89;","DOI":"10.1016\/j.jot.2022.10.012"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Guo P, Liu L, Yang X, Li M, Zhao Q, Wu H. Irisin improves BBB dysfunction in SAP rats by inhibiting MMP-9 via the ERK\/NF-kappaB signaling pathway. Cell Signal 2022; 93: 110300;","DOI":"10.1016\/j.cellsig.2022.110300"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Helito PVP, Helito CP, Rodrigues MB. Anterolateral ligament MRI of the knee in ACL injuries: MRI abnormalities association with instability. Eur Radiol 2023; 33(2): 1456-64;","DOI":"10.1007\/s00330-022-09062-1"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Gomez-de-Tejada-Romero MJ, Murias-Henriquez C, Saavedra-Santana P, Sablon-Gonzalez N, Abreu DR, Sosa-Henriquez M. Influence of serum uric acid on bone and fracture risk in postmenopausal women. Aging Clinical and Experimental Research 2024; 36(1): 156;","DOI":"10.1007\/s40520-024-02819-2"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Eriksson AL, Friedrich N, Karlsson MK, Ljunggren O, Lorentzon M, Nethander M, et al. Serum Glycine Levels Are Associated With Cortical Bone Properties and Fracture Risk in Men. J Clin Endocrinol Metab 2021; 106(12): e5021-e9;","DOI":"10.1210\/clinem\/dgab544"}],"container-title":["Journal of Medical Biochemistry"],"original-title":["Uloga FOXO3 i irisina u proceni zadnjeg ukr\u0161tenog ligamenta i funkcionalnog oporavka kolena nakon hirur\u0161kog le\u010denja preloma tibijalne avulzije kod insercije zadnjeg ukr\u0161tenog ligamenta"],"language":"en","link":[{"URL":"https:\/\/aseestant.ceon.rs\/index.php\/jomb\/article\/download\/60053\/28839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/scindeks-clanci.ceon.rs\/data\/pdf\/1452-8258\/2026\/1452-82582604802S.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:18:12Z","timestamp":1776262692000},"score":1,"resource":{"primary":{"URL":"https:\/\/scindeks.ceon.rs\/Article.aspx?artid=1452-82582604802S"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.5937\/jomb0-60053","relation":{},"ISSN":["1452-8258","1452-8266"],"issn-type":[{"value":"1452-8258","type":"print"},{"value":"1452-8266","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}