{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:18:17Z","timestamp":1787897897427,"version":"build-2784847793"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune dysfunction and chronic low-grade inflammation contribute substantially to morbidity and cardiovascular risk in patients undergoing hemodialysis (HD). Both exercise-based interventions and melatonin supplementation have demonstrated immunomodulatory and anti-inflammatory potential; however, their combined long-term effects remain unclear. This study investigated whether a 12-week intradialytic concurrent training (ICT) program with melatonin supplementation could improve hematological and immune cell profiles in HD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty HD patients were randomly allocated to ICT with melatonin (ICT-MEL), ICT with placebo (ICT-PLA), or control with placebo (C-PLA). ICT groups trained three times per week. During the intervention, participants received either 3\u00a0mg of melatonin (ICT-MEL) or placebo (ICT-PLA and C-PLA) nightly before nocturnal sleep. Pre- and post-intervention blood samples were analyzed for hematological parameters, adaptive lymphocyte subsets (CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and B cells), innate lymphocytes (natural killer [NK] cells), and monocyte subsets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hematological measures remained stable from pre-to post-intervention across all groups. In contrast, the ICT-MEL intervention induced significant within-group improvements in T-cell immunity, including increases in CD4\n                      <jats:sup>+<\/jats:sup>\n                      percentage (p = 0.007), CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell count (p &amp;lt; 0.05), and CD8\n                      <jats:sup>+<\/jats:sup>\n                      percentage (p &amp;lt; 0.001), accompanied by a decrease in the CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio (p &amp;lt; 0.05). One-way ANOVA of \u0394 changes confirmed a significantly greater reduction in the CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio in ICT-MEL compared with both ICT-PLA and C-PLA (p &amp;lt; 0.05), along with greater increases in CD4\n                      <jats:sup>+<\/jats:sup>\n                      percentage, CD8\n                      <jats:sup>+<\/jats:sup>\n                      count, and CD8\n                      <jats:sup>+<\/jats:sup>\n                      percentage. Following the intervention, CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell count was significantly higher in the ICT-PLA group compared with the C-PLA group (p &amp;lt; 0.05). B-cell percentage increased significantly from pre-to post-intervention only in the ICT-PLA group (p = 0.017), with\n                      <jats:italic>post hoc<\/jats:italic>\n                      analyses indicating a greater increase compared with C-PLA (p &amp;lt; 0.05). NK-cell counts and percentages remained unchanged across all groups. Notably, intermediate monocytes (CD14\n                      <jats:sup>++<\/jats:sup>\n                      CD16\n                      <jats:sup>+<\/jats:sup>\n                      ) decreased significantly from pre-to post-intervention in the ICT-MEL group in both absolute count (p = 0.02) and percentage (p = 0.017), while classical and non-classical monocyte subsets showed no significant changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ICT combined with melatonin supplementation was associated with favorable changes in immune cell populations in patients undergoing HD, including improved T-cell profiles and reduced intermediate monocyte subsets. These findings suggest potentially beneficial immunological adaptations and are consistent with a synergistic effect of exercise and MEL supplementation in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1880592","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:33:49Z","timestamp":1787895229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic effects of intradialytic concurrent training and melatonin supplementation on immune cell adaptations in hemodialysis patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Houssem","family":"Marzougui","sequence":"first","affiliation":[{"name":"Research Laboratory Molecular Bases of Human Pathology LR19ES13, Faculty of Medicine","place":["University of Sfax, Tunisia"]},{"name":"EM2S, LR19JS01, High Institute of Sport and Physical Education of Sfax, University of 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