{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:43:23Z","timestamp":1774878203010,"version":"3.50.1"},"reference-count":33,"publisher":"Baishideng Publishing Group Inc.","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Stem Cells"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n          <jats:p>The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.<\/jats:p>\n          <jats:p>AIM<\/jats:p>\n          <jats:p>To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EXAD) and exogenous mitochondria (mitoEx) protect the lung from ARDS complicated by SS.<\/jats:p>\n          <jats:p>METHODS<\/jats:p>\n          <jats:p>In vitro  study, including L2 cells treated with lipopolysaccharide (LPS) and in vivo  study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EXAD), 4 (ARDS-SS + mitoEx), and 5 (ARDS-SS + EXAD + mitoEx), were included in the present study.<\/jats:p>\n          <jats:p>RESULTS<\/jats:p>\n          <jats:p>In vitro  study showed an abundance of mitoEx found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (P  &lt; 0.001). The protein levels of inflammation [interleukin (IL)-1\u03b2\/tumor necrosis factor (TNF)-\u03b1\/nuclear factor-\u03baB\/toll-like receptor (TLR)-4\/matrix-metalloproteinase (MMP)-9\/oxidative-stress (NOX-1\/NOX-2)\/apoptosis (cleaved-caspase3\/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EXAD treatment than without EXAD treatment, whereas the protein expressions of cellular junctions [occluding\/\u03b2-catenin\/zonula occludens (ZO)-1\/E-cadherin] exhibited an opposite pattern of inflammation (all P  &lt; 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+\/CD14+\/CD68+\/CD11b\/c+\/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all P  &lt; 0.0001), whereas arterial oxygen-saturation (SaO2%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury\/fibrosis area and inflammatory\/DNA-damaged markers (CD68+\/\u03b3-H2AX) displayed an identical pattern of SaO2% among the groups (all P  &lt; 0.0001). The protein expressions of inflammatory (TLR-4\/MMP-9\/IL-1\u03b2\/TNF-\u03b1)\/oxidative stress (NOX-1\/NOX-2\/p22phox\/oxidized protein)\/mitochondrial-damaged (cytosolic-cytochrome-C\/dynamin-related protein 1)\/autophagic (beclin-1\/Atg-5\/ratio of LC3B-II\/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1\/Nrf-2]\/cellular junctions (ZO-1\/E-cadherin)\/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all P  &lt; 0.0001).<\/jats:p>\n          <jats:p>CONCLUSION<\/jats:p>\n          <jats:p>Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.<\/jats:p>","DOI":"10.4252\/wjsc.v16.i6.690","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T03:15:49Z","timestamp":1719285349000},"page":"690-707","source":"Crossref","is-referenced-by-count":2,"title":["Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis"],"prefix":"10.4252","volume":"16","author":[{"given":"Kun-Chen","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Feng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jui-Ning","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John Y","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Ju","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Lin","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Hsun","family":"Sung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hon-Kan","family":"Yip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2060","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31827c09f8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.116.suppl_1.74S-a"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050333"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.2.525"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421801"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901686"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/cc11144"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800385"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12199"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000617"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19312"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004285"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/5425346"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60331"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1420.016"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1977.116.4.589"},{"key":"B17","unstructured":"Yip HK, Shao PL, Wallace CG, Sheu JJ, Sung PH, Lee MS. 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