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The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF\u2010\u03b21, Smad3, IL\u20106, BAX, Wnt\u20107, FN, and miRNA145\u20105p are determined using qRT\u2010PCR. Histology assessment using H&amp;E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup\u2010shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGF\u03b21, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA\u2010145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.<\/jats:p>","DOI":"10.1002\/adbi.202500152","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:29:35Z","timestamp":1754562575000},"source":"Crossref","is-referenced-by-count":1,"title":["Adipose Mesenchymal Stem Cell\u2010Derived Exosomes in Conjunction with Roflumilast Ameliorate Chronic Kidney Disease Through the Modulation of Fibrosis and Inflammation"],"prefix":"10.1002","volume":"9","author":[{"given":"Mohamed","family":"Ali","sequence":"first","affiliation":[{"name":"Biochemistry Department Faculty of Science Zagazig University  Zagazig 44519 Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed H.","family":"Sherif","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Science Zagazig University  Zagazig 44519 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