{ "abstract": "Diabetic peripheral neuropathy (DPN) affects up to half of people with diabetes and lacks disease-modifying therapy. Here, we profiled MSC-EV biodistribution and multiomic programs across diabetic models, with key nerve repair established in db/db mice and corroborated in high-fat diet/streptozotocin- and methionine-choline-deficient mice. Systemically administered EVs predominantly accumulated in the liver and improved peripheral nerve structure and function, with benefits supported by glycemia-controlled or glycemia-adjusted analyses rather than being fully explained by systemic glycemic changes. EV treatment was associated with reduced circulating injury markers, attenuated spinal inflammatory responses, and improved endothelial junction integrity. Mechanistically, EV-encapsulated miR-24-3p repressed hepatic CD74, coinciding with reduced MHC II/NF-κB activity in macrophages. Hepatic CD74 overexpression promoted systemic inflammation and peripheral nerve injury, whereas pharmacologic NF-κB inhibition recapitulated EV-associated benefits. Together, these data define a liver-to-nerve causal axis and support EV-mediated restraint of hepatic CD74-NF-κB signaling as a cross-organ strategy for DPN repair.", "abstract_shown": true, "affiliations": [ "Key Laboratory of Central Nervous System Diseases, Xi’an Jiaotong University, Xi’an 71003, China.", "Department of Neurosurgery, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an 71003, China.", "Shaanxi LonEV Biotechnology Limited Company, Xi’an 712046, China.", "Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072 Shaanxi, China.", "Department of Nuclear Medicine, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an 71003, China.", "Western University of Health Sciences Medical Center, Specialty Clinics, WesternU Health, 795 E Second Street, Suite 7, 2nd Floor, Pomona, CA 91766, USA.", "MoodNote LLC, P.O. Box 9287, Newport Beach, CA 92658, USA.", "6th Department of Health Care, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, PLA General Hospital, Beijing 100853, China.", "Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an 710032, China." ], "article_type": "Research Article", "arxiv": null, "author_total": 16, "authors": [ { "affs": [ 0, 1 ], "name": "Hao Yang", "orcid": "0009-0002-3793-853X" }, { "affs": [ 0, 1 ], "name": "Yu Miao", "orcid": "0009-0001-6471-7591" }, { "affs": [ 0, 1, 2 ], "name": "Panpan Meng", "orcid": "0009-0004-9511-6555" }, { "affs": [ 3, 4 ], "name": "Jinyun Niu", "orcid": "0009-0006-9761-1343" }, { "affs": [ 0, 1 ], "name": "Junxiu Xi", "orcid": "0009-0003-3236-2647" }, { "affs": [ 0, 1 ], "name": "Zhiying Zou", "orcid": "0009-0004-2642-1871" }, { "affs": [ 1 ], "name": "Yue Hei", "orcid": "0000-0003-2375-8933" }, { "affs": [ 0, 1 ], "name": "Jiahui Zhao", "orcid": "0009-0002-1620-8028" }, { "affs": [ 1 ], "name": "Qiang Luo", "orcid": "0009-0002-1872-9935" }, { "affs": [ 0 ], "name": "Sirou Huang", "orcid": "0009-0004-5733-4594" }, { "affs": [ 0, 1 ], "name": "Mingjun Hu", "orcid": "0009-0008-1131-5530" }, { "affs": [ 3 ], "name": "Lianbing Zhang", "orcid": "0000-0001-7803-6028" }, { "affs": [ 5, 6 ], "name": "Andrius Baskys", "orcid": "0000-0001-6280-5005" }, { "affs": [ 7 ], "name": "Yabin Wang", "orcid": "0000-0002-7966-6117" }, { "affs": [ 8 ], "name": "Xia Li", "orcid": "0000-0003-2679-9917" }, { "affs": [ 0, 1 ], "name": "Qianfa Long", "orcid": "0000-0001-8848-9688" } ], "bibtex": "https://research.draconitic.com/paper/346gv4sf011vh.bib", "cited_by": 0, "doi": "10.1126/sciadv.aei3312", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721967/?tool=EBI", "id": "346gv4sf011vh", "issns": [ "2375-2548" ], "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aei3312", "language": "eng", "licence": "CC-BY-NC", "licence_label": "CC BY-NC", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Biomedicine and Life Sciences" ], [ "heading", "Health and Medicine" ], [ "heading", "Immunology" ], [ "heading", "Research Article" ], [ "heading", "SciAdv r-articles" ] ], "openalex": null, "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721967/pdf/?tool=EBI", "pmcid": "PMC13721967", "pmid": "42962021", "published": "2026-10-30", "publisher": "American Association for the Advancement of Science (AAAS)", "ris": "https://research.draconitic.com/paper/346gv4sf011vh.ris", "sources": [ { "first_seen": "2026-10-31T00:20:30Z", "native_id": "10.1126/sciadv.aei3312", "source": "feed-science", "url": "https://www.science.org/doi/abs/10.1126/sciadv.aei3312" }, { "first_seen": "2026-10-31T00:20:32Z", "native_id": "10.1126/sciadv.aei3312", "source": "crossref", "url": "https://www.science.org/doi/10.1126/sciadv.aei3312" }, { "first_seen": "2026-10-31T12:21:37Z", "native_id": "PMC:PMC13721967", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13721967" }, { "first_seen": "2026-11-02T03:21:21Z", "native_id": "MED:42962021", "source": "europepmc", "url": "https://europepmc.org/article/MED/42962021" }, { "first_seen": "2026-11-03T12:22:34Z", "native_id": "PMC13721967", "source": "pmc", "url": "https://doi.org/10.1126/sciadv.aei3312" } ], "subjects": [ { "field": "biology", "origin": "heading:Immunology", "subfield": "immunology" } ], "title": "Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy", "title_text": "Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy", "type": "peer-reviewed", "updated_at": "2026-11-03T12:22:34Z", "url": "https://research.draconitic.com/paper/346gv4sf011vh", "venue": "Science Advances", "versions": [] }