{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T05:16:21Z","timestamp":1764479781617,"version":"3.46.0"},"reference-count":55,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960791"],"award-info":[{"award-number":["81960791"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neutropenia is a common complication in oncology patients receiving chemotherapy, and rapid regeneration of functional neutrophils is critical for effective management. Bletilla striata polysaccharide (BSP) has shown therapeutic potential, but its mechanisms and molecular targets remain unclear. Here, we demonstrate that BSP accelerates the recovery of white blood cells, particularly neutrophils, in a chemotherapy-induced neutropenia (CIN) mouse model with cyclophosphamide (CY). The regenerated neutrophils retained phagocytic activity against bacteria, and BSP treatment significantly reduced mortality in the endotoxin-induced mouse death model. Furthermore, BSP enhanced the repopulation of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and promoted cell-cycle entry, resulting in increased frequencies of long-term hematopoietic stem cells (LT-HSCs), multipotent progenitors 2 (MPP2), and MPP3\/4 subsets. Both in vitro colony formation and in vivo competitive transplantation assays confirmed that BSP reshapes hematopoietic reconstitution and corrects aberrant myeloid differentiation. PCR array analysis of HSPCs indicated that this process is mediated by C\/EBP\u03b5 and its downstream genes (LTF, LCN2, and ELANE). Consistently, BSP failed to support myeloid reconstitution following C\/EBP\u03b5 knockdown in vitro. In a C\/EBP\u03b5 knockout mouse model, HSPCs repopulation and regeneration were impaired, and BSP failed to promote neutrophil recovery after CY challenge or the mobilization of MPP2 and MPP3\/4 subsets. The regulatory effects of BSP on C\/EBP\u03b5 target genes were also abolished. In conclusion, our findings identify C\/EBP\u03b5 as a key mediator of BSP activity, driving HSPCs repopulation and restoring hematopoietic function. These results highlight BSP as a potential therapeutic strategy for chemotherapy-induced neutropenia.<\/jats:p>","DOI":"10.3390\/cells14231888","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T08:26:57Z","timestamp":1764318417000},"page":"1888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bletilla Striata Polysaccharide Alleviates Neutropenia by Promoting C\/EBP\u03b5-Dependent Hematopoietic Reconstitution"],"prefix":"10.3390","volume":"14","author":[{"given":"Yaru","family":"Cui","sequence":"first","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM, Jiangxi University of Chinese Medicine, Nanchang 330004, China"},{"name":"Department of Cardiovascular Sciences and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Luo","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM, Jiangxi University of Chinese Medicine, Nanchang 330004, China"},{"name":"Department of Cardiovascular Sciences and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulin","family":"Feng","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilin","family":"Yang","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanying","family":"Chen","sequence":"additional","affiliation":[{"name":"National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Chinese Medicine, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Effective Material Basis of TCM, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-2179","authenticated-orcid":false,"given":"Jun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences and Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/cncr.11882","article-title":"Chemotherapy-Induced Neutropenia: Risks, Consequences, and New Directions for Its Management","volume":"100","author":"Crawford","year":"2004","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nature08533","article-title":"Forcing Cells to Change Lineages","volume":"462","author":"Graf","year":"2009","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1517\/14656566.2015.1055248","article-title":"Therapeutic Strategies for Chemotherapy-Induced Neutropenia in Patients with Solid Tumors","volume":"16","author":"Koinis","year":"2015","journal-title":"Expert Opin. 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