{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:08:00Z","timestamp":1790168880644,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cyclophosphamide (CTX) is a widely used chemotherapeutic agent, but its efficacy is often limited by leukopenia, a common adverse effect for which effective preventive strategies are currently lacking. In this study, oligopeptides were prepared from a blend of three edible tortoise species (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Cuora trifasciata<\/jats:italic>\n                    <\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Mauremys mutica<\/jats:italic>\n                    <\/jats:styled-content>\n                    , and\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Chinemys reevesii<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) and evaluated for their potential to alleviate CTX\u2010induced leukopenia. The resulting Tortoise Oligopeptides (TOPs) were characterized primarily as small molecules with molecular weights under 5\u2009kDa and peptide lengths between 4 and 15 amino acids, rich in glycine, glutamic acid, and proline. In a mouse model, TOPs administration significantly ameliorated CTX\u2010induced leukopenia in a dose\u2010dependent manner, attenuated pathological damage in the spleen and femur, and correlated with elevated serum levels of IL\u20104, IL\u20101\u03b2, TNF\u2010\u03b1, and IFN\u2010\u03b3. In CTX\u2010treated tumor\u2010bearing mice, TOPs not only reduced leukopenia but also enhanced the antitumor efficacy of CTX. Correlation analyses linked leukocyte recovery to increased relative abundance of gut microbiota genera such as\n                    <jats:italic>Colidextribacter<\/jats:italic>\n                    ,\n                    <jats:italic>Tyzzerella<\/jats:italic>\n                    ,\n                    <jats:italic>Prevotellaceae_UCG_001<\/jats:italic>\n                    , and\n                    <jats:italic>Rikenella<\/jats:italic>\n                    . KEGG pathway analysis and fecal microbiota transplantation (FMT) experiments indicated that TOPs alleviate CTX\u2010induced granulocytopenia partly through modulation of the gut microbiota. Additionally, LC\u2013MS\/MS sequencing combined with bioinformatic prediction and molecular docking identified several peptides\u2014including PAIPAPPVGPGPK, FSFPTLPF, and PGLPFHP\u2014with high binding affinity to key tumor targets (BCL\u20102, MDM2, EGFR), suggesting intrinsic antitumor properties. These findings indicate that TOPs may serve as a specialized medical food to mitigate CTX\u2010induced leukopenia through multimodal mechanisms involving immunonutrition, gut microbiota regulation, and direct antitumor peptide effects.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71078","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T06:37:44Z","timestamp":1760683064000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tortoise Oligopeptides Augment Cyclophosphamide's Antitumor Activity Through Dual Modulation of Therapeutic Efficacy and Hematologic Toxicity"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhuotao","family":"Fu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Guangdong Clinical Research Academy of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Yu","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Meng","sequence":"additional","affiliation":[{"name":"The Affiliated TCM Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Haikou Hospital of Traditional Chinese Medicine  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojun","family":"Huang","sequence":"additional","affiliation":[{"name":"Haikou Hospital of Traditional Chinese Medicine  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Li","sequence":"additional","affiliation":[{"name":"Haikou Hospital of Traditional Chinese Medicine  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linchun","family":"Fu","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7014-3643","authenticated-orcid":false,"given":"Zhitong","family":"Deng","sequence":"additional","affiliation":[{"name":"Haikou Hospital of Traditional Chinese Medicine  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c04778"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2009.146"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3967\/bes2014.012"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2023.107693"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2023.102541"},{"key":"e_1_2_11_7_1","unstructured":"He S.2015.\u201cSeparation Purification of Anticancer Pepetides From Curotrifasciata and Preparation of 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