{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:22:44Z","timestamp":1775766164845,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"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":["41806153"],"award-info":[{"award-number":["41806153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The aim of this study was to explore the immunomodulatory effects of the Meretrix meretrix oligopeptide (MMO, QLNWD) in cyclophosphamide (CTX)-induced immune-deficient mice. Compared to untreated, CTX-induced immune-deficient mice, the spleen and thymus indexes of mice given moderate (100 mg\/kg) and high (200 mg\/kg) doses of MMO were significantly higher (p &lt; 0.05), and body weight loss was alleviated. Hematoxylin-eosin (H&amp;E) staining revealed that MMO reduced spleen injury, thymus injury, and liver injury induced by CTX in mice. Furthermore, MMO boosted the production of immunoglobulin G (IgG) and hemolysin in the serum and promoted the proliferation and differentiation of spleen T-lymphocytes. Taken together, our findings suggest that MMO plays a vital role in protection against immunosuppression in CTX-induced immune-deficient mice and could be a potential immunomodulatory candidate for use in functional foods or immunologic adjuvants.<\/jats:p>","DOI":"10.3390\/molecules24244452","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T11:16:23Z","timestamp":1575544583000},"page":"4452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Immunomodulatory Effects of the Meretrix Meretrix Oligopeptide (QLNWD) on Immune-Deficient Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Ye","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglei","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Hailisheng Group Co., Ltd., Zhoushan 316021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Tian","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-208X","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guofang","family":"Ding","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuisu","family":"Yang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.cell.2018.05.049","article-title":"New Flavors in Immunomodulation","volume":"173","author":"Deguine","year":"2018","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1134\/S207908641806004X","article-title":"Immunomodulating Effects of Cold Stress","volume":"8","author":"Gein","year":"2018","journal-title":"Biol. Bull. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.cofs.2018.04.006","article-title":"Role of probiotics and prebiotics in immunomodulation","volume":"20","author":"Yahfoufi","year":"2018","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11434-016-1105-z","article-title":"Immunomodulation of artemisinin and its derivatives","volume":"61","author":"Yao","year":"2016","journal-title":"Sci. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"620","DOI":"10.3109\/07357909409023048","article-title":"Application of chemical immunomodulators to the treatment of cancer and AIDS","volume":"12","author":"Turowski","year":"1994","journal-title":"Cancer Invest."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1016\/j.bmc.2019.05.050","article-title":"Opportunities and challenges for the development of covalent chemical immunomodulators","volume":"27","author":"Backus","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.semcancer.2012.02.008","article-title":"New insights into chronic inflammation-induced immunosuppression","volume":"22","author":"Kanterman","year":"2012","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.bcab.2019.01.008","article-title":"A comprehensive review on Phyllanthus derived natural products as potential chemotherapeutic and immunomodulators for a wide range of human disease","volume":"17","author":"Seyed","year":"2019","journal-title":"Biocatal. Agr. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jpba.2005.11.012","article-title":"HPLC determination of phenolic acids and antioxidant activity in concentrated peat extract\u2014a natural immunomodulator","volume":"41","author":"Tarnawski","year":"2006","journal-title":"J. Pharmaceut. Biomed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.foodres.2017.06.053","article-title":"The immune-enhancing activity of Cervus nippon mantchuricus extract (NGE) in RAW264.7 macrophage cells and immunosuppressed mice","volume":"99","author":"Hong","year":"2017","journal-title":"Food Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.virusres.2008.12.013","article-title":"A natural tetranortriterpenoid with immunomodulating properties as a potential anti-HSV agent","volume":"141","author":"Bueno","year":"2009","journal-title":"Virus Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.3390\/md9061142","article-title":"Antioxidant and Antiproliferative Activities of Heated Sterilized Pepsin Hydrolysate Derived from Half-Fin Anchovy (Setipinna taty)","volume":"9","author":"Song","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Huang, F., Zhao, S., Yu, F., Yang, Z., and Ding, G. (2017). Protective Effects and Mechanism of Meretrix meretrix Oligopeptides against Nonalcoholic Fatty Liver Disease. Mar. Drugs, 15.","DOI":"10.3390\/md15020031"},{"key":"ref_14","first-page":"771","article-title":"A novel anti-proliferative pentapeptide (ILYMP) isolated fromCyclina sinensisprotein hydrolysate induces apoptosis of DU-145 prostate cancer cells","volume":"18","author":"Yu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_15","first-page":"375","article-title":"Bioactive Peptides:Absorption, Utilization and Functionality","volume":"34","author":"Pang","year":"2013","journal-title":"Food Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.foodchem.2008.07.086","article-title":"Immunomodulatory effects of marine oligopeptide preparation from Chum Salmon (Oncorhynchus keta) in mice","volume":"113","author":"Yang","year":"2009","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103420","DOI":"10.1016\/j.jff.2019.103420","article-title":"Immunomodulatory effects of collagen hydrolysates from yak (Bos grunniens) bone on cyclophosphamide-induced immunosuppression in BALB\/c mice","volume":"60","author":"Gao","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, W., Ye, S.W., Zhang, Z.W., Tang, J.C., Jin, H.X., Huang, F.F., Yang, Z.S., Tang, Y.P., Chen, Y., and Ding, G.F. (2019). Purification and Characterization of a Novel Pentadecapeptide from Protein Hydrolysates of Cyclina sinensis and Its Immunomodulatory Effects on RAW264.7 Cells. Mar. Drugs, 17.","DOI":"10.3390\/md17010030"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103408","DOI":"10.1016\/j.jff.2019.06.010","article-title":"Immunoenhancement effects of pentadecapeptide derived from Cyclina sinensis on immune-deficient mice induced by Cyclophosphamide","volume":"60","author":"Yu","year":"2019","journal-title":"J. Funct. Foods."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Huang, F.F., Wang, J.J., Yu, F.M., Tang, Y.P., Ding, G.F., Yang, Z.S., and Sun, Y. (2018). Protective Effect of Meretrix meretrix Oligopeptides on High-Fat-Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. Mar. Drugs, 16.","DOI":"10.3390\/md16020039"},{"key":"ref_21","first-page":"24","article-title":"Immunomodulatory effects of Meretrix meretrix oligopeptides on RAW264.7 cells","volume":"43","author":"Ye","year":"2019","journal-title":"J. Fish. China"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/ijo.2017.297","article-title":"Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice(Article)","volume":"42","author":"Kyung","year":"2018","journal-title":"Int. J. Obesity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejphar.2014.01.073","article-title":"Exogenous administration of spermine improves glucose utilization and decreases bodyweight in mice","volume":"729","author":"Sadasivan","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.bbrc.2009.08.161","article-title":"Rutecarpine ameliorates bodyweight gain through the inhibition of orexigenic neuropeptides NPY and AgRP in mice","volume":"389","author":"Kim","year":"2009","journal-title":"Biochem. Bioph. Res. Co."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.2147\/IJN.S66318","article-title":"Tolerance-like innate immunity and spleen injury: A novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions","volume":"9","author":"Deng","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9285","DOI":"10.1007\/s11033-012-1677-x","article-title":"Effect of polysaccharides extract ofrhizoma atractylodis macrocephalaeon thymus, spleen and cardiac indexes, caspase-3 activity ratio, Smac\/DIABLO and HtrA2\/Omi protein and mRNA expression levels in aged rats","volume":"39","author":"Guo","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.brainres.2018.05.036","article-title":"Lipopolysaccharide Preconditioning Increased the Level of Regulatory B cells in the Spleen after Acute Ischaemia\/Reperfusion in Mice","volume":"1701","author":"Zhe","year":"2018","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cellimm.2012.03.010","article-title":"Kinetics of rebounding of lymphoid and myeloid cells in mouse peripheral blood, spleen and bone marrow after treatment with cyclophosphamide","volume":"276","author":"Salem","year":"2012","journal-title":"Cell. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Brian, J., Jason, C., and John, C. (2018). Reduction of MHC-I expression limits T-lymphocyte-mediated killing of Cancer-initiating cells. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4389-3"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00251-014-0799-9","article-title":"Hematopoiesis in the equine fetal liver suggests immune preparedness","volume":"66","author":"Battista","year":"2014","journal-title":"Immunogenetics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vidarsson, G., Dekkers, G., and Rispens, T. (2014). IgG Subclasses and Allotypes: From Structure to Effector Functions. Front. Immuno., 5.","DOI":"10.3389\/fimmu.2014.00520"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbi.2017.03.001","article-title":"Nociceptive neuronal Fc-gamma receptor I is involved in IgG immune complex induced pain in the rat","volume":"62","author":"Jiang","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.idairyj.2014.09.010","article-title":"Galactooligosaccharides reduce infection caused by Listeria monocytogenes and modulate IgG and IgA levels in mice","volume":"41","author":"Sangwan","year":"2015","journal-title":"Int. Dairy J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.3168\/jds.2013-6758","article-title":"Immunomodulatory and hypoallergenic properties of milk protein hydrolysates in ICR mice, Journal of Dairy Science","volume":"96","author":"Pan","year":"2013","journal-title":"J. Dairy Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ijbiomac.2011.11.015","article-title":"An immunostimulatory polysaccharide (SCP-IIa) from the fruit of Schisandra chinensis (Turcz.)","volume":"50","author":"Chen","year":"2012","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1007\/s10068-018-0414-1","article-title":"Oligopeptide derived from solid-state fermented cottonseed meal significantly affect the immunomodulatory in balb\/c mice treated with cyclophosphamide","volume":"27","author":"Liu","year":"2018","journal-title":"Food Sci. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.vetimm.2017.02.004","article-title":"Evaluation of blood T-lymphocyte subpopulations involved in host cellular immunity in dogs with mammary cancer","volume":"186","author":"Karayannopoulou","year":"2017","journal-title":"Vet. Immunol. Immunop."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Actor, J. (2014). T Lymphocytes: Ringleaders of Adaptive Immune Function. Introductory Immunology, Academic Press. [1st ed.].","DOI":"10.1016\/B978-0-12-420030-2.00004-4"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0022-1759(90)90159-S","article-title":"Quantification of proliferative and suppressive responses of human T lymphocytes following ConA stimulation","volume":"126","author":"Otto","year":"1990","journal-title":"J. Immunol. Methods"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1016\/j.vaccine.2011.04.045","article-title":"Immunization of mice with the non-toxic HC50 domain of botulinum neurotoxin presented by rabies virus particles induces a strong immune response affording protection against high-dose botulinum neurotoxin challenge","volume":"29","author":"Mustafa","year":"2011","journal-title":"Vaccine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.imlet.2009.01.005","article-title":"Tr1 regulatory T cells induced by ConA pretreatment prevent mice from ConA-induced hepatitis","volume":"122","author":"Ye","year":"2009","journal-title":"Immunol. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.vaccine.2018.01.034","article-title":"Immunization with Pseudomonas aeruginosa outer membrane vesicles stimulates protective immunity in mice","volume":"36","author":"Zhang","year":"2018","journal-title":"Vaccine"},{"key":"ref_44","first-page":"1","article-title":"Prevention of Cyclophosphamide-Induced Immunosuppression in Mice with the Antimicrobial Peptide Sublancin","volume":"2018","author":"Wang","year":"2018","journal-title":"Clin. Dev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.29219\/fnr.v62.1296","article-title":"Immunomodulatory activity ofLactobacillus plantarumKLDS1.0318 in cyclophosphamide-treated mice","volume":"62","author":"Meng","year":"2018","journal-title":"Food Nutr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ecoenv.2018.06.055","article-title":"Mechanism and effects of Zearalenone on mouse T lymphocytes activation in vitro","volume":"162","author":"Cai","year":"2018","journal-title":"Ecotox. Environ. Safe"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.imbio.2011.03.001","article-title":"The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by ConA or PMA\/ionomycin","volume":"216","author":"Ye","year":"2011","journal-title":"Immunobiology"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4452\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:23Z","timestamp":1760190023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,5]]},"references-count":47,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24244452"],"URL":"https:\/\/doi.org\/10.3390\/molecules24244452","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,5]]}}}