{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T13:00:22Z","timestamp":1775134822868,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Project of Chinese Medicine in TCM Bureau of Guangdong Province","award":["20254092"],"award-info":[{"award-number":["20254092"]}]},{"name":"Research Foundation of Medical Science and Technology of Guangdong Province","award":["A2024378"],"award-info":[{"award-number":["A2024378"]}]},{"name":"Guangdong Medical Research Fund Project","award":["B2025732"],"award-info":[{"award-number":["B2025732"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Immunosuppression is a serious side effect of chemotherapeutic agents such as cyclophosphamide (CTX) and significantly increases the risk of infection in patients. Porcupine (Hystrix brachyura) bezoar (PB), a traditional medicine derived from the Hystrix brachyura species of porcupine, is renowned for its antioxidant and anti-inflammatory properties. However, its immunomodulatory potential has not been adequately investigated. This study aimed to systematically evaluate the protective effects of PB against CTX-induced immunosuppression and the underlying mechanisms in a rat model. Methods: An immunosuppression model was established in rats through the injection of CTX. The effects of PB on immune function were evaluated through the measurement of serum immunoglobulin (IgA and IgG) and pro-inflammatory cytokine (IL-6 and TNF-\u03b1) levels, as well as through a histopathological examination of immune organs. The mechanisms were further elucidated by analysing changes in serum metabolites and gut microbiota composition using integrated metabolomics and 16S rRNA sequencing. Results: Treatment with PB significantly alleviated CTX-induced immunosuppression, as demonstrated by elevated serum levels of IgA and IgG and reduced concentrations of IL-6 and TNF-\u03b1. PB also improved the architecture of spleen and thymus tissues. Metabolomic analysis revealed that PB regulated glycerophospholipid metabolism and steroid hormone biosynthesis, thereby reducing pro-inflammatory metabolites such as prostaglandin F2\u03b1. Furthermore, PB modulated the gut microbiota, increasing the abundance of beneficial bacteria (e.g., Bacteroidota and Lachnospiraceae) and decreasing that of harmful bacteria (e.g., Romboutsia and Clostridium sensu stricto). Conclusions: This study demonstrates that PB can effectively counteract CTX-induced immunosuppression in rats. This immunomodulatory effect is linked to changes in the gut microbiota and the regulation of specific metabolic pathways. These findings provide a scientific basis for the potential use of PB as an immunoadjuvant therapy, offering new insights into the mechanisms of traditional medicines.<\/jats:p>","DOI":"10.3390\/ph19040563","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:51:03Z","timestamp":1775130663000},"page":"563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Immunomodulatory Effects of Porcupine Bezoar on Cyclophosphamide-Induced Immunosuppression in Rats"],"prefix":"10.3390","volume":"19","author":[{"given":"Ji","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kien-Seng","family":"Lim","sequence":"additional","affiliation":[{"name":"Miracle Medicine Sdn Bhd, F-01-10, Level 1, Block F, Sunway Geo Avenue, Jalan Lagoon Selatan, Sunway South Quay, Bandar Sunway, Subang Jaya 47500, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Lei","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Qing","family":"Sim","sequence":"additional","affiliation":[{"name":"Miracle Medicine Sdn Bhd, F-01-10, Level 1, Block F, Sunway Geo Avenue, Jalan Lagoon Selatan, Sunway South Quay, Bandar Sunway, Subang Jaya 47500, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-8535","authenticated-orcid":false,"given":"Qinqiang","family":"Long","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Jiyuan Neurohealth Industry Research Institute of Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Jiyuan Neurohealth Industry Research Institute of Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e714","DOI":"10.1002\/mco2.714","article-title":"The Interaction of Innate Immune and Adaptive Immune System","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1146\/annurev-immunol-032713-120236","article-title":"Metabolic Regulation of Immune Responses","volume":"32","author":"Ganeshan","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_3","first-page":"197","article-title":"Innate Immune Recognitio","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1177\/0300891618766173","article-title":"The Evolving Landscape of Criteria for Evaluating Tumor Response in the Era of Cancer Immunotherapy: From Karnofsky to iRECIST","volume":"104","author":"Inno","year":"2018","journal-title":"Tumori"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1007\/s00120-021-01569-7","article-title":"Management von Nebenwirkungen der Chemotherapie und deren Langzeitfolgen","volume":"60","author":"Zraik","year":"2021","journal-title":"Urologe"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Neupane, R., Boddu, S.H.S., Abou-Dahech, M.S., Bachu, R.D., Terrero, D., Babu, R.J., and Tiwari, A.K. (2021). Transdermal Delivery of Chemotherapeutics: Strategies, Requirements, and Opportunities. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13070960"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.semcancer.2025.02.010","article-title":"Immunosenescence and Immunotherapy in Elderly Patients with Hepatocellular Carcinoma","volume":"111","author":"Zhang","year":"2025","journal-title":"Semin. Cancer Biol."},{"key":"ref_9","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/agm2.70028","article-title":"Cancer Burden in Chinese Older Adults: Insights Into Incidence, Mortality, and Global Comparisons Using GLOBOCAN 2022","volume":"8","author":"Zheng","year":"2025","journal-title":"Aging Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1016\/j.talanta.2011.08.034","article-title":"Analysis of Anticancer Drugs: A Review","volume":"85","author":"Nussbaumer","year":"2011","journal-title":"Talanta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e002630","DOI":"10.1136\/jitc-2021-002630","article-title":"COVID-19 in Immunocompromised Populations: Implications for Prognosis and Repurposing of Immunotherapies","volume":"9","author":"Goldman","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1053\/j.ro.2021.10.009","article-title":"Pneumonia in the Immunocompromised Host","volume":"57","author":"Murali","year":"2022","journal-title":"Semin. Roentgenol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrclinonc.2009.146","article-title":"Cyclophosphamide and Cancer: Golden Anniversary","volume":"6","author":"Emadi","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.2165\/00003088-200544110-00003","article-title":"Clinical Pharmacokinetics of Cyclophosphamide","volume":"44","author":"Huitema","year":"2005","journal-title":"Clin. Pharmacokinet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/bjc.1980.17","article-title":"Distribution and Pharmacokinetics of Cyclophosphamide in the Rat","volume":"41","author":"Talha","year":"1980","journal-title":"Br. J. Cancer"},{"key":"ref_17","first-page":"243","article-title":"Effects of Astragalus Polysaccharides on Immunological Function of the Immunosuppressional Model Mice Caused by Cyclophosphamide","volume":"31","author":"Shi","year":"2016","journal-title":"Chin. J. Tradit. Chin. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115865","DOI":"10.1016\/j.intimp.2025.115865","article-title":"Investigation of the Immunomodulatory Effects and Molecular Mechanisms of Cichoric Acid on Cyclophosphamide-Induced Immunosuppression in Mice","volume":"168","author":"Bai","year":"2026","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1002\/jsfa.13271","article-title":"Sciadonic Acid Ameliorates Cyclophosphamide-Induced Immunosuppression by Modulating the Immune Response and Altering the Gut Microbiota","volume":"104","author":"Chen","year":"2024","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","first-page":"13","article-title":"Porcupine Stones","volume":"43","author":"Duffin","year":"2013","journal-title":"Pharm. Hist."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113138","DOI":"10.1016\/j.jep.2020.113138","article-title":"Determination Toxic Effects of Hystrix Brachyura Bezoar Extracts Using Cancer Cell Lines and Embryo Zebrafish (Danio Rerio) Models and Identification of Active Principles through GC-MS Analysis","volume":"262","author":"Ahmed","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","first-page":"555651","article-title":"In Vitro Evaluation of Porcupine Bezoar Extracts as Anticancer Agent on A549 -A Preliminary Study","volume":"5","year":"2017","journal-title":"Adv. Biotechnol. Micorbiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108841","DOI":"10.1016\/j.biopha.2019.108841","article-title":"Anticancer Activity of Grassy Hystrix Brachyura Bezoar and Its Mechanisms of Action: An in Vitro and in Vivo Based Study","volume":"114","author":"Khan","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Firus Khan, A.Y., Abdullah Asuhaimi, F., Jalal, T.K., Roheem, F.O., Natto, H.A., Johan, M.F., Ahmed, Q.U., and Abdul Wahab, R. (2019). Hystrix Brachyura Bezoar Characterization, Antioxidant Activity Screening, and Anticancer Activity on Melanoma Cells (A375): A Preliminary Study. Antioxidants, 8.","DOI":"10.3390\/antiox8020039"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"366","DOI":"10.4103\/pr.pr_145_16","article-title":"Antioxidant and Intracellular Reactive Oxygen Species\/Reactive Nitrogen Species Scavenging Activities of Three Porcupine Bezoars from Hystrix Brachyura","volume":"9","author":"Yew","year":"2017","journal-title":"Pharmacogn. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4103\/pm.pm_620_18","article-title":"Tannic Acid-Rich Porcupine Bezoars Induce Apoptosis and Cell Cycle Arrest in Human Colon Cancer Cells","volume":"15","author":"Yew","year":"2019","journal-title":"Pharmacogn. Mag."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/imr.13407","article-title":"The Importance of IgG Glycosylation\u2014What Did We Learn after Analyzing over 100,000 Individuals","volume":"328","author":"Lauc","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.imlet.2014.01.015","article-title":"IgG-Effector Functions: \u201cThe Good, The Bad and The Ugly\u201d","volume":"160","author":"Kapur","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00011-013-0633-0","article-title":"TNF-\u03b1 Signalling and Inflammation: Interactions between Old Acquaintances","volume":"62","year":"2013","journal-title":"Inflamm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-94-024-0921-5_4","article-title":"Regulation of IL-6 in Immunity and Diseases","volume":"941","author":"Tanaka","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4149\/neo_2014_026","article-title":"Coexpression of IL-6 and TNF-\u03b1: Prognostic Significance on Breast Cancer Outcome","volume":"61","author":"Tripsianis","year":"2014","journal-title":"Neoplasma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cyto.2015.05.008","article-title":"The Differential Expression of IL-4 and IL-13 and Its Impact on Type-2 Immunity","volume":"75","author":"Bao","year":"2015","journal-title":"Cytokine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40364-020-00228-x","article-title":"Roles of IFN-\u03b3 in Tumor Progression and Regression: A Review","volume":"8","author":"Jorgovanovic","year":"2020","journal-title":"Biomark. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S1074-7613(02)00471-5","article-title":"IFN-\u03b3 Represses IL-4 Expression via IRF-1 and IRF-2","volume":"17","author":"Elser","year":"2002","journal-title":"Immunity"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1139\/o89-011","article-title":"Regulation of Phosphatidylcholine Metabolism in Mammalian Hearts","volume":"67","author":"Hatch","year":"1989","journal-title":"Biochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/MOL.0b013e3282fee935","article-title":"Role of Phosphatidylcholine Biosynthesis in the Regulation of Lipoprotein Homeostasis","volume":"19","author":"Vance","year":"2008","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/med.20098","article-title":"Novel Cyclooxygenase-Catalyzed Bioactive Prostaglandin F2alpha from Physiology to New Principles in Inflammation","volume":"27","author":"Basu","year":"2007","journal-title":"Med. Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19087","DOI":"10.1074\/jbc.M117.792978","article-title":"The Phospholipase PNPLA7 Functions as a Lysophosphatidylcholine Hydrolase and Interacts with Lipid Droplets through Its Catalytic Domain","volume":"292","author":"Heier","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"111940","DOI":"10.1016\/j.celrep.2022.111940","article-title":"Hepatic Phosphatidylcholine Catabolism Driven by PNPLA7 and PNPLA8 Supplies Endogenous Choline to Replenish the Methionine Cycle with Methyl Groups","volume":"42","author":"Hirabayashi","year":"2023","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112677","DOI":"10.1016\/j.biopha.2022.112677","article-title":"LCAT- Targeted Therapies: Progress, Failures and Future","volume":"147","author":"Yang","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Gao, M., Zhang, W., Li, X., Li, S., Wang, W., and Han, P. (2025). LCAT in Cancer Biology: Embracing Epigenetic Regulation, Immune Interactions, and Therapeutic Implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041453"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1089\/dna.2018.4286","article-title":"Inhibition of PLA2G4A Reduces the Expression of Lung Cancer-Related Cytokines","volume":"37","author":"Zhang","year":"2018","journal-title":"DNA Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e148028","DOI":"10.1172\/jci.insight.148028","article-title":"PLA2G4A Promotes Right-Sided Colorectal Cancer Progression by Inducing CD39+\u03b3\u03b4 Treg Polarization","volume":"6","author":"Zhan","year":"2021","journal-title":"JCI Insight"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Vogel, L.K., S\u00e6b\u00f8, M., H\u00f8yer, H., Kopp, T.I., Vogel, U., Godiksen, S., Frenzel, F.B., Hamfjord, J., Bowitz-Lothe, I.M., and Johnson, E. (2014). Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105254"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1007\/s10753-019-01085-z","article-title":"Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers","volume":"42","author":"Wu","year":"2019","journal-title":"Inflammation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/ncpgasthep0259","article-title":"Mechanisms of Disease: The Role of Intestinal Barrier Function in the Pathogenesis of Gastrointestinal Autoimmune Diseases","volume":"2","author":"Fasano","year":"2005","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1152\/physrev.00003.2008","article-title":"Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer","volume":"91","author":"Fasano","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1515\/cclm-2025-0318","article-title":"Biomarkers in Body Fluids and Their Detection Techniques for Human Intestinal Permeability Assessment","volume":"63","author":"Zhang","year":"2025","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.alcohol.2008.03.131","article-title":"Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences","volume":"42","author":"Purohit","year":"2008","journal-title":"Alcohol"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.clinre.2014.12.005","article-title":"The Role of Serum Intestinal Fatty Acid Binding Protein Levels and D-Lactate Levels in the Diagnosis of Acute Intestinal Ischemia","volume":"39","author":"Shi","year":"2015","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"142015","DOI":"10.1016\/j.ijbiomac.2025.142015","article-title":"Ginseng Polysaccharides Ameliorate Colorectal Tumorigenesis through Lachnospiraceae-Mediated Immune Modulation","volume":"307","author":"Zong","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Vacca, M., Celano, G., Calabrese, F.M., Portincasa, P., Gobbetti, M., and De Angelis, M. (2020). The Controversial Role of Human Gut Lachnospiraceae. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040573"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41571-023-00803-9","article-title":"Towards Modulating the Gut Microbiota to Enhance the Efficacy of Immune-Checkpoint Inhibitors","volume":"20","author":"Simpson","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41392-020-00443-w","article-title":"Metabolism Pathways of Arachidonic Acids: Mechanisms and Potential Therapeutic Targets","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/563\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:59:56Z","timestamp":1775131196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/4\/563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ph19040563"],"URL":"https:\/\/doi.org\/10.3390\/ph19040563","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}