{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T18:38:46Z","timestamp":1766428726225,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LOEWE Centre DRUID"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pathogens"],"abstract":"<jats:p>Human cryptosporidiosis caused by the zoonotic apicomplexan parasite Cryptosporidium parvum represents a neglected and re-emerging poverty-related disease. C. parvum possesses minimalistic metabolic capacities and highly depends on its intestinal epithelial host cell for intracellular replication. Based on previous results showing that glycolysis and glutaminolysis inhibition diminished C. parvum replication in vitro, we here investigated the impact of the olive oil component oleocanthal on C. parvum infection in HCT-8 cells under physioxia (5% O2) and hyperoxia (21% O2). Oleocanthal targets a broad spectrum of regulatory molecules, amongst which mTOR represents a master regulator of glycolysis and glutaminolysis. Using a host cell pre-treatment as well as a pre- and post-infection treatment protocol, 5 \u00b5M oleocanthal reduced C. parvum infection rates between 51% and 94%. Host cellular metabolic conversion rates linked oleocanthal-induced inhibition of C. parvum infection with an impairment in glutaminolysis, representing an important metabolic pathway in intestinal cells. The principal involvement of mTOR in C. parvum inhibition was confirmed by another mTOR-inhibitor (PP242, 0.5 \u00b5M), which also reduced C. parvum infection by 70\u201377%. Given that oleocanthal is not a selective mTOR inhibitor, we assume that this compound drives a multi-target-based inhibition of asexual C. parvum replication, amongst which mTOR is addressed.<\/jats:p>","DOI":"10.3390\/pathogens14101002","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:22:47Z","timestamp":1759483367000},"page":"1002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro Inhibition of Cryptosporidium parvum Infection by the Olive Oil Component Oleocanthal"],"prefix":"10.3390","volume":"14","author":[{"given":"M. Nguele","family":"Ampama","sequence":"first","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"},{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Hanke","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1360-2209","authenticated-orcid":false,"given":"Zahady D.","family":"Vel\u00e1squez","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0402-6480","authenticated-orcid":false,"given":"Nadine B.","family":"W\u00e4ber","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-8492","authenticated-orcid":false,"given":"Carlos","family":"Hermosilla","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-1020","authenticated-orcid":false,"given":"Anja","family":"Taubert","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9104-7677","authenticated-orcid":false,"given":"Sybille","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpara.2017.09.004","article-title":"Foodborne cryptosporidiosis","volume":"48","author":"Ryan","year":"2018","journal-title":"Int. J. Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.tvjl.2007.09.022","article-title":"The public health and clinical significance of Giardia and Cryptosporidium in domestic animals","volume":"177","author":"Thompson","year":"2008","journal-title":"Vet. J."},{"key":"ref_3","unstructured":"CDC (2024, June 14). Clinical Care of Crypto. Cryptosporidium (\u201cCrypto\u201d), Available online: https:\/\/www.cdc.gov\/cryptosporidium\/hcp\/clinical-care\/index.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10.1128","DOI":"10.1128\/AAC.00023-21","article-title":"Spontaneous Selection of Cryptosporidium Drug Resistance in a Calf Model of Infection","volume":"65","author":"Hasan","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1128\/IAI.68.4.2315-2322.2000","article-title":"Cryptosporidium parvum Induces Host Cell Actin Accumulation at the Host-Parasite Interface","volume":"68","author":"Elliott","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.exppara.2008.12.014","article-title":"Cryptosporidium: Genomic and biochemical features","volume":"124","author":"Rider","year":"2010","journal-title":"Exp. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41467-024-44696-3","article-title":"Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum","volume":"15","author":"Xu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13567-023-01172-y","article-title":"Cryptosporidium parvum competes with the intestinal epithelial cells for glucose and impairs systemic glucose supply in neonatal calves","volume":"54","author":"Dengler","year":"2023","journal-title":"Vet. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.compbiolchem.2018.09.002","article-title":"In-silico screening of small molecule inhibitors against Lactate Dehydrogenase (LDH) of Cryptosporidium parvum","volume":"77","author":"Dhal","year":"2018","journal-title":"Comput. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/jeu.12690","article-title":"The Action of the Hexokinase Inhibitor 2-deoxy-d-glucose on Cryptosporidium parvum and the Discovery of Activities against the Parasite Hexokinase from Marketed Drugs","volume":"66","author":"ltahan","year":"2019","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kayamba, F., Faya, M., Pooe, O.J., Kushwaha, B., Kushwaha, N.D., Obakachi, V.A., Nyamori, V.O., and Karpoormath, R. (2021). Lactate dehydrogenase and malate dehydrogenase: Potential antiparasitic targets for drug development studies. Bioorg. Med. Chem., 50.","DOI":"10.1016\/j.bmc.2021.116458"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"V\u00e9lez, J., Velasquez, Z., Silva, L.M.R., G\u00e4rtner, U., Failing, K., Daugschies, A., Mazurek, S., Hermosilla, C., and Taubert, A. (2021). Metabolic Signatures of Cryptosporidium parvum-Infected HCT-8 Cells and Impact of Selected Metabolic Inhibitors on C. parvum Infection under Physioxia and Hyperoxia. Biology, 10.","DOI":"10.3390\/biology10010060"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, S., Roellig, D.M., Guo, Y., Li, N., Frace, M.A., Tang, K., Zhang, L., Feng, Y., and Xiao, L. (2016). Evolution of mitosome metabolism and invasion-related proteins in Cryptosporidium. BMC Genom., 17.","DOI":"10.1186\/s12864-016-3343-5"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.parint.2010.04.005","article-title":"Diversity in mitochondrial metabolic pathways in parasitic protists Plasmodium and Cryptosporidium","volume":"59","author":"Mogi","year":"2010","journal-title":"Parasitol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1016\/j.cub.2021.04.028","article-title":"Parallel functional reduction in the mitochondria of apicomplexan parasites","volume":"31","author":"Mathur","year":"2021","journal-title":"Curr. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"V\u00e9lez, J., Silva, L.M.R., G\u00e4rtner, U., Daugschies, A., Mazurek, S., Hermosilla, C., and Taubert, A. (2021). First Metabolic Insights into Ex Vivo Cryptosporidium parvum-Infected Bovine Small Intestinal Explants Studied under Physioxic Conditions. Biology, 10.","DOI":"10.3390\/biology10100963"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.molcel.2012.05.043","article-title":"Glutaminolysis activates Rag-mTORC1 signaling","volume":"47","author":"Oppliger","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17530","DOI":"10.1074\/jbc.M112.359638","article-title":"Structure-Activity Analysis of Niclosamide Reveals Potential Role for Cytoplasmic pH in Control of Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling","volume":"287","author":"Fonseca","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.abb.2014.06.023","article-title":"AMPK inhibits cardiac hypertrophy by promoting autophagy via mTORC1","volume":"558","author":"Li","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41556-018-0205-1","article-title":"mTOR as a central hub of nutrient signalling and cell growth","volume":"21","author":"Kim","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3892\/ijo.2020.5152","article-title":"Critical role of mTOR in regulating aerobic glycolysis in carcinogenesis (Review)","volume":"58","author":"Fan","year":"2021","journal-title":"Int. J. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1152\/physrev.00026.2020","article-title":"Regulation and Metabolic Functions of mTORC1 and mTORC2","volume":"101","author":"Szwed","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4814","DOI":"10.1038\/s41467-021-25079-4","article-title":"Two parallel pathways connect glutamine metabolism and mTORC1 activity to regulate glutamoptosis","volume":"12","author":"Bodineau","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Paquette, M., El-Houjeiri, L., and Pause, A. (2018). mTOR Pathways in Cancer and Autophagy. Cancers, 10.","DOI":"10.3390\/cancers10010018"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zou, Z., Tao, T., Li, H., and Zhu, X. (2020). mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00396-1"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s12935-022-02706-8","article-title":"Recent advances and limitations of mTOR inhibitors in the treatment of cancer","volume":"22","author":"Ali","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Marafie, S.K., Al-Mulla, F., and Abubaker, J. (2024). mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116141"},{"key":"ref_28","first-page":"109","article-title":"mTORC1, the maestro of cell metabolism and growth","volume":"39","author":"He","year":"2025","journal-title":"Genes Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jchromb.2017.11.027","article-title":"Metabolite identification and pharmacokinetic profiling of PP242, an ATP-competitive inhibitor of mTOR using ultra high-performance liquid chromatography and mass spectrometry","volume":"1072","author":"Rashid","year":"2018","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nm.2091","article-title":"Effective and selective targeting of Ph+ leukemia cells using a TORC1\/2 kinase inhibitor","volume":"16","author":"Janes","year":"2010","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1002\/ptr.5434","article-title":"Olive Oil-derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies","volume":"29","author":"Khanfar","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C350","DOI":"10.1152\/ajpcell.00191.2015","article-title":"Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A Review in the Theme: Cellular Responses to Hypoxia","volume":"309","author":"Zheng","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1038\/s41564-019-0539-x","article-title":"Life cycle progression and sexual development of the apicomplexan parasite Cryptosporidium parvum","volume":"4","author":"Tandel","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Di Paola, F.J., Cardoso, L.H., Nikitopoulou, E., Kulik, B., R\u00fchl, S., Eva, A., Sommer, N., Linn, T., Gnaiger, E., and Failing, K. (2025). Impact of mtG3PDH inhibitors on proliferation and metabolism of androgen receptor-negative prostate cancer cells: Role of extracellular pyruvate. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0325509"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1002\/ptr.6722","article-title":"Anticancer molecular mechanisms of oleocanthal","volume":"34","author":"Quintero","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Jannati, S., Patel, A., Patnaik, R., and Banerjee, Y. (2025). Oleocanthal as a Multifunctional Anti-Cancer Agent: Mechanistic Insights, Advanced Delivery Strategies, and Synergies for Precision Oncology. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125521"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.prevetmed.2015.01.005","article-title":"Cryptosporidium parvum infection and associated risk factors in dairy calves in western France","volume":"118","author":"Delafosse","year":"2015","journal-title":"Prev. Vet. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100147","DOI":"10.1016\/j.crpvbd.2023.100147","article-title":"Prevalence, risk factors and molecular epidemiology of neonatal cryptosporidiosis in calves: The Argentine perspective","volume":"4","author":"Garro","year":"2023","journal-title":"Curr. Res. Parasitol. Vector. Borne. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sone, B., Ambe, L.A., Ampama, M.N., Ajohkoh, C., Che, D., Nguinkal, J.A., Taubert, A., Hermosilla, C., and Kamena, F. (2025). Prevalence and Molecular Characterization of Cryptosporidium Species in Diarrheic Children in Cameroon. Pathogens, 14.","DOI":"10.3390\/pathogens14030287"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wu, S., Shao, T., Xie, J., Li, J., Sun, L., Zhang, Y., Zhao, L., Wang, L., Li, X., and Zhang, L. (2024). MiR-199a-3p regulates HCT-8 cell autophagy and apoptosis in response to Cryptosporidium parvum infection by targeting MTOR. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06632-5"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.neuroscience.2017.03.059","article-title":"Oleocanthal Ameliorates Amyloid-beta Oligomers Toxicity on Astrocytes and Neuronal Cells: In-vitro Studies","volume":"352","author":"Batarseh","year":"2017","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11007","DOI":"10.1007\/s13277-016-4984-3","article-title":"Blockage of glutaminolysis enhances the sensitivity of ovarian cancer cells to PI3K\/mTOR inhibition involvement of STAT3 signaling","volume":"37","author":"Guo","year":"2016","journal-title":"Tumour. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.molimm.2023.01.002","article-title":"Cryptosporidium parvum maintains intracellular survival by activating the host cellular EGFR-PI3K\/Akt signaling pathway","volume":"154","author":"Yang","year":"2023","journal-title":"Mol. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00253-019-10257-8","article-title":"Targeting PI3K\/AKT\/mTOR-mediated autophagy for tumor therapy","volume":"104","author":"Xu","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Priyamvada, S., Jayawardena, D., Bhalala, J., Kumar, A., Anbazhagan, A.N., Alrefai, W.A., Borthakur, A., and Dudeja, P.K. (2021). Cryptosporidium parvum infection induces autophagy in intestinal epithelial cells. Cell Microbiol., 23.","DOI":"10.1111\/cmi.13298"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/437045a","article-title":"Phytochemistry: Ibuprofen-like activity in extra-virgin olive oil","volume":"437","author":"Beauchamp","year":"2005","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1021\/ol052106a","article-title":"Synthesis and assignment of absolute configuration of (-)-oleocanthal: A potent, naturally occurring non-steroidal anti-inflammatory and anti-oxidant agent derived from extra virgin olive oils","volume":"7","author":"Smith","year":"2005","journal-title":"Org. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gonzalez-Rodriguez, M., Ait Edjoudi, D., Cordero-Barreal, A., Farrag, M., Varela-Garcia, M., Torrijos-Pulpon, C., Ruiz-Fernandez, C., Capuozzo, M., Ottaiano, A., and Lago, F. (2023). Oleocanthal, an Antioxidant Phenolic Compound in Extra Virgin Olive Oil (EVOO): A Comprehensive Systematic Review of Its Potential in Inflammation and Cancer. Antioxidants, 12.","DOI":"10.3390\/antiox12122112"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.freeradbiomed.2025.04.031","article-title":"Secoiridoid-enriched extra virgin olive oil extracts enhance mitochondrial activity and antioxidant response in colorectal cancer cells: The role of Oleacein and Oleocanthal in PPAR\u03b3 interaction","volume":"235","author":"Leo","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1182\/blood.2021013201","article-title":"The STAT3-MYC axis promotes survival of leukemia stem cells by regulating SLC1A5 and oxidative phosphorylation","volume":"139","author":"Amaya","year":"2022","journal-title":"Blood"},{"key":"ref_52","first-page":"2189","article-title":"Glutamine affects T24 bladder cancer cell proliferation by activating STAT3 through ROS and glutaminolysis","volume":"44","author":"Sun","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"43475","DOI":"10.18632\/oncotarget.9782","article-title":"(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma","volume":"7","author":"Pei","year":"2016","journal-title":"Oncotarget"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"105895","DOI":"10.1016\/j.rvsc.2025.105895","article-title":"Niclosamid modulates chronic Cryptosporidium-induced ileocecal adenocarcinoma in immunocompromised infected mice via targeting IL-6\/IL-22-STAT3 axis","volume":"196","author":"Bayomy","year":"2025","journal-title":"Res. Vet. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3233\/JAD-200405","article-title":"A Randomized Clinical Trial of Greek High Phenolic Early Harvest Extra Virgin Olive Oil in Mild Cognitive Impairment: The MICOIL Pilot Study","volume":"78","author":"Tsolaki","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1024120","DOI":"10.3389\/fimmu.2023.1024120","article-title":"Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials","volume":"14","author":"Long","year":"2023","journal-title":"Front Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115520","DOI":"10.1016\/j.ejca.2025.115520","article-title":"Olive oil consumption and risk of breast cancer: Prospective results from the Moli-sani Study, and a systematic review of observational studies and randomized clinical trials","volume":"224","author":"Ruggiero","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Siddique, A.B., King, J.A., Meyer, S.A., Abdelwahed, K., Busnena, B., and El Sayed, K. (2020). Safety Evaluations of Single Dose of the Olive Secoiridoid S-(-)-Oleocanthal in Swiss Albino Mice. Nutrients, 12.","DOI":"10.3390\/nu12020314"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lopez-Yerena, A., Vallverdu-Queralt, A., Mols, R., Augustijns, P., Lamuela-Raventos, R.M., and Escribano-Ferrer, E. (2020). Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020134"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Nikou, T., Sakavitsi, M.E., Kalampokis, E., and Halabalaki, M. (2022). Metabolism and Bioavailability of Olive Bioactive Constituents Based on In Vitro, In Vivo and Human Studies. Nutrients, 14.","DOI":"10.3390\/nu14183773"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tajmim, A., Cuevas-Ocampo, A.K., Siddique, A.B., Qusa, M.H., King, J.A., Abdelwahed, K.S., Sonju, J.J., and El Sayed, K.A. (2021). (-)-Oleocanthal Nutraceuticals for Alzheimer\u2019s Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model. Nutrients, 13.","DOI":"10.3390\/nu13051702"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/1002\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:27:44Z","timestamp":1759483664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/1002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":61,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pathogens14101002"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14101002","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]}}}