{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:15:20Z","timestamp":1780485320076,"version":"3.54.1"},"reference-count":61,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PO FESR Sicilia 2014\/2020","award":["08TP1041100162"],"award-info":[{"award-number":["08TP1041100162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thrombosis is a key process that determines acute coronary syndrome and ischemic stroke and is the leading cause of morbidity and mortality in the world, together with cancer. Platelet adhesion and subsequent activation and aggregation are critical processes that cause thrombus formation after endothelial damage. To date, high hopes are associated with compounds of natural origin, which show anticoagulant action without undesirable effects and can be proposed as supportive therapies. We investigated the effect of the new combination of four natural compounds, escin\u2013bromelain\u2013ginkgo biloba\u2013sage miltiorrhiza (EBGS), on the initial process of the coagulation cascade, which is the adhesion of platelets to activated vascular endothelium. Our results demonstrated that EBGS pretreatment of endothelial cells reduces platelet adhesion even in the presence of the monocyte\u2013lymphocyte population. Our data indicate that EBGS exerts its effects by inhibiting the transcription of adhesion molecules, including P-selectin, platelet membrane glycoprotein GP1b, integrins \u03b1V and \u03b23, and reducing the secretion of the pro-inflammatory cytokines interleukin 6, interleukin 8, and the metalloproteinases MMP-2 and MMP-9. Furthermore, we demonstrated that EBGS inhibited the expression of focal adhesion kinase (FAK), strictly involved in platelet adhesion, and whose activity is correlated with that of integrin \u03b23. The results shown in this manuscript suggest a possible inhibitory role of the new combination EBGS in the reduction in platelet adhesion to activated endothelium, thus possibly preventing coagulation cascade initiation.<\/jats:p>","DOI":"10.3390\/ijms25179252","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:26:51Z","timestamp":1724750811000},"page":"9252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Combination of Natural Compounds Escin\u2013Bromelain\u2013Ginkgo Biloba\u2013Sage Miltiorrhiza (EBGS) Reduces Platelet Adhesion to TNF\u03b1-Activated Vascular Endothelium through FAK Signaling"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6630-1768","authenticated-orcid":false,"given":"Maria Magdalena","family":"Barreca","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Biology and Genetics Section, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-1303","authenticated-orcid":false,"given":"Stefania","family":"Raimondo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Biology and Genetics Section, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-835X","authenticated-orcid":false,"given":"Alice","family":"Conigliaro","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Biology and Genetics Section, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Siragusa","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Haematology Section, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-2936","authenticated-orcid":false,"given":"Mariasanta","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Haematology Section, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9935-1040","authenticated-orcid":false,"given":"Riccardo","family":"Alessandro","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Biology and Genetics Section, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-0793","authenticated-orcid":false,"given":"Chiara","family":"Corrado","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Biology and Genetics Section, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health","volume":"80","author":"Vaduganathan","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between inflammation and thrombosis in cardiovascular pathology","volume":"18","author":"Stark","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1016\/j.thromres.2014.03.016","article-title":"Biological basis and pathological relevance of microvascular thrombosis","volume":"133","author":"Pfeiler","year":"2014","journal-title":"Thromb. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1084\/jem.184.1.165","article-title":"A human tumor necrosis factor p75 receptor agonist stimulates in vitro T cell proliferation but does not produce inflammation or shock in the baboon","volume":"184","author":"Welborn","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1365-2230.1996.tb00007.x","article-title":"Endothelial cell activation in cutaneous vasculitis","volume":"21","author":"Jurd","year":"1996","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/1097-0029(20000801)50:3<184::AID-JEMT2>3.0.CO;2-H","article-title":"TNF alpha and the TNF receptor superfamily: Structure-function relationship(s)","volume":"50","author":"Idriss","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.gendis.2023.02.008","article-title":"Long noncoding RNA (lncRNA) H19: An essential developmental regulator with expanding roles in cancer, stem cell differentiation, and metabolic diseases","volume":"10","author":"Liao","year":"2023","journal-title":"Genes Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e22241","DOI":"10.1097\/MD.0000000000022241","article-title":"Quercetin inhibits TNF-alpha induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro","volume":"99","author":"Chen","year":"2020","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1126\/science.288.5475.2351","article-title":"A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling","volume":"288","author":"Chan","year":"2000","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/micc.12040","article-title":"Diversity in mechanisms of endothelium-dependent vasodilation in health and disease","volume":"20","author":"Durand","year":"2013","journal-title":"Microcirculation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/386616a0","article-title":"Release of gelatinase A during platelet activation mediates aggregation","volume":"386","author":"Sawicki","year":"1997","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154157","DOI":"10.1016\/j.cyto.2017.09.013","article-title":"Platelet-derived chemokines in inflammation and atherosclerosis","volume":"122","author":"Bakogiannis","year":"2019","journal-title":"Cytokine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1182\/blood.V92.10.3684","article-title":"Shear-dependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein Ib-IX-V complex","volume":"92","author":"Fredrickson","year":"1998","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1538-7836.2011.04274.x","article-title":"Advances in our understanding of the molecular basis of disorders of platelet function","volume":"9","author":"Nurden","year":"2011","journal-title":"J. Thromb. Haemost"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood.2019003336","article-title":"Activation and suppression of hematopoietic integrins in hemostasis and immunity","volume":"135","author":"Nolte","year":"2020","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jiang, P., Lan, Y., Luo, J., Ren, Y.L., Liu, D.G., Pang, J.X., Liu, J., Li, J., Wang, C., and Cai, J.P. (2014). Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling. BMC Cell Biol., 15.","DOI":"10.1186\/1471-2121-15-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1189\/jlb.0708400","article-title":"Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases","volume":"85","author":"Zwaginga","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1080\/09537104.2021.1902970","article-title":"Endothelial transmigration of platelets depends on soluble factors released by activated endothelial cells and monocytes","volume":"32","author":"Huilcaman","year":"2021","journal-title":"Platelets"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1002\/ptr.7261","article-title":"Citrus flavonoids as potential therapeutic agents: A review","volume":"36","author":"Alam","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, H., Sureda, A., Devkota, H.P., Pittala, V., Barreca, D., Silva, A.S., Tewari, D., Xu, S., and Nabavi, S.M. (2020). Curcumin, the golden spice in treating cardiovascular diseases. Biotechnol. Adv., 38.","DOI":"10.1016\/j.biotechadv.2019.01.010"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Barreca, M.M., Alessandro, R., and Corrado, C. (2023). Effects of Flavonoids on Cancer, Cardiovascular and Neurodegenerative Diseases: Role of NF-kappaB Signaling Pathway. Int. J. Mol. Sci, 24.","DOI":"10.20944\/preprints202305.0824.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/cbin.11963","article-title":"Nobiletin and xanthohumol counteract the TNFalpha-mediated activation of endothelial cells through the inhibition of the NF-kappaB signaling pathway","volume":"47","author":"Corrado","year":"2023","journal-title":"Cell Biol. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3109\/03008208509089840","article-title":"The structure of rat tail tendon fascicles","volume":"14","author":"Rowe","year":"1985","journal-title":"Connect. Tissue Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0014-2999(96)00645-0","article-title":"Effect of aescine on hypoxia-induced activation of human endothelial cells","volume":"315","author":"Arnould","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1055\/s-2007-967118","article-title":"Aescin protection of human vascular endothelial cells exposed to cobalt chloride mimicked hypoxia and inflammatory stimuli","volume":"73","author":"Montopoli","year":"2007","journal-title":"Planta Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.2147\/DDDT.S207720","article-title":"Escin: A review of its anti-edematous, anti-inflammatory, and venotonic properties","volume":"13","author":"Gallelli","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hikisz, P., and Bernasinska-Slomczewska, J. (2021). Beneficial Properties of Bromelain. Nutrients, 13.","DOI":"10.3390\/nu13124313"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Varilla, C., Marcone, M., Paiva, L., and Baptista, J. (2021). Bromelain, a Group of Pineapple Proteolytic Complex Enzymes (Ananas comosus) and Their Possible Therapeutic and Clinical Effects. A Summary. Foods, 10.","DOI":"10.3390\/foods10102249"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3892\/br.2016.720","article-title":"Potential role of bromelain in clinical and therapeutic applications","volume":"5","author":"Rathnavelu","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/j.ijbiomac.2020.08.141","article-title":"Extraction, structure and bioactivities of the polysaccharides from Ginkgo biloba: A review","volume":"162","author":"Fang","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118811","DOI":"10.1016\/j.carbpol.2021.118811","article-title":"Hair-growth promoting effect and anti-inflammatory mechanism of Ginkgo biloba polysaccharides","volume":"278","author":"Li","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1002\/ptr.3168","article-title":"In vitro and ex vivo antiangiogenic activity of Salvia officinalis","volume":"24","author":"Keshavarz","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_35","first-page":"5125","article-title":"Danshen (Salvia miltiorrhiza Bunge): A Prospective Healing Sage for Cardiovascular Diseases","volume":"23","author":"Chen","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.115.306841","article-title":"Global Burden of Thrombosis: Epidemiologic Aspects","volume":"118","author":"Wendelboe","year":"2016","journal-title":"Circ. Res."},{"key":"ref_37","first-page":"785","article-title":"Thrombosis and platelets: An update","volume":"38","author":"Koupenova","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1056\/NEJMra0801082","article-title":"Mechanisms of thrombus formation","volume":"359","author":"Furie","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114035","DOI":"10.1016\/j.ejmech.2021.114035","article-title":"Progress of thrombus formation and research on the structure-activity relationship for antithrombotic drugs","volume":"228","author":"Li","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature06797","article-title":"Triggers, targets and treatments for thrombosis","volume":"451","author":"Mackman","year":"2008","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lichota, A., Szewczyk, E.M., and Gwozdzinski, K. (2020). Factors Affecting the Formation and Treatment of Thrombosis by Natural and Synthetic Compounds. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217975"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12989-017-0237-x","article-title":"Ambient air pollution and thrombosis","volume":"15","author":"Robertson","year":"2018","journal-title":"Part Fibre Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.bmc.2003.12.039","article-title":"Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa)","volume":"12","author":"Polla","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s10787-019-00612-6","article-title":"Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases","volume":"27","author":"Vazhappilly","year":"2019","journal-title":"Inflammopharmacology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1055\/s-0031-1273084","article-title":"Diet and thrombosis risk: Nutrients for prevention of thrombotic disease","volume":"37","author":"Phang","year":"2011","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1021\/bi9016022","article-title":"Control of integrin alphaIIb beta3 outside-in signaling and platelet adhesion by sensing the physical properties of fibrin(ogen) substrates","volume":"49","author":"Podolnikova","year":"2010","journal-title":"Biochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1182\/blood-2004-04-1257","article-title":"Integrins: Dynamic scaffolds for adhesion and signaling in platelets","volume":"104","author":"Shattil","year":"2004","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/44599","article-title":"Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function","volume":"401","author":"Law","year":"1999","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1242\/jcs.045112","article-title":"Cellular functions of FAK kinases: Insight into molecular mechanisms and novel functions","volume":"123","author":"Schaller","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/cphy.c170049","article-title":"Platelet-Activation Mechanisms and Vascular Remodeling","volume":"8","author":"Rubenstein","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"27742","DOI":"10.1074\/jbc.270.46.27742","article-title":"Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain","volume":"270","author":"Avraham","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13045-019-0709-6","article-title":"Platelet integrin alphaIIbbeta3: Signal transduction, regulation, and its therapeutic targeting","volume":"12","author":"Huang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1161\/ATVBAHA.118.311787","article-title":"Focal Adhesion Kinases in Platelet Function and Thrombosis","volume":"39","author":"Guidetti","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2015.03.019","article-title":"Garcinol: Current status of its anti-oxidative, anti-inflammatory and anti-cancer effects","volume":"362","author":"Liu","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lim, S.H., Lee, H.S., Lee, C.H., and Choi, C.I. (2021). Pharmacological Activity of Garcinia indica (Kokum): An Updated Review. Pharmaceuticals, 14.","DOI":"10.3390\/ph14121338"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cao, H., Al Mamun Bhuyan, A., Umbach, A.T., Ma, K., Borst, O., Gawaz, M., Zhang, S., Nurnberg, B., and Lang, F. (2019). Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis. Toxins, 11.","DOI":"10.3390\/toxins11070382"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"121791","DOI":"10.1016\/j.lfs.2023.121791","article-title":"Garcinol acts as a novel integrin alpha(IIb)beta(3) inhibitor in human platelets","volume":"326","author":"Hsia","year":"2023","journal-title":"Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kong, D.H., Kim, Y.K., Kim, M.R., Jang, J.H., and Lee, S. (2018). Emerging Roles of Vascular Cell Adhesion Molecule-1 (VCAM-1) in Immunological Disorders and Cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041057"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1172\/JCI11871","article-title":"A major role for VCAM-1, but not ICAM-1, in early atherosclerosis","volume":"107","author":"Cybulsky","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zhang, M., Sun, J., Chen, B., Zhao, Y., Gong, H., You, Y., and Qi, R. (2018). Ginkgolide B inhibits platelet and monocyte adhesion in TNFalpha-treated HUVECs under laminar shear stress. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2284-8"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.cardiores.2006.12.013","article-title":"Paracrine up-regulation of monocyte cyclooxygenase-2 by platelets: Role of transforming growth factor-beta1","volume":"74","author":"Eligini","year":"2007","journal-title":"Cardiovasc. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:04Z","timestamp":1760110984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,26]]},"references-count":61,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179252"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179252","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,26]]}}}