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Polymerization of HbS causes sickling of red blood cells (RBCs) evidenced by acute adverse events and persistent inflammatory state, vasculopathy and organ damage. Sickled RBCs cause an anemic condition and vaso-occlusive crisis which trigger leukocytes, endothelial cells, and platelets. Due to these events, SCD patients unveiled an elevated level of pro-inflammatory cytokines, which contribute to the ongoing inflammatory state, oxidative stress, and other severe complications. SCD patients also experience neuropathic, inflammatory, and nociceptive pain. The discovery of novel therapeutic approaches and targets to counteract and manage inflammation in SCD are needed. Our study aimed to better understand the role of macrophages in SCD inflammation by first investigating their phenotype and then studying the iron metabolism involvement in the inflammatory processes. Therefore, given the importance to find novel therapeutic approach to contain and manage inflammation in these patients, and considering the role of CB2 and TRPV1 in this process, we decided to investigate the expression of these receptors and the effects of their stimulation on inflammatory state in SCD macrophages.<\/jats:p>","DOI":"10.1038\/s41598-025-15028-2","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T10:53:32Z","timestamp":1754650412000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CB2 and TRPV1 receptors in inflammatory state of macrophages from sickle cell anemia pediatric\/young adults"],"prefix":"10.1038","volume":"15","author":[{"given":"Giuseppe","family":"Di Feo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Giliberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeksha","family":"Rana-Seyfert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Maddalena","family":"Marrapodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Casale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakeel","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silverio","family":"Perrotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Roberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Di Paola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"issue":"8","key":"15028_CR1","doi-asserted-by":"publisher","first-page":"e585","DOI":"10.1016\/S2352-3026(23)00118-7","volume":"10","author":"Global","year":"2023","unstructured":"Global National prevalence and mortality burden of sickle cell disease, 2000\u20132021: a systematic analysis from the global burden of disease study 2021. 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