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The present study was aimed at revealing the metabolic changes that occurred in the cellular lipid pattern of acute and chronic myeloid leukaemia cells following treatment with cannabidiol (CBD). CBD is a non-psychoactive compound present in Cannabis sativa L., which has shown an antiproliferative action in these type of cancer cells. CBD treatment reduced cell viability and initiated apoptotic and necrotic processes in both cancer cell lines in a time and dose-dependent manner, showing acute myeloid leukaemia (HL-60) cells greater sensitivity than chronic myeloid leukaemia ones (K-562), without differences in the activation of caspases 3/7. Then, control and treated cells of HL-60 and K-562 cell lines were studied through an untargeted lipidomic approach. The treatment was carried out with CBD at a concentration of 10 μM for HL-60 cells and 23 µM CBD for K-562 cells for 48 h. After the extraction of the lipid content from cell lysates, the samples were analysed by UHPLC-QTOF-MS/MS both in the positive and the negative ionization modes. The comprehensive characterization of cellular lipids unveiled several classes significantly affected by CBD treatment. Most of the differences correspond to phospholipids, including cardiolipins (CL), phosphatidylcholines (PC) and phosphosphingolipids (SM), and also triacylglycerols (TG), being many TG species increased after CBD treatment in the acute and chronic models, whereas phospholipids were found to be decreased. The results highlight some important lipid alterations related to CBD treatment, plausibly connected with different metabolic mechanisms involved in the process of cell death by apoptosis in cancer cell lines., Competing Interests: Declarations. Competing interests: The authors declare no conflict of interest., (© 2025. The Author(s).)

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls. We found that the index patient had a novel form of erythroderma characterized by increased interleukin (IL)-13- and IL-17-producing γVδ2 T cells, basophils, and activated platelets. Whole-genome sequencing of PBMCs and immunofluorescence staining of skin biopsies revealed increased expression of Th2- (IL-13, IL-4Rα) and Th17-associated markers (IL-17, IL-17Rα) and non-functional mutations associated with Th2 and Th17 signaling, demonstrating that PBMCs can reflect cutaneous disease pathology. Targeted intervention via dual dupilumab and secukinumab therapy resulted in complete disease control and reduction of immunopathogenic cell populations and cytokines. This study highlights a novel form of erythroderma with concomitant Th2 and Th17 dysregulation and introduces a minimally invasive peripheral blood-based immunophenotyping platform that offers a personalized medicine approach to the management of systemic inflammatory diseases., Competing Interests: Declarations. Competing interests: Dr. Shawn Kwatra is an advisory board member/consultant for Abbvie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Galderma, Genzada Pharmaceuticals, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi. He is also on the Executive Board of the Skin of Color Society. All other authors have no conflicts of interest to report. A provisional patent application (patent no. is 63/422,061) was filed for the workflow used in the creation of this manuscript on November 3, 2022., (© 2024. The Author(s).)