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• Curcumin against cancer cells. Lung cancer, colon cancer and Leukemia are among the ten most common cancers worldwide with high incidence of recurrence, metastasis and chemoresistance. Limitations of therapy have been attributed to cancer stem cells (CSCs). The natural multi-targeting agent curcumin (turmeric) has shown significant anti-cancer effects. In this study the authors investigated the effect of curcumin on cancer cell viability, proliferation and suppression of CSCs markers (CD44, CD133, ALDH1) in vitro. Additionally, as limitations for curcumin application arise from its poor bioavailability, the stability of curcumin in different media conditions was investigated. The effect of curcumin on three cancer cell lines (A549, HCT116, 183E95) was investigated with MTT-assay, Flowcytometry, Immunofluorescence and western blotting. Stability of curcumin (diferuloylmethane) and curcuminoids (bisdemetoxycurcumin; desmetoxycurcumin) was determined by HPLC technique in A549 cells in different culture systems (culture medium with/without 10 % FCS, culture medium and cells with/without 10 % FCS) every three hours for over 24 h. Curcumin suppressed cell viability and proliferation as well as expression of CD44 in a time- and dose-dependent manner in all cell lines. Exemplary immunofluorescent and western blot investigation of HCT116 demonstrated that curcumin down-regulated CD44, CD133 and ALDH1 time-dependently. Stability of curcumin was markedly prolonged in a medium supplemented with 10 % FCS independent of application to cell cultures. The most stable curcuminoid over time was bisdemetoxycurcumin and the least stable was Curcumin. The results underline the immense potential of curcumin as an anti-cancer agent by targeting CSCs and further demonstrate that adequate media composition can significantly enhance curcumin stability in vitro. [ABSTRACT FROM AUTHOR]

Dysregulated platelet aggregation is a fatal condition in many bacterial- and virus-induced diseases. However, classical antithrombotics cannot completely prevent immunothrombosis, due to the unaddressed mechanisms towards inflammation. Thus, targeting platelet hyperactivation together with inflammation might provide new treatment options in diseases, characterized by immunothrombosis, such as COVID-19 and sepsis. The aim of this study was to investigate the antiaggregatory effect and mode of action of 1.8-cineole, a monoterpene derived from the essential oil of eucalyptus leaves, known for its anti-inflammatory proprieties. Platelet activity was monitored by measuring the expression and release of platelet activation markers, i.e., P-selectin, CD63 and CCL5, as well as platelet aggregation, upon treatment with 1.8-cineole and stimulation with several classical stimuli and bacteria. A kinase activity assay was used to elucidate the mode of action, followed by a detailed analysis of the involvement of the adenylyl-cyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway by Western blot and ELISA. 1.8-cineole prevented the expression and release of platelet activation markers, as well as platelet aggregation, upon induction of aggregation with classical stimuli and immunological agonists. Mechanistically, 1.8- cineole influences the activation of the AC-cAMP-PKA pathway, leading to higher cAMP levels and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Finally, blocking the adenosine A 2A receptor reversed the antithrombotic effect of 1.8-cineole. Given the recognized anti-inflammatory attributes of 1.8-cineole, coupled with our findings, 1.8-cineole might emerge as a promising candidate for treating conditions marked by platelet activation and abnormal inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

1,8-cineole (Eucalyptol), a naturally occurring compound derived from botanical sources such as eucalyptus, rosemary, and camphor laurel, has a long history of use in traditional medicine and exhibits an array of biological properties, including anti-inflammatory, antioxidant, antimicrobial, bronchodilatory, analgesic, and pro-apoptotic effects. Recent evidence has also indicated its potential role in managing conditions such as Alzheimer's disease, neuropathic pain, and cancer. This review spotlights the health advantages of 1,8-cineole, as demonstrated in clinical trials involving patients with respiratory disorders, including chronic obstructive pulmonary disease, asthma, bronchitis, and rhinosinusitis. In addition, we shed light on potential therapeutic applications of 1,8-cineole in various conditions, such as depression, epilepsy, peptic ulcer disease, diarrhea, cardiac-related heart diseases, and diabetes mellitus. A comprehensive understanding of 1,8-cineole's pharmacodynamics and safety aspects as well as developing effective formulations, might help to leverage its therapeutic value. This thorough review sets the stage for future research on diverse health benefits and potential uses of 1,8-cineole in tackling complex medical conditions. • 1,8-cineole is a naturally occurring compound. • 1,8-cineole exerts anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. • 1,8-cineole modulates key signaling pathways. • 1,8-cineole is clinically applied in rhinosinusitis, COPD, asthma, and bronchitis. [ABSTRACT FROM AUTHOR]

Blood donor age has become a major concern due to the age-associated variations in the content and concentration of circulating extracellular nano-sized vesicles (EVs), including exosomes. These EVs mirror the state of their parental cells and transfer it to the recipient cells via biological messengers such as microRNAs (miRNAs, miRs). Since the behavior of hematopoietic stem cells (HSCs) is potentially affected by the miRs of plasma-derived EVs, a better understanding of the content of EVs is important for the safety and efficacy perspectives in blood transfusion medicine. Herein, we investigated whether the plasma-derived EVs of young (18–25 years) and elderly human donors (45–60 years) can deliver "youth" or "aging" signals into human umbilical cord blood (hUCB)-derived HSCs in vitro. The results showed that EVs altered the growth functionality and differentiation of HSCs depending on the age of the donor from which they are derived. EVs of young donors could ameliorate the proliferation and self-renewal potential of HSCs whereas those of aged donors induced senescence-associated differentiation in the target cells, particularly toward the myeloid lineage. These findings were confirmed by flow cytometric analysis of surface markers and microarray profiling of genes related to stemness (e.g., SOX-1, Nanog) and differentiation (e.g., PU-1). The results displayed an up-regulation of miR-29 and miR-96 and a down-regulation of miR-146 in EVs derived from elderly donors. The higher expression of miR-29 and miR-96 contributed to the diminished expression of CDK-6 and CDKN1A (p21), promoting senescence fate via cell growth suppression, while the lower expression of miR-146 positively regulates TRAF-6 expression to accelerate biological aging. Our findings reveal that plasma-derived EVs from young donors can reverse the aging-associated changes in HSCs, while vice versa, the EVs from elderly donors rather promote the senescence process. [ABSTRACT FROM AUTHOR]