Green synthesis of NiO nanoparticles using Calendula officinalis extract: Chemical charactrization, antioxidant, cytotoxicity, and anti-esophageal carcinoma properties

In this study, nickel nanoparticles (NiONPs) have been successfully synthesized in an aqueous medium using the aqueous extract from the leaves of Calendula officinalis. The synthesized NiONPs were characterized using different techniques. According to the XRD analysis, the mean crystal size for NiONPs was found to be 33.17 nm. In addition, SEM images exhibited a uniform spherical morphology with a size of 60.39 nm for the NiONPs. The anti-esophageal carcinoma potentials of C. officinalis leaf aqueous extract, and NiONPs were assessed by the MTT assay against distal esophageal adenocarcinoma (FLO-1), gastroesophageal junction adenocarcinoma (ESO26), human caucasian esophageal carcinoma (OE33), and human esophageal squamous cell carcinoma (KYSE-270) cell lines. This study showed that NiONPs had excellent cell death and anti-cancer effects against esophageal carcinoma cell lines. The IC50 of NiONPs were 380, 263, 229, and 251 µg/mL against FLO-1, ESO26, OE33, and KYSE-270 cell lines, respectively. Among the studied cell lines, the best anti-esophageal cancer activities of NiONPs were gained in the cell line of OE33. The antioxidant activity of NiONPs was investigated using the DPPH test. In the antioxidant test, NiONPs prevented the oxidation of 50 of the DPPH molecules at a concentration of 204 µg/mL. Considering the obtained results, it can be suggested that NiONPs may be administrated as a chemotherapeutic supplement/drug to treat esophageal carcinoma. © 2021 The Author(s

Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells

Clonal hematopoiesis (CH) is defined as a single hematopoietic stem/progenitor cell (HSPC) gaining selective advantage over a broader range of HSPCs. When linked to somatic mutations in myeloid malignancy-associated genes, such as TET2-mediated clonal hematopoiesis of indeterminate potential or CHIP, it represents increased risk for hematological malignancies and cardiovascular disease. IL1β is elevated in patients with CHIP, however, its effect is not well understood. Here we show that IL1β promotes expansion of pro-inflammatory monocytes/macrophages, coinciding with a failure in the demethylation of lymphoid and erythroid lineage associated enhancers and transcription factor binding sites, in a mouse model of CHIP with hematopoietic-cell-specific deletion of Tet2. DNA-methylation is significantly lost in wild type HSPCs upon IL1β administration, which is resisted by Tet2-deficient HSPCs, and thus IL1β enhances the self-renewing ability of Tet2-deficient HSPCs by upregulating genes associated with self-renewal and by resisting demethylation of transcription factor binding sites related to terminal differentiation. Using aged mouse models and human progenitors, we demonstrate that targeting IL1 signaling could represent an early intervention strategy in preleukemic disorders. In summary, our results show that Tet2 is an important mediator of an IL1β-promoted epigenetic program to maintain the fine balance between self-renewal and lineage differentiation during hematopoiesis.The expansion of cells with TET2 mutations within the blood is associated with increased risk for all-cause mortality, development of leukemia and cardiovascular disease. Here authors show IL1 promotes the clonal expansion TET2 knockout cells, enhancing their self-renewal, promoting their myeloid bias and impairing an IL1 driven loss of methylation at lymphoid and erythroid regulatory elements