1,721,164 research outputs found
Chromatin plasticity in mechanotransduction
Full text linkLiving organisms can detect and respond to physical forces at the cellular level. The pathways that transmit these forces to the nucleus allow cells to react quickly and consistently to environmental changes. Mechanobiology involves the interaction between physical forces and biological processes and is crucial for driving embryonic development and adapting to environmental cues during adulthood. Molecular studies have shown that cells can sense mechanical signals directly through membrane receptors linked to the cytoskeleton or indirectly through biochemical cascades that can influence gene expression for environmental adaptation. This review will explore the role of epigenetic modifications, emphasizing the 3D genome architecture and nuclear structures as responders to mechanical stimuli, which ensure cellular memory and adaptability. Understanding how mechanical cues are transduced and regulate cell functioning, governing processes such as cell programming and reprogramming, is essential for advancing our knowledge of human diseases
In vitro and in vivo effects of recombinant interferon gamma on the growth of hematopoietic progenitor cells from patients with myelodysplastic syndrome.
No full textRecombinant interferon gamma (rIFN-gamma) has been shown to have antiproliferative effects on normal and leukemic hematopoietic cells, to induce cell differentiation and to modulate hematopoietic growth factor production. We have studied the effects of rIFN-gamma on the growth of hematopoietic progenitors from 3 patients with myelodysplastic syndrome who were treated with rIFN-gamma (0.01 mg/m2 given subcutaneously three times a week) as part of an Italian pilot study. When bone marrow cells were cultured in semisolid medium in the continuous presence of rIFN-gamma (10-10(4) U/ml), inhibition of colony formation was the most common response. However, an enhancement of hematopoietic progenitor growth was observed in one patient at the lowest concentration tested (10 U/ml). Preincubation of bone marrow mononuclear cells with low concentrations of rIFN-gamma in suspension culture for 5 days induced or enhanced in vitro colony formation in two cases; again, higher concentrations resulted in inhibition of hematopoietic progenitor growth. Two patients showed a slight improvement of in vitro progenitor growth after one month of treatment with rIFN-gamma. Although preliminary, these data indicate that rIFN-gamma may have both stimulatory and inhibitory effects on myelodysplastic hematopoiesis, depending on both the effective concentrations and the interactions with accessory cells
Arachidonic acid stimulates endothelial progenitor cell proliferation through an increase in Ca2+ concentration and nitric oxide production
Full text linkErythrophagocytosis increases the expression of erythroid potentiating activity mRNA in human monocyte-macrophages.
No full textThe aim of the present study was to evaluate whether the erythropoietic response to hemolysis can be mediated by other regulatory peptides in addition to erythropoietin. For this purpose, we have investigated the influence of erythrophagocytosis by human monocytes and macrophages on the mRNA expression of several growth factor genes, including interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF) and erythroid potentiating activity (EPA), which are supposed to influence erythropoiesis. Immunologically mediated erythrophagocytosis increased the expression of EPA mRNA (2 to 3 times). Such increase appeared to be specifically associated with phagocytosis of erythrocytes, since phagocytosis of yeast microorganisms or antibody-coated latex particles had no effect on EPA gene expression. Yeast, however, powerfully stimulated the expression of GM-CSF, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNAs which, with the exception of G-CSF, were not influenced by erythrophagocytosis. Erythropoietin and IL-3 mRNAs were never detected in cultured monocytes, either in control or in treated samples. Our findings may suggest that phagocytosis of erythrocytes by monocytes/macrophages increases the expression, and possibly the production, of EPA. This could in turn potentiate the erythropoietic response to extravascular hemolysis by increasing the number of cells responsive to erythropoietin. Thus, EPA might be a mediator of an end-product positive feedback on the rate of red cell production
Inhibition of c-ABL expression in hematopoietic progenitor cells using antisense oligodeoxynucleotides
No full textFrom cancer patients to cancer survivors: the issue of Cardioncology--a biological perspective.
No full textc-abl function in normal and chronic myelogenous leukemia hematopoiesis: in vitro studies with antisense oligomers.
No full textBy using antisense oligomers the functional role of the c-abl proto-oncogene in the in vitro growth of bone marrow hematopoietic progenitors from normal subjects and patients with chronic myelogenous leukemia (CML) has been evaluated. Light density bone marrow cells (LDBMs) were depleted of adherent cells, pre-incubated for 15 h with the appropriate oligomer at a concentration of 14 microns, and then plated in methylcellulose for the evaluation of colony formation. Both anti-exon Ia and anti-exon Ib antisense oligomers produced a significant inhibition of normal day 14 CFU-GM growth in vitro (n = 5, 41 +/- 11%, and 36 +/- 7%, respectively; p less than 0.01). In contrast, normal BFU-E growth was not significantly influenced by antisense oligomers (n = 5, 14 +/- 21% and 7 +/- 19%, respectively; p less than 0.05). These findings were confirmed by plating CD34 positive progenitors. When interleukin 3 (IL-3) (100 ng/ml) was added to the culture medium during the preincubation of LDBMCs, the inhibitory effects of antisense oligomers on normal CFU-GM growth were abolished. Seven patients with CML were also studied, all of whom had cytogenetic evidence of 100% clonal hematopoiesis. In five patients in the chronic phase, antisense oligomers were inhibitory on in vitro growth of both day 14 CFU-GM (37 +/- 20% and 37 +/- 15%, p less than 0.05) and BFU-E (45 +/- 15% and 41 +/- 11%, p less than 0.05), and this inhibition was not removed by pre-incubation with IL-3. No significant effect was observed on cluster or colony formation in two patients with CML in accelerated or blastic phase, and on in vitro growth of clonogenic cells from the Ph1-positive K-562 cell line. These findings (i) confirm previous observations showing a lineage specific requirement of c-abl function in normal hematopoiesis, and (ii) suggest that the residual c-abl expression has a role in chronic phase CML hematopoiesis, as its inhibition impairs both myeloid and erythroid colony formation in vitro
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