Uptake of Non-Transferrin Iron by Erythroid Cells

Most of the iron in the plasma is bound to transferrin (Tf) and is taken up by cells through their surface Tf receptors (TfRs). Under pathological conditions of iron-overload, the plasma iron which is in excess of the binding capacity of Tf is present as non-Tf-bound iron. We probed the uptake of non-Tf iron and its consequences on the oxidative status of peripheral RBC and reticulocytes as well as developing erythroid precursors grown in vitro. The cells were exposed to ferrous ammonium sulfate under Tf-supplemented and Tf-free conditions. Using flow cytometry techniques, we found that both the TfR-deficient mature RBC and their TfR-containing precursors at all stages of maturation can take up non-Tf iron that accumulates as redox-active labile iron and generates reactive oxygen species. Such a mechanism may account for ineffective erythropoiesis of developing precursors in the bone marrow and for the shortening of the lifespan of mature RBCs in the circulation

Thalassemic DNA-Containing Red Blood Cells Are under Oxidative Stress

We studied the nature of enucleated RBCs containing DNA remnants, Howell-Jolly (HJ) RBCs and reticulocytes (retics), that are characteristically present in the circulation of thalassemic patients, especially after splenectomy. Using flow cytometry methodology, we measured oxidative status parameters of these cells in patients with β-thalassemia. In each patient studied, these cells had higher content of reactive oxygen species and exposed phosphatidylserine compared with their DNA-free counterparts. These results suggest that oxidative stress in thalassemic developing erythroid precursors might, through DNA-breakage, generate HJ-retics and HJ-RBCs and that oxidative stress-induced externalization of phosphatidylserine is involved in the removal of these cells from the circulation by the spleen, a mechanism similar to that of the removal of senescent RBCs

Therapeutic Hemoglobin Levels after Gene Transfer in β-Thalassemia Mice and in Hematopoietic Cells of β-Thalassemia and Sickle Cells Disease Patients

Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients

ZAPOŠLJAVANJE ZA SCENARIJE ODRŽIVOG RAZVOJA EKONOMSKIH SEKTORA U REGIONU HARKOVA

The article is devoted to the study of the emergence and deepening of staffing gaps that affect the development of the region under the influence of transforming production dominants in the conditions of Economy 4.0. In the course of the study, the system of factors for the emergence of staffing gaps that affect the sustainable development of the region is generalized. A matrix approach to determining staffing gaps is proposed and sectorial scenarios for preventing them in Kharkiv region economy are developed. The assumption about the perspective structure of economy sectors in Kharkiv region according to the scenarios of inertial and innovative ways of development of Ukraine is formed.Ovaj članak se bavi proučavanjem pojave i produbljavanja jaza u zapošljavanju koji utiče na razvoj regije pod uticajem transformišuće proizvodne dominante u uslovima Ekonomije 4.0. U sklopu rada, daje se generalizacija sistema faktora za pojavu jaza u zapošljavanju koji utiče na održivi razvoj regije. Predstavljena je matrica kojea određuje jaz u zapošljavanju i razvijeni su sektorski scenariji za sprečavanje ovog jaza u regionalnoj ekonomiji Harkova. Stvorena je pretpostavka o mogućoj strukturi ekonomskih sektora u regionu Harkova prema scenarijima inertnog, odnosno inovativnog načina razvoja Ukrajine

Spatial forms of organizing innovative infrastructure of Ukraine in terms of sustainable development

The article is devoted to the study of spatial forms of organizing innovative infrastructure of Ukraine in terms of sustainable development. In the course of the study, modern trends of innovative development of the regions in Ukraine are highlighted. The peculiarities of implementing innovative policy in the context of smart specialization strategy are analyzed. Diagnostics of processes of formation and development of innovative infrastructure in regions of Ukraine is carried out. A conceptual approach to assessing the level of innovation infrastructure development is proposed

Effects of rapamycin on accumulation of alpha-, beta- and gamma-globin mRNAs in erythroid precursor cells from beta-thalassaemia patients

We studied the effects of rapamycin on cultures of erythroid progenitors derived from the peripheral blood of 10 beta-thalassaemia patients differing widely with respect to their potential to produce foetal haemoglobin (HbF). For this, we employed the two-phase liquid culture procedure for growing erythroid progenitors, high performance liquid chromatography for analysis of HbF production and reverse transcription polymerase chain reaction for quantification of the accumulation of globin mRNAs. The results demonstrated that rapamycin induced an increase of HbF in cultures from all the beta-thalassaemia patients studied and an increase of their overall Hb content/cell. The inducing effect of rapamycin was restricted to gamma-globin mRNA accumulation, being only minor for beta-globin and none for alpha-globin mRNAs. The ability of rapamycin to preferentially increase gamma-globin mRNA content and production of HbF in erythroid precursor cells from beta-thalassaemia patients is of great importance as this agent (also known as sirolimus or rapamune) is already in clinical use as an anti-rejection agent following kidney transplantation. These data suggest that rapamycin warrants further evaluation as a potential therapeutic drug in beta-thalassaemia and sickle cell anaemia

Erythroid differentiation ability of butyric acid analogues: Identification of basal chemical structures of new inducers of foetal haemoglobin

Several investigations have demonstrated a mild clinical status in patients with β-globin disorders and congenital high persistence of foetal haemoglobin. This can be mimicked by a pharmacological increase of foetal γ-globin genes expression and foetal haemoglobin production. Our goal was to apply a multistep assay including few screening methods (benzidine staining, RT-PCR and HPLC analyses) and erythroid cellular model systems (the K562 cell line and erythroid precursors collected from peripheral blood) to select erythroid differentiation agents with foetal haemoglobin inducing potential. With this methodology, we have identified a butyric acid derivative, namely the 4174 cyclopropanecarboxylic acid compound, able to induce erythroid differentiation without antiproliferative effect in K562 cells and increase of γ-globin gene expression in erythroid precursor cells. The results are relevant for pharmacological treatments of haemoglobinopathies, including β-thalassaemia and sickle cell anaemia