A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway.

Current status of platelet manufacturing in 3D or bioreactors.

Blood shortages for transfusion are global issues of grave concern. As in vitro manufactured platelets are promising substitutes for blood donation, recent research has shown progresses including different cell sources, different bioreactors, and three-dimensional materials. The first-in-human clinical trial of cultured platelets using induced pluripotent stem cell-derived platelets began in Japan and demonstrated its quality, safety, and efficacy.

Irradiation is not sufficient to eradicate residual immortalized erythroid cells in in vitro-generated red blood cell products.

Background: The generation of immortalized erythroid progenitor cell lines capable of producing enough red blood cells (RBCs) for blood transfusion typically requires the overexpression of oncogenes in stem cells or progenitor cells to permanently proliferate immature cells. It is essential that any live oncogene-expressing cells are eliminated from the final RBC products for clinical use.

Study Design And Methods: It is believed that safety issues may be resolved by using a leukoreduction filter or by irradiating the final products, as is conventionally done in blood banks; however, this has never been proven to be effective.

Current status of red blood cell manufacturing in 3D culture and bioreactors.

Owing to donor-related issues, blood shortages and transfusion-related adverse reactions have become global issues of grave concern. manufactured red blood cells (RBCs) are promising substitutes for blood donation. In the United Kingdom, a clinical trial for allogeneic mini transfusion of cultured RBCs derived from primary hematopoietic stem cells has recently begun.

The inactivation and destruction of viruses by reactive oxygen species generated through physical and cold atmospheric plasma techniques: Current status and perspectives.

Background: Outbreaks of airborne viral infections, such as COVID-19, can cause panic regarding other severe respiratory syndrome diseases that may develop and affect public health. It is therefore necessary to develop control methods that offer protection against such viruses.

Aim Of Review: To identify a feasible solution for virus deactivation, we critically reviewed methods of generating reactive oxygen species (ROS), which can attack a wide range of molecular targets to induce antiviral activity, accounting for their flexibility in facilitating host defense mechanisms against a comprehensive range of pathogens.

Red cell manufacturing using parallel stirred-tank bioreactors at the final stages of differentiation enhances reticulocyte maturation.

The aim of this study was to develop a robust, quality controlled, and reproducible erythroid culture system to obtain high numbers of mature erythroblasts and red blood cells (RBCs). This was achieved using a fully controlled stirred-tank bioreactor by the design of experiments (DOE) methods in the serum-free medium by defining the appropriate culture parameters. Human cord blood CD34+ cells were first cultured in static flasks and then inoculated to stirred-tank bioreactors.

Role of Plasma Gelsolin Protein in the Final Stage of Erythropoiesis and in Correction of Erythroid Dysplasia In Vitro.

Gelsolin, an actin-remodeling protein, is involved in cell motility, cytoskeletal remodeling, and cytokinesis and is abnormally expressed in many cancers. Recently, human recombinant plasma gelsolin protein (pGSN) was reported to have important roles in cell cycle and maturation of primary erythroblasts. However, the role of human plasma gelsolin in late stage erythroblasts prior to enucleation and putative clinical relevance in patients with myelodysplastic syndrome (MDS) and hemato-oncologic diseases have not been reported.

Improvement of Red Blood Cell Maturation by Serum-Free Medium Optimization.

Despite recent studies on media additives, the low viability and dysplastic features of terminally mature erythroid cells are still major problems in enhancing erythroid cell yields . Moreover, research on enhancing terminal erythropoiesis has been focused on the immature stage of erythroid cells such as burst forming unit-erythroid and colony forming unit-erythroid. Here, we tested many commercially available serum-free culture media and developed a superior culture media formulation compared with the conventional control for higher expansion-fold, higher viability, and therefore enhanced red cell productivity.

The effects of plasma gelsolin on human erythroblast maturation for erythrocyte production.

Gelsolin is an actin binding protein present in blood plasma and in cytoplasm of cells including macrophages. Gelsolin has important functions in cell cycle regulation, apoptotic regulation, and morphogenesis. Even though bone marrow macrophages and serum factors are critical for regulating erythropoiesis, the role of gelsolin on human erythroblasts has not been studied.

Mbd2-CP2c loop drives adult-type globin gene expression and definitive erythropoiesis.

During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes.

Red blood cell generation by three-dimensional aggregate cultivation of late erythroblasts.

Stem cell-derived erythroid cells hold great potential for the treatment of blood-loss anemia and for erythropoiesis research; however, cultures using conventional flat plates or bioreactors have failed to show promising results. By mimicking the in vivo bone marrow (BM) environment in which most erythroid cells are physically aggregated, we show that a three-dimensional (3D) aggregate culture system facilitates erythroid cell maturation and red blood cell (RBC) production more effectively than two-dimensional high-density cell cultivation. Late erythroblasts (polychromatic or orthochromatic erythroblasts) were differentiated from cord blood CD34(+) cells over 15 days and then allowed to form tight aggregates at a minimum density of 1×10(7) cells/mL for 2-3 days.

De novo hairy cell leukemia with a major BCR/ABL1 rearrangement: a case report with a literature review.

Hairy cell leukemia (HCL) is a very rare mature B-cell neoplasm and its simultaneous occurrence with chronic myeloid leukemia has been reported in only three cases. The pathogenesis and relationship of the two diseases are not clear. Here we report a case of HCL expressing a BCR/ABL1 clone, which showed molecular remission of the fusion clones and achieved partial remission over nine months of cladribine therapy.

The RNA in reticulocytes is not just debris: it is necessary for the final stages of erythrocyte formation.

Reticulocytes contain both RNA and micro-organelles and represent the last stage of erythropoiesis before full maturation to red blood cells (RBCs). Even though there is continuing synthesis of hemoglobin and membrane-bound proteins in reticulocytes, the small amount of RNA that they contain has been regarded as non-functional residual material. Here we show that this residual RNA is both functional and essential for further reticulocyte maturation.

Randomized controlled trials in endourology: a quality assessment.

Purpose: To analyze the quality of studies reporting randomized clinical trials (RCTs) in the field of endourology.

Materials And Methods: RCTs published in the Journal of Endourology from 1993 until 2011 were identified. The Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool (CCRBT) were used to assess the quality of the studies.

Autonomous control of terminal erythropoiesis via physical interactions among erythroid cells.

In vitro erythropoiesis has been studied extensively for its application in the manufacture of transfusable erythrocytes. Unfortunately, culture conditions have not been as effective as in vivo growth conditions, where bone marrow macrophages are known to be a key regulator of erythropoiesis. This study focused on the fact that some erythroblasts are detached from macrophages and only contact other erythroblasts.

Topical treatment of the buccal mucosa and wounded skin in rats with a triamcinolone acetonide-loaded hydrogel prepared using an electron beam.

In this study, a triamcinolone acetonide-loaded hydrogel was prepared by electron beam irradiation and evaluated for use as a buccal mucoadhesive drug delivery system. A poloxamer was modified to have vinyl end groups for preparation of the hydrogel via an irradiation cross-linking reaction. Carbopol was introduced to improve the mucoadhesive properties of the hydrogel.

Preparation and irradiation of Pluronic F127-based thermoreversible and mucoadhesive hydrogel for local delivery of naproxen.

To improve physical properties and modulate the mucoadhesive hydrogel formulation via cross-linking by radiation, hydrogels were prepared using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer carbopol 934P (C934P). As a model drug, naproxen was loaded in the hydrogel formulation. Sol-gel transition temperatures of hydrogels were measured by the tube-inversion method.

Red blood cell engineering in stroma and serum/plasma-free conditions and long term storage.

In vitro generation of artificial red blood cells (RBCs) is very important to overcome insufficient and unsafe blood supply. Despite recent progresses in RBCs engineering from several stem cell sources, none of them could succeed in generation of functional RBCs in the absence of serum/plasma and feeder cells. Without the elimination of serum and plasma, human RBC engineering in a large scale is impossible, especially for the future bioreactor system.

Direct and differential effects of stem cell factor on the neovascularization activity of endothelial progenitor cells.

Aims: Previous studies on the role of stem cell factor (SCF) in endothelial progenitor cell (EPC)-mediated neovascularization have focused on the EPC mobilization and homing process. However, the direct effects of SCF on neovascularization activity of EPCs have not been characterized. We sought to determine whether SCF regulates the neovascularization ability of EPCs by comparing its roles in mature endothelial cells.

Enhanced production of red blood cells in suspension by electrostatic interactions with culture plates.

Enucleation of erythroblasts, a critical step in the generation of red blood cells (RBCs), occurs at a low rate without cocultured stromal cells. Previously, the surface properties of the cell culture plate were not considered in the enucleation process, because the cells exist in suspension. Here, we show that a significantly higher rate of enucleation of erythroblasts occurred on the positively charged plates than on the negatively charged surfaces or the both negatively and positively charged plates.

Two-step maturation of immature DCs with proinflammatory cytokine cocktail and poly(I:C) enhances migratory and T cell stimulatory capacity.

Effective induction of cell-mediated immune responses strongly depends on the ability of dendritic cells (DCs) to produce Th1-polarizing cytokines, migrate to lymph nodes and stimulate T cells through antigen-presenting complex and costimulatory molecules. While various protocols for optimizing DC maturation with single or multiple stimuli mimicking infections or inflammatory milieu have been proposed for the generation of DCs with features desired for clinical application, stepwise maturation of DCs by these multiple stimuli has not been systemically assessed. Among the combinations of several immune-modulating factors with known effects on DC maturation, we found that stepwise DC maturation with cytokine cocktail (TNF-alpha+IL-6+IL-1 beta+PGE(2)) followed by poly(I:C) stimulation enhanced the production of IL-12 with strong allostimulatory capacity.