Biocompatibility of magnetic nanoparticles synthesized through green routed with a focus on hematological and histological analysis.

The interaction of metal nanoparticles (MNPs) with blood cells and tissues is essential from the perspectives of biocompatibility and the production of novel drug delivery systems. In the present study, biosynthesized-Fe3O4 nanoparticles (bio-Fe3O4 NPs) were prepared and bio-modified using Daphne mucronata Royle leaf extracts. The physicochemical properties of bio-Fe3O4 NPs were determined using UV-Visible spectroscopy, Energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) analyses. According to the SEM analysis, the bio-Fe3O4 NPs are spherical-shaped with a size range of 10-30 nm. Antibacterial effects of bio-Fe3O4 NPs against Staphylococcus aureus ATCC 43300 and Pseudomonas aeruginosa ATCC 27853 bacteria were measured by minimum inhibition/bactericidal concentrations (MIC and MBC tests). Result showed that the bio-Fe3O4 NPs (300 ppm) revealed highest antibacterial effect on S. aureus ATCC 43300. Also, bio-Fe3O4 NPs have different cell viability in the human breast cancer cell line (MCF-7) and mouse embryonic fibroblast (MEF). The interaction of bio-Fe3O4 NPs with blood cells and the complete blood count (CBC) factor illustrated that the morphology of blood cells and platelet clumping did not influence by nanoparticles. Furthermore, histological analysis of the liver, spleen, and kidney did not show any abnormality upon exposure to 100 mg kg-1 bio-Fe3O4 NPs treated samples. Hence, the biosynthesized Fe3O4 NPs are a good candidate for applications in medical fields.

The role of catecholamines in mesenchymal stem cell fate.

Mesenchymal stem cells (MSCs) are multipotent stem cells found in many adult tissues, especially bone marrow (BM) and are capable of differentiation into various lineage cells such as osteoblasts, adipocytes, chondrocytes and myocytes. Moreover, MSCs can be mobilized from connective tissue into circulation and from there to damaged sites to contribute to regeneration processes. MSCs commitment and differentiation are controlled by complex activities involving signal transduction through cytokines and catecholamines. There has been an increasing interest in recent years in the neural system, functioning in the support of stem cells like MSCs. Recent efforts have indicated that the catecholamine released from neural and not neural cells could be affected characteristics of MSCs. However, there have not been review studies of most aspects involved in catecholamines-mediated functions of MSCs. Thus, in this review paper, we will try to describe the current state of catecholamines in MSCs destination and discuss strategies being used for catecholamines for migration of these cells to damaged tissues. Then, the role of the nervous system in the induction of osteogenesis, adipogenesis, chondrogenesis and myogenesis from MSCs is discussed. Recent progress in studies of signaling transduction of catecholamines in determination of the final fate of MSCs is highlighted. Hence, the knowledge of interaction between MSCs with the neural system could be applied towards the development of new diagnostic and treatment alternatives for human diseases.

The role of the nervous system in hematopoietic stem cell mobilization.

Hematopoietic stem cells (HSCs) and blood cell progenitors, such as maturing leucocytes, steadily enter from bone marrow (BM) into the circulation under steady-state conditions, and their mobilization is dramatically amplified during stress conditions and by mediators such as granulocyte colony-stimulating factor (G-CSF). This mobilization is dependent upon bone remodeling, the proteolytic enzymes of bone marrow-derived stromal cells, and adhesion molecules such as integrin, but the main mechanisms controlling this traffic are still unclear. The nervous system, as the most important regulator of the body, can affect the mobilization network by secreting catecholamines, so that denervation of catecholaminergic fibers in the BM of mice could lead to declining mobilization in steady state and stress situations, even in the presence of other intact environmental factors in the BM. Thus, due to the importance of the nervous system, we have attempted to give a general overview of how the nervous system is involved in the mobilization of HSCs in this review. Then, we will try to describe the mobilization process induced by the nervous system, which consists of 3 mechanisms: stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4), proteolytic enzymes, and bone remodeling.

Long noncoding RNAs (lncRNAs) in human lymphomas.

Lymphomas are a diverse group of haematologic malignancies, which occur in infection-fighting cells of the lymphatic system. Long non-coding RNAs (lncRNAs) are non-coding RNAs, which have recently received significant attention as the main mediators of gene expression. In this review, we summarize the current knowledge on lncRNAs involved in lymphomas, their molecular functions, as well as their potential clinical value. Relevant literature was identified by a PubMed search of English language papers using the following terms: Lymphoma, LncRNA, leukemia, proliferation, apoptosis, and prognosis. LncRNAs are imperative for lymphoma carcinogenesis through affecting apoptosis, cell proliferation, invasion, and response to chemotherapy. The expression level of lncRNAs can affect chemotherapy-induced apoptosis. Taken together, lncRNA dysregulation in lymphoma cells is not only an epiphenomenon but also lncRNA transcription is critically related to the initiation and progression of lymphomas. Aberrant expression of lncRNAs can lead to the transformation of normal lymphocytes into lymphoma cells.

Hematological parameters and X-ray exposure among medical radiation workers: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to explore the effect of occupational exposure to X-ray on hematological parameters. RESEARCH DESIGN AND METHODS: A systematic search was conducted in the Scopus, PubMed, Web of Science, and Embase databases up to April 2020. The methodological quality was assessed by Joanna Briggs Institute (JBI) Critical Appraisal Checklist . The random-effects model was used to estimate the effect size (standard difference in means (SDMs)). RESULTS: Out of 1750 identified citations, ten studies met the inclusion criteria The overall effect size did not show any significant difference between the two groups (SMDs ranged from -0.382 ± 0.29 for white blood cells (WBC), 0.213 ± 0.40 for platelet, -0.323 ± 0.0.16 for mean corpuscular volume (MCV), 0.553 ± 0.41 for mean corpuscular hemoglobin concentration (MCHC), -1.615 ± 1.41 for monocyte, 0.418 ± 0.49 for lymphocyte (P-value>0.05). Only the effect size of red blood cells was significantly higher than that of the control group (SMD = 1.06 ± 0.28; 95% CI: 0.504, 1.615; P-value = 0.001). CONCLUSION: The long-term and low-dose radiation may have no significant effect on blood parameters. Future studies are suggested to use other tests such as dicentric chromosome assay (DCA), cytogenetic tests, and modern tests besides blood count parameters.

Red Blood Cells are Appropriate Carrier for Coagulation Factor VIII.

AIMS: Factor VIII (FVIII) replacement therapy remains a primary treatment for hemophilia A, however, the development of FVIII antibodies (inhibitors) and short half-life of the FVIII products are the major complications. Erythrocytes may prevent rapid removal of drugs from plasma. Erythrocytes are biocompatible and non-immunogenic drug delivery. In this study, in vitro activity of FVIII encapsulated by human erythrocytes was investigated. METHODS: FVIII was loaded into erythrocytes using the hypo-osmotic dialysis technique. FVIII activity assay has been analyzed using Activated Partial Thromboplastin Time (APTT). Presence of FVIII on erythrocytes was detected by western blotting and flowcytometry using specific monoclonal antibody (abcam, U.K) against FVIII. Moreover, the osmotic fragility and hematologic parameters of FVIII-loaded carrier erythrocytes were measured. RESULTS: Our results indicated that FVIII could not cross the membrane, where plenty of FVIII was found on the surface of the carrier erythrocyte. Flow cytometery results showed that 11% of the loaded carrier erythrocytes was positive for FVIII protein on their surface. The greatest activation of FVIII in both groups including lysate and non-lysate FVIII-loaded RBCs was observed on the first day, and the coagulant activity of this factor was gradually reduced on days 3 and 5. In 1:50 dilution of both groups, significant differences in FVIII activity were observed in 1:50 dilution of both groups, especially on the 5th day. CONCLUSION: This study aims to introduce erythrocytes as appropriate carriers for FVIII to prolong the dosing intervals in the effective and safe levels for a relatively longer time.

New role of hypoxia in pathophysiology of multiple myeloma through miR-210.

Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an important role in hematological malignancies. In an attempt to elucidate the specificity of the pathways of hypoxia and miR-210 in suppression of osteoblastic differentiation in MM patients, we examined the effect of miR-210 and hypoxia on expression of important cytokines and genes of myeloma cells. Differentiation of BM-MSCs towards osteoblastic cells in response to microvesicles (MVs) was also investigated. Finally, we proposed a molecular model on how HIF-1α may promote bone lesions in MM patients. To validate the effect of miR-210 and HIF-1α on targeted genes, the shRNA of HIF-1α and off-hsa-miR-210 were transfected into RPMI-8226 cells. BM-MSCs were cultured in osteoblastic inducer and 50 µg/mL of MVs derived from both hypoxic and normoxic myeloma cells. We designed an in vitro study to establish the effects of HIF-1α and miR-210 on the crosstalk between MM and osteoblasts. We here showed that hypoxia-induced miR-210 increased the mRNA expression of VLA-4, CXCR4, IL-6 and TGF-ß in myeloma cells. MiR-210 is mandatory for the hypoxia-increased resistance of MM cells to melphalan. Moreover, MVs derived from hypoxic myeloma cells substantially decreased osteoblast differentiation. Considered comprehensively, our findings explain one of the reasons of bone loss that occurs at the sites of MM and a nascent crosstalk model in MM pathogenesis.

Sex chromosome changes in leukemia: cytogenetics and molecular aspects.

BACKGROUND AND OBJECTIVE: Sex chromosome loss (SCL) can occur in older men as a physiological phenomenon or as an acquired abnormality in leukemia. Loss of chromosome Y and loss of chromosome X are acquired disorders that are mainly observed in patients over 80 years as well as in myeloid and lymphoid malignancies. In this review, we examine the cytogenetic and molecular changes of sex chromosomes in leukemia. METHODS: Relevant English language literature were searched and retrieved from PubMed search engine (1990-2016). The following keywords were used: 'Sex chromosomes', 'Leukemia' and 'Cytogenetics'. RESULTS: The loss of tumor suppressor genes along with these chromosomal abnormalities in the majority of malignant cells in bone marrow (BM) has raised the question whether this is an age-related phenomenon or has occurred as a result of clonal abnormality. On the other hand, the presence of these chromosomal abnormalities in a number of genetic diseases associated with leukemia leads to progression of malignancy, and their role in peripheral blood stem cell transplantation confirm the finding that these chromosomal abnormalities can play an important role in clonal abnormality. CONCLUSION: The presence of these abnormalities can cause genetic instability in BM and result in the development of a malignant clone and progression of the disease. In addition, the evaluation of SCL together with the genes involved in these chromosomes can contribute to predict the disease prognosis as well as monitoring of malignancy.

Chitosan coated tungsten trioxide nanoparticles as a contrast agent for X-ray computed tomography.

Recent advances have shown that inorganic nanoparticles (NPs) based on heavy elements are highly appropriate for X-ray computed tomography (CT). In this contribution, tungsten trioxide NPs are prepared by the electrical arc discharge (EAD) method in DI water. The effect of chitosan (CTS) and glutaraldehyde (GTA) as coating and cross-linking agent, respectively, on the hydrodynamic size and zeta potential of prepared tungsten trioxide NPs is investigated. It is found that zeta potential increases by increasing the amounts of CTS. Meanwhile, by increasing the volume of glutaraldehyde (GTA), the final particle size increases whereas the zeta potential deceases. Chitosan coated tungsten trioxide demonstrated no significant cytotoxicity at concentration up to 5mg/mL after 24h. Finally, the X-ray attenuation of prepared chitosan coated tungsten trioxide NPs are higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations.

Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis.

BACKGROUNDS: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults and is characterized by a clonal accumulation of mature apoptosis-resistant neoplastic cells. It is also a heterogeneous disease with a variable clinical outcome. Here, we present a review of currently known (epi)genetic alterations that are related to the etiology, progression and chemo-refractoriness of CLL. Relevant literature was identified through a PubMed search (1994-2014) of English-language papers using the terms CLL, signaling pathway, cytogenetic abnormality, somatic mutation, epigenetic alteration and micro-RNA. RESULTS: CLL is characterized by the presence of gross chromosomal abnormalities, epigenetic alterations, micro-RNA expression alterations, immunoglobulin heavy chain gene mutations and other genetic lesions. The expression of unmutated immunoglobulin heavy chain variable region (IGHV) genes, ZAP-70 and CD38 proteins, the occurrence of chromosomal abnormalities such as 17p and 11q deletions and mutations of the NOTCH1, SF3B1 and BIRC3 genes have been associated with a poor prognosis. In addition, mutations in tumor suppressor genes, such as TP53 and ATM, have been associated with refractoriness to conventional chemotherapeutic agents. Micro-RNA expression alterations and aberrant methylation patterns in genes that are specifically deregulated in CLL, including the BCL-2, TCL1 and ZAP-70 genes, have also been encountered and linked to distinct clinical parameters. CONCLUSIONS: Specific chromosomal abnormalities and gene mutations may serve as diagnostic and prognostic indicators for disease progression and survival. The identification of these anomalies by state-of-the-art molecular (cyto)genetic techniques such as fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), single nucleotide polymorphism (SNP) microarray-based genomic profiling and next-generation sequencing (NGS) can be of paramount help for the clinical management of these patients, including optimal treatment design. The efficacy of novel therapeutics should to be tested according to the presence of these molecular lesions in CLL patients.

G-CSF induces up-regulation of CXCR4 expression in human hematopoietic stem cells by beta-adrenergic agonist.

Introduction C-X-C chemokine receptor type 4/stromal-derived factor-1 (CXCR4/SDF-1) axis dynamically mediates hematopoietic stem cell trafficking in the bone marrow (BM). Granulocyte colony-stimulating factor (G-CSF) as the most effective mobilizing agent induces SDF-1 secretion from BM stromal cells into circulation that recruit CXCR4+ cells such as hematopoietic stem cells (HSCs) into circulation. However, the direct effect of G-CSF on CXCR4 expression of HSC remains unknown. The nervous system regulates HSC migration with effecting on adrenergic receptors. On the other hand, interaction of G-CSF and catecholamines has been demonstrated; hence, we examined the direct effect of G-CSF and catecholamine on CXCR4 expression. Material and methods After enrichment of CD34+ HSCs from the cord blood with magnetic-activated cell sorting (MACS), these cells were exposed to G-CSF (100 ng/ml), epinephrine (10 µM), isoproterenol (10 µM), and propranolol (1 µM) separately and together. Results Our results showed that G-CSF have no direct effect on CXCR4 expression on human CD34+ cells in vitro and treating HSCs with epinephrine leads to significantly increased CXCR4 in 1, 3, and 5 hours. Epinephrine and G-CSF-induced up-regulation of CXCR4 mRNA is dependent on beta receptors, so incubation of HSCs with propranolol led to inhibition of such increased expression. In addition, isoproterenol and agonist of beta receptors would significantly increase the expression of CXCR4 approximately 4- and 12-fold after 1-hour incubation, respectively. Discussion Co-stimulation of enriched HSCs with G-CSF and isoproterenol resulted to a further enhanced CXCR4 levels. In general, G-CSF-induced CXCR4 expression is the indirect mechanism and is specifically regulated through beta-adrenergic receptors.

The role of notch signaling in bone marrow niche.

OBJECTIVE: Bone marrow (BM) niche is a three-dimensional structure composed of a series of cells and it is one of the most controversial topics in hematological malignancies, leukemia, and even metastasis. Here, we review the relationship between Notch signaling and different fates of stem cells and other BM niche cells. METHODS: Relevant English-language literature were searched and retrieved from PubMed (2000-2013) using the terms Notch signaling, BM niche, and microRNAs (miRNAs). DISCUSSION: Notch signaling pathway is a signaling system involved in cellular processes such as proliferation, differentiation, and apoptosis. The notch signaling pathway components are associated with interaction between leukemic, metastatic, and normal cells and their microenvironment. miRNAs play an important role in expression and regulation of signaling molecules. It is necessary to evaluate the relationship between aberrant miRNA expression and notch signaling such as miR-128 and miR-30 in glioma and angiogenesis with notch signaling, respectively. CONCLUSIONS: Characterizing malignant cells and future studies focus on better understanding the variety of cancers and apoptosis with activated Notch signaling pathway, may remain promising this signaling system as a safe and effective therapeutic target.