Diagnosis and Treatment Management in Patients with Autoimmune Neutropenia

Autoimmune neutropenia (AIN) is the frequent cause of neutropenia in infants and children. AIN is associated with a reduced neutrophil count, which is due to aberrant cell-mediated or humoral immune response. In this review, we will discuss the available diagnostic approaches and management of the diseases. We collected data from PubMed, Google Scholar, Medline, Web of Science databases, using a group of key words, such as neutropenia, autoimmune, diagnosis and management from 2000 until 2019. The most important aspects of primary assessment in the affected children were family history and physical examinations. Diagnostic methods in this disease are granulocyte indirect agglutination test (GAT) and granulocyte immunofluorescence test (GIFT). However, the sensitivity and specificity of these tests are low. In these patients, injection of granulocyte-colony stimulating factor (G-CSF), is the first line of treatment. Despite low prevalence, autoimmune neutropenia is a clinically significant disease and it is critical to identify it and pursue effective treatment in these patients

Effect of PEGylation on assembly morphology and cellular uptake of poly ethyleneimine-cholesterol conjugates for delivery of sorafenib tosylate in hepatocellular carcinoma

Introduction: Sorafenib (SFB) is an FDA-approved chemotherapeutic agent with a high partition coefficient (log P = 4.34) for monotherapy of hepatocellular carcinoma (HCC). The oral bioavailability is low and variable, so it was aimed to study the application of the polymeric nanoassembly of cholesterol conjugates of branched polyethyleneimine (PEI) for micellar solubilization of SFB and to investigate the impact of the polymer PEGylation on the physicochemical and cellular characteristics of the lipopolymeric dispersions. Methods: Successful synthesis of cholesterol-PEI lipopolymers, either native or PEGylated, was confirmed by FTIR, 1H-NMR, pyrene assay methods. The nanoassemblies were also characterized in terms of morphology, particle size distribution and zeta-potential by TEM and dynamic light scattering (DLS). The SFB loading was optimized using general factorial design. Finally, the effect of particle characteristics on cellular uptake and specific cytotoxicity was investigated by flow cytometry and MTT assay in HepG2 cells. Results: Transmission electron microscopy (TEM) showed that PEGylation of the lipopolymers reduces the size and changes the morphology of the nanoassembly from rod-like to spherical shape. However, PEGylation of the lipopolymer increased critical micelle concentration (CMC) and reduced the drug loading. Moreover, the particle shape changes from large rods to small spheres promoted the cellular uptake and SFB-related cytotoxicity. Conclusion: The combinatory effects of enhanced cellular uptake and reduced general cytotoxicity can present PEGylated PEI-cholesterol conjugates as a potential carrier for delivery of poorly soluble chemotherapeutic agents such as SFB in HCC that certainly requires further investigations in vitro and in vivo

Bioinformatics-Guided Discovery of miRNAs Involved in Apoptosis Modulated by Parthenolide Combined with Vincristine in The NALM6 Cell Line

Objective: Acute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement inconventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from theTanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induceapoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone onthe apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line.Materials and Methods: In this experimental study, cell viability and metabolic activity were determined through MTTassay and PI staining. Flow cytometry was applied to evaluate the rate of apoptosis. The expression of miRNAs wasassessed using real-time polymerase chain reaction. Bioinformatic analyses, including Cytoscape, RNAhybrid, andsignaling pathway analysis were employed to investigate the association of miR-17-5p, miR-181b-5p and miR-125b-5p with apoptosis. Further, molecular docking served to validate the modulation of these miRNAs by parthenolide andvincristine treatment.Results: The MTT assay indicated that 7.7 μM of parthenolide decreased the metabolic activity to 50% after 48 hours. PIstaining analysis indicated that at concentrations below the half maximal inhibitory concentration, parthenolide caused50% cell death. Flow cytometric analysis indicated that parthenolide (1.925 μM) in combination with vincristine (1.2 nM)induced apoptosis in 83.2% of the cells. Real-time quantitative reverse transcription polymerase chain reaction (qRTPCR)analysis showed significant changes in the expression levels of miR-17-5p, miR-125b-5p, and miR-181b-5p.Moreover, the combination therapy downregulated the expression of miRNAs significantly. This was consistent with ourbioinformatic analysis demonstrating that the studied miRNAs are regulators of apoptosis. Finally, molecular dockingvalidated the modulation of the miRNAs by parthenolide and vincristine.Conclusion: Parthenolide in combination with vincristine triggers apoptosis at a high rate in the NALM6 cell line.Moreover, this combination therapy can decrease the expression of miR-17-5p, miR-181b-5p, and miR-125b-5p

The effect of aquatic training and vitamin D3 supplementation on bone metabolism in postmenopausal obese women

Purpose: Despite prevalence of studies indicating the positive effect of land-based exercise on bone metabolism, there are limited findings regarding the effect of aquatic exercise. The present study aimed to evaluate the effects of aquatic training and vitamin D3 supplementation on femur bone mineral density (BMD), serum 25(OH)D, and parathyroid hormone (PTH) in postmenopausal obese women with vitamin D insufficiency. Methods: 40 postmenopausal obese women were randomly divided into four groups of aquatic training + vitamin D3 intake group; (ATD), aquatic training with placebo intake group (AT), vitamin D3 intake group (D), and control group with placebo intake (CON). AT groups performed aerobic aquatic exercises for 8 weeks. Vitamin D3 supplementation groups consumed oral dose of 4000 IU/d for 8 weeks. Results: The femur BMD was significantly higher in the ATD than the AT and D and CON groups; in AT it was higher than the D and CON groups. Serum 25(OH)D level in the ATD was more than AT and CON, and in the D was more than the CON and AT. PTH in the ATD group was lower compared to AT, D, and CON groups. PTH was lower in the AT and D compared to the CON. Conclusion: In postmenopausal obese women with vitamin D insufficiency or deficiency, combining vitamin D supplementation and aquatic training was the most effective method for improving bone metabolism; Vitamin D supplementation (alone) was not sufficient to affect some of bone metabolism indices; Aquatic training could not improve serum vitamin D. By priority, ATD, AT, and D indicated better bone related metabolism indices

miR-4284 and miR-4484 as Putative Biomarkers for Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. MicroRNAs (miRNAs) are endogenous small RNA, which can regulate gene expression at the post-transcriptional level. MiRNA profiling has shown a great potential as novel diagnostic and prognostic biomarkers. The present study was performed at the Nemazee Teaching Hospital (Shiraz, Iran) from 2011 to 2013.The aim of this study was to assess the deregulation of miRNAs profiles in DLBL against hyperplasic reactive lymph node as a normal. This could serve as a biomarker for DLBL. The miRCURY LNATM microarray was used on the total RNA, which was extracted from formalin-fixed paraffin-embedded tissue of 24 de novo diffuse large B-cell lymphoma patients and 14 normal lymph nodes. The greatest changes were detected in miR-4284 and miR-4484 level in patient’s lymphoma samples. These miRNAs can act as a diagnostic biomarker for DLBL

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs have been also utilized for the treatment of skin disorders, imaging, and biosensing applications. Despite the widespread transdermal applications of NPs, their delivery across the stratum corneum, which is the main skin barrier, has remained challenging. Microneedle array (MN) technology has recently revealed promising outcomes in the delivery of various formulations, especially NPs to deliver both hydrophilic and hydrophobic therapeutic agents. The present work reviews the advancements in the application of MNs and NPs for an effective transdermal delivery of a wide range of therapeutics in cancer chemotherapy and immunotherapy, photothermal and photodynamic therapy, peptide/protein vaccination, and the gene therapy of various diseases. In addition, this paper provides an overall insight on MNs’ challenges and summarizes the recent achievements in clinical trials with future outlooks on the transdermal delivery of a wide range of nanomedicines

The stability of triphasic oil-in-water Pickering emulsions can be improved by physical modification of hordein- and secalin-based submicron particles

The main objective of this work was to study the capability of either non-modified or physically-modified beta-hordein and gamma-secalin particles as Pickering emulsion stabilizers. A comparison was performed with zein-based particles as a commercial source of prolamins. Protein dispersions in ethanol-water medium were subjected to different heat treatments and then characterized. A simple anti-solvent precipitation method in combination with sonication was applied to fabricate colloidal submicron particles. Analyses of the fluorescence intensity and thiol group content revealed heat-induced conformational changes of individual protein molecules but not protein aggregation. SEM micrographs confirmed the formation of spherical-shaped submicron and nano-particles. Ultrasound treatment relatively decreased the interfacial tension of prolamin-based particles. Contact angle results suggested the possible superiority of hordein and secalin particles to zein ones in Pickering stabilization. A predominant elastic gel-like behavior (i.e., G' > G '') along with different dependencies on the angular frequency was observed in dynamic frequency sweep test of Pickering emulsions. The shear thinning behavior of all samples was attributed to the deflocculation of oil droplets. The final emulsion characteristics were influenced by the particle type and the applied physical treatments. It was found that hordein-based particles have the ability to develop emulsion-foam (triphasic) structures with the physical stability at least 20 times higher than those prepared by zein-based particles. The results of this study may help in the design of Pickering systems using prolamin-based natural particles