Metabolic features of neutrophilic differentiation of HL-60 cells in hyperglycemic environments.

Introduction: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study.

Research Design And Methods: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression.

Neutrophils, an emerging new therapeutic platform.

Neutrophils possess unique characteristics that render them indispensable to health, and patients with irregular neutrophil counts or functions suffer from increased morbidity and mortality. As neutrophils are short-lived postmitotic cells, genetic aberrations cannot be corrected directly in neutrophils and must be targeted in their progenitors. Neutrophils are increasingly being contemplated for a range of therapeutic applications, including restoration or modulation of immune function and targeting of solid tumors.

Soluble factors in COVID-19 mRNA vaccine-induced myocarditis causes cardiomyoblast hypertrophy and cell injury: a case report.

Background: Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood.

A cross-sectional study evidences regulations of leukocytes in the colostrum of mothers with obesity.

Background: Breastmilk is a dynamic fluid whose initial function is to provide the most adapted nutrition to the neonate. Additional attributes have been recently ascribed to breastmilk, with the evidence of a specific microbiota and the presence of various components of the immune system, such as cytokines and leukocytes. The composition of breastmilk varies through time, according to the health status of mother and child, and altogether contributes to the future health of the infant.

A pseudovirus-based platform to measure neutralizing antibodies in Mexico using SARS-CoV-2 as proof-of-concept.

The gold-standard method to evaluate a functional antiviral immune response is to titer neutralizing antibodies (NAbs) against a viral pathogen. This is historically performed using an in vitro assay of virus-mediated infection, which requires BSL-3 facilities. As these are insufficient in Latin American countries, including Mexico, scant information is obtained locally about viral pathogens NAb, using a functional assay.

Corrigendum: Immobilization of Growth Factors for Cell Therapy Manufacturing.

[This corrects the article DOI: 10.3389/fbioe.2020.

Immobilization of Growth Factors for Cell Therapy Manufacturing.

Cell therapy products exhibit great therapeutic potential but come with a deterring price tag partly caused by their costly manufacturing processes. The development of strategies that lead to cost-effective cell production is key to expand the reach of cell therapies. Growth factors are critical culture media components required for the maintenance and differentiation of cells in culture and are widely employed in cell therapy manufacturing.

The role of B cells in heart failure and implications for future immunomodulatory treatment strategies.

Despite numerous demonstrations that the immune system is activated in heart failure, negatively affecting patients' outcomes, no definitive treatment strategy exists directed to modulate the immune system. In this review, we present the evidence that B cells contribute to the development of hypertrophy, inflammation, and maladaptive tissue remodelling. B cells produce antibodies that interfere with cardiomyocyte function, which culminates as the result of recruitment and activation of a variety of innate and structural cell populations, including neutrophils, macrophages, fibroblasts, and T cells.

Manufactured Neutrophils for Treatment of Neutropenia-A Process Economic Evaluation.

Neutropenia is a common side-effect of acute myeloid leukemia (AML) chemotherapy characterized by a critical drop in neutrophil blood concentration. Neutropenic patients are prone to infections, experience poorer clinical outcomes, and require expensive medical care. Although transfusions of donor neutrophils are a logical solution to neutropenia, this approach has not gained clinical traction, primarily due to challenges associated with obtaining sufficiently large numbers of neutrophils from donors whilst logistically managing their extremely short shelf-life.

HIF prolyl hydroxylase inhibitor FG-4497 enhances mouse hematopoietic stem cell mobilization via VEGFR2/KDR.

In normoxia, hypoxia-inducible transcription factors (HIFs) are rapidly degraded within the cytoplasm as a consequence of their prolyl hydroxylation by oxygen-dependent prolyl hydroxylase domain (PHD) enzymes. We have previously shown that hematopoietic stem and progenitor cells (HSPCs) require HIF-1 for effective mobilization in response to granulocyte colony-stimulating factor (G-CSF) and CXCR4 antagonist AMD3100/plerixafor. Conversely, HIF PHD inhibitors that stabilize HIF-1 protein in vivo enhance HSPC mobilization in response to G-CSF or AMD3100 in a cell-intrinsic manner.

Universal Alternative Splicing of Noncoding Exons.

The human transcriptome is so large, diverse, and dynamic that, even after a decade of investigation by RNA sequencing (RNA-seq), we have yet to resolve its true dimensions. RNA-seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed targeted single-molecule and short-read RNA-seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution.

Genomic insights into human colonization.

(Karassova V, Weissfeiler J, Kraszanay E, Acta Microbiol Acad Sci Hung 12:275-82, 1965) is a slow-growing nontuberculous species found in environmental niches, and recently evidenced as an opportunistic Human pathogen. We report here the genome of a clinical isolate of (MsiGto) obtained from a patient in Guanajuato, Mexico. With a size of 6,684,413 bp, the genomic sequence of strain MsiGto is the largest of the three genomes reported to date.

HIF-1α-stabilizing agent FG-4497 rescues human CD34 cell mobilization in response to G-CSF in immunodeficient mice.

Granulocyte colony-stimulating factor (G-CSF) is used routinely in the clinical setting to mobilize hematopoietic stem progenitor cells (HSPCs) into the patient's blood for collection and subsequent transplantation. However, a significant proportion of patients who have previously received chemotherapy or radiotherapy and require autologous HSPC transplantation cannot mobilize the minimal threshold of mobilized HSPCs to achieve rapid and successful hematopoietic reconstitution. Although several alternatives to the G-CSF regime have been tested, few are used in the clinical setting.

Fms-like tyrosine kinase 3 (Flt3) ligand depletes erythroid island macrophages and blocks medullar erythropoiesis in the mouse.

The cytokines granulocyte colony-stimulating factor (G-CSF) and Flt3 ligand (Flt3-L) mobilize hematopoietic stem and progenitor cells into the peripheral blood of primates, humans, and mice. We recently reported that G-CSF administration causes a transient blockade of medullar erythropoiesis by suppressing erythroblastic island (EI) macrophages in the bone marrow. In the study described here, we investigated the effect of mobilizing doses of Flt3-L on erythropoiesis in mice in vivo.

Filling the void: allogeneic myeloid cells for transplantation.

Purpose Of Review: The success of allogeneic haematopoietic stem and progenitor cell (HSPC) transplantations remains inconsistent. Umbilical cord blood (UCB) is a promising source of HSPCs for transplantation, but low cell yield hampers its widespread use. Multiple strategies are being developed to manipulate UCB to either increase HSPC content or enhance bone marrow homing upon transfusion.

Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients.

In animals, immunomodulatory dendritic cells (DCs) exposed to autoantigen can suppress experimental arthritis in an antigen-specific manner. In rheumatoid arthritis (RA), disease-specific anti-citrullinated peptide autoantibodies (ACPA or anti-CCP) are found in the serum of about 70% of RA patients and are strongly associated with HLA-DRB1 risk alleles. This study aimed to explore the safety and biological and clinical effects of autologous DCs modified with a nuclear factor κB (NF-κB) inhibitor exposed to four citrullinated peptide antigens, designated "Rheumavax," in a single-center, open-labeled, first-in-human phase 1 trial.

Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing.

We compared quantitative RT-PCR (qRT-PCR), RNA-seq and capture sequencing (CaptureSeq) in terms of their ability to assemble and quantify long noncoding RNAs and novel coding exons across 20 human tissues. CaptureSeq was superior for the detection and quantification of genes with low expression, showed little technical variation and accurately measured differential expression. This approach expands and refines previous annotations and simultaneously generates an expression atlas.

Genome-wide discovery of human splicing branchpoints.

During the splicing reaction, the 5' intron end is joined to the branchpoint nucleotide, selecting the next exon to incorporate into the mature RNA and forming an intron lariat, which is excised. Despite a critical role in gene splicing, the locations and features of human splicing branchpoints are largely unknown. We use exoribonuclease digestion and targeted RNA-sequencing to enrich for sequences that traverse the lariat junction and, by split and inverted alignment, reveal the branchpoint.

Absolute counting of neutrophils in whole blood using flow cytometry.

Absolute neutrophil count (ANC) is used clinically to monitor physiological dysfunctions such as myelosuppression or infection. In the research laboratory, ANC is a valuable measure to monitor the evolution of a wide range of disease states in disease models. Flow cytometry (FCM) is a fast, widely used approach to confidently identify thousands of cells within minutes.

Targeted sequencing for gene discovery and quantification using RNA CaptureSeq.

RNA sequencing (RNAseq) samples the majority of expressed genes infrequently, owing to the large size, complex splicing and wide dynamic range of eukaryotic transcriptomes. This results in sparse sequencing coverage that can hinder robust isoform assembly and quantification. RNA capture sequencing (CaptureSeq) addresses this challenge by using oligonucleotide probes to capture selected genes or regions of interest for targeted sequencing.

Concise review: next-generation cell therapies to prevent infections in neutropenic patients.

High-dose chemotherapy is accompanied by an obligate period of neutropenia. Resulting bacterial and fungal infections are the leading cause of morbidity and mortality in neutropenic patients despite prophylactic antimicrobials and hematopoietic growth factor supplements. Replacing neutrophils in the patient through transfusion of donor cells is a logical solution to prevent fulminant infections.

Surface-modified microprojection arrays for intradermal biomarker capture, with low non-specific protein binding.

Minimally invasive biosensors are of great interest for rapid detection of disease biomarkers for diagnostic screening at the point-of-care. Here we introduce a device which extracts disease-specific biomarkers directly from the upper dermis, without the needle and syringe or resource-intensive blood processing. Using antigen-specific antibodies raised in mice as a model system, we confirm the analytical specificity and sensitivity of the antibody capture and extraction in comparison to the conventional methods based on needle/syringe blood draw followed by processing and antigen-specific ELISAs.

A broad spectrum, one-step reverse-transcription PCR amplification of the neuraminidase gene from multiple subtypes of influenza A virus.

Background: The emergence of high pathogenicity strains of Influenza A virus in a variety of human and animal hosts, with wide geographic distribution, has highlighted the importance of rapid identification and subtyping of the virus for outbreak management and treatment. Type A virus can be classified into subtypes according to the viral envelope glycoproteins, hemagglutinin and neuraminidase. Here we review the existing specificity and amplification of published primers to subtype neuraminidase genes and describe a new broad spectrum primer pair that can detect all 9 neuraminidase subtypes.