CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents.

Prognostic implications of CD9 in childhood acute lymphoblastic leukemia: insights from a nationwide multicenter study in China.

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter.

Deep genomic characterization highlights complexities and prognostic markers of pediatric acute myeloid leukemia.

Pediatric acute myeloid leukemia (AML) is an uncommon but aggressive hematological malignancy. The poor outcome is attributed to inadequate prognostic classification and limited treatment options. A thorough understanding on the genetic basis of pediatric AML is important for the development of effective approaches to improve outcomes.

Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines.

Background: Immunity acquired from natural SARS-CoV-2 infection and vaccine wanes overtime. This longitudinal prospective study compared the effect of a booster vaccine (BNT162b2) in inducing the mucosal (nasal) and serological antibody between Covid-19 recovered patients and healthy unexposed subjects with two dose of mRNA vaccine (vaccine-only group).

Method: Eleven recovered patients and eleven gender-and-age matched unexposed subjects who had mRNA vaccines were recruited.

Pharmacogenomic Profiling of Pediatric Acute Myeloid Leukemia to Identify Therapeutic Vulnerabilities and Inform Functional Precision Medicine.

Unlabelled: Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models.

Suppression of influenza virus infection by rhinovirus interference - at the population, individual and cellular levels.

Background: Influenza virus (IV) and the rhinovirus (RV) are the two most common circulating respiratory viruses circulating. Natural viral interference has been suggested between them. The effect of such at the population level has been described in temperate region, while its effect at the individual and cellular levels warrants further validation.

R4 RGS proteins as fine tuners of immature and mature hematopoietic cell trafficking.

G-protein-coupled receptors (GPCRs) are the largest and most diverse group of membrane receptors. They are involved in almost every physiologic process and consequently have a pivotal role in an extensive number of pathologies, including genetic, neurologic, and immune system disorders. Indeed, the vast array of GPCRs mechanisms have led to the development of a tremendous number of drug therapies and already account for about a third of marketed drugs.

Mucosal Antibody Response to SARS-CoV-2 in Paediatric and Adult Patients: A Longitudinal Study.

Background: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied.

Methods: Conjunctival fluid (CF, = 140) and nasal epithelial lining fluid (NELF, = 424) obtained by paper strips and plasma ( = 153) were collected longitudinally from SARS-CoV-2 paediatric ( = 34) and adult ( = 47) patients.

The Mucosal and Serological Immune Responses to the Novel Coronavirus (SARS-CoV-2) Vaccines.

Background: Although the serological antibody responses induced by SARS-CoV-2 vaccines are well characterized, little is known about their ability to elicit mucosal immunity.

Objectives: This study aims to examine and compare the mucosal and systemic responses of recipients of two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac).

Methods: Serial blood and nasal epithelial lining fluid (NELF) samples were collected from the recipients of either Comirnaty or CoronaVac.

, , , and their interaction as genetic predictors of 6-mercaptopurine intolerance in chinese patients with acute lymphoblastic leukemia.

Inter-individual variance in 6-mercaptopurine (6-MP) dose intensity is common in patients with acute lymphoblastic leukemia (ALL). We aimed to evaluate the association of common variants of , , , and with 6-MP dose intensity and toxicity in pediatric ALL patients. In this cohort, 13.

R4 RGS proteins suppress engraftment of human hematopoietic stem/progenitor cells by modulating SDF-1/CXCR4 signaling.

Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM) microenvironment are tightly regulated by the chemokine stromal cell-derived factor-1 (SDF-1) and its G-protein-coupled receptor C-X-C motif chemokine receptor 4 (CXCR4), which on engagement with G-protein subunits, trigger downstream migratory signals. Regulators of G-protein signaling (RGS) are GTPase-accelerating protein of the Gα subunit and R4 subfamily members have been implicated in SDF-1-directed trafficking of mature hematopoietic cells, yet their expression and influence on HSPCs remain mostly unknown. Here, we demonstrated that human CD34+ cells expressed multiple R4 RGS genes, of which RGS1, RGS2, RGS13, and RGS16 were significantly upregulated by SDF-1 in a CXCR4-dependent fashion.

The miR-223/nuclear factor I-A axis regulates inflammation and cellular functions in intestinal tissues with necrotizing enterocolitis.

We previously demonstrated that microRNA(miR)-223 is overexpressed in intestinal tissue of infants with necrotizing enterocolitis (NEC). The objective of the current study was to identify the target gene of miR-223 and to investigate the role of the miR-223/nuclear factor I-A (NFIA) axis in cellular functions that underpin the pathophysiology of NEC. The target gene of miR-223 was identified by in silico target prediction bioinformatics, luciferase assay, and western blotting.

A Prospective Cohort Study of Fecal miR-223 and miR-451a as Noninvasive and Specific Biomarkers for Diagnosis of Necrotizing Enterocolitis in Preterm Infants.

Objective: The objective of this study is to evaluate the usefulness of fecal microRNA (miR)-223 and miR-451a, as novel noninvasive biomarkers for early diagnosis of necrotizing enterocolitis (NEC) in preterm infants.

Methods: Among the top-listed target miRNAs in our previous differential microarray analysis, miR-223 and miR-451a were quantified in a pilot validation case-controlled study (NEC vs. non-NEC/nonsepsis infants; n = 6 in each group).

Association between genetic variations in GSH-related and MT genes and low-dose methylmercury exposure in children and women of childbearing age: a pilot study.

Background: Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics.

Objective: To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age.

Methods: A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community.

CD9 blockade suppresses disease progression of high-risk pediatric B-cell precursor acute lymphoblastic leukemia and enhances chemosensitivity.

CD9 has been implicated in cancer progression but its prognostic relevance and therapeutic potential in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are largely unknown. In a cohort of pediatric BCP-ALL patients, we found that CD9 cases had a significantly lower 5-year relapse-free survival rate than CD9 cases. Multivariate analysis demonstrated that CD9 positivity independently predicted inferior survival outcomes, and could be applied with established prognostic features, including prednisone response and cytogenetic status, to refine patient stratification.

Dysregulation of miR-431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis.

The level of microRNA (miR)-431 was found to be markedly up-regulated in intestinal tissue of necrotizing enterocolitis (NEC). The objective of this study was to identify the target gene of miR-431 and to investigate the role of the miR-431-FOXA1 axis in the pathophysiology of NEC. The target gene of miR-431 was identified by in silico target prediction bioinformatics, luciferase assay, and Western blotting.

Plasma miR-1290 Is a Novel and Specific Biomarker for Early Diagnosis of Necrotizing Enterocolitis-Biomarker Discovery with Prospective Cohort Evaluation.

Objective: To discover specific circulating microRNA (miRNA) biomarkers for the early differentiation of necrotizing enterocolitis (NEC) from neonatal sepsis and inflammatory conditions.

Study Design: The study comprised 3 distinct phases: differential microarray analysis to compare plasma miRNA expression profiles of NEC vs sepsis and non-NEC/nonsepsis cases, a case-control study to quantify dysregulated miRNAs as potential specific biomarkers of NEC, and a prospective cohort study to assess the diagnostic usefulness of the best miRNA biomarker(s).

Results: A distinct miRNA expression profile was observed in the NEC compared with the sepsis and non-NEC/nonsepsis groups.

Rapid Identification of Bacterial Antibiotic Resistance by qPCR in Infants with Gram-Negative Septicaemia: A Proof-of-Concept Study.

Background: Neonatal sepsis remains an important cause of neonatal morbidity and mortality. Tools to rapidly predict antibiotic resistance in neonatal sepsis would be extremely valuable.

Objectives: To develop quantitative polymerase chain reaction (qPCR) primer/probe sets that can rapidly detect antibiotic resistance genes common to a neonatal unit, and to investigate the feasibility of direct detection of antibiotic resistance genes in whole blood of infants with Gram-negative septicaemia without first isolating the organism.

Regulation of Circulating Hematopoietic Stem/Progenitor Cells in Preterm Infants with Septicemia.

Preterm infants are at high risk of developing severe sepsis. Circulating hematopoietic stem and progenitor cells (HSPCs; CD45CD34) have been suggested to play a vital role in the host immunological defense against invading pathogens. The objectives were to investigate the regulation of circulating HSPCs in preterm infants during infection episodes, and to assess the relationship of CD45CD34 cells with immunological mediators and differential leukocyte populations.

Dysregulated expression of arginine metabolic enzymes in human intestinal tissues of necrotizing enterocolitis and response of CaCO2 cells to bacterial components.

The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation.

Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation.

Background: Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology.

Methods: We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group).

Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells and its growth promoting activity.

Makorin-2 (MKRN2) is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively.

Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues: dysregulation of functional pathways.

Objective: To provide a comprehensive database of gene regulation and compare differentially regulated molecular networks in human tissues of necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP).

Background: Both NEC and SIP are devastating surgical emergencies associated with high morbidity and mortality in preterm infants. Their pathophysiology and molecular mechanisms remain unclear.

Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan.

In newborn infants, the innate cellular system plays a crucial role in the first line of defense against pathogens. Neutrophils are the most abundant leukocytes, and their response to the commonly encountered nosocomial bacterial (Gram positive) infection in newborns remains largely unclear. In this study, a genome-wide expression array analysis was performed on CB neutrophils after challenge by PGN in vitro and compared with neutrophils in CTL cultures without PGN.