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).

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.

Understanding and Improving Diagnostic Tests: The Clinician Perspective.

Recent advances in molecular and mass screening technologies have paved the way for discovery of novel diagnostic tests and/or biomarkers for accurate identification of specific diseases and organ injuries. However, new diagnostic tests/biomarkers should be subjected to thorough evaluation before introduction into routine clinical practice. This review focuses on the up-to-date methodology in designing and evaluating diagnostic tests/biomarkers, and assessing their clinical utilities for improving health care efficiency, cost-effectiveness and outcomes.

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.

An update on biomarkers of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) remains a devastating surgical emergency with high morbidity and mortality in preterm infants. Slow but steady progress has been made in past years searching for novel biomarkers of NEC, for both surveillance and diagnostic purposes. This review primarily focuses on recent discoveries: clinical applications of different categories of biomarkers for surveillance, early diagnosis, and predicting severity and prognosis; and understanding of pathophysiological mechanisms as a basis to rationalize the search for 'gut-associated specific biomarkers' of NEC.

MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target.

Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis.

Neonatal Haemophagocytic Lymphohistiocytosis Associated with Maternal Adult-Onset Still's Disease.

Neonatal haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially lethal condition. We recently encountered a preterm infant who developed severe HLH associated with maternal adult-onset Still's disease, which to our knowledge has not been previously reported. The infant presented with fever, generalised lymphadenopathy, transient erythematous skin rash, hepatosplenomegaly, ascites, pancytopenia, marked hyperferritinaemia, and hypofibrinogenaemia, which were features similar to maternal presentation during late pregnancy.

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.

Adrenocortical insufficiency and refractory hypotension in preterm infants.

Preterm, very low birthweight (VLBW) infants are prone to life-threatening hypotension secondary to hypothalamic-pituitary-adrenal axis immaturity, resulting in adrenocortical insufficiency. Clinical presentations of inotrope-resistant refractory hypotension are usually evident, but interpretation of serum cortisol may pose much difficulty to front-line neonatologists. This review examines the salient pathophysiology of adrenocortical insufficiency in the immediate postnatal period, characterises its endocrinological abnormalities, and describes the typical and variant clinical presentations.

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.

Attitudes of Parents and Health Care Workers to Major Surgery for High-Risk Preterm Infants.

Objectives: To assess preferences of health care workers (HCWs) and parents of term and preterm infants to adverse health outcomes, and how perceived surgical mortality influences decision-making.

Study Design: A total of 536 participants (157 HCWs, 201 parents of term infants, and 178 parents of preterm infants) were recruited to take part in a structured interview. Preferences related to treatment of a critically ill preterm infant with necrotizing enterocolitis were measured by health state rank permutation analysis and pivotal risk analysis.

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).

Response of levetiracetam in neonatal seizures.

Aim: To review the clinical response to levetiracetam (LEV) in neonatal seizure management in intensive care unit.

Methods: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted.

The use of laboratory biomarkers for surveillance, diagnosis and prediction of clinical outcomes in neonatal sepsis and necrotising enterocolitis.

Biomarkers have been used to differentiate systemic neonatal infection and necrotising enterocolitis (NEC) from other non-infective neonatal conditions that share similar clinical features. With increasing understanding in biochemical characteristics of different categories of biomarkers, a specific mediator or a panel of mediators have been used in different aspects of clinical management in neonatal sepsis/NEC. This review focuses on how these biomarkers can be used in real-life clinical settings for daily surveillance, bedside point-of-care testing, early diagnosis and predicting the severity and prognosis of neonatal sepsis/NEC.

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.

Study of Isobaric Interference in Quantification of Citrulline by Parallel Fragmentation Monitoring.

Parallel Fragmentation Monitoring (PFM), which is an analogue of selected reaction monitoring (SRM), is a recently developed method for quantification of small molecules by MALDI-TOF/TOF mass spectrometry (MS). It is well known that isobaric interference substances can be occasionally present in complex biological samples, and affect the accuracy of measurement by SRM. Unfortunately, by design it is not possible to assess whether isobaric interference happens in a SRM analysis.

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.

Biomarkers of necrotising enterocolitis.

Different categories of biomarkers of necrotising enterocolitis (NEC), including (i) non-specific mediators of the inflammatory cascade, e.g. acute phase reactants, chemokines, cytokines, and cell surface antigens, (ii) enhanced non-specific biomarkers, and (iii) specific gut-associated proteins, have distinctive biochemical characteristics and properties.

Neutrophil CD64 for daily surveillance of systemic infection and necrotizing enterocolitis in preterm infants.

Background: Early detection and treatment of infected preterm infants could decrease morbidity and mortality. Neutrophil CD64 has been shown to be an excellent early diagnostic biomarker of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). We aimed to study whether using CD64 as a daily surveillance biomarker could predict LOS/NEC before clinical manifestation.

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.