IL-17-related signature genes linked to human necrotizing enterocolitis

Abstract Objective Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units all over the world. The objective of the present study was to take advantage of RNA-Seq data from the analysis of intestinal specimens of preterm infants diagnosed with NEC. Function enrichments with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyse previous data in order to identify biological and functional processes, which could provide more insight into the pathogenesis of NEC in infants. Results Gene set enrichment analysis indicated that the most significant biological pathways over-represented in NEC neonates were closely associated with innate immune functions. One of the striking observations was the highly modulated expression of inflammatory genes related to the IL-17 pathway including such as pro-inflammatory cytokines (CXCL8), chemokines (CXCL5 and CXCL10) and antimicrobials (DEF5A, DEF6A, LCN2, NOS2) in the intestine of neonates diagnosed with NEC. Interestingly, the increase in IL-17 expression appeared to be under the IL-17F form, as reported in Crohn's disease, another inflammatory bowel disease. Further investigation is thus still needed to determine the precise role of IL-17F and its downstream targets in NEC.

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Identification of Inflammatory Genes, Pathways, and Immune Cells in Necrotizing Enterocolitis of Preterm Infant by Bioinformatics Approaches

BioMed Research International ◽

10.1155/2021/5568724 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Lili Zhang ◽

Lizhen Sun ◽

Mingli Wu ◽

Jie Huang

Keyword(s):

Gene Expression ◽

B Cells ◽

Rna Sequencing ◽

Necrotizing Enterocolitis ◽

Immune Cells ◽

Gastrointestinal Disease ◽

Gene Set Enrichment Analysis ◽

High Morbidity ◽

Expression Levels ◽

Gene Expression Levels

Background. Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal disease-causing high morbidity and mortality in premature infants. However, the underlying mechanism of the pathogenesis of NEC is still not fully understood. Methods. RNA sequencing of intestinal specimens from 9 NEC and 5 controls was employed to quantify the gene expression levels. RNA sequencing was employed to quantify the gene expression levels. DESeq2 tool was used to identify the differentially expressed genes. The biological function, pathways, transcription factors, and immune cells dysregulated in NEC were characterized by gene set enrichment analysis. Results. In the present study, we analyzed RNA sequencing data of NECs and controls and revealed that immune-related pathways were highly activated, while some cellular responses to external stimuli-related pathways were inactivated in NEC. Moreover, B cells, macrophages M1, and plasma cells were identified as the major cell types involved in NEC. Furthermore, we also found that inflammation-related transcription factor genes, such as STAT1, STAT2, and IRF2, were significantly activated in NEC, further suggesting that these TFs might play critical roles in NEC pathogenesis. In addition, NEC samples exhibited heterogeneity to some extent. Interestingly, two subgroups in the NEC samples were identified by hierarchical clustering analysis. Notably, B cells, T cells, Th1, and Tregs involved in adaptive immune were predicted to highly infiltrate into subgroup I, while subgroup II was significantly infiltrated by neutrophils. The heterogeneity of immune cells in NEC indicated that both innate and adaptive immunes might induce NEC-related inflammatory response. Conclusions. In summary, we systematically analyzed inflammation-related genes, signaling pathways, and immune cells to characterize the NEC pathogenesis and samples, which greatly improved our understanding of the roles of inflammatory responses in NEC.

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Unsuspected Hyperosmolality of Oral Solutions Contributing to Necrotizing Enterocolitis in Very-Low-Birth-Weight Infants

PEDIATRICS ◽

10.1542/peds.60.4.535 ◽

1977 ◽

Vol 60 (4) ◽

pp. 535-538

Author(s):

DIANA M. WILLIS ◽

JOANN CHABOT ◽

INGEBORG C. RADDE ◽

GRAHAM W. CHANCE

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Necrotizing Enterocolitis ◽

Neonatal Intensive Care ◽

Very Low Birth Weight ◽

Neonatal Intensive Care Units ◽

Low Birth Weight Infants ◽

Umbilical Vessel ◽

Causative Factors ◽

Nutritional Studies

In recent years necrotizing enterocolitis (NEC) has become a major problem in neonatal intensive care units. Recent incidences as high as 8% in all infants with a birth weight less than 2.5 kg and 14% in those with a birth weight less than 1.5 kg have been reported from one center.1Despite intensive searches for possible causative factors, no definite entity has been identified, but asphyxia,2 circulatory changes associated with exchange transfusion,3 umbilical vessel catheterization,4 immature immune status,5infection,6-8 and hypertonic feedings9 have all been implicated. In the course of a series of nutritional studies involving thriving very-low-birth-weight infants we

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Premature Activation of Immune Transcription Programs in Autoimmune-Predisposed Mouse Embryonic Stem Cells and Blastocysts

International Journal of Molecular Sciences ◽

10.3390/ijms21165743 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5743

Author(s):

Oktay Kirak ◽

Eugene Ke ◽

Kevin Y. Yang ◽

Anna Schwarz ◽

Lars Plate ◽

...

Keyword(s):

Histone Modifications ◽

Genetic Predisposition ◽

Autoimmune Diabetes ◽

Es Cells ◽

Embryonic Stem ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Immune Functions ◽

Active Expression

Autoimmune diabetes is a complex multifactorial disease with genetic and environmental factors playing pivotal roles. While many genes associated with the risk of diabetes have been identified to date, the mechanisms by which external triggers contribute to the genetic predisposition remain unclear. Here, we derived embryonic stem (ES) cell lines from diabetes-prone non-obese diabetic (NOD) and healthy C57BL/6 (B6) mice. While overall pluripotency markers were indistinguishable between newly derived NOD and B6 ES cells, we discovered several differentially expressed genes that normally are not expressed in ES cells. Several genes that reside in previously identified insulin-dependent diabetics (Idd) genomic regions were up-regulated in NOD ES cells. Gene set enrichment analysis showed that different groups of genes associated with immune functions are differentially expressed in NOD. Transcriptomic analysis of NOD blastocysts validated several differentially overexpressed Idd genes compared to B6. Genome-wide mapping of active histone modifications using ChIP-Seq supports active expression as the promoters and enhancers of activated genes are also marked by active histone modifications. We have also found that NOD ES cells secrete more inflammatory cytokines. Our data suggest that the known genetic predisposition of NOD to autoimmune diabetes leads to epigenetic instability of several Idd regions.

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Emerging Chryseobacterium indologenes Infection in Indian Neonatal Intensive Care Units: A Case Report

Antibiotics ◽

10.3390/antibiotics7040109 ◽

2018 ◽

Vol 7 (4) ◽

pp. 109 ◽

Cited By ~ 4

Author(s):

Rishika Mehta ◽

Ashish Pathak

Keyword(s):

Health Care ◽

Intensive Care ◽

Intensive Care Units ◽

Neonatal Intensive Care ◽

Multidrug Resistant ◽

Neonatal Intensive Care Units ◽

Indwelling Catheters ◽

Chryseobacterium Indologenes ◽

Life Threatening ◽

Health Care Associated Infections

Antibiotic-resistant pathogens and nosocomial infections constitute common and serious problems for neonates admitted to neonatal intensive care units worldwide. Chryseobacterium indologenes is a non-lactose-fermenting, gram-negative, health care-associated pathogen (HCAP). It is ubiquitous and intrinsically resistant to several antibiotics. Despite its low virulence, C. indologenes has been widely reported to cause life-threatening infections. Patients on chronic immunosuppressant drugs, harboring invasive devices and indwelling catheters become the nidus for C. indologenes. Typically, C. indologenes causes major health care-associated infections such as pneumonia, empyema, pyelonephritis, cystitis, peritonitis, meningitis, and bacteremia in patients harboring central venous catheters. Management of C. indologenes infection in neonates is not adequately documented owing to underreporting, particularly in India. Because of its multidrug resistance and the scant availability of data from the literature, the effective empirical treatment of C. indologenes is challenging. We present an uncommon case of bacteremia caused by C. indologenes in a preterm newborn baby with moderate respiratory distress syndrome who was successfully treated. We also provide a review of infections in the neonatal age group. Henceforth, in neonates receiving treatments involving invasive equipment use and long-term antibiotic therapy, multidrug resistant C. indologenes should be considered an HCAP.

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Potential Novel Therapeutic Targets In Epilepsy From The View of Intestinal Comorbidities - Inflammatory Bowel Disease

10.21203/rs.3.rs-960451/v1 ◽

2021 ◽

Author(s):

Mi Jiang ◽

Jia Li ◽

Zhi Song

Keyword(s):

Gene Expression ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Refractory Epilepsy ◽

Therapeutic Targets ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Hub Genes ◽

Inflammatory Bowel ◽

Novel Therapeutic

Abstract Background: Epilepsy is a complicated neurological disorder with almost 30% refractory. Recent years, several studies showed that epilepsy is associated with its comorbidities by shared molecular mechanisms. However, the association of epilepsy and digestive comorbidities are still unclear. In this study, we aim to explore the association between inflammatory bowel disease (IBD) and epilepsy, and to find promising therapeutic targets for refractory epilepsy. Methods: Two gene expression profiles (GSE134697 and GSE59071) were selected from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by GEO2R and the DESeq2 package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection DEGs and Gene Set Enrichment Analysis (GSEA) were conducted by clusterProfiler package. The protein-protein interactions (PPI) network was established by using STRING and visualized by Cytoscape. Genes in the most significant module identified by MCODE plug-in were considered as candidate hub genes. Validation of hub genes were performed by using the GSE143272 dataset. Results: Cytokine-cytokine receptor interaction pathway is identified as a communal pathway between IBD and epilepsy. CXCL8, CXCR4 and ITGAX were identified as the hub genes. Conclusions: The identification of the communal pathway and hub genes in this study contributes to a potential novel therapeutic target in refractory epilepsy.

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Exploratory Laparotomy for Necrotizing Enterocolitis

10.1093/med/9780190678333.003.0046 ◽

2018 ◽

Author(s):

Karla E. K. Wyatt ◽

Olutoyin A. Olutoye

Keyword(s):

Risk Factors ◽

Necrotizing Enterocolitis ◽

Premature Infants ◽

Neonatal Intensive Care ◽

Exploratory Laparotomy ◽

Anesthesia Care ◽

Comorbid Conditions ◽

Surgical Interventions ◽

Pediatric Anesthesiologist ◽

Inflammatory Bowel

Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease that commonly affects premature infants. The pathogenesis is multifactorial and poorly understood, although certain risk factors have been identified. This disease, more commonly detected in premature infants with accompanying cardiac and pulmonary comorbid conditions, is associated with increased morbidity and mortality. Multiorgan system homeostasis becomes critical for the pediatric anesthesiologist when approaching medical and surgical interventions for affected patients. This chapter focuses on the population at risk for developing necrotizing enterocolitis, medical and surgical management, providing anesthesia care in the neonatal intensive care unit, as well as perioperative considerations and complications.

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Characteristics of newborns with necrotizing enterocolitis in a third-level university hospital in Colombia

Colombia Medica ◽

10.25100/cm.v42i4.947 ◽

2011 ◽

pp. 468-475

Author(s):

Javier Torres ◽

Laura Lorena Espinosa ◽

Ángela Marcela García ◽

Alejandra María Mideros ◽

Enrique Usubillaga

Keyword(s):

Necrotizing Enterocolitis ◽

Neonatal Intensive Care ◽

Descriptive Analysis ◽

University Hospital ◽

Neonatal Intensive Care Units ◽

Low Weight ◽

Term Newborns ◽

Clinical Records ◽

Adequate Prenatal Care ◽

The City

Introduction: Necrotizing enterocolitis (NEC) is, over all newborn surgical afflictions, the most deathly, representing the main GI problem in neonatal intensive care units (NICU) and a medical/surgical emergency in which early diagnosis and opportune treatment may diminish surgical needs and mortality. Objective: To describe the features of patients with NEC attended at a third-level hospital NICU in the city of Cali in 2006. Method and materials: We conducted a pilot descriptive retrospective study that included 32 clinical records of newborns in the NICU (named CIRENA) from the Hospital Universitario del Valle (HUV) with NEC diagnosis. Finally, we made a descriptive analysis of the data by using the Epi-Info statistics program. Results: In 2006, 1555 newborns were admitted to HUV-CIRENA and 32 (2%) of them were diagnosed with NEC, a percentage that is similar to that of other countries; half of which weighed less than 1500 grams and only three pregnant women had adequate prenatal care, 17(53.1%) of these newborns were female and 15(46.9%) were male. Conclusions: Although the majority of NEC cases occurs in premature and/or very low weight children, it is outstanding the number of full-term newborns, either on gestational age and weight, that developed early NEC. There is a visible relationship among low birth weight, prematurity, and the development of NEC, especially in the higher degrees of the disease, where the tendency is the presentation of late NEC.

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Variations in Incidence of Necrotizing Enterocolitis in Canadian Neonatal Intensive Care Units

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-200410000-00012 ◽

2004 ◽

Vol 39 (4) ◽

pp. 366-372 ◽

Cited By ~ 90

Author(s):

Koravangattu Sankaran ◽

Barbara Puckett ◽

David S.C. Lee ◽

Mary Seshia ◽

Jill Boulton ◽

...

Keyword(s):

Intensive Care ◽

Intensive Care Units ◽

Necrotizing Enterocolitis ◽

Neonatal Intensive Care ◽

Neonatal Intensive Care Units

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Necrotizing Enterocolitis

10.1093/med/9780190685157.003.0001 ◽

2018 ◽

Author(s):

Jared Hylton ◽

Sarah Deverman

Keyword(s):

Necrotizing Enterocolitis ◽

Neonatal Intensive Care ◽

Clinical Presentation ◽

Pneumatosis Intestinalis ◽

Postoperative Management ◽

First Line ◽

Surgical Emergencies ◽

Threatening Condition ◽

Life Threatening ◽

Ventilatory Management

Necrotizing enterocolitis (NEC) is a potentially life-threatening condition that affects mainly preterm infants. It is one of the most common surgical emergencies in the neonatal intensive care unit. While medical management is the first line of treatment, if that fails, NEC becomes a surgical emergency, and the pediatric anesthesiologist must be prepared. This chapter covers the pathogenesis, risk factors, clinical presentation and diagnosis, prevention, medical and surgical management, pre- and intraoperative anesthetic assessment, and postoperative management of NEC. Topics covered include intestinal perforation, necrotizing enterocolitis, neonatal anesthesia, pneumatosis intestinalis, prematurity, and ventilatory management. The chapter ends with review questions on the chapter’s content.

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