Is necrotizing enterocolitis the same disease in term and preterm infants?

INTRODUCTION: Necrotizing enterocolitis predominantly affects preterm (PT) infants. The paucity of data regarding the clinical course in term infants makes it difficult to predict outcomes and counsel families. To identify predisposing factors and gain a better understanding of the clinical course of NEC in term infants, we reviewed our experience with term infants and compared it to outcomes in PT infants. METHODS: We performed a 10 year retrospective review of all infants admitted to our NICU with Bell stage 2 NEC or greater. Infants < 37 weeks gestation were considered PT. Term and PT infant comorbidities, outcomes and intraoperative findings were compared. RESULTS: Fifteen (12%) of 125 infants were term. Compared to PT infants, term infants were more likely to have congenital heart disease (33% term vs. 10% PT, p = 0.02) and develop NEC sooner (4 days in term vs. 17 days in PT, p < 0.001) but were less likely to require operative intervention (20% term vs. 38% PT; p = 0.17). There was no significant difference in Bell stage, survival and development of intestinal failure. NEC totalis occurred exclusively in PT infants. CONCLUSIONS: NEC in term infants has unique clinical features that distinguishes it from NEC in PT infants.

Non-Invasive microRNA Profiling in Saliva can Serve as a Biomarker of Alcohol Exposure and Its Effects in Humans.

Alcohol Use Disorder (AUD) is one of the most prevalent mental disorders worldwide. Considering the widespread occurrence of AUD, a reliable, cheap, non-invasive biomarker of alcohol consumption is desired by healthcare providers, clinicians, researchers, public health and criminal justice officials. microRNAs could serve as such biomarkers. They are easily detectable in saliva, which can be sampled from individuals in a non-invasive manner. Moreover, microRNAs expression is dynamically regulated by environmental factors, including alcohol. Since excessive alcohol consumption is a hallmark of alcohol abuse, we have profiled microRNA expression in the saliva of chronic, heavy alcohol abusers using microRNA microarrays. We observed significant changes in salivary microRNA expression caused by excessive alcohol consumption. These changes fell into three categories: downregulated microRNAs, upregulated microRNAs, and microRNAs upregulated de novo. Analysis of these combinatorial changes in microRNA expression suggests dysregulation of specific biological pathways leading to impairment of the immune system and development of several types of epithelial cancer. Moreover, some of the altered microRNAs are also modulators of inflammation, suggesting their contribution to pro-inflammatory mechanisms of alcohol actions. Establishment of the cellular source of microRNAs in saliva corroborated these results. We determined that most of the microRNAs in saliva come from two types of cells: leukocytes involved in immune responses and inflammation, and buccal cells, involved in development of epithelial, oral cancers. In summary, we propose that microRNA profiling in saliva can be a useful, non-invasive biomarker allowing the monitoring of alcohol abuse, as well as alcohol-related inflammation and early detection of cancer.

Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis.

Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid tumors, Men1 knockout (KO) mice, and Men1 null mouse embryonic fibroblast (MEF) cell lines. We demonstrated that inactivation of menin (the protein product of MEN1) increases activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by activating retinoblastoma-binding protein 5 (Rbbp5). The increased activity of DNMT1 mediates global DNA hypermethylation, which results in aberrant activation of the Wnt/ß-catenin signaling pathway through inactivation of Sox regulatory genes. Our study provides important insights into the role of menin in DNA methylation and its impact on the pathogenesis of MEN1 tumor development.

Seasonal variation of urinary microRNA expression in male goats (Capra hircus) as assessed by next generation sequencing.

Testosterone plays a key role in preparation of a male domesticated goat (Capra hircus) to breeding season including changes in the urogenital tract of a male goat (buck). microRNAs are important regulators of cellular metabolism, differentiation and function. They are powerful intermediaries of hormonal activity in the body, including the urogenital tract. We investigated seasonal changes in expression of microRNAs in goat buck urine and their potential consequences using next generation sequencing (microRNA-Seq). We determined the location of each microRNA gene in the goat genome. Testosterone was measured by radioimmunoassay and the androgen receptor binding sites (ARBS) in the promoters of the microRNA genes were determined by MatInspector. The overall impact of regulated microRNAs on cellular physiology was assessed by mirPath. We observed high testosterone levels during the breeding season and changes in the expression of forty microRNAs. Nineteen microRNAs were upregulated, while twenty-one were downregulated. We identified several ARBS in the promoters of regulated microRNAs. Notably, the mostly inhibited microRNA, miR-1246, has a unique set of several gene copy variants associated with a cluster of androgen receptor binding sites. Concomitant changes in regulated microRNA expression could promote transcription, proliferation and differentiation of urogenital tract cells. Together, these findings indicate that in a domesticated goat (Capra hircus), there are specific changes in the microRNA expression profile in buck urine during breeding season, which could be attributable to high testosterone levels during breeding, and could help in preparation of the urogenital tract for high metabolic demands of that season.