microRNA-mRNA Networks Linked to Inflammation and Immune System Regulation in Inflammatory Bowel Disease.

The molecular processes linked to the development and progression of Crohn's disease (CD) and ulcerative colitis (UC) are not completely understood. MicroRNAs (miRNAs) regulate gene expression and are indicated as diagnostic, prognostic, and predictive biomarkers in chronic degenerative diseases. Our objectives included the identification of global miRNA expression in CD and UC, as well as miRNA target genes, miRNA-mRNA interaction networks, and biological functions associated with these different forms of inflammatory bowel disease (IBD). METHODS: By performing a comprehensive meta-analysis, we integrated miRNA expression data from nine studies in IBD. We obtained detailed information on significantly deregulated miRNAs (fold change, FC ≥ 2 and p < 0.05), sample type and number, and platform applied for analysis in the training and validation sets. Further bioinformatic analyses were performed to identify miRNA target genes, by using the microRNA Data Integration Portal tool. We also sought to identify statistically enriched pathways of genes regulated by miRNAs using ToppGene Suite. Additional analyses were performed to filter for genes expressed in intestinal tissue using the European Bioinformatics Institute (EBI) database. RESULTS: Our findings showed the upregulation of 15 miRNAs in CD and 33 in UC. Conversely, six miRNAs were downregulated in CD, while seven were downregulated in UC. These results indicate a greater deregulation of miRNAs in UC compared to CD. Of note, miRNA target genes were enriched for immune system regulation pathways. Among significantly deregulated miRNAs with a higher number of miRNA-target gene interactions, we identified miR-199a-5p and miR-362-3p altered in CD, while among UC case patients, miRNA-target gene interactions were higher for miR-155-5p. CONCLUSIONS: The identified miRNAs play roles in regulating genes associated with immune system regulation and inflammation in IBD. Such miRNAs and their target genes have the potential to serve as clinically relevant biomarkers. These findings hold promise for enhancing the accuracy of diagnoses and facilitating the development of personalized treatment strategies for individuals with various forms of IBD.

Acetylcholinesterase Biosensor Based on Functionalized Renewable Carbon Platform for Detection of Carbaryl in Food.

Enzymatic electrochemical biosensors play an important role in the agri-food sector due to the need to develop sustainable, low-cost, and easy-to-use analytical devices. Such biosensors can be used to monitor pathogens, endocrine disruptors, and pesticides, such as carbaryl, widely used in many crops. The use of renewable carbon (RC) sources, provided from biomass pyrolysis has been often applied in the fabrication of such sensors. This material is a great candidate for biosensor fabrication due to the presence of surface functional groups, porosity, and moderate surface area. This work describes the functionalization of RC material through an acid treatment with a sulfonitric solution HNO3/H2SO4 (1:3) and the resulting material was characterized by scanning electron microscopy. The obtained RC functionalized (RCF) and the acetylcholinesterase enzyme (AChE) were applied in the construction of the electrochemical biosensor on glassy carbon (GC) electrode and used to detect carbaryl in apple samples. The GC/RCF/AChE biosensor was able to detect the carbaryl pesticide from 5.0 to 30.0 nmol L-1, displaying a LOD of 4.5 nmol L-1. The detection of carbaryl in apple samples presented recoveries between 102.5 to 118.6% through the standard addition method. The proposed biosensor is a promising renewable tool for food safety.

Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B.

This study proposed to determine global microRNA (miRNA) expression and miRNA-regulated pathways in Intestinal Neuronal Dysplasia type B (IND-B). Fifty patients (0-15 years old) with IND-B were included in the study. Peripheral blood samples were collected from all 50 patients and from 10 healthy asymptomatic children (controls). Rectal biopsies were collected from 29/50 patients; biopsy tissues were needle microdissected to isolate the different intestinal layers, for molecular analysis. Global miRNA expression was determined using TaqMan arrays. Correlation analysis between miRNA expression in plasma and biopsy samples as well as among tissues derived from the distinct intestinal layers was performed. Computational approaches were used for miRNA target prediction/identification of miRNA-regulated genes and enriched pathways biologically relevant to IND-B pathogenesis. miRNAs were statistically significantly deregulated (FC ≥ 2 and p ≤ 0.05) in submucosal and muscular layers: over-expressed (miR-146a and miR-146b) and under-expressed (miR-99a, miR-100, miR-130a, miR-133b, miR-145, miR-365, miR-374-5p, miR-451). Notably, let-7a-5p was highly over-expressed in patient plasma compared to healthy controls (FC = 17.4). In addition, miR-451 was significantly under-expressed in both plasma and all biopsy tissues from the same patients. Enriched pathways (p < 0.01) were axon guidance, nerve growth factor signalling, NCAM signalling for neurite out-growth, neuronal system and apoptosis. miRNA expression is deregulated in the submucosa and muscular layers of the rectum and detected in plasma from patients with IND-B. Biologically enriched pathways regulated by the identified miRNAs may play a role in IND-B disease pathogenesis, due to the activity related to the neurons of the enteric nervous system.

Genomic profile of a Li-Fraumeni-like syndrome patient with a 45,X/46,XX karyotype, presenting neither mutations in TP53 nor clinical stigmata of Turner syndrome.

Li-Fraumeni syndrome (LFS) is a hereditary disorder that predisposes patients to several types of cancer and is associated with TP53 germline mutations. Turner syndrome (TS) is one of the most common aneuploidies in women. Patients with TS have a higher risk of developing cancer, although multiple malignant tumors are extremely rare. Herein, we describe a patient with a 45,X/46,XX karyotype with no classic phenotype of TS. She presented with a clinical diagnosis of Li-Fraumeni-like syndrome (LFL), showing papillary thyroid carcinoma and fibrosarcoma of the left flank, and had no TP53 germline mutations. Genome-wide analysis of copy number variations (CNVs) was assessed in DNA from peripheral blood cells and saliva. A total of 109 rare CNVs in the blood cells, including mosaic loss of the X chromosome (76% of cells), were identified. In saliva, three rare CNVs were detected, all of them were also detected in the blood cells: loss of 8q24.11 (EXT1), gain of 16q24.3 (PRDM7 and GAS8), and the mosaic loss of the X chromosome (50% of cells). Results of conventional G-banding confirmed the 45,X/46,XX karyotype. Surprisingly, the patient presented with an apparently normal phenotype. The PRDM and GAS8 genes are potential candidates to be associated with the risk of developing cancer in this LFL/TS patient.