Gestational age at birth influences protein and RNA content in human milk extracellular vesicles.

Human milk extracellular vesicles (HM EVs) are proposed to protect against disease development in infants. This protection could in part be facilitated by the bioactive EV cargo of proteins and RNA. Notably, mothers birth infants of different gestational ages with unique needs, wherein the EV cargo of HM may diverge.

Reconsideration of the laminin receptor 67LR in colorectal cancer cells.

The 67 kDa laminin receptor (67LR) was identified as the first laminin receptor shown to be involved in the carcinogenesis of various cancers, including colorectal cancer. While the exact composition of this 67 kDa receptor remains unknown, it has been reported to be formed by the 37 kDa ribosomal protein SA (RPSA) covalently attached to another unidentified protein. The goal of this study was to clarify the molecular structure of 67LR to enhance our understanding of its role in malignancies.

Application of SWATH Mass Spectrometry and Machine Learning in the Diagnosis of Inflammatory Bowel Disease Based on the Stool Proteome.

Inflammatory bowel disease (IBD) flare-ups exhibit symptoms that are similar to other diseases and conditions, making diagnosis and treatment complicated. Currently, the gold standard for diagnosing and monitoring IBD is colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method.

The Combination of Gold and Silver Food Nanoparticles with Gluten Peptides Alters the Autophagic Pathway in Intestinal Crypt-like Cells.

Metallic nanoparticles (mNPs) are widely used as food additives and can interact with gliadin triggering an immune response, but evaluation of the effects on crypts, hypertrophic in celiac subjects, is still lacking. This study evaluated the effects of gold and silver mNPs in combination with gliadin on crypt-like cells (HIEC-6). Transmission electron microscopy (TEM) was used to evaluate gliadin-mNP aggregates in cells.

High-fat diet reveals the impact of Sar1b defects on lipid and lipoprotein profile and cholesterol metabolism.

Biallelic pathogenic variants of the Sar1b gene cause chylomicron retention disease (CRD) whose central phenotype is the inability to secrete chylomicrons. Patients with CRD experience numerous clinical symptoms such as gastrointestinal, hepatic, neuromuscular, ophthalmic, and cardiological abnormalities. Recently, the production of mice expressing either a targeted deletion or mutation of Sar1b recapitulated biochemical and gastrointestinal defects associated with CRD.

Integrin α7β1 represses intestinal absorptive cell differentiation.

Intestinal epithelial cell differentiation is a highly controlled and orderly process occurring in the crypt so that cells migrating out to cover the villi are already fully functional. Absorptive cell precursors, which originate from the stem cell population located in the lower third of the crypt, are subject to several cycles of amplification in the transit amplifying (TA) zone, before reaching the terminal differentiation compartment located in the upper third. There is a large body of evidence that absorptive cell differentiation is halted in the TA zone through various epigenetic, transcriptional and intracellular signalling events or mechanisms allowing the transient expansion of this cell population but how these mechanisms are themself regulated remains obscure.

Primary Cilium Identifies a Quiescent Cell Population in the Human Intestinal Crypt.

Primary cilia are sensory antennae located at the cell surface which mediate a variety of extracellular signals involved in development, tissue homeostasis, stem cells and cancer. Primary cilia are found in an extensive array of vertebrae cells but can only be generated when cells become quiescent. The small intestinal epithelium is a rapidly self-renewing tissue organized into a functional unit called the crypt-villus axis, containing progenitor and differentiated cells, respectively.

Fibrin(ogen) Is Constitutively Expressed by Differentiated Intestinal Epithelial Cells and Mediates Wound Healing.

Fibrinogen is a large molecule synthesized in the liver and released in the blood. Circulating levels of fibrinogen are upregulated after bleeding or clotting events and support wound healing. In the context of an injury, thrombin activation drives conversion of fibrinogen to fibrin.

Differential influence of YAP1 and TAZ on differentiation of intestinal epithelial cell: A review.

Intestinal cell stemness, proliferation and differentiation are complex processes all occurring in distinct compartments of the crypt that need to be closely regulated to ensure proper epithelial renewal. The involvement of the Hippo pathway in intestinal epithelial proliferation and regeneration after injury via the regulation of its effectors YAP1 and TAZ has been well-documented over the last decade. The implication of YAP1 and TAZ on intestinal epithelial cell differentiation is less clear.

Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1.

Intestinal cell lineage differentiation is a tightly regulated mechanism that involves several intracellular signaling pathways affecting the expression of a variety of transcription factors, which ultimately regulate cell specific gene expression. Absorptive and goblet cells are the two main epithelial cell types of the intestine. Previous studies from our group using an shRNA knockdown approach have shown that YAP1, one of the main Hippo pathway effectors, inhibits the differentiation of these two cell types.

Lipocalin-2 and calprotectin as stool biomarkers for predicting necrotizing enterocolitis in premature neonates.

Background: Necrotizing enterocolitis (NEC) is a major challenge for premature infants in neonatal intensive care units and efforts toward the search for indicators that could be used to predict the development of the disease have given limited results until now.

Methods: In this study, stools from 132 very low birth weight infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction. Eight infants (~6%) received a stage 3 NEC diagnosis.

Review of Methodological Approaches to Human Milk Small Extracellular Vesicle Proteomics.

Proteomics can map extracellular vesicles (EVs), including exosomes, across disease states between organisms and cell types. Due to the diverse origin and cargo of EVs, tailoring methodological and analytical techniques can support the reproducibility of results. Proteomics scans are sensitive to in-sample contaminants, which can be retained during EV isolation procedures.

Dietary Nanoparticles Interact with Gluten Peptides and Alter the Intestinal Homeostasis Increasing the Risk of Celiac Disease.

The introduction of metallic nanoparticles (mNPs) into the diet is a matter of concern for human health. In particular, their effect on the gastrointestinal tract may potentially lead to the increased passage of gluten peptides and the activation of the immune response. In consequence, dietary mNPs could play a role in the increasing worldwide celiac disease (CeD) incidence.

Sar1b mutant mice recapitulate gastrointestinal abnormalities associated with chylomicron retention disease.

Chylomicron retention disease (CRD) is an autosomal recessive disorder associated with biallelic Sar1b mutations leading to defects in intracellular chylomicron (CM) trafficking and secretion. To date, a direct cause-effect relationship between CRD and Sar1b mutation has not been established, but genetically modified animal models provide an opportunity to elucidate unrecognized aspects of these mutations. To examine the physiological role and molecular mechanisms of Sar1b function, we generated mice expressing either a targeted deletion or mutation of human Sar1b using the CRISPR-Cas9 system.

Multitarget Stool mRNA Test for Detecting Colorectal Cancer Lesions Including Advanced Adenomas.

Current approved non-invasive screening methods for colorectal cancer (CRC) include FIT and DNA-FIT testing, but their efficacy for detecting precancerous lesions that are susceptible to progressing to CRC such as advanced adenomas (AA) remains limited, thus requiring further options to improve the detection of CRC lesions at earlier stages. One of these is host mRNA stool testing. The aims of the present study were to identify specific stool mRNA targets that can predict AA and to investigate their stability under a clinical-like setting.

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

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.

From Congenital Disorders of Fat Malabsorption to Understanding Intra-Enterocyte Mechanisms Behind Chylomicron Assembly and Secretion.

During the last two decades, a large body of information on the events responsible for intestinal fat digestion and absorption has been accumulated. In particular, many groups have extensively focused on the absorptive phase in order to highlight the critical "players" and the main mechanisms orchestrating the assembly and secretion of chylomicrons (CM) as essential vehicles of alimentary lipids. The major aim of this article is to review understanding derived from basic science and clinical conditions associated with impaired packaging and export of CM.

Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa.

Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs.

The Hippo Pathway Effector YAP1 Regulates Intestinal Epithelial Cell Differentiation.

The human intestine is covered by epithelium, which is continuously replaced by new cells provided by stem cells located at the bottom of the glands. The maintenance of intestinal stem cells is supported by a niche which is composed of several signaling proteins including the Hippo pathway effectors YAP1/TAZ. The role of YAP1/TAZ in cell proliferation and regeneration is well documented but their involvement on the differentiation of intestinal epithelial cells is unclear.

ILK supports RhoA/ROCK-mediated contractility of human intestinal epithelial crypt cells by inducing the fibrillogenesis of endogenous soluble fibronectin during the spreading process.

Background: Fibronectin (FN) assembly into an insoluble fibrillar matrix is a crucial step in many cell responses to extracellular matrix (ECM) properties, especially with regards to the integrin-related mechanosensitive signaling pathway. We have previously reported that the silencing of expression of integrin-linked kinase (ILK) in human intestinal epithelial crypt (HIEC) cells causes significant reductions in proliferation and spreading through concomitantly acquired impairment of soluble FN deposition. These defects in ILK-depleted cells are rescued by growth on exogenous FN.

Colorectal Cancer Research: Basic, Preclinical, and Clinical Approaches.

Colorectal cancer remains one of the deadliest cancers worldwide. It has become evident that further efforts in colorectal cancer research are required, from providing a better understanding of the cellular and molecular mechanisms leading to colorectal neoplasm initiation and progression from adenoma to metastasis, to generating reliable non-invasive detection tests for identifying lesions at early stages, as well as refining the current therapeutic and personalized approaches and developing new ones. The aim of this Special Issue is to cover all aspects of colorectal cancer research, including basic, preclinical, and clinical approaches.

Integrin α6β4 in Colorectal Cancer: Expression, Regulation, Functional Alterations and Use as a Biomarker.

Integrin α6β4 is one of the main laminin receptors and is primarily expressed by epithelial cells as an active component of hemidesmosomes. In this article, after a brief summary about integrins in the gut epithelium in general, I review the knowledge and clinical potential of this receptor in human colorectal cancer (CRC) cells. Most CRC cells overexpress both α6 and β4 subunits, in situ in primary tumours as well as in established CRC cell lines.