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Current Molecular Medicine 2018The mammalian intestine is not only an organ for food digestion and nutrient absorption but also an integral part of the immune and endocrine systems. The intestinal... (Review)
Review
The mammalian intestine is not only an organ for food digestion and nutrient absorption but also an integral part of the immune and endocrine systems. The intestinal epithelium under stressful environments requires epithelial cells to rapidly elicit changes in gene expression patterns to regulate their survival, adapt to stress, and maintain epithelial homeostasis. Recently, miRNAs have emerged as a novel class of posttranscriptional gene regulators that are fundamentally involved in many aspects of intestinal epithelial differentiation, architecture, and barrier function. In this review, we highlight the critical roles of miRNAs in both the crypt-villus axis of cellular self-renewal and inflammation in the mammalian intestinal mucosa and their impact on the microbiota. We also discuss the functions of specific miRNAs within the intestine to better understand the cellular mechanisms that promote intestinal homeostasis, and the influence of dietary components in the regulation of endogenous miRNA in the study of nutrition and gene regulation in intestinal health.
Topics: Animals; Cell Differentiation; Gastrointestinal Microbiome; Homeostasis; Humans; Inflammation; Intestinal Mucosa; MicroRNAs
PubMed: 30198431
DOI: 10.2174/1566524018666180907163638 -
Differentiation; Research in Biological... Sep 2016In this Review we summarize our current understanding of the biology of mesenchymal cells of the intestinal lamina propria focusing mainly on fibroblasts and... (Review)
Review
In this Review we summarize our current understanding of the biology of mesenchymal cells of the intestinal lamina propria focusing mainly on fibroblasts and myofibroblasts. The topics covered include 1) the embryonic origin of mesenchymal cells of the intestinal lamina propria and their heterogeneity in adults, 2) the role of the mesenchyme in intestinal development, 3) the physiological function of fibroblasts and myofibroblasts in adults as part of the intestinal stem cell niche and the mucosal immune system and 4) the involvement of fibroblasts and myofibroblasts in epithelial homeostasis upon injury and in the pathogenesis of diseases such as Inflammatory Bowel Diseases, fibrosis and cancer. We emphasize studies addressing the function of intestinal mesenchymal cells in vivo, and also discuss major open questions and current challenges in this field.
Topics: Animals; Fibroblasts; Humans; Intestinal Mucosa; Intestines; Mesoderm; Myofibroblasts; Stromal Cells
PubMed: 27165847
DOI: 10.1016/j.diff.2016.05.002 -
IUBMB Life Apr 2019Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive... (Review)
Review
Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive diffusion process. However, data obtained during the past 15 years showed that its absorption is actually mediated, at least in part, by cholesterol membrane transporters including the scavenger receptor class B type I (SR-BI), CD36 molecule (CD36), NPC1-like transporter 1 (NPC1L1), and ATP-binding cassettes A1 and G1 (ABCA1 and ABCG1). This review focuses on the absorption process of vitamin E across the enterocyte. A special attention is given to the regulation of this process, including the possible competition with other fat-soluble micronutrients, and the modulation of transporter expressions. Overall, recent results noticeably increased the comprehension of vitamin E intestinal transport, but additional investigations are still required to fully appreciate the mechanisms governing vitamin E bioavailability. © 2018 IUBMB Life, 71(4):416-423, 2019.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 1; ATP-Binding Cassette Transporters; Animals; Biological Availability; Biological Transport; CD36 Antigens; Chylomicrons; Enterocytes; Humans; Intestinal Absorption; Membrane Transport Proteins; Vitamin E
PubMed: 30308094
DOI: 10.1002/iub.1955 -
Der Ophthalmologe : Zeitschrift Der... Apr 2017Reconstruction of the conjunctiva is an essential part of ocular surface reconstruction. Clinically applied and experimentally tested tissue- and stem-cell-based... (Review)
Review
BACKGROUND
Reconstruction of the conjunctiva is an essential part of ocular surface reconstruction. Clinically applied and experimentally tested tissue- and stem-cell-based approaches are presented and evaluated.
MATERIALS AND METHODS
Current literature and our own results will be presented.
RESULTS
Autologous conjunctiva, mucous membrane of the mouth or nose, and amniotic membrane are routinely used for conjunctival reconstruction. Limitations are limited availability, involvement in autoimmune diseases, donor heterogeneity, and degradation in an inflamed environment. Experimentally tested matrices as tissues made from extracellular matrix proteins, synthetic polymers, temperature-sensitive culture dishes, and decellularized conjunctiva have been tested in vitro and partly in vivo. To replace conjunctival cells, cells of conjunctiva and mucous membrane of mouth and nose have been evaluated and show progenitor cell properties as well as secretory capacity (goblet cell differentiation).
CONCLUSIONS
Although different matrices are available for conjunctival reconstruction there is-due to specific limitations of existing tissues-a need for the development of new therapies for conjunctival replacement. Matrices produced in the laboratory have already been partly investigated in vivo and may thus be clinically applicable in the near future. Adult mucous membrane cells show many properties of conjunctival epithelium after expansion in vitro and thus are a promising cell source for conjunctival tissue engineering. Other stem cells sources require further evaluation.
Topics: Amnion; Conjunctiva; Evidence-Based Medicine; Extracellular Matrix; Humans; Mucous Membrane; Ophthalmologic Surgical Procedures; Plastic Surgery Procedures; Stem Cell Transplantation; Treatment Outcome
PubMed: 28005177
DOI: 10.1007/s00347-016-0419-1 -
Seminars in Nuclear Medicine Sep 2020The peritoneum is the largest and most complex serous membrane in the human body. The peritoneal membrane is composed of a layer of mesothelium supported by a thin layer... (Review)
Review
The peritoneum is the largest and most complex serous membrane in the human body. The peritoneal membrane is composed of a layer of mesothelium supported by a thin layer of connective tissue. The peritoneum is one continuous sheet, forming two layers and a potential space between them - the peritoneal cavity- which is subdivided into multiple communicating spaces containing small amount of serous fluid that facilitates frictionless movement of mobile intraabdominal viscera. Peritoneum also contributes to fluid exchange mechanism and plays a role in immune response. The peritoneum is subject to many neoplastic and non-neoplastic processes including infections, trauma, developmental and inflammatory processes. Different Nuclear Medicine imaging techniques can be used to diagnose peritoneal diseases, most of these techniques can be customized depending on the clinical scenario and expected findings. Peritoneal scintigraphy can detect abnormal peritoneal communication or compartmentalization. Several nuclear medicine techniques can help characterize intraperitoneal fluid collections and differentiate sterile from infected fluid. PET imaging plays an important role in imaging of different neoplastic and non-neoplastic peritoneal pathologies. Nuclear radiologists need to be familiar with peritoneal anatomy and pathology to interpret peritoneal findings in dedicated peritoneal nuclear medicine imaging studies, as part of more general nuclear medicine scans, or on CT or MRI component of hybrid imaging studies. The purpose of this article is to review the normal peritoneal anatomy, various pathologic processes involving the peritoneum, and different nuclear medicine and hybrid imaging techniques that can help detect, characterize, and follow up peritoneal pathology.
Topics: Humans; Nuclear Medicine; Peritoneum
PubMed: 32768005
DOI: 10.1053/j.semnuclmed.2020.04.005 -
American Journal of Physiology.... Apr 2016Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na(+)-K(+)-ATPase (NKA), Na(+)/H(+) exchangers (NHEs), epithelial Na(+) channels (ENaC), and K(+) channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.
Topics: Animals; Epithelial Cells; Epithelial Sodium Channels; Gastrointestinal Absorption; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Ion Transport; Membrane Transport Modulators; Potassium Channels; Signal Transduction; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase
PubMed: 26744474
DOI: 10.1152/ajpgi.00369.2015 -
Frontiers in Immunology 2019The Wnt signaling pathway is a conserved pathway involved in important cellular processes such as the control of embryonic development, cellular polarity, cellular... (Review)
Review
The Wnt signaling pathway is a conserved pathway involved in important cellular processes such as the control of embryonic development, cellular polarity, cellular migration, and cell proliferation. In addition to playing a central role during embryogenesis, this pathway is also an essential part of adult homeostasis. Indeed, it controls the proliferation of epithelial cells in different organs such as intestine, lung, and kidney, and guarantees the maintenance of the mucosa in physiological conditions. The origin of this molecular pathway is the binding between Wnt ligands (belonging to a family of 19 different homologous secreted glycoproteins) and their specific membrane receptors, from the Frizzled receptor family. This specific interaction triggers the activation of the signaling cascade, which in turn activates or suppresses the expression of different genes in order to change the behavior of the cell. On the other hand, alterations of this pathway have been described in pathological conditions such as inflammation, fibrosis, and cancer. In recent years, macrophages-among other cell types-have emerged as a potential source of Wnt ligands. Due to their high plasticity, macrophages, which are central to the innate immune response, are capable of adopting different phenotypes depending on their microenvironment. In the past, two different phenotypes were described: a proinflammatory phenotype-M1 macrophages-and an anti-inflammatory phenotype-M2 macrophages-and a selective expression of Wnt ligands has been associated with said phenotypes. However, nowadays it is assumed that macrophages move through a continual spectrum of functional phenotypes. In both physiological and pathological (inflammation, fibrosis and cancer) conditions, the accumulation and polarization of macrophages conditions the future of the tissue, facilitating various scenarios, such as resolution of inflammation, activation of fibrosis, and cancer development due to the modulation of the Wnt signaling pathway, in autocrine and paracrine manner. In this work, we provide an overview of studies that have explored the role of macrophages and how they act as a source of Wnt ligands and as mediators of mucosal integrity.
Topics: Humans; Immunity, Innate; Inflammation; Ligands; Macrophages; Mucous Membrane; Neoplasms; Protein Binding; Wnt Proteins; Wnt Signaling Pathway
PubMed: 31608072
DOI: 10.3389/fimmu.2019.02297 -
Hearing Research Sep 2022It is a common belief that the mammalian cochlea achieves its exquisite sensitivity, frequency selectivity, and dynamic range through an outer hair cell-based active...
It is a common belief that the mammalian cochlea achieves its exquisite sensitivity, frequency selectivity, and dynamic range through an outer hair cell-based active process, or cochlear amplification. As a sound-induced traveling wave propagates from the cochlear base toward the apex, outer hair cells at a narrow region amplify the low level sound-induced vibration through a local feedback mechanism. This widely accepted theory has been tested by measuring sound-induced sub-nanometer vibrations within the organ of Corti in the sensitive living cochleae using heterodyne low-coherence interferometry and optical coherence tomography. The aim of this short review is to summarize experimental findings on the cochlear active process by the authors' group. Our data show that outer hair cells are able to generate substantial forces for driving the cochlear partition at all audible frequencies in vivo. The acoustically induced reticular lamina vibration is larger and more broadly tuned than the basilar membrane vibration. The reticular lamina and basilar membrane vibrate approximately in opposite directions at low frequencies and in the same direction at the best frequency. The group delay of the reticular lamina is larger than that of the basilar membrane. The magnitude and phase differences between the reticular lamina and basilar membrane vibration are physiologically vulnerable. These results contradict predictions based on the local feedback mechanism but suggest a global hydromechanical mechanism for cochlear amplification. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.
Topics: Animals; Basilar Membrane; Cochlea; Hair Cells, Auditory, Outer; Mammals; Organ of Corti; Sound; Vibration
PubMed: 34922772
DOI: 10.1016/j.heares.2021.108407 -
Biochimica Et Biophysica Acta Aug 2014Tumor microenvironment is a complex system composed of a largely altered extracellular matrix with different cell types that determine angiogenic responses and tumor... (Review)
Review
BACKGROUND
Tumor microenvironment is a complex system composed of a largely altered extracellular matrix with different cell types that determine angiogenic responses and tumor progression. Upon the influence of hypoxia, tumor cells secrete cytokines that activate stromal cells to produce proteases and angiogenic factors. In addition to stromal ECM breakdown, proteases exert various pro- or anti-tumorigenic functions and participate in the release of various ECM fragments, named matrikines or matricryptins, capable to act as endogenous angiogenesis inhibitors and to limit tumor progression.
SCOPE OF REVIEW
We will focus on the matrikines derived from the NC1 domains of the different constitutive chains of basement membrane-associated collagens and mainly collagen IV.
MAJOR CONCLUSIONS
The putative targets of the matrikine control are the proliferation and invasive properties of tumor or inflammatory cells, and the angiogenic and lymphangiogenic responses. Collagen-derived matrikines such as canstatin, tumstatin or tetrastatin for example, decrease tumor growth in various cancer models. Their anti-cancer activities comprise anti-proliferative effects on tumor or endothelial cells by induction of apoptosis or cell cycle blockade and the induction of a loss of their migratory phenotype. They were used in various preclinical therapeutic strategies: i) induction of their overexpression by cancer cells or by the host cells, ii) use of recombinant proteins or synthetic peptides or structural analogues designed from the structure of the active sequences, iii) used in combined therapies with conventional chemotherapy or radiotherapy.
GENERAL SIGNIFICANCE
Collagen-derived matrikines strongly inhibited tumor growth in many preclinical cancer models in mouse. They constitute a new family of anti-cancer agents able to limit cancer progression. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
Topics: Animals; Antineoplastic Agents; Basement Membrane; Clinical Trials as Topic; Collagen; Humans; Peptide Fragments; Tumor Microenvironment
PubMed: 24406397
DOI: 10.1016/j.bbagen.2013.12.029 -
International Journal of Molecular... Jun 2021In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier... (Review)
Review
In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier wash-out, the development of new carriers for gynecological use is necessary. Furthermore, high individual anatomical and physiological variability resulting in unsatisfactory therapeutic efficacy of lipophilic active substances requires application of multicompartment drug delivery systems. This manuscript provides an up-to-date comprehensive review of the literature on emulsion-based vaginal dosage forms (EVDF) including macroemulsions, microemulsions, nanoemulsions, multiple emulsions and self-emulsifying drug delivery systems. The first part of the paper discusses (i) the influence of anatomical-physiological conditions on therapeutic efficacy of drug forms after local and systemic administration, (ii) characterization of EVDF components and the manufacturing techniques of these dosage forms and (iii) methods used to evaluate the physicochemical and pharmaceutical properties of emulsion-based vaginal dosage forms. The second part of the paper presents (iv) the results of biological and in vivo studies as well as (v) clinical evaluation of EVDF safety and therapeutic efficacy across different indications.
Topics: Administration, Intravaginal; Chemical Phenomena; Drug Carriers; Drug Compounding; Drug Delivery Systems; Emulsions; Female; Humans; Microbiota; Mucous Membrane; Pharmaceutical Preparations; Theranostic Nanomedicine
PubMed: 34208652
DOI: 10.3390/ijms22126455