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American Journal of Respiratory Cell... Mar 2019The human lung is constantly exposed to the environment and potential pathogens. As the interface between host and environment, the respiratory epithelium has evolved... (Review)
Review
The human lung is constantly exposed to the environment and potential pathogens. As the interface between host and environment, the respiratory epithelium has evolved sophisticated sensing mechanisms as part of its defense against pathogens. In this review, we examine how the respiratory epithelium senses and responds to influenza A virus, the biggest cause of respiratory viral deaths worldwide.
Topics: Humans; Influenza A virus; Influenza, Human; Lung; Respiratory Mucosa
PubMed: 30372120
DOI: 10.1165/rcmb.2018-0247TR -
Gut Microbes Jan 2017Intestinal infections are a global challenge, connected to malnutrition and inadequate hygiene in developing countries, and to expanding antibiotic resistance in... (Review)
Review
Intestinal infections are a global challenge, connected to malnutrition and inadequate hygiene in developing countries, and to expanding antibiotic resistance in developed countries. In general, a healthy host is capable of fighting off gut pathogens or at least to recover from infections quickly. The underlying protective mechanism, termed colonization resistance, is provided by indigenous commensal communities (microbiota) that are shaped and aided by the host's epithelial and innate immune system. Commensal-pathogen interactions are governed by competition for a suitable niche for replication and stable colonization, nutrient availability, species-specific alterations of the metabolic environment, changes in oxygen tension and release of chemicals and proteinaceous toxins (bacteriocins). This protective intestinal milieu is further reinforced by antimicrobial factors and chemicals secreted by the epithelial barrier, by dendritic cell sensing and by homeostasis between T-cell subsets (Treg/Th17) in the lamina propria. The 3 players (host-microbiota-pathogen) communicate via direct interactions or secreted factors. Our recent manuscript illustrates that reactive oxygen species (ROS) are an integral part of colonization resistance and should be considered an interkingdom antivirulence strategy.
Topics: Animals; Dendritic Cells; Gastrointestinal Microbiome; Humans; Hydrogen Peroxide; Intestinal Mucosa; T-Lymphocyte Subsets
PubMed: 28080210
DOI: 10.1080/19490976.2017.1279378 -
Annals of the American Thoracic Society Nov 2018The respiratory system is protected from inhaled particles and microbes by the mucociliary system. This system differs between animal species, where pigs and humans have... (Review)
Review
The respiratory system is protected from inhaled particles and microbes by the mucociliary system. This system differs between animal species, where pigs and humans have numerous submucosal glands. The polymer-forming mucin, MUC5B, is packed in a highly organized way in granules of the mucus-secreting cells in the glands. Upon secretion, the packed MUC5B is flushed out by a chloride- and bicarbonate-rich fluid from the cystic fibrosis transmembrane conductance regulator-expressing serosal cells located at the most distal part of the gland. The bicarbonate raises the pH and removes calcium from the N terminus of MUC5B, allowing the mucin to be pulled out into a linear polymer. Thousands of such polymers gather in bundles in the submucosal gland duct, and these bundles appear at the opening of the glands. They are moved by the beating cilia, and sweep over the airway surface and are patchily coated with the MUC5AC mucin from the surface goblet cells. The movement of these bundles is controlled by the MUC5AC mucin attachment/detachment to the goblet cells. Thus, higher animals with submucosal glands and large diameters of the proximal airways are efficiently cleaned by the thick mucus bundles sweeping the airway surface and moving particles and bacteria toward the larynx.
Topics: Animals; Disease Models, Animal; Humans; Lung Diseases; Mucins; Mucociliary Clearance; Respiratory Mucosa; Secretory Vesicles; Swine
PubMed: 30431338
DOI: 10.1513/AnnalsATS.201804-238AW -
Asian Pacific Journal of Allergy and... Jun 2022Due to the high prevalence of both obstructive sleep apnea syndrome (OSA) and end-stage renal disease (ESRD), the co-existence of both conditions in peritoneal dialysis...
BACKGROUND
Due to the high prevalence of both obstructive sleep apnea syndrome (OSA) and end-stage renal disease (ESRD), the co-existence of both conditions in peritoneal dialysis is demonstrated. Because OSA-induced chronic intermittent hypoxia is well-known, the hypoxia might worsen peritoneal membrane.
OBJECTIVE
We tested the influence of chronic intermittent hypoxia upon peritoneal membrane in a Sprague-Dawley rat model.
METHODS
Normal saline or 3.86% glucose peritoneal dialysis fluid (PDF) were intra-peritoneally administered twice a day as negative (NSS group) and positive controls (PDF group), respectively. Intermittent hypoxia was induced by using a hypoxic chamber with 10% O2 for 8 hours a day plus twice-daily NSS injection (IH group).
RESULTS
At 12 weeks of the experiments, high serum TNF-α and IL-6 (but not IL-10) with normal renal and liver functions were demonstrated in the IH group (but not the PDF group). In parallel, local cytokines (TNF-α, IL-6, and IL10 in peritoneal membrane) and peritoneal membrane thickness were increased whereas peritoneal membrane hypoxia (hypoxyprobeTM and hypoxia-inducible factor-1α; HIF-1α) was induced in both PDF and IH groups (more prominent in the PDF group). However, the increased vascular density in submesothelial area was established only in the PDF group.
CONCLUSION
Intermittent hypoxia model induced local peritoneal membrane inflammation and enhanced peritoneal membrane thickness, at least in part, through a mechanism of hypoxia-induced HIF-1α. Although peritoneal membrane alterations from PDF were more prominent than intermittent hypoxia, the combination between intermittent hypoxia with PDF utilization might facilitate peritoneal membrane failure, which will need more study.
Topics: Animals; Cytokines; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; Peritoneum; Rats; Rats, Sprague-Dawley; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha
PubMed: 31837216
DOI: 10.12932/AP-290519-0570 -
Investigative Ophthalmology & Visual... Jan 2022To highlight the cellular, matrix, and hydration changes associated with opacity that occurs in the corneal stroma after injury. (Review)
Review
PURPOSE
To highlight the cellular, matrix, and hydration changes associated with opacity that occurs in the corneal stroma after injury.
METHODS
Review of the literature.
RESULTS
The regulated transition of keratocytes to corneal fibroblasts and myofibroblasts, and of bone marrow-derived fibrocytes to myofibroblasts, is in large part modulated by transforming growth factor beta (TGFβ) entry into the stroma after injury to the epithelial basement membrane (EBM) and/or Descemet's membrane. The composition, stoichiometry, and organization of the stromal extracellular matrix components and water is altered by corneal fibroblast and myofibroblast production of large amounts of collagen type I and other extracellular matrix components-resulting in varying levels of stromal opacity, depending on the intensity of the healing response. Regeneration of EBM and/or Descemet's membrane, and stromal cell production of non-EBM collagen type IV, reestablishes control of TGFβ entry and activity, and triggers TGFβ-dependent myofibroblast apoptosis. Eventually, corneal fibroblasts also disappear, and repopulating keratocytes reorganize the disordered extracellular matrix to reestablish transparency.
CONCLUSIONS
Injuries to the cornea produce varying amounts of corneal opacity depending on the magnitude of cellular and molecular responses to injury. The EBM and Descemet's membrane are key regulators of stromal cellularity through their modulation of TGFβ. After injury to the cornea, depending on the severity of the insult, and possibly genetic factors, trace opacity to severe scarring fibrosis develops. Stromal cellularity, and the functions of different cell types, are the major determinants of the level of the stromal opacity.
Topics: Animals; Apoptosis; Basement Membrane; Cicatrix; Corneal Injuries; Corneal Opacity; Epithelium, Corneal; Fibrosis; Humans; Wound Healing
PubMed: 35044454
DOI: 10.1167/iovs.63.1.22 -
Pflugers Archiv : European Journal of... Apr 2024The transport of bicarbonate across the enterocyte cell membrane regulates the intracellular as well as the luminal pH and is an essential part of directional fluid... (Review)
Review
The transport of bicarbonate across the enterocyte cell membrane regulates the intracellular as well as the luminal pH and is an essential part of directional fluid movement in the gut. Since the first description of "active" transport of HCO ions against a concentration gradient in the 1970s, the fundamental role of HCO transport for multiple intestinal functions has been recognized. The ion transport proteins have been identified and molecularly characterized, and knockout mouse models have given insight into their individual role in a variety of functions. This review describes the progress made in the last decade regarding novel techniques and new findings in the molecular regulation of intestinal HCO transport in the different segments of the gut. We discuss human diseases with defects in intestinal HCO secretion and potential treatment strategies to increase luminal alkalinity. In the last part of the review, the cellular and organismal mechanisms for acid/base sensing in the intestinal tract are highlighted.
Topics: Animals; Mice; Humans; Bicarbonates; Ion Transport; Enterocytes; Cell Membrane; Bodily Secretions; Hydrogen-Ion Concentration; Cystic Fibrosis Transmembrane Conductance Regulator
PubMed: 38374228
DOI: 10.1007/s00424-024-02914-3 -
Trends in Molecular Medicine Jan 2022The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a... (Review)
Review
The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a site for allergic sensitization to food. In this context, we focus on an important but overlooked part of the mucosal barrier in pathogenesis, the glycoprotein-rich mucus layer, and call attention to both beneficial and detrimental aspects of mucus-gut microbiome interactions. Studying the intricate links between the mucus barrier, the associated bacteria, and the mucosal immune system may advance our understanding of the mechanisms and inform prevention and treatment strategies in food allergy.
Topics: Bacteria; Food Hypersensitivity; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mucus
PubMed: 34810087
DOI: 10.1016/j.molmed.2021.10.004 -
International Journal of Molecular... Sep 2023The amniotic membrane (AM) is the innermost part of the fetal placenta, which surrounds and protects the fetus. Due to its structural components (stem cells, growth... (Review)
Review
The amniotic membrane (AM) is the innermost part of the fetal placenta, which surrounds and protects the fetus. Due to its structural components (stem cells, growth factors, and proteins), AMs display unique biological properties and are a widely available and cost-effective tissue. As a result, AMs have been used for a century as a natural biocompatible dressing for healing corneal and skin wounds. To further increase its properties and expand its applications, advanced hybrid materials based on AMs have recently been developed. One existing approach is to combine the AM with a secondary material to create composite membranes. This review highlights the increasing development of new multilayer composite-based AMs in recent years and focuses on the benefits of additive manufacturing technologies and electrospinning, the most commonly used strategy, in expanding their use for tissue engineering and clinical applications. The use of AMs and multilayer composite-based AMs in the context of nerve regeneration is particularly emphasized and other tissue engineering applications are also discussed. This review highlights that these electrospun multilayered composite membranes were mainly created using decellularized or de-epithelialized AMs, with both synthetic and natural polymers used as secondary materials. Finally, some suggestions are provided to further enhance the biological and mechanical properties of these composite membranes.
Topics: Pregnancy; Female; Humans; Amnion; Cornea; Tissue Engineering; Stem Cells; Polymers; Tissue Scaffolds
PubMed: 37833872
DOI: 10.3390/ijms241914424 -
International Journal of Molecular... Feb 2023Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing... (Review)
Review
Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood-brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain. A part of the drug may be lost by drainage through the lymphatic system, while a part may even enter the systemic circulation and reach the brain by crossing the BBB. Alternatively, drugs can be directly transported to the brain by axons of the olfactory nerve. To improve the effectiveness of drug delivery to the brain by the IN route, various types of nanocarriers and hydrogels and their combinations have been proposed. This review paper analyzes the main biomaterials-based strategies to enhance IN drug delivery to the brain, outlining unsolved challenges and proposing ways to address them.
Topics: Pharmaceutical Preparations; Brain; Administration, Intranasal; Blood-Brain Barrier; Drug Delivery Systems; Nasal Mucosa
PubMed: 36834804
DOI: 10.3390/ijms24043390 -
International Journal of Molecular... Aug 2021The unique biology of the intestinal epithelial barrier is linked to a low baseline oxygen pressure (pO), characterised by a high rate of metabolites circulating through... (Review)
Review
The unique biology of the intestinal epithelial barrier is linked to a low baseline oxygen pressure (pO), characterised by a high rate of metabolites circulating through the intestinal blood and the presence of a steep oxygen gradient across the epithelial surface. These characteristics require tight regulation of oxygen homeostasis, achieved in part by hypoxia-inducible factor (HIF)-dependent signalling. Furthermore, intestinal epithelial cells (IEC) possess metabolic identities that are reflected in changes in mitochondrial function. In recent years, it has become widely accepted that oxygen metabolism is key to homeostasis at the mucosae. In addition, the gut has a vast and diverse microbial population, the microbiota. Microbiome-gut communication represents a dynamic exchange of mediators produced by bacterial and intestinal metabolism. The microbiome contributes to the maintenance of the hypoxic environment, which is critical for nutrient absorption, intestinal barrier function, and innate and/or adaptive immune responses in the gastrointestinal tract. In this review, we focus on oxygen homeostasis at the epithelial barrier site, how it is regulated by hypoxia and the microbiome, and how oxygen homeostasis at the epithelium is regulated in health and disease.
Topics: Animals; Cell Hypoxia; Gastrointestinal Microbiome; Homeostasis; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Oxygen
PubMed: 34502078
DOI: 10.3390/ijms22179170