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Frontiers in Immunology 2021Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced bone remodeling and infection or inflammation are considered central to the pathogenesis of MRONJ. In recent years, increasing evidence has shown that bisphosphonates (BPs)-mediated immunity dysfunction is associated with the pathophysiology of MRONJ. In a healthy state, mucosal immunity provides the first line of protection against pathogens and oral mucosal immune cells defense against potentially invading pathogens by mediating the generation of protective immunoinflammatory responses. In addition, the immune system takes part in the process of bone remodeling and tissue repair. However, the treatment of BPs disturbs the mucosal and osteo immune homeostasis and thus impairs the body's ability to resist infection and repair from injury, thereby adding to the development of MRONJ. Here, we present the current knowledge about immunity dysfunction to shed light on the role of local immune disorder in the development of MRONJ.
Topics: Animals; Biomarkers; Bone Density Conservation Agents; Cytokines; Diphosphonates; Disease Susceptibility; Drug-Related Side Effects and Adverse Reactions; Humans; Immunity, Mucosal; Inflammation Mediators; Jaw; Mucous Membrane; Osteogenesis; Osteonecrosis; Signal Transduction; Wound Healing
PubMed: 33717086
DOI: 10.3389/fimmu.2021.606043 -
Journal of Cell Science Aug 2014The cell cortex is a dynamic and heterogeneous structure that governs cell identity and behavior. The ERM proteins (ezrin, radixin and moesin) are major architects of...
The cell cortex is a dynamic and heterogeneous structure that governs cell identity and behavior. The ERM proteins (ezrin, radixin and moesin) are major architects of the cell cortex, and they link plasma membrane phospholipids and proteins to the underlying cortical actin cytoskeleton. Recent studies in several model systems have uncovered surprisingly dynamic and complex molecular activities of the ERM proteins and have provided new mechanistic insight into how they build and maintain cortical domains. Among many well-established and essential functions of ERM proteins, this Cell Science at a Glance article and accompanying poster will focus on the role of ERMs in organizing the cell cortex during cell division and apical morphogenesis. These examples highlight an emerging appreciation that the ERM proteins both locally alter the mechanical properties of the cell cortex, and control the spatial distribution and activity of key membrane complexes, establishing the ERM proteins as a nexus for the physical and functional organization of the cell cortex and making it clear that they are much more than scaffolds. This article is part of a Minifocus on Establishing polarity.
Topics: Animals; Basement Membrane; Cell Polarity; DNA-Binding Proteins; Epithelial Cells; GTPase-Activating Proteins; Humans; Integrins; Neoplasms; Transcription Factors
PubMed: 24951115
DOI: 10.1242/jcs.098343 -
Biochimica Et Biophysica Acta Sep 2014There are many peptides known that inhibit the entry of enveloped viruses into cells, including one peptide that is successfully being used in the clinic as a drug. In... (Review)
Review
There are many peptides known that inhibit the entry of enveloped viruses into cells, including one peptide that is successfully being used in the clinic as a drug. In this review, we discuss the discovery, antiviral activity and mechanism of action of such peptides. While peptide entry inhibitors have been discovered by a wide variety of approaches (structure-based, accidental, intentional, rational and brute force) we show here that they share a common physical chemical property: they are at least somewhat hydrophobic and/or amphipathic and have a propensity to interact with membrane interfaces. We propose that this propensity drives a shared mechanism of action for many peptide entry inhibitors, involving direct interactions with viral and cellular membranes, as well as interactions with the complex hydrophobic protein/lipid interfaces that are exposed, at least transiently, during virus-cell fusion. By interacting simultaneously with the membrane interfaces and other critical hydrophobic surfaces, we hypothesize that peptide entry inhibitors can act by changing the physical chemistry of the membranes, and the fusion protein interfaces bridging them, and by doing so interfere with the fusion of cellular and viral membranes. Based on this idea, we propose that an approach that focuses on the interfacial hydrophobicity of putative entry inhibitors could lead to the efficient discovery of novel, broad-spectrum viral entry inhibitors. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
Topics: Cell Membrane; Genome, Viral; Hydrophobic and Hydrophilic Interactions; Membrane Fusion; Membranes; Peptides; Protein Conformation; Viral Envelope Proteins; Viral Fusion Proteins; Virion
PubMed: 24780375
DOI: 10.1016/j.bbamem.2014.04.015 -
International Journal of Molecular... Jun 2019Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first... (Review)
Review
Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, immune barrier, and biological barrier. Firstly, mycotoxins can disrupt the mechanical barrier function of the intestinal mucosa, by destroying the morphology and tissue integrity of the intestinal epithelium. Secondly, mycotoxins can cause changes in the composition of mucin monosaccharides and the expression of intestinal mucin, which in turn affects mucin function. Thirdly, mycotoxins can cause damage to the intestinal mucosal immune barrier function. Finally, the microbiotas of animals closely interact with ingested mycotoxins. Based on existing research, this article reviews the effects of mycotoxins on the intestinal mucosal barrier and its mechanisms.
Topics: Animals; Humans; Immunity, Innate; Intestinal Mucosa; Mucins; Mycotoxins
PubMed: 31174254
DOI: 10.3390/ijms20112777 -
International Journal of Molecular... Jan 2022Pleural injury and subsequent loculation is characterized by acute injury, sustained inflammation and, when severe, pathologic tissue reorganization. While fibrin... (Review)
Review
Pleural injury and subsequent loculation is characterized by acute injury, sustained inflammation and, when severe, pathologic tissue reorganization. While fibrin deposition is a normal part of the injury response, disordered fibrin turnover can promote pleural loculation and, when unresolved, fibrosis of the affected area. Within this review, we present a brief discussion of the current IPFT therapies, including scuPA, for the treatment of pathologic fibrin deposition and empyema. We also discuss endogenously expressed PAI-1 and how it may affect the efficacy of IPFT therapies. We further delineate the role of pleural mesothelial cells in the progression of pleural injury and subsequent pleural remodeling resulting from matrix deposition. We also describe how pleural mesothelial cells promote pleural fibrosis as myofibroblasts via mesomesenchymal transition. Finally, we discuss novel therapeutic targets which focus on blocking and/or reversing the myofibroblast differentiation of pleural mesothelial cells for the treatment of pleural fibrosis.
Topics: Animals; Disease Progression; Drug Delivery Systems; Fibrosis; Gene Expression Regulation; Humans; Plasminogen Activator Inhibitor 1; Pleura; Recombinant Proteins; Urokinase-Type Plasminogen Activator
PubMed: 35163509
DOI: 10.3390/ijms23031587 -
Hearing Research Sep 2022Cochlear distortions afford researchers and clinicians a glimpse into the conditions and properties of inner ear signal processing mechanisms. Until recently, our... (Review)
Review
Cochlear distortions afford researchers and clinicians a glimpse into the conditions and properties of inner ear signal processing mechanisms. Until recently, our examination of these distortions has been limited to measuring the vibration of the basilar membrane or recording acoustic distortion output in the ear canal. Despite its importance, the generation mechanism of cochlear distortion remains a substantial task to understand. The ability to measure the vibration of the reticular lamina in rodent models is a recent experimental advance. Surprising mechanical properties have been revealed. These properties merit both discussion in context with our current understanding of distortion, and appraisal of the significance of new interpretations of cochlear mechanics. This review focusses on some of the recent data from our research groups and discusses the implications of these data on our understanding of vocalization processing in the periphery, and their influence upon future experimental directions. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.
Topics: Acoustic Stimulation; Basement Membrane; Basilar Membrane; Cochlea; Hair Cells, Auditory, Outer; Vibration
PubMed: 34916081
DOI: 10.1016/j.heares.2021.108405 -
Sheng Li Xue Bao : [Acta Physiologica... Aug 2016Epicardium is one of the important components of the heart and plays a critical role in cardiogenesis. Moreover, further studies have shown that epicardium contributes... (Review)
Review
Epicardium is one of the important components of the heart and plays a critical role in cardiogenesis. Moreover, further studies have shown that epicardium contributes to post-injury heart regeneration. After heart injury, epicardium secretes various signaling factors, regulating the cardiomyocyte proliferation and neovascularization. In addition, epicardium differentiates into many kinds of cells which take part in the heart repair in response to heart damage. In this review, we summarize recent progress on epicardial function, related signaling pathways and the potential clinical application, and provide a reference for future studies in epicardium and heart regeneration.
Topics: Heart; Pericardium; Regeneration; Signal Transduction
PubMed: 27546512
DOI: No ID Found -
American Journal of Kidney Diseases :... Dec 2014The speed with which small solutes cross the peritoneal membrane, termed peritoneal solute transport rate (PSTR), is a key measure of individual membrane performance.... (Review)
Review
The speed with which small solutes cross the peritoneal membrane, termed peritoneal solute transport rate (PSTR), is a key measure of individual membrane performance. PSTR can be quantified easily by using the 4-hour dialysate to plasma creatinine ratio, which, although only an approximation to the diffusive characteristics of the membrane, has been well validated clinically in terms of its relationship to patient survival and changes in longitudinal membrane function. This has led to changes in peritoneal dialysis modality use and dialysis prescription. An important determinant of PSTR is intraperitoneal inflammation, as exemplified by local interleukin 6 production, which is largely independent of systemic inflammation and its relationship to comorbid conditions and increased mortality. There is no strong evidence to support the contention that the peritoneal membrane in some individuals with high PSTR is qualitatively different at the start of treatment; rather, it represents a spectrum that is determined in part by genetic factors. Both clinical and experimental evidence support the view that persistent intraperitoneal inflammation, detected as a continuously high or increasing PSTR, may predispose the membrane to progressive fibrosis.
Topics: Biological Transport; Dialysis Solutions; Humans; Inflammation; Male; Peritoneal Dialysis; Peritoneum; Young Adult
PubMed: 25176170
DOI: 10.1053/j.ajkd.2014.06.030 -
Ophthalmology Feb 2018Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise...
PURPOSE
Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies.
DESIGN
Clinicohistologic correlation study.
PARTICIPANTS
Thirty-six human donor globes.
METHODS
Vitreous bodies identified to have posterior vitreous detachment were examined with phase-contrast microscopy and confocal microscopy after immunohistochemically staining for collagen IV basement membrane markers, in addition to extracellular proteins that characterize the vitreoretinal junction (fibronectin, laminin) and vitreous gel (opticin) markers. The posterior retina similarly was stained to evaluate the internal limiting membrane. Findings were correlated to the clinical appearance of the posterior hyaloid membrane observed during slit-lamp biomicroscopy after posterior vitreous detachment and compared with previously published studies.
MAIN OUTCOME MEASURES
Morphologic appearance and molecular composition of the posterior hyaloid membrane.
RESULTS
Phase-contrast microscopy consistently identified a creased and distinct glassy membranous sheet enveloping the posterior vitreous surface, correlating closely with the posterior hyaloid membrane observed during slit-lamp biomicroscopy in patients with posterior vitreous detachment. Immunofluorescent confocal micrographs demonstrated the enveloping membranous structure identified on phase-contrast microscopy to show positive stain results for type IV collagen. Immunofluorescence of the residual intact internal limiting membrane on the retinal surface also showed positive stain results for type IV collagen.
CONCLUSIONS
The results of this study provide immunohistochemical evidence that the posterior hyaloid membrane is a true basement membrane enveloping the posterior hyaloid surface. Because this membranous structure is observed only after posterior vitreous detachment, the results of this study indicate that it forms part of the internal limiting membrane when the vitreous is in its attached state.
Topics: Adult; Aged; Aged, 80 and over; Basement Membrane; Collagen; Female; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Male; Microscopy, Acoustic; Microscopy, Confocal; Middle Aged; Prospective Studies; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 28867131
DOI: 10.1016/j.ophtha.2017.08.001 -
Hearing Research Sep 2022Intra organ of Corti (OC) vibrations differ from those measured at the basilar membrane (BM), with higher amplitudes and a wide-band nonlinearity extending well below a...
Intra organ of Corti (OC) vibrations differ from those measured at the basilar membrane (BM), with higher amplitudes and a wide-band nonlinearity extending well below a region's best frequency. The vibrations are boosted by the cochlear amplifier, the active processes within the mammalian hearing organ, and are thus sensitive to metabolic or pharmacological manipulation. We introduced salicylate, a known blocker of outer hair cell (OHC) based electromotility, into the perilymphatic space by applying sodium salicylate onto the round window membrane. Vibration patterns of an area of the OC were mapped with phase sensitive optical coherence tomography before and after treatment; distortion product otoacoustic emissions (DPOAEs) were measured at similar times to assess the cochlear condition. Following treatment, all regions showed a loss of vibration amplitude and tuning while OHC-region vibrations retained their wide-band nonlinearity. OC vibrations, which had been relatively confined in a region including OHCs and extending to the BM at the outer pillar foot, became less confined with structures lateral to the OHCs sometimes exhibiting the highest amplitudes. Vibrations and DPOAEs could recover to baseline levels over approximately three hours post treatment. 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; Salicylates; Vibration
PubMed: 34774368
DOI: 10.1016/j.heares.2021.108389