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Mutation Research. Reviews in Mutation... 2016Radiotherapy is one of the most effective treatment strategies for solid malignancies, including head-and-neck tumors (HNT). Oral mucositis is the most frequent, often... (Review)
Review
Radiotherapy is one of the most effective treatment strategies for solid malignancies, including head-and-neck tumors (HNT). Oral mucositis is the most frequent, often dose-limiting early adverse event of radio(chemo)therapy for HNT. The oral mucosal response is - like that of typical turnover tissues - based on radiation-induced impairment of epithelial proliferation and cell production, in face of ongoing physiological cell differentiation and cell loss, consequently resulting in hypoplasia and eventually mucosal ulceration. The regenerative epithelial response, i.e. repopulation, and hence the impact of overall treatment time, besides intrinsic radiosensitivity, is the dominant parameter of the radiation tolerance of oral mucosa in fractionated radiotherapy protocols. The epithelial changes are accompanied, at the molecular and cellular level, by various changes in non-epithelial cell populations, i.e. vascular endothelial cells, macrophages, and fibroblasts. An inflammatory response precedes and parallels the epithelial changes; this includes vasodilation associated with rheological consequences and the manifestation of local hypoxia, activation of macrophages and endothelial cells. During these processes, a variety of intra- and intercellular communication pathways are modulated; NF-κB associated signaling is one prominent example. The interactions of these extra-epithelial changes with epithelial hypoplasia, ulceration and regeneration currently remain largely unclear. Research on the molecular mechanisms underlying the clinical manifestation of oral mucositis will allow for identification of potential early biomarkers of oral mucosal morbidity and thus for individualization of patient follow-up and treatment, and also for the development of targeted strategies for prophylaxis and/or mitigation of oral mucositis. This review summarizes the features of the clinical manifestation of oral mucositis and its consequences, the "classical" radiobiological parameters of mucosal radiation sensitivity. It moreover focuses on the underlying "molecular" mechanisms, and on biology-based approaches for the amelioration of radiation-induced oral mucositis.
Topics: Cell Hypoxia; Humans; Mouth Mucosa; Radiation, Ionizing; Stomatitis
PubMed: 27919336
DOI: 10.1016/j.mrrev.2016.07.007 -
Journal of Leukocyte Biology Nov 2016All animals heal, and the ability to heal is requisite for human health. One aspect of repair that has always been considered to be essential for adequate healing is the... (Review)
Review
All animals heal, and the ability to heal is requisite for human health. One aspect of repair that has always been considered to be essential for adequate healing is the creation of a new vasculature via angiogenesis. As adult skin wounds heal, a period of rapid and robust capillary growth creates a vascular bed that has many fold more capillaries than does normal tissue. Over time, most of the newly formed capillaries regress, resulting in a final vascular density similar to that of normal skin. Certainly, new capillaries are necessary to bring nutrients, immune cells, and oxygen to healing wounds. Yet, the presumed functional importance of an overabundance of capillaries has recently been challenged, creating questions about whether excess capillary growth is truly necessary for healing. In particular, studies of wounds that heal exceptionally quickly and with less scar formation, such as those in fetal skin and oral mucosa, show that these tissues heal with a reduced angiogenic burst composed of more mature vessels that provide better oxygenation. The level of angiogenesis in wounds often correlates with the inflammatory response, largely because inflammatory cells produce an abundance of proangiogenic mediators. Both the selective reduction of inflammation and the selective reduction of angiogenesis have now been suggested as ways to improve scarring. These concepts link excessive inflammation and the production of a dense but poorly perfused capillary bed to inferior healing outcomes.
Topics: Angiogenic Proteins; Animals; Capillaries; Cicatrix; Endothelial Cells; Fetus; Fibrosis; Humans; Inflammation; Mouth Mucosa; Neovascularization, Physiologic; Pericytes; Prenatal Injuries; Regeneration; Skin; Wound Healing
PubMed: 27406995
DOI: 10.1189/jlb.4MR0316-102R -
In Vivo (Athens, Greece) 2019Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition... (Review)
Review
BACKGROUND
Reactive oxygen species (ROS) and free radicals are physiologically produced during cellular metabolism. When their balance is disrupted in favor of ROS, a condition called oxidative stress occurs. Oxidative stress represents a widespread phenomenon involved in several pathological conditions. The aim of the present review was to report current knowledge on oxidative stress related to oral mucosal diseases.
MATERIALS AND METHODS
Articles from 2000 to 2018 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: oxidative stress and oral lichen, oral pemphigus, aphthous stomatitis, oral leukoplakia, oral cancer, oral squamous cell carcinoma and oral carcinoma. All articles were independently screened for eligibility by the authors.
RESULTS
This narrative review integrates extensive information from all relevant published studies focusing on oxidative stress in oral mucosal diseases. We outline the pathogenetic function of oxidative stress in the most frequent inflammatory, potentially malignant and malignant diseases of the oral mucosa and provide detailed findings from human research.
CONCLUSION
Although variability in findings between individual studies exists, it justifies the conclusion that oxidative stress is a significant process in the oral mucosal diseases pathogenesis.
Topics: Free Radicals; Humans; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Oxidative Stress; Reactive Oxygen Species
PubMed: 30804105
DOI: 10.21873/invivo.11474 -
Oral Diseases Sep 2020A crucial aspect of mucosal HIV transmission is the interaction between HIV, the local environmental milieu and immune cells. The oral mucosa comprises many host cell... (Review)
Review
A crucial aspect of mucosal HIV transmission is the interaction between HIV, the local environmental milieu and immune cells. The oral mucosa comprises many host cell types including epithelial cells, CD4 + T cells, dendritic cells and monocytes/macrophages, as well as a diverse microbiome predominantly comprising bacterial species. While the oral epithelium is one of the first sites exposed to HIV through oral-genital contact and nursing infants, it is largely thought to be resistant to HIV transmission via mechanisms that are still unclear. HIV-1 infection is also associated with predisposition to secondary infections, such as tuberculosis, and other diseases including cancer. This review addresses the following questions that were discussed at the 8th World Workshop on Oral Health and Disease in AIDS held in Bali, Indonesia, 13 September -15 September 2019: (a) How does HIV infection affect epithelial cell signalling? (b) How does HIV infection affect the production of cytokines and other innate antimicrobial factors, (c) How is the mucosal distribution and function of immune cells altered in HIV infection? (d) How do T cells affect HIV (oral) pathogenesis and cancer? (e) How does HIV infection lead to susceptibility to TB infections?
Topics: CD4-Positive T-Lymphocytes; HIV Infections; Humans; Immunity, Innate; Immunity, Mucosal; Infant; Mouth Mucosa
PubMed: 32862519
DOI: 10.1111/odi.13470 -
International Journal of Molecular... May 2021The oral cavity is a portal into the digestive system, which exhibits unique sensory properties. Like facial skin, the oral mucosa needs to be exquisitely sensitive and... (Review)
Review
The oral cavity is a portal into the digestive system, which exhibits unique sensory properties. Like facial skin, the oral mucosa needs to be exquisitely sensitive and selective, in order to detect harmful toxins versus edible food. Chemosensation and somatosensation by multiple receptors, including transient receptor potential channels, are well-developed to meet these needs. In contrast to facial skin, however, the oral mucosa rarely exhibits itch responses. Like the gut, the oral cavity performs mechanical and chemical digestion. Therefore, the oral mucosa needs to be insensitive, to some degree, in order to endure noxious irritation. Persistent pain from the oral mucosa is often due to ulcers, involving both tissue injury and infection. Trigeminal nerve injury and trigeminal neuralgia produce intractable pain in the orofacial skin and the oral mucosa, through mechanisms distinct from those seen in the spinal area, which is particularly difficult to predict or treat. The diagnosis and treatment of idiopathic chronic pain, such as atypical odontalgia (idiopathic painful trigeminal neuropathy or post-traumatic trigeminal neuropathy) and burning mouth syndrome, remain especially challenging. The central integration of gustatory inputs might modulate chronic oral and facial pain. A lack of pain in chronic inflammation inside the oral cavity, such as chronic periodontitis, involves the specialized functioning of oral bacteria. A more detailed understanding of the unique neurobiology of pain from the orofacial skin and the oral mucosa should help us develop novel methods for better treating persistent orofacial pain.
Topics: Animals; Chronic Pain; Face; Facial Pain; Humans; Mice; Mouth; Mouth Mucosa; Neuralgia; Periodontitis; Skin; Skin Physiological Phenomena; Trigeminal Nerve Injuries; Trigeminal Neuralgia
PubMed: 34071720
DOI: 10.3390/ijms22115810 -
The American Journal of Pathology Sep 2023Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant...
Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.
Topics: Humans; Rats; Animals; Oral Submucous Fibrosis; Mouth Mucosa; Epithelial-Mesenchymal Transition; Myofibroblasts; Epithelial Cells
PubMed: 37328100
DOI: 10.1016/j.ajpath.2023.05.014 -
Autoimmunity Reviews Oct 2015A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes... (Review)
Review
A group of autoimmune diseases is characterised by autoantibodies against epithelial adhesion structures and/or tissue-tropic lymphocytes driving inflammatory processes resulting in specific pathology at the mucosal surfaces and the skin. The most frequent site of mucosal involvement in autoimmune diseases is the oral cavity. Broadly, these diseases include conditions affecting the cell-cell adhesion causing intra-epithelial blistering and those where autoantibodies or infiltration lymphocytes cause a loss of cell-matrix adhesion or interface inflammation. Clinically, patients present with blistering, erosions and ulcers that may affect the skin as well as further mucosal surfaces of the eyes, nose and genitalia. While the autoimmune disease may be suspected based on clinical manifestations, demonstration of tissue-bound and circulating autoantibodies, or lymphocytic infiltrates, by various methods including histological examination, direct and indirect immunofluorescence microscopy, immunoblotting and quantitative immunoassay is a prerequisite for definitive diagnosis. Given the frequency of oral involvement and the fact that oral mucosa is the initially affected site in many cases, the informed practitioner should be well acquainted with diagnostic and therapeutic aspects of autoimmune dermatosis with oral involvement. This paper reviews the pathogenesis and clinical presentation of these conditions in the oral cavity with a specific emphasis on their differential diagnosis and current management approaches.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Immunoglobulin A; Mouth Mucosa; Phenotype; Skin Diseases
PubMed: 26117595
DOI: 10.1016/j.autrev.2015.06.005 -
International Journal of Molecular... Sep 2023This is an attempt to briefly summarize the contributions to this second Special Issue of the on the barrier function of the skin and the oral mucosa [...].
This is an attempt to briefly summarize the contributions to this second Special Issue of the on the barrier function of the skin and the oral mucosa [...].
Topics: Mouth Mucosa; Skin
PubMed: 37761991
DOI: 10.3390/ijms241813690 -
Annals of Anatomy = Anatomischer... May 2020The oral mucosa protects the underlying tissue from mechanical damage as well as from the entry of exogenous particles and microorganisms. Telocytes (TCs) are disputed...
BACKGROUND
The oral mucosa protects the underlying tissue from mechanical damage as well as from the entry of exogenous particles and microorganisms. Telocytes (TCs) are disputed stromal cells featuring peculiarly long and thin processes with uneven calibre known as telopodes, which play a number of roles within the interstitia. The present study aimed to test the key markers recommended for discriminating between TCs and false TCs in samples of normal oral mucosa.
METHODS
Archived paraffin-embedded oral mucosa samples were tested by means of immunohistochemistry with the following markers: CD34, D2-40, CD31 and CD68.
RESULTS
The epithelial expression of CD68, D2-40 and CD34 was detected. Two subsets of CD34-expressing stromal cells were identified, large cells with telopodial processes, presumably of the hematopoietic lineage, and spindle-shaped TC-like cells. Macrophages and TC-like cells within the lamina propria expressed CD68. The lymphatic endothelia were found to express CD31 and D2-40, but not CD34. Sprouting lymphangiogenesis was demonstrated by the lymphatic endothelial tip cells, which were projecting thin processes within the connective stroma.
CONCLUSIONS
The epithelial expression of CD68 suggests the professional phagocytic potential of the oral epithelium. Regarding the TCs and TC-like cells in the oral mucosa they could not be accurately distinguished from other possible cell types, neither on morphological basis (evidence of telopodes) nor by use of panels of markers which include CD34.
Topics: Aged; Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Basement Membrane; Epithelial Cells; Humans; Lymphatic Vessels; Macrophages; Microscopy, Electron, Transmission; Middle Aged; Mouth Mucosa; Mucous Membrane; Phagocytes; Telocytes
PubMed: 31978570
DOI: 10.1016/j.aanat.2020.151462 -
Environmental Science and Pollution... Dec 2017This study reviews global trends in the publication of papers on the micronucleus test of the exfoliated cells of the oral mucosa in mammals as an approach for... (Review)
Review
This study reviews global trends in the publication of papers on the micronucleus test of the exfoliated cells of the oral mucosa in mammals as an approach for environmental biomonitoring. This test has been widely used due to its precision for the detection of chromosome damage. Our temporal analysis showed a significant increase (p < 0.05) in the publication of papers on the oral mucosa over the past 33 years. Brazil was the country that published most papers (24% of the total), followed by India (16%), the USA (10%), Mexico (7%), and Turkey (6%). A further 30 countries contributed the other 37% of the papers. Overall, 99% of the micronucleus studies involved human subjects, and only 1% involved other mammals. As many wild mammals are subject to the same environmental pressures as humans, in particular chemical pollution, it seems likely that many species are equally susceptible to genotoxicogical damage. We emphasize the importance of applying this technique to the analysis of the oral mucosa of wild mammals, as well as the evaluation of its effectiveness, as observed in humans, and the expansion of the available approaches to the monitoring of environmental quality.
Topics: Animals; Cell Nucleus; DNA Damage; Environmental Monitoring; Humans; Micronuclei, Chromosome-Defective; Micronucleus Tests; Mouth Mucosa; Mutagens
PubMed: 29152700
DOI: 10.1007/s11356-017-0727-2