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Journal of Cancer Research and... 2019Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disease affecting oral, oropharyngeal, and sometimes the esophageal mucosa. It is characterized by the... (Review)
Review
Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disease affecting oral, oropharyngeal, and sometimes the esophageal mucosa. It is characterized by the progressive fibrosis of the submucosal tissue. The pathogenesis of OSMF has been directly related to the habit of chewing areca nut and its commercial preparation, which is widespread in Indian subcontinent and Southeast Asia. The areca nut has been classified as a "group one human carcinogen." Oral squamous cell carcinoma in the background of OSMF is one of the most common malignancies in South and Southeast Asian countries. Malignant transformation has been reported in 7%-12% cases of OSMF. Histopathological spectrum of OSMF includes the apparent alterations observed in the epithelium and connective tissue. Epithelial atrophy and sometimes epithelial hyperplasia with or without dysplasia are the peculiar alterations seen in the epithelium. In the connective tissue, there is extracellular matrix remodeling which results in excessive collagenization. Further cross-linking of collagen leads to hyalinization which makes the collagen resistant to proteolysis. Owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu, that is, hypoxia. This tissue hypoxia elicits angiogenesis which may result in the malignant transformation of OSMF. Perpetual irritation of areca nut and its constituents to the oral mucosa leads to upregulation of pro-inflammatory cytokines and further juxtaepithelial inflammation. Thus, these coordinated reactions in epithelium and connective tissue leads the OSMF toward malignant transformation.
Topics: Animals; Atrophy; Cell Transformation, Neoplastic; Disease Progression; Disease Susceptibility; Extracellular Matrix; Humans; Hyperplasia; Mouth Mucosa; Mouth Neoplasms; Neovascularization, Pathologic; Oral Submucous Fibrosis
PubMed: 31169205
DOI: 10.4103/jcrt.JCRT_522_17 -
Journal of Proteomics Feb 2017Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve... (Comparative Study)
Comparative Study
UNLABELLED
Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing.
BIOLOGICAL SIGNIFICANCE
Mammalian vocal folds are a unique but delicate tissue. A considerable fraction of people is affected by voice problems, yet many of the underlying vocal fold pathologies are sparsely understood at the molecular level. One such pathology is vocal fold scarring - the tendency of vocal fold injuries to heal with scar formation -, which represents a clinical problem with highly suboptimal treatment modalities. This study employed proteomics to obtain comprehensive insight into the protein repertoire of vocal fold fibroblasts, which are the cells that predominantly synthesize the extracellular matrix in both physiological and pathophysiological conditions. Protein profiles were compared to paired fibroblasts from the oral mucosa, a neighboring tissue that is remarkably resistant to scarring. Bioinformatic analyses of the data revealed a number of pathways as well as single proteins (e.g. ECM-remodeling factors, transcription factors, enzymes) that were significantly different between the two fibroblast types. Thereby, this study has revealed novel interesting molecular targets which can be analyzed in the future for their impact on vocal fold wound healing.
Topics: Animals; Fibroblasts; Mouth Mucosa; Proteome; Proteomics; Sheep; Vocal Cords
PubMed: 28099887
DOI: 10.1016/j.jprot.2017.01.010 -
BMJ Case Reports Mar 2015Verruciform xanthoma (VX) of the oral cavity is a benign mucosal growth that often presents as a pink, yellow or grey raised plaque or papule with granular, papillary or...
Verruciform xanthoma (VX) of the oral cavity is a benign mucosal growth that often presents as a pink, yellow or grey raised plaque or papule with granular, papillary or verrucous surface morphology. Intraorally this often presents on the masticatory mucosa and extraorally often involves the skin and anogenital mucosa. There are several proposed aetiological factors and the clinical features of VX can be misleading; clinically it can resemble malignancy. Histopathological diagnosis is a key for the correct management of this lesion. Excision of this lesion is curative.
Topics: Biopsy; Diagnosis, Differential; Humans; Middle Aged; Mouth Diseases; Mouth Floor; Mouth Mucosa; Treatment Outcome; Xanthomatosis
PubMed: 25819830
DOI: 10.1136/bcr-2014-209216 -
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 -
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 -
PLoS Pathogens Apr 2022As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces of the human body. Commensalism is tightly controlled...
As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces of the human body. Commensalism is tightly controlled by complex interactions of the fungus and the host to preclude fungal elimination but also fungal overgrowth and invasion, which can result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance of the oral mucosa. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. Using an experimental model of C. albicans oral colonization in mice we explored fungal determinants of commensalism in the oral cavity. Transcript profiling of the oral isolate 101 in the murine tongue tissue revealed a characteristic metabolic profile tailored to the nutrient poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. Here we show that these immune evasive properties of isolate 101 are explained by a strong attenuation of a number of virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of NRG1 abolished the commensal behaviour of isolate 101, thereby establishing a central role of this factor in the commensal lifestyle of C. albicans in the oral niche of the host.
Topics: Animals; Candida albicans; Candidiasis, Oral; Fungal Proteins; Mice; Mouth Mucosa; Symbiosis; Virulence
PubMed: 35404986
DOI: 10.1371/journal.ppat.1010012 -
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 -
Advanced Healthcare Materials Feb 2019The oral mucosa is a minimally invasive and immunologically rich site that is underutilized for vaccination due to physiological and immunological barriers. To develop... (Review)
Review
The oral mucosa is a minimally invasive and immunologically rich site that is underutilized for vaccination due to physiological and immunological barriers. To develop effective oral mucosal vaccines, key questions regarding vaccine residence time, uptake, adjuvant formulation, dose, and delivery location must be answered. However, currently available dosage forms are insufficient to address all these questions. An ideal oral mucosal vaccine delivery system would improve both residence time and epithelial permeation while enabling efficient delivery of physicochemically diverse vaccine formulations. Microneedles have demonstrated these capabilities for dermal vaccine delivery. Additionally, microneedles enable precise control over delivery properties like depth, uniformity, and dosing, making them an ideal tool to study oral mucosal vaccination. Select studies have demonstrated the feasibility of microneedle-mediated oral mucosal vaccination, but they have only begun to explore the broad functionality of microneedles. This review describes the physiological and immunological challenges related to oral mucosal vaccine delivery and provides specific examples of how microneedles can be used to address these challenges. It summarizes and compares the few existing oral mucosal microneedle vaccine studies and offers a perspective for the future of the field.
Topics: Adjuvants, Immunologic; Animals; Drug Delivery Systems; Humans; Mouth Mucosa; Needles; Vaccination; Vaccines
PubMed: 30537400
DOI: 10.1002/adhm.201801180 -
PloS One 2016Immunohistochemistry was used to identify, enumerate, and describe the tissue distribution of Langerhans type (CD1a and CD207), myeloid (CD1c and CD141), and...
Immunohistochemistry was used to identify, enumerate, and describe the tissue distribution of Langerhans type (CD1a and CD207), myeloid (CD1c and CD141), and plasmacytoid (CD303 and CD304) dendritic cell subsets in oral mucosa of allergic and non-allergic individuals. Allergic individuals have more CD141+ myeloid cells in epithelium and more CD1a+ Langerhans cells in the lamina propria compared to healthy controls, but similar numbers for the other DC subtypes. Our data are the first to describe the presence of CD303+ plasmacytoid DCs in human oral mucosa and a dense intraepithelial network of CD141+ DCs. The number of Langerhans type DCs (CD1a and CD207) and myeloid DCs (CD1c), was higher in the oral mucosa than in the nasal mucosa of the same individual independent of the atopic status.
Topics: Adolescent; Adult; Case-Control Studies; Cell Count; Dendritic Cells; Female; Healthy Volunteers; Humans; Hypersensitivity; Immunohistochemistry; Male; Middle Aged; Mouth Mucosa; Nasal Mucosa; Young Adult
PubMed: 27166951
DOI: 10.1371/journal.pone.0154409 -
Cellular Microbiology Oct 2019The impact of oral commensal and pathogenic bacteria on peri-implant mucosa is not well understood, despite the high prevalence of peri-implant infections. Hence, we...
The impact of oral commensal and pathogenic bacteria on peri-implant mucosa is not well understood, despite the high prevalence of peri-implant infections. Hence, we investigated responses of the peri-implant mucosa to Streptococcus oralis or Aggregatibacter actinomycetemcomitans biofilms using a novel in vitro peri-implant mucosa-biofilm model. Our 3D model combined three components, organotypic oral mucosa, implant material, and oral biofilm, with structural assembly close to native situation. S. oralis induced a protective stress response in the peri-implant mucosa through upregulation of heat shock protein (HSP70) genes. Attenuated inflammatory response was indicated by reduced cytokine levels of interleukin-6 (IL-6), interleukin-8 (CXCL8), and monocyte chemoattractant protein-1 (CCL2). The inflammatory balance was preserved through increased levels of tumor necrosis factor-alpha (TNF-α). A. actinomycetemcomitans induced downregulation of genes important for cell survival and host inflammatory response. The reduced cytokine levels of chemokine ligand 1 (CXCL1), CXCL8, and CCL2 also indicated a diminished inflammatory response. The induced immune balance by S. oralis may support oral health, whereas the reduced inflammatory response to A. actinomycetemcomitans may provide colonisation advantage and facilitate later tissue invasion. The comprehensive characterisation of peri-implant mucosa-biofilm interactions using our 3D model can provide new knowledge to improve strategies for prevention and therapy of peri-implant disease.
Topics: Aggregatibacter actinomycetemcomitans; Biofilms; Cells, Cultured; Chemokine CCL2; Dental Implants; HSP70 Heat-Shock Proteins; Humans; Interleukin-6; Interleukin-8; Models, Immunological; Mouth Mucosa; Peri-Implantitis; Prosthesis-Related Infections; Streptococcus oralis; Titanium; Tumor Necrosis Factor-alpha
PubMed: 31270923
DOI: 10.1111/cmi.13078